CFR 2023 Title21 Vol8 ChapI

Title 21—Food and
Drugs
(This book contains Parts 800 to 1299)
Part
CHAPTER I—Food and Drug Administration, Department of

Health and Human Services (Continued) ........................... 800
aworley on LAPBH6H6L3 with DISTILLER
VerDate Sep<11>2014 15:46 Jun 06, 2023 Jkt 259078 PO 00000 Frm 00011 Fmt 8008 Sfmt 8008 Q:\21\21V8.TXT PC31
CHAPTER I—FOOD AND DRUG
ADMINISTRATION, DEPARTMENT OF HEALTH
AND HUMAN SERVICES (CONTINUED)
EDITORIAL NOTE: Nomenclature changes to chapter I appear at 59 FR 14366, Mar. 28, 1994;
68 FR 24879, May 9, 2003; and 69 FR 13717, Mar. 24, 2004.
SUBCHAPTER H—MEDICAL DEVICES
Part Page
800 General .................................................................... 7
801 Labeling .................................................................. 28
803 Medical device reporting ......................................... 64
806 Medical devices; reports of corrections and remov-
als ......................................................................... 81
807 Establishment registration and device listing for
manufacturers and initial importers of devices ... 85
808 Exemptions from Federal preemption of State and
local medical device requirements ....................... 103
809 In vitro diagnostic products for human use ............ 109
810 Medical device recall authority .............................. 118
812 Investigational device exemptions .......................... 125
813 [Reserved]
814 Premarket approval of medical devices .................. 146
820 Quality system regulation ...................................... 170
821 Medical device tracking requirements .................... 184
822 Postmarket surveillance ......................................... 191
830 Unique device identification ................................... 199
860 Medical device classification procedures ................ 208
861 Procedures for performance standards development 229
862 Clinical chemistry and clinical toxicology devices 233
864 Hematology and pathology devices ......................... 285
866 Immunology and microbiology devices ................... 317
868 Anesthesiology devices ........................................... 425
870 Cardiovascular devices ............................................ 450
872 Dental devices ......................................................... 493
874 Ear, nose, and throat devices .................................. 522
876 Gastroenterology-urology devices .......................... 539

878 General and plastic surgery devices ........................ 576
3
21 CFR Ch. I (4–1–23 Edition)
Part Page
880 General hospital and personal use devices .............. 611
882 Neurological devices ............................................... 640
884 Obstetrical and gynecological devices .................... 675
886 Ophthalmic devices ................................................. 705
888 Orthopedic devices .................................................. 735
890 Physical medicine devices ....................................... 768
892 Radiology devices .................................................... 793
895 Banned devices ........................................................ 812
898 Performance standard for electrode lead wires and
patient cables ....................................................... 818
SUBCHAPTER I—MAMMOGRAPHY QUALITY STANDARDS ACT
900 Mammography ........................................................ 820

SUBCHAPTER J—RADIOLOGICAL HEALTH
1000 General .................................................................... 860

1002 Records and reports ................................................. 863
1003 Notification of defects or failure to comply ............ 871
1004 Repurchase, repairs, or replacement of electronic
products ............................................................... 875
1005 Importation of electronic products ......................... 877
1010 Performance standards for electronic products:
General ................................................................. 880
1020 Performance standards for ionizing radiation emit-
ting products ........................................................ 886
1030 Performance standards for microwave and radio
frequency emitting products ................................ 918
1040 Performance standards for light-emitting products 921
SUBCHAPTER K—TOBACCO PRODUCTS
1100 General .................................................................... 946

1105 General .................................................................... 948
1107 Exemption requests and substantial equivalence
reports .................................................................. 949
1114 Premarket tobacco product applications ................ 987
1140 Cigarettes, smokeless tobacco, and covered to-
bacco products ...................................................... 1026
1141 Cigarette package and advertising warnings (eff.
until 11-6-23) ......................................................... 1032
1141 Required warnings for cigarette packages and ad-
vertisements (eff. 11-6-23) ..................................... 1036
1143 Minimum required warning statements .................. 1039
1150 User fees .................................................................. 1044
SUBCHAPTER L—REGULATIONS UNDER CERTAIN OTHER ACTS
ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION
1210 Regulations under the Federal Import Milk Act .... 1048
4
Food and Drug Administration, HHS
Part Page
1230 Regulations under the Federal Caustic Poison Act 1051
1240 Control of communicable diseases .......................... 1058
1250 Interstate conveyance sanitation ........................... 1063
1251–1270 [Reserved]
1271 Human cells, tissues, and cellular and tissue-based
products ............................................................... 1074
1272–1299 [Reserved]
SUBCHAPTER H—MEDICAL DEVICES
PART 800—GENERAL in the meaning of section 502(j) of the

act. By this regulation, this ruling is
Subpart A [Reserved] applicable to all preparations for oph-
thalmic use that are regulated as med-
Subpart B—Requirements for Specific ical devices, i.e., contact lens solu-
Medical Devices tions. By the regulation in § 200.50 of
this chapter, this ruling is applicable
Sec.
800.10 Contact lens solutions; sterility. to ophthalmic preparations that are
800.12 Contact lens solutions and tablets; regulated as drugs.
tamper-resistant packaging. (3) The containers shall be sterile at
800.20 Patient examination gloves and sur- the time of filling and closing, and the
geons’ gloves; sample plans and test container or individual carton shall be
method for leakage defects; adulteration. so sealed that the contents cannot be
800.30 Over-the-counter hearing aid con-
trols.
used without destroying the seal. The
packaging and labeling of these solu-
Subpart C—Administrative Practices and tions shall also comply with § 800.12 on
Procedures tamper-resistant packaging require-
ments.
800.55 Administrative detention. (b) Liquid ophthalmic preparations
800.75 Requests for supervisory review of
certain decisions made by the Center for
packed in multiple-dose containers
Devices and Radiological Health. should:
(1) Contain one or more suitable and
AUTHORITY: 21 U.S.C. 321, 334, 351, 352, 355,
harmless substances that will inhibit
360e, 360i, 360j, 360k, 361, 362, 371.
Section 800.30 also issued under Sec. 709, the growth of microorganisms; or
Pub. L. 115–52, 131 Stat. 1065–67. (2) Be so packaged as to volume and
type of container and so labeled as to
Subpart A [Reserved] duration of use and with such nec-
essary warnings as to afford adequate
protection and minimize the hazard of
Subpart B—Requirements for injury resulting from contamination
Specific Medical Devices during use.
§ 800.10 Contact lens solutions; ste- (c) Eye cups, eye droppers, and other
rility. dispensers intended for ophthalmic use
should be sterile, and may be regarded
(a)(1) Informed medical opinion is in as falling below their professed stand-
agreement that all preparations offered ard of purity or quality if they are not
or intended for ophthalmic use, includ- sterile. These articles, which are regu-
ing contact lens solutions, should be lated as medical devices unless pack-
sterile. It is further evident that such aged with the drugs with which they
preparations purport to be of such pu-
are to be used, should be packaged so
rity and quality as to be suitable for
as to maintain sterility until the pack-
safe use in the eye.
age is opened and be labeled, on or
(2) The Food and Drug Administra-
within the retail package, so as to af-
tion concludes that all such prepara-
ford adequate directions and necessary
tions, if they are not sterile, fall below
warnings to minimize the hazard of in-
their professed standard of purity or
jury resulting from contamination dur-
quality and may be unsafe. In a state-
ing use.
ment of policy issued on September 1,
1964, the Food and Drug Administra- [47 FR 50455, Nov. 5, 1982]
tion ruled that liquid preparations of-
fered or intended for ophthalmic use § 800.12 Contact lens solutions and
that are not sterile may be regarded as tablets; tamper-resistant packaging.
adulterated within the meaning of sec- (a) General. Unless contact lens solu-
tion 501(c) of the Federal Food, Drug, tions used, for example, to clean, dis-
and Cosmetic Act (the act), and, fur- infect, wet, lubricate, rinse, soak, or
ther, may be deemed misbranded with- store contact lenses and salt tablets or
§ 800.12 21 CFR Ch. I (4–1–23 Edition)
other dosage forms to be used to make processes. A tamper-resistant package

any such solutions are packaged in may involve an immediate-container
tamper-resistant retail packages, there and closure system or secondary-con-
is the opportunity for the malicious tainer or carton system or any com-
adulteration of these products with bination of systems intended to provide
risks both to individuals who unknow- a visual indication of package integ-
ingly purchase adulterated products rity. The tamper-resistant feature
and with loss of consumer confidence shall be designed to and shall remain
in the security of the packages of over- intact when handled in a reasonable
the-counter (OTC) health care prod- manner during manufacture, distribu-
ucts. The Food and Drug Administra- tion, and retail display.
tion has the authority and responsi- (c) Labeling. Each retail package of a
bility under the Federal Food, Drug, product covered by this section is re-
and Cosmetic Act (the act) to establish quired to bear a statement that is
a uniform national standard for tam- prominently placed so that consumers
per-resistant packaging of those OTC are alerted to the tamper-resistant fea-
products vulnerable to malicious adul- ture of the package. The labeling state-
teration that will improve the security ment is also required to be so placed
of OTC packaging and help assure the that it will be unaffected if the tamper-
safety and effectiveness of the products resistant feature of the package is
contained therein. A contact lens solu- breached or missing. If the tamper-re-
tion or tablet or other dosage form to sistant feature chosen to meet the re-
be used to make such a solution for requirement in paragraph (b) of this sec-
tail sale that is not packaged in a tam- tion is one that uses an identifying
per-resistant package and labeled in characteristic, that characteristic is
accordance with this section is adulter- required to be referred to in the label-
ated under section 501 of the act or ing statement. For example, the label-
misbranded under section 502 of the ing statement on a bottle with a shrink
act, or both. band could say ‘‘For your protection,
(b) Requirement for tamper-resistant this bottle has an imprinted seal
package. Each manufacturer and pack- around the neck.’’
er who packages for retail sale a prod- (d) Requests for exemptions from pack-
uct regulated as a medical device that aging and labeling requirements. A man-
is a solution intended for use with con- ufacturer or packer may request an ex-
tact lenses, e.g., for cleaning, dis- emption from the packaging and label-
infecting, wetting, lubricating, rinsing, ing requirements of this section. A re-
soaking, or storing contact lenses or quest for an exemption is required to
tablets or other dosage forms to be be submitted in the form of a citizen
used to make any such solution shall petition under § 10.30 of this chapter
package the product in a tamper-resist- and should be clearly identified on the
ant package, if this product is acces- envelope as a ‘‘Request for Exemption
sible to the public while held for sale. from Tamper-resistant Rule.’’ A peti-
A tamper-resistant package is one hav- tion for an exemption from a require-
ing an indicator or barrier to entry ment of this section is required to con-
which, if breached or missing, can rea- tain the same kind of information
sonably be expected to provide visible about the product as is specified for
evidence to consumers that tampering OTC drugs in § 211.132(d) of this chap-
has occurred. To reduce the likelihood ter.
of substitution of a tamper-resistant (e) Products subject to approved pre-
feature after tampering, the indicator market approval applications. Holders of
or barrier to entry is required to be disapproved premarket approval applica-
tinctive by design or by the use of an tions for products subject to this sec-
identifying characteristic (e.g., a pat- tion are required to submit supple-
tern, name, registered trademark, logo, ments to provide for changes in pack-
or picture). For purposes of this sec- aging to comply with the requirement
tion, the term ‘‘distinctive by design’’ of paragraph (b) of this section unless
means the package cannot be dupli- these changes do not affect the com-
cated with commonly available mate- position of the container, the torque
rial or through commonly available (tightness) of the container, or the
Food and Drug Administration, HHS § 800.20
composition of the closure component barrier to entry be distinctive by de-

in contact with the contents (cap liner sign. Products packaged for retail sale
or innerseal) as these features are de- after May 5, 1983, are required to be in
scribed in the approved premarket ap- compliance with all aspects of the reg-
proval application. Any supplemental ulations without regard to the retail
premarket approval application under level effective date.
this paragraph is required to include
[47 FR 50455, Nov. 5, 1982; 48 FR 1706, Jan. 14,
data sufficient to show that these 1983, as amended at 48 FR 16666, Apr. 19, 1983;
changes do not adversely affect the 48 FR 37625, Aug. 19, 1983; 53 FR 11252, Apr. 6,
product. 1988; 73 FR 34859, June 19, 2008]
(f) Effective date. Each product sub-
EFFECTIVE DATE NOTE: A document pub-
ject to this section is required to com- lished at 48 FR 41579, Sept. 16, 1983, stayed
ply with the requirements of this sec- the effective date of § 800.12(f)(3) until further
tion on the dates listed below except to notice.
the extent that a product’s manufac-
turer or packer has obtained an exemp- § 800.20 Patient examination gloves
tion from a packaging or labeling re- and surgeons’ gloves; sample plans
quirement: and test method for leakage defects;
(1) Initial effective date for packaging adulteration.
requirements. (i) The packaging require- (a) Purpose. The prevalence of human
ment in paragraph (b) of this section is immunodeficiency virus (HIV), which
effective on February 7, 1983 for each causes acquired immune deficiency
contact lens solution packaged for re- syndrome (AIDS), and its risk of trans-
tail sale on or after that date, except mission in the health care context,
for the requirement in paragraph (b) of have caused the Food and Drug Admin-
this section for a distinctive indicator istration (FDA) to look more closely at
or barrier to entry. the quality control of barrier devices,
(ii) The packaging requirement in such as surgeons’ gloves and patient
paragraph (b) of this section is effec- examination gloves (collectively
tive on May 5, 1983 for each tablet that known as medical gloves) to reduce the
is to be used to make a contact lens so- risk of transmission of HIV and other
lution and that is packaged for retail blood-borne infectious diseases. The
sale on or after that date. Centers for Disease Control (CDC) rec-
(2) Initial effective date for labeling re- ommend that health care workers wear
quirements. The requirement in para- medical gloves to reduce the risk of
graph (b) of this section that the indi- transmission of HIV and other blood-
cator or barrier to entry be distinctive borne infectious deseases. The CDC rec-
by design and the requirement in para- ommends that health care workers
graph (c) of this section for a labeling wear medical gloves when touching
statement are effective on May 5, 1983 blood or other body fluids, mucous
for each product subject to this section membranes, or nonintact skin of all pa-
packaged for retail sale on or after tients; when handling items or surfaces
that date, except that the requirement soiled with blood or other body fluids;
for a specific label reference to any and when performing venipuncture and
identifying characteristic is effective other vascular access procedures.
on February 6, 1984 for each affected Among other things, CDC’s rec-
product subject to this section pack- ommendation that health care pro-
aged for retail sale on or after that viders wear medical gloves dem-
date. onstrates the proposition that devices
(3) Retail level effective date. The tam- labeled as medical gloves purport to be
per-resistant packaging requirement of and are represented to be effective bar-
paragraph (b) of this section is effec- riers against the transmission of blood-
tive on February 6, 1984 for each prod- and fluid-borne pathogens. Therefore,
uct subject to this section that is held FDA, through this regulation, is defin-
for sale at retail level on or after that ing adulteration for patient examina-
date that was packaged for retail sale tion and surgeons’ gloves as a means of
before May 5, 1983. This does not in- assuring safe and effective devices.
clude the requirement in paragraph (b) (1) For a description of a patient ex-
of this section that the indicator or amination glove, see § 880.6250. Finger
§ 800.20 21 CFR Ch. I (4–1–23 Edition)
cots, however, are excluded from the (iii) Automatic water-dispensing ap-
test method and sample plans in para- paratus or manual device capable of de-
graphs (b) and (c) of this section. livering 1,000 ml of water;
(2) For a description of a surgeons’ (iv) Stand with horizontal rod for
glove, see § 878.4460 of this chapter. hanging the hook end of the plastic
(b)(1) General test method. For the pur- tube. The horizontal support rod must
poses of this part, FDA’s analysis of be capable of holding the weight of the
gloves for leaks and visual defects will total number of gloves that will be sus-
be conducted by a visual examination pended at any one time, e.g., five
and by a water leak test method, using gloves suspended will weigh about 5
kilograms (kg);
1,000 milliliters (ml) of water.
(v) Timer capable of measuring two
(i) Units examined. Each medical
minute intervals.
glove will be analyzed independently. (3) Visual defects and leak test proce-
When packaged as pairs, each glove is dures. Examine the sample and identify
considered separately, and both gloves code/lot number, size, and brand as ap-
will be analyzed. propriate. Continue the visual exam-
(ii) Identification of defects. For this ination using the following procedures:
test, defects include leaks detected (i) Visual defects examination. Inspect
when tested in accordance with para- the gloves for visual defects by care-
graph (b)(3) of this section. A leak is fully removing the glove from the
defined as the appearance of water on wrapper, box, or package. Visually ex-
the outside of the glove. This emer- amine each glove for defects. As noted
gence of water from the glove con- in paragraph (b)(1)(iii) of this section, a
stitutes a watertight barrier failure. visual defect observed in the top 40 mm
Other defects include tears, embedded of a glove will not be counted as a de-
foreign objects, extrusions of glove ma- fect for the purpose of this part. Vis-
terial on the exterior or interior sur- ually defective gloves do not require
face of the glove, gloves that are fused further testing, although they must be
together so that individual glove sepa- included in the total number of defec-
ration is impossible, gloves that adhere tive gloves counted for the sample.
to each other and tear when separated, (ii) Leak test set-up. (A) During this
or other visual defects that are likely procedure, ensure that the exterior of
to affect the barrier integrity. the glove remains dry. Attach the
(iii) Factors for counting defects. One glove to the plastic fill tube by bring-
defect in one glove is counted as one ing the cuff end to the 40 mm mark and
defect. A defect in both gloves in a pair fastening with elastic strapping to
of gloves is counted as two defects. If make a watertight seal.
multiple defects, as defined in para- (B) Add 1,000 ml of room temperature
graph (b)(1)(ii) of this section, are water (i.e., 20 (deg)C to 30 (deg)C) into
found in one glove, they are counted as the open end of the fill tube. The water
should pass freely into the glove. (With
one defect. Visual defects and leaks
some larger sizes of long-cuffed sur-
that are observed in the top 40 millime-
geons’ gloves, the water level may
ters (mm) of a glove will not be count-
reach only the base of the thumb. With
ed as a defect for the purposes of this
some smaller gloves, the water level
part.
may extend several inches up the fill
(2) Leak test materials. FDA considers tube.)
the following to be the minimum mate- (iii) Leak test examination. Imme-
rials required for this test : diately after adding the water, examine
(i) A 60 mm by 380 mm (clear) plastic the glove for water leaks. Do not
cylinder with a hook on one end and a squeeze the glove; use only minimum
mark scored 40 mm from the other end manipulation to spread the fingers to
(a cylinder of another size may be used check for leaks. Water drops may be
if it accommodates both cuff diameter blotted to confirm leaking.
and any water above the glove capac- (A) If the glove does not leak imme-
ity); diately, keep the glove/filling tube as-

(ii) Elastic strapping with velcro or sembly upright and hang the assembly
other fastening material; vertically from the horizontal rod,
10
using the wire hook on the open end of Procedures For Inspection By At-
the fill tube (do not support the filled tributes.’’
glove while transferring). (2) Sample sizes, inspection levels, and
(B) Make a second observation for minimum AQLs. FDA will use single
leaks 2 minutes after the water is normal sampling for lots of 1,200 gloves
added to the glove. Use only minimum or less and multiple normal sampling
manipulation of the fingers to check for all larger lots. FDA will use general
for leaks. inspection level II in determining the
(C) Record the number of defective sample size for any lot size. As shown
gloves. in the tables following paragraph (c)(3)
of this section, FDA considers a 1.5
(c) Sampling, inspection, acceptance,
AQL to be the minimum level of qual-
and adulteration. In performing the test
ity acceptable for surgeons’ gloves and
for leaks and other visual defects de- a 2.5 AQL to be the minimum level of
scribed in paragraph (b) of this section, quality acceptable for patient exam-
FDA will collect and inspect samples of ination gloves.
medical gloves, and determine when (3) Adulteration levels and accept/reject
the gloves are acceptable as set out in criteria. FDA considers a lot of medical
paragraphs (c)(1) through (c)(3) of this gloves to be adulterated when the num-
section. ber of defective gloves found in the
(1) Sample plans. FDA will collect tested sample meets or exceeds the ap-
samples from lots of medical gloves in plicable rejection number at the 1.5
accordance with agency sampling AQL for surgeons’ gloves or the 2.5
plans. These plans are based on sample AQL for patient examination gloves.
sizes, levels of sample inspection, and These acceptance and rejection num-
acceptable quality levels (AQLs) found bers are identified in the tables fol-
in the International Standard Organi- lowing paragraph (c)(3) of this section
zation’s standard ISO 2859, ‘‘Sampling as follows:
ACCEPT/REJECT CRITERIA AT 1.5 AQL FOR SURGEONS’ GLOVES
Number Defective
Lot Size Sample Sample Size Number Examined
Accept Reject
8 to 90 Single sample 8 0 1
501 to 1,200 Single sample 80 3 4
1,201 to 3,200 First 32 32 — 4

Second 32 64 1 5
Third 32 96 2 6
Fourth 32 128 3 7
Fifth 32 160 5 8
Sixth 32 192 7 9
Seventh 32 224 9 10
3,201 to 10,000 First 50 50 0 4

Second 50 100 1 6
Third 50 150 3 8
Fourth 50 200 5 10
Fifth 50 250 7 11
Sixth 50 300 10 12
Seventh 50 350 13 14
10,001 to 35,000 First 80 80 0 5

Second 80 160 3 8
Third 80 240 6 10
Fourth 80 320 8 13
Fifth 80 400 11 15
Sixth 80 480 14 17
Seventh 80 560 18 19
35,000 First 125 125 1 7

Second 125 250 4 10
11
§ 800.20 21 CFR Ch. I (4–1–23 Edition)
ACCEPT/REJECT CRITERIA AT 1.5 AQL FOR SURGEONS’ GLOVES—Continued

Number Defective
Accept Reject
Third 125 375 8 13

Fourth 125 500 12 17
Fifth 125 625 17 20
Sixth 125 750 21 23
Seventh 125 875 25 26
ACCEPT/REJECT CRITERIA AT 2.5 AQL FOR PATIENT EXAMINATION GLOVES

Number Defective
Accept Reject
1,201 to 3,200 First 32 32 0 4

Second 32 64 1 6
Third 32 96 3 8
Fourth 32 128 5 10
Fifth 32 160 7 11
Sixth 32 192 10 12
Seventh 32 224 13 14
3,201 to 10,000 First 50 50 0 5

Second 50 100 3 8
Third 50 150 6 10
Fourth 50 200 8 13
Fifth 50 250 11 15
Sixth 50 300 14 17
Seventh 50 350 18 19
10,001 to 35,000 First 80 80 1 7

Second 80 160 4 10
Third 80 240 8 13
Fourth 80 320 12 17
Fifth 80 400 17 20
Sixth 80 480 21 23
Seventh 80 560 25 26
35,000 and above First 125 125 2 9

Second 125 250 7 14
Third 125 375 13 19
Fourth 125 500 19 25
Fifth 125 625 25 29
Sixth 125 750 31 33
Seventh 125 875 37 38
(d) Compliance. Lots of gloves that as detention of imported products and

are sampled, tested, and rejected using seizure of domestic products.
procedures in paragraphs (b) and (c) of (2) Reconditioning. FDA may author-
this section, are considered adulterated ize the owner of the product, or the
within the meaning of section 501(c) of owner’s representative, to attempt to
the act. recondition, i.e., bring into compliance
(1) Detention and seizure. Lots of with the act, a lot or part of a lot of
gloves that are adulterated under sec- foreign gloves detained at importation,
tion 501(c) of the act are subject to ad- or a lot or part of a lot of seized domes-
ministrative and judicial action, such tic gloves.
12
(i) Modified sampling, inspection, and considers a lot or part of a lot of adul-
acceptance. If FDA authorizes recondi- terated gloves, that is reconditioned in
tioning of a lot or portion of a lot of accordance with paragraph (d)(2)(i) of
adulterated gloves, testing to confirm this section, to be acceptable when the
that the reconditioned gloves meet number of defective gloves found in the
AQLs must be performed by an inde- tested sample does not exceed the ac-
pendent testing facility. The following ceptance number in the appropriate ta-
tightened sampling plan must be fol- bles in paragraph (d)(2)(ii)(B) of this
lowed, as described in ISO 2859 ‘‘Sam- section for reconditioned surgeons’
pling Procedures for Inspection by At-
gloves or patient examination gloves.
tributes:’’
(A) General inspection level II, (B) FDA considers a reconditioned lot
(B) Single sampling plans for tight- of medical gloves to be adulterated
ened inspection, within the meaning of section 501(c) of
(C) 1.5 AQL for surgeons’ gloves, and the act when the number of defective
(D) 2.5 AQL for patient examination gloves found in the tested sample
gloves. meets or exceeds the applicable rejec-
(ii) Adulteration levels and acceptance tion number in the tables following
criteria for reconditioned gloves. (A) FDA paragraph (d)(2)(ii)(B) of this section:
ACCEPT/REJECT CRITERIA AT 1.5 AQL FOR RECONDITIONED SURGEONS’ GLOVES
Number Defective
Lot Size Sample Sample Size
Accept Reject
1,201 to 3,200 Single sample 125 3 4
3,201 to 10,000 Single sample 200 5 6
10,001 to 35,000 Single sample 315 8 9
35,000 and above Single sample 500 12 13
ACCEPT/REJECT CRITERIA AT 2.5 AQL FOR RECONDITIONED PATIENT EXAMINATION GLOVES

Number Defective
Lot Size Sample Sample Size
Accept Reject
1,201 to 3,200 Single sample 125 5 6
3,201 to 10,000 Single sample 200 8 9
10,001 to 35,000 Single sample 315 12 13
35,000 and above Single sample 500 18 19
[55 FR 51256, Dec. 12, 1990, as amended at 71 § 800.30 Over-the-counter hearing aid
FR 75876, Dec. 19, 2006] controls.
(a) Scope. This section specifies the

requirements for over-the-counter
(OTC) air-conduction hearing aids. Air-
13
§ 800.30 21 CFR Ch. I (4–1–23 Edition)
conduction hearing aids that satisfy impairment. The device, through tools,
the requirements in paragraphs (c) tests, or software, allows the user to
through (f) of this section are consid- control the hearing aid and customize
ered ‘‘available’’ over the counter as it to the user’s hearing needs. The de-
section 520(q)(1)(A)(v) of the Federal vice may use wireless technology or
Food, Drug, and Cosmetic Act uses the may include tests for self-assessment
term. Air-conduction hearing aids that of hearing loss. The device is available
do not meet the definition in section over-the-counter, without the super-
520(q) of the Federal Food, Drug, and vision, prescription, or other order, in-
Cosmetic Act or do not satisfy the fol- volvement, or intervention of a li-
lowing requirements are prescription censed person, to consumers through
hearing aids. Unless otherwise speci- in-person transactions, by mail, or on-
fied, the requirements in this section line, provided that the device satisfies
are in addition to other applicable re- the requirements in this section.
quirements, including but not limited Prescription hearing aid. A prescrip-
to special controls found in the appli- tion hearing aid is a hearing aid that is
cable classification regulation in part not an OTC hearing aid as defined in
874 of this chapter. this section or a hearing aid that does
(b) Definitions for the purposes of this not satisfy the requirements in this
section. This section uses the following section.
definitions: Rebuilt hearing aid. An OTC hearing
Air-conduction hearing aid. An air- aid is ‘‘rebuilt’’ if the manufacturer
conduction hearing aid is a hearing aid has inspected and tested the device,
that conducts sound to the ear through made any necessary modifications to
the air. ensure it meets applicable regulatory
Hearing aid. A hearing aid is any requirements, including the require-
wearable device designed for, offered ments in this section to be available
for the purpose of, or represented as OTC, and adequately reprocessed the
aiding persons with or compensating device for the next user.
for, impaired hearing. Sale. Sale includes a lease, rental, or
Licensed person. A licensed person is a any other purchase or exchange for
person as defined in section 201(e) of value.
the Federal Food, Drug, and Cosmetic Tools, tests, or software. Tools, tests,
Act that holds a license or degree for or software are components of the de-
the diagnosis, assessment, or treat- vice that, individually or in combina-
ment of hearing loss; or that holds a li- tion, allow a lay user to control the de-
cense to sell or distribute hearing aids. vice and customize it sufficiently, such
A person that must meet generally ap- as the device’s output, to meet the
plicable licensing or operating require- user’s hearing needs.
ments such as annual health and safety Used hearing aid. A hearing aid is
inspections, provided the generally ap- ‘‘used’’ if a user has worn it for any pe-
plicable licensing or operating require- riod of time. However, a hearing aid
ment is consistent with this section shall not be ‘‘used’’ merely because a
and other applicable requirements prospective user wore it as part of a
under the Federal Food, Drug, and Cos- bona fide hearing aid evaluation to de-
metic Act, is not a ‘‘licensed person’’ termine whether to select that par-
solely for that reason. A person that ticular hearing aid for that prospective
represents as a marketer, seller, dis- user. A hearing aid evaluation is ‘‘bona
penser, distributor, or customer sup- fide’’ if it was conducted in the pres-
port representative (or an equivalent ence of the dispenser or a hearing
description) is not a ‘‘licensed person’’ health professional selected by the dis-
solely by making such representations. penser to assist the prospective user in
Over-the-counter hearing aid. An over- making a determination.
the-counter (OTC) hearing aid is an air- (c) Labeling. An OTC hearing aid shall
conduction hearing aid that does not bear all of the following in the label-
require implantation or other surgical ing:
intervention, and is intended for use by (1) Outside package labeling. The out-
a person age 18 or older to compensate side package of an OTC hearing aid
for perceived mild to moderate hearing shall bear all of the following:
14
(i) Warnings and other important infor- (A) (A) Warning against use in people
mation. All of the following shall ap- younger than 18.
pear on the outside package:
(B) Symptoms suggesting perceived mild

to moderate hearing loss.
(C) Advice of availability of professional

services.
(D) ‘‘Red flag’’ conditions. ER17AU22.002</GPH>

ER17AU22.001</GPH>
15
ER17AU22.000</GPH>
§ 800.30 21 CFR Ch. I (4–1–23 Edition)
(E) Notice of contact information.
(F) Notice of manufacturer’s return pol-

icy.
(ii) Statement of build condition. If the vice’s common name on the principal
OTC hearing aid is used or rebuilt, the display panel may satisfy all or part of
outside package shall declare that fact. this requirement to the extent the
A sticker under and visible through the common name includes the marks.
outer wrapper will suffice to declare (iv) Indication of battery information.
ER17AU22.005</GPH>
such fact. The outside package shall indicate the

(iii) Statement of OTC availability. The type and number of batteries and
principal display panel shall bear the whether batteries are included in the
marks ‘‘OTC’’ and ‘‘hearing aid’’ with package.
the same prominence required under (v) Indication of control platform. The
ER17AU22.004</GPH>
§ 801.61(c) of this chapter for the de- outside package shall indicate whether
vice’s statement of identity. The de- a mobile device or other non-included
16
ER17AU22.003</GPH>
control platform is required. The indi- site or customer registration and with-
cation must include the type of plat- out requiring purchase of any product
form and how the platform connects to or service. The user instructional bro-
the device. chure shall include all of the following:
(2) Labeling, inside the package. The (i) The following warnings, which
manufacturer or distributor of an OTC shall appear in the following order and
hearing aid shall include a user in- prior to any content except the cover
structional brochure inside the pack- page:
age and shall make an electronic (A) Warning against use in people
version available for download without younger than 18.
(B) ‘‘Red flag’’ conditions.
(C) Warning about pain from device

placement.
ER17AU22.007</GPH>
17
ER17AU22.006</GPH>
§ 800.30 21 CFR Ch. I (4–1–23 Edition)
(ii) Any additional warnings the to any content except the cover page
manufacturer may include prior to the and the warnings under paragraphs
cautions and notices to users in para- (c)(2)(i) and (ii) of this section:
graph (c)(2)(iii) of this section. (A) Caution about hearing protection.
(iii) The following cautions and no-
tices for users, which shall appear prior
(B) Caution about excessive sound out-

put.
(C) Caution about components lodging

in ear.
ER17AU22.011</GPH>
ER17AU22.010</GPH>
(D) Advice to seek professional services.

ER17AU22.009</GPH>
18
ER17AU22.008</GPH>
(E) Note about user expectations.
(E) Note about reporting adverse events

to FDA.
(iv) An illustration(s) of the OTC (vii) Specific instructions for all of

hearing aid that indicates operating the following:
controls, user adjustments, and the (A) Instructions for sizing or insert-
battery compartment. ing the eartip of the OTC hearing aid
(v) Information on the function of all to prevent insertion past the depth
ER17AU22.014</GPH>
controls intended for user adjustment. limit and damage to the tympanic
(vi) A description of any accessory membrane.
that accompanies the OTC hearing aid, (B) The tools, tests, or software that
including but not limited to wax allow the user to control the OTC hear-
guards and accessories for use with a ing aid, including self-selection and
ER17AU22.013</GPH>
computer, television, or telephone. self-checking the performance of the

OTC hearing aid, and customize it to
19
ER17AU22.012</GPH>
§ 800.30 21 CFR Ch. I (4–1–23 Edition)
the user’s hearing needs, including in- all of the following clearly and perma-
formation about properly fitting nently, except as provided in paragraph
eartips. (c)(3)(iii) of this section:
(C) Use of the OTC hearing aid with (i) The serial number.
any accompanying accessories. (ii) If the battery is removable, a ‘‘+’’
(D) Maintenance and care of the OTC symbol to indicate the positive ter-
hearing aid, including how a lay user minal for battery insertion unless the
can clean, disinfect, and replace parts battery’s physical design prevents in-
or how to seek replacements, as well as serting the battery in the reversed po-
how to store the hearing aid when it sition.
will not be used for an extended period (iii) If the OTC hearing aid is used or
of time. rebuilt, the manufacturer shall phys-
(E) If the battery is replaceable or re- ically attach a removable tag to the
chargeable, how to replace or recharge hearing aid declaring that fact.
the battery, including a generic des- (4) Technical specifications. All of the
ignation of replacement batteries. following technical specifications shall
(F) Expected battery life. appear in the user instructional bro-
(G) Any other information necessary chure that accompanies the device.
for adequate directions for use as de- You may additionally include it on the
fined in § 801.5 of this chapter. outside package:
(viii) Identification of any known (i) The maximum output limit value
physiological side effects associated (Output Sound Pressure Level 90
with the use of the OTC hearing aid (OSPL90)).
that may warrant consultation with a (ii) The full-on gain value, which is
physician, referring to an ear-nose- the gain with a 50 decibel (dB) Sound
throat doctor when preferable, includ- Pressure Level (SPL) pure-tone input
ing if applicable, skin irritation and and volume set to full on.
accelerated accumulation of cerumen (iii) The total harmonic distortion
(ear wax). value.
(ix) The technical specifications re- (iv) The self-generated noise value.
quired by paragraph (c)(4) of this sec- (v) The latency value.
tion. (vi) The upper and lower cutoff fre-
(x) A description of commonly occur- quencies for bandwidth.
ring, avoidable events that could ad- (5) Software device labeling. OTC hear-
versely affect or damage the OTC hearing aid software that is not distributed
ing aid, including but not limited to, as with the hearing aid or amplification
applicable, ear wax buildup, drops, im- platform shall meet all of the following
mersion in water, or exposure to exces- labeling requirements. With respect to
sive heat. the information required under para-
(xi) If the hearing aid incorporates graphs (c)(1) through (4) of this section,
wireless technology in its program- the information must be provided in
ming or use, appropriate warnings, in- the software device labeling, as speci-
structions, and information relating to fied in paragraphs (c)(5)(i) through (v)
electromagnetic compatibility and of this section, rather than the loca-
wireless technology and human expo- tions (e.g., outside package labeling)
sure to non-ionizing radiation. specified in paragraphs (c)(1) through
(xii) Information on how and where (4):
to obtain repair service or replace- (i) Prior to first use of the software
ments, including at least one specific or obtaining payment information for
address where the user can go or send the software, whichever occurs first,
the OTC hearing aid to obtain such re- the labeling must clearly and promi-
pair service or replacements. nently present all of the following to
(xiii) If clinical or non-clinical stud- the prospective user. For each, the la-
ies were conducted by or for the manu- beling must remain visible until the
facturer to support the performance of user dismisses it or proceeds to the
the OTC hearing aid, a summary of all next step:
such studies. (A) Compatibility and minimum op-

(3) Labeling on the device. The labeling erating requirements for the software
on an OTC hearing aid itself shall bear device.
20
(B) Disclosures of any fees or pay- of 111 dB SPL at any frequency except
ments after first use or initial pay- as provided in paragraph (d)(2) of this
ment, including but not limited to any section.
fees or payments relating to subscrip- (2) Output limit for a device with acti-
tions, add-on features, or continued ac- vated input-controlled compression. An
cess to features or services. The disclo- OTC hearing aid that has input-con-
sures must name and briefly describe trolled compression activated shall not
what each fee or payment covers. exceed an output limit of 117 dB SPL at
(C) The information required under any frequency.
paragraphs (c)(1)(i), (iii), and (v) of this (e) Electroacoustic performance limits.
section. An OTC hearing aid shall perform with-
(ii) Prior to first use of the software, in all of the following electroacoustic
the labeling must clearly and promi- limits. Measure each electroacoustic
nently present all of the following to performance characteristic using an
the prospective user: acoustic coupler as described in para-
(A) The information required under graph (e)(6) of this section, where appli-
paragraph (c)(2)(i)(A) of this section, cable:
and it must remain visible until the (1) Output distortion control limits.
user acknowledges it. Test the output distortion of the OTC
(B) The information required under hearing aid as follows to ensure that it
paragraphs (c)(2)(i)(B) and (C), (c)(2)(ii), does not exceed the limit specified in
(iii), and (v), (c)(2)(vii)(B) and (G), and paragraphs (e)(1)(i) through (iii) of this
(c)(2)(viii) and (ix) of this section, and section.
the information must remain visible (i) The total harmonic distortion plus
until the user dismisses it or proceeds noise shall not exceed 5 percent for
to the next step. output levels within one of the fol-
(C) All other information required lowing sets of levels, depending on the
under paragraph (c)(2) of this section, test method:
to the extent applicable, and the infor- (A) Using sine wave-based testing,
mation must remain visible until the measure at 70 dB SPL and 100 dB SPL;
user dismisses it or proceeds to the or
next step. (B) Using a 500-hertz (Hz) one-third-
(iii) The software device labeling octave pulsed-noise signal, measure at
must include the information required 67 dB SPL and 97 dB SPL.
under paragraphs (c)(3)(i) and (c)(4) of (ii) You must measure the total har-
this section. monic distortion using a 500-Hz input
(iv) All of the software device label- tone with an analyzer that has a band-
ing must be accessible for review after width at least as wide as the frequency
acknowledgment, dismissal, or pro- limits of the OTC hearing aid.
ceeding to the next step. (iii) You must measure the output
(v) If there are changes to any of the distortion at the OTC hearing aid’s
labeling required under paragraph maximum volume and the input sound
(c)(5) of this section, the labeling with level to the OTC hearing aid adjusted
the changed information must be pre- to produce the required outputs.
sented to the user until the user dis- (2) Self-generated noise level limits.
misses it. Self-generated noise shall not exceed 32
(d) Output limits. The output limit for dBA. You must disable any methods
an OTC hearing aid shall be the device that artificially lower the apparent
maximum acoustic output sound pres- noise floor for the measurement. Such
sure level (SPL) with an acoustic cou- methods would include but are not lim-
pler as described in paragraph (e)(6) of ited to auto-muting and downward ex-
this section when the device input is a pansion.
90 dB SPL pure-tone, and the gain/vol- (3) Latency. Latency shall not exceed
ume control is full on. An OTC hearing 15 ms. You must measure the latency
aid shall not exceed the following lim- with a method that is accurate and re-
its at any of the frequencies at which peatable to within 1.5 ms.
the device is intended to operate: (4) Frequency response bandwidth. The

(1) General output limit. An OTC hear- lower cutoff frequency shall extend to
ing aid shall not exceed an output limit 250 Hz or below, and the upper cutoff
21
§ 800.30 21 CFR Ch. I (4–1–23 Edition)
frequency shall extend to 5 kHz or (6) Adequate reprocessing. If the OTC

greater. You must measure the fre- hearing aid is used or rebuilt, it must
quency response bandwidth as specified be adequately reprocessed for the next
in the Method for clause 4.1 in ANSI/ user prior to sale.
CTA–2051:2017. (g) Conditions for sale of an OTC hear-
(5) Frequency response smoothness. No ing aid. The sale of an OTC hearing aid
single peak in the one-third-octave fre- is subject to all of the following condi-
quency response shall exceed 12 dB rel- tions:
ative to the average levels of the one- (1) Age minimum. Sale to or for a per-
third-octave bands, two-thirds octave son younger than 18 years of age is pro-
above and below the peak. You must hibited.
measure the frequency response (2) Statement of OTC availability. Sale
smoothness using values for a diffuse of an OTC hearing aid is prohibited un-
field and the corrected one-third-oc- less its labeling bears the statement of
tave frequency insertion response as OTC availability required under para-
specified in the Method for clause 4.1 in graph (c)(1)(iii) of this section.
ANSI/CTA–2051:2017. (h) Effect on State law. Any State or
(6) Acoustic coupler choice. Where ap- local government requirement for an
plicable, use one of the following OTC hearing aid is preempted to the
acoustic couplers to measure following extent:
electroacoustic performance: (1) Preemption. No State or local gov-
(i) When compatible with the device ernment shall establish or continue in
design, a 2-cubic centimeter (cm3) effect any law, regulation, order, or
acoustic coupler; or other requirement specifically related
to hearing products that would restrict
(ii) When a 2-cm3 acoustic coupler is
or interfere with the servicing, mar-
not compatible with the device design,
keting, sale, dispensing, use, customer
an acoustic coupler that is a scientif-
support, or distribution of OTC hearing
ically valid and technically equivalent
aids through in-person transactions, by
alternative. You must document the
mail, or online, that is different from,
rationale for using an alternative
in addition to, or otherwise not iden-
acoustic coupler.
tical to, the regulations promulgated
(f) Design requirements. An OTC hear- under section 709(b) of the FDA Reau-
ing aid must conform to all of the fol- thorization Act of 2017, including any
lowing design requirements: State or local requirement for the su-
(1) Insertion depth. The design of an pervision, prescription, or other order,
OTC hearing aid shall limit the inser- involvement, or intervention of a li-
tion of the most medial component so censed person for consumers to access
that, when inserted, the component is OTC hearing aids.
reasonably expected to remain at least (2) Professional requirements—(i) Gen-
10 millimeters (mm) from the tympanic eral rule. The servicing, marketing,
membrane. sale, dispensing, customer support, or
(2) Use of atraumatic materials. The distribution of OTC hearing aids, or an
material for the eartip of an OTC hear- equivalent activity, whether through
ing aid shall be atraumatic. in-person transactions, by mail, or on-
(3) Proper physical fit. The design of line, shall not cause, require, or other-
an OTC hearing aid shall enable con- wise obligate a person providing such
sumers to readily achieve a safe, cus- services to obtain specialized licensing,
tomized, acoustically favorable, and certification, or any other State or
comfortable physical fit in the ear local sanction unless such requirement
canal and/or external ear. is generally applicable to the sale of
(4) Tools, tests, or software. The OTC any product or to all places of business
hearing aid shall, through tools, tests, regardless of whether they sell OTC
or software, permit a lay user to con- hearing aids. However, although a
trol the device and customize it to the State or local government may not re-
user’s hearing needs. quire the order, involvement, or inter-
(5) User-adjustable volume control. The vention of a licensed person for con-
OTC hearing aid shall have a user-ad- sumers to access OTC hearing aids, a
justable volume control. licensed person may service, market,
22
sell, dispense, provide customer sup- Subpart C—Administrative

port for, or distribute OTC hearing Practices and Procedures
aids.
(ii) Sale of OTC hearing aids is not an § 800.55 Administrative detention.
exemption. The servicing, marketing, (a) General. This section sets forth
sale, dispensing, customer support, or
the procedures for detention of medical
distribution of OTC hearing aids does
devices intended for human use be-
not exempt a person from any State or lieved to be adulterated or misbranded.
local government’s professional or es- Administrative detention is intended
tablishment requirements that are con- to protect the public by preventing dis-
sistent with this section.
tribution or use of devices encountered
(iii) Representations may create profes-
during inspections that may be adul-
sional obligations. A person shall not
terated or misbranded, until the Food
incur specialized obligations by rep-
and Drug Administration (FDA) has
resenting as a servicer, marketer, sell-
had time to consider what action it
er, dispenser, customer support rep-
should take concerning the devices,
resentative, or distributor (or an equiv-
and to initiate legal action, if appro-
alent description) of OTC hearing aids.
priate. Devices that FDA orders de-
However, a person representing as any
tained may not be used, moved, al-
other defined professional or establish-
tered, or tampered with in any manner
ment, or as a State licensed dispenser,
by any person during the detention pe-
is subject to applicable State and local
riod, except as authorized under para-
requirements even if the person under-
graph (h) of this section, until FDA
takes commercial or professional ac-
terminates the detention order under
tivities only in relation to OTC hearing
paragraph (j) of this section, or the de-
aids.
tention period expires, whichever oc-
(3) Private remedies. This section does
curs first.
not modify or otherwise affect the abil-
(b) Criteria for ordering detention. Ad-
ity of any person to exercise a private
ministrative detention of devices may
right of action under any State or Fed-
be ordered in accordance with this sec-
eral product liability, tort, warranty,
tion when an authorized FDA rep-
contract, or consumer protection law.
resentative, during an inspection under
(i) Incorporation by reference. ANSI/
section 704 of the Federal Food, Drug,
CTA–2051, ‘‘Personal Sound Amplifi-
and Cosmetic Act (the act), has reason
cation Performance Criteria,’’ dated
to believe that a device, as defined in
January 2017 (ANSI/CTA–2051:2017), is
section 201(h) of the act, is adulterated
incorporated by reference into this sec-
or misbranded.
tion with the approval of the Director (c) Detention period. The detention is
of the Office of the Federal Register to be for a reasonable period that may
under 5 U.S.C. 552(a) and 1 CFR part 51. not exceed 20 calendar days after the
This material is available for inspec- detention order is issued, unless the
tion at the Food and Drug Administra- FDA Division Director in whose divi-
tion and at the National Archives and sion the devices are located determines
Records Administration (NARA). Con- that a greater period is required to
tact the Dockets Management Staff, seize the devices, to institute injunc-
5630 Fishers Lane, Rm. 1061, Rockville, tion proceedings, or to evaluate the
MD 20852, 240–402–7500. For information need for legal action, in which case the
on the availability of this material at Division Director may authorize deten-
NARA, email: [email protected], or tion for 10 additional calendar days.
go to: www.archives.gov/federal-register/ The additional 10-calendar-day deten-
cfr/ibr-locations.html. The material may tion period may be ordered at the time
be obtained from Consumer Technology the detention order is issued or at any
Association (CTA), Technology & time thereafter. The entire detention
Standards Department, 1919 S Eads period may not exceed 30 calendar
Street, Arlington, VA 22202; phone: 703– days, except when the detention period
907–7600; fax: (703) 907–7693; email: is extended under paragraph (g)(6) of
[email protected], website:
this section. An authorized FDA rep-

www.cta.tech. resentative may, in accordance with
[87 FR 50748, Aug. 17, 2022] paragraph (j) of this section, terminate
23
§ 800.55 21 CFR Ch. I (4–1–23 Edition)
a detention before the expiration of the (e) Approval of detention order. A de-
detention period. tention order, before issuance, shall be
(d) Issuance of detention order. (1) The approved by the FDA Division Director
detention order shall be issued in writ- in whose division the devices are lo-
ing, in the form of a detention notice, cated. If prior written approval is not
signed by the authorized FDA rep- feasible, prior oral approval shall be
resentative who has reason to believe obtained and confirmed by written
that the devices are adulterated or memorandum within FDA as soon as
misbranded, and issued to the owner, possible.
operator, or agent in charge of the (f) Labeling or marking a detained de-
place where the devices are located. If vice. An FDA representative issuing a
the owner or the user of the devices is detention order under paragraph (d) of
different from the owner, operator, or this section shall label or mark the de-
agent in charge of the place where the vices with official FDA tags that in-
devices are detained, a copy of the de- clude the following information:
tention order shall be provided to the (1) A statement that the devices are
owner or user of the devices if the own- detained by the United States Govern-
er’s or user’s identity can be readily ment in accordance with section 304(g)
determined. of the Federal Food, Drug, and Cos-
(2) If detention of devices in a vehicle metic Act (21 U.S.C. 334(g)).
or other carrier is ordered, a copy of (2) A statement that the devices shall
the detention order shall be provided to not be used, moved, altered, or tam-
the shipper of record and the owner of pered with in any manner for the pe-
the vehicle or other carrier, if their riod shown, without the written per-
identities can be readily determined. mission of an authorized FDA rep-
(3) The detention order shall include resentative, except as authorized in
the following information: paragraph (h) of this section.
(i) A statement that the devices iden- (3) A statement that the violation of
tified in the order are detained for the a detention order or the removal or al-
period shown; teration of the tag is punishable by
(ii) A brief, general statement of the fine or imprisonment or both (section
reasons for the detention; 303 of the act, 21 U.S.C. 333).
(iii) The location of the devices; (4) The detention order number, the
(iv) A statement that these devices date and hour of the detention order,
are not to be used, moved, altered, or the detention period, and the name of
tampered with in any manner during the FDA representative who issued the
that period, except as permitted under detention order.
paragraph (h) of this section, without (g) Appeal of a detention order. (1) A
the written permission of an author- person who would be entitled to claim
ized FDA representative; the devices, if seized, may appeal a de-
(v) Identification of the detained detention order. Any appeal shall be sub-
vices; mitted in writing to the FDA Division
(vi) The detention order number; Director in whose division the devices
(vii) The date and hour of the deten- are located within 5 working days of
tion order; receipt of a detention order. If the ap-
(viii) The period of the detention; peal includes a request for an informal
(ix) The text of section 304(g) of the hearing, as defined in section 201(x) of
act and paragraph (g) (1) and (2) of this the act, the appellant shall request ei-
section; ther that a hearing be held within 5
(x) A statement that any informal working days after the appeal is filed
hearing on an appeal of a detention or that the hearing be held at a later
order shall be conducted as a regu- date, which shall not be later than 20
latory hearing under part 16 of this calendar days after receipt of a deten-
chapter, with certain exceptions de- tion order.
scribed in paragraph (g)(3) of this sec- (2) The appellant of a detention order
tion; and shall state the ownership or propri-
(xi) The mailing address, telephone etary interest the appellant has in the
number, and name of the FDA Division detained devices. If the detained de-
Director. vices are located at a place other than
24
an establishment owned or operated by days after the conclusion of the hear-

the appellant, the appellant shall ining. The detention period extends to
clude documents showing that the ap- the date of the decision even if the 5-
pellant would have legitimate author- working-day period for making the de-
ity to claim the devices if seized. cision extends beyond the otherwise
(3) Any informal hearing on an ap- applicable 20-calendar-day or 30-cal-
peal of a detention order shall be con- endar-day detention period.
ducted as a regulatory hearing pursu- (7) If the appellant appeals the deten-
ant to regulation in accordance with tion order but does not request a regu-
part 16 of this chapter, except that: latory hearing, the presiding officer
(i) The detention order under para- shall render a decision on the appeal
graph (d) of this section, rather than affirming or revoking the detention
the notice under § 16.22(a) of this chap- within 5 working days after the filing
ter, provides notice of opportunity for of the appeal.
a hearing under this section and is part (8) If the presiding officer affirms a
of the administrative record of the reg- detention order, the devices continue
ulatory hearing under § 16.80(a) of this to be detained until FDA terminates
chapter. the detention under paragraph (j) of
(ii) A request for a hearing under this this section or the detention period ex-
section should be addressed to the FDA pires, whichever occurs first.
Division Director. (9) If the presiding officer revokes a
(iii) The last sentence of § 16.24(e) of detention order, FDA shall terminate
this chapter, stating that a hearing the detention under paragraph (j) of
may not be required to be held at a this section.
time less than 2 working days after re- (h) Movement of detained devices. (1)
ceipt of the request for a hearing, does Except as provided in this paragraph
not apply to a hearing under this sec- (h), no person shall move detained de-
tion. vices within or from the place where
(iv) Paragraph (g)(4) of this section, they have been ordered detained until
rather than § 16.42(a) of this chapter, FDA terminates the detention under
describes the FDA employees who pre- paragraph (j) of this section or the de-
side at hearings under this section. tention period expires, whichever oc-
(4) The presiding officer of a regu- curs first.
latory hearing on an appeal of a deten- (2) If detained devices are not in final
tion order, who also shall decide the form for shipment, the manufacturer
appeal, shall be an Office of Regulatory may move them within the establish-
Affairs Program Director or another ment where they are detained to com-
FDA official senior to an FDA Division plete the work needed to put them in
Director who is permitted by § 16.42(a) final form. As soon as the devices are
of this chapter to preside over the moved for the purpose of the preceding
hearing. sentence, the individual responsible for
(5) If the appellant requests a regu- their movement shall orally notify the
latory hearing and requests that the FDA representative who issued the de-
hearing be held within 5 working days tention order, or another responsible
after the appeal is filed, the presiding division office official, of the move-
officer shall, within 5 working days, ment of the devices. As soon as the de-
hold the hearing and render a decision vices are put in final form, they shall
affirming or revoking the detention. be segregated from other devices, and
(6) If the appellant requests a regu- the individual responsible for their
latory hearing and requests that the movement shall orally notify the FDA
hearing be held at a date later than representative who issued the deten-
within 5 working days after the appeal tion order, or another responsible divi-
is filed, but not later than 20 calendar sion office official, of their new loca-
days after receipt of a detention order, tion. The devices put in final form
the presiding officer shall hold the shall not be moved further without
hearing at a date agreed upon by FDA FDA approval.
and the appellant. The presiding officer (3) The FDA representative who
shall decide whether to affirm or re- issued the detention order, or another
voke the detention within 5 working responsible division office official, may
25
§ 800.55 21 CFR Ch. I (4–1–23 Edition)
approve, in writing, the movement of under paragraph (d) of this section, the
detained devices for any of the fol- owner, operator, or agent in charge of
lowing purposes: any factory, warehouse, other estab-
(i) To prevent interference with an lishment, or consulting laboratory
establishment’s operations or harm to where detained devices are manufac-
the devices. tured, processed, packed, or held shall
(ii) To destroy the devices. have, or establish, and maintain ade-
(iii) To bring the devices into compli- quate records relating to how the de-
ance. tained devices may have become adul-
(iv) For any other purpose that the terated or misbranded, records on any
FDA representative who issued the de- distribution of the devices before and
tention order, or other responsible divi- after the detention period, records on
sion office official, believes is appro- the correlation of any in-process de-
priate in the case. tained devices that are put in final
(4) If an FDA representative approves
form under paragraph (h) of this sec-
the movement of detained devices
tion to the completed devices, records
under paragraph (h)(3) of this section,
of any changes in, or processing of, the
the detained devices shall remain seg-
regated from other devices and the per- devices permitted under the detention
son responsible for their movement order, and records of any other move-
shall immediately orally notify the of- ment under paragraph (h) of this sec-
ficial who approved the movement of tion. Records required under this para-
the devices, or another responsible graph shall be provided to the FDA on
FDA division office official, of the new request for review and copying. Any
location of the detained devices. FDA request for access to records re-
(5) Unless otherwise permitted by the quired under this paragraph shall be
FDA representative who is notified of, made at a reasonable time, shall state
or who approves, the movement of de- the reason or purpose for the request,
vices under this paragraph, the re- and shall identify to the fullest extent
quired tags shall accompany the de- practicable the information or type of
vices during and after movement and information sought in the records to
shall remain with the devices until which access is requested.
FDA terminates the detention or the (2) Records required under this para-
detention period expires, whichever oc- graph shall be maintained for a max-
curs first. imum period of 2 years after the
(i) Actions involving adulterated or mis- issuance of the detention order or for
branded devices. If FDA determines that such other shorter period as FDA di-
the detained devices, including any rects. When FDA terminates the deten-
that have been put in final form, are tion or when the detention period ex-
adulterated or misbranded, or both, it pires, whichever occurs first, FDA will
may initiate legal action against the advise all persons required under this
devices or the responsible individuals, paragraph to keep records concerning
or both, or request that the devices be that detention whether further record-
destroyed or otherwise brought into
keeping is required for the remainder
compliance with the act under FDA’s
of the 2-year, or shorter, period. FDA
supervision.
ordinarily will not require further rec-
(j) Detention termination. If FDA de-
cides to terminate a detention or when ordkeeping if the agency determines
the detention period expires, whichever that the devices are not adulterated or
occurs first, an FDA representative au- misbranded or that recordkeeping is
thorized to terminate a detention will not necessary to protect the public
issue a detention termination notice health, unless the records are required
releasing the devices to any person who under other regulations in this chapter
received the original detention order or (e.g., the good manufacturing practice
that person’s representative and will regulation in part 820 of this chapter).
remove, or authorize in writing the re- [44 FR 13239, Mar. 9, 1979, as amended at 49
moval of, the required labels or tags. FR 3174, Jan. 26, 1984; 69 FR 17292, Apr. 2,
(k) Recordkeeping requirements. (1) 2004; 79 FR 9412, Feb. 19, 2014; 82 FR 14147,
After issuance of a detention order Mar. 17, 2017; 85 FR 16555, Mar. 25, 2020]
26
§ 800.75 Requests for supervisory re- after the date of the decision involved.
view of certain decisions made by Any such request for supervisory re-
the Center for Devices and Radio- view not received by CDRH within 30
logical Health. days after the date of the decision in-
(a) Definitions. The following defini- volved is not eligible for review. Except
tions shall apply to this section: as provided in paragraph (b)(1)(ii) or
(1) FDA means the Food and Drug (iii) of this section, FDA will render a
Administration. decision within 45 days of the request
(2) 517A decision means a significant for supervisory review.
decision made by the Center for De- (ii) A person requesting supervisory
vices and Radiological Health, as set review under paragraph (b)(1)(i) may
forth in section 517A of the Federal request an in-person meeting or tele-
Food, Drug, and Cosmetic Act, and in- conference with the supervisor review-
cludes one of the following decisions: ing the request for supervisory review.
(i) A substantially equivalent order
Except as provided in paragraph
under § 807.100(a)(1) of this chapter, or a
(b)(1)(iii) of this section, if a request
not substantially equivalent order
for in-person meeting or teleconference
under § 807.100(a)(2) of this chapter;
(ii) An approval order under § 814.44(d) is included in the request for super-
of this chapter, an approvable letter visory review to CDRH, CDRH will
under § 814.44(e) of this chapter, a not schedule the meeting or teleconference
approvable letter under § 814.44(f) of to occur within 30 days of receipt of the
this chapter, or an order denying ap- request. Except as provided in para-
proval under § 814.45 of this chapter; graph (b)(1)(iii) of this section, a deci-
(iii) An approval order under sion will be rendered within 30 days of
§ 814.116(b) of this chapter, an approv- such meeting or teleconference.
able letter under § 814.116(c) of this (iii) The timeframes for CDRH to
chapter, a not approvable letter under render a decision provided in (b)(1)(i)
§ 814.116(d) of this chapter, or an order and (ii) of this section, and the time-
denying approval under § 814.118 of this frame to schedule an in-person meeting
chapter; or teleconference review in (b)(1)(ii) of
(iv) A grant or denial of a request for this section, do not apply if a matter
breakthrough device designation under related to the 517A decision under re-
section 515B of the Federal Food, Drug, view is referred by CDRH to external
and Cosmetic Act; experts, such as an advisory com-
(v) An approval order under § 812.30(a) mittee, as provided in § 10.75(b) of this
of this chapter or a disapproval order chapter.
under § 812.30(c) of this chapter; (2) Supervisory review. An initial or
(vi) A failure to reach agreement let- sequential request for supervisory re-
ter under section 520(g)(7) of the Fed- view within CDRH under § 10.75 of this
eral Food, Drug, and Cosmetic Act; or
chapter of a decision other than a 517A
(vii) A clinical hold determination
decision that is not received by CDRH
under section 520(g)(8) of the Federal
within 60 days after the date of the de-
Food, Drug, and Cosmetic Act.
(3) CDRH means the Center for De- cision involved will be denied as un-
vices and Radiological Health. timely, unless CDRH, for good cause,
(b) Submission of request—(1) Review of permits the request to be filed after 60
517A decisions. (i) An initial or sequen- days. An initial or sequential request
tial request for supervisory review for supervisory review within CDRH of
within CDRH of a 517A decision under a decision other than a 517A decision
§ 10.75 of this chapter must be addressed must be addressed to the next organi-
to the next organizational level or zational level or higher above the indi-
higher above the individual who made vidual who made the decision; sub-
the decision; submitted in electronic mitted in electronic format in accord-
format in accordance with section ance with section 745A(b) of the Fed-
745A(b) of the Federal Food, Drug, and eral Food, Drug, and Cosmetic Act,
Cosmetic Act; marked ‘‘Appeal: Re- when applicable; marked, ‘‘Appeal: Re-
quest for Supervisory Review’’; and request for Supervisory Review’’ in the
ceived by CDRH no later than 30 days subject line of the electronic request;
27
Pt. 801 21 CFR Ch. I (4–1–23 Edition)
and sent to the CDRH Ombudsman at 801.119 In vitro diagnostic products.

[email protected]. 801.122 Medical devices for processing, re-
packing, or manufacturing.
[84 FR 31477, July 2, 2019] 801.125 Medical devices for use in teaching,
law enforcement, research, and analysis.
PART 801—LABELING 801.127 Medical devices; expiration of ex-
emptions.
801.128 Exceptions or alternatives to label-
Subpart A—General Labeling Provisions ing requirements for medical devices
Sec. held by the Strategic National Stockpile.
801.1 Medical devices; name and place of
business of manufacturer, packer or dis- Subpart E—Other Exemptions
tributor.
801.150 Medical devices; processing, label-
801.3 Definitions.
ing, or repacking.
801.4 Meaning of intended uses.
801.5 Medical devices; adequate directions
for use. Subparts F–G [Reserved]
801.6 Medical devices; misleading state-
ments. Subpart H—Special Requirements for
801.15 Medical devices; prominence of re- Specific Devices
quired label statements.
801.405 Labeling of articles intended for lay
801.16 Medical devices; Spanish-language
use in the repairing and/or refitting of
version of certain required statements.
dentures.
801.18 Format of dates provided on a med-
801.410 Use of impact-resistant lenses in
ical device label.
eyeglasses and sunglasses.
Subpart B—Labeling Requirements for 801.415 Maximum acceptable level of ozone.
800.417 Chlorofluorocarbon propellants.
Unique Device Identification 801.422 Prescription hearing aid labeling.
801.20 Label to bear a unique device identi- 801.430 User labeling for menstrual tam-
fier. pons.
801.30 General exceptions from the require- 801.433 Warning statements for prescription
ment for the label of a device to bear a and restricted device products containing
unique device identifier. or manufactured with
801.35 Voluntary labeling of a device with a chlorofluorocarbons or other ozone-de-
unique device identifier. pleting substances.
801.40 Form of a unique device identifier. 801.435 User labeling for latex condoms.
801.45 Devices that must be directly marked 801.437 User labeling for devices that con-
with a unique device identifier. tain natural rubber.
801.50 Labeling requirements for stand- AUTHORITY: 21 U.S.C. 321, 331–334, 351, 352,
alone software. 360d, 360i, 360j, 371, 374.
801.55 Request for an exception from or al-
ternative to a unique device identifier re- SOURCE: 41 FR 6896, Feb. 13, 1976, unless
quirement. otherwise noted.
801.57 Discontinuation of legacy FDA iden-
tification numbers assigned to devices. Subpart A—General Labeling
Subpart C—Labeling Requirements for Provisions
Over-the-Counter Devices
§ 801.1 Medical devices; name and
801.60 Principal display panel. place of business of manufacturer,
801.61 Statement of identity. packer or distributor.
801.62 Declaration of net quantity of con- (a) The label of a device in package
tents. form shall specify conspicuously the
801.63 Medical devices; warning statements
for devices containing or manufactured name and place of business of the man-
with chlorofluorocarbons and other class ufacturer, packer, or distributor.
I ozone-depleting substances. (b) The requirement for declaration
of the name of the manufacturer, pack-
Subpart D—Exemptions From Adequate er, or distributor shall be deemed to be
Directions for Use satisfied, in the case of a corporation,
only by the actual corporate name
801.109 Prescription devices.
801.110 Retail exemption for prescription de- which may be preceded or followed by
vices. the name of the particular division of

801.116 Medical devices having commonly the corporation. Abbreviations for
known directions. ‘‘Company,’’ ‘‘Incorporated,’’ etc., may
28
be used and ‘‘The’’ may be omitted. In Device package means a package that
the case of an individual, partnership, contains a fixed quantity of a par-
or association, the name under which ticular version or model of a device.
the business is conducted shall be used. Expiration date means the date by
(c) Where a device is not manufac- which the label of a device states the
tured by the person whose name ap- device must or should be used.
pears on the label, the name shall be FDA, we, or us means the Food and
qualified by a phrase that reveals the Drug Administration.
connection such person has with such Finished device means any device or
device; such as, ‘‘Manufactured for accessory to any device that is suitable
___’’, ‘‘Distributed by _____’’, or any for use or capable of functioning.
other wording that expresses the facts. Global Unique Device Identification
(d) The statement of the place of Database (GUDID) means the database
business shall include the street ad- that serves as a repository of informa-
dress, city, State, and Zip Code; how- tion to facilitate the identification of
ever, the street address may be omitted medical devices through their distribu-
if it is shown in a current city direction and use.
tory or telephone directory. The re- Human cells, tissues, or cellular or tis-
quirement for inclusion of the ZIP sue-based product (HCT/P) regulated as a
Code shall apply only to consumer device means an HCT/P as defined in
commodity labels developed or revised § 1271.3(d) of this chapter that does not
after the effective date of this section. meet the criteria in § 1271.10(a) and that
In the case of nonconsumer packages, is also regulated as a device.
the ZIP Code shall appear on either the Implantable device means a device
label or the labeling (including the in- that is intended to be placed in a sur-
voice). gically or naturally formed cavity of
(e) If a person manufactures, packs, the human body. A device is regarded
or distributes a device at a place other as an implantable device for the purpose
than his principal place of business, the of this part only if it is intended to re-
label may state the principal place of main implanted continuously for a pe-
business in lieu of the actual place riod of 30 days or more, unless the
where such device was manufactured or Commissioner of Food and Drugs deter-
packed or is to be distributed, unless mines otherwise in order to protect
human health.
such statement would be misleading.
Label has the meaning set forth in
§ 801.3 Definitions. section 201(k) of the Federal Food,
Drug, and Cosmetic Act.
As used in this part: Labeler means:
Automatic identification and data cap- (1) Any person who causes a label to
ture (AIDC) means any technology that be applied to a device with the intent
conveys the unique device identifier or that the device will be commercially
the device identifier of a device in a distributed without any intended sub-
form that can be entered into an elec- sequent replacement or modification of
tronic patient record or other com- the label; and
puter system via an automated proc- (2) Any person who causes the label
ess. of a device to be replaced or modified
Center Director means the Director of with the intent that the device will be
the Center for Devices and Radio- commercially distributed without any
logical Health or the Director of the subsequent replacement or modifica-
Center for Biologics Evaluation and tion of the label, except that the addi-
Research, depending on which Center tion of the name of, and contact infor-
has been assigned lead responsibility mation for, a person who distributes
for the device. the device, without making any other
Combination product has the meaning changes to the label, is not a modifica-
set forth in § 3.2(e) of this chapter. tion for the purposes of determining
Convenience kit means two or more whether a person is a labeler.

different medical devices packaged to- Lot or batch means one finished device
gether for the convenience of the user. or more that consist of a single type,
29
§ 801.4 21 CFR Ch. I (4–1–23 Edition)
model, class, size, composition, or soft- cumstances surrounding the distribu-

ware version that are manufactured tion of the article. This objective in-
under essentially the same conditions tent may, for example, be shown by la-
and that are intended to have uniform beling claims, advertising matter, or
characteristics and quality within oral or written statements by such per-
specified limits. sons or their representatives. Objective
Shipping container means a container intent may be shown, for example, by
used during the shipment or transpor- circumstances in which the article is,
tation of devices, and whose contents with the knowledge of such persons or
may vary from one shipment to an- their representatives, offered or used
other. for a purpose for which it is neither la-
Specification means any requirement beled nor advertised; provided, how-
with which a device must conform. ever, that a firm would not be regarded
Unique device identifier (UDI) means as intending an unapproved new use for
an identifier that adequately identifies a device approved, cleared, granted
a device through its distribution and marketing authorization, or exempted
use by meeting the requirements of from premarket notification based
§ 830.20 of this chapter. A unique device solely on that firm’s knowledge that
identifier is composed of: such device was being prescribed or
(1) A device identifier—a mandatory, used by health care providers for such
fixed portion of a UDI that identifies use. The intended uses of an article
the specific version or model of a de- may change after it has been intro-
vice and the labeler of that device; and duced into interstate commerce by its
(2) A production identifier—a condi- manufacturer. If, for example, a pack-
tional, variable portion of a UDI that er, distributor, or seller intends an ar-
identifies one or more of the following ticle for different uses than those in-
when included on the label of the de- tended by the person from whom he or
vice: she received the article, such packer,
(i) The lot or batch within which a distributor, or seller is required to sup-
device was manufactured; ply adequate labeling in accordance
(ii) The serial number of a specific with the new intended uses.
device;
[86 FR 41401, Aug. 2, 2021]
(iii) The expiration date of a specific
device; EFFECTIVE DATE NOTE: At 82 FR 2217, Jan.
(iv) The date a specific device was 9, 2017, § 801.4 was revised, effective Feb. 8,
2017. At 82 FR 9501, Feb. 7, 2017, this amend-
manufactured;
ment was delayed until Mar. 21, 2017. At 82
(v) For an HCT/P regulated as a de- FR 14319, Mar. 20, 2017, this amendment was
vice, the distinct identification code further delayed until Mar. 19, 2018. At 83 FR
required by § 1271.290(c) of this chapter. 11639, Mar. 16, 2018 this amendment was de-
Universal product code (UPC) means layed indefinitely. For the convenience of
the product identifier used to identify the user, the revised text is set forth as fol-
an item sold at retail in the United lows:
States. § 801.4 Meaning of intended uses.
Version or model means all devices The words intended uses or words of similar
that have specifications, performance, import in §§ 801.5, 801.119, 801.122, and 1100.5 of
size, and composition, within limits set this chapter refer to the objective intent of
by the labeler. the persons legally responsible for the label-
ing of devices. The intent is determined by
[78 FR 58817, Sept. 24, 2013]
such persons’ expressions or may be shown
by the circumstances surrounding the dis-
§ 801.4 Meaning of intended uses. tribution of the article. This objective intent
The words intended uses or words of may, for example, be shown by labeling
similar import in §§ 801.5, 801.119, claims, advertising matter, or oral or writ-
801.122, and 1100.5 of this chapter refer ten statements by such persons or their rep-
to the objective intent of the persons resentatives. It may be shown, for example,
by circumstances in which the article is,
legally responsible for the labeling of
with the knowledge of such persons or their
an article (or their representatives). representatives, offered and used for a pur-
The intent may be shown by such per- pose for which it is neither labeled nor ad-
sons’ expressions, the design or com- vertised. The intended uses of an article may
position of the article, or by the cir- change after it has been introduced into
30
interstate commerce by its manufacturer. If, (f) Route or method of administra-
for example, a packer, distributor, or seller tion or application.
intends an article for different uses than
those intended by the person from whom he
(g) Preparation for use, i.e., adjust-
received the device, such packer, distributor, ment of temperature, or other manipu-
or seller is required to supply adequate label- lation or process.
ing in accordance with the new intended
uses. And if the totality of the evidence es- § 801.6 Medical devices; misleading
tablishes that a manufacturer objectively in- statements.
tends that a device introduced into inter-
state commerce by him is to be used for con- Among representations in the label-
ditions, purposes, or uses other than ones for ing of a device which render such de-
which it has been approved, cleared, granted vice misbranded is a false or mis-
marketing authorization, or is exempt from leading representation with respect to
premarket notification requirements (if another device or a drug or food or cos-
any), he is required, in accordance with sec- metic.
tion 502(f) of the Federal Food, Drug, and
Cosmetic Act, or, as applicable, duly promul-
§ 801.15 Medical devices; prominence
gated regulations exempting the device from
the requirements of section 502(f)(1), to pro-
of required label statements; use of
vide for such device adequate labeling that
symbols in labeling.
accords with such other intended uses. (a) A word, statement, or other infor-
mation required by or under authority
§ 801.5 Medical devices; adequate di- of the act to appear on the label may
rections for use.
lack that prominence and conspicuous-
Adequate directions for use means di- ness required by section 502(c) of the
rections under which the layman can act by reason, among other reasons, of:
use a device safely and for the purposes (1) The failure of such word, state-
for which it is intended. Section 801.4 ment, or information to appear on the
defines intended use. Directions for use part or panel of the label which is pre-
may be inadequate because, among sented or displayed under customary
other reasons, of omission, in whole or conditions of purchase;
in part, or incorrect specification of:
(2) The failure of such word, state-
(a) Statements of all conditions, pur-
ment, or information to appear on two
poses, or uses for which such device is
or more parts or panels of the label,
intended, including conditions, pur-
each of which has sufficient space
poses, or uses for which it is prescribed,
therefor, and each of which is so de-
recommended, or suggested in its oral,
signed as to render it likely to be,
written, printed, or graphic adver-
tising, and conditions, purposes, or under customary conditions of pur-
uses for which the device is commonly chase, the part or panel displayed;
used; except that such statements shall (3) The failure of the label to extend
not refer to conditions, uses, or pur- over the area of the container or pack-
poses for which the device can be safely age available for such extension, so as
used only under the supervision of a to provide sufficient label space for the
practitioner licensed by law and for prominent placing of such word, state-
which it is advertised solely to such ment, or information;
practitioner. (4) Insufficiency of label space for the
(b) Quantity of dose, including usual prominent placing of such word, state-
quantities for each of the uses for ment, or information, resulting from
which it is intended and usual quan- the use of label space for any word,
tities for persons of different ages and statement, design, or device which is
different physical conditions. not required by or under authority of
(c) Frequency of administration or the act to appear on the label;
application. (5) Insufficiency of label space for the
(d) Duration of administration or ap- placing of such word, statement, or in-
plication. formation, resulting from the use of
(e) Time of administration or appli- label space to give materially greater
cation, in relation to time of meals, conspicuousness to any other word,

time of onset of symptoms, or other statement, or information, or to any
time factors. design or device; or
31
§ 801.15 21 CFR Ch. I (4–1–23 Edition)
(6) Smallness or style of type in in the case of articles distributed sole-

which such word, statement, or infor- ly in Puerto Rico or in a Territory
mation appears, insufficient back- where the predominant language is one
ground contrast, obscuring designs or other than English, the predominant
vignettes, or crowding with other writ- language may be used;
ten, printed, or graphic matter. (E) A symbol not accompanied by ad-
(b) No exemption depending on insuf- jacent explanatory text that:
ficiency of label space, as prescribed in (1) Is established in a standard devel-
regulations promulgated under section oped by a standards development orga-
502(b) of the act, shall apply if such in- nization (SDO);
sufficiency is caused by: (2) Is not contained in a standard
(1) The use of label space for any that is recognized by FDA under its au-
word, statement, design, or device thority in section 514(c) of the act or is
which is not required by or under au- contained in a standard that is recog-
thority of the act to appear on the nized by FDA but is not used according
label; to the specifications for use of the sym-
(2) The use of label space to give bol set forth in FDA’s section 514(c)
greater conspicuousness to any word, recognition;
statement, or other information than (3) Is determined by the manufac-
is required by section 502(c) of the act; turer to be likely to be read and under-
or stood by the ordinary individual under
(3) The use of label space for any rep- customary conditions of purchase and
resentation in a foreign language. use in compliance with section 502(c) of
(c)(1)(i) All words, statements, and the act;
other information required by or under (4) Is used according to the specifica-
authority of the act to appear on the tions for use of the symbol set forth in
label or labeling for a device shall ap- the SDO-developed standard; and
pear thereon in one or more of the fol- (5) Is explained in a paper or elec-
lowing formats: tronic symbols glossary that is in-
(A) The English language; cluded in the labeling for the device
(B) In the case of articles distributed and the labeling on or within the pack-
solely in Puerto Rico or in a Territory age containing the device bears a
where the predominant language is one prominent and conspicuous statement
other than English, the predominant identifying the location of the symbols
language may be substituted for glossary that is written in English or,
English; in the case of articles distributed sole-
(C) A symbol accompanied by adja- ly in Puerto Rico or in a Territory
cent explanatory English text, or text where the predominant language is one
in the predominant language of the other than English, the predominant
Territory, in the case of articles dis- language may be used;
tributed solely in Puerto Rico or in a (F) The symbol statement ‘‘Rx only’’
Territory where the predominant lan- or ‘‘) only’’ may be used as provided
guage is one other than English; under § 801.109(b)(1).
(D) A symbol not accompanied by ad- (ii) The use of symbols in device la-
jacent explanatory text that: beling which do not meet the require-
(1) Is contained in a standard that ments of paragraph (c)(1)(i) of this sec-
FDA recognizes under its authority in tion renders a device misbranded under
section 514(c) of the act; section 502(c) of the act.
(2) Is used according to the specifica- (iii) For purposes of paragraph
tions for use of the symbol set forth in (c)(1)(i) of this section:
FDA’s section 514(c) recognition; and (A) An SDO is an organization that is
(3) Is explained in a paper or elec- nationally or internationally recog-
tronic symbols glossary that is in- nized and that follows a process for
cluded in the labeling for the device standard development that is trans-
and the labeling on or within the pack- parent, (i.e., open to public scrutiny),
age containing the device bears a where the participation is balanced,
prominent and conspicuous statement where an appeals process is included,

identifying the location of the symbols where the standard is not in conflict
glossary that is written in English or, with any statute, regulation, or policy
32
under which FDA operates, and where two digits; followed by the day, using
the standard is national or inter- two digits; each separated by hyphens.
national in scope. For example, January 2, 2014, must be
(B) The term ‘‘symbols glossary’’ presented as 2014–01–02.
means a compiled listing of: (b) Exceptions. (1) A combination
(1) Each SDO-established symbol product that properly bears a National
used in the labeling for the device; Drug Code (NDC) number is not subject
(2) The title and designation number to the requirements of paragraph (a) of
of the SDO-developed standard con- this section.
taining the symbol; (2) If the device is an electronic prod-
(3) The title of the symbol and its ref- uct to which a standard is applicable
erence number, if any, in the standard; under subchapter J of this chapter, Ra-
and diological Health, the date of manufac-
(4) The meaning or explanatory text ture shall be presented as required by
for the symbol as provided in the FDA § 1010.3(a)(2)(ii) of this chapter.
recognition or, if FDA has not recog-
nized the standard or portion of the [78 FR 58818, Sept. 24, 2013]
standard in which the symbol is lo-
cated or the symbol is not used accord- Subpart B—Labeling Requirements
ing to the specifications for use of the for Unique Device Identification
symbol set forth in FDA’s section
514(c) recognition, the explanatory text § 801.20 Label to bear a unique device
as provided in the standard. identifier.
(2) If the label contains any represen- (a) In general. (1) The label of every
tation in a foreign language, all words, medical device shall bear a unique de-
statements, and other information re- vice identifier (UDI) that meets the re-
quired by or under authority of the act quirements of this subpart and part 830
to appear on the label shall appear of this chapter.
thereon in the foreign language.
(2) Every device package shall bear a
(3) If the labeling contains any rep-
UDI that meets the requirements of
resentation in a foreign language, all
this subpart and part 830 of this chap-
words, statements, and other informa-
ter.
tion required by or under authority of
the act to appear on the label or label- (b) Exceptions. Exceptions to the gen-
ing shall appear on the labeling in the eral rule of paragraph (a) of this sec-
foreign language. tion are provided by §§ 801.30, 801.45, and
801.128(f)(2), and § 801.55 provides a
[41 FR 6896, Feb. 13, 1976, as amended at 81 means to request an exception or alter-
FR 38930, June 15, 2016] native not provided by those provi-
sions.
§ 801.16 Medical devices; Spanish-lan-
guage version of certain required [78 FR 58818, Sept. 24, 2013]
statements.
If devices restricted to prescription § 801.30 General exceptions from the
use only are labeled solely in Spanish requirement for the label of a de-
for distribution in the Commonwealth vice to bear a unique device identi-
fier.
of Puerto Rico where Spanish is the
predominant language, such labeling is (a) In general. The following types of
authorized under § 801.15(c). devices are excepted from the require-
ment of § 801.20; a device within one or
§ 801.18 Format of dates provided on a more of the following exceptions is not
medical device label. required to bear a unique device identi-
(a) In general. Whenever the label of a fier (UDI):
medical device includes a printed expi- (1) A finished device manufactured
ration date, date of manufacture, or and labeled prior to the compliance
any other date intended to be brought date established by FDA for § 801.20 re-
to the attention of the user of the de- garding the device. This exception ex-
vice, the date must be presented in the pires with regard to a particular device
following format: The year, using four 3 years after the compliance date es-
digits; followed by the month, using tablished by FDA for the device.
33
§ 801.35 21 CFR Ch. I (4–1–23 Edition)
(2) A class I device that FDA has by (2) A device constituent of such a
regulation exempted from the good combination product whose compo-
manufacturing practice requirements nents are physically, chemically, or
of part 820 of this chapter, exclusive of otherwise combined or mixed and pro-
any continuing requirement for record- duced as a single entity as described by
keeping under §§ 820.180 and 820.198. § 3.2(e)(1) of this chapter is not subject
(3) Individual single-use devices, all to the requirements of § 801.20.
of a single version or model, that are (3) Each device constituent of such a
distributed together in a single device combination product, other than one
package, intended to be stored in that described by § 3.2(e)(1) of this chapter,
device package until removed for use, must bear a UDI on its label unless
and which are not intended for indi- paragraph (a)(11) of this section ap-
vidual commercial distribution. This plies.
exception is not available for any (c) Exception for shipping containers.
implantable device. The device package This rule does not require a UDI to be
containing these individual devices is placed on any shipping container.
not excepted from the requirement of (d) The UDI of a class I device is not
§ 801.20, and must bear a UDI. required to include a production identi-
(4) A device used solely for research, fier.
teaching, or chemical analysis, and not
intended for any clinical use. [78 FR 58818, Sept. 24, 2013]
(5) A custom device within the mean-
ing of § 812.3(b) of this chapter. § 801.35 Voluntary labeling of a device
with a unique device identifier.
(6) An investigational device within
the meaning of part 812 of this chapter. (a) The labeler of a device that is not
(7) A veterinary medical device not required to bear a unique device identi-
intended for use in the diagnosis of dis- fier (UDI) may voluntarily comply with
ease or other conditions in man, in the § 801.20. If a labeler voluntarily includes
cure, mitigation, treatment, or preven- a UDI for a device, the labeler may vol-
tion of disease in man, or intended to untarily provide information con-
affect the structure or any function of cerning the device under subpart E of
the body of man. part 830 of this chapter.
(8) A device intended for export from (b) A device may bear both a Uni-
the United States. versal Product Code (UPC) and a UDI
(9) A device held by the Strategic Na- on its label and packages.
tional Stockpile and granted an excep-
[78 FR 58818, Sept. 24, 2013]
tion or alternative under § 801.128(f)(2).
(10) A device for which FDA has es-
§ 801.40 Form of a unique device iden-
tablished a performance standard tifier.
under section 514(b) of the Federal
Food, Drug, and Cosmetic Act and has (a) Every unique device identifier
provided therein an exception from the (UDI) must meet the technical require-
requirement of § 801.20, or for which ments of § 830.20 of this chapter. The
FDA has recognized all or part of a per- UDI must be presented in two forms:
formance standard under section 514(c) (1) Easily readable plain-text, and
of the Federal Food, Drug, and Cos- (2) Automatic identification and data
metic Act and has included an excep- capture (AIDC) technology.
tion from the requirement of § 801.20 (b) The UDI must include a device
within the scope of that recognition. identifier segment. Whenever a device
(11) A device packaged within the im- label includes a lot or batch number, a
mediate container of a combination serial number, a manufacturing date,
product or convenience kit, provided an expiration date, or for a human cell,
that the label of the combination prod- tissue, or cellular or tissue-based prod-
uct or convenience kit bears a UDI. uct (HCT/P) regulated as a device, a
(b) National Drug Code (NDC) Numbers. distinct identification code as required
If a combination product properly by § 1271.290(c) of this chapter, the UDI
bears an NDC number on its label— must include a production identifier

(1) The combination product is not segment that conveys such informa-
subject to the requirements of § 801.20. tion.
34
(c) If the AIDC technology is not evi- (e) Exception to be noted in design his-
dent upon visual examination of the tory file. A labeler that decides to make
label or device package, the label or de- use of an exception under paragraph (d
vice package must disclose the pres- of this section) must document the
ence of AIDC technology. basis of that decision in the design his-
(d) A class I device that bears a Uni- tory file required by § 820.30(j) of this
versal Product Code (UPC) on its label chapter.
and device packages is deemed to meet
[78 FR 58818, Sept. 24, 2013]
all requirements of subpart B of this
part. The UPC will serve as the unique § 801.50 Labeling requirements for
device identifier required by § 801.20. stand-alone software.
[78 FR 58818, Sept. 24, 2013] (a) Stand-alone software that is not
distributed in packaged form (e.g.,
§ 801.45 Devices that must be directly
marked with a unique device iden- when downloaded from a Web site) is
tifier. deemed to meet the UDI labeling re-
quirements of this subpart if it com-
(a) In general. A device that must plies with the requirements of para-
bear a unique device identifier (UDI) on graph (b) of this section and conveys
its label must also bear a permanent the version number in its production
marking providing the UDI on the de- identifier.
vice itself if the device is intended to (b) Regardless of whether it is or is
be used more than once and intended to not distributed in packaged form,
be reprocessed before each use. stand-alone software regulated as a
(b) UDI for direct marking. The UDI medical device must provide its unique
provided through a direct marking on a device identifier through either or both
device may be: of the following:
(1) Identical to the UDI that appears
(1) An easily readable plain-text
on the label of the device, or
statement displayed whenever the soft-
(2) A different UDI used to distin- ware is started;
guish the unpackaged device from any
(2) An easily readable plain-text
device package containing the device.
statement displayed through a menu
(c) Form of a UDI when provided as a command (e.g., an ‘‘About * * *’’ com-
direct marking. When a device must bear mand).
a UDI as a direct marking, the UDI
(c) Stand-alone software that is dis-
may be provided through either or both
tributed in both packaged form and in
of the following:
a form that is not packaged (e.g., when
(1) Easily readable plain-text;
downloaded from a Web site) may be
(2) Automatic identification and data identified with the same device identi-
capture (AIDC) technology, or any al- fier.
ternative technology, that will provide
the UDI of the device on demand. [78 FR 58818, Sept. 24, 2013]
(d) Exceptions. The requirement of
paragraph (a) of this section shall not § 801.55 Request for an exception from
apply to any device that meets any of or alternative to a unique device
the following criteria: identifier requirement.
(1) Any type of direct marking would (a) A labeler may submit a request
interfere with the safety or effective- for an exception from or alternative to
ness of the device; the requirement of § 801.20 or any other
(2) The device cannot be directly requirement of this subpart for a speci-
marked because it is not techno- fied device or a specified type of device.
logically feasible; A written request for an exception or
(3) The device is a single-use device alternative must:
and is subjected to additional proc- (1) Identify the device or devices that
essing and manufacturing for the pur- would be subject to the exception or al-
pose of an additional single use. ternative;
(4) The device has been previously (2) Identify the provisions of this sub-
marked under paragraph (a) of this sec- part that are the subject of the request
tion. for an exception or alternative;
35
§ 801.57 21 CFR Ch. I (4–1–23 Edition)
(3) If requesting an exception, explain fication of the device through its dis-
why you believe the requirements of tribution and use. Any labeler may
this subpart are not technologically make use of an exception or alter-
feasible; native granted under this section, pro-
(4) If requesting an alternative, de- vided that such use satisfies all safe-
scribe the alternative and explain why guards or conditions that are part of
it would provide for more accurate, the exception or alternative.
precise, or rapid device identification (d) FDA may initiate and grant an
than the requirements of this subpart exception or alternative if we deter-
or how the alternative would better en- mine that the exception or alternative
sure the safety or effectiveness of the is in the best interest of the public
device that would be subject to the al- health. Any such exception or alter-
ternative;
native will remain in effect only so
(5) Provide, if known, the number of
long as there remains a public health
labelers and the number of devices that
need for the exception or alternative.
would be affected if we grant the re-
quested exception or alternative; and (e) The Center Director may rescind
(6) Provide other requested informa- an exception or alternative granted
tion that the Center Director needs to under this section if, after providing an
clarify the scope and effects of the re- opportunity for an informal hearing as
quested exception or alternative. defined in section 201(x) of the Federal
(b) A written request for an exception Food, Drug, and Cosmetic Act and
or alternative must be submitted by under part 16 of this chapter, the Cen-
sending it: ter Director determines that the excep-
(1) If the device is regulated by the tion or alternative no longer satisfies
Center for Biologics Evaluation and the criteria described in this paragraph
Research (CBER), by email to: (e) or that any safeguard or condition
[email protected] or by cor- required under this paragraph (e) has
respondence to: Food and Drug Admin- not been met.
istration, Center for Biologics Evalua-
[78 FR 58818, Sept. 24, 2013, as amended at 80
tion and Research, Document Control FR 18093, Apr. 3, 2015; 81 FR 11428, Mar. 4,
Center, 10903 New Hampshire Ave., 2016; 85 FR 18441, Apr. 2, 2020]
Bldg. 71, Rm. G112, Silver Spring, MD
20993. § 801.57 Discontinuation of legacy FDA
(2) In all other cases, by email to: identification numbers assigned to
[email protected], or by cor- devices.
respondence to: UDI Regulatory Policy (a) On the date your device must bear
Support, Center for Devices and Radio- a unique device identifier (UDI) on its
logical Health, Food and Drug Admin- label, any National Health-Related
istration, 10903 New Hampshire Ave.,
Item Code (NHRIC) or National Drug
Bldg. 32, Rm. 3293, Silver Spring, MD
Code (NDC) number assigned to that
20993–0002.
device is rescinded, and you may no
(c) The Center Director may grant an
longer provide an NHRIC or NDC num-
exception or alternative, either in re-
ber on the label of your device or on
sponse to a request or on his or her own
initiative, if the Center Director deter- any device package.
mines that an exception is appropriate (b) If your device is not required to
because the requirements of this sub- bear a UDI on its label, any NHRIC or
part are not technologically feasible, NDC number assigned to that device is
or that an alternative would provide rescinded as of September 24, 2018, and
for more accurate, precise, or rapid de- beginning on that date, you may no
vice identification than the require- longer provide an NHRIC or NDC num-
ments of this subpart or would better ber of the label of your device or on
ensure the safety or effectiveness of any device package.
the device that would be subject to the (c) A labeler who has been assigned
alternative. If we grant an exception or an FDA labeler code to facilitate use of
alternative, we may include any safe- NHRIC or NDC numbers may continue
guards or conditions deemed appro- to use that labeler code under a system
priate to ensure the adequate identi- for the issuance of UDIs, provided that—
36
(1) Such use is consistent with the tents for all packages of substantially
framework of the issuing agency that the same size, the term area of the prin-
operates that system; and cipal display panel means the area of
(2) No later than September 24, 2014, the side or surface that bears the prin-
the labeler submits, and obtains FDA cipal display panel, which area shall
approval of, a request for continued use be:
of the assigned labeler code. A request (a) In the case of a rectangular pack-
for continued use of an assigned labeler age where one entire side properly can
code must be submitted by email to: be considered to be the principal dis-
[email protected], or by cor- play panel side, the product of the
respondence to: UDI Regulatory Policy height times the width of that side;
Support, Center for Devices and Radio- (b) In the case of a cylindrical or
logical Health, Food and Drug Admin- nearly cylindrical container, 40 percent
istration, 10903 New Hampshire Ave., of the product of the height of the con-
Bldg. 32, Rm. 3293, Silver Spring, MD tainer times the circumference; and
20993–0002.
(c) In the case of any other shape of
(d) Each request for continued use of
container, 40 percent of the total sur-
an assigned labeler code must provide—
face of the container: Provided, how-
(1) The name, mailing address, email
ever, That where such container pre-
address, and phone number of the label-
sents an obvious ‘‘principal display
er who is currently using the labeler
panel’’ such as the top of a triangular
code;
or circular package, the area shall con-
(2) The owner/operator account iden-
tification used by the labeler to submit sist of the entire top surface.
registration and listing information In determining the area of the prin-
using FDA’s Unified Registration and cipal display panel, exclude tops, bot-
Listing System (FURLS). toms, flanges at the tops and bottoms
(3) The FDA labeler code that the la- of cans, and shoulders and necks of bot-
beler wants to continue using. tles or jars. In the case of cylindrical
or nearly cylindrical containers, infor-
FR 11428, Mar. 4, 2016; 85 FR 18441, Apr. 2, mation required by this part to appear
2020] on the principal display panel shall ap-
pear within that 40 percent of the cir-
Subpart C—Labeling Require- cumference which is most likely to be
displayed, presented, shown, or exam-
ments for Over-the-Counter ined under customary conditions of dis-
Devices play for retail sale.
§ 801.60 Principal display panel.
§ 801.61 Statement of identity.
The term principal display panel, as it
(a) The principal display panel of an
applies to over-the-counter devices in
package form and as used in this part, over-the-counter device in package
means the part of a label that is most form shall bear as one of its principal
likely to be displayed, presented, features a statement of the identity of
shown, or examined under customary the commodity.
conditions of display for retail sale. (b) Such statement of identity shall
The principal display panel shall be be in terms of the common name of the
large enough to accommodate all the device followed by an accurate state-
mandatory label information required ment of the principal intended ac-
to be placed thereon by this part with tion(s) of the device. Such statement
clarity and conspicuousness and with- shall be placed in direct conjunction
out obscuring designs, vignettes, or with the most prominent display of the
crowding. Where packages bear alter- name and shall employ terms descrip-
nate principal display panels, informative of the principal intended action(s).
tion required to be placed on the prin- The indications for use shall be in-
cipal display panel shall be duplicated cluded in the directions for use of the
on each principal display panel. For device, as required by section 502(f)(1)

the purpose of obtaining uniform type of the act and by the regulations in
size in declaring the quantity of con- this part.
37
§ 801.62 21 CFR Ch. I (4–1–23 Edition)
(c) The statement of identity shall be at 68 °F (20 °C). See also paragraph (p)
presented in bold face type on the prin- of this section.
cipal display panel, shall be in a size (c) The declaration may contain com-
reasonably related to the most promi- mon or decimal fractions. A common
nent printed matter on such panel, and fraction shall be in terms of halves,
shall be in lines generally parallel to quarters, eighths, sixteenths, or thirty-
the base on which the package rests as seconds; except that if there exists a
it is designed to be displayed. firmly established, general consumer
usage and trade custom of employing
§ 801.62 Declaration of net quantity of different common fractions in the net
contents. quantity declaration of a particular
(a) The label of an over-the-counter commodity, they may be employed. A
device in package form shall bear a common fraction shall be reduced to
declaration of the net quantity of con- its lowest terms; a decimal fraction
tents. This shall be expressed in the shall not be carried out to more than
terms of weight, measure, numerical two places. A statement that includes
count, or a combination of numerical small fractions of an ounce shall be
count and weight, measure, or size: deemed to permit smaller variations
Provided, That: than one which does not include such
(1) In the case of a firmly established fractions.
general consumer usage and trade cus- (d) The declaration shall be located
on the principal display panel of the
tom of declaring the quantity of a de-
label, and with respect to packages
vice in terms of linear measure or
bearing alternate principal panels it
measure of area, such respective term
shall be duplicated on each principal
may be used. Such term shall be aug-
display panel.
mented when necessary for accuracy of
(e) The declaration shall appear as a
information by a statement of the
distinct item on the principal display
weight, measure, or size of the indi-
panel, shall be separated, by at least a
vidual units or of the entire device.
space equal to the height of the let-
(2) If the declaration of contents for a tering used in the declaration, from
device by numerical count does not other printed label information appear-
give accurate information as to the ing above or below the declaration and,
quantity of the device in the package, by at least a space equal to twice the
it shall be augmented by such state- width of the letter ‘‘N’’ of the style of
ment of weight, measure, or size of the type used in the quantity of contents
individual units or of the total weight, statement, from other printed label in-
measure, or size of the device as will formation appearing to the left or right
give such information; for example, of the declaration. It shall not include
‘‘100 tongue depressors, adult size’’, ‘‘1 any term qualifying a unit of weight,
rectal syringe, adult size’’, etc. When- measure, or count, such as ‘‘giant pint’’
ever the Commissioner determines for and ‘‘full quart’’, that tends to exag-
a specific packaged device that an ex- gerate. It shall be placed on the prin-
isting practice of declaring net quan- cipal display panel within the bottom
tity of contents by weight, measure, 30 percent of the area of the label panel
numerical count, or a combination of in lines generally parallel to the base
these does not facilitate value on which the package rests as it is de-
comparisions by consumers, he shall by signed to be displayed: Provided, That:
regulation designate the appropriate (1) On packages having a principal
term or terms to be used for such arti- display panel of 5 square inches or less
cle. the requirement for placement within
(b) Statements of weight of the con- the bottom 30 percent of the area of the
tents shall be expressed in terms of av- label panel shall not apply when the
oirdupois pound and ounce. A state- declaration of net quantity of contents
ment of liquid measure of the contents meets the other requirements of this
shall be expressed in terms of the U.S. part; and
gallon of 231 cubic inches and quart, (2) In the case of a device that is mar-
pint, and fluid-ounce subdivisions keted with both outer and inner retail
thereof, and shall express the volume containers bearing the mandatory label
38
information required by this part and than 5 but not more than 25 square
the inner container is not intended to inches.
be sold separately, the net quantity of (3) Not less than three-sixteenths
contents placement requirement of this inch in height on packages the prin-
section applicable to such inner con- cipal display panel of which has an
tainer is waived. area of more than 25 but not more than
(3) The principal display panel of a 100 square inches.
device marketed on a display card to (4) Not less than one-fourth inch in
which the immediate container is af- height on packages the principal dis-
fixed may be considered to be the display panel of which has an area of more
play panel of the card, and the type than 100 square inches, except not less
size of the net quantity of contents than one-half inch in height if the area
statement is governed by the dimen- is more than 400 square inches.
sions of the display card. Where the declaration is blown, em-
(f) The declaration shall accurately bossed, or molded on a glass or plastic
reveal the quantity of device in the surface rather than by printing, typ-
package exclusive of wrappers and ing, or coloring, the lettering sizes
other material packed therewith. specified in paragraphs (h)(1) through
(g) The declaration shall appear in (4) of this section shall be increased by
conspicuous and easily legible boldface one-sixteenth of an inch.
print or type in distinct contrast (by (i) On packages containing less than
typography, layout, color, embossing, 4 pounds or 1 gallon and labeled in
or molding) to other matter on the terms of weight or fluid measure:
package; except that a declaration of (1) The declaration shall be expressed
net quantity blown, embossed, or mold- both in ounces, with identification by
ed on a glass or plastic surface is per- weight or by liquid measure and, if ap-
missible when all label information is plicable (1 pound or 1 pint or more) fol-
so formed on the surface. Requirements lowed in parentheses by a declaration
of conspicuousness and legibility shall in pounds for weight units, with any re-
include the specifications that: mainder in terms of ounces or common
or decimal fractions of the pound (see
(1) The ratio of height to width of the
examples set forth in paragraphs (k) (1)
letter shall not exceed a differential of
and (2) of this section), or in the case of
3 units to 1 unit, i.e., no more than 3
liquid measure, in the largest whole
times as high as it is wide.
units (quarts, quarts and pints, or
(2) Letter heights pertain to upper pints, as appropriate) with any remain-
case or capital letters. When upper and der in terms of fluid ounces or common
lower case or all lower case letters are or decimal fractions of the pint or
used, it is the lower case letter ‘‘o’’ or quart (see examples set forth in para-
its equivalent that shall meet the min- graphs (k) (3) and (4) of this section). If
imum standards. the net weight of the package is less
(3) When fractions are used, each than 1 ounce avoirdupois or the net
component numeral shall meet one- fluid measure is less than 1 fluid ounce,
half the minimum height standards. the declaration shall be in terms of
(h) The declaration shall be in letters common or decimal fractions of the re-
and numerals in a type size established spective ounce and not in terms of
in relationship to the area of the prin- drams.
cipal display panel of the package and (2) The declaration may appear in
shall be uniform for all packages of more than one line. The term ‘‘net
substantially the same size by com- weight’’ shall be used when stating the
plying with the following type speci- net quantity of contents in terms of
fications: weight. Use of the terms ‘‘net’’ or ‘‘net
(1) Not less than one-sixteenth inch contents’’ in terms of fluid measure or
in height on packages the principal dis- numerical count is optional. It is suffi-
play panel of which has an area of 5 cient to distinguish avoirdupois ounce
square inches or less. from fluid ounce through association of
(2) Not less than one-eighth inch in terms; for example, ‘‘Net wt. 6 oz’’ or
height on packages the principal dis- ‘‘6 oz net wt.,’’ and ‘‘6 fl oz’’ or ‘‘net
play panel of which has an area of more contents 6 fl oz.’’
39
§ 801.62 21 CFR Ch. I (4–1–23 Edition)
(j) On packages containing 4 pounds rentheses following the declaration in

or 1 gallon or more and labeled in terms of inches and any remainder
terms of weight or fluid measure, the shall be in terms of inches or common
declaration shall be expressed in or decimal fractions of the foot or
pounds for weight units with any re- yard; if applicable, as in the case of ad-
mainder in terms of ounces or common hesive tape, the initial declaration in
or decimal fractions of the pound; in linear inches shall be preceded by a
the case of fluid measure, it shall be statement of the width. Examples of
expressed in the largest whole unit, linear measure are ‘‘86 inches (2 yd 1 ft
i.e., gallons, followed by common or 2 in)’’, ‘‘90 inches (21⁄2 yd)’’, ‘‘30 inches
decimal fractions of a gallon or by the (2.5 ft)’’, ‘‘3⁄4 inch by 36 in (1 yd)’’, etc.
next smaller whole unit or units (n) On packages labeled in terms of
(quarts or quarts and pints), with any area measure, the declaration shall be
remainder in terms of fluid ounces or expressed both in terms of square
common or decimal fractions of the inches and, if applicable (1 square foot
pint or quart; see paragraph (k)(5) of or more), the largest whole square unit
this section. (square yards, square yards and square
(k) Examples: (1) A declaration of 11⁄2 feet, square feet). The declaration in
pounds weight shall be expressed as terms of the largest whole units shall
‘‘net wt. 24 oz (1 lb 8 oz),’’ or ‘‘Net wt. be in parentheses following the dec-
24 oz (11⁄2 lb)’’ or ‘‘Net wt. 24 oz (1.5 lb).’’ laration in terms of square inches and
(2) A declaration of three-fourths any remainder shall be in terms of
pound avoirdupois weight shall be ex- square inches or common or decimal
pressed as ‘‘Net wt. 12 oz.’’. fractions of the square foot or square
(3) A declaration of 1 quart liquid yard; for example, ‘‘158 sq inches (1 sq
measure shall be expressed as ‘‘Net ft 14 sq in)’’.
contents 32 fl oz (1 qt)’’ or ‘‘32 fl oz (1 (o) Nothing in this section shall pro-
qt).’’ hibit supplemental statements at loca-
(4) A declaration of 13⁄4 quarts liquid tions other than the principal display
measure shall be expressed as, ‘‘Net panel(s) describing in nondeceptive
contents 56 fl oz (1 qt 1 pt 8 oz)’’ or terms the net quantity of contents,
‘‘Net contents 56 fl oz (1 qt 1.5 pt),’’ but provided that such supplemental state-
not in terms of quart and ounce such as ments of net quantity of contents shall
‘‘Net contents 56 fl oz (1 qt 24 oz).’’ not include any term qualifying a unit
(5) A declaration of 21⁄2 gallons liquid of weight, measure, or count that tends
measure shall be expressed as ‘‘Net to exaggerate the amount of the device
contents 2 gal 2 qt’’, ‘‘Net contents 2.5 contained in the package; for example,
gallons,’’ or ‘‘Net contents 21⁄2 gal’’ but ‘‘giant pint’’ and ‘‘full quart’’. Dual or
not as ‘‘2 gal 4 pt’’. combination declarations of net quan-
(l) For quantities, the following ab- tity of contents as provided for in para-
breviations and none other may be em- graphs (a) and (i) of this section are not
ployed. Periods and plural forms are regarded as supplemental net quantity
optional: statements and shall be located on the
gallon gal liter l principal display panel.
milliliter ml cubic centimeter cc
quart qt yard yd
(p) A separate statement of net quan-
pint pt feet or foot ft tity of contents in terms of the metric
ounce oz inch in system of weight or measure is not re-
pound lb meter m garded as a supplemental statement
grain gr centimeter cm
kilogram kg millimeter mm and an accurate statement of the net
gram g fluid fl quantity of contents in terms of the
milligram mg square sq metric system of weight or measure
microgram mcg weight wt
may also appear on the principal dis-
(m) On packages labeled in terms of play panel or on other panels.
linear measure, the declaration shall (q) The declaration of net quantity of
be expressed both in terms of inches contents shall express an accurate
and, if applicable (1 foot or more), the statement of the quantity of contents
largest whole units (yards, yards and of the package. Reasonable variations
feet, feet). The declaration in terms of caused by loss or gain of moisture dur-
the largest whole units shall be in pa- ing the course of good distribution
40
practice or by unavoidable deviations Subpart D—Exemptions From

in good manufacturing practice will be Adequate Directions for Use
recognized. Variations from stated
quantity of contents shall not be un- § 801.109 Prescription devices.
reasonably large.
A device which, because of any poten-
§ 801.63 Medical devices; warning tiality for harmful effect, or the meth-
statements for devices containing od of its use, or the collateral measures
or manufactured with necessary to its use is not safe except
chlorofluorocarbons and other class under the supervision of a practitioner
I ozone-depleting substances. licensed by law to direct the use of
(a) All over-the-counter devices con- such device, and hence for which ‘‘ade-
quate directions for use’’ cannot be
taining or manufactured with
prepared, shall be exempt from section
chlorofluorocarbons, halons, carbon
502(f)(1) of the act if all the following
tetrachloride, methyl chloride, or any
conditions are met:
other class I substance designated by
(a) The device is:
the Environmental Protection Agency
(EPA) shall carry one of the following (1)(i) In the possession of a person, or
his agents or employees, regularly and
warnings:
lawfully engaged in the manufacture,
(1) The EPA warning statement:
transportation, storage, or wholesale
WARNING: Contains [or Manufactured with, or retail distribution of such device; or
if applicable] [insert name of substance], a sub- (ii) In the possession of a practi-
stance which harms public health and envi- tioner, such as physicians, dentists,
ronment by destroying ozone in the upper at- and veterinarians, licensed by law to
mosphere. use or order the use of such device; and
(2) The alternative statement: (2) Is to be sold only to or on the pre-
scription or other order of such practi-
NOTE: The indented statement below is re-
tioner for use in the course of his pro-
quired by the Federal government’s Clean
Air Act for all products containing or manu-
fessional practice.
factured with chlorofluorocarbons (CFC’s) (b) The label of the device, other than
[or other class I substance, if applicable]: surgical instruments, bears:
WARNING: Contains [or Manufactured with, (1) The symbol statement ‘‘Rx only’’
if applicable] [insert name of substance], a sub- or ‘‘) only’’ or the statement ‘‘Caution:
stance which harms public health and envi- Federal law restricts this device to sale
ronment by destroying ozone in the upper at- by or on the order of a ___’’, the blank
mosphere. to be filled with the word ‘‘physician’’,
CONSULT WITH YOUR PHYSICIAN,
‘‘dentist’’, ‘‘veterinarian’’, or with the
HEALTH PROFESSIONAL, OR SUPPLIER descriptive designation of any other
IF YOU HAVE ANY QUESTION ABOUT THE practitioner licensed by the law of the
USE OF THIS PRODUCT. State in which the practitioner prac-
tices to use or order the use of the de-
(b) The warning statement shall be vice; and
clearly legible and conspicuous on the (2) The method of its application or
product, its immediate container, its use.
outer packaging, or other labeling in (c) Labeling on or within the package
accordance with the requirements of 40 from which the device is to be dis-
CFR part 82 and appear with such pensed bears information for use, in-
prominence and conspicuousness as to cluding indications, effects, routes,
render it likely to be read and under- methods, and frequency and duration
stood by consumers under normal con- of administration, and any relevant
ditions of purchase. This provision does hazards, contraindications, side effects,
not replace or relieve a person from and precautions under which practi-
any requirements imposed under 40 tioners licensed by law to administer
CFR part 82. the device can use the device safely
[61 FR 20101, May 3, 1996]

and for the purpose for which it is in-
tended, including all purposes for
which it is advertised or represented:
41
§ 801.110 21 CFR Ch. I (4–1–23 Edition)
Provided, however, That such informa- cautionary statements, if any, con-

tion may be omitted from the dis- tained in such order.
pensing package if, but only if, the ar-
ticle is a device for which directions, § 801.116 Medical devices having com-
hazards, warnings, and other informa- monly known directions.
tion are commonly known to practi- A device shall be exempt from sec-
tioners licensed by law to use the de- tion 502(f)(1) of the act insofar as ade-
vice. Upon written request, stating rea- quate directions for common uses
sonable grounds therefor, the Commis- thereof are known to the ordinary indi-
sioner will offer an opinion on a pro- vidual.
posal to omit such information from
§ 801.119 In vitro diagnostic products.
the dispensing package under this pro-
viso. A product intended for use in the di-
(d) Any labeling, as defined in section agnosis of disease and which is an in
201(m) of the act, whether or not it is vitro diagnostic product as defined in
on or within a package from which the § 809.3(a) of this chapter shall be
device is to be dispensed, distributed by deemed to be in compliance with the
or on behalf of the manufacturer, pack- requirements of this part and section
er, or distributor of the device, that 502(f)(1) of the Federal Food, Drug, and
furnishes or purports to furnish infor- Cosmetic Act if it meets the require-
mation for use of the device contains ments of subpart B of this part and the
adequate information for such use, in- requirements of § 809.10 of this chapter.
cluding indications, effects, routes, [78 FR 58820, Sept. 24, 2013]
methods, and frequency and duration
of administration and any relevant § 801.122 Medical devices for proc-
hazards, contraindications, side effects, essing, repacking, or manufac-
and precautions, under which practi- turing.
tioners licensed by law to employ the A device intended for processing, re-
device can use the device safely and for packing, or use in the manufacture of
the purposes for which it is intended, another drug or device shall be exempt
including all purposes for which it is from section 502(f)(1) of the act if its
advertised or represented. This infor- label bears the statement ‘‘Caution:
mation will not be required on so- For manufacturing, processing, or re-
called reminder—piece labeling which packing’’.
calls attention to the name of the de-
vice but does not include indications or § 801.125 Medical devices for use in
teaching, law enforcement, re-
other use information. search, and analysis.
(e) All labeling, except labels and
cartons, bearing information for use of A device subject to § 801.109 shall be
the device also bears the date of the exempt from section 502(f)(1) of this act
issuance or the date of the latest revi- if shipped or sold to, or in the posses-
sion of such labeling. sion of, persons regularly and lawfully
engaged in instruction in pharmacy,
[41 FR 6896, Feb. 13, 1976, as amended at 81 chemistry, or medicine not involving
FR 38930, June 15, 2016] clinical use, or engaged in law enforce-
ment, or in research not involving clin-
§ 801.110 Retail exemption for pre- ical use, or in chemical analysis, or
scription devices.
physical testing, and is to be used only
A device subject to § 801.109 shall be for such instruction, law enforcement,
exempt at the time of delivery to the research, analysis, or testing.
ultimate purchaser or user from sec-
tion 502(f)(1) of the act if it is delivered § 801.127 Medical devices; expiration
by a licensed practitioner in the course of exemptions.
of his professional practice or upon a (a) If a shipment or delivery, or any
prescription or other order lawfully part thereof, of a device which is ex-
issued in the course of his professional empt under the regulations in this sec-
practice, with labeling bearing the tion is made to a person in whose pos-
name and address of such licensed prac- session the article is not exempt, or is
titioner and the directions for use and made for any purpose other than those
42
specified, such exemption shall expire, (i) Identify the specified lots,
with respect to such shipment or deliv- batches, or other units of the medical
ery or part thereof, at the beginning of device that would be subject to the ex-
that shipment or delivery. The causing ception or alternative;
of an exemption to expire shall be con- (ii) Identify the labeling provision(s)
sidered an act which results in such de- listed in paragraph (f) of this section
vice being misbranded unless it is dis- that are the subject of the exception or
posed of under circumstances in which alternative request;
it ceases to be a drug or device. (iii) Explain why compliance with
(b) The exemptions conferred by the labeling provision(s) could ad-
§§ 801.119, 801.122, and 801.125 shall con- versely affect the safety, effectiveness,
tinue until the devices are used for the or availability of the specified lots,
purposes for which they are exempted, batches, or other units of a medical de-
or until they are relabeled to comply vice that are or will be held in the
with section 502(f)(1) of the act. If, how- Strategic National Stockpile;
ever, the device is converted, or manu- (iv) Describe any proposed safeguards
factured into a form limited to pre- or conditions that will be implemented
scription dispensing, no exemption so that the labeling of the device in-
shall thereafter apply to the article un- cludes appropriate information nec-
less the device is labeled as required by essary for the safe and effective use of
§ 801.109. the device, given the anticipated cir-
cumstances of use of the device;
§ 801.128 Exceptions or alternatives to (v) Provide a draft of the proposed la-
labeling requirements for medical beling of the specified lots, batches, or
devices held by the Strategic Na- other units of the medical device sub-
tional Stockpile. ject to the exception or alternative;
(a) The appropriate FDA Center Di- and
rector may grant an exception or alter- (vi) Provide any other information
native to any provision listed in para- requested by the Center Director in
support of the request.
graph (f) of this section and not explic-
(c) The Center Director must respond
itly required by statute, for specified
in writing to all requests under this
lots, batches, or other units of a med-
section. The Center Director may im-
ical device, if the Center Director de-
pose appropriate conditions when
termines that compliance with such la-
granting such an exception or alter-
beling requirement could adversely af-
native under this section.
fect the safety, effectiveness, or avail-
(d) A grant of an exception or alter-
ability of such devices that are or will
native under this section will include
be included in the Strategic National
any safeguards or conditions deemed
Stockpile.
appropriate by the Center Director so
(b)(1)(i) A Strategic National Stock- that the labeling of devices subject to
pile official or any entity that manu- the exception or alternative includes
factures (including labeling, packing, the information necessary for the safe
relabeling, or repackaging), distrib- and effective use of the device, given
utes, or stores devices that are or will the anticipated circumstances of use.
be included in the Strategic National (e) If the Center Director grants a re-
Stockpile may submit, with written quest for an exception or alternative to
concurrence from a Strategic National the labeling requirements under this
Stockpile official, a written request for section:
an exception or alternative described (1) The Center Director may deter-
in paragraph (a) of this section to the mine that the submission and grant of
Center Director. a written request under this section
(ii) The Center Director may grant satisfies the provisions relating to pre-
an exception or alternative described market notification submissions under
in paragraph (a) of this section on his § 807.81(a)(3) of this chapter.
or her own initiative. (2)(i) For a Premarket Approval Ap-
(2) A written request for an exception plication (PMA)-approved device, the

or alternative described in paragraph submission and grant of a written re-
(a) of this section must: quest under this section satisfies the
43
§ 801.150 21 CFR Ch. I (4–1–23 Edition)
provisions relating to submission of device will not be adulterated or mis-

PMA supplements under § 814.39 of this branded within the meaning of the act
chapter; however, upon completion of such processing, la-
(ii) The grant of the request must be beling, or repacking. Such person and
identified in a periodic report under such operator shall each keep a copy of
§ 814.84 of this chapter. such agreement until 2 years after the
(f) The Center Director may grant an final shipment or delivery of such de-
exception or alternative under this sec- vice from such establishment, and shall
tion to the following provisions of this make such copies available for inspec-
chapter, to the extent that the require- tion at any reasonable hour to any offi-
ments in these provisions are not ex- cer or employee of the Department who
plicitly required by statute: requests them.
(1) § 801.1(d); (b) An exemption of a shipment or
(2) Subpart B of this part and part 830 other delivery of a device under para-
of this chapter in its entirety; graph (a)(1) of this section shall, at the
(3) § 801.60; beginning of the act of removing such
(4) § 801.61; shipment or delivery, or any part
(5) § 801.62; thereof, from such establishment, be-
(6) § 801.63; come void ab initio if the device com-
(7) § 801.109; and prising such shipment, delivery, or part
(8) Part 801, subpart H. is adulterated or misbranded within
[72 FR 73601, Dec. 28, 2007, as amended at 78 the meaning of the act when so re-
FR 58820, Sept. 24, 2013] moved.
(c) An exemption of a shipment or
Subpart E—Other Exemptions other delivery of a device under para-
graph (a)(2) of this section shall be-
§ 801.150 Medical devices; processing, come void ab initio with respect to the
labeling, or repacking. person who introduced such shipment
(a) Except as provided by paragraphs or delivery into interstate commerce
(b) and (c) of this section, a shipment upon refusal by such person to make
or other delivery of a device which is, available for inspection a copy of the
in accordance with the practice of the agreement, as required by such para-
trade, to be processed, labeled, or re- graph (a)(2).
packed, in substantial quantity at an (d) An exemption of a shipment or
establishment other than that where other delivery of a device under para-
originally processed or packed, shall be graph (a)(2) of this section shall expire:
exempt, during the time of introduc- (1) At the beginning of the act of re-
tion into and movement in interstate moving such shipment or delivery, or
commerce and the time of holding in any part thereof, from such establish-
such establishment, from compliance ment if the device comprising such
with the labeling and packaging re- shipment, delivery, or part is adulter-
quirements of section 502(b) and (f) of ated or misbranded within the meaning
the act if: of the act when so removed; or
(1) The person who introduced such (2) Upon refusal by the operator of
shipment or delivery into interstate the establishment where such device is
commerce is the operator of the estab- to be processed, labeled, or repacked,
lishment where such device is to be to make available for inspection a copy
processed, labeled, or repacked; or of the agreement, as required by such
(2) In case such person is not such op- clause.
erator, such shipment or delivery is (e) As it is a common industry prac-
made to such establishment under a tice to manufacture and/or assemble,
written agreement, signed by and con- package, and fully label a device as
taining the post office addresses of sterile at one establishment and then
such person and such operator, and ship such device in interstate com-
containing such specifications for the merce to another establishment or to a
processing, labeling, or repacking, as contract sterilizer for sterilization, the
the case may be, of such device in such Food and Drug Administration will ini-
establishment as will insure, if such tiate no regulatory action against the
specifications are followed, that such device as misbranded or adulterated
44
when the nonsterile device is labeled pairing, refitting, or cushioning of ill-

sterile, provided all the following con- fitting, broken, or irritating dentures.
ditions are met: It is the opinion of dental authorities
(1) There is in effect a written agree- and the Food and Drug Administration
ment which: that to properly repair and properly
(i) Contains the names and post office refit dentures a person must have pro-
addresses of the firms involved and is fessional knowledge and specialized
signed by the person authorizing such technical skill. Laymen cannot be ex-
shipment and the operator or person in pected to maintain the original
charge of the establishment receiving vertical dimension of occlusion and the
the devices for sterilization. centric relation essential in the proper
(ii) Provides instructions for main- repairing or refitting of dentures. The
taining proper records or otherwise ac- continued wearing of improperly re-
counting for the number of units in paired or refitted dentures may cause
each shipment to insure that the num- acceleration of bone resorption, soft
ber of units shipped is the same as the tissue hyperplasia, and other irrep-
number received and sterilized. arable damage to the oral cavity. Such
(iii) Acknowledges that the device is articles designed for lay use should be
nonsterile and is being shipped for fur- limited to emergency or temporary sit-
ther processing, and uations pending the services of a li-
(iv) States in detail the sterilization censed dentist.
process, the gaseous mixture or other (b) The Food and Drug Administra-
media, the equipment, and the testing tion therefore regards such articles as
method or quality controls to be used unsafe and misbranded under the Fed-
by the contract sterilizer to assure eral Food, Drug, and Cosmetic Act, un-
that the device will be brought into less the labeling:
full compliance with the Federal Food, (1)(i) Limits directions for use for
Drug, and Cosmetic Act. denture repair kits to emergency re-
(2) Each pallet, carton, or other des- pairing pending unavoidable delay in
ignated unit is conspicuously marked obtaining professional reconstruction
to show its nonsterile nature when it is of the denture;
introduced into and is moving in inter- (ii) Limits directions for use for den-
state commerce, and while it is being ture reliners, pads, and cushions to
held prior to sterilization. Following temporary refitting pending unavoid-
sterilization, and until such time as it able delay in obtaining professional re-
is established that the device is sterile construction of the denture;
and can be released from quarantine, (2) Contains in a conspicuous manner
each pallet, carton, or other designated the word ‘‘emergency’’ preceding and
unit is conspicuously marked to show modifying each indication-for-use
that it has not been released from statement for denture repair kits and
quarantine, e.g., ‘‘sterilized—awaiting the word ‘‘temporary’’ preceding and
test results’’ or an equivalent designa- modifying each indication-for-use
tion. statement for reliners, pads, and cush-
ions; and
Subparts F–G [Reserved] (3) Includes a conspicuous warning
statement to the effect:
Subpart H—Special Requirements (i) For denture repair kits: ‘‘Warn-
for Specific Devices ing—For emergency repairs only. Long
term use of home-repaired dentures
§ 801.405 Labeling of articles intended may cause faster bone loss, continuing
for lay use in the repairing and/or irritation, sores, and tumors. This kit
refitting of dentures. for emergency use only. See Dentist
(a) The American Dental Association Without Delay.’’
and leading dental authorities have ad- (ii) For denture reliners, pads, and
vised the Food and Drug Administra- cushions: ‘‘Warning—For temporary use
tion of their concern regarding the only. Longterm use of this product may
safety of denture reliners, repair kits, lead to faster bone loss, continuing ir-
pads, cushions, and other articles mar- ritation, sores, and tumors. For Use
keted and labeled for lay use in the re- Only Until a Dentist Can Be Seen.’’
45
§ 801.410 21 CFR Ch. I (4–1–23 Edition)
(c) Adequate directions for use re- to the claims of usefulness will be re-
quire full information of the temporary garded as false and misleading under
and emergency use recommended in sections 201(n) and 502(a) of the Federal
order for the layman to understand the Food, Drug, and Cosmetic Act.
limitations of usefulness, the reasons (e) Regulatory action may be initi-
therefor, and the importance of adher- ated with respect to any article found
ing to the warnings. Accordingly, the within the jurisdiction of the act con-
labeling should contain substantially trary to the provisions of this policy
the following information: statement after 90 days following the
(1) For denture repair kits: Special date of publication of this section in
training and tools are needed to repair the FEDERAL REGISTER.
dentures to fit properly. Home-repaired
dentures may cause irritation to the § 801.410 Use of impact-resistant
gums and discomfort and tiredness lenses in eyeglasses and sunglasses.
while eating. Long term use may lead (a) Examination of data available on
to more troubles, even permanent the frequency of eye injuries resulting
changes in bones, teeth, and gums, from the shattering of ordinary crown
which may make it impossible to wear glass lenses indicates that the use of
dentures in the future. For these rea- such lenses constitutes an avoidable
sons, dentures repaired with this kit hazard to the eye of the wearer.
should be used only in an emergency (b) The consensus of the ophthalmic
until a dentist can be seen. Dentures community is that the number of eye
that don’t fit properly cause irritation injuries would be substantially reduced
and injury to the gums and faster bone by the use in eyeglasses and sunglasses
loss, which is permanent. Dentures of impact-resistant lenses.
that don’t fit properly cause gum (c)(1) To protect the public more ade-
changes that may require surgery for quately from potential eye injury, eye-
correction. Continuing irritation and glasses and sunglasses must be fitted
injury may lead to cancer in the with impact-resistant lenses, except in
mouth. You must see your dentist as those cases where the physician or op-
soon as possible. tometrist finds that such lenses will
(2) For denture reliners, pads, and not fulfill the visual requirements of
cushions: Use of these preparations or the particular patient, directs in writ-
devices may temporarily decrease the ing the use of other lenses, and gives
discomfort; however, their use will not written notification thereof to the pa-
make the denture fit properly. Special tient.
training and tools are needed to repair (2) The physician or optometrist
a denture to fit properly. Dentures that shall have the option of ordering glass
do not fit properly cause irritation and lenses, plastic lenses, or laminated
injury to the gums and faster bone glass lenses made impact resistant by
loss, which is permanent and may re- any method; however, all such lenses
quire a completely new denture. shall be capable of withstanding the
Changes in the gums caused by den- impact test described in paragraph
tures that do not fit properly may re- (d)(2) of this section.
quire surgery for correction. Con- (3) Each finished impact-resistant
tinuing irritation and injury may lead glass lens for prescription use shall be
to cancer in the mouth. You must see individually tested for impact resist-
your dentist as soon as possible. ance and shall be capable of with-
(3) If the denture relining or repair- standing the impact test described in
ing material forms a permanent bond paragraph (d)(2) of this section. Raised
with the denture, a warning statement multifocal lenses shall be impact re-
to the following effect should be in- sistant but need not be tested beyond
cluded: ‘‘This reliner becomes fixed to initial design testing. Prism segment
the denture and a completely new den- multifocal, slab-off prism, lenticular
ture may be required because of its cataract, iseikonic, depressed segment
use.’’ one-piece multifocal, bioconcave,
(d) Labeling claims exaggerating the myodisc and minus lenticular, custom
usefulness or the safety of the material laminate and cemented assembly
or failing to disclose all facts relevant lenses shall be impact resistant but
46
need not be subjected to impact test- a laminar layer, if any, and across a
ing. To demonstrate that all other complete diameter into two or more
types of impact-resistant lenses, in- separate pieces, or if any lens material
cluding impact-resistant laminated visible to the naked eyes becomes de-
glass lenses (i.e., lenses other than tached from the ocular surface. The
those described in the three preceding test shall be conducted with the lens
sentences of this paragraph (c)(3)), are supported by a tube (1-inch inside di-
capable of withstanding the impact ameter, 11⁄4-inch outside diameter, and
test described in this regulation, the approximately 1-inch high) affixed to a
manufacturer of these lenses shall sub- rigid iron or steel base plate. The total
ject to an impact test a statistically weight of the base plate and its rigidly
significant sampling of lenses from attached fixtures shall be not less than
each production batch, and the lenses 27 pounds. For lenses of small min-
so tested shall be representative of the imum diameter, a support tube having
finished forms as worn by the wearer, an outside diameter of less than 11⁄4
including finished forms that are of inches may be used. The support tube
minimal lens thickness and have been shall be made of rigid acrylic plastic,
subjected to any treatment used to im- steel, or other suitable substance and
part impact resistance. All non- shall have securely bonded on the top
prescription lenses and plastic pre- edge a 1⁄8- by 1⁄8-inch neoprene gasket
scription lenses tested on the basis of having a hardness of 40 ±5, as deter-
statistical significance shall be tested mined by ASTM Method D 1415–88,
in uncut-finished or finished form. ‘‘Standard Test Method for Rubber
(d)(1) For the purpose of this regula- Property—International Hardness’’ a
tion, the impact test described in para- minimum tensile strength of 1,200
graph (d)(2) of this section shall be the pounds, as determined by ASTM Meth-
‘‘referee test,’’ defined as ‘‘one which od D 412–98A, ‘‘Standard Test Methods
will be utilized to determine compli- for Vulcanized Rubber and Thermo-
ance with a regulation.’’ The referee plastic Elastomers—Tension,’’ and a
test provides the Food and Drug Ad- minimum ultimate elongation of 400
ministration with the means of exam- percent, as determined by ASTM Meth-
ining a medical device for performance od D 412–68 (Both methods are incor-
and does not inhibit the manufacturer porated by reference and are available
from using equal or superior test meth- from the American Society for Testing
ods. A lens manufacturer shall conduct Materials, 100 Barr Harbor Dr., West
tests of lenses using the impact test de- Conshohocken, Philadelphia, PA 19428,
scribed in paragraph (d)(2) of this sec- or available for inspection at the Cen-
tion or any equal or superior test. ter for Devices and Radiological
Whatever test is used, the lenses shall Health’s Library, 9200 Corporate Blvd.,
be capable of withstanding the impact Rockville, MD 20850, or at the National
test described in paragraph (d)(2) of Archives and Records Administration
this section if the Food and Drug Ad- (NARA). For information on the avail-
ministration examines them for per- ability of this material at NARA, call
formance. 202–741–6030, or go to: http://
(2) In the impact test, a 5⁄8-inch steel www.archives.gov/federal_register/
ball weighing approximately 0.56 ounce code_of_federal_regulations/
is dropped from a height of 50 inches ibr_locations.html. The diameter or con-
upon the horizontal upper surface of tour of the lens support may be modi-
the lens. The ball shall strike within a fied as necessary so that the 1⁄8- by 1⁄8-
5⁄8-inch diameter circle located at the inch neoprene gasket supports the lens
geometric center of the lens. The ball at its periphery.
may be guided but not restricted in its (e) Copies of invoice(s), shipping doc-
fall by being dropped through a tube ument(s), and records of sale or dis-
extending to within approximately 4 tribution of all impact resistant lenses,
inches of the lens. To pass the test, the including finished eyeglasses and sun-
lens must not fracture; for the purpose glasses, shall be kept and maintained
of this section, a lens will be consid- for a period of 3 years; however, the
ered to have fractured if it cracks names and addresses of individuals pur-
through its entire thickness, including chasing nonprescription eyeglasses and
47
§ 801.415 21 CFR Ch. I (4–1–23 Edition)
sunglasses at the retail level need not as a germicide, it must be present in a

be kept and maintained by the retailer. concentration far greater than that
The records kept in compliance with which can be safely tolerated by man
this paragraph shall be made available and animals.
upon request at all reasonable hours by (b) Although undesirable physio-
any officer or employee of the Food logical effects on the central nervous
and Drug Administration or by any system, heart, and vision have been re-
other officer or employee acting on be- ported, the predominant physiological
half of the Secretary of Health and effect of ozone is primary irritation of
Human Services and such officer or em- the mucous membranes. Inhalation of
ployee shall be permitted to inspect ozone can cause sufficient irritation to
and copy such records, to make such the lungs to result in pulmonary
inventories of stock as he deems nec- edema. The onset of pulmonary edema
essary, and otherwise to check the cor- is usually delayed for some hours after
rectness of such inventories. exposure; thus, symptomatic response
(f) In addition, those persons con- is not a reliable warning of exposure to
ducting tests in accordance with para- toxic concentrations of ozone. Since ol-
graph (d) of this section shall maintain factory fatigue develops readily, the
the results thereof and a description of odor of ozone is not a reliable index of
the test method and of the test appa- atmospheric ozone concentration.
ratus for a period of 3 years. These (c) A number of devices currently on
records shall be made available upon the market generate ozone by design or
request at any reasonable hour by any as a byproduct. Since exposure to
officer or employee acting on behalf of ozone above a certain concentration
the Secretary of Health and Human can be injurious to health, any such de-
Services. The persons conducting tests vice will be considered adulterated and/
shall permit the officer or employee to or misbranded within the meaning of
inspect and copy the records, to make sections 501 and 502 of the act if it is
such inventories of stock as the officer used or intended for use under the fol-
or employee deems necessary, and oth- lowing conditions:
erwise to check the correctness of the (1) In such a manner that it gen-
inventories. erates ozone at a level in excess of 0.05
(g) For the purpose of this section, part per million by volume of air circu-
the term ‘‘manufacturer’’ includes an lating through the device or causes an
importer for resale. Such importer may accumulation of ozone in excess of 0.05
have the tests required by paragraph part per million by volume of air (when
(d) of this section conducted in the measured under standard conditions at
country of origin but must make the 25 °C (77 °F) and 760 millimeters of mer-
results thereof available, upon request, cury) in the atmosphere of enclosed
to the Food and Drug Administration, space intended to be occupied by people
as soon as practicable. for extended periods of time, e.g.,
(h) All lenses must be impact-resist- houses, apartments, hospitals, and of-
ant except when the physician or op- fices. This applies to any such device,
tometrist finds that impact-resistant whether portable or permanent or part
lenses will not fulfill the visual re- of any system, which generates ozone
quirements for a particular patient. by design or as an inadvertent or inci-
(i) This statement of policy does not dental product.
apply to contact lenses. (2) To generate ozone and release it
[41 FR 6896, Feb. 13, 1976, as amended at 44 into the atmosphere in hospitals or
FR 20678, Apr. 6, 1979; 47 FR 9397, Mar. 5, 1982; other establishments occupied by the
65 FR 3586, Jan. 24, 2000; 65 FR 44436, July 18, ill or infirm.
2000; 69 FR 18803, Apr. 9, 2004] (3) To generate ozone and release it
into the atmosphere and does not indi-
§ 801.415 Maximum acceptable level of cate in its labeling the maximum ac-
ozone. ceptable concentration of ozone which
(a) Ozone is a toxic gas with no may be generated (not to exceed 0.05
known useful medical application in part per million by volume of air circu-
specific, adjunctive, or preventive ther- lating through the device) as estab-
apy. In order for ozone to be effective lished herein and the smallest area in
48
which such device can be used so as not gaged in the sale of hearing aids to any
to produce an ozone accumulation in member of the consuming public or any
excess of 0.05 part per million. employee, agent, salesperson, and/or
(4) In any medical condition for representative of such a person.
which there is no proof of safety and ef- Hearing aid. A hearing aid is any
fectiveness. wearable device designed for, offered
(5) To generate ozone at a level less for the purpose of, or represented as
than 0.05 part per million by volume of aiding persons with or compensating
air circulating through the device and for, impaired hearing.
it is labeled for use as a germicide or Prescription hearing aid. A prescrip-
deodorizer. tion hearing aid is a hearing aid that is
(d) This section does not affect the not an over-the-counter (OTC) hearing
present threshold limit value of 0.10 aid as defined in § 800.30 of this chapter
part per million (0.2 milligram per or a hearing aid that does not satisfy
cubic meter) of ozone exposure for an 8- the requirements in § 800.30 of this
hour-day exposure of industrial work- chapter.
ers as recommended by the American
Rebuilt hearing aid. A prescription
Conference of Governmental Industrial
hearing aid is ‘‘rebuilt’’ if the manufac-
Hygienists.
turer has inspected and tested the de-
(e) The method and apparatus speci-
vice, made any necessary modifications
fied in 40 CFR part 50, or any other
to ensure it meets applicable regu-
equally sensitive and accurate method,
latory requirements, including the re-
may be employed in measuring ozone
pursuant to this section. quirements in this section, and ade-
quately reprocessed the device for the
§ 801.417 Chlorofluorocarbon propel- next user.
lants. Sale. Sale includes a lease, rental, or
The use of chlorofluorocarbon in de- any other purchase or exchange for
vices as propellants in self-pressurized value.
containers is generally prohibited ex- Used hearing aid. A hearing aid is
cept as provided in § 2.125 of this chap- ‘‘used’’ if a user has worn it for any pe-
ter. riod of time. However, a hearing aid
shall not be ‘‘used’’ merely because a
[43 FR 11318, Mar. 17, 1978]
prospective user wore it as part of a
§ 801.422 Prescription hearing aid la- bona fide hearing aid evaluation to de-
beling. termine whether to select that par-
ticular hearing aid for that prospective
(a) Scope. This section specifies the
user. A hearing aid evaluation is ‘‘bona
labeling requirements for prescription
fide’’ if it was conducted in the pres-
hearing aids. Any hearing aid that does
ence of the dispenser or a hearing
not satisfy the requirements of § 800.30
health professional selected by the dis-
of this chapter shall be a prescription
penser to assist the prospective user in
device. Unless otherwise specified, the
making a determination.
requirements in this section are in ad-
dition to other applicable require- (c) Labeling. A prescription hearing
ments, including but not limited to aid shall bear all of the following label-
special controls found in the applicable ing:
classification regulation in part 874 of (1) Outside package labeling. The out-
this chapter. This section does not side package of a prescription hearing
apply to group auditory trainers. aid shall bear all of the following:
(b) Definitions for the purposes of this (i) Warnings and other important infor-
section. This section uses the following mation. All of the following shall ap-
definitions: pear on the outside package:
Dispenser. A dispenser is any person, (A) Warning against use in people
as defined in section 201(e) of the Fed- younger than 18 without prior medical
eral Food, Drug, and Cosmetic Act, en- evaluation.
49
§ 801.422 21 CFR Ch. I (4–1–23 Edition)
(B) ‘‘Red flag’’ conditions.
(C) Note about device trial options.
ER17AU22.017</GPH>
(ii) Statement of build condition. If the (iii) Indication of battery information.

prescription hearing aid is used or re- The outside package shall indicate the
built, the outside package shall declare type and number of batteries and
that fact. A sticker under and visible whether batteries are included in the
through the outer wrapper will suffice package.
ER17AU22.016</GPH>
to declare such fact. (iv) Indication of control platform.

That outside package shall indicate
50
ER17AU22.015</GPH>
whether a mobile device or other non- site or customer registration and with-
included control platform is required. out requiring purchase of any product
The indication must include the type or service. The user instructional bro-
of platform and how the platform con- chure shall include all of the following:
nects to the device. (i) The following warnings, which
(2) Labeling, inside the package. The shall appear in the following order and
manufacturer or distributor of a pre- prior to any content except the cover
scription hearing aid shall include a page:
user instructional brochure inside the (A) Warning against use in people
package and shall make an electronic younger than 18 without prior medical
version available for download without evaluation.
(B) ‘‘Red flag’’ conditions, addressed to

dispensers.
ER17AU22.019</GPH>
51
ER17AU22.018</GPH>
§ 801.422 21 CFR Ch. I (4–1–23 Edition)
(C) Warning to dispensers about very

high-output devices.
(D) Additional warnings. Any addi- (ii) The following cautions and no-
tional warnings the manufacturer may tices for users, which shall appear prior
include prior to the cautions and no- to any content, except the cover page
tices to users in paragraph (c)(2)(ii) of and the warnings under paragraph
this section. (c)(2)(i) of this section:
(A) Caution about hearing protection.
(B) Caution about excessive sound out-

put.
(C) Caution about components lodging

in ear.
ER17AU22.023</GPH>
ER17AU22.022</GPH>
(D) Note about user expectations.

ER17AU22.021</GPH>
52
ER17AU22.020</GPH>
(E) Note about reporting adverse events

to FDA.
(F) Note about hearing loss in people

younger than 18 and fitting devices.
ER17AU22.025</GPH>
53
ER17AU22.024</GPH>
§ 801.422 21 CFR Ch. I (4–1–23 Edition)
(iii) An illustration(s) of the prescrip- user can clean, disinfect, and replace
tion hearing aid that indicates oper- parts or how to seek replacements, as
ating controls, user adjustments, and well as how to store the hearing aid
the battery compartment. when it will not be used for an ex-
(iv) Information on the function of tended period of time.
all controls intended for user adjust- (C) If the battery is replaceable or re-
ment. chargeable, how to replace or recharge
(v) A description of any accessory the battery, including a generic des-
that accompanies the prescription ignation of replacement batteries.
hearing aid, including but not limited (D) Expected battery life.
to wax guards, and accessories for use
(vii) Identification of any known
with a computer, television, or tele-
physiological side effects associated
phone.
with the use of the prescription hear-
(vi) Specific instructions for all of
the following: ing aid that may warrant consultation
(A) Use of the prescription hearing with a physician, referring to an ear-
aid with any accompanying acces- nose-throat doctor when preferable, in-
cluding if applicable, skin irritation
sories.
(B) Maintenance and care of the pre- and accelerated accumulation of ceru-
scription hearing aid, including how a men (ear wax).
54
ER17AU22.026</GPH>
(viii) The technical specifications re- that accompanies the device, including
quired by paragraph (c)(4) of this sec- all of the following:
tion unless such specifications appear (i) Saturation output curve (Satura-
in separate labeling accompanying the tion Sound Pressure Level (SSPL) 90
prescription hearing aid. curve).
(ix) A description of commonly oc- (ii) Frequency response curve.
curring, avoidable events that could (iii) Average saturation output (High
adversely affect or damage the pre- Frequency (HF)-Average SSPL 90).
scription hearing aid, including but not
(iv) Average full-on gain (HF-Average
limited to, as applicable, ear wax build-
up, drops, immersion in water, or expo- full-on gain).
sure to excessive heat. (v) Reference test gain.
(x) If the hearing aid incorporates (vi) Frequency range.
wireless technology in its program- (vii) Total harmonic distortion.
ming or use, appropriate warnings, in- (viii) Equivalent input noise.
structions, and information relating to (ix) Latency, measured using a meth-
electromagnetic compatibility and od that is accurate and repeatable to
wireless technology and human expo- within 1.5 ms.
sure to non-ionizing radiation. (x) Battery current drain.
(xi) Information on how and where to (xi) Induction coil sensitivity (tele-
obtain repair service or replacements, phone coil aids only).
including at least one specific address (xii) Input-output curve (only for
where the user can go or send the pre-
hearing aids with automatic gain con-
scription hearing aid to obtain such re-
trol).
pair service or replacements.
(xii) If clinical or non-clinical studies (xiii) Attack and release times (only
were conducted by or for the manufac- for hearing aids with automatic gain
turer to support the performance of the control).
prescription hearing aid, a summary of (5) Software device labeling. Prescrip-
all such studies. tion hearing aid software that is not
(3) Labeling on the device. The labeling distributed with the hearing aid or am-
on a prescription hearing aid itself plification platform shall meet all of
shall bear all of the following clearly the following labeling requirements.
and permanently, except as provided in With respect to the information re-
paragraph (c)(3)(iii) of this section: quired under paragraphs (c)(1) through
(i) The serial number. (4) of this section, the information
(ii) If the battery is removable, a ‘‘+’’ must be provided in the software device
symbol to indicate the positive ter- labeling, as specified in paragraphs
minal for battery insertion unless the (c)(5)(i) through (v) of this section,
battery’s physical design prevents in- rather than the locations (e.g., outside
serting the battery in the reversed po- package labeling) specified in para-
sition. graphs (c)(1) through (4).
(iii) If the prescription hearing aid is (i) Prior to first use of the software
used or rebuilt, the manufacturer shall
or obtaining payment information for
physically attach a removable tag to
the software, whichever occurs first,
the hearing aid declaring that fact.
(4) Technical specifications. You must the labeling must clearly and promi-
determine the technical specification nently present all of the following to
values for the prescription hearing aid the prospective user. For each, the la-
labeling in accordance with the test beling must remain visible until the
procedures of ANSI/ASA S3.22–2014 user dismisses it or proceeds to the
(R2020), except as provided in para- next step:
graph (c)(4)(ix) of this section for la- (A) Compatibility and minimum op-
tency. Technical specifications and erating requirements for the software
their associated values that are useful device.
in selecting, fitting, and checking the (B) Disclosures of any fees or pay-
performance of the prescription hear- ments after first use or initial pay-
ing aid shall appear in the user instruc- ment, including but not limited to any
tional brochure or in separate labeling
55
§ 801.430 21 CFR Ch. I (4–1–23 Edition)
fees or payments relating to subscrip- National Archives and Records Admin-

tions, add-on features, or continued ac- istration (NARA). Contact the Dockets
cess to features or services. The disclo- Management Staff, 5630 Fishers Lane,
sures must name and briefly describe Rm. 1061, Rockville, MD 20852, 240–402–
what each fee or payment covers. 7500. For information on the avail-
(C) The information required under ability of this material at NARA,
paragraphs (c)(1)(i) and (iv) of this sec- email: [email protected], or go to:
tion. www.archives.gov/federal-register/cfr/ibr-
(ii) Prior to first use of the software, locations.html. The material may be ob-
the labeling must clearly and promi- tained from the Acoustical Society of
nently present all of the following to America (ASA), 1305 Walt Whitman
the prospective user: Road, Suite 300, Melville, NY 11747;
(A) The information required under phone: (631) 390–0215; fax: (631) 923–2875;
paragraph (c)(2)(i)(A) of this section, email: [email protected].
and it must remain visible until the
user acknowledges it. [87 FR 50755, Aug. 17, 2022]
(B) The information required under
§ 801.430 User labeling for menstrual
paragraphs (c)(2)(i)(B) through (D) and tampons.
(c)(2)(ii), (iv), (vii), and (viii) of this
section, and the information must re- (a) This section applies to scented or
main visible until the user dismisses it scented deodorized menstrual tampons
or proceeds to the next step. as identified in § 884.5460 and unscented
(C) All other information required menstrual tampons as identified in
under paragraph (c)(2) of this section, § 884.5470 of this chapter.
to the extent applicable, and the infor- (b) Data show that toxic shock syn-
mation must remain visible until the drome (TSS), a rare but serious and
user dismisses it or proceeds to the sometimes fatal disease, is associated
next step. with the use of menstrual tampons. To
(iii) The software device labeling protect the public and to minimize the
must include the information required serious adverse effects of TSS, men-
under paragraphs (c)(3)(i) and (c)(4) of strual tampons shall be labeled as set
this section. forth in paragraphs (c), (d), and (e) of
(iv) All of the software device label- this section and tested for absorbency
ing must be accessible for review after as set forth in paragraph (f) of this sec-
acknowledgment, dismissal, or pro- tion.
ceeding to the next step. (c) If the information specified in
(v) If there are changes to any of the paragraph (d) of this section is to be in-
labeling required under paragraph cluded as a package insert, the fol-
(c)(5) of this section, the labeling with lowing alert statement shall appear
the changed information must be pre- prominently and legibly on the pack-
sented to the user until the user dis- age label:
misses it.
(6) Misbranding. A prescription hear- ATTENTION: Tampons are associated with
Toxic Shock Syndrome (TSS). TSS is a rare
ing aid that is not labeled as required
but serious disease that may cause death.
under this section and § 801.109 is mis- Read and save the enclosed information.
branded under sections 201(n), 502(a),
and/or 502(f) of the Federal Food, Drug, (d) The labeling of menstrual tam-
and Cosmetic Act. pons shall contain the following con-
(d) Incorporation by reference. ANSI/ sumer information prominently and
ASA S3.22–2014 (R2020), ‘‘AMERICAN legibly, in such terms as to render the
NATIONAL STANDARD Specification information likely to be read and un-
of Hearing Aid Characteristics,’’ dated derstood by the ordinary individual
June 5, 2020, is incorporated by ref- under customary conditions of pur-
erence into this section with the ap- chase and use:
proval of the Director of the Office of (1)(i) Warning signs of TSS, e.g., sud-
the Federal Register under 5 U.S.C. den fever (usually 102° or more) and
552(a) and 1 CFR part 51. This material vomiting, diarrhea, fainting or near
is available for inspection at the Food fainting when standing up, dizziness, or
and Drug Administration and at the a rash that looks like a sunburn;
56
(ii) What to do if these or other signs (2) The package label shall include an
of TSS appear, including the need to explanation of the ranges of absorb-
remove the tampon at once and seek ency and a description of how con-
medical attention immediately; sumers can use a range of absorbency,
(2) The risk of TSS to all women and its corresponding absorbency term,
using tampons during their menstrual to make comparisons of absorbency of
period, especially the reported higher tampons to allow selection of the tam-
risks to women under 30 years of age pons with the minimum absorbency
and teenage girls, the estimated inci- needed to control menstrual flow in
dence of TSS of 1 to 17 per 100,000 men- order to reduce the risk of contracting
struating women and girls per year, TSS.
and the risk of death from contracting (f) A manufacturer shall measure the
TSS; absorbency of individual tampons using
(3) The advisability of using tampons the test method specified in paragraph
with the minimum absorbency needed (f)(2) of this section and calculate the
to control menstrual flow in order to mean absorbency of a production run,
reduce the risk of contracting TSS; lot, or batch by rounding to the nearest
(4) Avoiding the risk of getting tam- 0.1 gram.
pon-associated TSS by not using tam- (1) A manufacturer shall design and
pons, and reducing the risk of getting implement a sampling plan that in-
TSS by alternating tampon use with cludes collection of probability sam-
sanitary napkin use during menstrual ples of adequate size to yield consistent
periods; and tolerance intervals such that the prob-
(5) The need to seek medical atten- ability is 90 percent that at least 90
tion before again using tampons if TSS percent of the absorbencies of indi-
warning signs have occurred in the vidual tampons within a brand and
past, or if women have any questions type are within the range of absorb-
about TSS or tampon use. ency stated on the package label.
(e) The statements required by para- (2) In the absorbency test, an
graph (e) of this section shall be promi- unlubricated condom, with tensile
nently and legibly placed on the pack- strength between 17 Mega Pascals
age label of menstrual tampons in con- (MPa) and 30 MPa, as measured accord-
formance with section 502(c) of the ing to the procedure in the American
Federal Food, Drug, and Cosmetic Act Society for Testing and Materials
(the act) (unless the menstrual tam- (ASTM) D 3492–97, ‘‘Standard Specifica-
pons are exempt under paragraph (g) of tion for Rubber Contraceptives (Male
this section). Condoms)’’ 1 for determining tensile
(1) Menstrual tampon package labels strength, which is incorporated by ref-
shall bear one of the following absorb- erence in accordance with 5 U.S.C.
ency terms representing the absorb- 552(a), is attached to the large end of a
ency of the production run, lot, or glass chamber (or a chamber made
batch as measured by the test de- from hard transparent plastic) with a
scribed in paragraph (f)(2) of this sec- rubber band (see figure 1) and pushed
tion;
1The Director of the Federal Register ap-
Ranges of absorbency in Corresponding term of ab- proves this incorporation by reference in ac-
grams 1 sorbency
cordance with 5 U.S.C. 552(a) and 1 CFR part
6 and under Light absorbency 51. You may obtain a copy from the Amer-
ican Society for Testing and Materials Inter-
6 to 9 Regular absorbency national, 100 Barr Harbor Dr., P.O. Box C700,
West Conshohocken, PA 19428–2959, 610–832–
9 to 12 Super absorbency
9578, www.astm.org. You may inspect a copy
12 to 15 Super plus absorbency at the FDA Main Library, 10903 New Hamp-
shire Ave., Bldg. 2, 3d floor, Silver Spring,
15 to 18 Ultra absorbency MD 20993–0002, 301–796–2039, or at the Na-
tional Archives and Records Administration
Above 18 No term
(NARA). For information on the availability
1These ranges are defined, respectively, as follows: Less
of this material at NARA, call 202–741–2139,
than or equal to 6 grams (g); greater than 6 g up to and in- or go to: http://www.archives.gov/fed-
cluding 9 g; greater than 9 g up to and including 12 g; greater
than 12 g up to and including 15 g; greater than 15 g up to eral_register/code_of_federal_regulations/
and including 18 g; and greater than 18 g. ibr_locations.html.
57
§ 801.430 21 CFR Ch. I (4–1–23 Edition)
through the small end of the chamber chloride, 0.5 gram Certified Reagent
using a smooth, finished rod. The Acid Fushsin, 1,000 milliliters distilled
condom is pulled through until all water) is then pumped through the in-
slack is removed. The tip of the fusion needle at a rate of 50 milliliters
condom is cut off and the remaining per hour. The test shall be terminated
end of the condom is stretched over the when the tampon is saturated and the
end of the tube and secured with a rub- first drop of fluid exits the apparatus.
ber band. A preweighed (to the nearest (The test result shall be discarded if
0.01 gram) tampon is placed within the fluid is detected in the folds of the
condom membrane so that the center
condom before the tampon is satu-
of gravity of the tampon is at the cen-
rated). The water is then drained and
ter of the chamber. An infusion needle
(14 gauge) is inserted through the sep- the tampon is removed and imme-
tum created by the condom tip until it diately weighed to the nearest 0.01
contacts the end of the tampon. The gram. The absorbency of the tampon is
outer chamber is filled with water determined by subtracting its dry
pumped from a temperature-controlled weight from this value. The condom
waterbath to maintain the average shall be replaced after 10 tests or at the
temperature at 27±1 °C. The water re- end of the day during which the
turns to the waterbath as shown in fig- condom is used in testing, whichever
ure 2. Syngyna fluid (10 grams sodium occurs first.
58
59
ER01FE93.026</GPH>
§ 801.430 21 CFR Ch. I (4–1–23 Edition)
(3) The Food and Drug Administra- test method specified in this section if
tion may permit the use of an absorb- each of the following conditions is met:
ency test method different from the (i) The manufacturer presents evi-
dence, in the form of a citizen petition
60
ER01FE93.027</GPH>
submitted in accordance with the re- prominence and conspicuousness as to

quirements of § 10.30 of this chapter, render it likely to be read and under-
demonstrating that the alternative stood by consumers under normal con-
test method will yield results that are ditions of purchase.
equivalent to the results yielded by the (b)(1) For prescription and restricted
test method specified in this section; device products, the following alter-
and native warning statement may be used:
(ii) FDA approves the method and
has published notice of its approval of NOTE: The indented statement below is re-
quired by the Federal government’s Clean
the alternative test method in the FED- Air Act for all products containing or manu-
ERAL REGISTER. factured with chlorofluorocarbons (CFC’s)
(g) Any menstrual tampon intended [or name of other class I substance, if appli-
to be dispensed by a vending machine cable]:
is exempt from the requirements of
This product contains [or is manufactured
this section. with, if applicable] [insert name of substance],
(h) Any menstrual tampon that is not a substance which harms the environment by
labeled as required by paragraphs (c), destroying ozone in the upper atmosphere.
(d), and (e) of this section and that is Your physician has determined that this
initially introduced or initially deliv- product is likely to help your personal
ered for introduction into commerce health. USE THIS PRODUCT AS DIRECTED,
after March 1, 1990, is misbranded UNLESS INSTRUCTED TO DO OTHERWISE
under sections 201(n), 502 (a) and (f) of BY YOUR PHYSICIAN. If you have any ques-
tions about alternatives, consult with your
the act.
physician.
(Information collection requirements con- (2) The warning statement shall be
tained in paragraphs (e) and (f) were ap- clearly legible and conspicuous on the
proved by the Office of Management and product, its immediate container, its
Budget under control number 0910–0257)
outer packaging, or other labeling in
[47 FR 26989, June 22, 1982, as amended at 54 accordance with the requirements of 40
FR 43771, Oct. 26, 1989; 55 FR 17600, Apr. 26, CFR part 82 and appear with such
1990; 65 FR 3586, Jan. 24, 2000; 65 FR 44436, prominence and conspicuousness as to
July 18, 2000; 65 FR 62284, Oct. 18, 2000; 69 FR
render it likely to be read and under-
18803, Apr. 9, 2004; 69 FR 52171, Aug. 25, 2004;
75 FR 20914, Apr. 22, 2010] stood by consumers under normal con-
ditions of purchase.
§ 801.433 Warning statements for pre- (3) If the warning statement in para-
scription and restricted device graph (b)(1) of this section is used, the
products containing or manufac- following warning statement must be
tured with chlorofluorocarbons or placed on the package labeling in-
other ozone-depleting substances. tended to be read by the physician
(a)(1) All prescription and restricted (physician package insert) after the
device products containing or manufac- ‘‘How supplied’’ section, which de-
tured with chlorofluorocarbons, halons, scribes special handling and storage
carbon tetrachloride, methyl chloride, conditions on the physician labeling:
or any other class I substance des- NOTE: The indented statement below is re-
ignated by the Environmental Protec- quired by the Federal government’s Clean
tion Agency (EPA) shall, except as pro- Air Act for all products containing or manu-
vided in paragraph (b) of this section, factured with chlorofluorocarbons (CFC’s)
bear the following warning statement: [or name of other class I substance, if appli-
cable]:
WARNING: Contains [or Manufactured with,
if applicable] [insert name of substance], a sub- WARNING: Contains [or Manufactured with,
stance which harms public health and envi- if applicable] [insert name of substance], a sub-
ronment by destroying ozone in the upper at- stance which harms public health and envi-
mosphere. ronment by destroying ozone in the upper at-
mosphere.
(2) The warning statement shall be
A notice similar to the above WARNING
clearly legible and conspicuous on the
has been placed in the information for the
product, its immediate container, its patient [or patient information leaflet, if ap-
outer packaging, or other labeling in plicable] of this product under Environ-

accordance with the requirements of 40 mental Protection Agency (EPA) regula-
CFR part 82 and appear with such tions. The patient’s warning states that the
61
§ 801.435 21 CFR Ch. I (4–1–23 Edition)
patient should consult his or her physician if tween 15 and 30 °C for the lifetime of
there are questions about alternatives. the product (real time storage).
(c) This section does not replace or (e) If a product fails the physical and
relieve a person from any requirements mechanical integrity tests commonly
imposed under 40 CFR part 82. used by industry after the completion
[61 FR 20101, May 3, 1996]
of the accelerated storage tests de-
scribed in paragraphs (d)(1) and (d)(2) of
§ 801.435 User labeling for latex this section, the product expiration
condoms. date must be demonstrated by real
(a) This section applies to the subset time storage conditions described in
of condoms as identified in § 884.5300 of paragraph (d)(3) of this section. If all of
this chapter, and condoms with the products tested after storage at
spermicidal lubricant as identified in temperatures as described in para-
§ 884.5310 of this chapter, which prod- graphs (d)(1) and (d)(2) of this section
ucts are formed from latex films. pass the manufacturer’s physical and
(b) Data show that the material in- mechanical integrity tests, the manu-
tegrity of latex condoms degrade over facturer may label the product with an
time. To protect the public health and expiration date of up to 5 years from
minimize the risk of device failure, the date of product packaging. If the
latex condoms must bear an expiration extrapolated expiration date under
date which is supported by testing as paragraphs (d)(1) and (d)(2) of this sec-
described in paragraphs (d) and (h) of tion is used, the labeled expiration date
this section. must be confirmed by physical and me-
(c) The expiration date, as dem- chanical integrity tests performed at
onstrated by testing procedures re- the end of the stated expiration period
quired by paragraphs (d) and (h) of this as described in paragraph (d)(3) of this
section, must be displayed prominently section. If the data from tests fol-
and legibly on the primary packaging lowing real time storage described in
(i.e., individual package), and higher paragraph (d)(3) of this section fails to
levels of packaging (e.g., boxes of confirm the extrapolated expiration
condoms), in order to ensure visibility date, the manufacturer must, at that
of the expiration date by consumers. time, relabel the product to reflect the
(d) Except as provided under para- actual shelf life.
graph (f) of this section, the expiration
(f) Products that already have estab-
date must be supported by data dem-
lished shelf life data based upon real
onstrating physical and mechanical in-
time storage and testing and have such
tegrity of the product after three dis-
crete and representative lots of the storage and testing data available for
product have been subjected to each of inspection are not required to confirm
the following conditions: such data using accelerated and inter-
(1) Storage of unpackaged bulk prod- mediate aging data described in para-
uct for the maximum amount of time graphs (d)(1) and (d)(2) of this section.
the manufacturer allows the product to If, however, such real time expiration
remain unpackaged, followed by stor- dates were based upon testing of prod-
age of the packaged product at 70 °C ucts that were not first left
(plus or minus 2 °C) for 7 days; unpackaged for the maximum amount
(2) Storage of unpackaged bulk prod- of time as described in paragraph (d)(3)
uct for the maximum amount of time of this section, the real time testing
the manufacturer allows the product to must be confirmed by testing products
remain unpackaged, followed by stor- consistent with the requirements of
age of the packaged product at a se- paragraph (d)(3) of this section. This
lected temperature between 40 and 50 testing shall be initiated no later than
°C (plus or minus 2 °C) for 90 days; and the effective date of this regulation.
(3) Storage of unpackaged bulk prod- Until the confirmation testing in ac-
uct for the maximum amount of time cordance with paragraph (d)(3) of this
the manufacturer allows the product to section is completed, the product may
remain unpackaged, followed by stor- remain on the market labeled with the
age of the packaged product at a mon- expiration date based upon previous
itored or controlled temperature be- real time testing.
62
(g) If a manufacturer uses testing volves the use of natural latex in a con-
data from one product to support expi- centrated colloidal suspension. Prod-
ration dating on any variation of that ucts are formed from natural rubber
product, the manufacturer must docu- latex by dipping, extruding, or coating.
ment and provide, upon request, an ap- (2) The term ‘‘dry natural rubber’’
propriate justification for the applica- means rubber that is produced by the
tion of the testing data to the vari- dry natural rubber process that in-
ation of the tested product. volves the use of coagulated natural
(h) If a latex condom contains a latex in the form of dried or milled
spermicide, and the expiration date sheets. Products are formed from dry
based on spermicidal stability testing natural rubber by compression mold-
is different from the expiration date ing, extrusion, or by converting the
based upon latex integrity testing, the sheets into a solution for dipping.
product shall bear only the earlier ex- (3) The term ‘‘contacts humans’’
piration date. means that the natural rubber con-
(i) The time period upon which the tained in a device is intended to con-
expiration date is based shall start tact or is likely to contact the user or
with the date of packaging.
patient. This includes contact when
(j) As provided in part 820 of this
the device that contains natural rubber
chapter, all testing data must be re-
is connected to the patient by a liquid
tained in each company’s files, and
path or an enclosed gas path; or the de-
shall be made available upon request
vice containing the natural rubber is
for inspection by the Food and Drug
fully or partially coated with a powder,
Administration.
and such powder may carry natural
(k) Any latex condom not labeled
with an expiration date as required by rubber proteins that may contaminate
paragraph (c) of this section, and ini- the environment of the user or patient.
tially delivered for introduction into (c) Devices containing natural rubber
interstate commerce after the effective shall be labeled as set forth in para-
date of this regulation is misbranded graphs (d) through (h) of this section.
under sections 201(n) and 502(a) and (f) Each required labeling statement shall
of Federal Food, Drug, and Cosmetic be prominently and legibly displayed
Act (21 U.S.C. 321(n) and 352(a) and (f)). in conformance with section 502(c) of
the Federal Food, Drug, and Cosmetic
[62 FR 50501, Sept. 26, 1997] Act (the act) (21 U.S.C. 352(c)).
§ 801.437 User labeling for devices that (d) Devices containing natural rubber
contain natural rubber. latex that contacts humans, as de-
scribed in paragraph (b) of this section,
(a) Data in the Medical Device Re- shall bear the following statement in
porting System and the scientific lit- bold print on the device labeling:
erature indicate that some individuals
‘‘Caution: This Product Contains
are at risk of severe anaphylactic reac-
Natural Rubber Latex Which May
tions to natural latex proteins. This la-
Cause Allergic Reactions.’’
beling regulation is intended to mini-
mize the risk to individuals sensitive This statement shall appear on all de-
to natural latex proteins and protect vice labels, and other labeling, and
the public health. shall appear on the principal display
(b) This section applies to all devices panel of the device packaging, the out-
composed of or containing, or having side package, container or wrapper,
packaging or components that are and the immediate device package,
composed of, or contain, natural rubber container, or wrapper.
that contacts humans. The term ‘‘nat- (e) Devices containing dry natural
ural rubber’’ includes natural rubber rubber that contacts humans, as de-
latex, dry natural rubber, and syn- scribed in paragraph (b) of this section,
thetic latex or synthetic rubber that that are not already subject to para-
contains natural rubber in its formula- graph (d) of this section, shall bear the
tion. following statement in bold print on
(1) The term ‘‘natural rubber latex’’ the device labeling:

means rubber that is produced by the ‘‘This Product Contains Dry Natural
natural rubber latex process that in- Rubber.’’
63
This statement shall appear on all de- tions relate to device packaging that uses
vice labels, and other labeling, and ‘‘cold seal’’ adhesives.
shall appear on the principal display [62 FR 51029, Sept. 30, 1997, as amended at 63
panel of the device packaging, the out- FR 46175, Aug. 31, 1998]
side package, container or wrapper,
and the immediate device package, PART 803—MEDICAL DEVICE
container, or wrapper. REPORTING
(f) Devices that have packaging con-
taining natural rubber latex that con- Subpart A—General Provisions
tacts humans, as described in para- Sec.
graph (b) of this section, shall bear the 803.1 What does this part cover?
following statement in bold print on 803.3 How does FDA define the terms used
the device labeling: in this part?
803.9 What information from the reports do
‘‘Caution: The Packaging of This
we disclose to the public?
Product Contains Natural Rubber 803.10 Generally, what are the reporting re-
Latex Which May Cause Allergic Reac- quirements that apply to me?
tions.’’ 803.11 What form should I use to submit re-
ports of individual adverse events and
This statement shall appear on the where do I obtain these forms?
packaging that contains the natural 803.12 How do I submit initial and supple-
rubber, and the outside package, con- mental or followup reports?
tainer, or wrapper. 803.13 Do I need to submit reports in
(g) Devices that have packaging con- English?
803.15 How will I know if you require more
taining dry natural rubber that con- information about my medical device re-
tacts humans, as described in para- port?
graph (b) of this section, shall bear the 803.16 When I submit a report, does the in-
following statement in bold print on formation in my report constitute an ad-
the device labeling: mission that the device caused or con-
tributed to the reportable event?
‘‘The Packaging of This Product Con- 803.17 What are the requirements for devel-
tains Dry Natural Rubber.’’ oping, maintaining, and implementing
This statement shall appear on the written MDR procedures that apply to
packaging that contains the natural me?
803.18 What are the requirements for estab-
rubber, and the outside package, con- lishing and maintaining MDR files or
tainer, or wrapper. records that apply to me?
(h) Devices that contain natural rub- 803.19 Are there exemptions, variances, or
ber that contacts humans, as described alternative forms of adverse event re-
in paragraph (b) of this section, shall porting requirements?
not contain the term ‘‘hypoallergenic’’ Subpart B—Generally Applicable Require-
on their labeling. ments for Individual Adverse Event Re-
(i) Any affected person may request ports
an exemption or variance from the re-
quirements of this section by submit- 803.20 How do I complete and submit an in-
dividual adverse event report?
ting a citizen petition in accordance 803.21 Where can I find the reporting codes
with § 10.30 of this chapter. for adverse events that I use with med-
(j) Any device subject to this section ical device reports?
that is not labeled in accordance with 803.22 What are the circumstances in which
paragraphs (d) through (h) of this sec- I am not required to file a report?
803.23 Where can I find information on how
tion and that is initially introduced or to prepare and submit an MDR in elec-
initially delivered for introduction into tronic format?
interstate commerce after the effective
date of this regulation is misbranded Subpart C—User Facility Reporting
under sections 201(n) and 502(a), (c), and Requirements
(f) of the act (21 U.S.C. 321(n) and 803.30 If I am a user facility, what reporting
352(a), (c), and (f)). requirements apply to me?
803.32 If I am a user facility, what informa-

NOTE TO § 801.437: Paragraphs (f) and (g) are
tion must I submit in my individual ad-
stayed until June 27, 1999, as those regula- verse event reports?
64
803.33 If I am a user facility, what must I in- (b) This part supplements and does
clude when I submit an annual report? not supersede other provisions of this
chapter, including the provisions of
Subpart D—Importer Reporting
part 820 of this chapter.
Requirements
(c) References in this part to regu-
803.40 If I am an importer, what reporting latory sections of the Code of Federal
requirements apply to me? Regulations are to chapter I of title 21,
803.42 If I am an importer, what informa- unless otherwise noted.
tion must I submit in my individual ad-
verse event reports? § 803.3 How does FDA define the terms
used in this part?
Subpart E—Manufacturer Reporting
Requirements Some of the terms we use in this part
are specific to medical device reporting
803.50 If I am a manufacturer, what report- and reflect the language used in the
ing requirements apply to me? statute (law). Other terms are more
803.52 If I am a manufacturer, what infor-
general and reflect our interpretation
mation must I submit in my individual
adverse event reports? of the law. This section defines the fol-
803.53 If I am a manufacturer, in which cir- lowing terms as used in this part:
cumstances must I submit a 5-day re- (a) Ambulatory surgical facility (ASF)
port? means a distinct entity that operates
803.56 If I am a manufacturer, in what cir- for the primary purpose of furnishing
cumstances must I submit a supple- same day outpatient surgical services
mental or followup report and what are
to patients. An ASF may be either an
the requirements for such reports?
803.58 Foreign manufacturers. independent entity (i.e., not a part of a
provider of services or any other facil-
AUTHORITY: 21 U.S.C. 352, 360, 360i, 360j, 371, ity) or operated by another medical en-
374.
tity (e.g., under the common owner-
SOURCE: 79 FR 8846, Feb. 14, 2014, unless ship, licensure, or control of an entity).
otherwise noted. An ASF is subject to this regulation
regardless of whether it is licensed by a
Subpart A—General Provisions Federal, State, municipal, or local gov-
ernment or regardless of whether it is
§ 803.1 What does this part cover? accredited by a recognized accredita-
(a) This part establishes the require- tion organization. If an adverse event
ments for medical device reporting for meets the criteria for reporting, the
device user facilities, manufacturers, ASF must report that event regardless
importers, and distributors. If you are of the nature or location of the medical
a device user facility, you must report service provided by the ASF.
deaths and serious injuries that a de- (b) Become aware means that an em-
vice has or may have caused or contrib- ployee of the entity required to report
uted to, establish and maintain adverse has acquired information that reason-
event files, and submit summary an- ably suggests a reportable adverse
nual reports. If you are a manufacturer event has occurred.
or importer, you must report deaths (1) If you are a device user facility,
and serious injuries that your device you are considered to have ‘‘become
has or may have caused or contributed aware’’ when medical personnel, as de-
to, you must report certain device mal- fined in this section, who are employed
functions, and you must establish and by or otherwise formally affiliated
maintain adverse event files. If you are with your facility, obtain information
a manufacturer, you must also submit about a reportable event.
specified followup. These reports help (2) If you are a manufacturer, you are
us to protect the public health by help- considered to have become aware of an
ing to ensure that devices are not adul- event when any of your employees be-
terated or misbranded and are safe and comes aware of a reportable event that
effective for their intended use. If you is required to be reported within 30 cal-
are a medical device distributor, you endar days or that is required to be re-
must maintain records (files) of inci- ported within 5 work days because we
dents, but you are not required to re- had requested reports in accordance
port these incidents. with § 803.53(b). You are also considered
65
§ 803.3 21 CFR Ch. I (4–1–23 Edition)
to have become aware of an event when Other devices are not labeled as to
any of your employees with manage- their respective EOL, but are expected
ment or supervisory responsibilities to remain operational through activi-
over persons with regulatory, sci- ties such as maintenance, repairs, or
entific, or technical responsibilities, or upgrades, for an estimated period of
whose duties relate to the collection time.
and reporting of adverse events, be- (g) FDA, we, us, or Agency means the
comes aware, from any information, in- Food and Drug Administration.
cluding any trend analysis, that a re- (h) Five-day report means a medical
portable MDR event or events neces- device report that must be submitted
sitates remedial action to prevent an by a manufacturer to us under § 803.53
unreasonable risk of substantial harm within 5 work days.
to the public health. (i) Hospital means a distinct entity
(3) If you are an importer, you are that operates for the primary purpose
considered to have become aware of an of providing diagnostic, therapeutic
event when any of your employees be- (such as medical, occupational, speech,
comes aware of a reportable event that physical), surgical, and other patient
is required to be reported by you with- services for specific and general med-
in 30 days. ical conditions. Hospitals include gen-
(c) Caused or contributed means that a eral, chronic disease, rehabilitative,
death or serious injury was or may psychiatric, and other special-purpose
have been attributed to a medical de- facilities. A hospital may be either
vice, or that a medical device was or independent (e.g., not a part of a pro-
may have been a factor in a death or vider of services or any other facility)
serious injury, including events occur- or may be operated by another medical
ring as a result of: entity (e.g., under the common owner-
(1) Failure, ship, licensure, or control of another
(2) Malfunction, entity). A hospital is covered by this
(3) Improper or inadequate design, regulation regardless of whether it is
(4) Manufacture, licensed by a Federal, State, municipal
(5) Labeling, or or local government or whether it is
(6) User error. accredited by a recognized accredita-
(d) Device user facility means a hos- tion organization. If an adverse event
pital, ambulatory surgical facility, meets the criteria for reporting, the
nursing home, outpatient diagnostic hospital must report that event regard-
facility, or outpatient treatment facil- less of the nature or location of the
ity as defined in this section, which is medical service provided by the hos-
not a physician’s office, as defined in pital.
this section. School nurse offices and (j) Importer means any person who
employee health units are not device imports a device into the United States
user facilities. and who furthers the marketing of a
(e) Distributor means any person device from the original place of manu-
(other than the manufacturer or im- facture to the person who makes final
porter) who furthers the marketing of delivery or sale to the ultimate user,
a device from the original place of but who does not repackage or other-
manufacture to the person who makes wise change the container, wrapper, or
final delivery or sale to the ultimate labeling of the device or device pack-
user, but who does not repackage or age. If you repackage or otherwise
otherwise change the container, wrap- change the container, wrapper, or la-
per, or labeling of the device or device beling, you are considered a manufac-
package. If you repackage or otherwise turer as defined in this section.
change the container, wrapper, or la- (k) Malfunction means the failure of a
beling, you are considered a manufac- device to meet its performance speci-
turer as defined in this section. fications or otherwise perform as in-
(f) Expected life of a device means the tended. Performance specifications in-
time that a device is expected to re- clude all claims made in the labeling
main functional after it is placed into for the device. The intended perform-
use. Certain implanted devices have ance of a device refers to the intended
specified ‘‘end of life’’ (EOL) dates. use for which the device is labeled or
66
marketed, as defined in § 801.4 of this gests that a device has or may have
chapter. caused or contributed to a death or se-
(l) Manufacturer means any person rious injury or
who manufactures, prepares, propa- (2) An event that manufacturers or
gates, compounds, assembles, or proc- importers become aware of that rea-
esses a device by chemical, physical, sonably suggests that one of their mar-
biological, or other procedure. The keted devices:
term includes any person who either: (i) May have caused or contributed to
(1) Repackages or otherwise changes a death or serious injury, or
the container, wrapper, or labeling of a (ii) Has malfunctioned and that the
device in furtherance of the distribu- device or a similar device marketed by
tion of the device from the original the manufacturer or importer would be
place of manufacture; likely to cause or contribute to a death
(2) Initiates specifications for devices or serious injury if the malfunction
that are manufactured by a second were to recur.
party for subsequent distribution by (p) Medical personnel means an indi-
the person initiating the specifica- vidual who:
tions; (1) Is licensed, registered, or certified
(3) Manufactures components or ac- by a State, territory, or other gov-
cessories that are devices that are erning body, to administer health care;
ready to be used and are intended to be (2) Has received a diploma or a degree
commercially distributed and intended in a professional or scientific dis-
to be used as is, or are processed by a cipline;
licensed practitioner or other qualified (3) Is an employee responsible for re-
person to meet the needs of a par- ceiving medical complaints or adverse
ticular patient; or event reports; or
(4) Is the U.S. agent of a foreign man- (4) Is a supervisor of these persons.
ufacturer. (q) Nursing home means:
(m) Manufacturer or importer report (1) An independent entity (i.e., not a
number. This number uniquely identi- part of a provider of services or any
fies each individual adverse event re- other facility) or one operated by an-
port submitted by a manufacturer or other medical entity (e.g., under the
importer. This number consists of the common ownership, licensure, or con-
following three parts: trol of an entity) that operates for the
(1) The FDA registration number for primary purpose of providing:
the manufacturing site of the reported (i) Skilled nursing care and related
device, or the registration number for services for persons who require med-
the importer. If the manufacturing site ical or nursing care;
or the importer does not have an estab- (ii) Hospice care to the terminally ill;
lishment registration number, we will or
assign a temporary MDR reporting (iii) Services for the rehabilitation of
number until the site is registered in the injured, disabled, or sick.
accordance with part 807 of this chap- (2) A nursing home is subject to this
ter. We will inform the manufacturer regulation regardless of whether it is
or importer of the temporary MDR re- licensed by a Federal, State, munic-
porting number; ipal, or local government or whether it
(2) The four-digit calendar year in is accredited by a recognized accredita-
which the report is submitted; and tion organization. If an adverse event
(3) The five-digit sequence number of meets the criteria for reporting, the
the reports submitted during the year, nursing home must report that event
starting with 00001. (For example, the regardless of the nature or location of
complete number will appear as fol- the medical service provided by the
lows: 1234567–2011–00001.) nursing home.
(n) MDR means medical device re- (r) Outpatient diagnostic facility
port. means:
(o) MDR reportable event (or reportable (1) A distinct entity that:
event) means: (i) Operates for the primary purpose

(1) An event that user facilities be- of conducting medical diagnostic tests
come aware of that reasonably sug- on patients,
67
§ 803.3 21 CFR Ch. I (4–1–23 Edition)
(ii) Does not assume ongoing respon- less of the nature or location of the
sibility for patient care, and medical service provided by the out-
(iii) Provides its services for use by patient treatment facility.
other medical personnel. (t) Patient of the facility means any
(2) Outpatient diagnostic facilities individual who is being diagnosed or
include outpatient facilities providing treated and/or receiving medical care
radiography, mammography, at or under the control or authority of
ultrasonography, electrocardiography, the facility. This includes employees of
magnetic resonance imaging, comput- the facility or individuals affiliated
erized axial tomography, and in vitro with the facility who, in the course of
testing. An outpatient diagnostic facil- their duties, suffer a device-related
ity may be either independent (i.e., not death or serious injury that has or may
a part of a provider of services or any have been caused or contributed to by
other facility) or operated by another a device used at the facility.
medical entity (e.g., under the common (u) Physician’s office means a facility
ownership, licensure, or control of an that operates as the office of a physi-
entity). An outpatient diagnostic facil- cian or other health care professional
ity is covered by this regulation re- for the primary purpose of examina-
gardless of whether it is licensed by a tion, evaluation, and treatment or re-
Federal, State, municipal, or local gov- ferral of patients. Examples of physi-
ernment or whether it is accredited by cian offices include: Dentist offices,
a recognized accreditation organiza- chiropractor offices, optometrist of-
tion. If an adverse event meets the cri- fices, nurse practitioner offices, school
teria for reporting, the outpatient di- nurse offices, school clinics, employee
agnostic facility must report that health clinics, or freestanding care
event regardless of the nature or loca- units. A physician’s office may be inde-
tion of the medical service provided by pendent, a group practice, or part of a
the outpatient diagnostic facility. Health Maintenance Organization.
(s) Outpatient treatment facility means
(v) Remedial action means any action
a distinct entity that operates for the
other than routine maintenance or
primary purpose of providing nonsur-
servicing of a device where such action
gical therapeutic (medical, occupa-
is necessary to prevent recurrence of a
tional, or physical) care on an out-
reportable event.
patient basis or in a home health care
(w) Serious injury means an injury or
setting. Outpatient treatment facili-
illness that:
ties include ambulance providers, res-
cue services, and home health care (1) Is life-threatening,
groups. Examples of services provided (2) Results in permanent impairment
by outpatient treatment facilities in- of a body function or permanent dam-
clude the following: Cardiac age to a body structure, or
defibrillation, chemotherapy, radio- (3) Necessitates medical or surgical
therapy, pain control, dialysis, speech intervention to preclude permanent
or physical therapy, and treatment for impairment of a body function or per-
substance abuse. An outpatient treat- manent damage to a body structure.
ment facility may be either inde- Permanent means irreversible impair-
pendent (i.e., not a part of a provider of ment or damage to a body structure or
services or any other facility) or oper- function, excluding trivial impairment
ated by another medical entity (e.g., or damage.
under the common ownership, licen- (x) User facility report number means
sure, or control of an entity). An out- the number that uniquely identifies
patient treatment facility is covered each report submitted by a user facil-
by this regulation regardless of wheth- ity to manufacturers and to us. This
er it is licensed by a Federal, State, number consists of the following three
municipal, or local government or parts:
whether it is accredited by a recog- (1) The user facility’s 10-digit Centers
nized accreditation organization. If an for Medicare and Medicaid Services
adverse event meets the criteria for re- (CMS) number (if the CMS number has
porting, the outpatient treatment fa- fewer than 10 digits, fill the remaining
cility must report that event regard- spaces with zeros);
68
(2) The four-digit calendar year in (v) For an HCT/P regulated as a de-
which the report is submitted; and vice, the distinct identification code
(3) The four-digit sequence number of required by § 1271.290(c) of this chapter.
the reports submitted for the year,
[79 FR 8846, Feb. 14, 2014, as amended at 80
starting with 0001. (For example, a FR 10587, Feb. 27, 2015]
complete user facility report number
will appear as follows: 1234560000–2011– § 803.9 What information from the re-
0001. If a user facility has more than ports do we disclose to the public?
one CMS number, it must select one
that will be used for all of its MDR re- (a) We may disclose to the public any
ports. If a user facility has no CMS report, including any FDA record of a
number, it should use all zeros in the telephone report, submitted under this
appropriate space in its initial report part. Our disclosures are governed by
(e.g., 0000000000–2011–0001). We will as- part 20 of this chapter.
sign a number for future use and send (b) Before we disclose a report to the
that number to the user facility. This public, we will delete the following:
number is used in our record of the ini- (1) Any information that constitutes
tial report, in subsequent reports, and trade secret or confidential commer-
in any correspondence with the user fa- cial or financial information under
cility. If a facility has multiple sites, § 20.61 of this chapter;
the primary site may submit reports (2) Any personal, medical, and simi-
for all sites and use one reporting num- lar information, including the serial
ber for all sites if the primary site pro- number of implanted devices, which
vides the name, address, and CMS num- would constitute an invasion of per-
ber for each respective site.) sonal privacy under § 20.63 of this chap-
(y) Work day means Monday through ter. However, if a patient requests a re-
Friday, except Federal holidays. port, we will disclose to that patient
(z) [Reserved] all the information in the report con-
(aa) Human cell, tissue, or cellular or cerning that patient, as provided in
tissue-based product (HCT/P) regulated as § 20.61 of this chapter; and
a device means an HCT/P as defined in (3) Any names and other identifying
§ 1271.3(d) of this chapter that does not information of a third party that vol-
meet the criteria in § 1271.10(a) and that untarily submitted an adverse event
is also regulated as a device. report.
(bb) Unique device identifier (UDI) (c) We may not disclose the identity
means an identifier that adequately of a device user facility that makes a
identifies a device through its distribu-
report under this part except in con-
tion and use by meeting the require-
nection with:
ments of § 830.20 of this chapter. A
unique device identifier is composed of: (1) An action brought to enforce sec-
(1) A device identifier—a mandatory, tion 301(q) of the Federal Food, Drug,
fixed portion of a UDI that identifies and Cosmetic Act (21 U.S.C. 331(q)), in-
the specific version or model of a de- cluding the failure or refusal to furnish
vice and the labeler of that device; and material or information required by
(2) A production identifier—a condi- section 519 of the Federal Food, Drug,
tional, variable portion of a UDI that and Cosmetic Act (21 U.S.C. 360i));
identifies one or more of the following (2) A communication to a manufac-
when included on the label of the de- turer of a device that is the subject of
vice: a report required to be submitted by a
(i) The lot or batch within which a user facility under § 803.30; or
device was manufactured; (3) A disclosure to employees of the
(ii) The serial number of a specific Department of Health and Human
device; Services, to the Department of Justice,
(iii) The expiration date of a specific or to the duly authorized committees
and subcommittees of the Congress.
device;
(iv) The date a specific device was
manufactured.
69
§ 803.10 21 CFR Ch. I (4–1–23 Edition)
§ 803.10 Generally, what are the re- § 803.11 What form should I use to sub-
porting requirements that apply to mit reports of individual adverse
me? events and where do I obtain these
forms?
(a) If you are a device user facility,
you must submit reports (described in (a) If you are a manufacturer or im-
subpart C of this part), as follows: porter, you must submit reports of in-
(1) Submit reports of individual ad- dividual adverse events to FDA in an
verse events no later than 10 work days electronic format in accordance with
§ 803.12(a) and § 803.20, unless granted an
after the day that you become aware of
exemption under § 803.19.
a reportable event:
(b) Importer reports submitted to de-
(i) Submit reports of device-related
vice manufacturers may be in paper
deaths to us and to the manufacturer, format or an electronic format that in-
if known, or cludes all required data fields to ensure
(ii) Submit reports of device-related that the manufacturer has all required
serious injuries to the manufacturers information.
or, if the manufacturer is unknown, (c) If you are a user facility, you
submit reports to us. must submit reports of individual ad-
(2) Submit annual reports (described verse events in accordance with
in § 803.33) to us. § 803.12(b) and § 803.20.
(b) If you are an importer, you must (d) Form FDA 3500A is available on
submit reports (described in subpart D the internet at https://
of this part), as follows: www.accessdata.fda.gov/scripts/
(1) Submit reports of individual ad- medwatch/index.cfm.
verse events no later than 30 calendar [79 FR 8846, Feb. 14, 2014, as amended at 80
days after the day that you become FR 10587, Feb. 27, 2015; 85 FR 18441, Apr. 2,
aware of a reportable event: 2020]
(i) Submit reports of device-related
deaths or serious injuries to us and to § 803.12 How do I submit initial and
the manufacturer or supplemental or followup reports?
(ii) Submit reports of device-related (a) Manufacturers and importers
malfunctions to the manufacturer. must submit initial and supplemental
(2) [Reserved] or followup reports to FDA in an elec-
(c) If you are a manufacturer, you tronic format that FDA can process,
must submit reports (described in sub- review, and archive.
part E of this part) to us, as follows: (b) User facilities that submit their
(1) Submit reports of individual ad- reports and additional information to
verse events no later than 30 calendar FDA electronically must use an elec-
tronic format that FDA can process,
days after the day that you become
review, and archive. User facilities that
aware of a reportable death, serious in-
submit their reports to FDA on paper
jury, or malfunction. must submit any written report or ad-
(2) Submit reports of individual additional information required under
verse events no later than 5 work days this part to FDA, CDRH, Medical De-
after the day that you become aware vice Reporting, P.O. Box 3002, Rock-
of: ville, MD 20847–3002, using Form FDA
(i) A reportable event that requires 3500A. Each report must be identified
remedial action to prevent an unrea- (e.g., ‘‘User Facility Report’’ or ‘‘An-
sonable risk of substantial harm to the nual Report’’).
public health or (c) If you are confronted with a pub-
(ii) A reportable event for which we lic health emergency, this can be
made a written request. brought to FDA’s attention by con-
(3) Submit supplemental reports if tacting FDA’s Office of Crisis Manage-
you obtain information that you did ment, Emergency Operations Center by
not submit in an initial report. telephone, 24-hours a day, at 301–796–
8240 or toll free at 866–300–4374, followed

by the submission of an email to: emer-
[email protected].
70
NOTE: This action does not satisfy your ob- § 803.17 What are the requirements for
ligation to report under part 803. developing, maintaining, and imple-
(d) You may submit a voluntary tele- menting written MDR procedures
phone report to the MedWatch office at that apply to me?
800–FDA–1088. You may also obtain in- If you are a user facility, importer,
formation regarding voluntary report- or manufacturer, you must develop,
ing from the MedWatch office at 800–
maintain, and implement written MDR
FDA–1088. You may also find the vol-
procedures for the following:
untary Form FDA 3500 and instructions
to complete it at: http://www.fda.gov/ (a) Internal systems that provide for:
Safety/MedWatch/HowToReport/ (1) Timely and effective identifica-
DownloadForms/default.htm. tion, communication, and evaluation of
events that may be subject to MDR re-
§ 803.13 Do I need to submit reports in quirements;
English? (2) A standardized review process or
Yes. You must submit all reports re- procedure for determining when an
quired by this part in English. event meets the criteria for reporting
under this part; and
§ 803.15 How will I know if you require (3) Timely transmission of complete
more information about my medical medical device reports to manufactur-
device report? ers or to us, or to both if required.
(a) We will notify you in writing if we (b) Documentation and record-
require additional information and will keeping requirements for:
tell you what information we need. We (1) Information that was evaluated to
will require additional information if determine if an event was reportable;
we determine that protection of the (2) All medical device reports and in-
public health requires additional or formation submitted to manufacturers
clarifying information for medical de- and/or us;
vice reports submitted to us and in (3) Any information that was evalu-
cases when the additional information ated for the purpose of preparing the
is beyond the scope of FDA reporting submission of annual reports; and
forms or is not readily accessible to us. (4) Systems that ensure access to in-
(b) In any request under this section, formation that facilitates timely fol-
we will state the reason or purpose for lowup and inspection by us.
the information request, specify the
due date for submitting the informa- § 803.18 What are the requirements for
tion, and clearly identify the reported establishing and maintaining MDR
event(s) related to our request. If we files or records that apply to me?
verbally request additional informa- (a) If you are a user facility, im-
tion, we will confirm the request in
porter, or manufacturer, you must es-
writing.
tablish and maintain MDR event files.
§ 803.16 When I submit a report, does You must clearly identify all MDR
the information in my report con- event files and maintain them to facili-
stitute an admission that the device tate timely access.
caused or contributed to the report- (b)(1) For purposes of this part,
able event? ‘‘MDR event files’’ are written or elec-
No. A report or other information tronic files maintained by user facili-
submitted by you, and our release of ties, importers, and manufacturers.
that report or information, is not nec- MDR event files may incorporate ref-
essarily an admission that the device, erences to other information (e.g.,
or you or your employees, caused or medical records, patient files, engi-
contributed to the reportable event. neering reports), in lieu of copying and
You do not have to admit and may maintaining duplicates in this file.
deny that the report or information Your MDR event files must contain:
submitted under this part constitutes (i) Information in your possession or
an admission that the device, you, or references to information related to

your employees, caused or contributed the adverse event, including all docu-
to a reportable event. mentation of your deliberations and
71
§ 803.19 21 CFR Ch. I (4–1–23 Edition)
decision making processes used to de- life of the device, whichever is greater.
termine if a device-related death, seri- You must maintain copies of these
ous injury, or malfunction was or was records for this period even if you no
not reportable under this part; longer distribute the device.
(ii) Copies of all reports submitted (3) You must maintain the device
under this part (whether paper or elec- complaint files established under this
tronic), and of all other information re- section at your principal business es-
lated to the event that you submitted tablishment. If you are also a manufac-
to us or other entities such as an im- turer, you may maintain the file at the
porter, distributor, or manufacturer; same location as you maintain your
and complaint file under part 820 of this
(iii) Copies of all electronic acknowl- chapter. You must permit any author-
edgments FDA sends you in response to ized FDA employee, at all reasonable
electronic MDR submissions. times, to access, to copy, and to verify
(2) If you are a user facility, im- the records required by this part.
porter, or manufacturer, you must per- (e) If you are a manufacturer, you
mit any authorized FDA employee, at may maintain MDR event files as part
all reasonable times, to access, to copy, of your complaint file, under part 820 of
and to verify the records required by this chapter, if you prominently iden-
this part. tify these records as MDR reportable
(c) If you are a user facility, you events. We will not consider your sub-
must retain an MDR event file relating mitted MDR report to comply with this
to an adverse event for a period of 2
part unless you evaluate an event in
years from the date of the event. If you
accordance with the quality system re-
are a manufacturer or importer, you
quirements described in part 820 of this
must retain an MDR event file relating
chapter. You must document and main-
to an adverse event for a period of 2
tain in your MDR event files an expla-
years from the date of the event or a
nation of why you did not submit or
period of time equivalent to the ex-
could not obtain any information re-
pected life of the device, whichever is
quired by this part, as well as the re-
greater. If the device is no longer dis-
sults of your evaluation of each event.
tributed, you still must maintain MDR
event files for the time periods de- § 803.19 Are there exemptions,
scribed in this paragraph (c). variances, or alternative forms of
(d)(1) If you are a device distributor, adverse event reporting require-
you must establish and maintain de- ments?
vice complaint records (files). Your
(a) We exempt the following persons
records must contain any incident in-
from the adverse event reporting re-
formation, including any written, elec-
tronic, or oral communication, either quirements in this part:
received or generated by you, that al- (1) A licensed practitioner who pre-
leges deficiencies related to the iden- scribes or administers devices intended
tity (e.g., labeling), quality, durability, for use in humans and manufactures or
reliability, safety, effectiveness, or per- imports devices solely for use in diag-
formance of a device. You must also nosing and treating persons with whom
maintain information about your eval- the practitioner has a ‘‘physician-pa-
uation of the allegations, if any, in the tient’’ relationship;
incident record. You must clearly iden- (2) An individual who manufactures
tify the records as device incident devices intended for use in humans
records and file these records by device solely for this person’s use in research
name. You may maintain these records or teaching and not for sale. This in-
in written or electronic format. You cludes any person who is subject to al-
must back up any file maintained in ternative reporting requirements under
electronic format. the investigational device exemption
(2) You must retain copies of the re- regulations (described in part 812 of
quired device incident records for a pe- this chapter), which require reporting
riod of 2 years from the date of inclu- of all adverse device effects; and
sion of the record in the file or for a pe- (3) Dental laboratories or optical lab-
riod of time equivalent to the expected oratories.
72
(b) If you are a manufacturer, im- Subpart B—Generally Applicable

porter, or user facility, you may re- Requirements for Individual
quest an exemption or variance from
any or all of the reporting require-
Adverse Event Reports
ments in this part, including the re- § 803.20 How do I complete and submit
quirements of § 803.12. You must submit an individual adverse event report?
the request to the Center for Devices (a) What form must I complete and sub-
and Radiological Health (CDRH) in mit?
writing at [email protected]. (1) If you are a health professional or
Your request must include information consumer or other entity, you may
necessary to identify you and the de- submit voluntary reports to FDA re-
vice; a complete statement of the regarding devices or other FDA-regulated
quest for exemption, variance, or alter- products using the Form FDA 3500.
native reporting; and an explanation (2) To submit a mandatory report in
why your request is justified. If you are written form, a user facility must use
requesting an exemption from the re- Form FDA 3500A.
quirement to submit reports to FDA in (3) An electronic submission of a
electronic format under § 803.12(a), your mandatory report from a user facility,
request should indicate for how long importer, or manufacturer must con-
you will require this exemption. tain the information from the applica-
(c) If you are a manufacturer, im- ble blocks of Form FDA 3500A. All elec-
porter, or user facility, we may grant tronic submissions must include infor-
in writing an exemption or variance mation about the patient, the event,
from, or alternative to, any or all of the device, and the ‘‘initial reporter.’’
the reporting requirements in this An electronic submission from a user
part, and may change the frequency of facility or importer must include the
reporting to quarterly, semiannually, information from block F. An elec-
annually or other appropriate time pe- tronic submission from a manufacturer
riod. We may grant these modifications must include the information from
in response to your request, as de- blocks G and H. If you are a manufac-
scribed in paragraph (b) of this section, turer and you receive a report from a
or at our discretion. When we grant user facility or importer, you must in-
modifications to the reporting require- corporate that information in your
ments, we may impose other reporting electronic submission and include any
requirements to ensure the protection corrected or missing information.
of public health. (b) To whom must I submit reports and
(d) We may revoke or modify in writ- when?
ing an exemption, variance, or alter- (1) If you are a user facility, you
native reporting requirement if we de- must submit MDR reports to:
termine that revocation or modifica- (i) The manufacturer and to us no
tion is necessary to protect the public later than 10 work days after the day
health. that you become aware of information
(e) If we grant your request for a re- that reasonably suggests that a device
porting modification, you must submit has or may have caused or contributed
any reports or information required in to a death or
our approval of the modification. The (ii) The manufacturer no later than
conditions of the approval will replace 10 work days after the day that you be-
and supersede the regular reporting re- come aware of information that rea-
quirement specified in this part until sonably suggests that a device has or
such time that we revoke or modify the may have caused or contributed to a
alternative reporting requirements in serious injury. If the manufacturer is
accordance with paragraph (d) of this not known, you must submit this re-
section or until the date specified in port to us.
our response granting your variance, at (2) If you are an importer, you must
which time the provisions of this part submit MDR reports to:
will again apply. (i) The manufacturer and to us, no
[79 FR 8846, Feb. 14, 2014, as amended at 85 later than 30 calendar days after the
FR 18441, Apr. 2, 2020; 88 FR 16879, Mar. 21, day that you become aware of informa-
2023] tion that reasonably suggests that a
73
§ 803.21 21 CFR Ch. I (4–1–23 Edition)
device has or may have caused or con- whether or not a device-related event
tributed to a death or serious injury or was reportable.
(ii) The manufacturer, no later than
30 calendar days after receiving infor- § 803.21 Where can I find the reporting
mation that a device you market has codes for adverse events that I use
with medical device reports?
malfunctioned and that this device or a
similar device that you market would (a) The MedWatch Medical Device
be likely to cause or contribute to a Reporting Code Instruction Manual
death or serious injury if the malfunc- contains adverse event codes for use
tion were to recur. with Form FDA 3500A. You may obtain
(3) If you are a manufacturer, you the coding manual from FDA’s website
must submit MDR reports to us: at: https://www.fda.gov/medical-devices/
(i) No later than 30 calendar days mandatory-reporting-requirements-manu-
after the day that you become aware of facturers-importers-and-device-user-facili-
information that reasonably suggests ties/mdr-adverse-event-codes.
that a device may have caused or con- (b) We may sometimes use additional
tributed to a death or serious injury or coding of information on the reporting
(ii) No later than 30 calendar days forms or modify the existing codes. If
after the day that you become aware of we do make modifications, we will en-
information that reasonably suggests a sure that we make the new coding in-
device has malfunctioned and that this formation available to all reporters.
device or a similar device that you [79 FR 8846, Feb. 14, 2014, as amended at 85
market would be likely to cause or FR 18441, Apr. 2, 2020]
contribute to a death or serious injury
if the malfunction were to recur; or § 803.22 What are the circumstances in
(iii) Within 5 work days if required by which I am not required to file a re-
§ 803.53. port?
(c) What kind of information reason- (a) If you become aware of informa-
ably suggests that a reportable event has tion from multiple sources regarding
occurred? the same patient and same reportable
(1) Any information, including pro- event, you may submit one medical de-
fessional, scientific, or medical facts, vice report.
observations, or opinions, may reason- (b) You are not required to submit a
ably suggest that a device has caused medical device report if:
or may have caused or contributed to (1) You are a user facility, importer,
an MDR reportable event. An MDR re- or manufacturer, and you determine
portable event is a death, a serious in- that the information received is erro-
jury, or, if you are a manufacturer or neous in that a device-related adverse
importer, a malfunction that would be event did not occur. You must retain
likely to cause or contribute to a death documentation of these reports in your
or serious injury if the malfunction MDR files for the time periods speci-
were to recur. fied in § 803.18.
(2) If you are a user facility, im- (2) You are a manufacturer or im-
porter, or manufacturer, you do not porter and you did not manufacture or
have to report an adverse event if you import the device about which you
have information that would lead a have adverse event information. When
person who is qualified to make a med- you receive reportable event informa-
ical judgment reasonably to conclude tion in error, you must forward this in-
that a device did not cause or con- formation to us with a cover letter ex-
tribute to a death or serious injury, or plaining that you did not manufacture
that a malfunction would not be likely or import the device in question.
to cause or contribute to a death or se-
rious injury if it were to recur. Persons § 803.23 Where can I find information
qualified to make a medical judgment on how to prepare and submit an
include physicians, nurses, risk man- MDR in electronic format?
agers, and biomedical engineers. You (a) You may obtain information on
must keep in your MDR event files (de- how to prepare and submit reports in
scribed in § 803.18) the information that an electronic format that FDA can
the qualified person used to determine process, review, and archive at: http://
74
www.fda.gov/ForIndustry/FDAeSubmitter/ evaluating information that you do not

ucm107903.htm. reasonably know.
(b) We may sometimes update infor-
mation on how to prepare and submit § 803.32 If I am a user facility, what in-
formation must I submit in my indi-
reports electronically. If we do make vidual adverse event reports?
modifications, we will ensure that we
alert reporters by updating the eMDR You must include the following infor-
Web page. mation in your report, if reasonably
known to you, as described in
§ 803.30(b). These types of information
Subpart C—User Facility Reporting correspond generally to the elements of
Requirements Form FDA 3500A:
(a) Patient information (Form FDA
§ 803.30 If I am a user facility, what re-
porting requirements apply to me? 3500A, Block A). You must submit the
following:
(a) You must submit reports to the (1) Patient name or other identifier;
manufacturer or to us, or both, as spec- (2) Patient age at the time of event,
ified in paragraphs (a)(1) and (a)(2) of or date of birth;
this section as follows: (3) Patient gender; and
(1) Reports of death. You must submit (4) Patient weight.
a report to us as soon as practicable (b) Adverse event or product problem
but no more than 10 work days after (Form FDA 3500A, Block B). You must
the day that you become aware of in- submit the following:
formation, from any source, that rea- (1) Identification of adverse event or
sonably suggests that a device has or product problem;
may have caused or contributed to the (2) Outcomes attributed to the ad-
death of a patient of your facility. You verse event (e.g., death or serious in-
must also submit the report to the de- jury). An outcome is considered a seri-
vice manufacturer, if known. You must ous injury if it is:
submit the information required by (i) A life-threatening injury or ill-
§ 803.32. Reports sent to the Agency ness;
must be submitted in accordance with (ii) A disability resulting in perma-
the requirements of § 803.12(b). nent impairment of a body function or
(2) Reports of serious injury. You must permanent damage to a body structure;
submit a report to the manufacturer of or
the device no later than 10 work days (iii) An injury or illness that requires
after the day that you become aware of intervention to prevent permanent im-
information, from any source, that rea- pairment of a body structure or func-
sonably suggests that a device has or tion;
may have caused or contributed to a (3) Date of event;
serious injury to a patient of your fa- (4) Date of this report;
cility. If the manufacturer is not (5) Description of event or problem,
known, you must submit the report to including a discussion of how the de-
us. You must report information re- vice was involved, nature of the prob-
quired by § 803.32. Reports sent to the lem, patient followup or required treat-
Agency must be submitted in accord- ment, and any environmental condi-
ance with the requirements of § 803.12 tions that may have influenced the
(b). event;
(b) What information does FDA con- (6) Description of relevant tests, in-
sider ‘‘reasonably known’’ to me? You cluding dates and laboratory data; and
must submit all information required (7) Description of other relevant his-
in this subpart C that is reasonably tory, including preexisting medical
known to you. This information in- conditions.
cludes information found in documents (c) Device information (Form FDA
that you possess and any information 3500A, Block D). You must submit the
that becomes available as a result of following:
reasonable followup within your facil- (1) Brand name;

ity. You are not required to evaluate or (2) Product Code, if known, and Com-
investigate the event by obtaining or mon Device Name;
75
§ 803.33 21 CFR Ch. I (4–1–23 Edition)
(3) Manufacturer name, city, and clude the report number of the initial
state; report;
(4) Model number, catalog number, (8) Date of your report (month, day,
serial number, lot number, or other year);
identifying number; expiration date; (9) Approximate age of device;
and unique device identifier (UDI) that (10) Event problem codes—patient
appears on the device label or on the code and device code (refer to the
device package; ‘‘MedWatch Medical Device Reporting
(5) Operator of the device (health pro- Code Instructions’’);
fessional, lay user/patient, other); (11) Whether a report was sent to us
(6) Date of device implantation and the date it was sent (month, day,
(month, day, year), if applicable; year);
(7) Date of device explantation (12) Location where the event oc-
(month, day, year), if applicable; curred;
(8) Whether the device is a single-use (13) Whether the report was sent to
device that was reprocessed and reused the manufacturer and the date it was
on a patient (Yes, No)? sent (month, day, year); and
(9) If the device is a single-use device (14) Manufacturer name and address,
that was reprocessed and reused on a if available.
patient (yes to paragraph (c)(8) of this [79 FR 8846, Feb. 14, 2014, as amended at 80
section), the name and address of the FR 10587, Feb. 27, 2015]
reprocessor;
(10) Whether the device was available § 803.33 If I am a user facility, what
must I include when I submit an an-
for evaluation and whether the device nual report?
was returned to the manufacturer; if
so, the date it was returned to the (a) You must submit to us an annual
manufacturer; and report on Form FDA 3419. You must
(11) Concomitant medical products submit an annual report by January 1,
and therapy dates. (Do not report prod- of each year. You may obtain this form
ucts that were used to treat the event.) on the internet at: https://www.fda.gov/
(d) Initial reporter information media/72292/download.
(Form FDA 3500A, Block E). You must (b) You must clearly identify your
submit the following: annual report as such. You must sub-
(1) Name, address, and telephone mit your annual report to FDA, CDRH,
number of the reporter who initially Medical Device Reporting, P.O. Box
provided information to you, or to the 3002, Rockville, MD 20847–3002. Your an-
manufacturer or distributor; nual report must include:
(1) Your CMS provider number used
(2) Whether the initial reporter is a
for medical device reports, or the num-
health professional;
ber assigned by us for reporting pur-
(3) Occupation; and
poses in accordance with § 803.3;
(4) Whether the initial reporter also (2) Reporting year;
sent a copy of the report to us, if (3) Your name and complete address;
known. (4) Total number of reports attached
(e) User facility information (Form or summarized;
FDA 3500A, Block F). You must submit (5) Date of the annual report and re-
the following: port numbers identifying the range of
(1) An indication that this is a user medical device reports that you sub-
facility report (by marking the user fa- mitted during the report period (e.g.,
cility box on the form); 1234567890–2011–0001 through 1000);
(2) Your user facility number; (6) Name, position title, and com-
(3) Your address; plete address of the individual des-
(4) Your contact person; ignated as your contact person respon-
(5) Your contact person’s telephone sible for reporting to us and whether
number; that person is a new contact for you;
(6) Date that you became aware of and
the event (month, day, year); (7) Information for each reportable
(7) Type of report (initial or fol- event that occurred during the annual
lowup); if it is a followup, you must in- reporting period including:
76
(i) Report number; your own research, testing, evaluation,

(ii) Name and address of the device servicing, or maintenance of one of
manufacturer; your devices, that reasonably suggests
(iii) Device brand name and common that one of your devices has malfunc-
name; tioned and that this device or a similar
(iv) Product model, catalog, serial, device that you market would be likely
and lot number and unique device iden- to cause or contribute to a death or se-
tifier (UDI) that appears on the device rious injury if the malfunction were to
label or on the device package; recur. You must submit the informa-
(v) A brief description of the event tion required by § 803.42. Reports to
reported to the manufacturer and/or manufacturers may be made in accord-
us; and ance with § 803.11(b).
(vi) Where the report was submitted,
i.e., to the manufacturer, importer, or § 803.42 If I am an importer, what in-
us. formation must I submit in my indi-
(c) In lieu of submitting the informa- vidual adverse event reports?
tion in paragraph (b)(7) of this section, You must include the following infor-
you may submit a copy of each medical mation in your report, if the informa-
device report that you submitted to tion is known or should be known to
the manufacturers and/or to us during you, as described in § 803.40. These
the reporting period. types of information correspond gen-
(d) If you did not submit any medical erally to the format of Form FDA
device reports to manufacturers or us 3500A:
during the time period, you do not need (a) Patient information (Form FDA
to submit an annual report. 3500A, Block A). You must submit the
[79 FR 8846, Feb. 14, 2014, as amended at 80 following:
FR 10587, Feb. 27, 2015; 85 FR 18442, Apr. 2, (1) Patient name or other identifier;
2020] (2) Patient age at the time of event,
or date of birth;
Subpart D—Importer Reporting (3) Patient gender; and
Requirements (4) Patient weight.
(b) Adverse event or product problem
§ 803.40 If I am an importer, what re- (Form FDA 3500A, Block B). You must
porting requirements apply to me? submit the following:
(a) Reports of deaths or serious injuries. (1) Identification of adverse event or
You must submit a report to us, and a product problem;
copy of this report to the manufac- (2) Outcomes attributed to the ad-
turer, as soon as practicable, but no verse event (e.g., death or serious in-
later than 30 calendar days after the jury). An outcome is considered a seri-
day that you receive or otherwise be- ous injury if it is:
come aware of information from any (i) A life-threatening injury or ill-
source, including user facilities, indi- ness;
viduals, or medical or scientific lit- (ii) A disability resulting in perma-
erature, whether published or unpub- nent impairment of a body function or
lished, that reasonably suggests that permanent damage to a body structure;
one of your marketed devices may have or
caused or contributed to a death or se- (iii) An injury or illness that requires
rious injury. You must submit the in- intervention to prevent permanent im-
formation required by § 803.42. Reports pairment of a body structure or func-
sent to the Agency must be submitted tion;
in accordance with the requirements of (3) Date of event;
§ 803.12(a). (4) Date of this report;
(b) Reports of malfunctions. You must (5) Description of the event or prob-
submit a report to the manufacturer as lem, including a discussion of how the
soon as practicable but no later than 30 device was involved, nature of the
calendar days after the day that you problem, patient followup or required
receive or otherwise become aware of treatment, and any environmental con-

information from any source, including ditions that may have influenced the
user facilities, individuals, or through event;
77
§ 803.50 21 CFR Ch. I (4–1–23 Edition)
(6) Description of relevant tests, in- (1) An indication that this is an im-
cluding dates and laboratory data; and porter report (by marking the importer
(7) Description of other relevant pa- box on the form);
tient history, including preexisting (2) Your importer report number;
medical conditions. (3) Your address;
(c) Device information (Form FDA (4) Your contact person;
3500A, Block D). You must submit the (5) Your contact person’s telephone
following: number;
(1) Brand name; (6) Date that you became aware of
(2) Product Code, if known, and Com- the event (month, day, year);
mon Device Name; (7) Type of report (initial or fol-
(3) Manufacturer name, city, and lowup). If it is a followup report, you
state; must include the report number of
(4) Model number, catalog number, your initial report;
serial number, lot number, or other (8) Date of your report (month, day,
identifying number; expiration date; year);
and unique device identifier (UDI) that (9) Approximate age of device;
appears on the device label or on the (10) Event problem codes—patient
device package; code and device code (refer to FDA
(5) Operator of the device (health pro- MedWatch Medical Device Reporting
fessional, lay user/patient, other); Code Instructions);
(6) Date of device implantation (11) Whether a report was sent to us
(month, day, year), if applicable; and the date it was sent (month, day,
(7) Date of device explanation year);
(month, day, year), if applicable; (12) Location where event occurred;
(8) Whether the device is a single-use (13) Whether a report was sent to the
device that was reprocessed and reused manufacturer and the date it was sent
on a patient (Yes, No)? (month, day, year); and
(9) If the device is a single-use device (14) Manufacturer name and address,
that was reprocessed and reused on a if available.
patient (yes to paragraph (c)(8) of this [79 FR 8846, Feb. 14, 2014, as amended at 80
section), the name and address of the FR 10587, Feb. 27, 2015]
reprocessor;
(10) Whether the device was available Subpart E—Manufacturer
for evaluation, and whether the device
was returned to the manufacturer, and
Reporting Requirements
if so, the date it was returned to the § 803.50 If I am a manufacturer, what
manufacturer; and reporting requirements apply to
(11) Concomitant medical products me?
and therapy dates. (Do not report prod- (a) If you are a manufacturer, you
ucts that were used to treat the event.) must report to us the information re-
(d) Initial reporter information quired by § 803.52 in accordance with
(Form FDA 3500A, Block E). You must the requirements of § 803.12(a), no later
submit the following: than 30 calendar days after the day
(1) Name, address, and telephone that you receive or otherwise become
number of the reporter who initially aware of information, from any source,
provided information to the manufac- that reasonably suggests that a device
turer, user facility, or distributor; that you market:
(2) Whether the initial reporter is a (1) May have caused or contributed to
health professional; a death or serious injury or
(3) Occupation; and (2) Has malfunctioned and this device
(4) Whether the initial reporter also or a similar device that you market
sent a copy of the report to us, if would be likely to cause or contribute
known. to a death or serious injury, if the mal-
(e) Importer information (Form FDA function were to recur.

3500A, Block F). You must submit the (b) What information does FDA con-
following: sider ‘‘reasonably known’’ to me?
78
(1) You must submit all information jury). An outcome is considered a seri-
required in this subpart E that is rea- ous injury if it is:
sonably known to you. We consider the (i) A life-threatening injury or ill-
following information to be reasonably ness;
known to you: (ii) A disability resulting in perma-
(i) Any information that you can ob- nent impairment of a body function or
tain by contacting a user facility, im- permanent damage to a body structure;
porter, or other initial reporter; or
(ii) Any information in your posses- (iii) An injury or illness that requires
sion; or intervention to prevent permanent im-
(iii) Any information that you can pairment of a body structure or func-
obtain by analysis, testing, or other tion;
evaluation of the device. (3) Date of event;
(2) You are responsible for obtaining (4) Date of this report;
and submitting to us information that (5) Description of the event or prob-
is incomplete or missing from reports lem, including a discussion of how the
submitted by user facilities, importers, device was involved, nature of the
and other initial reporters. problem, patient followup or required
(3) You are also responsible for con- treatment, and any environmental con-
ducting an investigation of each event ditions that may have influenced the
and evaluating the cause of the event. event;
If you cannot submit complete infor- (6) Description of relevant tests, in-
mation on a report, you must provide a cluding dates and laboratory data; and
statement explaining why this infor- (7) Other relevant patient history in-
mation was incomplete and the steps cluding preexisting medical conditions.
you took to obtain the information. If (c) Device information (Form FDA
you later obtain any required informa- 3500A, Block D). You must submit the
tion that was not available at the time following:
you filed your initial report, you must (1) Brand name;
submit this information in a supple- (2) Product Code, if known, and Com-
mental report under § 803.56 in accord- mon Device Name;
ance with the requirements of (3) Manufacturer name, city, and
§ 803.12(a). state;
(4) Model number, catalog number,
§ 803.52 If I am a manufacturer, what
information must I submit in my in- serial number, lot number, or other
dividual adverse event reports? identifying number; expiration date;
and unique device identifier (UDI) that
You must include the following infor- appears on the device label or on the
mation in your reports, if known or device package;
reasonably known to you, as described (5) Operator of the device (health pro-
in § 803.50(b). These types of informa- fessional, lay user/patient, other);
tion correspond generally to the for- (6) Date of device implantation
mat of Form FDA 3500A: (month, day, year), if applicable;
(a) Patient information (Form FDA (7) Date of device explantation
3500A, Block A). You must submit the (month, day, year), if applicable;
following: (8) Whether the device is a single-use
(1) Patient name or other identifier; device that was reprocessed and reused
(2) Patient age at the time of event, on a patient (Yes, No)?
or date of birth; (9) If the device is a single-use device
(3) Patient gender; and that was reprocessed and reused on a
(4) Patient weight. patient (yes to paragraph (c)(8) of this
(b) Adverse event or product problem section), the name and address of the
(Form FDA 3500A, Block B). You must reprocessor;
submit the following: (10) Whether the device was available
(1) Identification of adverse event or for evaluation, and whether the device
product problem; was returned to the manufacturer, and

(2) Outcomes attributed to the ad- if so, the date it was returned to the
verse event (e.g., death or serious in- manufacturer; and
79
§ 803.53 21 CFR Ch. I (4–1–23 Edition)
(11) Concomitant medical products (8) Whether the use of the device was
and therapy dates. (Do not report prod- initial, reuse, or unknown;
ucts that were used to treat the event.) (9) Whether remedial action was re-
(d) Initial reporter information ported as a removal or correction
(Form FDA 3500A, Block E). You must under section 519(f) of the Federal
submit the following: Food, Drug, and Cosmetic Act, and if it
(1) Name, address, and telephone was, provide the correction/removal re-
number of the reporter who initially port number; and
provided information to you, or to the (10) Your additional narrative; and/or
user facility or importer; (11) Corrected data, including:
(2) Whether the initial reporter is a (i) Any information missing on the
health professional; user facility report or importer report,
(3) Occupation; and including any event codes that were
(4) Whether the initial reporter also not reported, or information corrected
sent a copy of the report to us, if on these forms after your verification;
known. (ii) For each event code provided by
(e) Reporting information for all the user facility under § 803.32(e)(10) or
manufacturers (Form FDA 3500A, the importer under § 803.42(e)(10), you
Block G). You must submit the fol- must include a statement of whether
lowing: the type of the event represented by
(1) Your reporting office’s contact the code is addressed in the device la-
name and address and device manufac- beling; and
turing site; (iii) If your report omits any required
(2) Your contact person’s telephone information, you must explain why
number; this information was not provided and
(3) Your report sources; the steps taken to obtain this informa-
(4) Date received by you (month, day, tion.
year);
(5) PMA/510k Number and whether or [79 FR 8846, Feb. 14, 2014, as amended at 80
not the product is a combination prod- FR 10587, Feb. 27, 2015]
uct;
(6) Type of report being submitted § 803.53 If I am a manufacturer, in
(e.g., 5-day, initial, followup); and which circumstances must I submit
a 5-day report?
(7) Your report number.
(f) Device manufacturer information You must submit a 5-day report to us
(Form FDA 3500A, Block H). You must with the information required by
submit the following: § 803.52 in accordance with the require-
(1) Type of reportable event (death, ments of § 803.12(a) no later than 5 work
serious injury, malfunction, etc.); days after the day that you become
(2) Type of followup report, if appli- aware that:
cable (e.g., correction, response to FDA (a) An MDR reportable event neces-
request, etc); sitates remedial action to prevent an
(3) If the device was returned to you unreasonable risk of substantial harm
and evaluated by you, you must in- to the public health. You may become
clude a summary of the evaluation. If aware of the need for remedial action
you did not perform an evaluation, you from any information, including any
must explain why you did not perform trend analysis or
an evaluation; (b) We have made a written request
(4) Device manufacture date (month, for the submission of a 5-day report. If
day, year); you receive such a written request
(5) Whether the device was labeled from us, you must submit, without fur-
for single use; ther requests, a 5-day report for all
(6) Evaluation codes (including event subsequent events of the same nature
codes, method of evaluation, result, that involve substantially similar de-
and conclusion codes) (refer to FDA vices for the time period specified in
MedWatch Medical Device Reporting the written request. We may extend
Code Instructions); the time period stated in the original

(7) Whether remedial action was written request if we determine it is in
taken and the type of action; the interest of the public health.
80
§ 803.56 If I am a manufacturer, in and evaluation of the event to comport

what circumstances must I submit a with the requirements of § 803.50;
supplemental or followup report (3) Forward MDR complaints to the
and what are the requirements for foreign manufacturer and maintain
such reports? documentation of this requirement;
If you are a manufacturer, when you (4) Maintain complaint files in ac-
obtain information required under this cordance with § 803.18; and
part that you did not provide because (5) Register, list, and submit pre-
it was not known or was not available market notifications in accordance
when you submitted the initial report, with part 807 of this chapter.
you must submit the supplemental in- EFFECTIVE DATE NOTE: At 79 FR 8846, Feb.
formation to us within 30 calendar days 14, 2014, part 803 was revised. At 79 FR 8855,
of the day that you receive this infor- Feb. 14, 2014, § 803.58 was stayed indefinitely.
mation. You must submit the supple-
mental or followup report in accord- PART 806—MEDICAL DEVICES; RE-
ance with the requirements of PORTS OF CORRECTIONS AND
§ 803.12(a). On a supplemental or fol- REMOVALS
lowup report, you must:
(a) Indicate that the report being Subpart A—General Provisions
submitted is a supplemental or fol-
lowup report; Sec.
806.1 Scope.
(b) Submit the appropriate identi- 806.2 Definitions.
fication numbers of the report that you
are updating with the supplemental in- Subpart B—Reports and Records
formation (e.g., your original manufac-
turer report number and the user facil- 806.10 Reports of corrections and removals.
806.20 Records of corrections and removals
ity or importer report number of any not required to be reported.
report on which your report was based), 806.30 FDA access to records.
if applicable; and 806.40 Public availability of reports.
(c) Include only the new, changed, or AUTHORITY: 21 U.S.C. 352, 360, 360i, 360j, 371,
corrected information. 374.
§ 803.58 Foreign manufacturers. SOURCE: 62 FR 27191, May 19, 1997, unless

otherwise noted.
(a) Every foreign manufacturer
whose devices are distributed in the Subpart A—General Provisions
United States shall designate a U.S.
agent to be responsible for reporting in § 806.1 Scope.
accordance with § 807.40 of this chapter. (a) This part implements the provi-
The U.S. designated agent accepts re- sions of section 519(g) of the Federal
sponsibility for the duties that such Food, Drug, and Cosmetic Act (the act)
designation entails. Upon the effective requiring device manufacturers and
date of this regulation, foreign manu- importers to report promptly to the
facturers shall inform FDA, by letter, Food and Drug Administration (FDA)
of the name and address of the U.S. certain actions concerning device cor-
agent designated under this section rections and removals, and to maintain
and § 807.40 of this chapter, and shall records of all corrections and removals
update this information as necessary. regardless of whether such corrections
Such updated information shall be sub- and removals are required to be re-
mitted to FDA, within 5 days of a ported to FDA.
change in the designated agent infor- (b) The following actions are exempt
mation. from the reporting requirements of this
(b) U.S.-designated agents of foreign part:
manufacturers are required to: (1) Actions taken by device manufac-
(1) Report to FDA in accordance with turers or importers to improve the per-
§§ 803.50, 803.52, 803.53, and 803.56; formance or quality of a device but
(2) Conduct, or obtain from the for- that do not reduce a risk to health
eign manufacturer the necessary infor- posed by the device or remedy a viola-
mation regarding, the investigation tion of the act caused by the device.
81
§ 806.2 21 CFR Ch. I (4–1–23 Edition)
(2) Market withdrawal as defined in commercially distributed and are in-

§ 806.2(i) tended to be used as is, or are processed
(3) Routine servicing as defined in by a licensed practitioner or other
§ 806.2(l). qualified person to meet the needs of a
(4) Stock recovery as defined in particular patient.
§ 806.2(m). (i) Market withdrawal means a correc-
[62 FR 27191, May 19, 1997, as amended at 63 tion or removal of a distributed device
FR 42232, Aug. 7, 1998; 84 FR 12083, Apr. 1, that involves a minor violation of the
2019] act that would not be subject to legal
action by FDA or that involves no vio-
§ 806.2 Definitions. lation of the act, e.g., normal stock ro-
As used in this part: tation practices.
(a) Act means the Federal Food, (j) Removal means the physical re-
Drug, and Cosmetic Act. moval of a device from its point of use
(b) Agency or FDA means the Food to some other location for repair,
and Drug Administration. modification, adjustment, relabeling,
(c) Consignee means any person or destruction, or inspection.
firm that has received, purchased, or (k) Risk to health means
used a device subject to correction or (1) A reasonable probability that use
removal. of, or exposure to, the product will
(d) Correction means the repair, modi- cause serious adverse health con-
fication, adjustment, relabeling, de- sequences or death; or
struction, or inspection (including pa-
(2) That use of, or exposure to, the
tient monitoring) of a device without
product may cause temporary or medi-
its physical removal from its point of
cally reversible adverse health con-
use to some other location.
sequences, or an outcome where the
(e) Correction or removal report number
probability of serious adverse health
means the number that uniquely iden-
consequences is remote.
tifies each report submitted.
(f) Human cell, tissue, or cellular or tis- (l) Routine servicing means any regu-
sue-based product (HCT/P) regulated as a larly scheduled maintenance of a de-
device means an HCT/P as defined in vice, including the replacement of
§ 1271.3(d) of this chapter that does not parts at the end of their normal life ex-
meet the criteria in § 1271.10(a) and that pectancy, e.g., calibration, replace-
is also regulated as a device. ment of batteries, and responses to
(g) Importer means, for the purposes normal wear and tear. Repairs of an
of this part, any person who imports a unexpected nature, replacement of
device into the United States. parts earlier than their normal life ex-
(h) Manufacturer means any person pectancy, or identical repairs or re-
who manufactures, prepares, propa- placements of multiple units of a de-
gates, compounds, assembles, or proc- vice are not routine servicing.
esses a device by chemical, physical, (m) Stock recovery means the correc-
biological, or other procedures. The tion or removal of a device that has
term includes any person who: not been marketed or that has not left
(1) Repackages or otherwise changes the direct control of the manufacturer,
the container, wrapper, or labeling of a i.e., the device is located on the prem-
device in furtherance of the distribu- ises owned, or under the control of, the
tion of the device from the original manufacturer, and no portion of the
place of manufacture to the person who lot, model, code, or other relevant unit
makes final delivery or sale to the ulti- involved in the corrective or removal
mate user or consumer; action has been released for sale or use.
(2) Initiates specifications for devices (n) Unique device identifier (UDI)
that are manufactured by a second means an identifier that adequately
party for subsequent distribution by identifies a device through its distribu-
the person initiating the specification and use by meeting the require-
tions; or ments of § 830.20 of this chapter. A UDI
(3) Manufactures components or ac- is composed of:

cessories which are devices that are (1) A device identifier—a mandatory,
ready to be used and are intended to be fixed portion of a UDI that identifies
82
the specific version or model of a de- the complete number for the first cor-
vice and the labeler of that device; and rection report submitted on June 1,
(2) A production identifier—a condi- 1997, will appear as follows for a firm
tional, variable portion of a UDI that with the registration number 1234567:
identifies one or more of the following 1234567–6/1/97–001–C. The second correc-
when included on the label of the de- tion report number submitted by the
vice: same firm on July 1, 1997, would be
(i) The lot or batch within which a 1234567–7/1/97–002–C etc. For removals,
device was manufactured; the number will appear as follows:
(ii) The serial number of a specific 1234567–6/1/97–001–R and 1234567–7/1/97–
device; 002–R, etc. Firms that do not have a
(iii) The expiration date of a specific seven digit registration number may
device; use seven zeros followed by the month,
(iv) The date a specific device was date, year, and sequence number (i.e.
manufactured. 0000000–6/1/97–001–C for corrections and
(v) For an HCT/P regulated as a de- 0000000–7/1/97–001–R for removals). Re-
vice, the distinct identification code ports received without a seven digit
required by § 1271.290(c) of this chapter. registration number will be assigned a
[62 FR 27191, May 19, 1997, as amended at 63 seven digit central file number by the
FR 42232, Aug. 7, 1998; 78 FR 58821, Sept. 24, district office reviewing the reports.
2013] (2) The name, address, and telephone
number of the manufacturer or im-
Subpart B—Reports and Records porter, and the name, title, address,
and telephone number of the manufac-
§ 806.10 Reports of corrections and re- turer or importer representative re-
movals.
sponsible for conducting the device
(a) Each device manufacturer or im- correction or removal.
porter shall submit a written report to (3) The brand name and the common
FDA of any correction or removal of a name, classification name, or usual
device initiated by such manufacturer name of the device and the intended
or importer if the correction or reuse of the device.
moval was initiated:
(4) Marketing status of the device,
(1) To reduce a risk to health posed
i.e., any applicable premarket notifica-
by the device; or
tion number, premarket approval num-
(2) To remedy a violation of the act
ber, or indication that the device is a
caused by the device which may
preamendments device, and the device
present a risk to health unless the in-
formation has already been provided as listing number. A manufacturer or im-
set forth in paragraph (f) of this sec- porter that does not have an FDA es-
tion or the corrective or removal ac- tablishment registration number shall
tion is exempt from the reporting re- indicate in the report whether it has
quirements under § 806.1(b). ever registered with FDA.
(b) The manufacturer or importer (5) The unique device identifier (UDI)
shall submit any report required by that appears on the device label or on
paragraph (a) of this section within 10- the device package, or the device iden-
working days of initiating such correc- tifier, universal product code (UPC),
tion or removal. model, catalog, or code number of the
(c) The manufacturer or importer device and the manufacturing lot or se-
shall include the following information rial number of the device or other iden-
in the report: tification number.
(1) The seven digit registration num- (6) The manufacturer’s name, ad-
ber of the entity responsible for sub- dress, telephone number, and contact
mission of the report of corrective or person if different from that of the per-
removal action (if applicable), the son submitting the report.
month, day, and year that the report is (7) A description of the event(s) giv-
made, and a sequence number (i.e., 001 ing rise to the information reported
for the first report, 002 for the second and the corrective or removal actions
report, 003 etc.), and the report type that have been, and are expected to be
designation ‘‘C’’ or ‘‘R’’. For example, taken.
83
§ 806.20 21 CFR Ch. I (4–1–23 Edition)
(8) Any illness or injuries that have facturer or importer need not admit,
occurred with use of the device. If ap- and may deny, that the report or infor-
plicable, include the medical device re- mation submitted under this section
port numbers. constitutes an admission that the de-
(9) The total number of devices man- vice caused or contributed to a death
ufactured or distributed subject to the or serious injury.
correction or removal and the number (f) No report of correction or removal
in the same batch, lot, or equivalent is required under this part, if a report
unit of production subject to the cor- of the correction or removal is required
rection or removal. and has been submitted under parts 803
(10) The date of manufacture or dis- or 1004 of this chapter.
tribution and the device’s expiration [62 FR 27191, May 19, 1997, as amended at 63
date or expected life. FR 42232, Aug. 7, 1998; 69 FR 11311, Mar. 10,
(11) The names, addresses, and tele- 2004; 78 FR 58821, Sept. 24, 2013]
phone numbers of all domestic and for-
eign consignees of the device and the § 806.20 Records of corrections and re-
dates and number of devices distrib- movals not required to be reported.
uted to each such consignee. (a) Each device manufacturer or im-
(12) A copy of all communications reporter who initiates a correction or re-
garding the correction or removal and moval of a device that is not required
the names and addresses of all recipi- to be reported to FDA under § 806.10
ents of the communications not pro- shall keep a record of such correction
vided in accordance with paragraph or removal.
(c)(11) of this section. (b) Records of corrections and remov-
(13) If any required information is als not required to be reported to FDA
not immediately available, a state- under § 806.10 shall contain the fol-
ment as to why it is not available and lowing information:
when it will be submitted. (1) The brand name, common or usual
(d) If, after submitting a report under name, classification, name and product
this part, a manufacturer or importer code if known, and the intended use of
determines that the same correction or the device.
removal should be extended to addi- (2) The unique device identifier (UDI)
tional lots or batches of the same de- of the device, or the device identifier,
vice, the manufacturer or importer universal product code (UPC), model,
shall within 10-working days of initi- catalog, or code number of the device
ating the extension of the correction or and the manufacturing lot or serial
removal, amend the report by submit- number of the device or other identi-
ting an amendment citing the original fication number.
report number assigned according to (3) A description of the event(s) giv-
paragraph (c)(1) of this section, all of ing rise to the information reported
the information required by paragraph and the corrective or removal action
(c)(2), and any information required by that has been, and is expected to be
paragraphs (c)(3) through (c)(12) of this taken.
section that is different from the infor- (4) Justification for not reporting the
mation submitted in the original re- correction or removal action to FDA,
port. The manufacturer or importer which shall contain conclusions and
shall also provide a statement in ac- any followups, and be reviewed and
cordance with paragraph (c)(13) of this evaluated by a designated person.
section for any required information (5) A copy of all communications re-
that is not readily available. garding the correction or removal.
(e) A report submitted by a manufac- (c) The manufacturer or importer
turer or importer under this section shall retain records required under this
(and any release by FDA of that report section for a period of 2 years beyond
or information) does not necessarily re- the expected life of the device, even if
flect a conclusion by the manufacturer, the manufacturer or importer has
importer, or FDA that the report or in- ceased to manufacture or import the
formation constitutes an admission device. Records required to be main-

that the device caused or contributed tained under paragraph (b) of this sec-
to a death or serious injury. A manu- tion must be transferred to the new
84
Food and Drug Administration, HHS Pt. 807
manufacturer or importer of the device 807.21 How to register establishments and

and maintained for the required period list devices.
of time. 807.22 Times for establishment registration
and device listing.
[62 FR 27191, May 19, 1997, as amended at 63 807.25 Information required for device es-
FR 42233, Aug. 7, 1998; 78 FR 58821, Sept. 24, tablishment registration and device list-
2013] ing.
807.26 Additional listing information.
§ 806.30 FDA access to records.
807.28 Updating device listing information.
Each device manufacturer or im- 807.34 Summary of requirements for owners
porter required under this part to or operators granted a waiver from sub-
maintain records and every person who mitting required information electroni-
is in charge or custody of such records cally.
shall, upon request of an officer or em- 807.35 Notification of registrant.
ployee designated by FDA and under 807.37 Public availability of establishment
section 704(e) of the act, permit such registration and device listing informa-
officer or employee at all reasonable tion.
times to have access to, and to copy 807.39 Misbranding by reference to estab-
and verify, such records and reports. lishment registration or to registration
number.
[63 FR 42233, Aug. 7, 1998]
Subpart C—Procedures for Foreign Device
§ 806.40 Public availability of reports. Establishments
(a) Any report submitted under this
part is available for public disclosure 807.40 Establishment registration and de-
vice listing for foreign establishments
in accordance with part 20 of this chap-
importing or offering for import devices
ter.
into the United States.
(b) Before public disclosure of a re-
807.41 Identification of importers and per-
port, FDA will delete from the report: sons who import or offer for import.
(1) Any information that constitutes
trade secret or confidential commer- Subpart D—Exemptions
cial or financial information under
§ 20.61 of this chapter; and 807.65 Exemptions for device establish-
(2) Any personnel, medical, or similar ments.
information, including the serial num-
bers of implanted devices, which would Subpart E—Premarket Notification
constitute a clearly unwarranted inva- Procedures
sion of personal privacy under § 20.63 of 807.81 When a premarket notification sub-
this chapter or 5 U.S.C. 552(b)(6); pro- mission is required.
vided, that except for the information 807.85 Exemption from premarket notifica-
under § 20.61 of this chapter or 5 U.S.C. tion.
552(b)(4), FDA will disclose to a patient 807.87 Information required in a premarket
who requests a report all the informa- notification submission.
tion in the report concerning that pa- 807.90 Format of a premarket notification
tient. submission.
807.92 Content and format of a 510(k) sum-
PART 807—ESTABLISHMENT REG- mary.
807.93 Content and format of a 510(k) state-
ISTRATION AND DEVICE LISTING ment.
FOR MANUFACTURERS AND INI- 807.94 Format of class III certification.
TIAL IMPORTERS OF DEVICES 807.95 Confidentiality of information.
807.97 Misbranding by reference to pre-
Subpart A—General Provisions market notification.
807.100 FDA action on a premarket notifica-
Sec.
tion.
807.3 Definitions.
AUTHORITY: 21 U.S.C. 321, 331, 351, 352, 360,
Subpart B—Procedures for Device 360c, 360e, 360i, 360j, 360bbb–8b, 371, 374, 379k–
Establishments 1, 381, 393; 42 U.S.C. 264, 271.
807.20 Who must register and submit a de- SOURCE: 42 FR 42526, Aug. 23, 1977, unless
vice list? otherwise noted.
85
§ 807.3 21 CFR Ch. I (4–1–23 Edition)
Subpart A—General Provisions (3) Initiation of specifications for de-

vices that are manufactured by a sec-
§ 807.3 Definitions. ond party for subsequent commercial
(a) Act means the Federal Food, distribution by the person initiating
Drug, and Cosmetic Act. specifications.
(b) Commercial distribution means any (e) Official correspondent means the
distribution of a device intended for person designated by the owner or op-
human use which is held or offered for erator of an establishment as respon-
sale but does not include the following: sible for the following:
(1) Internal or interplant transfer of (1) The annual registration of the es-
a device between establishments within tablishment;
the same parent, subsidiary, and/or af- (2) Contact with the Food and Drug
filiate company; Administration for device listing;
(2) Any distribution of a device in- (3) Maintenance and submission of a
tended for human use which has in ef- current list of officers and directors to
fect an approved exemption for inves- the Food and Drug Administration
tigational use under section 520(g) of upon the request of the Commissioner;
the act and part 812 of this chapter; and
(3) Any distribution of a device, be- (4) The receipt of pertinent cor-
fore the effective date of part 812 of respondence from the Food and Drug
this chapter, that was not introduced Administration directed to and involv-
or delivered for introduction into inter- ing the owner or operator and/or any of
state commerce for commercial dis- the firm’s establishments.
tribution before May 28, 1976, and that
(f) Owner or operator means the cor-
is classified into class III under section
poration, subsidiary, affiliated com-
513(f) of the act: Provided, That the de-
pany, partnership, or proprietor di-
vice is intended solely for investiga-
rectly responsible for the activities of
tional use, and under section
the registering establishment.
501(f)(2)(A) of the act the device is not
(g) Initial importer means any im-
required to have an approved pre-
porter who furthers the marketing of a
market approval application as pro-
device from a foreign manufacturer to
vided in section 515 of the act; or
(4) For foreign establishments, the the person who makes the final deliv-
distribution of any device that is nei- ery or sale of the device to the ulti-
ther imported nor offered for import mate consumer or user, but does not
into the United States. repackage, or otherwise change the
(c) Establishment means a place of container, wrapper, or labeling of the
business under one management at one device or device package.
general physical location at which a (h) Any term defined in section 201 of
device is manufactured, assembled, or the act shall have that meaning.
otherwise processed. (i) Restricted device means a device for
(d) Manufacture, preparation, propaga- which a requirement restricting sale,
tion, compounding, assembly, or proc- distribution, or use has been estab-
essing of a device means the making by lished by a regulation issued under sec-
chemical, physical, biological, or other tion 520(e) of the act, by order as a con-
procedures of any article that meets dition of premarket approval under
the definition of device in section section 515(d)(1)(B)(ii) of the act, or by
201(h) of the act. These terms include a performance standard issued in ac-
the following activities: cordance with sections 514(a)(2)(B)(v)
(1) Repackaging or otherwise chang- and 514(b) of the act.
ing the container, wrapper, or labeling (j) Classification name means the term
of any device package in furtherance of used by the Food and Drug Administra-
the distribution of the device from the tion and its classification panels to de-
original place of manufacture to the scribe a device or class of devices for
person who makes final delivery or sale purposes of classifying devices under
to the ultimate consumer; section 513 of the act.
(2) Initial importation of devices (k) Product code means the code used
manufactured in foreign establish- by FDA to identify the generic cat-
ments; or egory of a device.
86
(l) Representative sampling of advertise- mation, as defined in § 20.61 of this

ments means typical advertising mate- chapter.
rial that gives the promotional claims (q) Class III certification means a cer-
made for the device. tification that the submitter of the
(m) Representative sampling of any 510(k) has conducted a reasonable
other labeling means typical labeling search of all known information about
material (excluding labels and package the class III device and other similar,
inserts) that gives the promotional legally marketed devices.
claims made for the device. (r) Class III summary means a sum-
(n) Material change includes any mary of the types of safety and effec-
change or modification in the labeling tiveness problems associated with the
or advertisements that affects the type of device being compared and a ci-
identity or safety and effectiveness of tation to the information upon which
the device. These changes may include, the summary is based. The summary
but are not limited to, changes in the must be comprehensive and describe
common or usual or proprietary name, the problems to which the type of de-
declared ingredients or components, in- vice is susceptible and the causes of
tended use, contraindications, warn- such problems.
ings, or instructions for use. Changes (s) United States agent means a person
that are not material may include residing or maintaining a place of busi-
graphic layouts, grammar, or correc- ness in the United States whom a for-
tion of typographical errors which do eign establishment designates as its
agent. This definition excludes mail-
not change the content of the labeling,
boxes, answering machines or services,
changes in lot number, and, for devices
or other places where an individual
where the biological activity or known
acting as the foreign establishment’s
composition differs with each lot pro-
agent is not physically present.
duced, the labeling containing the ac-
(t) Wholesale distributor means any
tual values for each lot.
person (other than the manufacturer or
(o) 510(k) summary (summary of any the initial importer) who distributes a
information respecting safety and ef- device from the original place of manu-
fectiveness) means a summary, sub- facture to the person who makes the
mitted under section 513(i) of the act, final delivery or sale of the device to
of the safety and effectiveness informa- the ultimate consumer or user.
tion contained in a premarket notifica- (u) Fiscal year means the FDA fiscal
tion submission upon which a deter- year, which runs from October 1
mination of substantial equivalence through September 30.
can be based. Safety and effectiveness (v) FURLS means the Food and Drug
information refers to safety and effec- Administration’s Unified
tiveness data and information sup- Registration and Listing System,
porting a finding of substantial equiva- (w) FDA premarket submission number
lence, including all adverse safety and means the number assigned by FDA to
effectiveness information. a premarket device submission, such as
(p) 510(k) statement means a state- a Premarket Approval Application
ment, made under section 513(i) of the (PMA); Humanitarian Device Exemp-
act, asserting that all information in a tion (HDE); New Drug Application
premarket notification submission re- (NDA); Biologics License Application
garding safety and effectiveness will be (BLA); de novo classification petition;
made available within 30 days of re- or Premarket Notification (510(k)).
quest by any person if the device de- (x) Importer means, for purposes of
scribed in the premarket notification this part, a company or individual in
submission is determined to be sub- the United States that is an owner,
stantially equivalent. The information consignee, or recipient, even if not the
to be made available will be a duplicate initial owner, consignee, or recipient,
of the premarket notification submis- of the foreign establishment’s device
sion, including any adverse safety and that is imported into the United
effectiveness information, but exclud- States. An importer does not include

ing all patient identifiers, and trade se- the consumer or patient who ulti-
cret or confidential commercial infor- mately purchases, receives, or uses the
87
§ 807.20 21 CFR Ch. I (4–1–23 Edition)
device, unless the foreign establish- of a device intended for human use, in-
ment ships the device directly to the cluding any person who:
consumer or patient. (1) Initiates or develops specifica-
(y) Person who imports or offers for im- tions for a device that is to be manu-
port means, for purposes of this part, factured by a second party;
an agent, broker, or other entity, other (2) Sterilizes or otherwise makes a
than a carrier, that the foreign estab- device for or on behalf of a specifica-
lishment uses to facilitate the import tions developer or any other person;
of its device into the United States. (3) Repackages or relabels a device;
[42 FR 42526, Aug. 23, 1977, as amended at 43 (4) Reprocesses a single use device
FR 37997, Aug. 25, 1978; 57 FR 18066, Apr. 28, that has previously been used on a pa-
1992; 58 FR 46522, Sept. 1, 1993; 59 FR 64295, tient;
Dec. 14, 1994; 60 FR 63606, Dec. 11, 1995; 63 FR (5) Acts as an initial importer as de-
51826, Sept. 29, 1998; 66 FR 59159, Nov. 27, 2001; fined in § 807.3(g), except that initial
77 FR 45940, Aug. 2, 2012] importers may fulfill their listing obli-
gation for any device for which they
Subpart B—Procedures for Device did not initiate or develop the speci-
Establishments fications for the device or repackage or
relabel the device by submitting the
§ 807.20 Who must register and submit name and address of the manufacturer.
a device list? Initial importers shall also be prepared
(a) An owner or operator of an estab- to submit, when requested by FDA, the
lishment not exempt under section proprietary name, if any, and the com-
510(g) of the Federal Food, Drug, and mon or usual name of each device for
Cosmetic Act or subpart D of this part which they are the initial importer;
who is engaged in the manufacture, (6) Manufactures components or ac-
preparation, propagation, cessories that are ready to be used for
compounding, assembly, or processing any intended health-related purpose
of a device intended for human use and are packaged or labeled for com-
shall register and submit listing infor- mercial distribution for such health-re-
mation for those devices in commercial lated purpose, e.g. blood filters, hemo-
distribution, except that registration dialysis tubing, or devices which of ne-
and listing information may be sub- cessity must be further processed by a
mitted by the parent, subsidiary, or af- licensed practitioner or other qualified
filiate company for all the domestic or person to meet the needs of a par-
foreign establishments under the con- ticular patient, e.g., a manufacturer of
trol of one of these organizations when ophthalmic lens blanks.
operations are conducted at more than (b) Registration or listing does not
one establishment and there exists constitute an admission or agreement
joint ownership and control among all or determination that a product is a
the establishments. The term ‘‘device’’ device within the meaning of section
includes all in vitro diagnostic prod- 201(h) of the Federal Food, Drug, and
ucts and in vitro diagnostic biological Cosmetic Act.
products not subject to licensing under (c) Registration and listing require-
section 351 of the Public Health Service ments shall not pertain to any person
Act. An owner or operator of an estab- who acts as a wholesale distributor, as
lishment located in any State as de- defined in § 807.3(t), and who does not
fined in section 201(a)(1) of the Federal manufacture, repackage, process, or
Food, Drug, and Cosmetic Act shall relabel a device.
register its name, places of business, (d) Owners and operators of establish-
and all establishments and list the de- ments or persons engaged in the recov-
vices whether or not the output of the ery, screening, testing, processing,
establishments or any particular de- storage, or distribution of human cells,
vice so listed enters interstate com- tissues, and cellular and tissue-based
merce. The registration and listing re- products, as defined in § 1271.3(d) of this
quirements shall pertain to any person chapter, that are regulated under the
who is engaged in the manufacture, Federal Food, Drug, and Cosmetic Act
preparation, propagation, must register and list those human
compounding, assembly, or processing cells, tissues, and cellular and tissue-
88
based products with the Center for Bio- Radiological Health, Food and Drug
logics Evaluation and Research on Administration, 10903 New Hampshire
Form FDA 3356 following the proce- Ave., Bldg. 66, Rm.1432, Silver Spring,
dures set out in subpart B of part 1271 MD 20993–0002, that includes the fol-
of this chapter, instead of the proce- lowing information:
dures for registration and listing con- (1) The name and address of the de-
tained in this part, except that the advice establishment(s) to be registered,
ditional listing information require- a contact person for the owner or oper-
ments of § 807.26 remain applicable. ator of the establishment, and the tele-
(e) Owners and operators of establish- phone number at which that person can
ments that manufacture devices li- be reached. If the establishment has al-
censed under section 351 of the Public ready registered in the past, the letter
Health Service Act as well as licensed should also include the owner or oper-
biological products used in the manu- ator number, registration number, and
facture of a licensed device must reg- any listing numbers previously as-
ister and list following the procedures signed by FDA for devices manufac-
set out in part 607 of this chapter, in- tured at that establishment.
stead of the procedures for registration (2) Information about whether the
and listing contained in this part. company is an initial importer as de-
[77 FR 45941, Aug. 2, 2012] fined in § 807.3(g) and, if so, whether it
also conducts any other activities or
§ 807.21 How to register establish- operations relating to devices.
ments and list devices. (3) A statement that use of the Inter-
(a) Owners or operators of establish- net is not reasonable for the person re-
ments that are subject to the registra- questing the waiver, and an expla-
tion and listing requirements of this nation of why such use is not reason-
part must provide the following infor- able. The statement must be signed by
mation to us using our electronic de- the owner or operator of the establish-
vice registration and listing system, ment, or by a person employed by the
except as provided in paragraphs (b), owner or operator who is authorized to
(c), and (d) of this section: make the declaration on behalf of the
(1) Initial establishment registration owner or operator.
information as required by §§ 807.22(a) (c) Those owners or operators who
and 807.25; have obtained a waiver from filing reg-
(2) Updates to registration informa- istration and listing information elec-
tion as required by §§ 807.22(b) and tronically should refer to § 807.34 for in-
807.25; formation on how to submit such infor-
(3) Initial device listing information mation by postal mail.
as required by §§ 807.22(a), 807.25, and (d) When additional device listing in-
807.28; formation (e.g., copies of labeling or
(4) Updates to device listing informa- advertisements) is requested by FDA as
tion as required by §§ 807.22(b), 807.25, described at § 807.26(e), such informa-
and 807.28, including updates to reflect tion may be submitted by postal mail
the discontinuance or resumption of or electronically by email, but will not
the commercial distribution of a pre- be submitted using the FDA electronic
viously-listed device as specified at device registration and listing system.
paragraphs (d) and (e) of § 807.28.
(b) If the information under § 807.21(a) [77 FR 45941, Aug. 2, 2012, as amended at 85
cannot be submitted electronically, a FR 18442, Apr. 2, 2020]
waiver may be requested. Waivers will
be granted only if use of electronic § 807.22 Times for establishment reg-
means is not reasonable for the person istration and device listing.
requesting the waiver. To request a (a) Initial registration and listing. An
waiver, applicants must send a letter owner or operator of an establishment
to the Imports and Registration and who has not previously entered into an
Listing Team, Division of Regulatory operation described in § 807.20(a) shall
Programs 2, Office of Regulatory Pro- register within 30 days after entering

grams, Office of Product Evaluation into such an operation and submit de-
and Quality, Center for Devices and vice listing information at that time.
89
§ 807.25 21 CFR Ch. I (4–1–23 Edition)
(b) Registration and listing updates. requirements of this part shall provide
Owners or operators shall review and such information to us by using the
update all of their establishment reg- FDA electronic device registration and
istration and device listing informa- listing system, unless granted a waiver
tion that is on file at FDA, docu- from electronic submission in accord-
menting any changes that were not ance with § 807.21(b). Electronic submis-
previously reported as follows: sions of registration and listing infor-
(1) Annual registration for each fiscal mation must comply with part 11 of
year is required for all establishments. this chapter, except for the require-
Annual registration shall take place ments in § 11.10(b), (c), and (e), and the
during the period beginning on October corresponding requirements in § 11.30 of
1 and ending on December 31 of each this chapter. Those owners or opera-
fiscal year; tors granted a waiver from electronic
(2) Updates to the registration infor- submission should refer to paragraphs
mation as described in § 807.25(b) shall (c) and (g) of this section and § 807.34
be made within 30 days of any change for instructions on how to submit de-
to such information; vice registration and listing informa-
(3) Every fiscal year, during the pe- tion.
riod beginning on October 1 and ending (b) Registration information required
on December 31, owners or operators to be submitted includes: The name
shall review and update all of their de- and mailing address of the device es-
vice listing information that is on file tablishment; the Web site address of
at FDA, reporting any changes or dele- the device establishment, if any; the
tions to listings and any new listings name, address, phone number, fax num-
that were not previously reported. The ber, and email address of the owner or
accuracy of all information on file operator; the name, address, phone
must be confirmed each year regardless number, fax number, and email address
of whether any changes were made to of the establishment’s official cor-
the owner or operator’s list of devices; respondent; and all trade names used
and by the establishment.
(4) Changes to listing information (c) Owners or operators who have
may also be made at other times, such been granted a waiver from electronic
as when a device is introduced into filing must submit the establishment
commercial distribution, when a registration information described in
change is made to a previously-listed paragraph (b) of this section, except for
device, or when a previously-listed de- the Web site and email address infor-
vice is removed from commercial dis- mation, in paper form using the proce-
tribution. dures set forth in § 807.34.
(c) Failure to submit required informa- (d) Each owner or operator is re-
tion. Failure to submit any of the required to maintain a listing of all offi-
quired information on time, as speci- cers, directors, and partners for each
fied in paragraphs (a) and (b) of this establishment registered by the owner
section, will put the establishment in a or operator and to furnish this infor-
‘‘failed to register’’ or ‘‘failed to list’’ mation to FDA upon request.
status as applicable. The establishment (e) For each establishment, an offi-
will not be considered active and the cial correspondent must be designated
establishment registration and device by the owner or operator to serve as a
listing information may not appear on point of contact with FDA on matters
the FDA Web site until such time as relating to the registration of device
the owner or operator submits and establishments and the listing of de-
FDA processes the required informa- vice products. Each owner or operator
tion. shall also provide FDA with the name
[77 FR 45942, Aug. 2, 2012] of a contact person at the owner or op-
erator’s offices who will be responsible
§ 807.25 Information required for de- for identifying the official cor-
vice establishment registration and respondent for each establishment. The
device listing.
owner or operator contact person will

(a) All owners or operators that are be the official correspondent in the
subject to the registration and listing event no one else has been properly
90
designated. The official correspondent emption for each device listed that is
is responsible for: subject to sections 505, 510(k), 513(f)(2),
(1) Providing FDA with all required 515, or 520(m) of the Federal Food,
registration and listing information Drug, and Cosmetic Act, which in-
electronically unless a waiver from cludes devices that are not exempt
electronic submission has been granted from premarket notification and ap-
in accordance with § 807.21(b); proval.
(2) Receiving all correspondence from (5) Each activity or process that is
FDA concerning registration and list- conducted on or done to the device at
ing; each establishment, such as manufac-
(3) Supplying, when requested by turing, repacking, relabeling, devel-
FDA, the names of all officers, direc- oping specifications, remanufacturing,
tors, and partners; and single-use device reprocessing, con-
(4) Receiving communications from tract manufacturing, contract steri-
FDA by email, or by postal mail if the lizing, or manufacturing for export
owner or operator has been granted a only.
waiver from the requirement to file [77 FR 45942, Aug. 2, 2012]
registration and listing information
electronically. § 807.26 Additional listing information.
(f) The designation of an official cor- (a) Each owner or operator shall
respondent does not in any manner af- maintain a historical file containing
fect the liability of the owner or oper- the labeling and advertisements in use
ator of the establishment or any other on the date of initial listing, and in use
individual under section 301(p) or any after October 10, 1978, but before the
other provision of the Federal Food, date of initial listing, as follows:
Drug, and Cosmetic Act. (1) For each device subject to section
(g) Device listing information must 514 or 515 of the act that is not a re-
be submitted to FDA electronically un- stricted device, a copy of all labeling
less a waiver from electronic submis- for the device;
sion has been granted in accordance (2) For each restricted device, a copy
with § 807.21(b). Owners or operators of all labeling and advertisements for
who have been granted a waiver must the device;
submit the required device listing in- (3) For each device that is neither re-
formation, including information restricted nor subject to section 514 or
quired by this paragraph, § 807.28, and 515 of the act, a copy of all labels,
any listing information requested by package inserts, and a representative
FDA under § 807.26(e), in paper form sampling of any other labeling.
using the procedures set forth in (b) In addition to the requirements
§ 807.34. The information required for set forth in paragraph (a) of this sec-
each device listed includes: tion, each owner or operator shall
(1) The current registration number maintain in the historical file any la-
and name of each establishment under beling or advertisements in which a
the ownership and control of the owner material change has been made any-
or operator where the device is manu- time after initial listing.
factured, repackaged, relabeled, or oth- (c) Each owner or operator may dis-
erwise processed, or where specifica- card labeling and advertisements from
tions are developed. the historical file 3 years after the date
(2) The product code for each device of the last shipment of a discontinued
that is exempt from premarket notifi- device by an owner or operator.
cation and approval or which was in (d) Location of the file:
commercial distribution prior to May (1) Currently existing systems for
28, 1976. maintenance of labeling and adver-
(3) The proprietary or brand name(s) tising may be used for the purpose of
under which each device is marketed. maintaining the historical file as long
(4) The FDA-assigned premarket sub- as the information included in the sys-
mission number of the approved appli- tems fulfills the requirements of this
cation, cleared premarket notification, section, but only if the labeling and ad-
granted de novo classification petition, vertisements are retrievable in a time-
or approved humanitarian device ex- ly manner.
91
§ 807.28 21 CFR Ch. I (4–1–23 Edition)
(2) The contents of the historical file the names of all distributors for whom
may be physically located in more than it has been manufactured.
one place in the establishment or in (f) Labeling, advertisements, and
more than one establishment provided other information to be submitted
there exists joint ownership and con- upon request in accordance with para-
trol among all the establishments graph (e) of this section may be sub-
maintaining the historical file. If no mitted by postal mail or electronically
joint ownership and control exists, the by email, but will not be submitted
registered establishment must provide using the FDA electronic device reg-
the Food and Drug Administration istration and listing system. Electronic
with a letter authorizing the establish- submissions of such information must
ment outside its control to maintain comply with part 11 of this chapter, ex-
the historical file. cept for the requirements in § 11.10 (a),
(3) A copy of the certification and (c) through (h), and (k), and the cor-
disclosure statements as required by responding requirements in § 11.30 of
part 54 of this chapter shall be retained this chapter. The information provided
and physically located at the establish- in electronic format must be in a form
ment maintaining the historical file. that we can process, review, and ar-
(e) Each owner or operator shall be chive.
prepared to submit to the Food and [43 FR 37999, Aug. 25, 1978, as amended at 51
Drug Administration, only upon spe- FR 33033, Sept. 18, 1986; 63 FR 5253, Feb. 2,
cific request, the following informa- 1998. Redesignated and amended at 77 FR
tion: 45943, Aug. 2, 2012]
(1) For a device subject to section 514
or 515 of the act that is not a restricted § 807.28 Updating device listing infor-
device, a copy of all labeling for the de- mation.
vice. (a) Updating of device listing infor-
(2) For a device that is a restricted mation is required if an additional es-
device, a copy of all labeling for the de- tablishment begins to engage in any of
vice, a representative sampling of ad- the activities described in § 807.3(d)
vertisements for the device, and for with respect to a listed device, such as
good cause, a copy of all advertise- manufacturing, developing specifica-
ments for a particular device. A re- tions, repackaging, relabeling, or oth-
quest for all advertisements will, where erwise processing the device. Updating
feasible, be accompanied by an expla- of the listing is also required if an es-
nation of the basis for such request. tablishment begins performing another
(3) For a device that is neither a reactivity on or to the device, or ceases
stricted device, nor subject to section to perform an activity on or to the de-
514 of 515 of the act, the label and pack- vice that had previously been identi-
age insert for the device and a rep- fied on the device listing.
resentative sampling of any other la- (b) An owner or operator shall create
beling for the device. a new device listing using the FDA
(4) For a particular device, a state- electronic device registration and list-
ment of the basis upon which the reg- ing system:
istrant has determined that the device (1) If introducing into commercial
is not subject to section 514 or 515 of distribution an exempt device identi-
the act. fied with a product code that is not
(5) For a particular device, a state- currently listed by the owner or oper-
ment of the basis upon which the reg- ator; or
istrant has determined the device is (2) If introducing into commercial
not a restricted device. distribution a non-exempt device with
(6) For a particular device, a state- an FDA premarket submission number
ment of the basis for determining that that is not currently listed by the
the product is a device rather than a owner or operator.
drug. (c) All device listings for foreign es-
(7) For a device that the owner or op- tablishments must be submitted before
erator has manufactured for distribu- the device may be imported or offered
tion under a label other than its own, for import into the United States.
92
(d) An owner or operator who discon- (b) As specified in § 807.22(b)(1) and

tinues commercial distribution of a de- (b)(3), all owners or operators shall up-
vice shall discontinue the device list- date their establishment registration
ing using the FDA electronic device and device listings annually during the
registration and listing system. A de- period beginning on October 1 and end-
vice listing is considered discontinued ing on December 31 of each fiscal year.
if: (c) Failure to submit any of the re-
(1) All devices under an exempt prod- quired information on time, as speci-
uct code have been discontinued or fied in § 807.22(a) and (b), will put the
(2) All devices associated with an establishment in a ‘‘failed to register’’
FDA premarket submission number or ‘‘failed to list’’ status as applicable.
have been discontinued. The establishment will not be consid-
(e) If commercial distribution of a ered active and the establishment reg-
discontinued device is resumed, the istration and device listing informa-
owner or operator must reactivate the tion may not appear on the FDA Web
previously-discontinued listing using site until the required information is
the electronic device registration and submitted to and processed by FDA.
listing system. Any changes to the list- [77 FR 45943, Aug. 2, 2012, as amended at 85
ing information for the product that is FR 18442, Apr. 2, 2020]
the subject of the listing such as a new
establishment, new activity, or new § 807.35 Notification of registrant.
proprietary name must be made using (a) The Food and Drug Administra-
the electronic device registration and tion will assign each device establish-
listing system at the time the listing is ment a registration number after
reactivated. verifying the initial establishment reg-
(f) FDA will assign one listing num- istration information that has been
ber for all devices exempt from pre- submitted. The owner or operator of
market notification requirements the establishment will also be assigned
under a single product code. For prod- an identifying number. Both numbers
ucts not exempt from premarket noti- will be sent to the official cor-
fication requirements, a single listing respondent by email, or by postal mail
number will be assigned by FDA for if the owner or operator has been
each FDA premarket submission num- granted a waiver from the requirement
ber. to file registration and listing informa-
[77 FR 45943, Aug. 2, 2012] tion electronically.
(b) Owners or operators of device es-
§ 807.34 Summary of requirements for tablishments who also manufacture or
owners or operators granted a process biological products (including
waiver from submitting required in- devices licensed under section 351 of
formation electronically. the Public Health Service Act) or drug
(a) For initial registration and list- products at the same establishment
ing, owners or operators who have been must also register and list those prod-
granted a waiver from electronic filing ucts under part 607 or part 207 of this
using the procedures set forth in chapter, as appropriate. Registration
§ 807.21(b) must send a letter containing and listing for human blood and blood
all of the registration and listing infor- products, devices licensed under sec-
mation described in §§ 807.22, 807.25 (and tion 351 of the Public Health Service
§ 807.26 when such information is re- Act, and licensed biological products
quested by FDA), at the times de- used in the manufacture of a device li-
scribed in § 807.22, to: The Imports and censed under section 351 of the Public
Registration and Listing Team, Divi- Health Service Act, are subject to part
sion of Regulatory Programs 2, Office 607 of this chapter; registration and
of Regulatory Programs, Office of listing for all other drug products (in-
Product Evaluation and Quality, Cen- cluding other biological products that
ter for Devices and Radiological are also regulated as drug products) are
Health, Food and Drug Administration, subject to part 207 of this chapter.
10903 New Hampshire Ave., Bldg. 66, (c) Although establishment registra-
Rm. 1432, Silver Spring, MD 20993–0002. tion and device listing are required to
93
§ 807.37 21 CFR Ch. I (4–1–23 Edition)
engage in the device activities de- § 807.39 Misbranding by reference to

scribed in § 807.20, validation of reg- establishment registration or to
istration and the assignment of a de- registration number.
vice listing number in itself does not Registration of a device establish-
establish that the holder of the reg- ment or assignment of a registration
istration is legally qualified to deal in number does not in any way denote ap-
such devices and does not represent a
proval of the establishment or its prod-
determination by the Food and Drug
ucts. Any representation that creates
Administration as to the status of any
an impression of official approval be-
device.
cause of registration or possession of a
[69 FR 11312, Mar. 10, 2004, as amended at 77 registration number is misleading and
FR 45943, Aug. 2, 2012] constitutes misbranding.
§ 807.37 Public availability of estab-
lishment registration and device Subpart C—Procedures for Foreign
listing information. Device Establishments
(a) Establishment registration and
§ 807.40 Establishment registration
device listing information is available and device listing for foreign estab-
for public inspection in accordance lishments importing or offering for
with section 510(f) of the Federal Food, import devices into the United
Drug, and Cosmetic Act and will be States.
posted on the FDA website, with the
exception of the information identified (a) Any establishment within any
in paragraph (b) of this section. Re- foreign country engaged in the manu-
quests for information by persons who facture, preparation, propagation,
do not have access to the internet compounding, or processing of a device
should be directed to the Imports and that is imported or offered for import
Registration and Listing Team, Divi- into the United States shall register
sion of Regulatory Programs 2, Office such establishment and list such de-
of Regulatory Programs, Office of vices using the FDA electronic device
Product Evaluation and Quality, Cen- registration and listing system in con-
ter for Devices and Radiological formance with the procedures in this
Health, Food and Drug Administration, section, § 807.41, and subpart B of this
10903 New Hampshire Ave., Bldg. 66, part. The official correspondent for the
Rm.1432, Silver Spring, MD 20993–0002. foreign establishment shall facilitate
In addition, there will be available for communication between the foreign es-
inspection at each of the Food and tablishment’s management and rep-
Drug Administration district offices resentatives of FDA for matters relat-
the same information for firms within ing to the registration of device estab-
the geographical area of such district lishments and the listing of device
offices. Upon request, verification of a products.
registration number or location of a (b) Each foreign establishment re-
registered establishment will be pro- quired to register under paragraph (a)
vided. of this section shall submit the name,
(b) The following listing information address, and phone number of its
will not be available for public inspec- United States agent as part of its ini-
tion or posted on the FDA Web site: tial and updated registration informa-
(1) For contract manufacturers, con- tion in accordance with subpart B of
tract sterilizers, and private label man- this part. Each foreign establishment
ufacturers, the proprietary or brand shall designate only one United States
name(s) under which a device is mar- agent and may designate the United
keted and the FDA-assigned premarket States agent to act as its official cor-
submission number, if this information respondent.
would reveal a confidential business re- (1) The United States agent shall re-
lationship; side or maintain a place of business in
(2) FDA-assigned listing numbers.
the United States.

[77 FR 45943, Aug. 2, 2012, as amended at 85 (2) Upon request from FDA, the
FR 18442, Apr. 2, 2020] United States agent shall assist FDA
94
in communications with the foreign es- (b) Upon initial registration, annu-
tablishment, respond to questions con- ally, and at the time of any changes,
cerning the foreign establishment’s each foreign establishment required to
products that are imported or offered register and list as provided in
for import into the United States, and § 807.40(a) must, using the FDA elec-
assist FDA in scheduling inspections of tronic device registration and listing
the foreign establishment. If the agen- system, submit the name, address, tele-
cy is unable to contact the foreign es- phone and fax numbers, email address,
tablishment directly or expeditiously, and registration number, if any has
FDA may provide information or docu- been assigned, of each person who im-
ments to the United States agent, and ports or offers for import the establish-
such an action shall be considered to be ment’s devices into the United States.
equivalent to providing the same infor- The term ‘‘person who imports or of-
mation or documents to the foreign es- fers for import,’’ which is defined in
tablishment. § 807.3(y), includes agents, brokers, or
(3) The foreign establishment or the other parties used by the foreign estab-
United States agent shall report lishment to facilitate the import of its
device into the United States.
changes in the United States agent’s
(c) For each individual or organiza-
name, address, or phone number to
tion identified by the foreign establish-
FDA within 10-business days of the
ment under paragraphs (a) and (b) of
change.
this section, the foreign establishment
(c) No device may be imported or of- must submit to FDA electronically the
fered for import into the United States current FDA premarket submission
unless it is the subject of a device list- number and any other identifying in-
ing as required under subpart B of this formation that is known to the estab-
part and is manufactured, prepared, lishment for each device being im-
propagated, compounded, or processed ported or offered for import by the
at a registered foreign establishment; named individuals or organizations.
however, this restriction does not
apply to devices imported or offered for [77 FR 45944, Aug. 2, 2012]
import under the investigational use
provisions of part 812 of this chapter. Subpart D—Exemptions
(d) The device establishment reg-
§ 807.65 Exemptions for device estab-
istration and device listing informa- lishments.
tion shall be in the English language.
The following classes of persons are
[66 FR 59160, Nov. 27, 2001, as amended at 77 exempt from registration in accord-
FR 45944, Aug. 2, 2012] ance with § 807.20 under the provisions
of section 510(g)(1), (g)(2), and (g)(3) of
§ 807.41 Identification of importers the act, or because the Commissioner
and persons who import or offer for
import. of Food and Drugs has found, under
section 510(g)(5) of the act, that such
(a) Upon initial registration, annu- registration is not necessary for the
ally, and at the time of any changes, protection of the public health. The ex-
each foreign establishment required to emptions in paragraphs (d), (e), (f), and
register and list as provided in (i) of this section are limited to those
§ 807.40(a) must, using the FDA elec- classes of persons located in any State
tronic device registration and listing as defined in section 201(a)(1) of the
system, submit the name, address, tele- act.
phone and fax numbers, email address, (a) A manufacturer of raw materials
and registration number, if any has or components to be used in the manu-
been assigned, of any importer (defined facture or assembly of a device who
in § 807.3(x)) of the establishment’s de- would otherwise not be required to reg-
vices that is known to the foreign es- ister under the provisions of this part.
tablishment. The foreign establishment (b) A manufacturer of devices to be
must also specify which of the estab- used solely for veterinary purposes.
lishment’s listed products each im- (c) A manufacturer of general pur-

porter receives from the foreign estab- pose articles such as chemical reagents
lishment. or laboratory equipment whose uses
95
§ 807.81 21 CFR Ch. I (4–1–23 Edition)
are generally known by persons trained pursuant to § 807.20 must submit a pre-
in their use and which are not labeled market notification submission to the
or promoted for medical uses. Food and Drug Administration at least
(d) Licensed practitioners, including 90 days before he proposes to begin the
physicians, dentists, and optometrists, introduction or delivery for introduc-
who manufacture or otherwise alter de- tion into interstate commerce for com-
vices solely for use in their practice. mercial distribution of a device in-
(e) Pharmacies, surgical supply out- tended for human use which meets any
lets, or other similar retail establish- of the following criteria:
ments making final delivery or sale to (1) The device is being introduced
the ultimate user. This exemption also into commercial distribution for the
applies to a pharmacy or other similar first time; that is, the device is not of
retail establishment that purchases a the same type as, or is not substan-
device for subsequent distribution tially equivalent to, (i) a device in
under its own name, e.g., a properly la- commercial distribution before May 28,
beled health aid such as an elastic ban- 1976, or (ii) a device introduced for
dage or crutch, indicating ‘‘distributed commercial distribution after May 28,
by’’ or ‘‘manufactured for’’ followed by 1976, that has subsequently been reclas-
the name of the pharmacy. sified into class I or II.
(f) Persons who manufacture, pre- (2) The device is being introduced
pare, propagate, compound, or process into commercial distribution for the
devices solely for use in research, first time by a person required to reg-
teaching, or analysis and do not intro- ister, whether or not the device meets
duce such devices into commercial dis- the criteria in paragraph (a)(1) of this
tribution. section.
(g) [Reserved] (3) The device is one that the person
(h) Carriers by reason of their re- currently has in commercial distribu-
ceipt, carriage, holding or delivery of tion or is reintroducing into commer-
devices in the usual course of business cial distribution, but that is about to
as carriers. be significantly changed or modified in
(i) Persons who dispense devices to design, components, method of manu-
the ultimate consumer or whose major facture, or intended use. The following
responsibility is to render a service constitute significant changes or modi-
necessary to provide the consumer (i.e., fications that require a premarket no-
patient, physician, layman, etc.) with a tification:
device or the benefits to be derived (i) A change or modification in the
from the use of a device; for example, a device that could significantly affect
hearing aid dispenser, optician, clinical the safety or effectiveness of the de-
laboratory, assembler of diagnostic x- vice, e.g., a significant change or modi-
ray systems, and personnel from a hos- fication in design, material, chemical
pital, clinic, dental laboratory, composition, energy source, or manu-
orthotic or prosthetic retail facility, facturing process.
whose primary responsibility to the ul- (ii) A major change or modification
timate consumer is to dispense or pro- in the intended use of the device.
vide a service through the use of a pre- (b)(1) A premarket notification under
viously manufactured device. this subpart is not required for a device
[42 FR 42526, Aug. 23, 1977, as amended at 58 for which a premarket approval appli-
FR 46523, Sept. 1, 1993; 61 FR 44615, Aug. 28, cation under section 515 of the act, or
1996; 65 FR 17136, Mar. 31, 2000; 66 FR 59160, for which a petition to reclassify under
Nov. 27, 2001] section 513(f)(2) of the act, is pending
before the Food and Drug Administra-
Subpart E—Premarket Notification tion.
Procedures (2) The appropriate FDA Center Di-
rector may determine that the submis-
§ 807.81 When a premarket notification sion and grant of a written request for
submission is required. an exception or alternative under
(a) Except as provided in paragraph § 801.128 or § 809.11 of this chapter satis-

(b) of this section, each person who is fies the requirement in paragraph (a)(3)
required to register his establishment of this section.
96
(c) In addition to complying with the and, if known, its appropriate panel;
requirements of this part, owners or or, if the owner or operator determines
operators of device establishments that that the device has not been classified
manufacture radiation-emitting elec- under such section, a statement of that
tronic products, as defined in § 1000.3 of determination and the basis for the
this chapter, shall comply with the re- person’s determination that the device
porting requirements of part 1002 of is not so classified.
this chapter. (d) Action taken by the person re-
[42 FR 42526, Aug. 23, 1977, as amended at 72 quired to register to comply with the
FR 73601, Dec. 28, 2007] requirements of the act under section
514 for performance standards.
§ 807.85 Exemption from premarket
notification. (e) Proposed labels, labeling, and ad-
vertisements sufficient to describe the
(a) A custom device is exempt from device, its intended use, and the direc-
premarket notification requirements of tions for its use. Where applicable, pho-
this subpart if the device is within the
tographs or engineering drawings
meaning of section 520(b) of the Fed-
should be supplied.
eral Food, Drug, and Cosmetic Act.
(1) It is intended for use by a patient (f) A statement indicating the device
named in the order of the physician or is similar to and/or different from
dentist (or other specially qualified other products of comparable type in
person); or commercial distribution, accompanied
(2) It is intended solely for use by a by data to support the statement. This
physician or dentist (or other specially information may include an identifica-
qualified person) and is not generally tion of similar products, materials, de-
available to, or generally used by, sign considerations, energy expected to
other physicians or dentists (or other be used or delivered by the device, and
specially qualified persons). a description of the operational prin-
(b) A distributor who places a device ciples of the device.
into commercial distribution for the (g) Where a person required to reg-
first time under his own name and a re- ister intends to introduce into com-
packager who places his own name on a mercial distribution a device that has
device and does not change any other undergone a significant change or
labeling or otherwise affect the device modification that could significantly
shall be exempted from the premarket affect the safety or effectiveness of the
notification requirements of this sub- device, or the device is to be marketed
part if: for a new or different indication for
(1) The device was in commercial dis- use, the premarket notification sub-
tribution before May 28, 1976; or
mission must include appropriate sup-
(2) A premarket notification submis-
porting data to show that the manufac-
sion was filed by another person.
turer has considered what con-
[42 FR 42526, Aug. 23, 1977, as amended at 81 sequences and effects the change or
FR 70340, Oct. 12, 2016] modification or new use might have on
§ 807.87 Information required in a pre- the safety and effectiveness of the de-
market notification submission. vice.
(h) A 510(k) summary as described in
Each premarket notification submis-
§ 807.92 or a 510(k) statement as de-
sion shall contain the following infor-
scribed in § 807.93.
mation:
(a) The device name, including both (i) A financial certification or disclo-
the trade or proprietary name and the sure statement or both, as required by
common or usual name or classifica- part 54 of this chapter.
tion name of the device. (j) For a submission supported by
(b) The establishment registration clinical data:
number, if applicable, of the owner or (1) If the data are from clinical inves-
operator submitting the premarket no- tigations conducted in the United
tification submission. States, a statement that each inves-

(c) The class in which the device has tigation was conducted in compliance
been put under section 513 of the act with applicable requirements in the
97
§ 807.90 21 CFR Ch. I (4–1–23 Edition)
protection of human subjects regula- (l) A statement that the submitter

tions in part 50 of this chapter, the in- believes, to the best of his or her
stitutional review boards regulations knowledge, that all data and informa-
in part 56 of this chapter, or was not tion submitted in the premarket notifi-
subject to the regulations under § 56.104 cation are truthful and accurate and
or § 56.105, and the investigational de- that no material fact has been omitted.
vice exemptions regulations in part 812 (m) Any additional information re-
of this chapter, or if the investigation garding the device requested by the
was not conducted in compliance with Commissioner that is necessary for the
those regulations, a brief statement of Commissioner to make a finding as to
the reason for the noncompliance. whether or not the device is substan-
(2) If the data are from clinical inves- tially equivalent to a device in com-
tigations conducted outside the United mercial distribution. A request for ad-
States, the requirements under § 812.28 ditional information will advise the
of this chapter apply. If any such inves- owner or operator that there is insuffi-
tigation was not conducted in accord- cient information contained in the
ance with good clinical practice (GCP) original premarket notification sub-
as described in § 812.28(a) of this chap- mission for the Commissioner to make
ter, include either a waiver request in this determination and that the owner
accordance with § 812.28(c) of the chap- or operator may either submit the re-
ter or a brief statement of the reason quested data or a new premarket noti-
for not conducting the investigation in fication containing the requested infor-
accordance with GCP and a description mation at least 90 days before the
of steps taken to ensure that the data owner or operator intends to market
and results are credible and accurate the device, or submit a premarket ap-
and that the rights, safety, and well- proval application in accordance with
being of subjects have been adequately section 515 of the act. If the additional
protected. information is not submitted within 30
(k) For submissions claiming sub- days following the date of the request,
stantial equivalence to a device which the Commissioner will consider the
has been classified into class III under premarket notification to be with-
section 513(b) of the act: drawn.
(1) Which was introduced or delivered
for introduction into interstate com- (Information collection requirements in this
merce for commercial distribution be- section were approved by the Office of Man-
fore December 1, 1990; and agement and Budget (OMB) and assigned
OMB control number 0910–0281)
(2) For which no final regulation re-
quiring premarket approval has been [42 FR 42526, Aug. 23, 1977, as amended at 57
issued under section 515(b) of the act, a FR 18066, Apr. 28, 1992; 59 FR 64295, Dec. 14,
summary of the types of safety and ef- 1994; 63 FR 5253, Feb. 2, 1998; 83 FR 7385, Feb.
fectiveness problems associated with 21, 2018]
the type of devices being compared and
§ 807.90 Format of a premarket notifi-
a citation to the information upon cation submission.
which the summary is based (class III
summary). The 510(k) submitter shall Each premarket notification submis-
also certify that a reasonable search of sion pursuant to this part shall be sub-
all information known or otherwise mitted in accordance with this section.
available about the class III device and Each submission shall:
other similar legally marketed devices (a)(1) For devices regulated by the
has been conducted (class III certifi- Center for Devices and Radiological
cation), as described in § 807.94. This in- Health, be addressed to the current ad-
formation does not refer to informa- dress displayed on the website https://
tion that already has been submitted www.fda.gov/cdrhsubmissionaddress.
to the Food and Drug Administration (2) For devices regulated by the Cen-
(FDA) under section 519 of the act. ter for Biologics Evaluation and Re-
FDA may require the submission of the search, be addressed to the current ad-
adverse safety and effectiveness data dress displayed on the website https://
described in the class III summary or www.fda.gov/AboutFDA/CentersOffices/
citation. OfficeofMedicalProductsandTobacco/
98
CBER/ucm385240.htm; or for devices reg- regarding substantial equivalence is a

ulated by the Center for Drug Evalua- device that was legally marketed prior
tion and Research, be addressed to the to May 28, 1976, or a device which has
Central Document Room, Center for been reclassified from class III to class
Drug Evaluation and Research, Food II or I (the predicate), or a device
and Drug Administration, 5901–B which has been found to be substan-
Ammendale Rd., Beltsville, MD 20705– tially equivalent through the 510(k)
1266. Information about devices regu- premarket notification process;
lated by the Center for Biologics Eval- (4) A description of the device that is
uation and Research is available at the subject of the premarket notifica-
https://www.fda.gov/ tion submission, such as might be
BiologicsBloodVaccines/ found in the labeling or promotional
BloodBloodProducts/ApprovedProducts/ material for the device, including an
default.htm. explanation of how the device func-
(3) All inquiries regarding a pre- tions, the scientific concepts that form
market notification submission should the basis for the device, and the signifi-
be sent to the address in this section or cant physical and performance charac-
one of the current addresses displayed teristics of the device, such as device
on the Food and Drug Administration’s design, material used, and physical
website. properties;
(b) [Reserved] (5) A statement of the intended use of
(c) Be submitted as a single version the device that is the subject of the
in electronic format.
premarket notification submission, in-
(d) Be submitted separately for each
cluding a general description of the
product the manufacturer intends to
diseases or conditions that the device
market.
will diagnose, treat, prevent, cure, or
(e) Designated ‘‘510(k) Notification’’
mitigate, including a description,
in the cover letter.
where appropriate, of the patient popu-
[42 FR 42526, Aug. 23, 1977, as amended at 53 lation for which the device is intended.
FR 11252, Apr. 6, 1988; 55 FR 11169, Mar. 27, If the indication statements are dif-
1990; 65 FR 17137, Mar. 31, 2000; 70 FR 14986, ferent from those of the legally mar-
Mar. 24, 2005; 75 FR 20915, Apr. 22, 2010; 80 FR
keted device identified in paragraph
18094, Apr. 3, 2015; 84 FR 68339, Dec. 16, 2019]
(a)(3) of this section, the 510(k) sum-
§ 807.92 Content and format of a 510(k) mary shall contain an explanation as
summary. to why the differences are not critical
(a) A 510(k) summary shall be in suf- to the intended therapeutic, diag-
ficient detail to provide an under- nostic, prosthetic, or surgical use of
standing of the basis for a determina- the device, and why the differences do
tion of substantial equivalence. FDA not affect the safety and effectiveness
will accept summaries as well as of the device when used as labeled; and
amendments thereto until such time as (6) If the device has the same techno-
FDA issues a determination of substan- logical characteristics (i.e., design, ma-
tial equivalence. All 510(k) summaries terial, chemical composition, energy
shall contain the following informa- source) as the predicate device identi-
tion: fied in paragraph (a)(3) of this section,
(1) The submitter’s name, address, a summary of the technological char-
telephone number, a contact person, acteristics of the new device in com-
and the date the summary was pre- parison to those of the predicate de-
pared; vice. If the device has different techno-
(2) The name of the device, including logical characteristics from the predi-
the trade or proprietary name if appli- cate device, a summary of how the
cable, the common or usual name, and technological characteristics of the de-
the classification name, if known; vice compare to a legally marketed de-
(3) An identification of the legally vice identified in paragraph (a)(3) of
marketed device to which the sub- this section.
mitter claims equivalence. A legally (b) 510(k) summaries for those pre-
marketed device to which a new device market submissions in which a deter-
may be compared for a determination mination of substantial equivalence is
99
§ 807.93 21 CFR Ch. I (4–1–23 Edition)
also based on an assessment of per- information, but excluding all patient iden-
formance data shall contain the fol- tifiers, and trade secret and confidential
lowing information: commercial information, as defined in 21
CFR 20.61.
(1) A brief discussion of the nonclin-
ical tests submitted, referenced, or re- (2) The statement in paragraph (a)(1)
lied on in the premarket notification of this section should be signed by the
submission for a determination of sub- certifier, made on a separate page of
stantial equivalence; the premarket notification submission,
(2) A brief discussion of the clinical and clearly identified as ‘‘510(k) state-
tests submitted, referenced, or relied ment.’’
on in the premarket notification sub- (b) All requests for information in-
mission for a determination of substan- cluded in paragraph (a) of this section
tial equivalence. This discussion shall shall be made in writing to the cer-
include, where applicable, a description tifier, whose name will be published by
of the subjects upon whom the device FDA on the list of premarket notifica-
was tested, a discussion of the safety or tion submissions for which substantial
effectiveness data obtained from the equivalence determinations have been
testing, with specific reference to ad- made.
verse effects and complications, and (c) The information provided to re-
any other information from the clin- questors will be a duplicate of the pre-
ical testing relevant to a determina- market notification submission, in-
tion of substantial equivalence; and cluding any adverse information, but
(3) The conclusions drawn from the excluding all patient identifiers, and
nonclinical and clinical tests that dem- trade secret and confidential commer-
onstrate that the device is as safe, as cial information as defined in § 20.61 of
effective, and performs as well as or this chapter.
better than the legally marketed de-
vice identified in paragraph (a)(3) of [59 FR 64295, Dec. 14, 1994]
this section.
(c) The summary should be in a sepa- § 807.94 Format of a class III certifi-
cation.
rate section of the submission, begin-
ning on a new page and ending on a (a) A class III certification submitted
page not shared with any other section as part of a premarket notification
of the premarket notification submis- shall state as follows:
sion, and should be clearly identified as I certify, in my capacity as (position held
a ‘‘510(k) summary.’’ in company), of (company name), that I have
(d) Any other information reasonably conducted a reasonable search of all infor-
deemed necessary by the agency. mation known or otherwise available about
the types and causes of safety or effective-
[57 FR 18066, Apr. 28, 1992, as amended at 59
ness problems that have been reported for
FR 64295, Dec. 14, 1994]
the (type of device). I further certify that I
am aware of the types of problems to which
§ 807.93 Content and format of a 510(k)
the (type of device) is susceptible and that,
statement.
to the best of my knowledge, the following
(a)(1) A 510(k) statement submitted summary of the types and causes of safety or
as part of a premarket notification effectiveness problems about the (type of de-
shall state as follows: vice) is complete and accurate.
I certify that, in my capacity as (the posi- (b) The statement in paragraph (a) of
tion held in company by person required to this section should be signed by the
submit the premarket notification, pref- certifier, clearly identified as ‘‘class III
erably the official correspondent in the certification,’’ and included at the be-
firm), of (company name), I will make avail- ginning of the section of the premarket
able all information included in this pre-
market notification on safety and effective-
notification submission that sets forth
ness within 30 days of request by any person the class III summary.
if the device described in the premarket no- [59 FR 64296, Dec. 14, 1994]
tification submission is determined to be
substantially equivalent. The information I § 807.95 Confidentiality of information.
agree to make available will be a duplicate

of the premarket notification submission, in- (a) The Food and Drug Administra-
cluding any adverse safety and effectiveness tion will disclose publicly whether
100
there exists a premarket notification the establishment or individuals in an

submission under this part: advertising or law firm pursuant to
(1) Where the device is on the mar- commercial arrangements with appro-
ket, i.e., introduced or delivered for in- priate safeguards for secrecy;
troduction into interstate commerce (iv) That the person has taken pre-
for commercial distribution; cautions to protect the confidentiality
(2) Where the person submitting the of the intent to market the device; and
premarket notification submission has (v) That the person understands that
disclosed, through advertising or any the submission to the government of
other manner, his intent to market the false information is prohibited by 18
device to scientists, market analysts, U.S.C. 1001 and 21 U.S.C. 331(q); and
exporters, or other individuals who are (2) The Commissioner agrees that the
not employees of, or paid consultants intent to market the device is con-
to, the establishment and who are not fidential commercial information.
in an advertising or law firm pursuant
(c) Where the Commissioner deter-
to commercial arrangements with ap-
mines that the person has complied
propriate safeguards for secrecy; or
with the procedures described in para-
(3) Where the device is not on the
graph (b) of this section with respect to
market and the intent to market the
a device that is not on the market and
device has not been so disclosed, except
where the intent to market the device
where the submission is subject to an
has not been disclosed, and the Com-
exception under paragraph (b) or (c) of
missioner agrees that the intent to
this section.
market the device is confidential com-
(b) The Food and Drug Administra-
tion will not disclose publicly the ex- mercial information, the Commissioner
istence of a premarket notification will not disclose the existence of the
submission for a device that is not on submission for 90 days from the date of
the market and where the intent to its receipt by the agency. In addition,
market the device has not been dis- the Commissioner will continue not to
closed for 90 days from the date of re- disclose the existence of such a submis-
ceipt of the submission, if: sion for the device for an additional
(1) The person submitting the pre- time when any of the following occurs:
market notification submission re- (1) The Commissioner requests in
quests in the submission that the Food writing additional information regard-
and Drug Administration hold as con- ing the device pursuant to § 807.87(h), in
fidential commercial information the which case the Commissioner will not
intent to market the device and sub- disclose the existence of the submis-
mits a certification to the Commis- sion until 90 days after the Food and
sioner: Drug Administration’s receipt of a
(i) That the person considers his incomplete premarket notification sub-
tent to market the device to be con- mission;
fidential commercial information; (2) The Commissioner determines
(ii) That neither the person nor, to that the device intended to be intro-
the best of his knowledge, anyone else, duced is a class III device and cannot
has disclosed through advertising or be marketed without premarket ap-
any other manner, his intent to mar- proval or reclassification, in which
ket the device to scientists, market an- case the Commissioner will not dis-
alysts, exporters, or other individuals, close the existence of the submission
except employees of, or paid consult- unless a petition for reclassification is
ants to, the establishment or individ- submitted under section 513(f)(2) of the
uals in an advertising or law firm pur- act and its existence can be disclosed
suant to commercial arrangements under § 860.5(d) of this chapter; or
with appropriate safeguards for se- (d) FDA will make a 510(k) summary
crecy; of the safety and effectiveness data
(iii) That the person will imme- available to the public within 30 days
diately notify the Food and Drug Ad- of the issuance of a determination that
ministration if he discloses the intent the device is substantially equivalent

to market the device to anyone, except to another device. Accordingly, even
employees of, or paid consultants to, when a 510(k) submitter has complied
101
§ 807.97 21 CFR Ch. I (4–1–23 Edition)
with the conditions set forth in para- § 807.100 FDA action on a premarket
graphs (b) and (c) of this section, con- notification.
fidentiality for a premarket notifica- (a) After review of a premarket noti-
tion submission cannot be granted be-
fication, FDA will:
yond 30 days after FDA issues a deter-
(1) Issue an order declaring the device
mination of equivalency.
to be substantially equivalent to a le-
(e) Data or information submitted
gally marketed predicate device;
with, or incorporated by reference in, a
premarket notification submission (2) Issue an order declaring the device
(other than safety and effectiveness to be not substantially equivalent to
data that have not been disclosed to any legally marketed predicate device;
the public) shall be available for disclo- (3) Request additional information;
sure by the Food and Drug Administra- or
tion when the intent to market the de- (4) Withhold the decision until a cer-
vice is no longer confidential in accord- tification or disclosure statement is
ance with this section, unless exempt submitted to FDA under part 54 of this
from public disclosure in accordance chapter.
with part 20 of this chapter. Upon final (5) Advise the applicant that the pre-
classification, data and information re- market notification is not required.
lating to safety and effectiveness of a Until the applicant receives an order
device classified in class I (general con- declaring a device substantially equiv-
trols) or class II (performance stand- alent, the applicant may not proceed to
ards) shall be available for public dis- market the device.
closure. Data and information relating (b) FDA will determine that a device
to safety and effectiveness of a device is substantially equivalent to a predi-
classified in class III (premarket ap- cate device using the following cri-
proval) that have not been released to teria:
the public shall be retained as con-
(1) The device has the same intended
fidential unless such data and informa-
use as the predicate device; and
tion become available for release to the
public under § 860.5(d) or other provi- (2) The device:
sions of this chapter. (i) Has the same technological char-
acteristics as the predicate device; or
[42 FR 42526, Aug. 23, 1977, as amended at 53 (ii)(A) Has different technological
FR 11252, Apr. 6, 1988; 57 FR 18067, Apr. 28,
characteristics, such as a significant
1992; 59 FR 64296, Dec. 14, 1994; 84 FR 68339,
Dec. 16, 2019] change in the materials, design, energy
source, or other features of the device
§ 807.97 Misbranding by reference to from those of the predicate device;
premarket notification. (B) The data submitted establishes
Submission of a premarket notifica- that the device is substantially equiva-
tion in accordance with this subpart, lent to the predicate device and con-
and a subsequent determination by the tains information, including clinical
Commissioner that the device intended data if deemed necessary by the Com-
for introduction into commercial dis- missioner, that demonstrates that the
tribution is substantially equivalent to device is as safe and as effective as a
a device in commercial distribution be- legally marketed device; and
fore May 28, 1976, or is substantially (C) Does not raise different questions
equivalent to a device introduced into of safety and effectiveness than the
commercial distribution after May 28, predicate device.
1976, that has subsequently been reclas- (3) The predicate device has not been
sified into class I or II, does not in any removed from the market at the initia-
way denote official approval of the de- tive of the Commissioner of Food and
vice. Any representation that creates Drugs or has not been determined to be
an impression of official approval of a misbranded or adulterated by a judicial
device because of complying with the order.
premarket notification regulations is

misleading and constitutes mis- [57 FR 58403, Dec. 10, 1992, as amended at 63
branding. FR 5253, Feb. 2, 1998]
102
PART 808—EXEMPTIONS FROM lates to the safety or effectiveness of

FEDERAL PREEMPTION OF STATE the device or to any other matter in-
AND LOCAL MEDICAL DEVICE cluded in a requirement applicable to
the device under the Federal Food,
REQUIREMENTS Drug, and Cosmetic Act.
(c) Exempting from preemption certain
Subpart A—General Provisions
State or local requirements respecting de-
Sec. vices. Section 521(b) of the Federal
808.1 Scope. Food, Drug, and Cosmetic Act contains
808.3 Definitions. a provision whereby the Commissioner
808.5 Advisory opinions. of Food and Drugs may, upon applica-
Subpart B—Exemption Procedures tion by a State or political subdivision,
allow imposition of a requirement
808.20 Application. which is different from, or in addition
808.25 Procedures for processing an applica- to, any requirement applicable under
tion. the Federal Food, Drug, and Cosmetic
808.35 Revocation of an exemption.
Act to the device (and which is thereby
Subpart C—Listing of Specific State and preempted) by promulgating a regula-
Local Exemptions tion in accordance with this part ex-
empting the State or local requirement
808.53 [Reserved] from preemption. The granting of an
808.55 California exemption does not affect the applica-
808.57—808.101 [Reserved]
bility to the device of any require-
AUTHORITY: 21 U.S.C. 360j, 360k, 371. ments under the Federal Food, Drug,
Section 808.1 also issued under Sec. 709, and Cosmetic Act. The Commissioner
Public Law 115–52, 131 Stat. 1065–67. may promulgate an exemption regula-
SOURCE: 43 FR 18665, May 2, 1978, unless tion for the preempted requirement if
otherwise noted. he makes either of the following find-
ings:
Subpart A—General Provisions (1) That the requirement is more
stringent than a requirement under the
§ 808.1 Scope. Federal Food, Drug, and Cosmetic Act
(a) Introduction. This part prescribes applicable to the device; or
procedures for the submission, review, (2) That the requirement is required
and approval of applications for exemp- by compelling local conditions and
tion from Federal preemption of State compliance with the requirement
and local requirements applicable to would not cause the device to be in vio-
medical devices under section 521 of lation of any applicable requirement
the Federal Food, Drug, and Cosmetic under the Federal Food, Drug, and Cos-
Act. metic Act.
(b) General rule for State and local re- (d) Meaning of ‘‘requirements applica-
quirements respecting devices. Section ble to a device.’’ State or local require-
521(a) of the Federal Food, Drug, and ments are preempted only when the
Cosmetic Act contains special provi- Food and Drug Administration has es-
sions governing the regulation of de- tablished specific counterpart regula-
vices by States and localities. That tions or there are other specific re-
section prescribes a general rule that quirements applicable to a particular
after May 28, 1976, no State or political device under the Federal Food, Drug,
subdivision of a State may establish or and Cosmetic Act, thereby making any
continue in effect any requirement existing divergent State or local re-
with respect to a medical device in- quirements applicable to the device dif-
tended for human use having the force ferent from, or in addition to, the spe-
and effect of law (whether established cific Food and Drug Administration re-
by statute, ordinance, regulation, or quirements. There are other State or
court decision), which is different local requirements that affect devices
from, or in addition to, any require- that are not preempted by section
ment applicable to such device under 521(a) of the Federal Food, Drug, and
any provision of the Federal Food, Cosmetic Act because they are not
Drug, and Cosmetic Act and which re- ‘‘requirements applicable to a device’’
103
§ 808.1 21 CFR Ch. I (4–1–23 Edition)
within the meaning of section 521(a) of of devices in unlicensed establish-

the Federal Food, Drug, and Cosmetic ments. However, Federal regulations
Act. The following are examples of issued under sections 519 and 520(f) of
State or local requirements that are the Federal Food, Drug, and Cosmetic
not regarded as preempted by section Act may impose requirements for
521 of the Federal Food, Drug, and Cos- records and reports and good manufac-
metic Act: turing practices beyond those pre-
(1) Section 521(a) does not preempt scribed in State or local requirements.
State or local requirements of general If there is a conflict between such regu-
applicability where the purpose of the lations and State or local require-
requirement relates either to other ments, the Federal regulations shall
products in addition to devices (e.g., re- prevail.
quirements such as general electrical (ii) Generally, section 521(a) does not
codes, and the Uniform Commercial preempt a State or local requirement
Code (warranty of fitness)), or to unfair prohibiting the manufacture of adul-
trade practices in which the require- terated or misbranded devices. Where,
ments are not limited to devices. however, such a prohibition has the ef-
(2) Section 521(a) does not preempt fect of establishing a substantive re-
State or local requirements that are quirement for a specific device, e.g., a
equal to, or substantially identical to, specific labeling requirement, then the
requirements imposed by or under the prohibition will be preempted if the re-
Federal Food, Drug, and Cosmetic Act. quirement is different from, or in addi-
(3) Section 521(a) does not preempt tion to, a Federal requirement estab-
State or local permits, licensing, reg- lished under the Federal Food, Drug,
istration, certification, or other re- and Cosmetic Act. In determining
quirements relating to the approval or whether such a requirement is pre-
sanction of the practice of medicine, empted, the determinative factor is
dentistry, optometry, pharmacy, nurs- how the requirement is interpreted and
ing, podiatry, or any other of the heal- enforced by the State or local govern-
ing arts or allied medical sciences or
ment and not the literal language of
related professions or occupations that
the statute, which may be identical to
administer, dispense, or sell devices.
a provision in the Federal Food, Drug,
However, regulations issued under sec-
and Cosmetic Act.
tion 520(e) or (g) of the Federal Food,
Drug, and Cosmetic Act may impose (7) Section 521(a) does not preempt
restrictions on the sale, distribution, State or local provisions respecting
or use of a device beyond those pre- delegations of authority and related
scribed in State or local requirements. administrative matters relating to de-
If there is a conflict between such re- vices.
strictions and State or local require- (8) Section 521(a) does not preempt a
ments, the Federal regulations shall State or local requirement whose sole
prevail. purpose is raising revenue or charging
(4) Section 521(a) does not preempt fees for services, registration, or regu-
specifications in contracts entered into latory programs.
by States or localities for procurement (9) Section 521(a) does not preempt
of devices. State or local requirements of the
(5) Section 521(a) does not preempt types that have been developed under
criteria for payment of State or local the Atomic Energy Act of 1954 (42
obligations under Medicaid and similar U.S.C. 2011 note), as amended, Sub-
Federal, State or local health-care pro- chapter C—Electronic Product Radi-
grams. ation Control of the Federal Food,
(6)(i) Section 521(a) does not preempt Drug, and Cosmetic Act (formerly the
State or local requirements respecting Radiation Control for Health and Safe-
general enforcement, e.g., require- ty Act of 1968), and other Federal stat-
ments that State inspection be per- utes, until such time as the Food and
mitted of factory records concerning Drug Administration issues specific re-
all devices, registration, and licensing quirements under the Federal Food,
requirements for manufacturers and Drug, and Cosmetic Act applicable to
others, and prohibition of manufacture these types of devices.
104
(10) Part 820 of this chapter (21 CFR aids, as defined under section 520(q) of
part 820) (CGMP requirements) does the Federal Food, Drug, and Cosmetic
not preempt remedies created by Act, through in-person transactions, by
States or Territories of the United mail, or online; and
States, the District of Columbia, or the (2) Is different from, in addition to,
Commonwealth of Puerto Rico. or otherwise not identical to, the regu-
(e) Determination of equivalence or dif- lations issued under section 709(b) of
ference of requirements applicable to a de- the FDA Reauthorization Act of 2017.
vice. It is the responsibility of the Food
and Drug Administration, subject to [43 FR 18665, May 2, 1978, as amended at 45
FR 67336, Oct. 10, 1980; 61 FR 52654, Oct. 7,
review by Federal courts, to determine
1996; 73 FR 34859, June 19, 2008; 87 FR 50761,
whether a State or local requirement is Aug. 17, 2022]
equal to, or substantially identical to,
requirements imposed by or under the § 808.3 Definitions.
Federal Food, Drug, and Cosmetic Act,
or is different from, or in addition to, Compelling local conditions includes
such requirements, in accordance with any factors, considerations, or cir-
the procedures provided by this part. cumstances prevailing in, or char-
However, it is the responsibility of acteristic of, the geographic area or
States and political subdivisions to de- population of the State or political
termine initially whether to seek ex- subdivision that justify exemption
emptions from preemption. Any State from preemption.
or political subdivision whose require- More stringent refers to a requirement
ments relating to devices are pre- of greater restrictiveness or one that is
empted by section 521(a) may petition expected to afford to those who may be
the Commissioner of Food and Drugs exposed to a risk of injury from a de-
for exemption from preemption, in ac- vice a higher degree of protection than
cordance with the procedures provided is afforded by a requirement applicable
by this part. to the device under the Federal Food,
(f) Applicability of Federal requirements Drug, and Cosmetic Act.
respecting devices. The Federal require- Political subdivision or locality means
ment with respect to a device applies any lawfully established local govern-
whether or not a corresponding State mental unit within a State which unit
or local requirement is preempted or has the authority to establish or con-
exempted from preemption. As a result, tinue in effect any requirement having
if a State or local requirement that the the force and effect of law with respect
Food and Drug Administration has ex- to a device intended for human use.
empted from preemption is not as State means any State or Territory of
broad in its application as the Federal the United States, including but not
requirement, the Federal requirement limited to, the District of Columbia
applies to all circumstances not cov- and the Commonwealth of Puerto Rico.
ered by the State or local requirement. Substantially identical to refers to the
(g) Exemptions not applicable to certain fact that a State or local requirement
State or local government requirements does not significantly differ in effect
specifically related to hearing products. from a Federal requirement.
An exemption under this part shall not
apply to any State or local government [87 FR 50762, Aug. 17, 2022]
law, regulation, order, or other require-
ment specifically related to hearing § 808.5 Advisory opinions.
products, including any requirement (a) Any State, political subdivision,
for the supervision, prescription, or or other interested person may request
other order, involvement, or interven- an advisory opinion from the Commis-
tion of a licensed person for consumers sioner with respect to any general mat-
to access over-the-counter hearing ter concerning preemption of State or
aids, that: local device requirements or with re-
(1) Would restrict or interfere with spect to whether the Food and Drug
the servicing, marketing, sale, dis- Administration regards particular

pensing, use, customer support, or dis- State or local requirements, or pro-
tribution of over-the-counter hearing posed requirements, as preempted.
105
§ 808.20 21 CFR Ch. I (4–1–23 Edition)
(1) Such an advisory opinion may be State or political subdivision so as to

requested and may be granted in ac- have the force and effect of law. How-
cordance with § 10.85 of this chapter. ever, an application for exemption may
(2) The Food and Drug Administra- be submitted before the effective date
tion, in its discretion and after con- of the requirement.
sultation with the State or political (b) An application for exemption
subdivision, may treat a request by a shall be in the form of a letter to the
State or political subdivision for an ad- Commissioner of Food and Drugs and
visory opinion as an application for ex- shall be signed by an individual who is
emption from preemption under authorized to request the exemption on
§ 808.20. behalf of the State or political subdivi-
(b) The Commissioner may issue an sion. An original and two copies of the
advisory opinion relating to a State or letter and any accompanying material,
local requirement on his own initiative as well as any subsequent reports or
when he makes one of the following de- correspondence concerning an applica-
terminations: tion, shall be submitted to the Division
(1) A requirement with respect to a of Dockets Management (HFA–305),
device for which an application for ex- Food and Drug Administration, 5630
emption from preemption has been sub- Fishers Lane, rm. 1061, Rockville, MD
mitted under § 808.20 is not preempted 20852. The outside wrapper of any appli-
by section 521(a) of the Federal Food, cation, report, or correspondence
Drug, and Cosmetic Act because it is: should indicate that it concerns an ap-
(i) Equal to or substantially identical plication for exemption from preemp-
to a requirement under the Federal tion of device requirements.
Food, Drug, and Cosmetic Act applica- (c) For each requirement for which
ble to the device, or (ii) is not a re- an exemption is sought, the application
quirement within the meaning of sec- shall include the following information
tion 521 of the Federal Food, Drug, and to the fullest extent possible, or an ex-
Cosmetic Act and therefore is not pre- planation of why such information has
empted; not been included:
(2) A proposed State or local require- (1) Identification and a current copy
ment with respect to a device is not el- of any statute, rule, regulation, or or-
igible for exemption from preemption dinance of the State or political sub-
because the State or local requirement division considered by the State or po-
has not been issued in final form. In litical subdivision to be a requirement
such a case, the advisory opinion may which is preempted, with a reference to
indicate whether the proposed require- the date of enactment, promulgation,
ment would be preempted and, if it
or issuance in final form. The applica-
would be preempted, whether the Food
tion shall also include, where avail-
and Drug Administration would pro-
able, copies of any legislative history
pose to grant an exemption from pre-
or background materials pertinent to
emption;
enactment, promulgation, or issuance
(3) Issuance of such an advisory opin-
of the requirement, including hearing
ion is in the public interest.
reports or studies concerning develop-
[43 FR 18665, May 2, 1978, as amended at 87 ment or consideration of the require-
FR 50761, Aug. 17, 2022] ment. If the requirement has been sub-
ject to any judicial or administrative
Subpart B—Exemption Procedures interpretations, the State or political
subdivision shall furnish copies of such
§ 808.20 Application. judicial or administrative interpreta-
(a) Any State or political subdivision tions.
may apply to the Food and Drug Ad- (2) A comparison of the requirement
ministration for an exemption from of the State or political subdivision
preemption for any requirement that it and any applicable Federal require-
has enacted and that is preempted. An ments to show similarities and dif-
exemption may only be granted for a ferences.
requirement that has been enacted, (3) Information on the nature of the
promulgated, or issued in final form by problem addressed by the requirement
the authorized body or official of the of the State or political subdivision.
106
(4) Identification of which (or both) quest expedited action on such applica-
of the following bases is relied upon for tion.
seeking an exemption from preemp-
[43 FR 18665, May 2, 1978; 43 FR 22010, May 23,
tion: 1978, as amended at 49 FR 3646, Jan. 30, 1984;
(i) The requirement is more stringent 59 FR 14365, Mar. 28, 1994; 87 FR 50761, Aug.
than a requirement applicable to a de- 17, 2022]
vice under the Federal Food, Drug, and
Cosmetic Act. If the State or political § 808.25 Procedures for processing an
subdivision relies upon this basis for application.
exemption from preemption, the appli- (a) Upon receipt of an application for
cation shall include information, data, an exemption from preemption sub-
or material showing how and why the
mitted in accordance with § 808.20, the
requirement of the State or political
Commissioner shall notify the State or
subdivision is more stringent than re-
political subdivision of the date of such
quirements under the Federal Food,
receipt.
(ii) The requirement is required by (b) If the Commissioner finds that an
compelling local conditions, and com- application does not meet the require-
pliance with the requirement would ments of § 808.20, he shall notify the
not cause the device to be in violation State or political subdivision of the de-
of any applicable requirement under ficiencies in the application and of the
the Federal Food, Drug, and Cosmetic opportunity to correct such defi-
Act. If the State or political subdivi- ciencies. A deficient application may
sion relies upon this basis for exemp- be corrected at any time.
tion from preemption, the application (c) After receipt of an application
shall include information, data, or ma- meeting the requirements of § 808.20,
terial showing why compliance with the Commissioner shall review such ap-
the requirement of the State or polit- plication and determine whether to
ical subdivision would not cause a de- grant or deny an exemption from pre-
vice to be in violation of any applicable emption for each requirement which is
requirement under the Federal Food, the subject of the application. The
Drug, and Cosmetic Act and why the Commissioner shall then issue in the
requirement is required by compelling FEDERAL REGISTER a proposed regula-
local conditions. The application shall tion either to grant or to deny an ex-
also explain in detail the compelling emption from preemption. The Com-
local conditions that justify the re- missioner shall also issue in the FED-
quirement. ERAL REGISTER a notice of opportunity
(5) The title of the chief administra- to request an oral hearing before the
tive or legal officers of that State or Commissioner or the Commissioner’s
local agency that has primary respon- designee.
sibility for administration of the re- (d) A request for an oral hearing may
quirement. be made by the State or political sub-
(6) When requested by the Food and division or any other interested person.
Drug Administration, any records con- Such request shall be submitted to the
cerning administration of any require- Division of Dockets Management with-
ment which is the subject of an exemp- in the period of time prescribed in the
tion or an application for an exemption notice and shall include an explanation
from preemption. of why an oral hearing, rather than
(7) Information on how the public submission of written comments only,
health may be benefitted and how is essential to the presentation of
interstate commerce may be affected, views on the application for exemption
if an exemption is granted. from preemption and the proposed reg-
(8) Any other pertinent information ulation.
respecting the requirement voluntarily (e) If a timely request for an oral
submitted by the applicant. hearing is made, the Commissioner
(d) If litigation regarding applica- shall review such a request and may
bility of the requirement is pending, grant a legislative-type informal oral

the State or political subdivision may hearing pursuant to part 15 of this
so indicate in its application and re- chapter by publishing in the FEDERAL
107
§ 808.35 21 CFR Ch. I (4–1–23 Edition)
REGISTER a notice of the hearing in ac- graph (g) of this section constitutes
cordance with § 15.20 of this chapter. final agency action.
The scope of the oral hearing shall be
[43 FR 18665, May 2, 1978, as amended at 87
limited to matters relevant to the ap-
FR 50761, Aug. 17, 2022]
plication for exemption from preemp-
tion and the proposed regulation. Oral § 808.35 Revocation of an exemption.
or written presentations at the oral
hearing which are not relevant to the (a) An exemption from preemption
application shall be excluded from the pursuant to a regulation under this
administrative record of the hearing. part shall remain effective until the
(f) If a request for hearing is not Commissioner revokes such exemption.
timely made or a notice of appearance (b) The Commissioner may by regula-
is not filed pursuant to § 15.21 of this tion, in accordance with § 808.25, revoke
chapter, the Commissioner shall con- an exemption from preemption for any
sider all written comments submitted of the following reasons:
and publish a final rule in accordance (1) An exemption may be revoked
with paragraph (g) of this section. upon the effective date of a newly es-
(g)(1) The Commissioner shall review tablished requirement under the Fed-
all written comments submitted on the eral Food, Drug, and Cosmetic Act
proposed rule and the administrative which, in the Commissioner’s view, ad-
record of the oral hearing, if an oral dresses the objectives of an exempt re-
hearing has been granted, and shall quirement and which is described,
publish in the FEDERAL REGISTER a when issued, as preempting a pre-
final rule in subpart C of this part iden- viously exempt State or local require-
tifying any requirement in the applica- ment.
tion for which exemption from preemp- (2) An exemption may be revoked
tion is granted, or conditionally grant- upon a finding that there has occurred
ed, and any requirement in the applica- a change in the bases listed in
tion for which exemption from preemp- § 808.20(c)(4) upon which the exemption
tion is not granted. was granted.
(2) The Commissioner may issue a (3) An exemption may be revoked if it
regulation granting or conditionally is determined that a condition placed
granting an application for an exemp- on the exemption by the regulation
tion from preemption for any require- under which the exemption was grant-
ment if the Commissioner makes ei- ed has not been met or is no longer
ther of the following findings:
being met.
(i) The requirement is more stringent
(4) An exemption may be revoked if a
than a requirement applicable to the
State or local jurisdiction fails to sub-
device under the Federal Food, Drug,
mit records as provided in § 808.20(c)(6).
and Cosmetic Act;
(5) An exemption may be revoked if a
(ii) The requirement is required by
State or local jurisdiction to whom the
compelling local conditions, and com-
pliance with the requirement would exemption was originally granted re-
not cause the device to be in violation quests revocation.
of any requirement applicable to the (6) An exemption may be revoked if it
device under the Federal Food, Drug, is determined that it is no longer in
and Cosmetic Act. the best interests of the public health
(3) The Commissioner may not grant to continue the exemption.
an application for an exemption from (c) An exemption that has been re-
preemption for any requirement with voked may be reinstated, upon request
respect to a device if the Commissioner from the State or political subdivision,
determines that the granting of an ex- if the Commissioner, in accordance
emption would not be in the best inter- with the procedures in § 808.25, deter-
est of public health, taking into ac- mines that the grounds for revocation
count the potential burden on inter- are no longer applicable except that
state commerce. the Commissioner may permit abbre-

(h) An advisory opinion pursuant to viated submissions of the documents
§ 808.5 or a regulation pursuant to para- and materials normally required for an
108
application for exemption under 809.40 Restrictions on the sale, distribution,

§ 808.20. and use of OTC test sample collection
systems for drugs of abuse testing.
FR 50761, Aug. 17, 2022] AUTHORITY: 21 U.S.C. 331, 351, 352, 355, 360b,
360c, 360d, 360h, 360i, 360j, 371, 372, 374, 381.
Subpart C—Listing of Specific
State and Local Exemptions Subpart A—General Provisions
§ 808.53 [Reserved] § 809.3 Definitions.
(a) In vitro diagnostic products are
§ 808.55 California.
those reagents, instruments, and sys-
The following California medical de- tems intended for use in the diagnosis
vice requirements are preempted under of disease or other conditions, includ-
section 521(a) of the Federal Food, ing a determination of the state of
Drug, and Cosmetic Act, and FDA has health, in order to cure, mitigate,
denied them exemption from preemp- treat, or prevent disease or its
tion:
sequelae. Such products are intended
(a) Medical devices; general provisions.
for use in the collection, preparation,
Sherman Food, Drug, and Cosmetic
Law, Division 21 of the California and examination of specimens taken
Health and Safety Code, sections 26207, from the human body. These products
26607, 26614, 26615, 26618, 26631, 26640, and are devices as defined in section 201(h)
26441, to the extent that they apply to of the Federal Food, Drug, and Cos-
devices; and metic Act (the act), and may also be bi-
(b) Ophthalmic devices; quality stand- ological products subject to section 351
ards. California Business and Profes- of the Public Health Service Act.
sions Code, section 2541.3 to the extent (b) A product class is all those prod-
that it requires adoption of the Amer- ucts intended for use for a particular
ican National Standards Institute determination or for a related group of
standards Z–80.1 and Z–80.2. determinations or products with com-
[87 FR 50762, Aug. 17, 2022] mon or related characteristics or those
intended for common or related uses. A
§§ 808.57—808.101 [Reserved] class may be further divided into sub-
classes when appropriate.
PART 809—IN VITRO DIAGNOSTIC (c) [Reserved]
PRODUCTS FOR HUMAN USE (d) Act means the Federal Food,
Subpart A—General Provisions [41 FR 6903, Feb. 13, 1976, as amended at 45
Sec. FR 7484, Feb. 1, 1980]
809.3 Definitions.
809.4 Confidentiality of submitted informa- § 809.4 Confidentiality of submitted in-
tion. formation.
Subpart B—Labeling Data and information submitted

under § 809.10(c) that are shown to fall
809.10 Labeling for in vitro diagnostic prod- within the exemption established in
ucts. § 20.61 of this chapter shall be treated
809.11 Exceptions or alternatives to labeling
as confidential by the Food and Drug
requirements for in vitro diagnostic
products for human use held by the Stra- Administration and any person to
tegic National Stockpile. whom the data and information are re-
ferred. The Food and Drug Administra-
Subpart C—Requirements for tion will determine whether informa-
Manufacturers and Producers tion submitted will be treated as con-
809.20 General requirements for manufac- fidential in accordance with the provi-
turers and producers of in vitro diag- sions of part 20 of this chapter.
nostic products.
[45 FR 7484, Feb. 1, 1980]
809.30 Restrictions on the sale, distribution
and use of analyte specific reagents.
109
§ 809.10 21 CFR Ch. I (4–1–23 Edition)
Subpart B—Labeling licensed by the law of the State in

which the practitioner practices to use
§ 809.10 Labeling for in vitro diag- or order the use of the device.
nostic products. (5) For a reagent, appropriate storage
(a) The label for an in vitro diag- instructions adequate to protect the
nostic product shall state the following stability of the product. When applica-
information, except where such infor- ble, these instructions shall include
mation is not applicable, or as other- such information as conditions of tem-
wise specified in a standard for a par- perature, light, humidity, and other
ticular product class or as provided in pertinent factors. For products requir-
paragraph (e) of this section. Section ing manipulation, such as reconstitu-
201(k) of the act provides that ‘‘a re- tion and/or mixing before use, appro-
quirement made by or under authority priate storage instructions shall be
of this act that any word, statement, provided for the reconstituted or mixed
or other information appear on the product which is to be stored in the
label shall not be considered to be com- original container. The basis for such
plied with unless such word, statement, instructions shall be determined by re-
or other information also appears on liable, meaningful, and specific test
the outside container or wrapper, if methods such as those described in
any there be, of the retail package of § 211.166 of this chapter.
such article, or is easily legible (6) For a reagent, a means by which
through the outside container or wrap- the user may be assured that the prod-
per.’’ uct meets appropriate standards of
(1) The proprietary name and estab- identity, strength, quality and purity
lished name (common or usual name), at the time of use. This shall be pro-
if any. vided, both for the product as provided
(2) The intended use or uses of the and for any resultant reconstituted or
product. mixed product, by including on the
(3) For a reagent, a declaration of the label one or more of the following:
established name (common or usual (i) An expiration date based upon the
name), if any, and quantity, proportion stated storage instructions.
or concentration of each reactive in- (ii) A statement of an observable in-
gredient; and for a reagent derived dication of an alteration of the prod-
from biological material, the source uct, e.g., turbidity, color change, pre-
and a measure of its activity. The cipitate, beyond its appropriate stand-
quantity, proportion, concentration, or ards.
activity shall be stated in the system (iii) Instructions for a simple method
generally used and recognized by the by which the user can reasonably de-
intended user, e.g., metric, inter- termine that the product meets its ap-
national units, etc. propriate standards.
(4) A statement of warnings or pre- (7) For a reagent, a declaration of the
cautions for users as established in the net quantity of contents, expressed in
regulations contained in 16 CFR part terms of weight or volume, numerical
1500 and any other warnings appro- count, or any combination of these or
priate to the hazard presented by the other terms which accurately reflect
product; and a statement ‘‘For In Vitro the contents of the package. The use of
Diagnostic Use’’ and any other limiting metric designations is encouraged,
statements appropriate to the intended wherever appropriate. If more than a
use of the product. The limiting state- single determination may be performed
ment appropriate to the intended use using the product, any statement of
of a prescription in vitro diagnostic the number of tests shall be consistent
product shall bear the symbol state- with instructions for use and amount
ment ‘‘Rx only’’ or ‘‘) only’’ or the of material provided.
statement ‘‘Caution: Federal law re- (8) Name and place of business of
stricts this device to sale by or on the manufacturer, packer, or distributor.
order of a ___’’, the blank to be filled (9) A lot or control number, identi-
with the word ‘‘physician’’, ‘‘dentist’’, fied as such, from which it is possible
‘‘veterinarian’’, or with the descriptive to determine the complete manufac-
designation of any other practitioner turing history of the product.
110
(i) If it is a multiple unit product, the (3) Summary and explanation of the
lot or control number shall permit test. Include a short history of the
tracing the identity of the individual methodology, with pertinent references
units. and a balanced statement of the special
(ii) For an instrument, the lot or con- merits and limitations of this method
trol number shall permit tracing the or product. If the product labeling re-
identity of all functional subassem- fers to any other procedure, appro-
blies. priate literature citations shall be in-
(iii) For multiple unit products which cluded and the labeling shall explain
require the use of included units to- the nature of any differences from the
gether as a system, all units should original and their effect on the results.
bear the same lot or control number, if (4) The chemical, physical, physio-
appropriate, or other suitable uniform logical, or biological principles of the
identification should be used. procedure. Explain concisely, with
(10) Except that for items in para- chemical reactions and techniques in-
graphs (a) (1) through (9) of this sec- volved, if applicable.
tion: (i) In the case of immediate con- (5) Reagents:
tainers too small or otherwise unable (i) A declaration of the established
to accommodate a label with sufficient name (common or usual name), if any,
space to bear all such information and and quantity, proportion or concentra-
which are packaged within an outer tion or each reactive ingredient; and
container from which they are removed for biological material, the source and
for use, the information required by a measure of its activity. The quantity,
paragraphs (a) (2), (3), (4), (5), (6) (ii),
proportion, concentration or activity
(iii) and (7) of this section may appear
shall be stated in the system generally
in the outer container labeling only.
used and recognized by the intended
(ii) In any case in which the presence user, e.g., metric, international units,
of this information on the immediate
etc. A statement indicating the pres-
container will interfere with the test,
ence of and characterizing any cata-
the information may appear on the
lytic or nonreactive ingredients, e.g.,
outside container or wrapper rather
buffers, preservatives, stabilizers.
than on the immediate container label.
(ii) A statement of warnings or pre-
(b) Labeling accompanying each
cautions for users as established in the
product, e.g., a package insert, shall
state in one place the following infor- regulations contained in 16 CFR part
mation in the format and order speci- 1500 and any other warnings appro-
fied below, except where such informa- priate to the hazard presented by the
tion is not applicable, or as specified in product; and a statement ‘‘For In Vitro
a standard for a particular product Diagnostic Use’’ and any other limiting
class. The labeling for a multiple-pur- statements appropriate to the intended
pose instrument used for diagnostic use of the product. The limiting state-
purposes, and not committed to spe- ment appropriate to the intended use
cific diagnostic procedures or systems, of a prescription in vitro diagnostic
may bear only the information indi- product shall bear the symbol state-
cated in paragraphs (b) (1), (2), (6), (14), ment ‘‘Rx only’’ or ‘‘) only’’ or the
and (15) of this section. The labeling for statement ‘‘Caution: Federal law re-
a reagent intended for use as a replace- stricts this device to sale by or on the
ment in a diagnostic system may be order of a ___’’, the blank to be filled
limited to that information necessary with the word ‘‘physician’’, ‘‘dentist’’,
to identify the reagent adequately and ‘‘veterinarian’’, or with the descriptive
to describe its proper use in the sys- designation of any other practitioner
tem. licensed by the law of the State in
(1) The proprietary name and estab- which the practitioner practices to use
lished name, i.e., common or usual or order the use of the device.
name, if any. (iii) Adequate instructions for recon-
(2) The intended use or uses of the stitution, mixing, dilution, etc.
product and the type of procedure, e.g., (iv) Appropriate storage instructions
qualitative or quantitative. adequate to protect the stability of the
111
§ 809.10 21 CFR Ch. I (4–1–23 Edition)
product. When applicable, these in- (ii) A list of all materials required
structions shall include such informa- but not provided. Include such details
tion as conditions of temperature, as sizes, numbers, types, and quality.
light, humidity, and other pertinent (iii) A description of the amounts of
factors. For products requiring manip- reagents necessary, times required for
ulation, such as reconstitution and/or specific steps, proper temperatures,
mixing before use, appropriate storage wavelengths, etc.
instructions shall be provided for the (iv) A statement describing the sta-
reconstituted or mixed product. The bility of the final reaction material to
basis for such instructions shall be de- be measured and the time within which
termined by reliable, meaningful, and it shall be measured to assure accurate
specific test methods such as those de-
results.
scribed in § 211.166 of this chapter.
(v) Details of calibration: Identify
(v) A statement of any purification
reference material. Describe prepara-
or treatment required for use.
tion of reference sample(s), use of
(vi) Physical, biological, or chemical
blanks, preparation of the standard
indications of instability or deteriora-
curve, etc. The description of the range
tion.
of calibration should include the high-
(6) Instruments:
est and the lowest values measurable
(i) Use or function.
by the procedure.
(ii) Installation procedures and spe-
(vi) Details of kinds of quality con-
cial requirements.
trol procedures and materials required.
(iii) Principles of operation.
If there is need for both positive and
(iv) Performance characteristics and negative controls, this should be stat-
specifications. ed. State what are considered satisfac-
(v) Operating instructions. tory limits of performance.
(vi) Calibration procedures including (9) Results: Explain the procedure for
materials and/or equipment to be used. calculating the value of the unknown.
(vii) Operational precautions and Give an explanation for each compo-
limitations. nent of the formula used for the cal-
(viii) Hazards. culation of the unknown. Include a
(ix) Service and maintenance infor- sample calculation, step-by-step, ex-
mation. plaining the answer. The values shall
(7) Specimen collection and prepara- be expressed to the appropriate number
tion for analysis, including a descrip- of significant figures. If the test pro-
tion of: vides other than quantitative results,
(i) Special precautions regarding provide an adequate description of ex-
specimen collection including special pected results.
preparation of the patient as it bears
(10) Limitation of the procedure: In-
on the validity of the test.
clude a statement of limitations of the
(ii) Additives, preservatives, etc., procedure. State known extrinsic fac-
necessary to maintain the integrity of
tors or interfering substances affecting
the specimen.
results. If further testing, either more
(iii) Known interfering substances.
specific or more sensitive, is indicated
(iv) Recommended storage, handling in all cases where certain results are
or shipping instructions for the protec- obtained, the need for the additional
tion and maintenance of stability of
test shall be stated.
the specimen.
(11) Expected values: State the
(8) Procedure: A step-by-step outline
range(s) of expected values as obtained
of recommended procedures from re-
ception of the specimen to obtaining with the product from studies of var-
results. List any points that may be ious populations. Indicate how the
useful in improving precision and accu- range(s) was established and identify
racy. the population(s) on which it was es-
tablished.
(i) A list of all materials provided,

e.g., reagents, instruments and equip-
ment, with instructions for their use.
112
(12) Specific performance characteris- beling meets the requirements of this

tics: Include, as appropriate, informa- paragraph.
tion describing such things as accu- (1) The label of a reagent shall bear
racy, precision, specificity, and sensi- the following information:
tivity. These shall be related to a gen- (i) The proprietary name and estab-
erally accepted method using biologi- lished name (common or usual name),
cal specimens from normal and abnor- if any, of the reagent.
mal populations. Include a statement (ii) A declaration of the established
summarizing the data upon which the name (common or usual name), if any,
specific performance characteristics and quantity, proportion or concentra-
are based. tion of the reagent ingredient (e.g., hy-
(13) Bibliography: Include pertinent drochloric acid: Formula weight 36.46,
references keyed to the text. assay 37.9 percent, specific gravity 1.192
(14) Name and place of business of at 60 °F); and for a reagent derived
manufacturer, packer, or distributor. from biological material, the source
(15) Date of issuance of the last revi- and where applicable a measure of its
sion of the labeling identified as such. activity. The quantity, proportion,
concentration or activity shall be stat-
(c) A shipment or other delivery of an
ed in the system generally used and
in vitro diagnostic product shall be ex-
recognized by the intended user, e.g.,
empt from the requirements of para-
metric, international units, etc.
graphs (a) and (b) of this section and
(iii) A statement of the purity and
from a standard promulgated under
quality of the reagent, including a
part 861 provided that the following quantitative declaration of any impuri-
conditions are met: ties present. The requirement for this
(1) In the case of a shipment or deliv- information may be met by a state-
ery for an investigation subject to part ment of conformity with a generally
812, if there has been compliance with recognized and generally available
part 812; or standard which contains the same in-
(2) In the case of a shipment or deliv- formation, e.g., those established by
ery for an investigation that is not the American Chemical Society, U.S.
subject to part 812 (see § 812.2(c)), if the Pharmacopeia, National Formulary,
following conditions are met: National Research Council.
(i) For a product in the laboratory re- (iv) A statement of warnings or pre-
search phase of development, and not cautions for users as established in the
represented as an effective in vitro di- regulations contained in 16 CFR part
agnostic product, all labeling bears the 1500 and any other warnings appro-
statement, prominently placed: ‘‘For priate to the hazard presented by the
Research Use Only. Not for use in diag- product; and a statement ‘‘For Labora-
nostic procedures.’’ tory Use.’’
(ii) For a product being shipped or de- (v) Appropriate storage instructions
livered for product testing prior to full adequate to protect the stability of the
commercial marketing (for example, product. When applicable, these in-
for use on specimens derived from hu- structions shall include such informa-
mans to compare the usefulness of the tion as conditions of temperature,
product with other products or proce- light, humidity, and other pertinent
dures which are in current use or rec- factors. The basis for such information
ognized as useful), all labeling bears shall be determined by reliable, mean-
the statement, prominently placed: ingful, and specific test methods such
‘‘For Investigational Use Only. The as those described in § 211.166 of this
performance characteristics of this chapter.
product have not been established.’’ (vi) A declaration of the net quantity
(d) The labeling of general purpose of contents, expressed in terms of
laboratory reagents (e.g., hydrochloric weight or volume, numerical count, or
acid) and equipment (e.g., test tubes any combination of these or other
and pipettes) whose uses are generally terms which accurately reflect the con-
known by persons trained in their use tents of the package. The use of metric
need not bear the directions for use re- designations is encouraged, wherever
quired by § 809.10(a) and (b), if their la- appropriate.
113
§ 809.10 21 CFR Ch. I (4–1–23 Edition)
(vii) Name and place of business of action with substances of known clin-
manufacturer, packer, or distributor. ical significance;
(viii) A lot or control number, identi- (v) A statement of warnings or pre-
fied as such, from which it is possible cautions for users as established in the
to determine the complete manufac- regulations contained in 16 CFR part
turing history of the product. 1500 and any other warnings appro-
(ix) In the case of immediate con- priate to the hazard presented by the
tainers too small or otherwise unable product;
to accommodate a label with sufficient (vi) The date of manufacture and ap-
space to bear all such information, and propriate storage instructions ade-
which are packaged within an outer quate to protect the stability of the
container from which they are removed product. When applicable, these in-
for use, the information required by structions shall include such informa-
paragraphs (d)(1)(ii), (iii), (iv), (v), and tion as conditions of temperature,
(vi) of this section may appear in the light, humidity, date of expiration, and
outer container labeling only. other pertinent factors. The basis for
(2) The label of general purpose lab- such instructions shall be determined
oratory equipment, e.g., a beaker or a by reliable, meaningful, and specific
pipette, shall bear a statement ade- test methods, such as those described
quately describing the product, its in § 211.166 of this chapter;
composition, and physical characteris- (vii) A declaration of the net quan-
tics if necessary for its proper use. tity of contents, expressed in terms of
(e)(1) The labeling for analyte spe- weight or volume, numerical count, or
cific reagents (e.g., monoclonal anti- any combination of these or other
bodies, deoxyribonucleic acid (DNA) terms that accurately reflect the con-
probes, viral antigens, ligands) shall tents of the package. The use of metric
bear the following information: designations is encouraged, wherever
(i) The proprietary name and estab- appropriate;
lished name (common or usual name), (viii) The name and place of business
if any, of the reagent; of manufacturer, packer, or dis-
(ii) A declaration of the established tributor;
name (common or usual name), if any; (ix) A lot or control number, identi-
(iii) The quantity, proportion, or con- fied as such, from which it is possible
centration of the reagent ingredient; to determine the complete manufac-
and for a reagent derived from biologi- turing history of the product;
cal material, the source and where ap- (x) For class I exempt ASR’s, the
plicable, a measure of its activity. The statement: ‘‘Analyte Specific Reagent.
quantity, proportion, concentration, or Analytical and performance character-
activity shall be stated in the system istics are not established’’; and
generally used and recognized by the (xi) For class II and III ASR’s, the
intended user, e.g., metric, inter- statement: ‘‘Analyte Specific Reagent.
national units, etc.; Except as a component of the approved/
(iv) A statement of the purity and cleared test (Name of approved/cleared
quality of the reagent, including a test), analytical and performance char-
quantitative declaration of any impuri- acteristics of this ASR are not estab-
ties present and method of analysis or lished.’’
characterization. The requirement for (2) In the case of immediate con-
this information may be met by a tainers too small or otherwise unable
statement of conformity with a gen- to accommodate a label with sufficient
erally recognized and generally avail- space to bear all such information, and
able standard that contains the same which are packaged within an outer
information, e.g., those established by container from which they are removed
the American Chemical Society, U.S. for use, the information required by
Pharmacopeia, National Formulary, paragraphs (e)(1) through (e)(6) of this
and National Research Council. The la- section may appear in the outer con-
beling may also include information tainer labeling only.
concerning chemical/molecular com- (f) The labeling for over-the-counter

position, nucleic acid sequence, binding (OTC) test sample collection systems
affinity, cross-reactivities, and inter- for drugs of abuse testing shall bear
114
the following information in language glossary that is written in English or,

appropriate for the intended users: in the case of articles distributed sole-
(1) Adequate instructions for speci- ly in Puerto Rico or in a Territory
men collection and handling, and for where the predominant language is one
preparation and mailing of the speci- other than English, the predominant
men to the laboratory for testing. language may be used;
(2) An identification system to en- (iii) A symbol not accompanied by
sure that specimens are not mixed up adjacent explanatory text that:
or otherwise misidentified at the lab- (A) Is established in a standard devel-
oratory, and that user anonymity is oped by a standards development orga-
maintained. nization (SDO);
(3) The intended use or uses of the (B) Is not contained in a standard
product, including what drugs are to be that is recognized by FDA under its au-
identified in the specimen, a quan- thority in section 514(c) of the act or is
titative description of the performance contained in a standard that is recog-
characteristics for those drugs (e.g., nized by FDA but is not used according
sensitivity and specificity) in terms to the specifications for use of the sym-
understandable to lay users, and the bol set forth in FDA’s section 514(c)
detection period. recognition;
(4) A statement that confirmatory (C) Is determined by the manufac-
testing will be conducted on all sam- turer to be likely to be read and under-
ples that initially test positive. stood by the ordinary individual under
(5) A statement of warnings or pre- customary conditions of purchase and
cautions for users as established in the use in compliance with section 502(c) of
regulations contained in 16 CFR part the act;
1500 and any other warnings appro- (D) Is used according to the specifica-
priate to the hazard presented by the tions for use of the symbol set forth in
product. the SDO-developed standard; and
(6) Adequate instructions on how to (E) Is explained in a paper or elec-
obtain test results from a person who tronic symbols glossary that is in-
can explain their meaning, including cluded in the labeling for the device
the probability of false positive and and the labeling on or within the pack-
false negative results, as well as how to age containing the device bears a
contact a trained health professional if prominent and conspicuous statement
additional information on interpreta- identifying the location of the symbols
tion of test results from the laboratory glossary that is written in English or,
or followup counseling is desired. in the case of articles distributed sole-
(7) Name and place of business of the ly in Puerto Rico or in a Territory
manufacturer, packer, or distributor. where the predominant language is one
(g)(1) The applicant may provide the other than English, the predominant
labeling information referenced in this language may be used; or
section in the form of: (iv) The symbol statement ‘‘Rx only’’
(i) A symbol accompanied by explan- or ‘‘) only’’ used as provided under
atory text adjacent to the symbol; paragraphs (a)(4) and (b)(5)(ii) of this
(ii) A symbol not accompanied by ad- section.
jacent explanatory text that: (2) The use of symbols in device la-
(A) Is contained in a standard that beling which do not meet the require-
FDA recognizes under its authority in ments of paragraph (g)(1) of this sec-
section 514(c) of the act; tion renders a device misbranded under
(B) Is used according to the specifica- section 502(c) of the act.
tions for use of the symbol set forth in (3) For purposes of paragraph (g)(1) of
FDA’s section 514(c) recognition; and this section:
(C) Is explained in a paper or elec- (i) An SDO is an organization that is
tronic symbols glossary that is in- nationally or internationally recog-
cluded in the labeling for the device nized and that follows a process for
and the labeling on or within the pack- standard development that is trans-
age containing the device bears a parent, (i.e., open to public scrutiny),
prominent and conspicuous statement where the participation is balanced,
identifying the location of the symbols where an appeals process is included,
115
§ 809.11 21 CFR Ch. I (4–1–23 Edition)
where the standard is not in conflict Stockpile official, a written request for
with any statute, regulation, or policy an exception or alternative described
under which FDA operates, and where in paragraph (a) of this section to the
the standard is national or inter- Center Director.
national in scope. (ii) The Center Director may grant
(ii) The term ‘‘symbols glossary’’ an exception or alternative described
means a compiled listing of: in paragraph (a) of this section on his
(A) Each SDO-established symbol or her own initiative.
used in the labeling for the device; (2) A written request for an exception
(B) The title and designation number or alternative described in paragraph
of the SDO-developed standard con- (a) of this section must:
taining the symbol; (i) Identify the specified lots,
(C) The title of the symbol and its batches, or other units of an in vitro
reference number, if any, in the stand- diagnostic product for human use that
ard; and would be subject to the exception or al-
(D) The meaning or explanatory text ternative;
for the symbol as provided in the FDA (ii) Identify the labeling provision(s)
recognition or, if FDA has not recog- listed in paragraph (f) of this section
nized the standard or portion of the that are the subject of the exception or
standard in which the symbol is lo- alternative request;
cated or the symbol is not used accord- (iii) Explain why compliance with
ing to the specifications for use of the such labeling provision(s) could ad-
symbol set forth in FDA’s section versely affect the safety, effectiveness,
514(c) recognition, the explanatory text or availability of the specified lots,
as provided in the standard. batches, or other units of the in vitro
[41 FR 6903, Feb. 13, 1976, as amended at 45 diagnostic product for human use that
FR 3750, Jan. 18, 1980; 45 FR 7484, Feb. 1, 1980; are or will be held in the Strategic Na-
47 FR 41107, Sept. 17, 1982; 47 FR 51109, Nov. tional Stockpile;
12, 1982; 48 FR 34470, July 29, 1983; 62 FR 62259, (iv) Describe any proposed safeguards
Nov. 21, 1997; 65 FR 18234, Apr. 7, 2000; 81 FR or conditions that will be implemented
38391, June 15, 2016]
so that the labeling of the product in-
§ 809.11 Exceptions or alternatives to cludes appropriate information nec-
labeling requirements for in vitro essary for the safe and effective use of
diagnostic products for human use the product, given the anticipated cir-
held by the Strategic National cumstances of use of the product;
Stockpile. (v) Provide a draft of the proposed la-
(a) The appropriate FDA Center Di- beling of the specified lots, batches, or
rector may grant an exception or alter- other units of the in vitro diagnostic
native to any provision listed in para- products for human use subject to the
graph (f) of this section and not explic- exception or alternative; and
itly required by statute, for specified (vi) Provide any other information
lots, batches, or other units of an in requested by the Center Director in
vitro diagnostic product for human support of the request.
use, if the Center Director determines (c) The Center Director must respond
that compliance with such labeling rein writing to all requests under this
quirement could adversely affect the section. The Center Director may im-
safety, effectiveness, or availability of pose appropriate conditions or safe-
such products that are or will be in- guards when granting such an excep-
cluded in the Strategic National tion or alternative under this section.
Stockpile. (d) A grant of an exception or alter-
(b)(1)(i) A Strategic National Stock- native under this section will include
pile official or any entity that manu- any safeguards or conditions deemed
factures (including labeling, packing, appropriate by the Center Director to
relabeling, or repackaging), distrib- ensure that the labeling of the product
utes, or stores an in vitro diagnostic subject to the exception or alternative
product for human use that is or will includes the information necessary for
be included in the Strategic National the safe and effective use of the prod-
Stockpile may submit, with written uct, given the anticipated cir-
concurrence from a Strategic National cumstances of use.
116
(e) If the Center Director grants a re- § 809.30 Restrictions on the sale, dis-
quest for an exception or alternative to tribution and use of analyte specific
the labeling requirements under this reagents.
section: (a) Analyte specific reagents (ASR’s)
(1) The Center Director may deter- (§ 864.4020 of this chapter) are restricted
mine that the submission and grant of devices under section 520(e) of the Fed-
a written request under this section eral Food, Drugs, and Cosmetic Act
satisfies the provisions relating to pre- (the act) subject to the restrictions set
market notification submissions under forth in this section.
§ 807.81(a)(3) of this chapter. (b) ASR’s may only be sold to:
(2)(i) For a Premarket Approval Ap- (1) In vitro diagnostic manufacturers;
(2) Clinical laboratories regulated
plication (PMA)-approved in vitro diag-
under the Clinical Laboratory Improve-
nostic product for human use, the sub-
ment Amendments of 1988 (CLIA), as
mission and grant of a written request
qualified to perform high complexity
under this section satisfies the provi- testing under 42 CFR part 493 or clin-
sions relating to submission of PMA ical laboratories regulated under VHA
supplements under § 814.39 of this chap- Directive 1106 (available from Depart-
ter; however, ment of Veterans Affairs, Veterans
(ii) The grant of the request must be Health Administration, Washington,
identified in a periodic report under DC 20420); and
§ 814.84 of this chapter. (3) Organizations that use the re-
(f) The Center Director may grant an agents to make tests for purposes other
exception or alternative under this sec- than providing diagnostic information
tion to the following provisions of this to patients and practitioners, e.g., fo-
part, to the extent that the require- rensic, academic, research, and other
ments in these provisions are not ex- nonclinical laboratories.
plicitly required by statute: (c) ASR’s must be labeled in accord-
(1) § 809.10(a)(1) through (a)(6) and ance with § 809.10(e).
(a)(9); (d) Advertising and promotional ma-
terials for ASR’s:
(2) § 809.10(b);
(1) Shall include the identity and pu-
(3) § 809.10(c)(2); rity (including source and method of
(4) § 809.10(d)(1)(i) through (d)(1)(v), acquisition) of the analyte specific rea-
(d)(1)(viii), and (d)(2); and gent and the identity of the analyte;
(5) § 809.10(e)(1)(i) through (e)(1)(vi) (2) Shall include the statement for
and (e)(1)(ix) through (e)(1)(xi). class I exempt ASR’s: ‘‘Analyte Spe-
[72 FR 73601, Dec. 28, 2007]
cific Reagent. Analytical and perform-
ance characteristics are not estab-
lished’’;
Subpart C—Requirements for (3) Shall include the statement for
Manufacturers and Producers class II or III ASR’s: ‘‘Analyte Specific
Reagent. Except as a component of the
§ 809.20 General requirements for approved/cleared test (name of ap-
manufacturers and producers of in proved/cleared test), analytical and
vitro diagnostic products. performance characteristics are not es-
(a) [Reserved] tablished’’; and
(b) Compliance with good manufac- (4) Shall not make any statement re-
turing practices. In vitro diagnostic garding analytical or clinical perform-
products shall be manufactured in ac- ance.
cordance with the good manufacturing (e) The laboratory that develops an
practices requirements found in part in-house test using the ASR shall in-
820 of this chapter and, if applicable, form the ordering person of the test re-
with § 610.44 of this chapter. sult by appending to the test report the
statement: ‘‘This test was developed
[41 FR 6903, Feb. 13, 1976, as amended at 42 and its performance characteristics de-
FR 42530, Aug. 23, 1977; 43 FR 31527, July 21, termined by (Laboratory Name). It has
1978; 66 FR 31165, June 11, 2001] not been cleared or approved by the
U.S. Food and Drug Administration.’’
117
§ 809.40 21 CFR Ch. I (4–1–23 Edition)
This statement would not be applicable tion of test results from the laboratory
or required when test results are gen- to the lay purchaser.
erated using the test that was cleared [65 FR 18234, Apr. 7, 2000]
or approved in conjunction with review
of the class II or III ASR.
PART 810—MEDICAL DEVICE
(f) Ordering in-house tests that are
developed using analyte specific re-
RECALL AUTHORITY
agents is limited under section 520(e) of
the act to physicians and other persons
authorized by applicable State law to Sec.
order such tests. 810.1 Scope.
(g) The restrictions in paragraphs (c) 810.2 Definitions.
810.3 Computation of time.
through (f) of this section do not apply 810.4 Service of orders.
when reagents that otherwise meet the
analyte specific reagent definition are Subpart B—Mandatory Medical Device
sold to: Recall Procedures
(1) In vitro diagnostic manufacturers;
810.10 Cease distribution and notification
or order.
(2) Organizations that use the re- 810.11 Regulatory hearing.
agents to make tests for purposes other 810.12 Written request for review of cease
than providing diagnostic information distribution and notification order.
to patients and practitioners, e.g., fo- 810.13 Mandatory recall order.
rensic, academic, research, and other 810.14 Cease distribution and notification or
mandatory recall strategy.
nonclinical laboratories. 810.15 Communications concerning a cease
[62 FR 62259, Nov. 21, 1997] distribution and notification or manda-
tory recall order.
§ 809.40 Restrictions on the sale, dis- 810.16 Cease distribution and notification or
mandatory recall order status reports.
tribution, and use of OTC test sam-
810.17 Termination of a cease distribution
ple collection systems for drugs of
and notification or mandatory recall
abuse testing. order.
(a) Over-the-counter (OTC) test sam- 810.18 Public notice.
ple collection systems for drugs of AUTHORITY: 21 U.S.C. 321, 331, 332, 333, 334,
abuse testing (§ 864.3260 of this chapter) 351, 352, 355, 360h, 360i, 371, 374, 375.
are restricted devices under section SOURCE: 61 FR 59018, Nov. 20, 1996, unless
520(e) of the Act subject to the restric- otherwise noted.
tions set forth in this section.
(b) Sample testing shall be performed Subpart A—General Provisions
in a laboratory using screening tests
that have been approved, cleared, or § 810.1 Scope.
otherwise recognized by the Food and Part 810 describes the procedures
Drug Administration as accurate and that the Food and Drug Administra-
reliable for the testing of such speci- tion will follow in exercising its med-
mens for identifying drugs of abuse or ical device recall authority under sec-
their metabolites. tion 518(e) of the Federal Food, Drug,
(c) The laboratory performing the and Cosmetic Act.
test(s) shall have, and shall be recog-
nized as having, adequate capability to § 810.2 Definitions.
reliably perform the necessary screen- As used in this part:
ing and confirmatory tests, including (a) Act means the Federal Food,
adequate capability to perform integ- Drug, and Cosmetic Act.
rity checks of the biological specimens (b) Agency or FDA means the Food
for possible adulteration. and Drug Administration.
(d) All OTC test sample collection (c) Cease distribution and notification
systems for drugs of abuse testing shall strategy or mandatory recall strategy
be labeled in accordance with § 809.10(f) means a planned, specific course of ac-

and shall provide an adequate system tion to be taken by the person named
to communicate the proper interpreta- in a cease distribution and notification
118
order or in a mandatory recall order, (m) Unique device identifier (UDI)

which addresses the extent of the noti- means an identifier that adequately
fication or recall, the need for public identifies a device through its distribu-
warnings, and the extent of effective- tion and use by meeting the require-
ness checks to be conducted. ments of § 830.20 of this chapter. A
(d) Consignee means any person or unique device identifier is composed of:
firm that has received, purchased, or (1) A device identifier—a mandatory,
used a device that is subject to a cease fixed portion of a UDI that identifies
distribution and notification order or a the specific version or model of a de-
mandatory recall order. Consignee does vice and the labeler of that device; and
not mean lay individuals or patients, (2) A production identifier—a condi-
i.e., nonhealth professionals. tional, variable portion of a UDI that
(e) Correction means repair, modifica- identifies one or more of the following
tion, adjustment, relabeling, destruc- when included on the label of the de-
tion, or inspection (including patient vice:
monitoring) of a device, without its (i) The lot or batch within which a
physical removal from its point of use device was manufactured;
to some other location. (ii) The serial number of a specific
(f) Device user facility means a hos- device;
pital, ambulatory surgical facility, (iii) The expiration date of a specific
nursing home, or outpatient treatment device;
or diagnostic facility that is not a phy- (iv) The date a specific device was
sician’s office. manufactured.
(v) For an HCT/P regulated as a de-
(g) Health professionals means practi-
vice, the distinct identification code
tioners, including physicians, nurses,
required by § 1271.290(c) of this chapter.
pharmacists, dentists, respiratory
therapists, physical therapists, tech- [61 FR 59018, Nov. 20, 1996, as amended at 78
nologists, or any other practitioners or FR 58821, Sept. 24, 2013]
allied health professionals that have a
role in using a device for human use. § 810.3 Computation of time.
(h) Human cell, tissue, or cellular or tis- In computing any period of time pre-
sue-based product (HCT/P) regulated as a scribed or allowed by this part, the day
device means an HCT/P as defined in of the act or event from which the des-
§ 1271.3(d) of this chapter that does not ignated period of time begins to run
meet the criteria in § 1271.10(a) and that shall not be included. The computation
is also regulated as a device. of time is based only on working days.
(i) Reasonable probability means that
it is more likely than not that an event § 810.4 Service of orders.
will occur. Orders issued under this part will be
(j) Serious, adverse health consequence served in person by a designated em-
means any significant adverse experi- ployee of FDA, or by certified or reg-
ence, including those that may be ei- istered mail or similar mail delivery
ther life-threatening or involve perma- service with a return receipt record re-
nent or long-term injuries, but exclud- flecting receipt, to the named person or
ing injuries that are nonlife-threat- designated agent at the named person’s
ening and that are temporary and rea- or designated agent’s last known ad-
sonably reversible. dress in FDA’s records.
(k) Recall means the correction or re-
moval of a device for human use where Subpart B—Mandatory Medical
FDA finds that there is a reasonable Device Recall Procedures
probability that the device would cause
serious, adverse health consequences or § 810.10 Cease distribution and notifi-
death. cation order.
(l) Removal means the physical re- (a) If, after providing the appropriate
moval of a device from its point of use person with an opportunity to consult
to some other location for repair, with the agency, FDA finds that there
modification, adjustment, relabeling, is a reasonable probability that a de-
destruction, or inspection. vice intended for human use would
119
§ 810.10 21 CFR Ch. I (4–1–23 Edition)
cause serious, adverse health con- (2) The total number of units of the
sequences or death, the agency may device estimated to be in distribution
issue a cease distribution and notifica- channels;
tion order requiring the person named (3) The total number of units of the
in the order to immediately: device estimated to be distributed to
(1) Cease distribution of the device; health professionals and device user fa-
(2) Notify health professionals and cilities;
device user facilities of the order; and (4) The total number of units of the
(3) Instruct these professionals and device estimated to be in the hands of
device user facilities to cease use of the
home users;
device.
(b) FDA will include the following in- (5) Distribution information, includ-
formation in the order: ing the names and addresses of all con-
(1) The requirements of the order re- signees;
lating to cessation of distribution and (6) A copy of any written communica-
notification of health professionals and tion used by the person named in the
device user facilities; order to notify health professionals and
(2) Pertinent descriptive information device user facilities;
to enable accurate and immediate iden- (7) A proposed strategy for complying
tification of the device subject to the with the cease distribution and notifi-
order, including, where known: cation order;
(i) The brand name of the device; (8) Progress reports to be made at
(ii) The common name, classification specified intervals, showing the names
name, or usual name of the device; and addresses of health professionals
(iii) The model, catalog, or product and device user facilities that have
code numbers of the device; been notified, names of specific individ-
(iv) The manufacturing lot numbers uals contacted within device user fa-
or serial numbers of the device or other cilities, and the dates of such contacts;
identification numbers; and
and
(v) The unique device identifier (UDI)
(9) The name, address, and telephone
that appears on the device label or on
the device package; and number of the person who should be
(3) A statement of the grounds for contacted concerning implementation
FDA’s finding that there is a reason- of the order.
able probability that the device would (e) FDA will provide the person
cause serious, adverse health con- named in a cease distribution and noti-
sequences or death. fication order with an opportunity for
(c) FDA may also include in the order a regulatory hearing on the actions re-
a model letter for notifying health pro- quired by the cease distribution and
fessionals and device user facilities of notification order and on whether the
the order and a requirement that noti- order should be modified, or vacated, or
fication of health professionals and de- amended to require a mandatory recall
vice user facilities be completed within of the device.
a specified timeframe. The model letter (f) FDA will also provide the person
will include the key elements of infor- named in the cease distribution and no-
mation that the agency in its discre- tification order with an opportunity, in
tion has determined, based on the cir- lieu of a regulatory hearing, to submit
cumstances surrounding the issuance a written request to FDA asking that
of each order, are necessary to inform the order be modified, or vacated, or
health professionals and device user fa- amended.
cilities about the order. (g) FDA will include in the cease dis-
(d) FDA may also require that the tribution and notification order the
person named in the cease distribution
name, address, and telephone number
and notification order submit any or
of an agency employee to whom any re-
all of the following information to the
quest for a regulatory hearing or agen-
agency by a time specified in the order:
cy review is to be addressed.
(1) The total number of units of the

device produced and the timespan of [61 FR 59018, Nov. 20, 1996, as amended at 78
the production; FR 58821, Sept. 24, 2013]
120
§ 810.11 Regulatory hearing. any provision of part 16 under § 10.19 of

(a) Any request for a regulatory hear- this chapter. As provided in § 16.26(b),
ing shall be submitted in writing to the after the hearing commences, the pre-
agency employee identified in the siding officer may issue a summary de-
order within the timeframe specified cision on any issue if the presiding offi-
by FDA. Under § 16.22(b) of this chapter, cer determines that there is no genuine
this timeframe ordinarily will not be and substantial issue of fact respecting
fewer than 3 working days after receipt that issue.
of the cease distribution and notifica- (d) If the person named in the cease
tion order. However, as provided in distribution and notification order does
§ 16.60(h) of this chapter, the Commis- not request a regulatory hearing with-
sioner of Food and Drugs or presiding in the timeframe specified by FDA in
officer may waive, suspend, or modify the cease distribution and notification
any provision of part 16 under § 10.19 of order, that person will be deemed to
this chapter, including those per- have waived his or her right to request
taining to the timing of the hearing. a hearing.
As provided in § 16.26(a), the Commis- (e) The presiding officer will ordi-
sioner or presiding officer may deny a narily hold any regulatory hearing re-
request for a hearing, in whole or in quested under paragraph (a) of this sec-
part, if he or she determines that no tion no fewer than 2 working days after
genuine and substantial issue of fact is receipt of the request for a hearing,
raised by the material submitted in the under § 16.24(e) of this chapter, and no
request. later than 10 working days after the
(b) If a request for a regulatory hear- date of issuance of the cease distribu-
ing is granted, the regulatory hearing tion and notification order. However,
shall be limited to: FDA and the person named in the order
(1) Reviewing the actions required by may agree to a later date or the pre-
the cease distribution and notification siding officer may determine that the
order, determining if FDA should af- hearing should be held in fewer than 2
firm, modify, or vacate the order, and days. Moreover, as provided for in
addressing an appropriate cease dis- § 16.60(h) of this chapter, the Commis-
tribution and notification strategy; sioner of Food and Drugs or presiding
and officer may waive, suspend, or modify
(2) Determining whether FDA should any provision of part 16 under § 10.19 of
amend the cease distribution and noti- this chapter, including those per-
fication order to require a recall of the taining to the timing of the hearing.
device that was the subject of the After the presiding officer prepares a
order. The hearing may also address written report of the hearing and the
the actions that might be required by a agency issues a final decision based on
recall order, including an appropriate the report, the presiding officer shall
recall strategy, if FDA later orders a provide the requestor written notifica-
recall. tion of the final decision to affirm,
(c) If a request by the person named modify, or vacate the order or to
in a cease distribution and notification amend the order to require a recall of
order for a regulatory hearing is grant- the device within 15 working days of
ed, the regulatory hearing will be con- conducting a regulatory hearing.
ducted in accordance with the proce-
dures set out in section 201(x) of the § 810.12 Written request for review of
act (21 U.S.C. 321(x)) and part 16 of this cease distribution and notification
chapter, except that the order issued order.
under § 810.10, rather than a notice (a) In lieu of requesting a regulatory
under § 16.22(a) of this chapter, provides hearing under § 810.11, the person
the notice of opportunity for a hearing named in a cease distribution and noti-
and is part of the administrative record fication order may submit a written re-
of the regulatory hearing under quest to FDA asking that the order be
§ 16.80(a) of this chapter. As provided in modified or vacated. Such person shall
§ 16.60(h) of this chapter, the Commis- address the written request to the
sioner of Food and Drugs or presiding agency employee identified in the
officer may waive, suspend, or modify order and shall submit the request
121
§ 810.13 21 CFR Ch. I (4–1–23 Edition)
within the timeframe specified in the ceipt of a written request for review of
order, unless FDA and the person a cease distribution and notification
named in the order agree to a later order under § 810.12.
date. (b) In a mandatory recall order, FDA
(b) A written request for review of a may:
cease distribution and notification (1) Specify that the recall is to ex-
order shall identify each ground upon tend to the wholesale, retail, or user
which the requestor relies in asking level;
that the order be modified or vacated, (2) Specify a timetable in accordance
as well as addressing an appropriate
with which the recall is to begin and be
cease distribution and notification
completed;
strategy, and shall address whether the
order should be amended to require a (3) Require the person named in the
recall of the device that was the sub- order to submit to the agency a pro-
ject of the order and the actions re- posed recall strategy, as described in
quired by such a recall order, including § 810.14, and periodic reports describing
an appropriate recall strategy. the progress of the mandatory recall,
(c) The agency official who issued the as described in § 810.16; and
cease distribution and notification (4) Provide the person named in the
order shall provide the requestor writ- order with a model recall notification
ten notification of the agency’s deci- letter that includes the key elements
sion to affirm, modify, or vacate the of information that FDA has deter-
order or amend the order to require a mined are necessary to inform health
recall of the device within 15 working professionals and device user facilities.
days of receipt of the written request. (c) FDA will not include in a manda-
The agency official shall include in tory recall order a requirement for:
this written notification: (1) Recall of a device from individ-
(1) A statement of the grounds for uals; or
the decision to affirm, modify, vacate, (2) Recall of a device from device user
or amend the order; and facilities, if FDA determines that the
(2) The requirements of any modified risk of recalling the device from the fa-
or amended order. cilities presents a greater health risk
§ 810.13 Mandatory recall order. than the health risk of not recalling
the device from use, unless the device
(a) If the person named in a cease dis- can be replaced immediately with an
tribution and notification order does equivalent device.
not request a regulatory hearing or (d) FDA will include in a mandatory
submit a request for agency review of recall order provisions for notification
the order, or, if the Commissioner of
to individuals subject to the risks asso-
Food and Drugs or the presiding officer
ciated with use of the device. If a sig-
denies a request for a hearing, or, if
nificant number of such individuals
after conducting a regulatory hearing
cannot be identified, FDA may notify
under § 810.11 or completing agency re-
such individuals under section 705(b) of
view of a cease distribution and notifi-
cation order under § 810.12, FDA deter- the act.
mines that the order should be amend- § 810.14 Cease distribution and notifi-
ed to require a recall of the device with cation or mandatory recall strategy.
respect to which the order was issued,
FDA shall amend the order to require (a) General. The person named in a
such a recall. FDA shall amend the cease distribution and notification
order to require such a recall within 15 order issued under § 810.10 shall comply
working days of issuance of a cease dis- with the order, which FDA will fashion
tribution and notification order if a as appropriate for the individual cir-
regulatory hearing or agency review of cumstances of the case. The person
the order is not requested, or within 15 named in a cease distribution and noti-
working days of denying a request for a fication order modified under § 810.11(e)
hearing, or within 15 working days of or § 810.12(c) or a mandatory recall

completing a regulatory hearing under order issued under § 810.13 shall develop
§ 810.11, or within 15 working days of re- a strategy for complying with the
122
order that is appropriate for the indi- ject to the risks associated with use of
vidual circumstances and that takes the recalled device. The notice may be
into account the following factors: provided through the individuals’
(1) The nature of the serious, adverse health professionals if FDA determines
health consequences related to the de- that such consultation is appropriate
vice; and would be the most effective meth-
(2) The ease of identifying the device; od of notifying patients.
(3) The extent to which the risk pre- (3) Effectiveness checks by the person
sented by the device is obvious to a named in the order are required to
health professional or device user facil- verify that all health professionals, de-
ity; and vice user facilities, consignees, and in-
(4) The extent to which the device is dividuals, as appropriate, have been no-
used by health professionals and device tified of the cease distribution and no-
user facilities. tification order or mandatory recall
(b) Submission and review. (1) The per- order and of the need to take appro-
son named in the cease distribution priate action. The person named in the
and notification order modified under cease distribution and notification
§ 810.11(e) or § 810.12(c) or mandatory re- order or the mandatory recall order
call order shall submit a copy of the
shall specify in the strategy the meth-
proposed strategy to the agency within
od(s) to be used in addition to written
the timeframe specified in the order.
communications as required by § 810.15,
(2) The agency will review the pro-
i.e., personal visits, telephone calls, or
posed strategy and make any changes
a combination thereof to contact all
to the strategy that it deems necessary
within 7 working days of receipt of the health professionals, device user facili-
proposed strategy. The person named ties, consignees, and individuals, as ap-
in the order shall act in accordance propriate. The agency may conduct ad-
with a strategy determined by FDA to ditional audit checks where appro-
be appropriate. priate.
(c) Elements of the strategy. A pro-
§ 810.15 Communications concerning a
posed strategy shall meet all of the fol- cease distribution and notification
lowing requirements: or mandatory recall order.
(1)(i) The person named in the order
shall specify the level in the chain of (a) General. The person named in a
distribution to which the cease dis- cease distribution and notification
tribution and notification order or order issued under § 810.10 or a manda-
mandatory recall order is to extend as tory recall order issued under § 810.13 is
follows: responsible for promptly notifying
(A) Consumer or user level, e.g., each health professional, device user
health professionals, consignee, or de- facility, consignee, or individual, as ap-
vice user facility level, including any propriate, of the order. In accordance
intermediate wholesale or retail level; with § 810.10(c) or § 810.13(b)(4), FDA
or may provide the person named in the
(B) Retail level, to the level imme- cease distribution and notification or
diately preceding the consumer or user mandatory recall order with a model
level, and including any intermediate letter for notifying each health profes-
level; or sional, device user facility, consignee,
(C) Wholesale level. or individual, as appropriate, of the
(ii) The person named in the order order. However, if FDA does not pro-
shall not recall a device from individ- vide the person named in the cease dis-
uals; and tribution and notification or manda-
(iii) The person named in the order tory recall order with a model letter,
shall not recall a device from device the person named in a cease distribu-
user facilities if FDA notifies the per- tion and notification order issued
son not to do so because of a risk deter- under § 810.10, or a mandatory recall
mination under § 810.13(c)(2). order issued under § 810.13, is respon-
(2) The person named in a recall sible for providing such notification.
order shall ensure that the strategy The purpose of the communication is
provides for notice to individuals sub- to convey:
123
§ 810.16 21 CFR Ch. I (4–1–23 Edition)
(1) That FDA has found that there is post card or a toll-free call to the per-
a reasonable probability that use of the son named in the order; and
device would cause a serious, adverse (6) Does not contain irrelevant quali-
health consequence or death; fications, promotional materials, or
(2) That the person named in the any other statement that may detract
order has ceased distribution of the de- from the message.
vice; (d) Followup communications. The per-
(3) That health professionals and de- son named in the cease distribution
vice user facilities should cease use of and notification order or mandatory
the device immediately; recall order shall ensure that followup
(4) Where appropriate, that the de- communications are sent to all who
vice is subject to a mandatory recall fail to respond to the initial commu-
order; and nication.
(5) Specific instructions on what (e) Responsibility of the recipient.
should be done with the device. Health professionals, device user facili-
(b) Implementation. The person named ties, and consignees who receive a com-
in a cease distribution and notification munication concerning a cease dis-
order, or a mandatory recall order, tribution and notification order or a
shall notify the appropriate person(s) mandatory recall order should imme-
of the order by verified written com- diately follow the instructions set
munication, e.g., telegram, mailgram, forth in the communication. Where ap-
or fax. The written communication and propriate, these recipients should im-
any envelope in which it is sent or en- mediately notify their consignees of
closed shall be conspicuously marked, the order in accordance with para-
preferably in bold red ink: ‘‘URGENT— graphs (b) and (c) of this section.
[DEVICE CEASE DISTRIBUTION AND § 810.16 Cease distribution and notifi-
NOTIFICATION ORDER] or [MANDA- cation or mandatory recall order
TORY DEVICE RECALL ORDER].’’ status reports.
Telephone calls or other personal con-
(a) The person named in a cease dis-
tacts may be made in addition to, but
tribution and notification order issued
not as a substitute for, the verified
under § 810.10 or a mandatory recall
written communication, and shall be
order issued under § 810.13 shall submit
documented in an appropriate manner.
periodic status reports to FDA to en-
(c) Contents. The person named in the able the agency to assess the person’s
order shall ensure that the notice of a progress in complying with the order.
cease distribution and notification The frequency of such reports and the
order or mandatory recall order: agency official to whom such reports
(1) Is brief and to the point; shall be submitted will be specified in
(2) Identifies clearly the device, size, the order.
lot number(s), code(s), or serial num- (b) Unless otherwise specified in the
ber(s), and any other pertinent descrip- order, each status report shall contain
tive information to facilitate accurate the following information:
and immediate identification of the de- (1) The number and type of health
vice; professionals, device user facilities,
(3) Explains concisely the serious, ad- consignees, or individuals notified
verse health consequences that may about the order and the date and meth-
occur if use of the device were contin- od of notification;
ued; (2) The number and type of health
(4) Provides specific instructions on professionals, device user facilities,
what should be done with the device; consignees, or individuals who have re-
(5) Provides a ready means for the responded to the communication and the
cipient of the communication to con- quantity of the device on hand at these
firm receipt of the communication and locations at the time they received the
to notify the person named in the order communication;
of the actions taken in response to the (3) The number and type of health
communication. Such means may in- professionals, device user facilities,

clude, but are not limited to, the re- consignees, or individuals who have not
turn of a postage-paid, self-addressed responded to the communication;
124
(4) The number of devices returned or (c) FDA will provide written notifica-
corrected by each health professional, tion to the person named in the order
device user facility, consignee, or indi- when a request for termination of a
vidual contacted, and the quantity of cease distribution and notification
products accounted for; order or a mandatory recall order has
(5) The number and results of effec- been granted or denied. FDA will re-
tiveness checks that have been made; spond to a written request for termi-
and nation of a cease distribution and noti-
(6) Estimated timeframes for comple- fication or recall order within 30 work-
tion of the requirements of the cease ing days of its receipt.
distribution and notification order or
§ 810.18 Public notice.
mandatory recall order.
(c) The person named in the cease The agency will make available to
distribution and notification order or the public in the weekly FDA Enforce-
recall order may discontinue the sub- ment Report a descriptive listing of
mission of status reports when the each new mandatory recall issued
agency terminates the order in accord- under § 810.13. The agency will delay
ance with § 810.17. public notification of orders when the
agency determines that such notifica-
§ 810.17 Termination of a cease dis- tion may cause unnecessary and harm-
tribution and notification or man- ful anxiety in individuals and that ini-
datory recall order. tial consultation between individuals
(a) The person named in a cease dis- and their health professionals is essen-
tribution and notification order issued tial.
order issued under § 810.13 may request PART 812—INVESTIGATIONAL
termination of the order by submitting DEVICE EXEMPTIONS
a written request to FDA. The person
submitting a request shall certify that Subpart A—General Provisions
he or she has complied in full with all
Sec.
of the requirements of the order and
812.1 Scope.
shall include a copy of the most cur- 812.2 Applicability.
rent status report submitted to the 812.3 Definitions.
agency under § 810.16. A request for ter- 812.5 Labeling of investigational devices.
mination of a recall order shall include 812.7 Prohibition of promotion and other
a description of the disposition of the practices.
recalled device. 812.10 Waivers.
(b) FDA may terminate a cease dis- 812.18 Import and export requirements.
tribution and notification order issued 812.19 Address for IDE correspondence.
Subpart B—Application and Administrative
order issued under § 810.13 when the
Action
agency determines that the person
named in the order: 812.20 Application.
(1) Has taken all reasonable efforts to 812.25 Investigational plan.
ensure and to verify that all health 812.27 Report of prior investigations.
professionals, device user facilities, 812.28 xxx
812.30 FDA action on applications.
consignees, and, where appropriate, in-
812.35 Supplemental applications.
dividuals have been notified of the 812.36 Treatment use of an investigational
cease distribution and notification device.
order, and to verify that they have 812.38 Confidentiality of data and informa-
been instructed to cease use of the de- tion.
vice and to take other appropriate ac-
tion; or Subpart C—Responsibilities of Sponsors
(2) Has removed the device from the 812.40 General responsibilities of sponsors.
market or has corrected the device so 812.42 FDA and IRB approval.
that use of the device would not cause 812.43 Selecting investigators and monitors.
serious, adverse health consequences or 812.45 Informing investigators.
death. 812.46 Monitoring investigations.
125
§ 812.1 21 CFR Ch. I (4–1–23 Edition)
812.47 Emergency research under § 50.24 of 502 of the act, registration, listing, and
this chapter. premarket notification under section
510, performance standards under sec-
Subpart D—IRB Review and Approval tion 514, premarket approval under sec-
812.60 IRB composition, duties, and function 515, a banned device regulation
tions. under section 516, records and reports
812.62 IRB approval. under section 519, restricted device re-
812.64 IRB’s continuing review. quirements under section 520(e), good
812.65 [Reserved] manufacturing practice requirements
812.66 Significant risk device determina-
tions. under section 520(f) except for the re-
quirements found in § 820.30, if applica-
Subpart E—Responsibilities of Investigators ble (unless the sponsor states an inten-
tion to comply with these require-
812.100 General responsibilities of investiga- ments under § 812.20(b)(3) or
tors.
812.110 Specific responsibilities of investiga-
§ 812.140(b)(4)(v)) and color additive re-
tors. quirements under section 721.
812.119 Disqualification of a clinical investi- (b) References in this part to regu-
gator. latory sections of the Code of Federal
Regulations are to chapter I of title 21,
Subpart F [Reserved] unless otherwise noted.
Subpart G—Records and Reports [45 FR 3751, Jan. 18, 1980, as amended at 59
FR 14366, Mar. 28, 1994; 61 FR 52654, Oct. 7,
812.140 Records. 1996]
812.145 Inspections.
812.150 Reports. § 812.2 Applicability.
AUTHORITY: 21 U.S.C. 331, 351, 352, 353, 355, (a) General. This part applies to all
360, 360c–360f, 360h–360j, 360bbb–8b, 371, 372, clinical investigations of devices to de-
374, 379e, 379k–1, 381, 382, 383; 42 U.S.C. 216, termine safety and effectiveness, ex-
241, 262, 263b–263n.
cept as provided in paragraph (c) of
SOURCE: 45 FR 3751, Jan. 18, 1980, unless this section.
otherwise noted. (b) Abbreviated requirements. The fol-
lowing categories of investigations are
Subpart A—General Provisions considered to have approved applica-
tions for IDE’s, unless FDA has noti-
§ 812.1 Scope. fied a sponsor under § 812.20(a) that ap-
(a) The purpose of this part is to en- proval of an application is required:
courage, to the extent consistent with (1) An investigation of a device other
the protection of public health and than a significant risk device, if the de-
safety and with ethical standards, the vice is not a banned device and the
discovery and development of useful sponsor:
devices intended for human use, and to (i) Labels the device in accordance
that end to maintain optimum freedom with § 812.5;
for scientific investigators in their pur- (ii) Obtains IRB approval of the in-
suit of this purpose. This part provides vestigation after presenting the re-
procedures for the conduct of clinical viewing IRB with a brief explanation of
investigations of devices. An approved why the device is not a significant risk
investigational device exemption (IDE) device, and maintains such approval;
permits a device that otherwise would (iii) Ensures that each investigator
be required to comply with a perform- participating in an investigation of the
ance standard or to have premarket ap- device obtains from each subject under
proval to be shipped lawfully for the the investigator’s care, informed con-
purpose of conducting investigations of sent under part 50 and documents it,
that device. An IDE approved under unless documentation is waived by an
§ 812.30 or considered approved under IRB under § 56.109(c).
§ 812.2(b) exempts a device from the re- (iv) Complies with the requirements
quirements of the following sections of of § 812.46 with respect to monitoring
the Federal Food, Drug, and Cosmetic investigations;

Act (the act) and regulations issued (v) Maintains the records required
thereunder: Misbranding under section under § 812.140(b) (4) and (5) and makes
126
the reports required under § 812.150(b) (5) A device intended solely for vet-
(1) through (3) and (5) through (10); erinary use.
(vi) Ensures that participating inves- (6) A device shipped solely for re-
tigators maintain the records required search on or with laboratory animals
by § 812.140(a)(3)(i) and make the re- and labeled in accordance with
ports required under § 812.150(a) (1), (2), § 812.5(c).
(5), and (7); and (7) A custom device as defined in
(vii) Complies with the prohibitions § 812.3(b), unless the device is being
in § 812.7 against promotion and other used to determine safety or effective-
practices. ness for commercial distribution.
(2) An investigation of a device other (d) Limit on certain exemptions. In the
than one subject to paragraph (e) of case of class II or class III device de-
this section, if the investigation was scribed in paragraph (c)(1) or (2) of this
begun on or before July 16, 1980, and to section, this part applies beginning on
be completed, and is completed, on or the date stipulated in an FDA regula-
before January 19, 1981. tion or order that calls for the submis-
(c) Exempted investigations. This part, sion of premarket approval applica-
with the exception of § 812.119, does not tions for an unapproved class III de-
apply to investigations of the following vice, or establishes a performance
categories of devices: standard for a class II device.
(e) Investigations subject to IND’s. A
(1) A device, other than a transi-
sponsor that, on July 16, 1980, has an
tional device, in commercial distribu-
effective investigational new drug ap-
tion immediately before May 28, 1976,
plication (IND) for an investigation of
when used or investigated in accord-
a device shall continue to comply with
ance with the indications in labeling in
the requirements of part 312 until 90
effect at that time.
days after that date. To continue the
(2) A device, other than a transi- investigation after that date, a sponsor
tional device, introduced into commer- shall comply with paragraph (b)(1) of
cial distribution on or after May 28, this section, if the device is not a sig-
1976, that FDA has determined to be nificant risk device, or shall have ob-
substantially equivalent to a device in tained FDA approval under § 812.30 of
commercial distribution immediately an IDE application for the investiga-
before May 28, 1976, and that is used or tion of the device.
investigated in accordance with the in-
dications in the labeling FDA reviewed [45 FR 3751, Jan. 18, 1980, as amended at 46
under subpart E of part 807 in deter- FR 8956, Jan. 27, 1981; 46 FR 14340, Feb. 27,
1981; 53 FR 11252, Apr. 6, 1988; 62 FR 4165, Jan.
mining substantial equivalence.
29, 1997; 62 FR 12096, Mar. 14, 1997]
(3) A diagnostic device, if the sponsor
complies with applicable requirements § 812.3 Definitions.
in § 809.10(c) and if the testing:
(a) Act means the Federal Food,
(i) Is noninvasive, Drug, and Cosmetic Act (sections 201–
(ii) Does not require an invasive sam- 901, 52 Stat. 1040 et seq., as amended (21
pling procedure that presents signifi- U.S.C. 301–392)).
cant risk, (b) A custom device means a device
(iii) Does not by design or intention within the meaning of section 520(b) of
introduce energy into a subject, and the Federal Food, Drug, and Cosmetic
(iv) Is not used as a diagnostic proce- Act.
dure without confirmation of the diag- (c) FDA means the Food and Drug
nosis by another, medically established Administration.
diagnostic product or procedure. (d) Implant means a device that is
(4) A device undergoing consumer placed into a surgically or naturally
preference testing, testing of a modi- formed cavity of the human body if it
fication, or testing of a combination of is intended to remain there for a period
two or more devices in commercial dis- of 30 days or more. FDA may, in order
tribution, if the testing is not for the to protect public health, determine
purpose of determining safety or effec- that devices placed in subjects for

tiveness and does not put subjects at shorter periods are also ‘‘implants’’ for
risk. purposes of this part.
127
§ 812.3 21 CFR Ch. I (4–1–23 Edition)
(e) Institution means a person, other this part, blood sampling that involves
than an individual, who engages in the simple venipuncture is considered
conduct of research on subjects or in noninvasive, and the use of surplus
the delivery of medical services to indi- samples of body fluids or tissues that
viduals as a primary activity or as an are left over from samples taken for
adjunct to providing residential or cus- noninvestigational purposes is also
todial care to humans. The term in- considered noninvasive.
cludes, for example, a hospital, retire- (l) Person includes any individual,
ment home, confinement facility, aca- partnership, corporation, association,
demic establishment, and device manu- scientific or academic establishment,
facturer. The term has the same mean- Government agency or organizational
ing as ‘‘facility’’ in section 520(g) of the unit of a Government agency, and any
act. other legal entity.
(f) Institutional review board (IRB) (m) Significant risk device means an
means any board, committee, or other investigational device that:
group formally designated by an insti- (1) Is intended as an implant and pre-
tution to review biomedical research sents a potential for serious risk to the
involving subjects and established, op- health, safety, or welfare of a subject;
erated, and functioning in conformance (2) Is purported or represented to be
with part 56. The term has the same for a use in supporting or sustaining
meaning as ‘‘institutional review com- human life and presents a potential for
mittee’’ in section 520(g) of the act. serious risk to the health, safety, or
(g) Investigational device means a de- welfare of a subject;
vice, including a transitional device, (3) Is for a use of substantial impor-
that is the object of an investigation. tance in diagnosing, curing, miti-
(h) Investigation means a clinical in- gating, or treating disease, or other-
vestigation or research involving one wise preventing impairment of human
or more subjects to determine the safe- health and presents a potential for se-
ty or effectiveness of a device. rious risk to the health, safety, or wel-
(i) Investigator means an individual fare of a subject; or
who actually conducts a clinical inves- (4) Otherwise presents a potential for
tigation, i.e., under whose immediate serious risk to the health, safety, or
direction the test article is adminis- welfare of a subject.
tered or dispensed to, or used involv- (n) Sponsor means a person who initi-
ing, a subject, or, in the event of an in- ates, but who does not actually con-
vestigation conducted by a team of in- duct, the investigation, that is, the in-
dividuals, is the responsible leader of vestigational device is administered,
that team. dispensed, or used under the immediate
(j) Monitor, when used as a noun, direction of another individual. A per-
means an individual designated by a son other than an individual that uses
sponsor or contract research organiza- one or more of its own employees to
tion to oversee the progress of an in- conduct an investigation that it has
vestigation. The monitor may be an initiated is a sponsor, not a sponsor-in-
employee of a sponsor or a consultant vestigator, and the employees are in-
to the sponsor, or an employee of or vestigators.
consultant to a contract research orga- (o) Sponsor-investigator means an indi-
nization. Monitor, when used as a verb, vidual who both initiates and actually
means to oversee an investigation. conducts, alone or with others, an in-
(k) Noninvasive, when applied to a di- vestigation, that is, under whose im-
agnostic device or procedure, means mediate direction the investigational
one that does not by design or inten- device is administered, dispensed, or
tion: (1) Penetrate or pierce the skin or used. The term does not include any
mucous membranes of the body, the oc- person other than an individual. The
ular cavity, or the urethra, or (2) enter obligations of a sponsor-investigator
the ear beyond the external auditory under this part include those of an in-
canal, the nose beyond the nares, the vestigator and those of a sponsor.
mouth beyond the pharynx, the anal (p) Subject means a human who par-
canal beyond the rectum, or the vagina ticipates in an investigation, either as
beyond the cervical os. For purposes of an individual on whom or on whose
128
specimen an investigational device is (b) Prohibitions. The labeling of an in-

used or as a control. A subject may be vestigational device shall not bear any
in normal health or may have a med- statement that is false or misleading in
ical condition or disease. any particular and shall not represent
(q) Termination means a discontinu- that the device is safe or effective for
ance, by sponsor or by withdrawal of the purposes for which it is being in-
IRB or FDA approval, of an investiga- vestigated.
tion before completion. (c) Animal research. An investiga-
(r) Transitional device means a device tional device shipped solely for re-
subject to section 520(l) of the act, that search on or with laboratory animals
is, a device that FDA considered to be shall bear on its label the following
a new drug or an antibiotic drug before statement: ‘‘CAUTION—Device for in-
May 28, 1976. vestigational use in laboratory animals
(s) Unanticipated adverse device effect or other tests that do not involve
means any serious adverse effect on human subjects.’’
health or safety or any life-threatening (d) The appropriate FDA Center Di-
problem or death caused by, or associ- rector, according to the procedures set
ated with, a device, if that effect, prob- forth in § 801.128 or § 809.11 of this chap-
lem, or death was not previously iden- ter, may grant an exception or alter-
tified in nature, severity, or degree of native to the provisions in paragraphs
incidence in the investigational plan or (a) and (c) of this section, to the extent
application (including a supplementary that these provisions are not explicitly
plan or application), or any other un- required by statute, for specified lots,
anticipated serious problem associated batches, or other units of a device that
with a device that relates to the rights, are or will be included in the Strategic
safety, or welfare of subjects. National Stockpile.
(t) Independent ethics committee (IEC)
means an independent review panel [45 FR 3751, Jan. 18, 1980, as amended at 45
that is responsible for ensuring the FR 58842, Sept. 5, 1980; 72 FR 73602, Dec. 28,
2007]
protection of the rights, safety, and
well-being of subjects involved in a § 812.7 Prohibition of promotion and
clinical investigation and is adequately other practices.
constituted to ensure that protection.
An institutional review board (IRB), as A sponsor, investigator, or any per-
defined in paragraph (f) of this section son acting for or on behalf of a sponsor
and subject to the requirements of part or investigator shall not:
56 of this chapter, is one type of IEC. (a) Promote or test market an inves-
tigational device, until after FDA has
[45 FR 3751, Jan. 18, 1980, as amended at 46
approved the device for commercial
FR 8956, Jan. 27, 1981; 48 FR 15622, Apr. 12,
1983; 81 FR 70340, Oct. 12, 2016; 83 FR 7385, distribution.
Feb. 21, 2018; 83 FR 7385, Feb. 21, 2018] (b) Commercialize an investigational
device by charging the subjects or in-
§ 812.5 Labeling of investigational de- vestigators for a device a price larger
vices. than that necessary to recover costs of
(a) Contents. An investigational de- manufacture, research, development,
vice or its immediate package shall and handling.
bear a label with the following infor- (c) Unduly prolong an investigation.
mation: the name and place of business If data developed by the investigation
of the manufacturer, packer, or dis- indicate in the case of a class III device
tributor (in accordance with § 801.1), that premarket approval cannot be jus-
the quantity of contents, if appro- tified or in the case of a class II device
priate, and the following statement: that it will not comply with an appli-
‘‘CAUTION—Investigational device. cable performance standard or an
Limited by Federal (or United States) amendment to that standard, the spon-
law to investigational use.’’ The label sor shall promptly terminate the inves-
or other labeling shall describe all rel- tigation.
evant contraindications, hazards, ad- (d) Represent that an investigational

verse effects, interfering substances or device is safe or effective for the pur-
devices, warnings, and precautions. poses for which it is being investigated.
129
§ 812.10 21 CFR Ch. I (4–1–23 Edition)
§ 812.10 Waivers. www.fda.gov/AboutFDA/CentersOffices/

OfficeofMedicalProductsandTobacco/
(a) Request. A sponsor may request
CBER/ucm385240.htm.
FDA to waive any requirement of this
part. A waiver request, with supporting (3) For devices regulated by the Cen-
documentation, may be submitted sep- ter for Drug Evaluation and Research,
arately or as part of an application to send it to Central Document Control
the address in § 812.19. Room, Center for Drug Evaluation and
Research, Food and Drug Administra-
(b) FDA action. FDA may by letter
tion, 5901–B Ammendale Rd., Beltsville,
grant a waiver of any requirement that
MD 20705–1266.
FDA finds is not required by the act
and is unnecessary to protect the (b) You must state on the outside
rights, safety, or welfare of human sub- wrapper of each submission what the
jects. submission is, for example, an ‘‘IDE ap-
(c) Effect of request. Any requirement plication,’’ a ‘‘supplemental IDE appli-
shall continue to apply unless and cation,’’ or a ‘‘correspondence con-
until FDA waives it. cerning an IDE (or an IDE applica-
tion).’’
§ 812.18 Import and export require- [71 FR 42048, July 25, 2006, as amended at 75
ments. FR 20915, Apr. 22, 2010; 80 FR 18094, Apr. 3,
(a) Imports. In addition to complying 2015; 84 FR 68339, Dec. 16, 2019]
with other requirements of this part, a
person who imports or offers for impor- Subpart B—Application and
tation an investigational device sub- Administrative Action
ject to this part shall be the agent of
the foreign exporter with respect to in- § 812.20 Application.
vestigations of the device and shall act (a) Submission. (1) A sponsor shall
as the sponsor of the clinical investiga- submit an application to FDA if the
tion, or ensure that another person sponsor intends to use a significant
acts as the agent of the foreign ex- risk device in an investigation, intends
porter and the sponsor of the investiga- to conduct an investigation that in-
tion. volves an exception from informed con-
(b) Exports. A person exporting an in- sent under § 50.24 of this chapter, or if
vestigational device subject to this FDA notifies the sponsor that an appli-
part shall obtain FDA’s prior approval, cation is required for an investigation.
as required by section 801(e) of the act (2) A sponsor shall not begin an in-
or comply with section 802 of the act. vestigation for which FDA’s approval
[45 FR 3751, Jan. 18, 1980, as amended at 62 of an application is required until FDA
FR 26229, May 13, 1997] has approved the application.
(3) A sponsor shall submit a signed
§ 812.19 Address for IDE correspond- ‘‘Application for an Investigational De-
ence. vice Exemption’’ (IDE application), to-
(a) If you are sending an application, gether with accompanying materials in
supplemental application, report, re- electronic format, to one of the ad-
quest for waiver, request for import or dresses in § 812.19, and if eCopy by reg-
export approval, or other correspond- istered mail or by hand. Subsequent
ence relating to matters covered by correspondence concerning an applica-
this part, you must send the submis- tion or a supplemental application
sion to the appropriate address as fol- shall be submitted in electronic format
lows: and if eCopy by registered mail or by
(1) For devices regulated by the Cen- hand.
ter for Devices and Radiological (4)(i) A sponsor shall submit a sepa-
Health, send it to the current address rate IDE for any clinical investigation
displayed on the website https:// involving an exception from informed
www.fda.gov/cdrhsubmissionaddress. consent under § 50.24 of this chapter.
(2) For devices regulated by the Cen- Such a clinical investigation is not
ter for Biologics Evaluation and Re- permitted to proceed without the prior
search, send it to the current address written authorization of FDA. FDA
displayed on the website https:// shall provide a written determination
130
30 days after FDA receives the IDE or been identified in accordance with
earlier. paragraph (b)(6) of this section.
(ii) If the investigation involves an (8) If the device is to be sold, the
exception from informed consent under amount to be charged and an expla-
§ 50.24 of this chapter, the sponsor shall nation of why sale does not constitute
prominently identify on the cover commercialization of the device.
sheet that the investigation is subject (9) A claim for categorical exclusion
to the requirements in § 50.24 of this under § 25.30 or § 25.34 or an environ-
chapter. mental assessment under § 25.40.
(b) Contents. An IDE application shall (10) Copies of all labeling for the de-
include, in the following order: vice.
(1) The name and address of the spon- (11) Copies of all forms and informa-
sor. tional materials to be provided to sub-
(2) A complete report of prior inves- jects to obtain informed consent.
tigations of the device and an accurate (12) Any other relevant information
summary of those sections of the inves- FDA requests for review of the applica-
tigational plan described in § 812.25(a) tion.
through (e) or, in lieu of the summary, (c) Additional information. FDA may
the complete plan. The sponsor shall request additional information con-
submit to FDA a complete investiga- cerning an investigation or revision in
tional plan and a complete report of the investigational plan. The sponsor
prior investigations of the device if no may treat such a request as a dis-
IRB has reviewed them, if FDA has approval of the application for pur-
found an IRB’s review inadequate, or if poses of requesting a hearing under
FDA requests them. part 16.
(3) A description of the methods, fa- (d) Information previously submitted.
cilities, and controls used for the man- Information previously submitted to
ufacture, processing, packing, storage, the Center for Devices and Radio-
and, where appropriate, installation of logical Health, the Center for Biologics
the device, in sufficient detail so that a Evaluation and Research, or the Center
person generally familiar with good for Drug Evaluation and Research, as
manufacturing practices can make a applicable, in accordance with this
knowledgeable judgment about the chapter ordinarily need not be resub-
quality control used in the manufac- mitted, but may be incorporated by
ture of the device. reference.
(4) An example of the agreements to [45 FR 3751, Jan. 18, 1980, as amended at 46
be entered into by all investigators to FR 8956, Jan. 27, 1981; 50 FR 16669, Apr. 26,
comply with investigator obligations 1985; 53 FR 11252, Apr. 6, 1988; 61 FR 51530,
under this part, and a list of the names Oct. 2, 1996; 62 FR 40600, July 29, 1997; 64 FR
and addresses of all investigators who 10942, Mar. 8, 1999; 73 FR 49942, Aug. 25, 2008;
have signed the agreement. 84 FR 68339, Dec. 16, 2019]
(5) A certification that all investiga-
tors who will participate in the inves- § 812.25 Investigational plan.
tigation have signed the agreement, The investigational plan shall in-
that the list of investigators includes clude, in the following order:
all the investigators participating in (a) Purpose. The name and intended
the investigation, and that no inves- use of the device and the objectives and
tigators will be added to the investiga- duration of the investigation.
tion until they have signed the agree- (b) Protocol. A written protocol de-
ment. scribing the methodology to be used
(6) A list of the name, address, and and an analysis of the protocol dem-
chairperson of each IRB that has been onstrating that the investigation is
or will be asked to review the inves- scientifically sound.
tigation and a certification of the ac- (c) Risk analysis. A description and
tion concerning the investigation analysis of all increased risks to which
taken by each such IRB. subjects will be exposed by the inves-
(7) The name and address of any in- tigation; the manner in which these
stitution at which a part of the inves- risks will be minimized; a justification
tigation may be conducted that has not for the investigation; and a description
131
§ 812.27 21 CFR Ch. I (4–1–23 Edition)
of the patient population, including the (3) If information on nonclinical lab-

number, age, sex, and condition. oratory studies is provided, a state-
(d) Description of device. A description ment that all such studies have been
of each important component, ingre- conducted in compliance with applica-
dient, property, and principle of oper- ble requirements in the good labora-
ation of the device and of each antici- tory practice regulations in part 58, or
pated change in the device during the if any such study was not conducted in
course of the investigation. compliance with such regulations, a
(e) Monitoring procedures. The spon- brief statement of the reason for the
sor’s written procedures for monitoring noncompliance. Failure or inability to
the investigation and the name and ad- comply with this requirement does not
dress of any monitor. justify failure to provide information
(f) Labeling. Copies of all labeling for on a relevant nonclinical test study.
the device.
(4)(i) If data from clinical investiga-
(g) Consent materials. Copies of all
forms and informational materials to tions conducted in the United States
be provided to subjects to obtain in- are provided, a statement that each in-
formed consent. vestigation was conducted in compli-
(h) IRB information. A list of the ance with applicable requirements in
names, locations, and chairpersons of the protection of human subjects regu-
all IRB’s that have been or will be lations in part 50 of this chapter, the
asked to review the investigation, and institutional review boards regulations
a certification of any action taken by in part 56 of this chapter, or was not
any of those IRB’s with respect to the subject to the regulations under § 56.104
investigation. or § 56.105, and the investigational de-
(i) Other institutions. The name and vice exemptions regulations in this
address of each institution at which a part, or if any such investigation was
part of the investigation may be con- not conducted in compliance with
ducted that has not been identified in those regulations, a brief statement of
paragraph (h) of this section. the reason for the noncompliance. Fail-
(j) Additional records and reports. A de- ure or inability to comply with these
scription of records and reports that requirements does not justify failure to
will be maintained on the investigation provide information on a relevant clin-
in addition to those prescribed in sub- ical investigation.
part G. (ii) If data from clinical investiga-
tions conducted outside the United
§ 812.27 Report of prior investigations.
States are provided to support the IDE,
(a) General. The report of prior inves- the requirements under § 812.28 apply. If
tigations shall include reports of all any such investigation was not con-
prior clinical, animal, and laboratory ducted in accordance with good clinical
testing of the device and shall be com- practice (GCP) as described in
prehensive and adequate to justify the § 812.28(a), the report of prior investiga-
proposed investigation. tions shall include either a waiver re-
(b) Specific contents. The report also quest in accordance with § 812.28(c) or a
shall include: brief statement of the reason for not
(1) A bibliography of all publications, conducting the investigation in accord-
whether adverse or supportive, that are
ance with GCP and a description of
relevant to an evaluation of the safety
steps taken to ensure that the data and
or effectiveness of the device, copies of
results are credible and accurate and
all published and unpublished adverse
that the rights, safety, and well-being
information, and, if requested by an
of subjects have been adequately pro-
IRB or FDA, copies of other significant
publications. tected. Failure or inability to comply
(2) A summary of all other unpub- with these requirements does not jus-
lished information (whether adverse or tify failure to provide information on a
supportive) in the possession of, or rea- relevant clinical investigation.
sonably obtainable by, the sponsor that [45 FR 3751, Jan. 18, 1980, as amended at 50
is relevant to an evaluation of the safe- FR 7518, Feb. 22, 1985; 83 FR 7385, Feb. 21,
ty or effectiveness of the device. 2018]
132
§ 812.28 Acceptance of data from clin- 814 of this chapter, as applicable, the
ical investigations conducted out- information in paragraph (b) of this
side the United States. section is submitted, as follows:
(a) Acceptance of data from clinical in- (i) For an investigation of a signifi-
vestigations conducted outside the United cant risk device, as defined in
States to support an IDE or a device mar- § 812.3(m), the supporting information
keting application or submission (an ap- as described in paragraph (b) of this
plication under section 515 or 520(m) of section is submitted.
the Federal Food, Drug, and Cosmetic (ii) For an investigation of a device,
Act, a premarket notification submission other than a significant risk device,
under section 510(k) of the Federal Food, the supporting information as de-
Drug, and Cosmetic Act, or a request for scribed in paragraphs (b)(1), (4), (5), (7)
De Novo classification under section through (9), and (11) of this section is
513(f)(2) of the Federal Food, Drug, and submitted, and the supporting informa-
Cosmetic Act). FDA will accept information as described in paragraph (b)(10) of
tion on a clinical investigation con- this section and the rationale for deter-
ducted outside the United States to mining the investigation is of a device
support an IDE or a device marketing other than a significant risk device are
application or submission if the inves- made available for agency review upon
tigation is well-designed and well-con- request by FDA.
ducted and the following conditions are (iii) For a device investigation that
met: meets the exemption criteria in
(1) A statement is provided that the § 812.2(c), the supporting information as
investigation was conducted in accord- described in paragraphs (b)(1), (4), (5),
ance with good clinical practice (GCP). (7) through (11) of this section and the
For the purposes of this section, GCP is rationale for determining the inves-
defined as a standard for the design, tigation meets the exemption criteria
conduct, performance, monitoring, au- in § 812.2(c) are made available for
diting, recording, analysis, and report- agency review upon request by FDA.
ing of clinical investigations in a way (3) FDA is able to validate the data
that provides assurance that the data from the investigation through an on-
and results are credible and accurate site inspection, or through other appro-
and that the rights, safety, and well- priate means, if the agency deems it
being of subjects are protected. GCP in- necessary.
cludes review and approval (or provi- (b) Supporting information. A sponsor
sion of a favorable opinion) by an inde- or applicant who submits data from a
pendent ethics committee (IEC) before clinical investigation conducted out-
initiating an investigation, continuing side the United States to support an
review of an ongoing investigation by IDE or a device marketing application
an IEC, and obtaining and documenting or submission, in addition to informa-
the freely given informed consent of tion required elsewhere in parts 807,
the subject (or a subject’s legally au- 812, and 814 of this chapter, as applica-
thorized representative, if the subject ble, shall provide a description of the
is unable to provide informed consent) actions the sponsor or applicant took
before initiating an investigation. GCP to ensure that the research conformed
does not require informed consent in to GCP as described in paragraph (a)(1)
life-threatening situations when the of this section. The description is not
IEC reviewing the investigation finds, required to duplicate information al-
before initiation of the investigation, ready submitted in the application or
that informed consent is not feasible submission. Instead, the description
and either that the conditions present must provide either the following in-
are consistent with those described in formation, as specified in paragraph
§ 50.23 or § 50.24(a) of this chapter, or (a)(2) of this section, or a cross-ref-
that the measures described in the pro- erence to another section of the appli-
tocol or elsewhere will protect the cation or submission where the infor-
rights, safety, and well-being of sub- mation is located:
jects. (1) The names of the investigators

(2) In addition to the information re- and the names and addresses of the re-
quired elsewhere in parts 807, 812, and search facilities and sites where
133
§ 812.28 21 CFR Ch. I (4–1–23 Edition)
records relating to the investigation (12) A description of how investiga-

are maintained; tors were trained to comply with GCP
(2) The investigator’s qualifications; (as described in paragraph (a)(1) of this
(3) A description of the research fa- section) and to conduct the investiga-
cility(ies); tion in accordance with the protocol,
(4) A detailed summary of the pro- and a statement on whether written
tocol and results of the investigation commitments by investigators to com-
and, should FDA request, case records ply with GCP and the protocol were ob-
maintained by the investigator or addi- tained. Any signed written commit-
tional background data such as hos- ments by investigators must be main-
pital or other institutional records; tained by the sponsor or applicant and
(5) Either a statement that the de- made available for agency review upon
vice used in the investigation con- request.
ducted outside the United States is (c) Waivers. (1) A sponsor or applicant
identical to the device that is the sub- may ask FDA to waive any applicable
ject of the submission or application, requirements under paragraphs (a)(1)
or a detailed description of the device and (b) of this section. A waiver re-
and each important component (includ- quest may be submitted in an IDE or in
ing all materials and specifications), an amendment or supplement to an
ingredient, property, and principle of IDE, in a device marketing application
operation of the device used in the in- or submission (an application under
vestigation conducted outside the section 515 or 520(m) of the Federal
United States and a comparison to the Food, Drug, and Cosmetic Act, a pre-
device that is the subject of the sub- market notification submission under
mission or application that indicates section 510(k) of the Federal Food,
how the device used in the investiga- Drug, and Cosmetic Act, or a request
tion is similar to and/or different from for De Novo classification under sec-
the device that is the subject of the tion 513(f)(2) of the Federal Food, Drug,
submission or application; and Cosmetic Act) or in an amendment
(6) If the investigation is intended to or supplement to a device marketing
support the safety and effectiveness of application or submission, or in a pre-
a device, a discussion demonstrating submission. A waiver request is re-
that the data and information con- quired to contain at least one of the
stitute valid scientific evidence within following:
the meaning of § 860.7 of this chapter; (i) An explanation why the sponsor’s
(7) The name and address of the IEC or applicant’s compliance with the re-
that reviewed the investigation and a quirement is unnecessary or cannot be
statement that the IEC meets the defi- achieved;
nition in § 812.3(t). The sponsor or ap- (ii) A description of an alternative
plicant must maintain records sup- submission or course of action that
porting such statement, including satisfies the purpose of the require-
records describing the qualifications of ment; or
IEC members, and make these records (iii) Other information justifying a
available for agency review upon re- waiver.
quest; (2) FDA may grant a waiver if it finds
(8) A summary of the IEC’s decision that doing so would be in the interest
to approve or modify and approve the of the public health.
investigation, or to provide a favorable (d) Records. A sponsor or applicant
opinion; must retain the records required by
(9) A description of how informed this section for a clinical investigation
consent was obtained; conducted outside the United States as
(10) A description of what incentives, follows:
if any, were provided to subjects to (1) If the investigation is submitted
participate in the investigation; in support of an IDE, for 2 years after
(11) A description of how the spon- the termination or completion of the
sor(s) monitored the investigation and IDE; and
ensured that the investigation was car- (2) If the investigation is submitted
ried out consistently with the protocol; in support of a premarket approval ap-
and plication, a notice of completion of a
134
product development protocol, a hu- the subjects and the importance of the
manitarian device exemption applica- knowledge to be gained, or informed
tion, a premarket notification submis- consent is inadequate, or the investiga-
sion, or a request for De Novo classi- tion is scientifically unsound, or there
fication, for 2 years after an agency de- is reason to believe that the device as
cision on that submission or applica- used is ineffective.
tion. (5) It is otherwise unreasonable to
(e) Clinical investigations conducted begin or to continue the investigation
outside of the United States that do not owing to the way in which the device is
meet conditions. For clinical investiga- used or the inadequacy of:
tions conducted outside the United (i) The report of prior investigations
States that do not meet the conditions or the investigational plan;
under paragraph (a) of this section, (ii) The methods, facilities, and con-
FDA may accept the information from trols used for the manufacturing, proc-
such clinical investigations to support essing, packaging, storage, and, where
an IDE or a device marketing applica- appropriate, installation of the device;
tion or submission if FDA believes that or
the data and results from such clinical (iii) Monitoring and review of the in-
investigation are credible and accurate vestigation.
and that the rights, safety, and well- (c) Notice of disapproval or withdrawal.
being of subjects have been adequately If FDA disapproves an application or
protected. proposes to withdraw approval of an
application, FDA will notify the spon-
[83 FR 7386, Feb. 21, 2018]
sor in writing.
§ 812.30 FDA action on applications. (1) A disapproval order will contain a
complete statement of the reasons for
(a) Approval or disapproval. FDA will disapproval and a statement that the
notify the sponsor in writing of the sponsor has an opportunity to request
date it receives an application. FDA a hearing under part 16.
may approve an investigation as pro- (2) A notice of a proposed withdrawal
posed, approve it with modifications, of approval will contain a complete
or disapprove it. An investigation may statement of the reasons for with-
not begin until:
drawal and a statement that the spon-
(1) Thirty days after FDA receives
sor has an opportunity to request a
the application at the address in § 812.19
hearing under part 16. FDA will provide
for the investigation of a device other
the opportunity for hearing before
than a banned device, unless FDA noti-
withdrawal of approval, unless FDA de-
fies the sponsor that the investigation
termines in the notice that continu-
may not begin; or
ation of testing under the exemption
(2) FDA approves, by order, an IDE
will result in an unreasonble risk to
for the investigation.
the public health and orders with-
(b) Grounds for disapproval or with-
drawal of approval before any hearing.
drawal. FDA may disapprove or with-
draw approval of an application if FDA [45 FR 3751, Jan. 18, 1980, as amended at 45
finds that: FR 58842, Sept. 5, 1980]
(1) There has been a failure to comply
with any requirement of this part or § 812.35 Supplemental applications.
the act, any other applicable regula- (a) Changes in investigational plan—(1)
tion or statute, or any condition of ap- Changes requiring prior approval. Except
proval imposed by an IRB or FDA. as described in paragraphs (a)(2)
(2) The application or a report con- through (a)(4) of this section, a sponsor
tains an untrue statement of a mate- must obtain approval of a supple-
rial fact, or omits material informa- mental application under § 812.30(a),
tion required by this part. and IRB approval when appropriate
(3) The sponsor fails to respond to a (see §§ 56.110 and 56.111 of this chapter),
request for additional information prior to implementing a change to an
within the time prescribed by FDA. investigational plan. If a sponsor in-
(4) There is reason to believe that the tends to conduct an investigation that
risks to the subjects are not out- involves an exception to informed con-
weighed by the anticipated benefits to sent under § 50.24 of this chapter, the
135
§ 812.35 21 CFR Ch. I (4–1–23 Edition)
sponsor shall submit a separate inves- clinical/animal testing, peer reviewed

tigational device exemption (IDE) ap- published literature, or other reliable
plication in accordance with § 812.20(a). information such as clinical informa-
(2) Changes effected for emergency use. tion gathered during a trial or mar-
The requirements of paragraph (a)(1) of keting.
this section regarding FDA approval of (B) Credible information to support
a supplement do not apply in the case changes to clinical protocols is defined
of a deviation from the investigational as the sponsor’s documentation sup-
plan to protect the life or physical porting the conclusion that a change
well-being of a subject in an emer- does not have a significant impact on
gency. Such deviation shall be reported the study design or planned statistical
to FDA within 5-working days after the analysis, and that the change does not
sponsor learns of it (see § 812.150(a)(4)).
affect the rights, safety, or welfare of
(3) Changes effected with notice to FDA
the subjects. Documentation shall in-
within 5 days. A sponsor may make cer-
clude information such as peer re-
tain changes without prior approval of
viewed published literature, the rec-
a supplemental application under para-
graph (a)(1) of this section if the spon- ommendation of the clinical investi-
sor determines that these changes gator(s), and/or the data gathered dur-
meet the criteria described in para- ing the clinical trial or marketing.
graphs (a)(3)(i) and (a)(3)(ii) of this sec- (iv) Notice of IDE change. Changes
tion, on the basis of credible informa- meeting the criteria in paragraphs
tion defined in paragraph (a)(3)(iii) of (a)(3)(i) and (a)(3)(ii) of this section
this section, and the sponsor provides that are supported by credible informa-
notice to FDA within 5-working days of tion as defined in paragraph (a)(3)(iii)
making these changes. of this section may be made without
(i) Developmental changes. The re- prior FDA approval if the sponsor sub-
quirements in paragraph (a)(1) of this mits a notice of the change to the IDE
section regarding FDA approval of a not later than 5-working days after
supplement do not apply to develop- making the change. Changes to devices
mental changes in the device (includ- are deemed to occur on the date the de-
ing manufacturing changes) that do vice, manufactured incorporating the
not constitute a significant change in design or manufacturing change, is dis-
design or basic principles of operation tributed to the investigator(s). Changes
and that are made in response to infor- to a clinical protocol are deemed to
mation gathered during the course of occur when a clinical investigator is
an investigation. notified by the sponsor that the change
(ii) Changes to clinical protocol. The should be implemented in the protocol
requirements in paragraph (a)(1) of this or, for sponsor-investigator studies,
section regarding FDA approval of a when a sponsor-investigator incor-
supplement do not apply to changes to porates the change in the protocol.
clinical protocols that do not affect:
Such notices shall be identified as a
(A) The validity of the data or infor-
‘‘notice of IDE change.’’
mation resulting from the completion
of the approved protocol, or the rela- (A) For a developmental or manufac-
tionship of likely patient risk to ben- turing change to the device, the notice
efit relied upon to approve the pro- shall include a summary of the rel-
tocol; evant information gathered during the
(B) The scientific soundness of the in- course of the investigation upon which
vestigational plan; or the change was based; a description of
(C) The rights, safety, or welfare of the change to the device or manufac-
the human subjects involved in the in- turing process (cross-referenced to the
vestigation. appropriate sections of the original de-
(iii) Definition of credible information. vice description or manufacturing
(A) Credible information to support de- process); and, if design controls were
velopmental changes in the device (in- used to assess the change, a statement
cluding manufacturing changes) in- that no new risks were identified by

cludes data generated under the design appropriate risk analysis and that the
control procedures of § 820.30, pre- verification and validation testing, as
136
appropriate, demonstrated that the de- begin a part of an investigation at a fa-

sign outputs met the design input re- cility until the IRB has approved the
quirements. If another method of as- investigation, FDA has received the
sessment was used, the notice shall in- certification of IRB approval, and FDA,
clude a summary of the information under § 812.30(a), has approved the sup-
which served as the credible informa- plemental application relating to that
tion supporting the change. part of the investigation (see
(B) For a protocol change, the notice § 56.103(a)).
shall include a description of the [50 FR 25909, June 24, 1985; 50 FR 28932, July
change (cross-referenced to the appro- 17, 1985, as amended at 61 FR 51531, Oct. 2,
priate sections of the original pro- 1996; 63 FR 64625, Nov. 23, 1998]
tocol); an assessment supporting the
conclusion that the change does not § 812.36 Treatment use of an investiga-
have a significant impact on the study tional device.
design or planned statistical analysis; (a) General. A device that is not ap-
and a summary of the information that proved for marketing may be under
served as the credible information sup- clinical investigation for a serious or
porting the sponsor’s determination immediately life-threatening disease or
that the change does not affect the condition in patients for whom no com-
rights, safety, or welfare of the sub- parable or satisfactory alternative de-
jects. vice or other therapy is available. Dur-
(4) Changes submitted in annual report. ing the clinical trial or prior to final
The requirements of paragraph (a)(1) of action on the marketing application, it
this section do not apply to minor may be appropriate to use the device in
changes to the purpose of the study, the treatment of patients not in the
risk analysis, monitoring procedures, trial under the provisions of a treat-
labeling, informed consent materials, ment investigational device exemption
and IRB information that do not affect: (IDE). The purpose of this section is to
(i) The validity of the data or infor- facilitate the availability of promising
mation resulting from the completion new devices to desperately ill patients
of the approved protocol, or the rela- as early in the device development
tionship of likely patient risk to ben- process as possible, before general mar-
efit relied upon to approve the pro- keting begins, and to obtain additional
tocol; data on the device’s safety and effec-
(ii) The scientific soundness of the tiveness. In the case of a serious dis-
investigational plan; or ease, a device ordinarily may be made
(iii) The rights, safety, or welfare of available for treatment use under this
the human subjects involved in the in- section after all clinical trials have
vestigation. Such changes shall be re- been completed. In the case of an im-
ported in the annual progress report mediately life-threatening disease, a
for the IDE, under § 812.150(b)(5). device may be made available for treat-
(b) IRB approval for new facilities. A ment use under this section prior to
sponsor shall submit to FDA a certifi- the completion of all clinical trials.
cation of any IRB approval of an inves- For the purpose of this section, an
tigation or a part of an investigation ‘‘immediately life-threatening’’ disease
not included in the IDE application. If means a stage of a disease in which
the investigation is otherwise un- there is a reasonable likelihood that
changed, the supplemental application death will occur within a matter of
shall consist of an updating of the in- months or in which premature death is
formation required by § 812.20(b) and (c) likely without early treatment. For
and a description of any modifications purposes of this section, ‘‘treatment
in the investigational plan required by use’’of a device includes the use of a de-
the IRB as a condition of approval. A vice for diagnostic purposes.
certification of IRB approval need not (b) Criteria. FDA shall consider the
be included in the initial submission of use of an investigational device under a
the supplemental application, and such treatment IDE if:
certification is not a precondition for (1) The device is intended to treat or

agency consideration of the applica- diagnose a serious or immediately life-
tion. Nevertheless, a sponsor may not threatening disease or condition;
137
§ 812.36 21 CFR Ch. I (4–1–23 Edition)
(2) There is no comparable or satis- pating in the treatment IDE and cer-
factory alternative device or other tification that no investigator will be
therapy available to treat or diagnose added to the treatment IDE before the
that stage of the disease or condition agreement is signed; and
in the intended patient population; (x) If the device is to be sold, the
(3) The device is under investigation price to be charged and a statement in-
in a controlled clinical trial for the dicating that the price is based on
same use under an approved IDE, or manufacturing and handling costs
such clinical trials have been com- only.
pleted; and (2) A licensed practitioner who re-
(4) The sponsor of the investigation is ceives an investigational device for
actively pursuing marketing approval/ treatment use under a treatment IDE
clearance of the investigational device is an ‘‘investigator’’ under the IDE and
with due diligence. is responsible for meeting all applica-
(c) Applications for treatment use. (1) A ble investigator responsibilities under
treatment IDE application shall in- this part and parts 50 and 56 of this
clude, in the following order: chapter.
(i) The name, address, and telephone (d) FDA action on treatment IDE appli-
number of the sponsor of the treatment cations—(1) Approval of treatment IDE’s.
IDE; Treatment use may begin 30 days after
(ii) The intended use of the device, FDA receives the treatment IDE sub-
the criteria for patient selection, and a mission at the address specified in
written protocol describing the treat- § 812.19, unless FDA notifies the sponsor
ment use; in writing earlier than the 30 days that
(iii) An explanation of the rationale the treatment use may or may not
for use of the device, including, as ap- begin. FDA may approve the treatment
propriate, either a list of the available use as proposed or approve it with
regimens that ordinarily should be modifications.
tried before using the investigational (2) Disapproval or withdrawal of ap-
device or an explanation of why the use proval of treatment IDE’s. FDA may dis-
of the investigational device is pref- approve or withdraw approval of a
erable to the use of available marketed treatment IDE if:
treatments; (i) The criteria specified in § 812.36(b)
(iv) A description of clinical proce- are not met or the treatment IDE does
dures, laboratory tests, or other meas- not contain the information required
ures that will be used to evaluate the in § 812.36(c);
effects of the device and to minimize (ii) FDA determines that any of the
risk; grounds for disapproval or withdrawal
(v) Written procedures for moni- of approval listed in § 812.30(b)(1)
toring the treatment use and the name through (b)(5) apply;
and address of the monitor; (iii) The device is intended for a seri-
(vi) Instructions for use for the de- ous disease or condition and there is
vice and all other labeling as required insufficient evidence of safety and ef-
under § 812.5(a) and (b); fectiveness to support such use;
(vii) Information that is relevant to (iv) The device is intended for an im-
the safety and effectiveness of the de- mediately life-threatening disease or
vice for the intended treatment use. In- condition and the available scientific
formation from other IDE’s may be in- evidence, taken as a whole, fails to pro-
corporated by reference to support the vide a reasonable basis for concluding
treatment use; that the device:
(viii) A statement of the sponsor’s (A) May be effective for its intended
commitment to meet all applicable reuse in its intended population; or
sponsibilities under this part and part (B) Would not expose the patients to
56 of this chapter and to ensure compli- whom the device is to be administered
ance of all participating investigators to an unreasonable and significant ad-
with the informed consent require- ditional risk of illness or injury;
ments of part 50 of this chapter; (v) There is reasonable evidence that

(ix) An example of the agreement to the treatment use is impeding enroll-
be signed by all investigators partici- ment in, or otherwise interfering with
138
the conduct or completion of, a con- § 812.38 Confidentiality of data and in-
trolled investigation of the same or an- formation.
other investigational device; (a) Existence of IDE. FDA will not dis-
(vi) The device has received mar- close the existence of an IDE unless its
keting approval/clearance or a com- existence has previously been publicly
parable device or therapy becomes disclosed or acknowledged, until FDA
available to treat or diagnose the same approves an application for premarket
indication in the same patient popu- approval of the device subject to the
lation for which the investigational de- IDE; or a notice of completion of a
vice is being used; product development protocol for the
(vii) The sponsor of the controlled device has become effective.
clinical trial is not pursuing marketing (b) Availability of summaries or data.
approval/clearance with due diligence; (1) FDA will make publicly available,
(viii) Approval of the IDE for the con- upon request, a detailed summary of
trolled clinical investigation of the de- information concerning the safety and
vice has been withdrawn; or effectiveness of the device that was the
(ix) The clinical investigator(s) basis for an order approving, dis-
named in the treatment IDE are not approving, or withdrawing approval of
qualified by reason of their scientific an application for an IDE for a banned
training and/or experience to use the device. The summary shall include in-
investigational device for the intended formation on any adverse effect on
treatment use. health caused by the device.
(3) Notice of disapproval or withdrawal. (2) If a device is a banned device or if
If FDA disapproves or proposes to with- the existence of an IDE has been pub-
draw approval of a treatment IDE, licly disclosed or acknowledged, data
FDA will follow the procedures set or information contained in the file is
forth in § 812.30(c). not available for public disclosure be-
(e) Safeguards. Treatment use of an fore approval of an application for pre-
investigational device is conditioned market approval or the effective date
upon the sponsor and investigators of a notice of completion of a product
complying with the safeguards of the development protocol except as pro-
IDE process and the regulations gov- vided in this section. FDA may, in its
erning informed consent (part 50 of this discretion, disclose a summary of se-
chapter) and institutional review lected portions of the safety and effec-
boards (part 56 of this chapter). tiveness data, that is, clinical, animal,
(f) Reporting requirements. The spon- or laboratory studies and tests of the
sor of a treatment IDE shall submit device, for public consideration of a
progress reports on a semi-annual basis specific pending issue.
to all reviewing IRB’s and FDA until (3) If the existence of an IDE file has
the filing of a marketing application. not been publicly disclosed or acknowl-
These reports shall be based on the pe- edged, no data or information in the
riod of time since initial approval of file are available for public disclosure
the treatment IDE and shall include except as provided in paragraphs (b)(1)
the number of patients treated with and (c) of this section.
the device under the treatment IDE, (4) Notwithstanding paragraph (b)(2)
the names of the investigators partici- of this section, FDA will make avail-
pating in the treatment IDE, and a able to the public, upon request, the in-
brief description of the sponsor’s ef- formation in the IDE that was required
forts to pursue marketing approval/ to be filed in Docket Number FDA–
clearance of the device. Upon filing of 1995–S–0036 in the Dockets Management
a marketing application, progress re- Staff (HFA–305), Food and Drug Admin-
ports shall be submitted annually in istration, 5630 Fishers Lane, Rm. 1061,
accordance with § 812.150(b)(5). The Rockville, MD 20852, for investigations
involving an exception from informed
sponsor of a treatment IDE is respon-
consent under § 50.24 of this chapter.
sible for submitting all other reports
Persons wishing to request this infor-

required under § 812.150.
mation shall submit a request under
[62 FR 48947, Sept. 18, 1997] the Freedom of Information Act.
139
§ 812.40 21 CFR Ch. I (4–1–23 Edition)
(c) Reports of adverse effects. Upon re- (1) The investigator’s curriculum
quest or on its own initiative, FDA vitae.
shall disclose to an individual on whom (2) Where applicable, a statement of
an investigational device has been used the investigator’s relevant experience,
a copy of a report of adverse device ef- including the dates, location, extent,
fects relating to that use. and type of experience.
(d) Other rules. Except as otherwise (3) If the investigator was involved in
provided in this section, the avail- an investigation or other research that
ability for public disclosure of data and was terminated, an explanation of the
information in an IDE file shall be han- circumstances that led to termination.
dled in accordance with § 814.9. (4) A statement of the investigator’s
[45 FR 3751, Jan. 18, 1980, as amended at 53 commitment to:
FR 11253, Apr. 6, 1988; 61 FR 51531, Oct. 2, 1996; (i) Conduct the investigation in ac-
88 FR 16880, Mar. 21, 2023] cordance with the agreement, the in-
vestigational plan, this part and other
Subpart C—Responsibilities of applicable FDA regulations, and condi-
Sponsors tions of approval imposed by the re-
viewing IRB or FDA;
§ 812.40 General responsibilities of (ii) Supervise all testing of the device
sponsors. involving human subjects; and
Sponsors are responsible for selecting (iii) Ensure that the requirements for
qualified investigators and providing obtaining informed consent are met.
them with the information they need (5) Sufficient accurate financial dis-
to conduct the investigation properly, closure information to allow the spon-
ensuring proper monitoring of the in- sor to submit a complete and accurate
vestigation, ensuring that IRB review certification or disclosure statement as
and approval are obtained, submitting required under part 54 of this chapter.
an IDE application to FDA, and ensur- The sponsor shall obtain a commit-
ing that any reviewing IRB and FDA ment from the clinical investigator to
are promptly informed of significant promptly update this information if
new information about an investiga- any relevant changes occur during the
tion. Additional responsibilities of course of the investigation and for 1
sponsors are described in subparts B year following completion of the study.
and G. This information shall not be sub-
§ 812.42 FDA and IRB approval. mitted in an investigational device ex-
emption application, but shall be sub-
A sponsor shall not begin an inves- mitted in any marketing application
tigation or part of an investigation involving the device.
until an IRB and FDA have both ap- (d) Selecting monitors. A sponsor shall
proved the application or supplemental select monitors qualified by training
application relating to the investiga- and experience to monitor the inves-
tion or part of an investigation. tigational study in accordance with
[46 FR 8957, Jan. 27, 1981] this part and other applicable FDA reg-
ulations.
§ 812.43 Selecting investigators and
monitors. [45 FR 3751, Jan. 18, 1980, as amended at 63
FR 5253, Feb. 2, 1998]
(a) Selecting investigators. A sponsor
shall select investigators qualified by § 812.45 Informing investigators.
training and experience to investigate
the device. A sponsor shall supply all investiga-
(b) Control of device. A sponsor shall tors participating in the investigation
ship investigational devices only to with copies of the investigational plan
qualified investigators participating in and the report of prior investigations
the investigation. of the device.
(c) Obtaining agreements. A sponsor
§ 812.46 Monitoring investigations.
shall obtain from each participating

investigator a signed agreement that (a) Securing compliance. A sponsor
includes: who discovers that an investigator is
140
not complying with the signed agree- (b) The sponsor also shall monitor
ment, the investigational plan, the re- such investigations to determine when
quirements of this part or other appli- an IRB determines that it cannot ap-
cable FDA regulations, or any condi- prove the research because it does not
tions of approval imposed by the re- meet the criteria in the exception in
viewing IRB or FDA shall promptly ei- § 50.24(a) of this chapter or because of
ther secure compliance, or discontinue other relevant ethical concerns. The
shipments of the device to the investi- sponsor promptly shall provide this in-
gator and terminate the investigator’s formation in writing to FDA, inves-
participation in the investigation. A tigators who are asked to participate
sponsor shall also require such an in- in this or a substantially equivalent
vestigator to dispose of or return the clinical investigation, and other IRB’s
device, unless this action would jeop- that are asked to review this or a sub-
ardize the rights, safety, or welfare of a stantially equivalent investigation.
subject. [61 FR 51531, Oct. 2, 1996, as amended at 64 FR
(b) Unanticipated adverse device effects. 10943, Mar. 8, 1999; 88 FR 16880, Mar. 21, 2023]
(1) A sponsor shall immediately con-
duct an evaluation of any unantici-
pated adverse device effect. Subpart D—IRB Review and
(2) A sponsor who determines that an Approval
unanticipated adverse device effect § 812.60 IRB composition, duties, and
presents an unreasonable risk to sub- functions.
jects shall terminate all investigations
or parts of investigations presenting An IRB reviewing and approving in-
that risk as soon as possible. Termi- vestigations under this part shall com-
nation shall occur not later than 5 ply with the requirements of part 56 in
working days after the sponsor makes all respects, including its composition,
this determination and not later than duties, and functions.
15 working days after the sponsor first [46 FR 8957, Jan. 27, 1981]
received notice of the effect.
(c) Resumption of terminated studies. If § 812.62 IRB approval.
the device is a significant risk device, (a) An IRB shall review and have au-
a sponsor may not resume a termi- thority to approve, require modifica-
nated investigation without IRB and tions in (to secure approval), or dis-
FDA approval. If the device is not a approve all investigations covered by
significant risk device, a sponsor may this part.
not resume a terminated investigation (b) If no IRB exists or if FDA finds
without IRB approval and, if the inves- that an IRB’s review is inadequate, a
tigation was terminated under para- sponsor may submit an application to
graph (b)(2) of this section, FDA ap- FDA.
proval.
[46 FR 8957, Jan. 27, 1981]
§ 812.47 Emergency research under
§ 50.24 of this chapter. § 812.64 IRB’s continuing review.
(a) The sponsor shall monitor the The IRB shall conduct its continuing
progress of all investigations involving review of an investigation in accord-
an exception from informed consent ance with part 56.
under § 50.24 of this chapter. When the [46 FR 8957, Jan. 27, 1981]
sponsor receives from the IRB informa-
tion concerning the public disclosures § 812.65 [Reserved]
under § 50.24(a)(7)(ii) and (iii) of this
chapter, the sponsor shall promptly § 812.66 Significant risk device deter-
submit to the IDE file and to Docket minations.
Number FDA–1995–S–0036 in the Dock- If an IRB determines that an inves-
ets Management Staff (HFA–305), Food tigation, presented for approval under
and Drug Administration, 5630 Fishers § 812.2(b)(1)(ii), involves a significant
Lane, Rm. 1061, Rockville, MD 20852, risk device, it shall so notify the inves-
copies of the information that was dis- tigator and, where appropriate, the
closed, identified by the IDE number. sponsor. A sponsor may not begin the
141
§ 812.100 21 CFR Ch. I (4–1–23 Edition)
investigation except as provided in part 54 of this chapter. The investi-

§ 812.30(a). gator shall promptly update this infor-
mation if any relevant changes occur
[46 FR 8957, Jan. 27, 1981]
during the course of the investigation
and for 1 year following completion of
Subpart E—Responsibilities of the study.
Investigators (e) Disposing of device. Upon comple-
tion or termination of a clinical inves-
§ 812.100 General responsibilities of in- tigation or the investigator’s part of an
vestigators.
investigation, or at the sponsor’s re-
An investigator is responsible for en- quest, an investigator shall return to
suring that an investigation is con- the sponsor any remaining supply of
ducted according to the signed agree- the device or otherwise dispose of the
ment, the investigational plan and ap- device as the sponsor directs.
plicable FDA regulations, for pro-
[45 FR 3751, Jan. 18, 1980, as amended at 63
tecting the rights, safety, and welfare FR 5253, Feb. 2, 1998]
of subjects under the investigator’s
care, and for the control of devices § 812.119 Disqualification of a clinical
under investigation. An investigator investigator.
also is responsible for ensuring that in- (a) If FDA has information indicating
formed consent is obtained in accord- that an investigator (including a spon-
ance with part 50 of this chapter. Addi- sor-investigator) has repeatedly or de-
tional responsibilities of investigators liberately failed to comply with the re-
are described in subpart G. quirements of this part, part 50, or part
[45 FR 3751, Jan. 18, 1980, as amended at 46 56 of this chapter, or has repeatedly or
FR 8957, Jan. 27, 1981] deliberately submitted to FDA or to
the sponsor false information in any
§ 812.110 Specific responsibilities of in- required report, the Center for Devices
vestigators. and Radiological Health, the Center for
(a) Awaiting approval. An investigator Biologics Evaluation and Research, or
may determine whether potential sub- the Center for Drug Evaluation and Re-
jects would be interested in partici- search will furnish the investigator
pating in an investigation, but shall written notice of the matter com-
not request the written informed con- plained of and offer the investigator an
sent of any subject to participate, and opportunity to explain the matter in
shall not allow any subject to partici- writing, or, at the option of the inves-
pate before obtaining IRB and FDA ap- tigator, in an informal conference. If
proval. an explanation is offered and accepted
(b) Compliance. An investigator shall by the applicable Center, the Center
conduct an investigation in accordance will discontinue the disqualification
with the signed agreement with the proceeding. If an explanation is offered
sponsor, the investigational plan, this but not accepted by the applicable Cen-
part and other applicable FDA regula- ter, the investigator will be given an
tions, and any conditions of approval opportunity for a regulatory hearing
imposed by an IRB or FDA. under part 16 of this chapter on the
(c) Supervising device use. An investi- question of whether the investigator is
gator shall permit an investigational eligible to receive test articles under
device to be used only with subjects this part and eligible to conduct any
under the investigator’s supervision. clinical investigation that supports an
An investigator shall not supply an in- application for a research or marketing
vestigational device to any person not permit for products regulated by FDA.
authorized under this part to receive (b) After evaluating all available in-
it. formation, including any explanation
(d) Financial disclosure. A clinical in- presented by the investigator, if the
vestigator shall disclose to the sponsor Commissioner determines that the in-
sufficient accurate financial informa- vestigator has repeatedly or delib-
tion to allow the applicant to submit erately failed to comply with the re-
complete and accurate certification or quirements of this part, part 50, or part
disclosure statements required under 56 of this chapter, or has repeatedly or
142
deliberately submitted to FDA or to whether the IDE should be reinstated.

the sponsor false information in any The determination that an investiga-
required report, the Commissioner will tion may not be considered in support
notify the investigator, the sponsor of of a research or marketing application
any investigation in which the investi- or a notification or petition submission
gator has been named as a participant, does not, however, relieve the sponsor
and the reviewing investigational re- of any obligation under any other ap-
view boards (IRBs) that the investi- plicable regulation to submit to FDA
gator is not eligible to receive test ar- the results of the investigation.
ticles under this part. The notification (e) If the Commissioner determines,
to the investigator, sponsor and IRBs after the unreliable data submitted by
will provide a statement of the basis the investigator are eliminated from
for such determination. The notifica- consideration, that the continued
tion also will explain that an investi-
clearance or approval of the product
gator determined to be ineligible to re-
for which the data were submitted can-
ceive test articles under this part will
not be justified, the Commissioner will
be ineligible to conduct any clinical in-
proceed to rescind clearance or with-
vestigation that supports an applica-
draw approval of the product in accord-
tion for a research or marketing per-
mit for products regulated by FDA, in- ance with the applicable provisions of
cluding drugs, biologics, devices, new the relevant statutes.
animal drugs, foods, including dietary (f) An investigator who has been de-
supplements, that bear a nutrient con- termined to be ineligible under para-
tent claim or a health claim, infant graph (b) of this section may be rein-
formulas, food and color additives, and stated as eligible when the Commis-
tobacco products. sioner determines that the investigator
(c) Each application or submission to has presented adequate assurances that
FDA under the provisions of this chap- the investigator will employ all test
ter containing data reported by an in- articles, and will conduct any clinical
vestigator who has been determined to investigation that supports an applica-
be ineligible to receive FDA-regulated tion for a research or marketing per-
test articles is subject to examination mit for products regulated by FDA,
to determine whether the investigator solely in compliance with the applica-
has submitted unreliable data that are ble provisions of this chapter.
essential to the continuation of an in-
[77 FR 25360, Apr. 30, 2012]
vestigation or essential to the clear-
ance or approval of a marketing appli-
cation, or essential to the continued Subpart F [Reserved]
marketing of an FDA-regulated prod-
uct. Subpart G—Records and Reports
(d) If the Commissioner determines,
after the unreliable data submitted by § 812.140 Records.
the investigator are eliminated from (a) Investigator records. A partici-
consideration, that the data remaining pating investigator shall maintain the
are inadequate to support a conclusion following accurate, complete, and cur-
that it is reasonably safe to continue
rent records relating to the investiga-
the investigation, the Commissioner
tor’s participation in an investigation:
will notify the sponsor, who shall have
an opportunity for a regulatory hear- (1) All correspondence with another
ing under part 16 of this chapter. If a investigator, an IRB, the sponsor, a
danger to the public health exists, how- monitor, or FDA, including required
ever, the Commissioner shall termi- reports.
nate the investigational device exemp- (2) Records of receipt, use or disposi-
tion (IDE) immediately and notify the tion of a device that relate to:
sponsor and the reviewing IRBs of the (i) The type and quantity of the de-
termination. In such case, the sponsor vice, the dates of its receipt, and the
shall have an opportunity for a regu- batch number or code mark.

latory hearing before FDA under part (ii) The names of all persons who re-
16 of this chapter on the question of ceived, used, or disposed of each device.
143
§ 812.140 21 CFR Ch. I (4–1–23 Edition)
(iii) Why and how many units of the mark. Records of disposition shall de-
device have been returned to the spon- scribe the batch number or code marks
sor, repaired, or otherwise disposed of. of any devices returned to the sponsor,
(3) Records of each subject’s case his- repaired, or disposed of in other ways
tory and exposure to the device. Case by the investigator or another person,
histories include the case report forms and the reasons for and method of dis-
and supporting data including, for ex- posal.
ample, signed and dated consent forms (3) Signed investigator agreements
and medical records including, for ex- including the financial disclosure in-
ample, progress notes of the physician, formation required to be collected
the individual’s hospital chart(s), and under § 812.43(c)(5) in accordance with
the nurses’ notes. Such records shall part 54 of this chapter.
include: (4) For each investigation subject to
(i) Documents evidencing informed § 812.2(b)(1) of a device other than a sig-
consent and, for any use of a device by nificant risk device, the records de-
the investigator without informed con- scribed in paragraph (b)(5) of this sec-
sent, any written concurrence of a li- tion and the following records, consoli-
censed physician and a brief descrip- dated in one location and available for
tion of the circumstances justifying FDA inspection and copying:
the failure to obtain informed consent. (i) The name and intended use of the
The case history for each individual device and the objectives of the inves-
shall document that informed consent tigation;
was obtained prior to participation in (ii) A brief explanation of why the de-
the study. vice is not a significant risk device:
(ii) All relevant observations, includ- (iii) The name and address of each in-
ing records concerning adverse device vestigator:
effects (whether anticipated or unan- (iv) The name and address of each
ticipated), information and data on the IRB that has reviewed the investiga-
condition of each subject upon enter- tion:
ing, and during the course of, the in- (v) A statement of the extent to
vestigation, including information which the good manufacturing practice
about relevant previous medical his- regulation in part 820 will be followed
tory and the results of all diagnostic in manufacturing the device; and
tests. (vi) Any other information required
(iii) A record of the exposure of each by FDA.
subject to the investigational device, (5) Records concerning adverse device
including the date and time of each effects (whether anticipated or unan-
use, and any other therapy. ticipated) and complaints and
(4) The protocol, with documents (6) Any other records that FDA re-
showing the dates of and reasons for quires to be maintained by regulation
each deviation from the protocol. or by specific requirement for a cat-
(5) Any other records that FDA re- egory of investigation or a particular
quires to be maintained by regulation investigation.
or by specific requirement for a cat- (c) IRB records. An IRB shall main-
egory of investigations or a particular tain records in accordance with part 56
investigation. of this chapter.
(b) Sponsor records. A sponsor shall (d) Retention period. An investigator
maintain the following accurate, com- or sponsor shall maintain the records
plete, and current records relating to required by this subpart during the in-
an investigation: vestigation and for a period of 2 years
(1) All correspondence with another after the latter of the following two
sponsor, a monitor, an investigator, an dates: The date on which the investiga-
IRB, or FDA, including required re- tion is terminated or completed, or the
ports. date that the records are no longer re-
(2) Records of shipment and disposi- quired for purposes of supporting a pre-
tion. Records of shipment shall include market approval application, a notice
the name and address of the consignee, of completion of a product develop-

type and quantity of device, date of ment protocol, a humanitarian device
shipment, and batch number or code exemption application, a premarket
144
notification submission, or a request port of any unanticipated adverse de-

for De Novo classification. vice effect occurring during an inves-
(e) Records custody. An investigator tigation as soon as possible, but in no
or sponsor may withdraw from the re- event later than 10 working days after
sponsibility to maintain records for the the investigator first learns of the ef-
period required in paragraph (d) of this fect.
section and transfer custody of the (2) Withdrawal of IRB approval. An in-
records to any other person who will vestigator shall report to the sponsor,
accept responsibility for them under within 5 working days, a withdrawal of
this part, including the requirements approval by the reviewing IRB of the
of § 812.145. Notice of a transfer shall be investigator’s part of an investigation.
given to FDA not later than 10 working
(3) Progress. An investigator shall
days after transfer occurs.
submit progress reports on the inves-
[45 FR 3751, Jan. 18, 1980, as amended at 45 tigation to the sponsor, the monitor,
FR 58843, Sept. 5, 1980; 46 FR 8957, Jan. 27, and the reviewing IRB at regular inter-
1981; 61 FR 57280, Nov. 5, 1996; 63 FR 5253, Feb.
2, 1998; 83 FR 7387, Feb. 21, 2018; 83 FR 7387,
vals, but in no event less often than
Feb. 21, 2018] yearly.
(4) Deviations from the investigational
§ 812.145 Inspections. plan. An investigator shall notify the
(a) Entry and inspection. A sponsor or sponsor and the reviewing IRB (see
an investigator who has authority to § 56.108(a) (3) and (4)) of any deviation
grant access shall permit authorized from the investigational plan to pro-
FDA employees, at reasonable times tect the life or physical well-being of a
and in a reasonable manner, to enter subject in an emergency. Such notice
and inspect any establishment where shall be given as soon as possible, but
devices are held (including any estab- in no event later than 5 working days
lishment where devices are manufac- after the emergency occurred. Except
tured, processed, packed, installed, in such an emergency, prior approval
used, or implanted or where records of by the sponsor is required for changes
results from use of devices are kept). in or deviations from a plan, and if
(b) Records inspection. A sponsor, IRB, these changes or deviations may affect
or investigator, or any other person the scientific soundness of the plan or
acting on behalf of such a person with the rights, safety, or welfare of human
respect to an investigation, shall per- subjects, FDA and IRB in accordance
mit authorized FDA employees, at rea- with § 812.35(a) also is required.
sonable times and in a reasonable man- (5) Informed consent. If an investi-
ner, to inspect and copy all records re- gator uses a device without obtaining
lating to an investigation. informed consent, the investigator
(c) Records identifying subjects. An in- shall report such use to the sponsor
vestigator shall permit authorized FDA and the reviewing IRB within 5 work-
employees to inspect and copy records ing days after the use occurs.
that identify subjects, upon notice that
(6) Final report. An investigator shall,
FDA has reason to suspect that ade-
within 3 months after termination or
quate informed consent was not ob-
completion of the investigation or the
tained, or that reports required to be
submitted by the investigator to the investigator’s part of the investigation,
sponsor or IRB have not been sub- submit a final report to the sponsor
mitted or are incomplete, inaccurate, and the reviewing IRB.
false, or misleading. (7) Other. An investigator shall, upon
request by a reviewing IRB or FDA,
§ 812.150 Reports. provide accurate, complete, and cur-
(a) Investigator reports. An investi- rent information about any aspect of
gator shall prepare and submit the fol- the investigation.
lowing complete, accurate, and timely (b) Sponsor reports. A sponsor shall
reports: prepare and submit the following com-
(1) Unanticipated adverse device effects. plete, accurate, and timely reports:
An investigator shall submit to the (1) Unanticipated adverse device effects.
sponsor and to the reviewing IRB a re- A sponsor who conducts an evaluation
145
of an unanticipated adverse device ef- that is not a significant risk device,

fect under § 812.46(b) shall report the re- the sponsor shall submit a final report
sults of such evaluation to FDA and to to all reviewing IRB’s within 6 months
all reviewing IRB’s and participating after termination or completion.
investigators within 10 working days (8) Informed consent. A sponsor shall
after the sponsor first receives notice submit to FDA a copy of any report by
of the effect. Thereafter the sponsor an investigator under paragraph (a)(5)
shall submit such additional reports of this section of use of a device with-
concerning the effect as FDA requests. out obtaining informed consent, within
(2) Withdrawal of IRB approval. A 5 working days of receipt of notice of
sponsor shall notify FDA and all re- such use.
viewing IRB’s and participating inves- (9) Significant risk device determina-
tigators of any withdrawal of approval tions. If an IRB determines that a de-
of an investigation or a part of an in- vice is a significant risk device, and
vestigation by a reviewing IRB within the sponsor had proposed that the IRB
5 working days after receipt of the consider the device not to be a signifi-
withdrawal of approval. cant risk device, the sponsor shall sub-
(3) Withdrawal of FDA approval. A mit to FDA a report of the IRB’s deter-
sponsor shall notify all reviewing IRB’s mination within 5 working days after
and participating investigators of any the sponsor first learns of the IRB’s de-
withdrawal of FDA approval of the in- termination.
vestigation, and shall do so within 5 (10) Other. A sponsor shall, upon re-
working days after receipt of notice of quest by a reviewing IRB or FDA, pro-
the withdrawal of approval. vide accurate, complete, and current
(4) Current investigator list. A sponsor information about any aspect of the in-
shall submit to FDA, at 6-month inter- vestigation.
vals, a current list of the names and [45 FR 3751, Jan. 18, 1980, as amended at 45
addresses of all investigators partici- FR 58843, Sept. 5, 1980; 48 FR 15622, Apr. 12,
pating in the investigation. The spon- 1983; 62 FR 48948, Sept. 18, 1997]
sor shall submit the first such list 6
months after FDA approval. PART 813 [RESERVED]
(5) Progress reports. At regular inter-
vals, and at least yearly, a sponsor
shall submit progress reports to all re-
PART 814—PREMARKET APPROVAL
viewing IRB’s. In the case of a signifi- OF MEDICAL DEVICES
cant risk device, a sponsor shall also
submit progress reports to FDA. A Subpart A—General
sponsor of a treatment IDE shall sub- Sec.
mit semi-annual progress reports to all 814.1 Scope.
reviewing IRB’s and FDA in accordance 814.2 Purpose.
with § 812.36(f) and annual reports in ac- 814.3 Definitions.
cordance with this section. 814.9 Confidentiality of data and informa-
tion in a premarket approval application
(6) Recall and device disposition. A
(PMA) file.
sponsor shall notify FDA and all re- 814.15 Research conducted outside the
viewing IRB’s of any request that an United States.
investigator return, repair, or other- 814.17 Service of orders.
wise dispose of any units of a device. 814.19 Product development protocol (PDP).
Such notice shall occur within 30 work-
ing days after the request is made and Subpart B—Premarket Approval
shall state why the request was made. Application (PMA)
(7) Final report. In the case of a sig- 814.20 Application.
nificant risk device, the sponsor shall 814.37 PMA amendments and resubmitted
notify FDA within 30 working days of PMAs.
the completion or termination of the 814.39 PMA supplements.
investigation and shall submit a final
report to FDA and all reviewing the Subpart C—FDA Action on a PMA
IRB’s and participating investigators 814.40 Time frames for reviewing a PMA.
within 6 months after completion or 814.42 Filing a PMA.
termination. In the case of a device 814.44 Procedures for review of a PMA.
146
814.45 Denial of approval of a PMA. tially equivalent to a device on the
814.46 Withdrawal of approval of a PMA. market before May 28, 1976, or to a de-
814.47 Temporary suspension of approval of
vice first marketed on, or after that
a PMA.
date, which has been classified into
Subpart D—Administrative Review class I or class II; or
[Reserved] (2) Is required to have an approved
premarket approval application (PMA)
Subpart E—Postapproval Requirements or a declared completed product devel-
814.80 General. opment protocol under a regulation
814.82 Postapproval requirements. issued under section 515(b) of the act;
814.84 Reports. or
(3) Was regulated by FDA as a new
Subparts F–G [Reserved] drug or antibiotic drug before May 28,
Subpart H—Humanitarian Use Devices 1976, and therefore is governed by sec-
tion 520(1) of the act.
814.100 Purpose and scope. (d) This part amends the conditions
814.102 Designation of HUD status. to approval for any PMA approved be-
814.104 Original applications.
814.106 HDE amendments and resubmitted fore the effective date of this part. Any
HDE’s. condition to approval for an approved
814.108 Supplemental applications. PMA that is inconsistent with this part
814.110 New indications for use. is revoked. Any condition to approval
814.112 Filing an HDE. for an approved PMA that is consistent
814.114 Timeframes for reviewing an HDE. with this part remains in effect.
814.116 Procedures for review of an HDE.
814.118 Denial of approval or withdrawal of [51 FR 26364, July 22, 1986, as amended at 79
approval of an HDE. FR 1740, Jan. 10, 2014]
814.120 Temporary suspension of approval of
an HDE. § 814.2 Purpose.
814.122 Confidentiality of data and informa-
tion. The purpose of this part is to estab-
814.124 Institutional Review Board require- lish an efficient and thorough device
ments. review process—
814.126 Postapproval requirements and re- (a) To facilitate the approval of
ports.
PMA’s for devices that have been
AUTHORITY: 21 U.S.C. 351, 352, 353, 360, 360c– shown to be safe and effective and that
360j, 360bbb–8b, 371, 372, 373, 374, 375, 379, 379e, otherwise meet the statutory criteria
379k–1, 381.
for approval; and
SOURCE: 51 FR 26364, July 22, 1986, unless (b) To ensure the disapproval of
otherwise noted. PMA’s for devices that have not been
shown to be safe and effective or that
Subpart A—General do not otherwise meet the statutory
criteria for approval. This part shall be
§ 814.1 Scope.
construed in light of these objectives.
(a) This section implements sections
515 and 515A of the act by providing § 814.3 Definitions.
procedures for the premarket approval
For the purposes of this part:
of medical devices intended for human
(a) Act means the Federal Food,
use.
(b) References in this part to regu- Drug, and Cosmetic Act (sections 201–
latory sections of the Code of Federal 902, 52 Stat. 1040 et seq., as amended (21
Regulations are to chapter I of title 21, U.S.C. 321–392)).
unless otherwise noted. (b) FDA means the Food and Drug
(c) This part applies to any class III Administration.
medical device, unless exempt under (c) IDE means an approved or consid-
section 520(g) of the act, that: ered approved investigational device
(1) Was not on the market (intro- exemption under section 520(g) of the
duced or delivered for introduction into act and parts 812 and 813.
commerce for commercial distribution) (d) Master file means a reference
before May 28, 1976, and is not substan- source that a person submits to FDA. A
147
§ 814.3 21 CFR Ch. I (4–1–23 Edition)
master file may contain detailed infor- (m) HDE means a premarket approval
mation on a specific manufacturing fa- application submitted pursuant to this
cility, process, methodology, or compo- subpart seeking a humanitarian device
nent used in the manufacture, proc- exemption from the effectiveness re-
essing, or packaging of a medical de- quirements of sections 514 and 515 of
vice. the act as authorized by section
(e) PMA means any premarket ap- 520(m)(2) of the act.
proval application for a class III med- (n) HUD (humanitarian use device)
ical device, including all information means a medical device intended to
submitted with or incorporated by ref- benefit patients in the treatment or di-
erence therein. ‘‘PMA’’ includes a new agnosis of a disease or condition that
drug application for a device under sec- affects or is manifested in not more
tion 520(1) of the act. than 8,000 individuals in the United
(f) PMA amendment means informa- States per year.
tion an applicant submits to FDA to (o) Newly acquired information means
modify a pending PMA or a pending data, analyses, or other information
PMA supplement. not previously submitted to the agen-
(g) PMA supplement means a supple- cy, which may include (but are not lim-
mental application to an approved ited to) data derived from new clinical
PMA for approval of a change or modi- studies, reports of adverse events, or
fication in a class III medical device, new analyses of previously submitted
including all information submitted data (e.g., meta-analyses) if the stud-
with or incorporated by reference ies, events or analyses reveal risks of a
therein. different type or greater severity or
(h) Person includes any individual, frequency than previously included in
partnership, corporation, association, submissions to FDA.
scientific or academic establishment, (p) Human cell, tissue, or cellular or tis-
Government agency, or organizational sue-based product (HCT/P) regulated as a
unit thereof, or any other legal entity. device means an HCT/P as defined in
(i) Statement of material fact means a § 1271.3(d) of this chapter that does not
representation that tends to show that meet the criteria in § 1271.10(a) and that
the safety or effectiveness of a device is also regulated as a device.
is more probable than it would be in (q) Unique device identifier (UDI)
the absence of such a representation. A means an identifier that adequately
false affirmation or silence or an omis- identifies a device through its distribu-
sion that would lead a reasonable per- tion and use by meeting the require-
son to draw a particular conclusion as ments of § 830.20 of this chapter. A
to the safety or effectiveness of a de- unique device identifier is composed of:
vice also may be a false statement of (1) A device identifier—a mandatory,
material fact, even if the statement fixed portion of a UDI that identifies
was not intended by the person making the specific version or model of a de-
it to be misleading or to have any pro- vice and the labeler of that device; and
bative effect. (2) A production identifier—a condi-
(j) 30-day PMA supplement means a tional, variable portion of a UDI that
supplemental application to an ap- identifies one or more of the following
proved PMA in accordance with when included on the label of the de-
§ 814.39(e). vice:
(k) Reasonable probability means that (i) The lot or batch within which a
it is more likely than not that an event device was manufactured;
will occur. (ii) The serial number of a specific
(l) Serious, adverse health consequences device;
means any significant adverse experi- (iii) The expiration date of a specific
ence, including those which may be ei- device;
ther life-threatening or involve perma- (iv) The date a specific device was
nent or long term injuries, but exclud- manufactured.
ing injuries that are nonlife-threat- (v) For an HCT/P regulated as a de-
ening and that are temporary and rea- vice, the distinct identification code
sonably reversible. required by § 1271.290(c) of this chapter.
148
(r) Universal product code (UPC) to public consideration of a specific

means the product identifier used to pending issue.
identify an item sold at retail in the (2) Notwithstanding paragraph (d)(1)
United States. of this section, FDA will make avail-
(s) Pediatric patients means patients able to the public upon request the in-
who are 21 years of age or younger formation in the IDE that was required
(that is, from birth through the twen- to be filed in Docket Number 95S–0158
ty-first year of life, up to but not in- in the Division of Dockets Management
cluding the twenty-second birthday) at (HFA–305), Food and Drug Administra-
the time of the diagnosis or treatment. tion, 12420 Parklawn Dr., rm. 1–23,
(t) Readily available means available Rockville, MD 20857, for investigations
in the public domain through com- involving an exception from informed
monly used public resources for con- consent under § 50.24 of this chapter.
ducting biomedical, regulatory, and Persons wishing to request this infor-
medical product research. mation shall submit a request under
the Freedom of Information Act.
[51 FR 26364, July 22, 1986, as amended at 61
FR 15190, Apr. 5, 1996; 61 FR 33244, June 26,
(e) Upon issuance of an order approv-
1996; 73 FR 49610, Aug. 22, 2008; 78 FR 58821, ing, or an order denying approval of
Sept. 24, 2013; 79 FR 1740, Jan. 10, 2014; 82 FR any PMA, FDA will make available to
26349, June 7, 2017] the public the fact of the existence of
the PMA and a detailed summary of in-
§ 814.9 Confidentiality of data and information submitted to FDA respect-
formation in a premarket approval ing the safety and effectiveness of the
application (PMA) file. device that is the subject of the PMA
(a) A ‘‘PMA file’’ includes all data and that is the basis for the order.
and information submitted with or in- (f) After FDA issues an order approv-
corporated by reference in the PMA, ing, or an order denying approval of
any IDE incorporated into the PMA, any PMA, the following data and infor-
any PMA supplement, any report under mation in the PMA file are imme-
§ 814.82, any master file, or any other diately available for public disclosure:
related submission. Any record in the (1) All safety and effectiveness data
PMA file will be available for public and information previously disclosed to
disclosure in accordance with the pro- the public, as such disclosure is defined
visions of this section and part 20. The in § 20.81.
confidentiality of information in a (2) Any protocol for a test or study
color additive petition submitted as unless the protocol is shown to con-
part of a PMA is governed by § 71.15. stitute trade secret or confidential
(b) The existence of a PMA file may commercial or financial information
not be disclosed by FDA before an ap- under § 20.61.
proval order is issued to the applicant (3) Any adverse reaction report, prod-
unless it previously has been publicly uct experience report, consumer com-
disclosed or acknowledged. plaint, and other similar data and in-
(c) If the existence of a PMA file has formation, after deletion of:
not been publicly disclosed or acknowl- (i) Any information that constitutes
edged, data or information in the PMA trade secret or confidential commer-
file are not available for public disclo- cial or financial information under
sure. § 20.61; and
(d)(1) If the existence of a PMA file (ii) Any personnel, medical, and simi-
has been publicly disclosed or acknowl- lar information disclosure of which
edged before an order approving, or an would constitute a clearly unwarranted
order denying approval of the PMA is invasion of personal privacy under
issued, data or information contained § 20.63; provided, however, that except
in the file are not available for public for the information that constitutes
disclosure before such order issues. trade secret or confidential commer-
FDA may, however, disclose a sum- cial or financial information under
mary of portions of the safety and ef- § 20.61, FDA will disclose to a patient
fectiveness data before an approval who requests a report all the informa-
order or an order denying approval of tion in the report concerning that pa-
the PMA issues if disclosure is relevant tient.
149
§ 814.15 21 CFR Ch. I (4–1–23 Edition)
(4) A list of components previously (1) Manufacturing methods or proc-

disclosed to the public, as such disclo- esses, including quality control proce-
sure is defined in § 20.81. dures.
(5) An assay method or other analyt- (2) Production, sales, distribution,
ical method, unless it does not serve and similar data and information, ex-
any regulatory purpose and is shown to cept that any compilation of such data
fall within the exemption in § 20.61 for and information aggregated and pre-
trade secret or confidential commer- pared in a way that does not reveal
cial or financial information. data or information which are not
(6) All correspondence and written available for public disclosure under
summaries of oral discussions relating this provision is available for public
to the PMA file, in accordance with the disclosure.
provisions of §§ 20.103 and 20.104. (3) Quantitative or semiquantitative
(g) All safety and effectiveness data formulas.
and other information not previously [51 FR 26364, July 22, 1986, as amended at 61
disclosed to the public are available for FR 51531, Oct. 2, 1996]
public disclosure if any one of the fol-
lowing events occurs and the data and § 814.15 Research conducted outside
the United States.
information do not constitute trade se-
cret or confidential commercial or fi- (a) Data to support PMA. If data from
nancial information under § 20.61: clinical investigations conducted out-
(1) The PMA has been abandoned. side the United States are submitted to
FDA will consider a PMA abandoned if: support a PMA, the applicant shall
(i)(A) The applicant fails to respond comply with the provisions in § 812.28 of
to a request for additional information this chapter, as applicable.
within 180 days after the date FDA (b) As sole basis for marketing approval.
issues the request or A PMA based solely on foreign clinical
data and otherwise meeting the cri-
(B) Other circumstances indicate
teria for approval under this part may
that further work is not being under-
be approved if:
taken with respect to it, and
(1) The foreign data are applicable to
(ii) The applicant fails to commu- the U.S. population and U.S. medical
nicate with FDA within 7 days after practice;
the date on which FDA notifies the ap- (2) The studies have been performed
plicant that the PMA appears to have by clinical investigators of recognized
been abandoned. competence; and
(2) An order denying approval of the (3) The data may be considered valid
PMA has issued, and all legal appeals without the need for an on-site inspec-
have been exhausted. tion by FDA or, if FDA considers such
(3) An order withdrawing approval of an inspection to be necessary, FDA can
the PMA has issued, and all legal ap- validate the data through an on-site in-
peals have been exhausted. spection or other appropriate means.
(4) The device has been reclassified. (c) Consultation between FDA and ap-
(5) The device has been found to be plicants. Applicants are encouraged to
substantially equivalent to a class I or meet with FDA officials in a ‘‘pre-
class II device. submission’’ meeting when approval
(6) The PMA is considered volun- based solely on foreign data will be
tarily withdrawn under § 814.44(g). sought.
(h) The following data and informa- [51 FR 26364, July 22, 1986; 51 FR 40415, Nov.
tion in a PMA file are not available for 7, 1986, as amended at 51 FR 43344, Dec. 2,
public disclosure unless they have been 1986; 83 FR 7387, Feb. 21, 2018]
previously disclosed to the public, as
such disclosure is defined in § 20.81, or § 814.17 Service of orders.
they relate to a device for which a Orders issued under this part will be
PMA has been abandoned and they no served in person by a designated officer
longer represent a trade secret or con- or employee of FDA on, or by reg-

fidential commercial or financial infor- istered mail to, the applicant or the
mation as defined in § 20.61: designated agent at the applicant’s or
150
designated agent’s last known address scientific concepts that form the basis
in FDA’s records. for the device, and the significant
physical and performance characteris-
§ 814.19 Product development protocol tics of the device. A brief description of
(PDP). the manufacturing process should be
A class III device for which a product included if it will significantly enhance
development protocol has been de- the reader’s understanding of the de-
clared completed by FDA under this vice. The generic name of the device as
chapter will be considered to have an well as any proprietary name or trade
approved PMA. name should be included.
(iii) Alternative practices and proce-
Subpart B—Premarket Approval dures. A description of existing alter-
Application (PMA) native practices or procedures for diag-
nosing, treating, preventing, curing, or
§ 814.20 Application. mitigating the disease or condition for
(a) The applicant or an authorized which the device is intended.
representative shall sign the PMA. If (iv) Marketing history. A brief descrip-
the applicant does not reside or have a tion of the foreign and U.S. marketing
place of business within the United history, if any, of the device, including
States, the PMA shall be countersigned a list of all countries in which the de-
by an authorized representative resid- vice has been marketed and a list of all
ing or maintaining a place of business countries in which the device has been
in the United States and shall identify withdrawn from marketing for any rea-
the representative’s name and address. son related to the safety or effective-
(b) Unless the applicant justifies an ness of the device. The description
omission in accordance with paragraph shall include the history of the mar-
(d) of this section, a PMA shall include keting of the device by the applicant
in electronic format: and, if known, the history of the mar-
(1) The name and address of the ap- keting of the device by any other per-
plicant. son.
(2) A table of contents that specifies
(v) Summary of studies. An abstract of
the volume and page number for each
any information or report described in
item referred to in the table. A PMA
the PMA under paragraph (b)(8)(ii) of
shall include separate sections on non-
this section and a summary of the re-
clinical laboratory studies and on clin-
sults of technical data submitted under
ical investigations involving human
paragraph (b)(6) of this section. Such
subjects. A PMA shall be submitted as
a single version. The applicant shall in- summary shall include a description of
clude information that it believes to be the objective of the study, a descrip-
trade secret or confidential commer- tion of the experimental design of the
cial or financial information in the study, a brief description of how the
PMA and identify the information that data were collected and analyzed, and a
it believes to be trade secret or con- brief description of the results, wheth-
fidential commercial or financial infor- er positive, negative, or inconclusive.
mation. This section shall include the fol-
(3) A summary in sufficient detail lowing:
that the reader may gain a general un- (A) A summary of the nonclinical
derstanding of the data and informa- laboratory studies submitted in the ap-
tion in the application. The summary plication;
shall contain the following informa- (B) A summary of the clinical inves-
tion: tigations involving human subjects
(i) Indications for use. A general de- submitted in the application including
scription of the disease or condition a discussion of subject selection and
the device will diagnose, treat, prevent, exclusion criteria, study population,
cure, or mitigate, including a descrip- study period, safety and effectiveness
tion of the patient population for data, adverse reactions and complica-
which the device is intended. tions, patient discontinuation, patient

(ii) Device description. An explanation complaints, device failures and replace-
of how the device functions, the basic ments, results of statistical analyses of
151
§ 814.20 21 CFR Ch. I (4–1–23 Edition)
the clinical investigations, contra- should reasonably be known to the ap-

indications and precautions for use of plicant. The applicant shall—
the device, and other information from (i) Provide adequate information to
the clinical investigations as appro- demonstrate how the device meets, or
priate (any investigation conducted justify any deviation from, any per-
under an IDE shall be identified as formance standard established under
such). section 514 of the Federal Food, Drug,
(vi) Conclusions drawn from the stud- and Cosmetic Act or under section 534
ies. A discussion demonstrating that of Subchapter C—Electronic Product
the data and information in the appli- Radiation Control of the Federal Food,
cation constitute valid scientific evi- Drug, and Cosmetic Act (formerly the
dence within the meaning of § 860.7 and Radiation Control for Health and Safe-
provide reasonable assurance that the ty Act of 1968); and
device is safe and effective for its in- (ii) Explain any deviation from a vol-
tended use. A concluding discussion untary standard.
shall present benefit and risk consider- (6) The following technical sections
ations related to the device including a
which shall contain data and informa-
discussion of any adverse effects of the
tion in sufficient detail to permit FDA
device on health and any proposed ad-
to determine whether to approve or
ditional studies or surveillance the ap-
deny approval of the application:
plicant intends to conduct following
approval of the PMA. (i) A section containing results of the
nonclinical laboratory studies with the
(4) A complete description of:
device including microbiological, toxi-
(i) The device, including pictorial
cological, immunological, biocompat-
representations;
ibility, stress, wear, shelf life, and
(ii) Each of the functional compo-
other laboratory or animal tests as ap-
nents or ingredients of the device if the
propriate. Information on nonclinical
device consists of more than one phys-
laboratory studies shall include a
ical component or ingredient;
statement that each such study was
(iii) The properties of the device rel-
conducted in compliance with part 58,
evant to the diagnosis, treatment, pre-
or, if the study was not conducted in
vention, cure, or mitigation of a dis-
compliance with such regulations, a
ease or condition;
brief statement of the reason for the
(iv) The principles of operation of the
noncompliance.
device; and
(ii) A section containing results of
(v) The methods used in, and the fa-
the clinical investigations involving
cilities and controls used for, the man-
ufacture, processing, packing, storage, human subjects with the device includ-
and, where appropriate, installation of ing clinical protocols, number of inves-
the device, in sufficient detail so that a tigators and subjects per investigator,
person generally familiar with current subject selection and exclusion cri-
good manufacturing practice can make teria, study population, study period,
a knowledgeable judgment about the safety and effectiveness data, adverse
quality control used in the manufac- reactions and complications, patient
ture of the device. discontinuation, patient complaints,
(5) Reference to any performance device failures and replacements, tab-
standard under section 514 of the Fed- ulations of data from all individual
eral Food, Drug, and Cosmetic Act or subject report forms and copies of such
under section 534 of Subchapter C— forms for each subject who died during
Electronic Product Radiation Control a clinical investigation or who did not
of the Federal Food, Drug, and Cos- complete the investigation, results of
metic Act (formerly the Radiation statistical analyses of the clinical in-
Control for Health and Safety Act of vestigations, device failures and re-
1968) in effect or proposed at the time placements, contraindications and pre-
of the submission and to any voluntary cautions for use of the device, and any
standard that is relevant to any aspect other appropriate information from the
of the safety or effectiveness of the de- clinical investigations. Any investiga-
vice and that is known to or that tion conducted under an IDE shall be
152
identified as such. Information on clin- tification showing that data and other
ical investigations involving human information from a single investigator
subjects shall include the following: are sufficient to demonstrate the safe-
(A) For clinical investigations con- ty and effectiveness of the device and
ducted in the United States, a state- to ensure reproducibility of test re-
ment with respect to each investiga- sults.
tion that it either was conducted in (8)(i) A bibliography of all published
compliance with the institutional re- reports not submitted under paragraph
view board regulations in part 56 of (b)(6) of this section, whether adverse
this chapter, or was not subject to the or supportive, known to or that should
regulations under § 56.104 or § 56.105, and reasonably be known to the applicant
that it was conducted in compliance and that concern the safety or effec-
with the informed consent regulations tiveness of the device.
in part 50 of this chapter; or if the in- (ii) An identification, discussion, and
vestigation was not conducted in com- analysis of any other data, informa-
pliance with those regulations, a brief tion, or report relevant to an evalua-
statement of the reason for the non- tion of the safety and effectiveness of
compliance. Failure or inability to the device known to or that should rea-
comply with these requirements does sonably be known to the applicant
not justify failure to provide informa- from any source, foreign or domestic,
tion on a relevant clinical investiga- including information derived from in-
tion. vestigations other than those proposed
(B) For clinical investigations con- in the application and from commer-
ducted in the United States, a state- cial marketing experience.
ment that each investigation was con-
(iii) Copies of such published reports
ducted in compliance with part 812 of
or unpublished information in the pos-
this chapter concerning sponsors of
session of or reasonably obtainable by
clinical investigations and clinical in-
the applicant if an FDA advisory com-
vestigators, or if the investigation was
mittee or FDA requests.
not conducted in compliance with
those regulations, a brief statement of (9) One or more samples of the device
the reason for the noncompliance. Fail- and its components, if requested by
ure or inability to comply with these FDA. If it is impractical to submit a
requirements does not justify failure to requested sample of the device, the ap-
provide information on a relevant clin- plicant shall name the location at
ical investigation. which FDA may examine and test one
(C) For clinical investigations con- or more devices.
ducted outside the United States that (10) Copies of all proposed labeling
are intended to support the PMA, the for the device. Such labeling may in-
requirements under § 812.28 of this clude, e.g., instructions for installation
chapter apply. If any such investiga- and any information, literature, or ad-
tion was not conducted in accordance vertising that constitutes labeling
with good clinical practice (GCP) as de- under section 201(m) of the Federal
scribed in § 812.28(a), include either a Food, Drug, and Cosmetic Act.
waiver request in accordance with (11) An environmental assessment
§ 812.28(c) or a brief statement of the under § 25.20(n) prepared in the applica-
reason for not conducting the inves- ble format in § 25.40, unless the action
tigation in accordance with GCP and a qualifies for exclusion under § 25.30 or
description of steps taken to ensure § 25.34. If the applicant believes that
that the data and results are credible the action qualifies for exclusion, the
and accurate and that the rights, safe- PMA shall under § 25.15(a) and (d) pro-
ty, and well-being of subjects have been vide information that establishes to
adequately protected. Failure or in- FDA’s satisfaction that the action re-
ability to comply with these require- quested is included within the excluded
ments does not justify failure to pro- category and meets the criteria for the
vide information on a relevant clinical applicable exclusion.
investigation. (12) A financial certification or dis-

(7) For a PMA supported solely by closure statement or both as required
data from one investigation, a jus- by part 54 of this chapter.
153
§ 814.20 21 CFR Ch. I (4–1–23 Edition)
(13) Information concerning uses in pe- shall be consistent with the data re-
diatric patients. The application must porting provisions of the protocol. The
include the following information, if applicant shall submit any update re-
readily available: port in electronic format and shall in-
(i) A description of any pediatric sub- clude in the report the number as-
populations (neonates, infants, chil- signed by FDA to the PMA. These up-
dren, adolescents) that suffer from the dates are considered to be amendments
disease or condition that the device is to the PMA. The time frame for review
intended to treat, diagnose, or cure; of a PMA will not be extended due to
and the submission of an update report un-
(ii) The number of affected pediatric less the update is a major amendment
patients. under § 814.37(c)(1). The applicant shall
(14) Such other information as FDA submit these reports—
may request. If necessary, FDA will ob- (1) 3 months after the filing date;
tain the concurrence of the appropriate (2) Following receipt of an approv-
FDA advisory committee before re- able letter; and
questing additional information. (3) At any other time as requested by
(c) Pertinent information in FDA FDA.
files specifically referred to by an ap- (f) If a color additive subject to sec-
plicant may be incorporated into a tion 721 of the Federal Food, Drug, and
PMA by reference. Information in a Cosmetic Act is used in or on the de-
master file or other information sub- vice and has not previously been listed
mitted to FDA by a person other than for such use, then, in lieu of submitting
the applicant will not be considered a color additive petition under part 71
part of a PMA unless such reference is of this chapter, at the option of the ap-
authorized in a record submitted to plicant, the information required to be
FDA by the person who submitted the submitted under part 71 may be sub-
information or the master file. If a mitted as part of the PMA. When sub-
master file is not referenced within 5 mitted as part of the PMA, the infor-
years after the date that it is sub- mation shall be submitted in electronic
mitted to FDA, FDA will return the format. A PMA for a device that con-
master file to the person who sub- tains a color additive that is subject to
mitted it. section 721 of the Federal Food, Drug,
(d) If the applicant believes that cer- and Cosmetic Act will not be approved
tain information required under para- until the color additive is listed for use
graph (b) of this section to be in a PMA in or on the device.
is not applicable to the device that is (g) Additional information on FDA
the subject of the PMA, and omits any policies and procedures, as well as
such information from its PMA, the ap- links to PMA guidance documents, is
plicant shall submit a statement that available on the Internet at http://
identifies the omitted information and www.fda.gov/MedicalDevices/
justifies the omission. The statement DeviceRegulationandGuidance/
shall be submitted as a separate sec- HowtoMarketYourDevice/
tion in the PMA and identified in the PremarketSubmissions/
table of contents. If the justification PremarketApprovalPMA/default.htm.
for the omission is not accepted by the (h) If you are sending a PMA, PMA
agency, FDA will so notify the appli- amendment, PMA supplement, or cor-
cant. respondence with respect to a PMA,
(e) The applicant shall periodically you must send the submission to the
update its pending application with appropriate address as follows:
new safety and effectiveness informa- (1) For devices regulated by the Cen-
tion learned about the device from on- ter for Devices and Radiological
going or completed studies that may Health, send it to the current address
reasonably affect an evaluation of the displayed on the website https://
safety or effectiveness of the device or www.fda.gov/cdrhsubmissionaddress.
that may reasonably affect the state- (2) For devices regulated by the Cen-
ment of contraindications, warnings, ter for Biologics Evaluation and Re-

precautions, and adverse reactions in search, send it to the current address
the draft labeling. The update report displayed on the website https://
154
www.fda.gov/AboutFDA/CentersOffices/ previously omitted), the review period

OfficeofMedicalProductsandTobacco/ may be extended up to 180 days.
CBER/ucm385240.htm. (2) If an applicant declines to submit
(3) For devices regulated by the Cen- a major amendment requested by FDA,
ter for Drug Evaluation and Research, the review period may be extended for
send it to: Central Document Control the number of days that elapse between
Room, Center for Drug Evaluation and the date of such request and the date
Research, Food and Drug Administra- that FDA receives the written response
tion, 5901–B Ammendale Rd., Beltsville, declining to submit the requested
MD 20705–1266. amendment.
(d) An applicant may on its own ini-
[51 FR 26364, July 22, 1986; 51 FR 40415, Nov. tiative withdraw a PMA or PMA sup-
7, 1986, as amended at 51 FR 43344, Dec. 2, plement. If FDA requests an applicant
1986; 55 FR 11169, Mar. 27, 1990; 62 FR 40600, to submit a PMA amendment and a
July 29, 1997; 63 FR 5253, Feb. 2, 1998; 65 FR
17137, Mar. 31, 2000; 65 FR 56480, Sept. 19, 2000;
written response to FDA’s request is
67 FR 9587, Mar. 4, 2002; 71 FR 42048, July 25, not received within 180 days of the date
2006; 72 FR 17399, Apr. 9, 2007; 73 FR 34859, of the request, FDA will consider the
June 19, 2008; 74 FR 14478, Mar. 31, 2009; 75 FR pending PMA or PMA supplement to be
20915, Apr. 22, 2010; 78 FR 18233, Mar. 26, 2013; withdrawn voluntarily by the appli-
79 FR 1740, Jan. 10, 2014; 80 FR 18094, Apr. 3, cant.
2015; 83 FR 7387, Feb. 21, 2018; 84 FR 68339, (e) An applicant may resubmit a
Dec. 16, 2019] PMA or PMA supplement after with-
drawing it or after it is considered
§ 814.37 PMA amendments and resub- withdrawn under paragraph (d) of this
mitted PMAs.
section, or after FDA has refused to ac-
(a) An applicant may amend a pend- cept it for filing, or has denied ap-
ing PMA or PMA supplement to revise proval of the PMA or PMA supplement.
existing information or provide addi- A resubmitted PMA or PMA supple-
tional information. ment shall comply with the require-
(b)(1) FDA may request the applicant ments of § 814.20 or § 814.39, respec-
to amend a PMA or PMA supplement tively, and shall include the PMA num-
with any information regarding the de- ber assigned to the original submission
vice that is necessary for FDA or the and the applicant’s reasons for resub-
appropriate advisory committee to mission of the PMA or PMA supple-
complete the review of the PMA or ment.
PMA supplement. [51 FR 26364, July 22, 1986, as amended at 79
(2) FDA may request the applicant to FR 1740, Jan. 10, 2014]
amend a PMA or PMA supplement with
information concerning pediatric uses § 814.39 PMA supplements.
as required under §§ 814.20(b)(13) and (a) After FDA’s approval of a PMA,
814.39(c)(2). an applicant shall submit a PMA sup-
(c) A PMA amendment submitted to plement for review and approval by
FDA shall include the PMA or PMA FDA before making a change affecting
supplement number assigned to the the safety or effectiveness of the device
original submission and, if submitted for which the applicant has an ap-
on the applicant’s own initiative, the proved PMA, unless the change is of a
reason for submitting the amendment. type for which FDA, under paragraph
FDA may extend the time required for (e) of this section, has advised that an
its review of the PMA, or PMA supple- alternate submission is permitted or is
ment, as follows: of a type which, under section
(1) If the applicant on its own initia- 515(d)(6)(A) of the act and paragraph (f)
tive or at FDA’s request submits a of this section, does not require a PMA
major PMA amendment (e.g., an supplement under this paragraph.
amendment that contains significant While the burden for determining
new data from a previously unreported whether a supplement is required is
study, significant updated data from a primarily on the PMA holder, changes
previously reported study, detailed new for which an applicant shall submit a
analyses of previously submitted data, PMA supplement include, but are not
or significant required information limited to, the following types of
155
§ 814.39 21 CFR Ch. I (4–1–23 Edition)
changes if they affect the safety or ef- review of, and FDA action on, a PMA
fectiveness of the device: supplement are the same as those pro-
(1) New indications for use of the de- vided in § 814.40 for a PMA.
vice. (2) The supplement must include the
(2) Labeling changes. following information:
(3) The use of a different facility or (i) Information concerning pediatric
establishment to manufacture, process, uses as required under § 814.20(b)(13).
or package the device. (ii) If information concerning the de-
(4) Changes in sterilization proce- vice that is the subject of the supple-
dures. ment was previously submitted under
(5) Changes in packaging. § 814.20(b)(13) or under this section in a
(6) Changes in the performance or de-
previous supplement, that information
sign specifications, circuits, compo-
may be included by referencing a pre-
nents, ingredients, principle of oper-
vious application or submission that
ation, or physical layout of the device.
contains the information. However, if
(7) Extension of the expiration date
additional information required under
of the device based on data obtained
under a new or revised stability or ste- § 814.20(b)(13) has become readily avail-
rility testing protocol that has not able to the applicant since the previous
been approved by FDA. If the protocol submission, the applicant must submit
has been approved, the change shall be that information as part of the supple-
reported to FDA under paragraph (b) of ment.
this section. (d)(1) After FDA approves a PMA,
(b) An applicant may make a change any change described in paragraph
in a device after FDA’s approval of a (d)(2) of this section to reflect newly
PMA for the device without submitting acquired information that enhances
a PMA supplement if the change does the safety of the device or the safety in
not affect the device’s safety or effec- the use of the device may be placed
tiveness and the change is reported to into effect by the applicant prior to the
FDA in postapproval periodic reports receipt under § 814.17 of a written FDA
required as a condition to approval of order approving the PMA supplement
the device, e.g., an editorial change in provided that:
labeling which does not affect the safe- (i) The PMA supplement and its mail-
ty or effectiveness of the device. ing cover are plainly marked ‘‘Special
(c)(1) All procedures and actions that PMA Supplement—Changes Being Ef-
apply to an application under § 814.20 fected’’;
also apply to PMA supplements except (ii) The PMA supplement provides a
that the information required in a sup- full explanation of the basis for the
plement is limited to that needed to changes;
support the change. A summary under (iii) The applicant has received ac-
§ 814.20(b)(3) is required for only a sup- knowledgement from FDA of receipt of
plement submitted for new indications the supplement; and
for use of the device, significant
(iv) The PMA supplement specifically
changes in the performance or design
identifies the date that such changes
specifications, circuits, components,
are being effected.
ingredients, principles of operation, or
physical layout of the device, or when (2) The following changes are per-
otherwise required by FDA. The appli- mitted by paragraph (d)(1) of this sec-
cant shall submit a PMA supplement in tion:
electronic format and shall include in- (i) Labeling changes that add or
formation relevant to the proposed strengthen a contraindication, warn-
changes in the device. A PMA supple- ing, precaution, or information about
ment shall include a separate section an adverse reaction for which there is
that identifies each change for which reasonable evidence of a causal asso-
approval is being requested and ex- ciation.
plains the reason for each such change. (ii) Labeling changes that add or
The applicant shall submit additional strengthen an instruction that is in-

information, if requested by FDA, in tended to enhance the safe use of the
electronic format. The time frames for device.
156
(iii) Labeling changes that delete shall describe in detail the change,
misleading, false, or unsupported indi- summarize the data or information
cations. supporting the change, and state that
(iv) Changes in quality controls or the change has been made in accord-
manufacturing process that add a new ance with the requirements of part 820
specification or test method, or other- of this chapter. The manufacturer may
wise provide additional assurance of distribute the device 30 days after the
purity, identity, strength, or reli- date on which FDA receives the 30-day
ability of the device. notice, unless FDA notifies the appli-
(e)(1) FDA will identify a change to a cant within 30 days from receipt of the
device for which an applicant has an notice that the notice is not adequate.
approved PMA and for which a PMA
If the notice is not adequate, FDA shall
supplement under paragraph (a) is not
inform the applicant in writing that a
required. FDA will identify such a
change in an advisory opinion under 135-day PMA supplement is needed and
§ 10.85, if the change applies to a ge- shall describe what further information
neric type of device, or in correspond- or action is required for acceptance of
ence to the applicant, if the change ap- such change. The number of days under
plies only to the applicant’s device. review as a 30-day notice shall be de-
FDA will require that a change for ducted from the 135-day PMA supple-
which a PMA supplement under para- ment review period if the notice meets
graph (a) is not required be reported to appropriate content requirements for a
FDA in: PMA supplement.
(i) A periodic report under § 814.84 or (g) The submission and grant of a
(ii) A 30-day PMA supplement under written request for an exception or al-
this paragraph. ternative under § 801.128 or § 809.11 of
(2) FDA will identify, in the advisory this chapter satisfies the requirement
opinion or correspondence, the type of in paragraph (a) of this section.
information that is to be included in
the report or 30-day PMA supplement. [51 FR 26364, July 22, 1986, as amended at 51
If the change is required to be reported FR 43344, Dec. 2, 1986; 63 FR 54044, Oct. 8, 1998;
67 FR 9587, Mar. 4, 2002; 69 FR 11313, Mar. 10,
to FDA in a periodic report, the change
2004; 72 FR 73602, Dec. 28, 2007; 73 FR 49610,
may be made before it is reported to
Aug. 22, 2008; 79 FR 1740, Jan. 10, 2014; 84 FR
FDA. If the change is required to be re- 68340, Dec. 16, 2019]
ported in a 30-day PMA supplement,
the change may be made 30 days after
FDA files the 30-day PMA supplement Subpart C—FDA Action on a PMA
unless FDA requires the PMA holder to
provide additional information, in- § 814.40 Time frames for reviewing a
PMA.
forms the PMA holder that the supple-
ment is not approvable, or disapproves Within 180 days after receipt of an
the supplement. The 30-day PMA sup- application that is accepted for filing
plement shall follow the instructions and to which the applicant does not
in the correspondence or advisory opin- submit a major amendment, FDA will
ion. Any 30-day PMA supplement that review the PMA and, after receiving
does not meet the requirements of the the report and recommendation of the
correspondence or advisory opinion appropriate FDA advisory committee,
will not be filed and, therefore, will not send the applicant an approval order
be deemed approved 30 days after re- under § 814.44(d), an approvable letter
ceipt. under § 814.44(e), a not approvable letter
(f) Under section 515(d) of the act, under § 814.44(f), or an order denying ap-
modifications to manufacturing proce- proval under § 814.45. The approvable
dures or methods of manufacture that
letter and the not approvable letter
affect the safety and effectiveness of a
will provide an opportunity for the ap-
device subject to an approved PMA do
plicant to amend or withdraw the ap-
not require submission of a PMA sup-
plication, or to consider the letter to
plement under paragraph (a) of this

section and are eligible to be the sub- be a denial of approval of the PMA
ject of a 30-day notice. A 30-day notice
157
§ 814.42 21 CFR Ch. I (4–1–23 Edition)
under § 814.45 and to request adminis- of the decision to accept the PMA for
trative review under section 515 (d)(4) filing. If FDA does not reverse its deci-
and (g) of the act. sion not to file the PMA, the applicant
may request reconsideration of the de-
FR 2045, Jan. 13, 2022] cision from the Director of the Office
of Product Evaluation and Quality, the
§ 814.42 Filing a PMA. Director of the Center for Biologics
(a) The filing of an application means Evaluation and Research, or the Direc-
that FDA has made a threshold deter- tor of the Center for Drug Evaluation
mination that the application is suffi- and Research, as applicable. The Direc-
ciently complete to permit a sub- tor’s decision will constitute final ad-
stantive review. Within 45 days after a ministrative action for the purpose of
PMA is received by FDA, the agency judicial review.
will notify the applicant whether the (e) FDA may refuse to file a PMA if
application has been filed. any of the following applies:
(b) If FDA does not find that any of (1) The application is incomplete be-
the reasons in paragraph (e) of this sec- cause it does not on its face contain all
tion for refusing to file the PMA ap- the information required under section
plies, the agency will file the PMA and 515(c)(1) (A)–(G) of the act;
will notify the applicant in writing of (2) The PMA does not contain each of
the filing. The notice will include the the items required under § 814.20 and
PMA reference number and the date justification for omission of any item
FDA filed the PMA. The date of filing is inadequate;
is the date that a PMA accepted for fil- (3) The applicant has a pending pre-
ing was received by the agency. The market notification under section
180-day period for review of a PMA 510(k) of the act with respect to the
starts on the date of filing. same device, and FDA has not deter-
(c) If FDA refuses to file a PMA, the mined whether the device falls within
agency will notify the applicant of the the scope of § 814.1(c).
reasons for the refusal. This notice will (4) The PMA contains a false state-
identify the deficiencies in the applica- ment of material fact.
tion that prevent filing and will in- (5) The PMA is not accompanied by a
clude the PMA reference number. statement of either certification or dis-
(d) If FDA refuses to file the PMA, closure as required by part 54 of this
the applicant may: chapter.
(1) Resubmit the PMA with addi- [51 FR 26364, July 22, 1986, as amended at 63
tional information necessary to comply FR 5254, Feb. 2, 1998; 73 FR 49942, Aug. 25,
with the requirements of section 2008; 85 FR 18442, Apr. 2, 2020]
515(c)(1) (A)–(G) of the act and § 814.20.
A resubmitted PMA shall include the § 814.44 Procedures for review of a
PMA reference number of the original PMA.
submission. If the resubmitted PMA is (a) FDA will begin substantive review
accepted for filing, the date of filing is of a PMA after the PMA is accepted for
the date FDA receives the resubmis- filing under § 814.42. FDA may refer the
sion; PMA to a panel on its own initiative,
(2) Request in writing within 10 and will do so upon request of an appli-
working days of the date of receipt of cant, unless FDA determines that the
the notice refusing to file the PMA, an application substantially duplicates in-
informal conference with the Director formation previously reviewed by a
of the associated Office of Health Tech- panel. If FDA refers an application to a
nology to review FDA’s decision not to panel, FDA will forward the PMA, or
file the PMA. FDA will hold the infor- relevant portions thereof, to each
mal conference within 10 working days member of the appropriate FDA panel
of its receipt of the request and will for review. During the review process,
render its decision on filing within 5 FDA may communicate with the appli-
working days after the informal con- cant as set forth under § 814.37(b), or
ference. If, after the informal con- with a panel to respond to questions
ference, FDA accepts the PMA for fil- that may be posed by panel members or
ing, the date of filing will be the date to provide additional information to
158
the panel. FDA will maintain a record placed on public display, and that cop-
of all communications with the appli- ies are available upon request. When a
cant and with the panel. notice of approval is published, data
(b) The advisory committee shall and information in the PMA file will be
submit a report to FDA which includes available for public disclosure in ac-
the committee’s recommendation and cordance with § 814.9.
the basis for such recommendation on (2) A request for copies of the current
the PMA. Before submission of this re- PMA approvals and denials document
port, the committee shall hold a public and for copies of summaries of safety
meeting to review the PMA in accord- and effectiveness shall be sent in writ-
ance with part 14. This meeting may be ing to the Freedom of Information
held by a telephone conference under Staff’s address listed on the Agency’s
§ 14.22(g). The advisory committee re- website at https://www.fda.gov.
port and recommendation may be in (e) FDA will send the applicant an
the form of a meeting transcript signed approvable letter if the application
by the chairperson of the committee. substantially meets the requirements
(c) FDA will complete its review of of this part and the agency believes it
the PMA and the advisory committee can approve the application if specific
report and recommendation and, with- additional information is submitted or
in the later of 180 days from the date of specific conditions are agreed to by the
filing of the PMA under § 814.42 or the applicant.
number of days after the date of filing (1) The approvable letter will de-
as determined under § 814.37(c), issue an scribe the information FDA requires to
approval order under paragraph (d) of be provided by the applicant or the
this section, an approvable letter under conditions the applicant is required to
paragraph (e) of this section, a not ap- meet to obtain approval. For example,
provable letter under paragraph (f) of FDA may require, as a condition to ap-
this section, or an order denying approval:
proval of the application under (i) The submission of certain infor-
§ 814.45(a). mation identified in the approvable let-
(d)(1) FDA will issue to the applicant ter, e.g., final labeling;
an order approving a PMA if none of (ii) The submission of additional in-
the reasons in § 814.45 for denying ap- formation concerning pediatric uses re-
proval of the application applies. FDA quired by § 814.20(b)(13);
will approve an application on the
(iii) An FDA inspection that finds the
basis of draft final labeling if the only
manufacturing facilities, methods, and
deficiencies in the application concern
controls in compliance with part 820
editorial or similar minor deficiencies
and, if applicable, that verifies records
in the draft final labeling. Such ap-
pertinent to the PMA;
proval will be conditioned upon the ap-
(iv) Restrictions imposed on the de-
plicant incorporating the specified la-
vice under section 515(d)(1)(B)(ii) or
beling changes exactly as directed and
520(e) of the act;
upon the applicant submitting to FDA
a copy of the final printed labeling be- (v) Postapproval requirements as de-
fore marketing. FDA will also give the scribed in subpart E of this part.
public notice of the order, including (2) In response to an approvable let-
notice of and opportunity for any inter the applicant may:
terested persons to request review (i) Amend the PMA as requested in
under section 515(d)(4) of the act. The the approvable letter; or
notice of approval will be placed on (ii) Consider the approvable letter to
FDA’s home page on the Internet be a denial of approval of the PMA
(http://www.fda.gov), and it will state under § 814.45 and request administra-
that a detailed summary of informative review under section 515(d)(4) of
tion respecting the safety and effec- the act by filing a petition in the form
tiveness of the device, which was the of a petition for reconsideration under
basis for the order approving the PMA, § 10.33; or
including information about any ad- (iii) Withdraw the PMA.

verse effects of the device on health, is (f) FDA will send the applicant a not
available on the Internet and has been approvable letter if the agency believes
159
§ 814.45 21 CFR Ch. I (4–1–23 Edition)
that the application may not be ap- (3) The applicant does not permit an
proved for one or more of the reasons authorized FDA employee an oppor-
given in § 814.45(a). The not approvable tunity to inspect at a reasonable time
letter will describe the deficiencies in and in a reasonable manner the facili-
the application, including each applica- ties, controls, and to have access to
ble ground for denial under section and to copy and verify all records per-
515(d)(2) (A)–(E) of the act, and, where tinent to the application;
practical, will identify measures re- (4) A nonclinical laboratory study
quired to place the PMA in approvable that is described in the PMA and that
form. In response to a not approvable is essential to show that the device is
letter, the applicant may: safe for use under the conditions pre-
(1) Amend the PMA as requested in scribed, recommended, or suggested in
the not approvable letter (such an its proposed labeling, was not con-
amendment will be considered a major ducted in compliance with the good
amendment under § 814.37(c)(1)); or laboratory practice regulations in part
(2) Consider the not approvable letter 58 and no reason for the noncompliance
to be a denial of approval of the PMA is provided or, if it is, the differences
under § 814.45 and request administra- between the practices used in con-
tive review under section 515(d)(4) of ducting the study and the good labora-
the act by filing a petition in the form tory practice regulations do not sup-
of a petition for reconsideration under port the validity of the study; or
§ 10.33; or (5) Any clinical investigation involv-
(3) Withdraw the PMA. ing human subjects described in the
(g) FDA will consider a PMA to have PMA, subject to the institutional re-
been withdrawn voluntarily if: view board regulations in part 56 of
(1) The applicant fails to respond in this chapter or informed consent regu-
writing to a written request for an lations in part 50 of this chapter or
amendment within 180 days after the GCP referenced in § 814.15(a) and de-
date FDA issues such request; scribed in § 812.28(a) of this chapter,
(2) The applicant fails to respond in was not conducted in compliance with
writing to an approvable or not approv- those regulations such that the rights
able letter within 180 days after the or safety of human subjects were not
date FDA issues such letter; or adequately protected or the supporting
(3) The applicant submits a written data were determined to be otherwise
notice to FDA that the PMA has been unreliable.
withdrawn. (b) FDA will issue any order denying
[51 FR 26364, July 22, 1986, as amended at 57 approval of the PMA in accordance
FR 58403, Dec. 10, 1992; 63 FR 4572, Jan. 30, with § 814.17. The order will inform the
1998; 79 FR 1740, Jan. 10, 2014; 87 FR 2045, Jan. applicant of the deficiencies in the
13, 2022] PMA, including each applicable ground
for denial under section 515(d)(2) of the
§ 814.45 Denial of approval of a PMA. act and the regulations under this part,
(a) FDA may issue an order denying and, where practical, will identify
approval of a PMA if the applicant fails measures required to place the PMA in
to follow the requirements of this part approvable form. The order will include
or if, upon the basis of the information a notice of an opportunity to request
submitted in the PMA or any other in- review under section 515(d)(4) of the
formation before the agency, FDA de- act.
termines that any of the grounds for (c) FDA will use the criteria specified
denying approval of a PMA specified in in § 860.7 to determine the safety and
section 515(d)(2) (A)–(E) of the act ap- effectiveness of a device in deciding
plies. In addition, FDA may deny ap- whether to approve or deny approval of
proval of a PMA for any of the fol- a PMA. FDA may use information
lowing reasons: other than that submitted by the appli-
(1) The PMA contains a false state- cant in making such determination.
ment of material fact; (d)(1) FDA will give the public notice
(2) The device’s proposed labeling of an order denying approval of the

does not comply with the requirements PMA. The notice will be placed on the
in part 801 or part 809; FDA’s home page on the Internet
160
(http://www.fda.gov), and it will state laboratory practice regulations in part

that a detailed summary of informa- 58 and no reason for the noncompliance
tion respecting the safety and effec- is provided or, if it is, the differences
tiveness of the device, including infor- between the practices used in con-
mation about any adverse effects of the ducting the study and the good labora-
device on health, is available on the tory practice regulations do not sup-
Internet and has been placed on public port the validity of the study.
display and that copies are available (4) Any clinical investigation involv-
upon request. When a notice of denial ing human subjects described in the
of approval is made publicly available, PMA, subject to the institutional re-
data and information in the PMA file view board regulations in part 56 of
will be available for public disclosure this chapter or informed consent regu-
in accordance with § 814.9. lations in part 50 of this chapter or
(2) A request for copies of the current GCP referenced in § 814.15(a) and de-
PMA approvals and denials document scribed in § 812.28(a) of this chapter,
and copies of summaries of safety and was not conducted in compliance with
effectiveness shall be sent in writing to those regulations such that the rights
the Freedom of Information Staff’s ad- or safety of human subjects were not
dress listed on the Agency’s Web site at adequately protected or the supporting
http://www.fda.gov. data were determined to be otherwise
(e) FDA will issue an order denying unreliable.
approval of a PMA after an approvable (b)(1) FDA may seek advice on sci-
or not approvable letter has been sent entific matters from any appropriate
and the applicant: FDA advisory committee in deciding
(1) Submits a requested amendment whether to withdraw approval of a
but any ground for denying approval of PMA.
the application under section 515(d)(2) (2) FDA may use information other
of the act still applies; or than that submitted by the applicant
(2) Notifies FDA in writing that the in deciding whether to withdraw ap-
requested amendment will not be sub- proval of a PMA.
mitted; or (c) Before issuing an order with-
(3) Petitions for review under section drawing approval of a PMA, FDA will
515(d)(4) of the act by filing a petition issue the holder of the approved appli-
in the form of a petition for reconsider- cation a notice of opportunity for an
ation under § 10.33. informal hearing under part 16.
(d) If the applicant does not request a
FR 4572, Jan. 30, 1998; 73 FR 34859, June 19, hearing or if after the part 16 hearing
2008; 76 FR 31470, June 1, 2011; 79 FR 68115, is held the agency decides to proceed
Nov. 14, 2014; 83 FR 7387, Feb. 21, 2018; 87 FR with the withdrawal, FDA will issue to
2045, Jan. 13, 2022] the holder of the approved application
an order withdrawing approval of the
§ 814.46 Withdrawal of approval of a application. The order will be issued
PMA. under § 814.17, will state each ground
(a) FDA may issue an order with- for withdrawing approval, and will in-
drawing approval of a PMA if, from any clude a notice of an opportunity for ad-
information available to the agency, ministrative review under section
FDA determines that: 515(e)(2) of the act.
(1) Any of the grounds under section (e) FDA will give the public notice of
515(e)(1) (A)–(G) of the act applies. an order withdrawing approval of a
(2) Any postapproval requirement im- PMA. The notice will be published in
posed by the PMA approval order or by the FEDERAL REGISTER and will state
regulation has not been met. that a detailed summary of informa-
(3) A nonclinical laboratory study tion respecting the safety and effec-
that is described in the PMA and that tiveness of the device, including infor-
is essential to show that the device is mation about any adverse effects of the
safe for use under the conditions pre- device on health, has been placed on
scribed, recommended, or suggested in public display and that copies are

its proposed labeling, was not con- available upon request. When a notice
ducted in compliance with the good of withdrawal of approval is published,
161
§ 814.47 21 CFR Ch. I (4–1–23 Edition)
data and information in the PMA file health consequences or death, the
will be available for public disclosure agency shall, under the authority of
in accordance with § 814.9. section 515(e)(3) of the act, issue an
order to the PMA holder temporarily
FR 7387, Feb. 21, 2018] suspending approval of the PMA.
(d) Permanent withdrawal of approval
§ 814.47 Temporary suspension of ap- of the PMA. If FDA issues an order tem-
proval of a PMA. porarily suspending approval of a PMA,
(a) Scope. (1) This section describes the agency shall proceed expeditiously,
the procedures that FDA will follow in but within 60 days, to hold a hearing on
exercising its authority under section whether to permanently withdraw ap-
515(e)(3) of the act (21 U.S.C. 360e(e)(3)). proval of the PMA in accordance with
This authority applies to the original section 515(e)(1) of the act and the pro-
PMA, as well as any PMA supple- cedures set out in § 814.46.
ment(s), for a medical device. [61 FR 15190, Apr. 5, 1996]
(2) FDA will issue an order tempo-
rarily suspending approval of a PMA if Subpart D—Administrative Review
FDA determines that there is a reason-
able probability that continued dis-
[Reserved]
tribution of the device would cause se-
rious, adverse health consequences or Subpart E—Postapproval
death. Requirements
(b) Regulatory hearing. (1) If FDA be-
lieves that there is a reasonable prob- § 814.80 General.
ability that the continued distribution A device may not be manufactured,
of a device subject to an approved PMA packaged, stored, labeled, distributed,
would cause serious, adverse health or advertised in a manner that is in-
consequences or death, FDA may ini- consistent with any conditions to ap-
tiate and conduct a regulatory hearing proval specified in the PMA approval
to determine whether to issue an order order for the device.
temporarily suspending approval of the
PMA. § 814.82 Postapproval requirements.
(2) Any regulatory hearing to deter- (a) FDA may impose postapproval re-
mine whether to issue an order tempo- quirements in a PMA approval order or
rarily suspending approval of a PMA by regulation at the time of approval
shall be initiated and conducted by of the PMA or by regulation subse-
FDA pursuant to part 16 of this chap- quent to approval. Postapproval re-
ter. If FDA believes that immediate ac- quirements may include as a condition
tion to remove a dangerous device from to approval of the device:
the market is necessary to protect the (1) Restriction of the sale, distribu-
public health, the agency may, in action, or use of the device as provided by
cordance with § 16.60(h) of this chapter, section 515(d)(1)(B)(ii) or 520(e) of the
waive, suspend, or modify any part 16 act.
procedure pursuant to § 10.19 of this (2) Continuing evaluation and peri-
chapter. odic reporting on the safety, effective-
(3) FDA shall deem the PMA holder’s ness, and reliability of the device for
failure to request a hearing within the its intended use. FDA will state in the
timeframe specified by FDA in the no- PMA approval order the reason or pur-
tice of opportunity for hearing to be a pose for such requirement and the
waiver. number of patients to be evaluated and
(c) Temporary suspension order. If the the reports required to be submitted.
PMA holder does not request a regu- (3) Prominent display in the labeling
latory hearing or if, after the hearing, of a device and in the advertising of
and after consideration of the adminis- any restricted device of warnings, haz-
trative record of the hearing, FDA de- ards, or precautions important for the
termines that there is a reasonable device’s safe and effective use, includ-
probability that the continued dis- ing patient information, e.g., informa-
tribution of a device under an approved tion provided to the patient on alter-
PMA would cause serious, adverse native modes of therapy and on risks
162
and benefits associated with the use of § 814.84 Reports.

the device.
(a) The holder of an approved PMA
(4) Inclusion of identification codes
shall comply with the requirements of
on the device or its labeling, or in the
part 803 and with any other require-
case of an implant, on cards given to
ments applicable to the device by other
patients if necessary to protect the
regulations in this subchapter or by
public health.
order approving the device.
(5) Maintenance of records that will
(b) Unless FDA specifies otherwise,
enable the applicant to submit to FDA
information needed to trace patients if any periodic report shall:
such information is necessary to pro- (1) Identify changes described in
tect the public health. Under section § 814.39(a) and changes required to be
519(a)(4) of the act, FDA will require reported to FDA under § 814.39(b).
that the identity of any patient be dis- (2) Contain a summary and bibliog-
closed in records maintained under this raphy of the following information not
paragraph only to the extent required previously submitted as part of the
for the medical welfare of the indi- PMA:
vidual, to determine the safety or ef- (i) Unpublished reports of data from
fectiveness of the device, or to verify a any clinical investigations or nonclin-
record, report, or information sub- ical laboratory studies involving the
mitted to the agency. device or related devices and known to
(6) Maintenance of records for speci- or that reasonably should be known to
fied periods of time and organization the applicant.
and indexing of records into identifi- (ii) Reports in the scientific lit-
able files to enable FDA to determine erature concerning the device and
whether there is reasonable assurance known to or that reasonably should be
of the continued safety and effective- known to the applicant. If, after re-
ness of the device. viewing the summary and bibliog-
(7) Submission to FDA at intervals raphy, FDA concludes that the agency
specified in the approval order of peri- needs a copy of the unpublished or pub-
odic reports containing the informa- lished reports, FDA will notify the ap-
tion required by § 814.84(b). plicant that copies of such reports
(8) Batch testing of the device. shall be submitted.
(9) Such other requirements as FDA (3) Identify changes made pursuant
determines are necessary to provide to an exception or alternative granted
reasonable assurance, or continued rea- under § 801.128 or § 809.11 of this chapter.
sonable assurance, of the safety and ef- (4) Identify each device identifier
fectiveness of the device.
currently in use for the device, and
(b) An applicant shall grant to FDA each device identifier for the device
access to any records and reports re-
that has been discontinued since the
quired under the provisions of this
previous periodic report. It is not nec-
part, and shall permit authorized FDA
essary to identify any device identifier
employees to copy and verify such
discontinued prior to December 23,
records and reports and to inspect at a
reasonable time and in a reasonable 2013.
manner all manufacturing facilities to [51 FR 26364, July 22, 1986, as amended at 51
verify that the device is being manu- FR 43344, Dec. 2, 1986; 67 FR 9587, Mar. 4, 2002;
factured, stored, labeled, and shipped 72 FR 73602, Dec. 28, 2007; 78 FR 58822, Sept.
under approved conditions. 24, 2013]
(c) Failure to comply with any post-
approval requirement constitutes a Subparts F–G [Reserved]
ground for withdrawal of approval of a
PMA. Subpart H—Humanitarian Use
(Approved by the Office of Management and Devices
Budget under control number 0910–0231)
[51 FR 26364, July 22, 1986, as amended at 51 SOURCE: 61 FR 33244, June 26, 1996, unless
FR 43344, Dec. 2, 1986] otherwise noted.
163
§ 814.100 21 CFR Ch. I (4–1–23 Edition)
§ 814.100 Purpose and scope. and an opportunity for an informal

hearing.
(a) This subpart H implements sec-
tions 515A and 520(m) of the act. [61 FR 33244, June 26, 1996, as amended at 63
(b) The purpose of section 520(m) is, FR 59220, Nov. 3, 1998; 73 FR 49942, Aug. 25,
2008; 79 FR 1740, Jan. 10, 2014; 82 FR 26349,
to the extent consistent with the pro- June 7, 2017; 85 FR 18442, Apr. 2, 2020]
tection of the public health and safety
and with ethical standards, to encour- § 814.102 Designation of HUD status.
age the discovery and use of devices in- (a) Request for designation. Prior to
tended to benefit patients in the treat- submitting an HDE application, the ap-
ment or diagnosis of diseases or condi- plicant shall submit a request for HUD
tions that affect or are manifested in designation to FDA’s Office of Orphan
not more than 8,000 individuals in the Products Development. The request
United States per year. This subpart shall contain the following:
provides procedures for obtaining: (1) A statement that the applicant re-
(1) HUD designation of a medical de- quests HUD designation for a rare dis-
vice; and ease or condition or a valid subset of a
(2) Marketing approval for the HUD disease or condition which shall be
notwithstanding the absence of reason- identified with specificity;
able assurance of effectiveness that (2) The name and address of the ap-
would otherwise be required under sec- plicant, the name of the applicant’s
tions 514 and 515 of the act. primary contact person and/or resident
(c) Section 515A of the act is intended agent, including title, address, and
to ensure the submission of readily telephone number;
available information concerning: (3) A description of the rare disease
(1) Any pediatric subpopulations or condition for which the device is to
(neonates, infants, children, adoles- be used, the proposed indication or in-
cents) that suffer from the disease or dications for use of the device, and the
condition that the device is intended to reasons why such therapy is needed. If
treat, diagnose, or cure; and the device is proposed for an indication
(2) The number of affected pediatric that represents a subset of a common
patients. disease or condition, a demonstration
(d) Although a HUD may also have that the subset is medically plausible
uses that differ from the humanitarian should be included;
use, applicants seeking approval of any (4) A description of the device and a
non-HUD use shall submit a PMA as re- discussion of the scientific rationale
quired under § 814.20, or a premarket for the use of the device for the rare
disease or condition; and
notification as required under part 807
(5) Documentation, with appended
of this chapter.
authoritative references, to dem-
(e) Obtaining marketing approval for onstrate that the device is designed to
a HUD involves two steps: treat or diagnose a disease or condition
(1) Obtaining designation of the de- that affects or is manifested in not
vice as a HUD from FDA’s Office of Or- more than 8,000 people in the United
phan Products Development, and States per year. If the device is for di-
(2) Submitting an HDE to the Office agnostic purposes, the documentation
of Product Evaluation and Quality must demonstrate that not more than
(OPEQ), Center for Devices and Radio- 8,000 patients per year would be sub-
logical Health (CDRH), the Center for jected to diagnosis by the device in the
Biologics Evaluation and Research United States. Authoritative ref-
(CBER), or the Center for Drug Evalua- erences include literature citations in
tion and Research (CDER), as applica- specialized medical journals, text-
ble. books, specialized medical society pro-
(f) A person granted an exemption ceedings, or governmental statistics
under section 520(m) of the act shall publications. When no such studies or
submit periodic reports as described in literature citations exist, the applicant
§ 814.126(b). may be able to demonstrate the preva-

(g) FDA may suspend or withdraw ap- lence of the disease or condition in the
proval of an HDE after providing notice United States by providing credible
164
conclusions from appropriate research § 814.104 Original applications.

or surveys.
(a) United States applicant or represent-
(b) FDA action. Within 45 days of re-
ative. The applicant or an authorized
ceipt of a request for HUD designation,
representative shall sign the HDE. If
FDA will take one of the following ac-
the applicant does not reside or have a
tions:
place of business within the United
(1) Approve the request and notify States, the HDE shall be countersigned
the applicant that the device has been by an authorized representative resid-
designated as a HUD based on the ining or maintaining a place of business
formation submitted; in the United States and shall identify
(2) Return the request to the appli- the representative’s name and address.
cant pending further review upon sub- (b) Contents. Unless the applicant jus-
mission of additional information. This tifies an omission in accordance with
action will ensue if the request is in- paragraph (d) of this section, an HDE
complete because it does not on its face shall include:
contain all of the information required
(1) A copy of or reference to the de-
under § 814.102(a). Upon receipt of this
termination made by FDA’s Office of
additional information, the review pe-
Orphan Products Development (in ac-
riod may be extended up to 45 days; or
cordance with § 814.102) that the device
(3) Disapprove the request for HUD
qualifies as a HUD;
designation based on a substantive re-
(2) An explanation of why the device
view of the information submitted.
would not be available unless an HDE
FDA may disapprove a request for HUD
were granted and a statement that no
designation if:
comparable device (other than another
(i) There is insufficient evidence to
HUD approved under this subpart or a
support the estimate that the disease
device under an approved IDE) is avail-
or condition for which the device is de-
able to treat or diagnose the disease or
signed to treat or diagnose affects or is
condition. The application also shall
manifested in not more than 8,000 peo-
contain a discussion of the risks and
ple in the United States per year;
benefits of currently available devices
(ii) FDA determines that, for a diag- or alternative forms of treatment in
nostic device, more than 8,000 patients the United States;
in the United States would be sub-
(3) An explanation of why the prob-
jected to diagnosis using the device per
able benefit to health from the use of
year; or
the device outweighs the risk of injury
(iii) FDA determines that the patient
or illness from its use, taking into ac-
population defined in the request is not
count the probable risks and benefits of
a medically plausible subset of a larger
currently available devices or alter-
population.
native forms of treatment. Such expla-
(c) Revocation of designation. FDA nation shall include a description, ex-
may revoke a HUD designation if the planation, or theory of the underlying
agency finds that: disease process or condition, and
(1) The request for designation con- known or postulated mechanism(s) of
tained an untrue statement of material action of the device in relation to the
fact or omitted material information; disease process or condition;
or (4) All of the information required to
(2) Based on the evidence available, be submitted under § 814.20(b), except
the device is not eligible for HUD des- that:
ignation. (i) In lieu of the summaries, conclu-
(d) Submission. The applicant shall sions, and results from clinical inves-
submit two copies of a completed, tigations required under
dated, and signed request for HUD des- § 814.20(b)(3)(v)(B), (b)(3)(vi), and the in-
ignation to: Office of Orphan Products troductory text of (b)(6)(ii), the appli-
Development (HF–35), Food and Drug cant shall include the summaries, con-
Administration, 5600 Fishers Lane, clusions, and results of all clinical ex-
Rockville, MD 20857.
perience or investigations (whether ad-

[61 FR 33244, June 26, 1996, as amended at 82 verse or supportive) reasonably obtain-
FR 26349, June 7, 2017] able by the applicant that are relevant
165
§ 814.106 21 CFR Ch. I (4–1–23 Edition)
to an assessment of the risks and prob- ments and supplements, as well as any
able benefits of the device and to the correspondence relating to an HDE,
extent the applicant includes data from must be provided in electronic format.
clinical investigations, the applicant These materials must be sent or deliv-
shall include the statements described ered to one of the following:
in § 814.20(b)(6)(ii)(A) and (B) with re- (1) For devices regulated by the Cen-
spect to clinical investigations con- ter for Devices and Radiological
ducted in the United States and the in- Health, send it to the current address
formation described in found on the website https://
§ 814.20(b)(6)(ii)(C) with respect to clin- www.fda.gov/cdrhsubmissionaddress.
ical investigations conducted outside
(2) For devices regulated by the Cen-
the United States; and
(ii) In addition to the proposed label- ter for Biologics Evaluation and Re-
ing requirement set forth in search, send it to the current address
§ 814.20(b)(10), the labeling shall bear displayed on the website https://
the following statement: Humanitarian www.fda.gov/AboutFDA/CentersOffices/
Device. Authorized by Federal law for OfficeofMedicalProductsandTobacco/
use in the [treatment or diagnosis] of CBER/ucm385240.htm.
[specify disease or condition]. The ef- (3) For devices regulated by the Cen-
fectiveness of this device for this use ter for Drug Evaluation and Research,
has not been demonstrated; send this information to the Central
(5) The amount to be charged for the Document Control Room, Center for
device and, if the amount is more than Drug Evaluation and Research, Food
$250, a report by an independent cer- and Drug Administration, 5901–B
tified public accountant, made in ac- Ammendale Rd., Beltsville, MD 20705–
cordance with the Statement on Stand- 1266.
ards for Attestation established by the
American Institute of Certified Public [61 FR 33244, June 26, 1996, as amended at 63
Accountants, or in lieu of such a re- FR 59220, Nov. 3, 1998; 73 FR 49942, Aug. 25,
2008; 75 FR 20915, Apr. 22, 2010; 79 FR 1740,
port, an attestation by a responsible
Jan. 10, 2014; 80 FR 18094, Apr. 3, 2015; 83 FR
individual of the organization,
7388, Feb. 21, 2018; 84 FR 68340, Dec. 16, 2019]
verifying that the amount charged does
not exceed the costs of the device’s re- § 814.106 HDE amendments and resub-
search, development, fabrication, and mitted HDE’s.
distribution. If the amount charged is
$250 or less, the requirement for a re- An HDE or HDE supplement may be
port by an independent certified public amended or resubmitted upon an appli-
accountant or an attestation by a re- cant’s own initiative, or at the request
sponsible individual of the organiza- of FDA, for the same reasons and in
tion is waived; and the same manner as prescribed for
(6) Information concerning pediatric PMA’s in § 814.37, except that the time-
uses of the device, as required by frames set forth in § 814.37(c)(1) and (d)
§ 814.20(b)(13). do not apply. If FDA requests an HDE
(c) Omission of information. If the ap- applicant to submit an HDE amend-
plicant believes that certain informa- ment, and a written response to FDA’s
tion required under paragraph (b) of request is not received within 75 days
this section is not applicable to the de- of the date of the request, FDA will
vice that is the subject of the HDE, and consider the pending HDE or HDE sup-
omits any such information from its plement to be withdrawn voluntarily
HDE, the applicant shall submit a by the applicant. Furthermore, if the
statement that identifies and justifies HDE applicant, on its own initiative or
the omission. The statement shall be at FDA’s request, submits a major
submitted as a separate section in the amendment as described in
HDE and identified in the table of con-
§ 814.37(c)(1), the review period may be
tents. If the justification for the omis-
extended up to 75 days.
sion is not accepted by the agency,
FDA will so notify the applicant. [63 FR 59220, Nov. 3, 1998]

(d) Address for submissions and cor-
respondence. All original HDEs, amend-
166
§ 814.108 Supplemental applications. cation of filing decisions, filing dates,

After FDA approval of an original the start of the 75-day review period,
HDE, an applicant shall submit supple- and applicant’s options in response to
ments in accordance with the require- FDA refuse to file decisions shall apply
ments for PMA’s under § 814.39, except to HDE’s.
that a request for a new indication for [61 FR 33244, June 26, 1996, as amended at 63
use of a HUD shall comply with re- FR 5254, Feb. 2, 1998; 63 FR 59221, Nov. 3, 1998]
quirements set forth in § 814.110. The
timeframes for review of, and FDA ac- § 814.114 Timeframes for reviewing an
tion on, an HDE supplement are the HDE.
same as those provided in § 814.114 for Within 75 days after receipt of an
an HDE. HDE that is accepted for filing and to
[63 FR 59220, Nov. 3, 1998]
which the applicant does not submit a
major amendment, FDA shall send the
§ 814.110 New indications for use. applicant an approval order, an approv-
able letter, a not approvable letter
(a) An applicant seeking a new indi-
(under § 814.116), or an order denying
cation for use of a HUD approved under
approval (under § 814.118).
this subpart H shall obtain a new des-
ignation of HUD status in accordance [63 FR 59221, Nov. 3, 1998]
with § 814.102 and shall submit an origi-
nal HDE in accordance with § 814.104. § 814.116 Procedures for review of an
(b) An application for a new indica- HDE.
tion for use made under § 814.104 may (a) Substantive review. FDA will begin
incorporate by reference any informa- substantive review of an HDE after the
tion or data previously submitted to HDE is accepted for filing under
the agency under an HDE. § 814.112. FDA may refer an original
HDE application to a panel on its own
§ 814.112 Filing an HDE. initiative, and shall do so upon the re-
(a) The filing of an HDE means that quest of an applicant, unless FDA de-
FDA has made a threshold determina- termines that the application substan-
tion that the application is sufficiently tially duplicates information pre-
complete to permit substantive review. viously reviewed by a panel. If the HDE
Within 30 days from the date an HDE is is referred to a panel, the agency shall
received by FDA, the agency will no- follow the procedures set forth under
tify the applicant whether the applica- § 814.44, with the exception that FDA
tion has been filed. FDA may refuse to will complete its review of the HDE
file an HDE if any of the following ap- and the advisory committee report and
plies: recommendations within 75 days from
(1) The application is incomplete be- receipt of an HDE that is accepted for
cause it does not on its face contain all filing under § 814.112 or the date of fil-
the information required under ing as determined under § 814.106,
§ 814.104(b); whichever is later. Within the later of
(2) FDA determines that there is a these two timeframes, FDA will issue
comparable device available (other an approval order under paragraph (b)
than another HUD approved under this of this section, an approvable letter
subpart or a device under an approved under paragraph (c) of this section, a
IDE) to treat or diagnose the disease or not approvable letter under paragraph
condition for which approval of the (d) of this section, or an order denying
HUD is being sought; or approval of the application under
(3) The application contains an un- § 814.118(a).
true statement of material fact or (b) Approval order. FDA will issue to
omits material information. the applicant an order approving an
(4) The HDE is not accompanied by a HDE if none of the reasons in § 814.118
statement of either certification or dis- for denying approval of the application
closure, or both, as required by part 54 applies. FDA will approve an applica-
of this chapter. tion on the basis of draft final labeling

(b) The provisions contained in if the only deficiencies in the applica-
§ 814.42(b), (c), and (d) regarding notifi- tion concern editorial or similar minor
167
§ 814.118 21 CFR Ch. I (4–1–23 Edition)
deficiencies in the draft final labeling. § 814.44(f), with the exception that if a
Such approval will be conditioned upon major HDE amendment is submitted,
the applicant incorporating the speci- the review period may be extended up
fied labeling changes exactly as di- to 75 days.
rected and upon the applicant submit- (e) FDA will consider an HDE to have
ting to FDA a copy of the final printed been withdrawn voluntarily if:
labeling before marketing. The notice (1) The applicant fails to respond in
of approval of an HDE will be placed on writing to a written request for an
the FDA’s home page on the internet amendment within 75 days after the
(https://www.fda.gov) in accordance date FDA issues such request;
with the rules and policies applicable (2) The applicant fails to respond in
to PMAs submitted under § 814.20. Fol- writing to an approvable or not approv-
lowing the issuance of an approval able letter within 75 days after the date
order, data and information in the HDE FDA issues such letter; or
file will be available for public disclo- (3) The applicant submits a written
sure in accordance with § 814.9(b) notice to FDA that the HDE has been
through (h), as applicable. withdrawn.
(c) Approvable letter. FDA will send [61 FR 33244, June 26, 1996, as amended at 63
the applicant an approvable letter if FR 59221, Nov. 3, 1998; 79 FR 1741, Jan. 10,
the application substantially meets the 2014; 87 FR 2045, Jan. 13, 2022]
requirements of this subpart and the
agency believes it can approve the ap- § 814.118 Denial of approval or with-
plication if specific additional informa- drawal of approval of an HDE.
tion is submitted or specific conditions (a) FDA may deny approval or with-
are agreed to by the applicant. The ap- draw approval of an application if the
provable letter will describe the infor- applicant fails to meet the require-
mation FDA requires to be provided by ments of section 520(m) of the act or of
the applicant or the conditions the ap- this part, or of any condition of ap-
plicant is required to meet to obtain proval imposed by an IRB or by FDA,
approval. For example, FDA may re- or any postapproval requirements im-
quire as a condition to approval: posed under § 814.126. In addition, FDA
(1) The submission of certain infor- may deny approval or withdraw ap-
mation identified in the approvable let- proval of an application if, upon the
ter, e.g., final labeling; basis of the information submitted in
(2) The submission of additional in- the HDE or any other information be-
formation concerning pediatric uses of fore the agency, FDA determines that:
the device, as required by § 814.20(b)(13); (1) There is a lack of a showing of
(3) Restrictions imposed on the de- reasonable assurance that the device is
vice under section 520(e) of the act; safe under the conditions of use pre-
(4) Postapproval requirements as described, recommended, or suggested in
scribed in subpart E of this part; and the labeling thereof;
(5) An FDA inspection that finds the (2) The device is ineffective under the
manufacturing facilities, methods, and conditions of use prescribed, rec-
controls in compliance with part 820 of ommended, or suggested in the labeling
this chapter and, if applicable, that thereof;
verifies records pertinent to the HDE. (3) The applicant has not dem-
(d) Not approvable letter. FDA will onstrated that there is a reasonable
send the applicant a not approvable basis from which to conclude that the
letter if the agency believes that the probable benefit to health from the use
application may not be approved for of the device outweighs the risk of in-
one or more of the reasons given in jury or illness, taking into account the
§ 814.118. The not approvable letter will probable risks and benefits of currently
describe the deficiencies in the applica- available devices or alternative forms
tion and, where practical, will identify of treatment;
measures required to place the HDE in (4) The application or a report sub-
approvable form. The applicant may mitted by or on behalf of the applicant
respond to the not approvable letter in contains an untrue statement of mate-

the same manner as permitted for not rial fact, or omits material informa-
approvable letters for PMA’s under tion;
168
(5) The device’s labeling does not (d) Before issuing an order with-
comply with the requirements in part drawing approval of an HDE, FDA will
801 or part 809 of this chapter; provide the applicant with notice and
(6) A nonclinical laboratory study an opportunity for a hearing as re-
that is described in the HDE and that quired for PMA’s under § 814.46(c) and
is essential to show that the device is (d), and will provide the public with no-
safe for use under the conditions pre- tice in accordance with § 814.46(e), as
scribed, recommended, or suggested in applicable.
its proposed labeling, was not con- [61 FR 33244, June 26, 1996, as amended at 63
ducted in compliance with the good FR 59221, Nov. 3, 1998; 87 FR 2045, Jan. 13,
laboratory practice regulations in part 2022]
58 of this chapter and no reason for the
noncompliance is provided or, if it is, § 814.120 Temporary suspension of ap-
the differences between the practices proval of an HDE.
used in conducting the study and the An HDE or HDE supplement may be
good laboratory practice regulations do temporarily suspended for the same
not support the validity of the study; reasons and in the same manner as pre-
(7) Any clinical investigation involv- scribed for PMA’s in § 814.47.
ing human subjects described in the
[63 FR 59221, Nov. 3, 1998]
HDE, subject to the institutional re-
view board regulations in part 56 of § 814.122 Confidentiality of data and
this chapter or the informed consent information.
regulations in part 50 of this chapter,
(a) Requirement for disclosure. The
was not conducted in compliance with
‘‘HDE file’’ includes all data and infor-
those regulations such that the rights
mation submitted with or referenced in
or safety of human subjects were not
the HDE, any IDE incorporated into
adequately protected;
the HDE, any HDE amendment or sup-
(8) The applicant does not permit an plement, any report submitted under
authorized FDA employee an oppor- § 814.126, any master file, or any other
tunity to inspect at a reasonable time related submission. Any record in the
and in a reasonable manner the facili- HDE file will be available for public
ties and controls, and to have access to disclosure in accordance with the pro-
and to copy and verify all records per- visions of this section and part 20 of
tinent to the application; or this chapter.
(9) The device’s HUD designation (b) Extent of disclosure. Disclosure by
should be revoked in accordance with FDA of the existence and contents of
§ 814.102(c). an HDE file shall be subject to the
(b) If FDA issues an order denying same rules that pertain to PMA’s
approval of an application, the agency under § 814.9(b) through (h), as applica-
will comply with the same notice and ble.
disclosure provisions required for
PMA’s under § 814.45(b) and (d), as ap- § 814.124 Institutional Review Board
plicable. requirements.
(c) FDA will issue an order denying (a) IRB approval. The HDE holder is
approval of an HDE after an approvable responsible for ensuring that a HUD
or not approvable letter has been sent approved under this subpart is adminis-
and the applicant: tered only in facilities having over-
(1) Submits a requested amendment sight by an Institutional Review Board
but any ground for denying approval of (IRB) constituted and acting pursuant
the application under § 814.118(a) still to part 56 of this chapter, including
applies; continuing review of use of the device.
(2) Notifies FDA in writing that the In addition, a HUD may be adminis-
requested amendment will not be sub- tered only if such use has been ap-
mitted; or proved by an IRB. If, however, a physi-
(3) Petitions for review under section cian in an emergency situation deter-
515(d)(4) of the act by filing a petition mines that approval from an IRB can-
in the form of a petition for reconsider- not be obtained in time to prevent seri-
ation under § 10.33 of this chapter. ous harm or death to a patient, a HUD
169
§ 814.126 21 CFR Ch. I (4–1–23 Edition)
may be administered without prior ap- device together with an explanation of

proval by an IRB. In such an emer- the basis for the estimate;
gency situation, the physician shall, (iv) Information describing the appli-
within 5 days after the use of the de- cant’s clinical experience with the de-
vice, provide written notification to vice since the HDE was initially ap-
the chairman of the IRB of such use. proved. This information shall include
Such written notification shall include safety information that is known or
the identification of the patient in- reasonably should be known to the ap-
volved, the date on which the device plicant, medical device reports made
was used, and the reason for the use. under part 803 of this chapter, any data
(b) Withdrawal of IRB approval. A generated from the postmarketing
holder of an approved HDE shall notify studies, and information (whether pub-
FDA of any withdrawal of approval for lished or unpublished) that is known or
the use of a HUD by a reviewing IRB reasonably expected to be known by
within 5 working days after being noti- the applicant that may affect an eval-
fied of the withdrawal of approval. uation of the safety of the device or
that may affect the statement of con-
[61 FR 33244, June 26, 1996, as amended at 63 traindications, warnings, precautions,
FR 59221, Nov. 3, 1998; 82 FR 26349, June 7,
2017]
and adverse reactions in the device’s
labeling; and
§ 814.126 Postapproval requirements (v) A summary of any changes made
and reports. to the device in accordance with sup-
plements submitted under § 814.108. If
(a) An HDE approved under this sub- information provided in the periodic
part H shall be subject to the post- reports, or any other information in
approval requirements and reports set the possession of FDA, gives the agen-
forth under subpart E of this part, as cy reason to believe that a device
applicable, with the exception of raises public health concerns or that
§ 814.82(a)(7). In addition, medical de- the criteria for exemption are no
vice reports submitted to FDA in com- longer met, the agency may require the
pliance with the requirements of part HDE holder to submit additional infor-
803 of this chapter shall also be sub- mation to demonstrate continued com-
mitted to the IRB of record. pliance with the HDE requirements.
(b) In addition to the reports identi- (2) Other. An HDE holder shall main-
fied in paragraph (a) of this section, tain records of the names and addresses
the holder of an approved HDE shall of the facilities to which the HUD has
prepare and submit the following com- been shipped, correspondence with re-
plete, accurate, and timely reports: viewing IRB’s, as well as any other in-
(1) Periodic reports. An HDE applicant formation requested by a reviewing
is required to submit reports in accord- IRB or FDA. Such records shall be
ance with the approval order. Unless maintained in accordance with the
FDA specifies otherwise, any periodic HDE approval order.
report shall include:
[61 FR 33244, June 26, 1996, as amended at 63
(i) An update of the information re-
FR 59221, Nov. 3, 1998; 71 FR 16228, Mar. 31,
quired under § 814.102(a) in a separately 2006; 82 FR 26349, June 7, 2017]
bound volume;
(ii) An update of the information re-
quired under § 814.104(b)(2), (b)(3), and
PART 820—QUALITY SYSTEM
(b)(5); REGULATION
(iii) The number of devices that have
been shipped or sold since initial mar-
keting approval under this subpart H Sec.
and, if the number shipped or sold ex- 820.1 Scope.
ceeds 8,000, an explanation and esti- 820.3 Definitions.
mate of the number of devices used per 820.5 Quality system.
patient. If a single device is used on
Subpart B—Quality System Requirements
multiple patients, the applicant shall

submit an estimate of the number of 820.20 Management responsibility.
patients treated or diagnosed using the 820.22 Quality audit.
170
820.25 Personnel. Subpart O—Statistical Techniques
Subpart C—Design Controls 820.250 Statistical techniques.
AUTHORITY: 21 U.S.C. 351, 352, 360, 360c, 360d,
820.30 Design controls.
360e, 360h, 360i, 360j, 360l, 371, 374, 381, 383; 42
U.S.C. 216, 262, 263a, 264.
Subpart D—Document Controls
SOURCE: 61 FR 52654, Oct. 7, 1996, unless
820.40 Document controls. otherwise noted.
Subpart E—Purchasing Controls Subpart A—General Provisions

820.50 Purchasing controls.
§ 820.1 Scope.
Subpart F—Identification and Traceability (a) Applicability. (1) Current good
manufacturing practice (CGMP) re-
820.60 Identification. quirements are set forth in this quality
820.65 Traceability.
system regulation. The requirements
Subpart G—Production and Process in this part govern the methods used
Controls in, and the facilities and controls used
for, the design, manufacture, pack-
820.70 Production and process controls. aging, labeling, storage, installation,
820.72 Inspection, measuring, and test and servicing of all finished devices in-
equipment. tended for human use. The require-
820.75 Process validation. ments in this part are intended to en-
sure that finished devices will be safe
Subpart H—Acceptance Activities and effective and otherwise in compli-
820.80 Receiving, in-process, and finished ance with the Federal Food, Drug, and
device acceptance. Cosmetic Act (the act). This part es-
820.86 Acceptance status. tablishes basic requirements applicable
to manufacturers of finished medical
Subpart I—Nonconforming Product devices. If a manufacturer engages in
820.90 Nonconforming product.
only some operations subject to the re-
quirements in this part, and not in oth-
Subpart J—Corrective and Preventive ers, that manufacturer need only com-
Action ply with those requirements applicable
to the operations in which it is en-
820.100 Corrective and preventive action. gaged. With respect to class I devices,
design controls apply only to those de-
Subpart K—Labeling and Packaging vices listed in § 820.30(a)(2). This regula-
Control tion does not apply to manufacturers
820.120 Device labeling. of components or parts of finished de-
820.130 Device packaging. vices, but such manufacturers are en-
couraged to use appropriate provisions
Subpart L—Handling, Storage, Distribution, of this regulation as guidance. Manu-
and Installation facturers of blood and blood compo-
nents used for transfusion or for fur-
820.140 Handling. ther manufacturing are not subject to
820.150 Storage.
this part, but are subject to subchapter
820.160 Distribution.
820.170 Installation.
F of this chapter. Manufacturers of
human cells, tissues, and cellular and
Subpart M—Records tissue-based products (HCT/Ps), as de-
fined in § 1271.3(d) of this chapter, that
820.180 General requirements. are medical devices (subject to pre-
820.181 Device master record. market review or notification, or ex-
820.184 Device history record. empt from notification, under an appli-
820.186 Quality system record. cation submitted under the device pro-
820.198 Complaint files.
visions of the act or under a biological
Subpart N—Servicing product license application under sec-

tion 351 of the Public Health Service
820.200 Servicing. Act) are subject to this part and are
171
§ 820.3 21 CFR Ch. I (4–1–23 Edition)
also subject to the donor-eligibility and Drug Administration (FDA) inspec-

procedures set forth in part 1271 sub- tion of the foreign facility for the pur-
part C of this chapter and applicable pose of determining compliance with
current good tissue practice procedures this part, it shall appear for purposes
in part 1271 subpart D of this chapter. of section 801(a) of the act, that the
In the event of a conflict between ap- methods used in, and the facilities and
plicable regulations in part 1271 and in controls used for, the design, manufac-
other parts of this chapter, the regula- ture, packaging, labeling, storage, in-
tion specifically applicable to the de- stallation, or servicing of any devices
vice in question shall supersede the produced at such facility that are of-
more general. fered for import into the United States
(2) The provisions of this part shall do not conform to the requirements of
be applicable to any finished device as section 520(f) of the act and this part
defined in this part, intended for and that the devices manufactured at
human use, that is manufactured, im- that facility are adulterated under sec-
ported, or offered for import in any tion 501(h) of the act.
State or Territory of the United (e) Exemptions or variances. (1) Any
States, the District of Columbia, or the person who wishes to petition for an
Commonwealth of Puerto Rico. exemption or variance from any device
(3) In this regulation the term quality system requirement is subject
‘‘where appropriate’’ is used several to the requirements of section 520(f)(2)
times. When a requirement is qualified of the Federal Food, Drug, and Cos-
by ‘‘where appropriate,’’ it is deemed metic Act. Petitions for an exemption
to be ‘‘appropriate’’ unless the manu- or variance shall be submitted accord-
facturer can document justification ing to the procedures set forth in § 10.30
otherwise. A requirement is ‘‘appro- of this chapter, the FDA’s administra-
priate’’ if nonimplementation could tive procedures. For guidance on how
reasonably be expected to result in the to proceed for a request for a variance,
product not meeting its specified re- contact Division of Regulatory Pro-
quirements or the manufacturer not grams 2, Office of Regulatory Pro-
being able to carry out any necessary grams, Office of Product Evaluation
corrective action. and Quality, Center for Devices and
(b) The quality system regulation in Radiological Health, Food and Drug
this part supplements regulations in Administration, 10903 New Hampshire
other parts of this chapter except Ave., Bldg. 66, Rm. 1438, Silver Spring,
where explicitly stated otherwise. In MD 20993–0002.
the event of a conflict between applica- (2) FDA may initiate and grant a
ble regulations in this part and in variance from any device quality sys-
other parts of this chapter, the regula- tem requirement when the agency de-
tions specifically applicable to the determines that such variance is in the
vice in question shall supersede any best interest of the public health. Such
other generally applicable require- variance will remain in effect only so
ments. long as there remains a public health
(c) Authority. Part 820 is established need for the device and the device
and issued under authority of sections would not likely be made sufficiently
501, 502, 510, 513, 514, 515, 518, 519, 520, available without the variance.
522, 701, 704, 801, 803 of the act (21 U.S.C. [61 FR 52654, Oct. 7, 1996, as amended at 65 FR
351, 352, 360, 360c, 360d, 360e, 360h, 360i, 17136, Mar. 31, 2000; 65 FR 66636, Nov. 7, 2000;
360j, 360l, 371, 374, 381, 383). The failure 69 FR 29829, May 25, 2005; 72 FR 17399, Apr. 9,
to comply with any applicable provi- 2007; 75 FR 20915, Apr. 22, 2010; 80 FR 29906,
sion in this part renders a device adul- May 22, 2015; 85 FR 18442, Apr. 2, 2020]
terated under section 501(h) of the act.
Such a device, as well as any person re- § 820.3 Definitions.
sponsible for the failure to comply, is (a) Act means the Federal Food,
subject to regulatory action. Drug, and Cosmetic Act, as amended
(d) Foreign manufacturers. If a manu- (secs. 201–903, 52 Stat. 1040 et seq., as
facturer who offers devices for import amended (21 U.S.C. 321–394)). All defini-
into the United States refuses to per- tions in section 201 of the act shall
mit or allow the completion of a Food apply to the regulations in this part.
172
(b) Complaint means any written, size, composition, or software version

electronic, or oral communication that that are manufactured under essen-
alleges deficiencies related to the iden- tially the same conditions and that are
tity, quality, durability, reliability, intended to have uniform characteris-
safety, effectiveness, or performance of tics and quality within specified limits.
a device after it is released for dis- (n) Management with executive respon-
tribution. sibility means those senior employees of
(c) Component means any raw mate- a manufacturer who have the authority
rial, substance, piece, part, software, to establish or make changes to the
firmware, labeling, or assembly which manufacturer’s quality policy and
is intended to be included as part of the quality system.
finished, packaged, and labeled device. (o) Manufacturer means any person
(d) Control number means any distinc- who designs, manufactures, fabricates,
tive symbols, such as a distinctive assembles, or processes a finished de-
combination of letters or numbers, or vice. Manufacturer includes but is not
both, from which the history of the limited to those who perform the func-
manufacturing, packaging, labeling, tions of contract sterilization, installa-
and distribution of a unit, lot, or batch tion, relabeling, remanufacturing, re-
of finished devices can be determined. packing, or specification development,
(e) Design history file (DHF) means a and initial distributors of foreign enti-
compilation of records which describes ties performing these functions.
the design history of a finished device.
(p) Manufacturing material means any
(f) Design input means the physical
material or substance used in or used
and performance requirements of a de-
to facilitate the manufacturing proc-
vice that are used as a basis for device
ess, a concomitant constituent, or a
design.
byproduct constituent produced during
(g) Design output means the results of
the manufacturing process, which is
a design effort at each design phase and
present in or on the finished device as
at the end of the total design effort.
a residue or impurity not by design or
The finished design output is the basis
intent of the manufacturer.
for the device master record. The total
finished design output consists of the (q) Nonconformity means the non-
device, its packaging and labeling, and fulfillment of a specified requirement.
the device master record. (r) Product means components, manu-
(h) Design review means a docu- facturing materials, in- process de-
mented, comprehensive, systematic ex- vices, finished devices, and returned
amination of a design to evaluate the devices.
adequacy of the design requirements, (s) Quality means the totality of fea-
to evaluate the capability of the design tures and characteristics that bear on
to meet these requirements, and to the ability of a device to satisfy fit-
identify problems. ness-for-use, including safety and per-
(i) Device history record (DHR) means formance.
a compilation of records containing the (t) Quality audit means a systematic,
production history of a finished device. independent examination of a manufac-
(j) Device master record (DMR) means turer’s quality system that is per-
a compilation of records containing the formed at defined intervals and at suf-
procedures and specifications for a fin- ficient frequency to determine whether
ished device. both quality system activities and the
(k) Establish means define, document results of such activities comply with
(in writing or electronically), and im- quality system procedures, that these
plement. procedures are implemented effec-
(l) Finished device means any device tively, and that these procedures are
or accessory to any device that is suit- suitable to achieve quality system ob-
able for use or capable of functioning, jectives.
whether or not it is packaged, labeled, (u) Quality policy means the overall
or sterilized. intentions and direction of an organi-
(m) Lot or batch means one or more zation with respect to quality, as es-
components or finished devices that tablished by management with execu-
consist of a single type, model, class, tive responsibility.
173
§ 820.5 21 CFR Ch. I (4–1–23 Edition)
(v) Quality system means the organi- (i) The lot or batch within which a
zational structure, responsibilities, device was manufactured;
procedures, processes, and resources for (ii) The serial number of a specific
implementing quality management. device;
(w) Remanufacturer means any person (iii) The expiration date of a specific
who processes, conditions, renovates, device;
repackages, restores, or does any other (iv) The date a specific device was
act to a finished device that signifi- manufactured.
cantly changes the finished device’s (v) For an HCT/P regulated as a de-
performance or safety specifications, vice, the distinct identification code
or intended use. required by § 1271.290(c) of this chapter.
(x) Rework means action taken on a (dd) Universal product code (UPC)
nonconforming product so that it will means the product identifier used to
fulfill the specified DMR requirements
identify an item sold at retail in the
before it is released for distribution.
United States.
(y) Specification means any require-
ment with which a product, process, [61 FR 52654, Oct. 7, 1996, as amended at 78 FR
service, or other activity must con- 58822, Sept. 24, 2013]
form.
(z) Validation means confirmation by § 820.5 Quality system.
examination and provision of objective Each manufacturer shall establish
evidence that the particular require- and maintain a quality system that is
ments for a specific intended use can appropriate for the specific medical de-
be consistently fulfilled. vice(s) designed or manufactured, and
(1) Process validation means estab- that meets the requirements of this
lishing by objective evidence that a part.
process consistently produces a result
or product meeting its predetermined Subpart B—Quality System
specifications.
Requirements
(2) Design validation means estab-
lishing by objective evidence that de- § 820.20 Management responsibility.
vice specifications conform with user
needs and intended use(s). (a) Quality policy. Management with
(aa) Verification means confirmation executive responsibility shall establish
by examination and provision of objec- its policy and objectives for, and com-
tive evidence that specified require- mitment to, quality. Management with
ments have been fulfilled. executive responsibility shall ensure
(bb) Human cell, tissue, or cellular or that the quality policy is understood,
tissue-based product (HCT/P) regulated as implemented, and maintained at all
a device means an HCT/P as defined in levels of the organization.
§ 1271.3(d) of this chapter that does not (b) Organization. Each manufacturer
meet the criteria in § 1271.10(a) and that shall establish and maintain an ade-
is also regulated as a device. quate organizational structure to en-
(cc) Unique device identifier (UDI) sure that devices are designed and pro-
means an identifier that adequately duced in accordance with the require-
identifies a device through its distribu- ments of this part.
tion and use by meeting the require- (1) Responsibility and authority. Each
ments of § 830.20 of this chapter. A manufacturer shall establish the appro-
unique device identifier is composed of: priate responsibility, authority, and
(1) A device identifier—a mandatory, interrelation of all personnel who man-
fixed portion of a UDI that identifies age, perform, and assess work affecting
the specific version or model of a de- quality, and provide the independence
vice and the labeler of that device; and and authority necessary to perform
(2) A production identifier—a condi- these tasks.
tional, variable portion of a UDI that (2) Resources. Each manufacturer
identifies one or more of the following shall provide adequate resources, in-
when included on the label of the de- cluding the assignment of trained per-
vice: sonnel, for management, performance
174
of work, and assessment activities, in- each quality audit, and reaudit(s)
cluding internal quality audits, to where taken, shall be made and such
meet the requirements of this part. reports shall be reviewed by manage-
(3) Management representative. Man- ment having responsibility for the
agement with executive responsibility matters audited. The dates and results
shall appoint, and document such ap- of quality audits and reaudits shall be
pointment of, a member of manage- documented.
ment who, irrespective of other respon-
sibilities, shall have established au- § 820.25 Personnel.
thority over and responsibility for: (a) General. Each manufacturer shall
(i) Ensuring that quality system re- have sufficient personnel with the nec-
quirements are effectively established essary education, background, train-
and effectively maintained in according, and experience to assure that all
ance with this part; and activities required by this part are cor-
(ii) Reporting on the performance of rectly performed.
the quality system to management (b) Training. Each manufacturer shall
with executive responsibility for reestablish procedures for identifying
view. training needs and ensure that all per-
(c) Management review. Management sonnel are trained to adequately per-
with executive responsibility shall re- form their assigned responsibilities.
view the suitability and effectiveness Training shall be documented.
of the quality system at defined inter- (1) As part of their training, per-
vals and with sufficient frequency ac- sonnel shall be made aware of device
cording to established procedures to defects which may occur from the im-
ensure that the quality system satis- proper performance of their specific
fies the requirements of this part and jobs.
the manufacturer’s established quality (2) Personnel who perform
policy and objectives. The dates and re- verification and validation activities
sults of quality system reviews shall be shall be made aware of defects and er-
documented. rors that may be encountered as part
(d) Quality planning. Each manufac- of their job functions.
turer shall establish a quality plan
which defines the quality practices, re-
sources, and activities relevant to de- Subpart C—Design Controls
vices that are designed and manufac- § 820.30 Design controls.
tured. The manufacturer shall estab-
lish how the requirements for quality (a) General. (1) Each manufacturer of
will be met. any class III or class II device, and the
(e) Quality system procedures. Each class I devices listed in paragraph (a)(2)
manufacturer shall establish quality of this section, shall establish and
system procedures and instructions. An maintain procedures to control the de-
outline of the structure of the docu- sign of the device in order to ensure
mentation used in the quality system that specified design requirements are
shall be established where appropriate. met.
(2) The following class I devices are
§ 820.22 Quality audit. subject to design controls:
Each manufacturer shall establish (i) Devices automated with computer
procedures for quality audits and con- software; and
duct such audits to assure that the (ii) The devices listed in the fol-
quality system is in compliance with lowing chart.
the established quality system require- Section Device
ments and to determine the effective-
ness of the quality system. Quality au- 868.6810 ........ Catheter, Tracheobronchial Suction.
878.4460 ........ Glove, Surgeon’s.
dits shall be conducted by individuals 880.6760 ........ Restraint, Protective.
who do not have direct responsibility 892.5650 ........ System, Applicator, Radionuclide, Manual.
for the matters being audited. Correc- 892.5740 ........ Source, Radionuclide Teletherapy.
tive action(s), including a reaudit of

deficient matters, shall be taken when (b) Design and development planning.
necessary. A report of the results of Each manufacturer shall establish and
175
§ 820.40 21 CFR Ch. I (4–1–23 Edition)
maintain plans that describe or ref- vidual(s) performing the review, shall
erence the design and development ac- be documented in the design history
tivities and define responsibility for file (the DHF).
implementation. The plans shall iden- (f) Design verification. Each manufac-
tify and describe the interfaces with turer shall establish and maintain pro-
different groups or activities that procedures for verifying the device design.
vide, or result in, input to the design Design verification shall confirm that
and development process. The plans the design output meets the design
shall be reviewed, updated, and ap- input requirements. The results of the
proved as design and development design verification, including identi-
evolves. fication of the design, method(s), the
(c) Design input. Each manufacturer date, and the individual(s) performing
shall establish and maintain proce- the verification, shall be documented
dures to ensure that the design require- in the DHF.
ments relating to a device are appro- (g) Design validation. Each manufac-
priate and address the intended use of turer shall establish and maintain pro-
the device, including the needs of the cedures for validating the device de-
user and patient. The procedures shall sign. Design validation shall be per-
include a mechanism for addressing informed under defined operating condi-
complete, ambiguous, or conflicting re- tions on initial production units, lots,
quirements. The design input require- or batches, or their equivalents. Design
ments shall be documented and shall be validation shall ensure that devices
reviewed and approved by a designated conform to defined user needs and in-
individual(s). The approval, including tended uses and shall include testing of
the date and signature of the indi- production units under actual or simu-
vidual(s) approving the requirements, lated use conditions. Design validation
shall be documented. shall include software validation and
(d) Design output. Each manufacturer risk analysis, where appropriate. The
shall establish and maintain proce- results of the design validation, includ-
dures for defining and documenting de- ing identification of the design, meth-
sign output in terms that allow an ade- od(s), the date, and the individual(s)
quate evaluation of conformance to de- performing the validation, shall be doc-
sign input requirements. Design output umented in the DHF.
procedures shall contain or make ref- (h) Design transfer. Each manufac-
erence to acceptance criteria and shall turer shall establish and maintain pro-
ensure that those design outputs that cedures to ensure that the device de-
are essential for the proper functioning sign is correctly translated into pro-
of the device are identified. Design out- duction specifications.
put shall be documented, reviewed, and (i) Design changes. Each manufac-
approved before release. The approval, turer shall establish and maintain pro-
including the date and signature of the cedures for the identification, docu-
individual(s) approving the output, mentation, validation or where appro-
shall be documented. priate verification, review, and ap-
(e) Design review. Each manufacturer proval of design changes before their
shall establish and maintain proce- implementation.
dures to ensure that formal docu- (j) Design history file. Each manufac-
mented reviews of the design results turer shall establish and maintain a
are planned and conducted at appro- DHF for each type of device. The DHF
priate stages of the device’s design de- shall contain or reference the records
velopment. The procedures shall ensure necessary to demonstrate that the de-
that participants at each design review sign was developed in accordance with
include representatives of all functions the approved design plan and the re-
concerned with the design stage being quirements of this part.
reviewed and an individual(s) who does
not have direct responsibility for the Subpart D—Document Controls
design stage being reviewed, as well as
§ 820.40 Document controls.
any specialists needed. The results of a

design review, including identification Each manufacturer shall establish
of the design, the date, and the indi- and maintain procedures to control all
176
documents that are required by this quirements. The evaluation shall be

part. The procedures shall provide for documented.
the following: (2) Define the type and extent of con-
(a) Document approval and distribu- trol to be exercised over the product,
tion. Each manufacturer shall des- services, suppliers, contractors, and
ignate an individual(s) to review for consultants, based on the evaluation
adequacy and approve prior to issuance results.
all documents established to meet the (3) Establish and maintain records of
requirements of this part. The ap- acceptable suppliers, contractors, and
proval, including the date and signa- consultants.
ture of the individual(s) approving the (b) Purchasing data. Each manufac-
document, shall be documented. Docu- turer shall establish and maintain data
ments established to meet the require- that clearly describe or reference the
ments of this part shall be available at specified requirements, including qual-
all locations for which they are des- ity requirements, for purchased or oth-
ignated, used, or otherwise necessary,
erwise received product and services.
and all obsolete documents shall be
Purchasing documents shall include,
promptly removed from all points of
where possible, an agreement that the
use or otherwise prevented from unin-
suppliers, contractors, and consultants
tended use.
agree to notify the manufacturer of
(b) Document changes. Changes to doc-
changes in the product or service so
uments shall be reviewed and approved
that manufacturers may determine
by an individual(s) in the same func-
whether the changes may affect the
tion or organization that performed
quality of a finished device. Purchasing
the original review and approval, un-
less specifically designated otherwise. data shall be approved in accordance
Approved changes shall be commu- with § 820.40.
nicated to the appropriate personnel in
a timely manner. Each manufacturer Subpart F—Identification and
shall maintain records of changes to Traceability
documents. Change records shall in-
clude a description of the change, iden- § 820.60 Identification.
tification of the affected documents, Each manufacturer shall establish
the signature of the approving indi- and maintain procedures for identi-
vidual(s), the approval date, and when fying product during all stages of re-
the change becomes effective. ceipt, production, distribution, and in-
stallation to prevent mixups.
Subpart E—Purchasing Controls
§ 820.65 Traceability.
§ 820.50 Purchasing controls.
Each manufacturer of a device that is
Each manufacturer shall establish intended for surgical implant into the
and maintain procedures to ensure that body or to support or sustain life and
all purchased or otherwise received whose failure to perform when properly
product and services conform to speci- used in accordance with instructions
fied requirements. for use provided in the labeling can be
(a) Evaluation of suppliers, contractors, reasonably expected to result in a sig-
and consultants. Each manufacturer nificant injury to the user shall estab-
shall establish and maintain the re- lish and maintain procedures for iden-
quirements, including quality require- tifying with a control number each
ments, that must be met by suppliers, unit, lot, or batch of finished devices
contractors, and consultants. Each and where appropriate components.
manufacturer shall:
The procedures shall facilitate correc-
(1) Evaluate and select potential sup- tive action. Such identification shall
pliers, contractors, and consultants on be documented in the DHR.

the basis of their ability to meet speci-
fied requirements, including quality re-
177
§ 820.70 21 CFR Ch. I (4–1–23 Edition)
Subpart G—Production and sonal practices, and clothing of per-

Process Controls sonnel if contact between such per-
sonnel and product or environment
§ 820.70 Production and process con- could reasonably be expected to have
trols. an adverse effect on product quality.
(a) General. Each manufacturer shall The manufacturer shall ensure that
develop, conduct, control, and monitor maintenance and other personnel who
production processes to ensure that a are required to work temporarily under
device conforms to its specifications. special environmental conditions are
Where deviations from device specifica- appropriately trained or supervised by
tions could occur as a result of the a trained individual.
manufacturing process, the manufac- (e) Contamination control. Each manu-
turer shall establish and maintain facturer shall establish and maintain
process control procedures that de-
procedures to prevent contamination of
scribe any process controls necessary
equipment or product by substances
to ensure conformance to specifica-
that could reasonably be expected to
tions. Where process controls are need-
ed they shall include: have an adverse effect on product qual-
(1) Documented instructions, stand- ity.
ard operating procedures (SOP’s), and (f) Buildings. Buildings shall be of
methods that define and control the suitable design and contain sufficient
manner of production; space to perform necessary operations,
(2) Monitoring and control of process prevent mixups, and assure orderly
parameters and component and device handling.
characteristics during production; (g) Equipment. Each manufacturer
(3) Compliance with specified ref- shall ensure that all equipment used in
erence standards or codes; the manufacturing process meets speci-
(4) The approval of processes and fied requirements and is appropriately
process equipment; and designed, constructed, placed, and in-
(5) Criteria for workmanship which stalled to facilitate maintenance, ad-
shall be expressed in documented justment, cleaning, and use.
standards or by means of identified and
(1) Maintenance schedule. Each manu-
approved representative samples.
facturer shall establish and maintain
(b) Production and process changes.
Each manufacturer shall establish and schedules for the adjustment, cleaning,
maintain procedures for changes to a and other maintenance of equipment to
specification, method, process, or pro- ensure that manufacturing specifica-
cedure. Such changes shall be verified tions are met. Maintenance activities,
or where appropriate validated accord- including the date and individual(s)
ing to § 820.75, before implementation performing the maintenance activities,
and these activities shall be docu- shall be documented.
mented. Changes shall be approved in (2) Inspection. Each manufacturer
accordance with § 820.40. shall conduct periodic inspections in
(c) Environmental control. Where envi- accordance with established procedures
ronmental conditions could reasonably to ensure adherence to applicable
be expected to have an adverse effect equipment maintenance schedules. The
on product quality, the manufacturer inspections, including the date and in-
shall establish and maintain proce- dividual(s) conducting the inspections,
dures to adequately control these envi- shall be documented.
ronmental conditions. Environmental (3) Adjustment. Each manufacturer
control system(s) shall be periodically shall ensure that any inherent limita-
inspected to verify that the system, in- tions or allowable tolerances are visi-
cluding necessary equipment, is ade-
bly posted on or near equipment re-
quate and functioning properly. These
quiring periodic adjustments or are
activities shall be documented and re-
readily available to personnel per-
viewed.
forming these adjustments.
(d) Personnel. Each manufacturer

shall establish and maintain require-
ments for the health, cleanliness, per-
178
(h) Manufacturing material. Where a able, the manufacturer shall use an

manufacturing material could reason- independent reproducible standard. If
ably be expected to have an adverse ef- no applicable standard exists, the man-
fect on product quality, the manufac- ufacturer shall establish and maintain
turer shall establish and maintain pro- an in-house standard.
cedures for the use and removal of such (2) Calibration records. The equipment
manufacturing material to ensure that identification, calibration dates, the
it is removed or limited to an amount individual performing each calibration,
that does not adversely affect the de- and the next calibration date shall be
vice’s quality. The removal or reduc- documented. These records shall be dis-
tion of such manufacturing material played on or near each piece of equip-
shall be documented. ment or shall be readily available to
(i) Automated processes. When com- the personnel using such equipment
puters or automated data processing and to the individuals responsible for
systems are used as part of production calibrating the equipment.
or the quality system, the manufac-
turer shall validate computer software § 820.75 Process validation.
for its intended use according to an es- (a) Where the results of a process
tablished protocol. All software cannot be fully verified by subsequent
changes shall be validated before ap- inspection and test, the process shall
proval and issuance. These validation be validated with a high degree of as-
activities and results shall be docu- surance and approved according to es-
mented. tablished procedures. The validation
activities and results, including the
§ 820.72 Inspection, measuring, and date and signature of the individual(s)
test equipment. approving the validation and where ap-
(a) Control of inspection, measuring, propriate the major equipment vali-
and test equipment. Each manufacturer dated, shall be documented.
shall ensure that all inspection, meas- (b) Each manufacturer shall establish
uring, and test equipment, including and maintain procedures for moni-
mechanical, automated, or electronic toring and control of process param-
inspection and test equipment, is suit- eters for validated processes to ensure
able for its intended purposes and is ca- that the specified requirements con-
pable of producing valid results. Each tinue to be met.
manufacturer shall establish and main- (1) Each manufacturer shall ensure
tain procedures to ensure that equip- that validated processes are performed
ment is routinely calibrated, inspected, by qualified individual(s).
checked, and maintained. The proce- (2) For validated processes, the moni-
dures shall include provisions for han- toring and control methods and data,
dling, preservation, and storage of the date performed, and, where appro-
equipment, so that its accuracy and priate, the individual(s) performing the
fitness for use are maintained. These process or the major equipment used
activities shall be documented. shall be documented.
(b) Calibration. Calibration proce- (c) When changes or process devi-
dures shall include specific directions ations occur, the manufacturer shall
and limits for accuracy and precision. review and evaluate the process and
When accuracy and precision limits are perform revalidation where appro-
not met, there shall be provisions for priate. These activities shall be docu-
remedial action to reestablish the lim- mented.
its and to evaluate whether there was
any adverse effect on the device’s qual- Subpart H—Acceptance Activities
ity. These activities shall be docu-
mented. § 820.80 Receiving, in-process, and fin-
(1) Calibration standards. Calibration ished device acceptance.
standards used for inspection, meas- (a) General. Each manufacturer shall
uring, and test equipment shall be establish and maintain procedures for
traceable to national or international acceptance activities. Acceptance ac-

standards. If national or international tivities include inspections, tests, or
standards are not practical or avail- other verification activities.
179
§ 820.86 21 CFR Ch. I (4–1–23 Edition)
(b) Receiving acceptance activities. or nonconformance of product with ac-

Each manufacturer shall establish and ceptance criteria. The identification of
maintain procedures for acceptance of acceptance status shall be maintained
incoming product. Incoming product throughout manufacturing, packaging,
shall be inspected, tested, or otherwise labeling, installation, and servicing of
verified as conforming to specified re- the product to ensure that only prod-
quirements. Acceptance or rejection uct which has passed the required ac-
shall be documented. ceptance activities is distributed, used,
(c) In-process acceptance activities. or installed.
Each manufacturer shall establish and
maintain acceptance procedures, where
appropriate, to ensure that specified Subpart I—Nonconforming
requirements for in-process product are Product
met. Such procedures shall ensure that
in-process product is controlled until § 820.90 Nonconforming product.
the required inspection and tests or (a) Control of nonconforming product.
other verification activities have been Each manufacturer shall establish and
completed, or necessary approvals are maintain procedures to control product
received, and are documented. that does not conform to specified re-
(d) Final acceptance activities. Each
quirements. The procedures shall ad-
manufacturer shall establish and main-
dress the identification, documenta-
tain procedures for finished device ac-
ceptance to ensure that each production, evaluation, segregation, and dis-
tion run, lot, or batch of finished deposition of nonconforming product.
vices meets acceptance criteria. Fin- The evaluation of nonconformance
ished devices shall be held in quar- shall include a determination of the
antine or otherwise adequately con- need for an investigation and notifica-
trolled until released. Finished devices tion of the persons or organizations re-
shall not be released for distribution sponsible for the nonconformance. The
until: evaluation and any investigation shall
(1) The activities required in the be documented.
DMR are completed; (b) Nonconformity review and disposi-
(2) the associated data and docu- tion. (1) Each manufacturer shall estab-
mentation is reviewed; lish and maintain procedures that de-
(3) the release is authorized by the fine the responsibility for review and
signature of a designated individual(s); the authority for the disposition of
and nonconforming product. The proce-
(4) the authorization is dated. dures shall set forth the review and dis-
(e) Acceptance records. Each manufac-
position process. Disposition of non-
turer shall document acceptance ac-
conforming product shall be docu-
tivities required by this part. These
mented. Documentation shall include
records shall include:
(1) The acceptance activities per- the justification for use of noncon-
formed; forming product and the signature of
(2) the dates acceptance activities the individual(s) authorizing the use.
are performed; (2) Each manufacturer shall establish
(3) the results; and maintain procedures for rework, to
(4) the signature of the individual(s) include retesting and reevaluation of
conducting the acceptance activities; the nonconforming product after re-
and work, to ensure that the product meets
(5) where appropriate the equipment its current approved specifications. Re-
used. These records shall be part of the work and reevaluation activities, in-
DHR. cluding a determination of any adverse
effect from the rework upon the prod-
§ 820.86 Acceptance status.
uct, shall be documented in the DHR.
Each manufacturer shall identify by

suitable means the acceptance status
of product, to indicate the conformance
180
Subpart J—Corrective and (a) Label integrity. Labels shall be

Preventive Action printed and applied so as to remain leg-
ible and affixed during the customary
§ 820.100 Corrective and preventive ac- conditions of processing, storage, han-
tion. dling, distribution, and where appro-
(a) Each manufacturer shall establish priate use.
and maintain procedures for imple- (b) Labeling inspection. Labeling shall
menting corrective and preventive ac- not be released for storage or use until
tion. The procedures shall include re- a designated individual(s) has exam-
quirements for: ined the labeling for accuracy includ-
(1) Analyzing processes, work oper- ing, where applicable, the correct
ations, concessions, quality audit re- unique device identifier (UDI) or uni-
ports, quality records, service records, versal product code (UPC), expiration
complaints, returned product, and date, control number, storage instruc-
other sources of quality data to iden- tions, handling instructions, and any
tify existing and potential causes of additional processing instructions. The
nonconforming product, or other qual- release, including the date and signa-
ity problems. Appropriate statistical ture of the individual(s) performing the
methodology shall be employed where examination, shall be documented in
necessary to detect recurring quality
the DHR.
problems;
(c) Labeling storage. Each manufac-
(2) Investigating the cause of
nonconformities relating to product, turer shall store labeling in a manner
processes, and the quality system; that provides proper identification and
(3) Identifying the action(s) needed to is designed to prevent mixups.
correct and prevent recurrence of non- (d) Labeling operations. Each manu-
conforming product and other quality facturer shall control labeling and
problems; packaging operations to prevent label-
(4) Verifying or validating the correc- ing mixups. The label and labeling used
tive and preventive action to ensure for each production unit, lot, or batch
that such action is effective and does shall be documented in the DHR.
not adversely affect the finished de- (e) Control number. Where a control
vice; number is required by § 820.65, that con-
(5) Implementing and recording trol number shall be on or shall accom-
changes in methods and procedures pany the device through distribution.
needed to correct and prevent identi-
fied quality problems; [61 FR 52654, Oct. 7, 1996, as amended at 78 FR
58822, Sept. 24, 2013]
(6) Ensuring that information related
to quality problems or nonconforming
§ 820.130 Device packaging.
product is disseminated to those di-
rectly responsible for assuring the Each manufacturer shall ensure that
quality of such product or the preven- device packaging and shipping con-
tion of such problems; and tainers are designed and constructed to
(7) Submitting relevant information protect the device from alteration or
on identified quality problems, as well damage during the customary condi-
as corrective and preventive actions, tions of processing, storage, handling,
for management review. and distribution.
(b) All activities required under this
section, and their results, shall be doc-
umented.
Subpart L—Handling, Storage,
Distribution, and Installation
Subpart K—Labeling and § 820.140 Handling.
Packaging Control Each manufacturer shall establish
§ 820.120 Device labeling. and maintain procedures to ensure that
mixups, damage, deterioration, con-
Each manufacturer shall establish

tamination, or other adverse effects to
and maintain procedures to control la-
beling activities. product do not occur during handling.
181
§ 820.150 21 CFR Ch. I (4–1–23 Edition)
§ 820.150 Storage. (b) The person installing the device

(a) Each manufacturer shall establish shall ensure that the installation, in-
and maintain procedures for the con- spection, and any required testing are
trol of storage areas and stock rooms performed in accordance with the man-
for product to prevent mixups, damage, ufacturer’s instructions and procedures
deterioration, contamination, or other and shall document the inspection and
adverse effects pending use or distribu- any test results to demonstrate proper
tion and to ensure that no obsolete, re- installation.
jected, or deteriorated product is used
or distributed. When the quality of Subpart M—Records
product deteriorates over time, it shall
be stored in a manner to facilitate § 820.180 General requirements.
proper stock rotation, and its condi- All records required by this part
tion shall be assessed as appropriate. shall be maintained at the manufac-
(b) Each manufacturer shall establish turing establishment or other location
and maintain procedures that describe
that is reasonably accessible to respon-
the methods for authorizing receipt
sible officials of the manufacturer and
from and dispatch to storage areas and
to employees of FDA designated to per-
stock rooms.
form inspections. Such records, includ-
§ 820.160 Distribution. ing those not stored at the inspected
establishment, shall be made readily
(a) Each manufacturer shall establish available for review and copying by
and maintain procedures for control
FDA employee(s). Such records shall be
and distribution of finished devices to
legible and shall be stored to minimize
ensure that only those devices ap-
deterioration and to prevent loss.
proved for release are distributed and
Those records stored in automated
that purchase orders are reviewed to
data processing systems shall be
ensure that ambiguities and errors are
backed up.
resolved before devices are released for
distribution. Where a device’s fitness (a) Confidentiality. Records deemed
for use or quality deteriorates over confidential by the manufacturer may
time, the procedures shall ensure that be marked to aid FDA in determining
expired devices or devices deteriorated whether information may be disclosed
beyond acceptable fitness for use are under the public information regula-
not distributed. tion in part 20 of this chapter.
(b) Each manufacturer shall main- (b) Record retention period. All records
tain distribution records which include required by this part shall be retained
or refer to the location of: for a period of time equivalent to the
(1) The name and address of the ini- design and expected life of the device,
tial consignee; but in no case less than 2 years from
(2) The identification and quantity of the date of release for commercial dis-
devices shipped; tribution by the manufacturer.
(3) The date shipped; and (c) Exceptions. This section does not
(4) Any control number(s) used. apply to the reports required by
§ 820.20(c) Management review, § 820.22
§ 820.170 Installation. Quality audits, and supplier audit re-
(a) Each manufacturer of a device reports used to meet the requirements of
quiring installation shall establish and § 820.50(a) Evaluation of suppliers, con-
maintain adequate installation and in- tractors, and consultants, but does
spection instructions, and where appro- apply to procedures established under
priate test procedures. Instructions these provisions. Upon request of a des-
and procedures shall include directions ignated employee of FDA, an employee
for ensuring proper installation so that in management with executive respon-
the device will perform as intended sibility shall certify in writing that the
after installation. The manufacturer management reviews and quality au-
shall distribute the instructions and dits required under this part, and sup-
procedures with the device or other- plier audits where applicable, have
wise make them available to the per- been performed and documented, the
son(s) installing the device. dates on which they were performed,
182
and that any required corrective action § 820.186 Quality system record.
has been undertaken.
Each manufacturer shall maintain a
§ 820.181 Device master record. quality system record (QSR). The QSR
shall include, or refer to the location
Each manufacturer shall maintain of, procedures and the documentation
device master records (DMR’s). Each of activities required by this part that
manufacturer shall ensure that each are not specific to a particular type of
DMR is prepared and approved in ac- device(s), including, but not limited to,
cordance with § 820.40. The DMR for the records required by § 820.20. Each
each type of device shall include, or manufacturer shall ensure that the
refer to the location of, the following QSR is prepared and approved in ac-
information: cordance with § 820.40.
(a) Device specifications including
appropriate drawings, composition, for- § 820.198 Complaint files.
mulation, component specifications,
(a) Each manufacturer shall main-
and software specifications;
tain complaint files. Each manufac-
(b) Production process specifications
turer shall establish and maintain pro-
including the appropriate equipment
cedures for receiving, reviewing, and
specifications, production methods,
evaluating complaints by a formally
production procedures, and production
designated unit. Such procedures shall
environment specifications;
ensure that:
(c) Quality assurance procedures and
(1) All complaints are processed in a
specifications including acceptance cri-
uniform and timely manner;
teria and the quality assurance equip-
(2) Oral complaints are documented
ment to be used;
upon receipt; and
(d) Packaging and labeling specifica-
(3) Complaints are evaluated to de-
tions, including methods and processes
termine whether the complaint rep-
used; and
resents an event which is required to
(e) Installation, maintenance, and
be reported to FDA under part 803 of
servicing procedures and methods.
this chapter, Medical Device Report-
§ 820.184 Device history record. ing.
(b) Each manufacturer shall review
Each manufacturer shall maintain and evaluate all complaints to deter-
device history records (DHR’s). Each mine whether an investigation is nec-
manufacturer shall establish and main- essary. When no investigation is made,
tain procedures to ensure that DHR’s the manufacturer shall maintain a
for each batch, lot, or unit are main- record that includes the reason no in-
tained to demonstrate that the device vestigation was made and the name of
is manufactured in accordance with the the individual responsible for the deci-
DMR and the requirements of this part. sion not to investigate.
The DHR shall include, or refer to the (c) Any complaint involving the pos-
location of, the following information: sible failure of a device, labeling, or
(a) The dates of manufacture; packaging to meet any of its specifica-
(b) The quantity manufactured; tions shall be reviewed, evaluated, and
(c) The quantity released for dis- investigated, unless such investigation
tribution; has already been performed for a simi-
(d) The acceptance records which lar complaint and another investiga-
demonstrate the device is manufac- tion is not necessary.
tured in accordance with the DMR; (d) Any complaint that represents an
(e) The primary identification label event which must be reported to FDA
and labeling used for each production under part 803 of this chapter shall be
unit; and promptly reviewed, evaluated, and in-
(f) Any unique device identifier (UDI) vestigated by a designated indi-
or universal product code (UPC), and vidual(s) and shall be maintained in a
any other device identification(s) and separate portion of the complaint files
control number(s) used.
or otherwise clearly identified. In addi-

[61 FR 52654, Oct. 7, 1996, as amended at 78 FR tion to the information required by
58822, Sept. 24, 2013] § 820.198(e), records of investigation
183
§ 820.200 21 CFR Ch. I (4–1–23 Edition)
under this paragraph shall include a verifying that the servicing meets the
determination of: specified requirements.
(1) Whether the device failed to meet (b) Each manufacturer shall analyze
specifications; service reports with appropriate statis-
(2) Whether the device was being used tical methodology in accordance with
for treatment or diagnosis; and § 820.100.
(3) The relationship, if any, of the de- (c) Each manufacturer who receives a
vice to the reported incident or adverse service report that represents an event
event. which must be reported to FDA under
(e) When an investigation is made part 803 of this chapter shall automati-
under this section, a record of the in- cally consider the report a complaint
vestigation shall be maintained by the and shall process it in accordance with
formally designated unit identified in the requirements of § 820.198.
paragraph (a) of this section. The (d) Service reports shall be docu-
record of investigation shall include: mented and shall include:
(1) The name of the device; (1) The name of the device serviced;
(2) The date the complaint was re-
(2) Any unique device identifier (UDI)
ceived;
or universal product code (UPC), and
(3) Any unique device identifier (UDI)
any other device identification(s) and
or universal product code (UPC), and
control number(s) used;
any other device identification(s) and
(3) The date of service;
control number(s) used;
(4) The name, address, and phone (4) The individual(s) servicing the de-
number of the complainant; vice;
(5) The nature and details of the com- (5) The service performed; and
plaint; (6) The test and inspection data.
(6) The dates and results of the inves- [61 FR 52654, Oct. 7, 1996, as amended at 69 FR
tigation; 11313, Mar. 10, 2004; 78 FR 58822, Sept. 24, 2013]
(7) Any corrective action taken; and
(8) Any reply to the complainant. Subpart O—Statistical Techniques
(f) When the manufacturer’s formally
designated complaint unit is located at § 820.250 Statistical techniques.
a site separate from the manufacturing
establishment, the investigated com- (a) Where appropriate, each manufac-
plaint(s) and the record(s) of investiga- turer shall establish and maintain pro-
tion shall be reasonably accessible to cedures for identifying valid statistical
the manufacturing establishment. techniques required for establishing,
(g) If a manufacturer’s formally des- controlling, and verifying the accept-
ignated complaint unit is located out- ability of process capability and prod-
side of the United States, records re- uct characteristics.
quired by this section shall be reason- (b) Sampling plans, when used, shall
ably accessible in the United States at be written and based on a valid statis-
either: tical rationale. Each manufacturer
(1) A location in the United States shall establish and maintain proce-
where the manufacturer’s records are dures to ensure that sampling methods
regularly kept; or are adequate for their intended use and
(2) The location of the initial dis- to ensure that when changes occur the
tributor. sampling plans are reviewed. These ac-
tivities shall be documented.
[61 FR 52654, Oct. 7, 1996, as amended at 69 FR
11313, Mar. 10, 2004; 71 FR 16228, Mar. 31, 2006;
78 FR 58822, Sept. 24, 2013] PART 821—MEDICAL DEVICE
TRACKING REQUIREMENTS
Subpart N—Servicing
§ 820.200 Servicing.
Sec.
(a) Where servicing is a specified re- 821.1 Scope.
quirement, each manufacturer shall es- 821.2 Exemptions and variances.

tablish and maintain instructions and 821.3 Definitions.
procedures for performing and 821.4 Imported devices.
184
Subpart B—Tracking Requirements is necessary for the effectiveness of

remedies prescribed by the act, such as
821.20 Devices subject to tracking.
821.25 Device tracking system and content patient notification (section 518(a) of
requirements: manufacturer require- the act) or device recall (section 518(e)
ments. of the act). Although these regulations
do not preclude a manufacturer from
Subpart C—Additional Requirements and involving outside organizations in that
Responsibilities manufacturer’s device tracking effort,
821.30 Tracking obligations of persons other the legal responsibility for complying
than device manufacturers: distributor with this part rests with manufactur-
requirements. ers who are subject to tracking orders,
and that responsibility cannot be al-
Subpart D—Records and Inspections tered, modified, or in any way abro-
821.50 Availability. gated by contracts or other agree-
821.55 Confidentiality. ments.
821.60 Retention of records. (c) The primary burden for ensuring
AUTHORITY: 21 U.S.C. 331, 351, 352, 360, 360e, that the tracking system works rests
360h, 360i, 371, 374. upon the manufacturer. A manufac-
SOURCE: 58 FR 43447, Aug. 16, 1993, unless turer or any other person, including a
otherwise noted. distributor, final distributor, or mul-
tiple distributor, who distributes a de-
Subpart A—General Provisions vice subject to tracking, who fails to
comply with any applicable require-
§ 821.1 Scope. ment of section 519(e) of the act or of
(a) The regulations in this part im- this part, or any person who causes
plement section 519(e) of the Federal such failure, misbrands the device
Food, Drug, and Cosmetic Act (the within the meaning of section 502(t)(2)
act), which provides that the Food and of the act and commits a prohibited act
Drug Administration may require a within the meaning of sections 301(e)
manufacturer to adopt a method of and 301(q)(1)(B) of the act.
tracking a class II or class III device, if (d) Any person subject to this part
the device meets one of the following who permanently discontinues doing
three criteria and FDA issues an order business is required to notify FDA at
to the manufacturer: the failure of the the time the person notifies any gov-
device would be reasonably likely to ernment agency, court, or supplier, and
have serious adverse health con- provide FDA with a complete set of its
sequences; or the device is intended to tracking records and information.
be implanted in the human body for However, if a person ceases distribu-
more than 1 year; or the device is a tion of a tracked device but continues
life-sustaining or life-supporting device to do other business, that person con-
used outside a device user facility. A tinues to be responsible for compliance
device that meets one of these criteria with this part unless another person,
and is the subject of an FDA order affirmatively and in writing, assumes
must comply with this part and is re- responsibility for continuing the track-
ferred to, in this part, as a ‘‘tracked de- ing of devices previously distributed
vice.’’
under this part. Further, if a person
(b) These regulations are intended to
subject to this part goes out of busi-
ensure that tracked devices can be
ness completely, but other persons ac-
traced from the device manufacturing
quire the right to manufacture or dis-
facility to the person for whom the de-
tribute tracked devices, those other
vice is indicated, that is, the patient.
Effective tracking of devices from the persons are deemed to be responsible
manufacturing facility, through the for continuing the tracking responsi-
distributor network (including dis- bility of the previous person under this
tributors, retailers, rental firms and part.
other commercial enterprises, device [58 FR 43447, Aug. 16, 1993, as amended at 67
user facilities, and licensed practi- FR 5951, Feb. 8, 2002; 73 FR 34860, June 19,
tioners) and, ultimately, to the patient 2008]
185
§ 821.2 21 CFR Ch. I (4–1–23 Edition)
§ 821.2 Exemptions and variances. bles, or processes a device or engages in

(a) A manufacturer, importer, or dis- any of the activities described in
tributor may seek an exemption or § 807.3(d) of this chapter.
variance from one or more require- (d) Device failure means the failure of
ments of this part. a device to perform or function as in-
(b) A request for an exemption or tended, including any deviations from
variance shall be submitted in the form the device’s performance specifications
of a petition under § 10.30 of this chap- or intended use.
ter and shall comply with the require- (e) Serious adverse health consequences
ments set out therein, except that a re- means any significant adverse experi-
sponse shall be issued in 90 days. The ence related to a device, including de-
Director or Deputy Directors, CDRH, vice-related events which are life-
or the Director or Principal Deputy Di- threatening or which involve perma-
rector of the Office of Product Evalua- nent or long-term injuries or illnesses.
tion and Quality, CDRH, shall issue re- (f) Device intended to be implanted in
sponses to requests under this section. the human body for more than 1 year
The petition shall also contain the fol-
means a device that is intended to be
lowing:
placed into a surgically or naturally
(1) The name of the device and device
class and representative labeling show- formed cavity of the human body for
ing the intended use(s) of the device; more than 1 year to continuously as-
(2) The reasons that compliance with sist, restore, or replace the function of
the tracking requirements of this part an organ system or structure of the
is unnecessary; human body throughout the useful life
(3) A complete description of alter- of the device. The term does not in-
native steps that are available, or that clude a device that is intended and
the petitioner has already taken, to en- used only for temporary purposes or
sure that an effective tracking system that is intended for explantation in 1
is in place; and year or less.
(4) Other information justifying the (g) Life-supporting or life-sustaining
exemption or variance. device used outside a device user facility
(c) An exemption or variance is not means a device which is essential, or
effective until the Director or Deputy yields information that is essential, to
Directors, CDRH, or the Director or the restoration or continuation of a
Principal Deputy Director of the Office bodily function important to the con-
of Product Evaluation and Quality, tinuation of human life that is in-
CDRH, approves the request under tended for use outside a hospital, nurs-
§ 10.30(e)(2)(i) of this chapter.
ing home, ambulatory surgical facility,
[58 FR 43447, Aug. 16, 1993, as amended at 59 or diagnostic or outpatient treatment
FR 31138, June 17, 1994; 67 FR 5951, Feb. 8, facility. Physicians’ offices are not de-
2002; 72 FR 17399, Apr. 9, 2007; 85 FR 18443, vice user facilities and, therefore, de-
Apr. 2, 2020; 86 FR 17065, Apr. 1, 2021]
vices used therein are subject to track-
§ 821.3 Definitions. ing if they otherwise satisfy the statu-
tory and regulatory criteria.
The following definitions and terms
apply to this part: (h) Distributor means any person who
(a) Act means the Federal Food, furthers the distribution of a device
Drug, and Cosmetic Act, 21 U.S.C. 321 et from the original place of manufacture
seq., as amended. to the person who makes delivery or
(b) Importer means the initial dis- sale to the ultimate user, i.e., the final
tributor of an imported device who is or multiple distributor, but who does
subject to a tracking order. ‘‘Importer’’ not repackage or otherwise change the
does not include anyone who only fur- container, wrapper, or labeling of the
thers the marketing, e.g., brokers, job- device or device package.
bers, or warehousers. (i) Final distributor means any person
(c) Manufacturer means any person, who distributes a tracked device in-
including any importer, repacker and/ tended for use by a single patient over
or relabeler, who manufactures, pre- the useful life of the device to the pa-
pares, propagates, compounds, assem- tient. This term includes, but is not
186
limited to, licensed practitioners, re- (v) For an HCT/P regulated as a de-
tail pharmacies, hospitals, and other vice, the distinct identification code
types of device user facilities. required by § 1271.290(c) of this chapter.
(j) Distributes means any distribution
[58 FR 43447, Aug. 16, 1993, as amended at 67
of a tracked device, including the char- FR 5951, Feb. 8, 2002; 78 FR 58822, Sept. 24,
itable distribution of a tracked device. 2013]
This term does not include the dis-
tribution of a device under an effective § 821.4 Imported devices.
investigational device exemption in ac-
For purposes of this part, the im-
cordance with section 520(g) of the act
porter of a tracked device shall be con-
and part 812 of this chapter or the dis-
sidered the manufacturer and shall be
tribution of a device for teaching, law
required to comply with all require-
enforcement, research, or analysis as
ments of this part applicable to manu-
specified in § 801.125 of this chapter.
facturers. Importers must keep all in-
(k) Multiple distributor means any de- formation required under this part in
vice user facility, rental company, or the United States.
any other entity that distributes a life-
sustaining or life-supporting device in-
tended for use by more than one pa- Subpart B—Tracking Requirements
tient over the useful life of the device.
§ 821.20 Devices subject to tracking.
(l) Licensed practitioner means a phy-
sician, dentist, or other health care (a) A manufacturer of any class II or
practitioner licensed by the law of the class III device that fits within one of
State in which he or she practices to the three criteria within § 821.1(a) must
use or order the use of the tracked de- track that device in accordance with
vice. this part, if FDA issues a tracking
(m) Any term defined in section 201 order to that manufacturer.
of the act shall have the same defini- (b) When responding to premarket
tion in this part. notification submissions and pre-
(n) Human cell, tissue, or cellular or tis- market approval applications, FDA
sue-based product (HCT/P) regulated as a will notify the sponsor by issuing an
device means an HCT/P as defined in order that states that FDA believes the
§ 1271.3(d) of this chapter that does not device meets the criteria of section
meet the criteria in § 1271.10(a) and that 519(e)(1) of the act and, by virtue of the
is also regulated as a device. order, the sponsor must track the de-
(o) Unique device identifier (UDI) vice.
means an identifier that adequately [67 FR 5951, Feb. 8, 2002]
identifies a device through its distribu-
tion and use by meeting the require- § 821.25 Device tracking system and
ments of § 830.20 of this chapter. A content requirements: manufac-
unique device identifier is composed of: turer requirements.
(1) A device identifier—a mandatory, (a) A manufacturer of a tracked de-
fixed portion of a UDI that identifies vice shall adopt a method of tracking
the specific version or model of a de- for each such type of device that it dis-
vice and the labeler of that device; and tributes that enables a manufacturer
(2) A production identifier—a condi- to provide FDA with the following in-
tional, variable portion of a UDI that formation in writing for each tracked
identifies one or more of the following device distributed:
when included on the label of the de- (1) Except as required by order under
vice: section 518(e) of the act, within 3 work-
(i) The lot or batch within which a ing days of a request from FDA, prior
device was manufactured; to the distribution of a tracked device
(ii) The serial number of a specific to a patient, the name, address, and
device; telephone number of the distributor,
(iii) The expiration date of a specific multiple distributor, or final dis-
device; tributor holding the device for dis-

(iv) The date a specific device was tribution and the location of the de-
manufactured. vice;
187
§ 821.25 21 CFR Ch. I (4–1–23 Edition)
(2) Within 10 working days of a re- (vi) The date the device was provided
quest from FDA for tracked devices for use by the patient;
that are intended for use by a single (vii) The name, address, and tele-
patient over the life of the device, after phone number of the prescribing physi-
distribution to or implantation in a pa- cian; and
tient: (viii) If and when applicable, the date
(i) The unique device identifier (UDI), the device was returned to the manu-
lot number, batch number, model num- facturer, permanently retired from use,
ber, or serial number of the device or or otherwise permanently disposed of.
other identifier necessary to provide (b) A manufacturer of a tracked de-
for effective tracking of the devices; vice shall keep current records in ac-
(ii) The date the device was shipped cordance with its standard operating
by the manufacturer; procedure of the information identified
(iii) The name, address, telephone in paragraphs (a)(1), (a)(2) and (a)(3)(i)
number, and social security number (if through (a)(3)(iii) of this section on
available) of the patient receiving the each tracked device released for dis-
device, unless not released by the pa- tribution for as long as such device is
tient under § 821.55(a); in use or in distribution for use.
(iv) The date the device was provided (c) A manufacturer of a tracked de-
to the patient; vice shall establish a written standard
(v) The name, mailing address, and operating procedure for the collection,
telephone number of the prescribing maintenance, and auditing of the data
physician; specified in paragraphs (a) and (b) of
(vi) The name, mailing address, and this section. A manufacturer shall
telephone number of the physician reg- make this standard operating proce-
ularly following the patient if different dure available to FDA upon request. A
than the prescribing physician; and manufacturer shall incorporate the fol-
(vii) If applicable, the date the device lowing into the standard operating pro-
was explanted and the name, mailing cedure:
address, and telephone number of the (1) Data collection and recording pro-
explanting physician; the date of the cedures, which shall include a proce-
patient’s death; or the date the device dure for recording when data which is
was returned to the manufacturer, per- required under this part is missing and
manently retired from use, or other- could not be collected and the reason
wise permanently disposed of. why such required data is missing and
(3) Except as required by order under could not be collected;
section 518(e) of the act, within 10 (2) A method for recording all modi-
working days of a request from FDA fications or changes to the tracking
for tracked devices that are intended system or to the data collected and
for use by more than one patient, after maintained under the tracking system,
the distribution of the device to the reasons for any modification or change,
multiple distributor: and dates of any modification or
(i) The unique device identifier (UDI), change. Modification and changes in-
lot number, batch number, model num- cluded under this requirement include
ber, or serial number of the device or modifications to the data (including
other identifier necessary to provide termination of tracking), the data for-
for effective tracking of the devices; mat, the recording system, and the file
(ii) The date the device was shipped maintenance procedures system; and
by the manufacturer; (3) A quality assurance program that
(iii) The name, address, and tele- includes an audit procedure to be run
phone number of the multiple dis- for each device product subject to
tributor; tracking, at not less than 6-month in-
(iv) The name, address, telephone tervals for the first 3 years of distribu-
number, and social security number (if tion and at least once a year there-
available) of the patient using the de- after. This audit procedure shall pro-
vice, unless not released by the patient vide for statistically relevant sampling
under § 821.55(a); of the data collected to ensure the ac-
(v) The location of the device; curacy of data and performance testing
188
of the functioning of the tracking sys- (b) A final distributor, upon sale or
tem. other distribution of a tracked device
(d) When a manufacturer becomes for use in or by the patient, shall
aware that a distributor, final dis- promptly provide the manufacturer
tributor, or multiple distributor has tracking the device with the following
not collected, maintained, or furnished information:
any record or information required by (1) The name and address of the final
this part, the manufacturer shall no- distributor,
tify the FDA district office responsible (2) The unique device identifier
for the area in which the distributor, (UDI), lot number, batch number,
final distributor, or multiple dis- model number, or serial number of the
tributor is located of the failure of device or other identifier used by the
such persons to comply with the remanufacturer to track the device;
quirements of this part. Manufacturers (3) The name, address, telephone
shall have taken reasonable steps to number, and social security number (if
obtain compliance by the distributor, available) of the patient receiving the
multiple distributor, or final dis- device, unless not released by the pa-
tributor in question before notifying tient under § 821.55(a);
FDA. (4) The date the device was provided
(e) A manufacturer may petition for to the patient or for use in the patient;
an exemption or variance from one or (5) The name, mailing address, and
more requirements of this part accord- telephone number of the prescribing
ing to the procedures in § 821.2 of this physician;
chapter. (6) The name, mailing address, and
telephone number of the physician reg-
[58 FR 43447, Aug. 16, 1993, as amended at 67 ularly following the patient if different
FR 5951, Feb. 8, 2002; 78 FR 58822, Sept. 24,
2013]
than the prescribing physician; and
(7) When applicable, the date the de-
vice was explanted and the name, mail-
Subpart C—Additional ing address, and telephone number of
Requirements and Responsibilities the explanting physician, the date of
the patient’s death, or the date the de-
§ 821.30 Tracking obligations of per- vice was returned to the manufacturer,
sons other than device manufactur-
ers: distributor requirements. permanently retired from use, or other-
wise permanently disposed of.
(a) A distributor, final distributor, or (c)(1) A multiple distributor shall
multiple distributor of any tracked de- keep written records of the following
vice shall, upon purchasing or other- each time such device is distributed for
wise acquiring any interest in such a use by a patient:
device, promptly provide the manufac- (i) The unique device identifier (UDI),
turer tracking the device with the fol- lot number, batch number, model num-
lowing information: ber, or serial number of the device or
(1) The name and address of the dis- other identifier used by the manufac-
tributor, final distributor or multiple turer to track the device;
distributor; (ii) The name, address, telephone
(2) The unique device identifier number, and social security number (if
(UDI), lot number, batch number, available) of the patient using the de-
model number, or serial number of the vice;
device or other identifier used by the (iii) The location of the device, un-
manufacturer to track the device; less not released by the patient under
(3) The date the device was received; § 821.55(a);
(4) The person from whom the device (iv) The date the device was provided
was received; for use by the patient;
(5) If and when applicable, the date (v) The name, address, and telephone
the device was explanted, the date of number of the prescribing physician;
the patient’s death, or the date the de- (vi) The name, address, and telephone
vice was returned to the distributor, number of the physician regularly fol-
permanently retired from use, or other- lowing the patient if different than the
wise permanently disposed of. prescribing physician; and
189
§ 821.50 21 CFR Ch. I (4–1–23 Edition)
(vii) When applicable, the date the turer or distributor within the United
device was permanently retired from States.
use or otherwise permanently disposed
of. FR 43690, July 14, 2000]
(2) Except as required by order under
section 518(e) of the act, any person § 821.55 Confidentiality.
who is a multiple distributor subject to
(a) Any patient receiving a device
the recordkeeping requirement of para-
subject to tracking requirements under
graph (c)(1) of this section shall, within
this part may refuse to release, or
5 working days of a request from the
refuse permission to release, the pa-
manufacturer or within 10 working
tient’s name, address, telephone num-
days of a request from FDA for the in-
ber, and social security number, or
formation identified in paragraph (c)(1)
other identifying information for the
of this section, provide such informa-
purpose of tracking.
tion to the manufacturer or FDA.
(b) Records and other information
(d) A distributor, final distributor, or
submitted to FDA under this part shall
multiple distributor shall make any
be protected from public disclosure to
records required to be kept under this
the extent permitted under part 20 of
part available to the manufacturer of
this chapter, and in accordance with
the tracked device for audit upon writ-
§ 20.63 of this chapter, information con-
ten request by an authorized represent-
tained in such records that would iden-
ative of the manufacturer.
tify patient or research subjects shall
(e) A distributor, final distributor, or
not be available for public disclosure
multiple distributor may petition for
except as provided in those parts.
an exemption or variance from one or
more requirements of this part accord- (c) Patient names or other identifiers
ing to the procedures in § 821.2. may be disclosed to a manufacturer or
other person subject to this part or to
[58 FR 43447, Aug. 16, 1993, as amended at 67 a physician when the health or safety
FR 5951, Feb. 8, 2002; 78 FR 58822, Sept. 24, of the patient requires that such per-
2013] sons have access to the information.
Such notification will be pursuant to
Subpart D—Records and agreement that the record or informa-
Inspections tion will not be further disclosed ex-
cept as the health aspects of the pa-
§ 821.50 Availability. tient requires. Such notification does
(a) Manufacturers, distributors, mul- not constitute public disclosure and
tiple distributors, and final distribu- will not trigger the availability of the
tors shall, upon the presentation by an same information to the public gen-
FDA representative of official creden- erally.
tials and the issuance of Form FDA 482 [58 FR 43447, Aug. 16, 1993, as amended at 67
at the initiation of an inspection of an FR 5951, Feb. 8, 2002]
establishment or person under section
704 of the act, make each record and all § 821.60 Retention of records.
information required to be collected
Persons required to maintain records
and maintained under this part and all
under this part shall maintain such
records and information related to the
records for the useful life of each
events and persons identified in such
tracked device they manufacture or
records available to FDA personnel.
distribute. The useful life of a device is
(b) Records and information ref-
the time a device is in use or in dis-
erenced in paragraph (a) of this section
tribution for use. For example, a record
shall be available to FDA personnel for
may be retired if the person maintain-
purposes of reviewing, copying, or any
ing the record becomes aware of the
other use related to the enforcement of
fact that the device is no longer in use,
the act and this part. Records required

has been explanted, returned to the
to be kept by this part shall be kept in
manufacturer, or the patient has died.
a centralized point for each manufac-
190
PART 822—POSTMARKET Subpart E—Responsibilities of

SURVEILLANCE Manufacturers
822.24 What are my responsibilities once I
Subpart A—General Provisions am notified that I am required to con-
duct postmarket surveillance?
Sec. 822.25 What are my responsibilities after my
822.1 What does this part cover? postmarket surveillance plan has been
822.2 What is the purpose of this part? approved?
822.3 How do you define the terms used in 822.26 If my company changes ownership,
this part? what must I do?
822.4 Does this part apply to me? 822.27 If I go out of business, what must I
do?
Subpart B—Notification 822.28 If I stop marketing the device subject
to postmarket surveillance, what must I
822.5 How will I know if I must conduct
do?
postmarket surveillance?
822.6 When will you notify me that I am re-
quired to conduct postmarket surveil-
Subpart F—Waivers and Exemptions
lance? 822.29 May I request a waiver of a specific
822.7 What should I do if I do not agree that requirement of this part?
postmarket surveillance is appropriate? 822.30 May I request exemption from the re-
quirement to conduct postmarket sur-
Subpart C—Postmarket Surveillance Plan veillance?
822.8 When, where, and how must I submit
my postmarket surveillance plan?
Subpart G—Records and Reports
822.9 What must I include in my submis- 822.31 What records am I required to keep?
sion? 822.32 What records are the investigators in
822.10 What must I include in my surveil- my surveillance plan required to keep?
lance plan? 822.33 How long must we keep the records?
822.11 What should I consider when design- 822.34 What must I do with the records if
ing my plan to conduct postmarket sur- the sponsor of the plan or an investigator
veillance? in the plan changes?
822.12 Do you have any information that 822.35 Can you inspect my manufacturing
will help me prepare my submission or site or other sites involved in my
design my postmarket surveillance plan? postmarket surveillance plan?
822.13 [Reserved] 822.36 Can you inspect and copy the records
822.14 May I reference information pre- related to my postmarket surveillance
viously submitted instead of submitting plan?
it again? 822.37 Under what circumstances would you
822.15 How long must I conduct postmarket inspect records identifying subjects?
surveillance of my device? 822.38 What reports must I submit to you?
Subpart D—FDA Review and Action AUTHORITY: 21 U.S.C. 331, 352, 360i, 360l, 371,
374.
822.16 What will you consider in the review
of my submission? SOURCE: 67 FR 38887, June 6, 2002, unless
822.17 How long will your review of my sub- otherwise noted.
mission take?
822.18 How will I be notified of your deci- Subpart A—General Provisions
sion?
822.19 What kinds of decisions may you § 822.1 What does this part cover?
make?
822.20 What are the consequences if I fail to This part implements section 522 of
submit a postmarket surveillance plan, the Federal Food, Drug, and Cosmetic
my plan is disapproved and I fail to sub- Act by providing procedures and re-
mit a new plan, or I fail to conduct sur- quirements for postmarket surveil-
veillance in accordance with my ap- lance of class II and class III devices
proved plan? that meet any of the following criteria:
822.21 What must I do if I want to make (a) Failure of the device would be
changes to my postmarket surveillance
plan after you have approved it?
reasonably likely to have serious ad-
822.22 What recourse do I have if I do not verse health consequences;
agree with your decision? (b) The device is intended to be im-

822.23 Is the information in my submission planted in the human body for more
considered confidential? than 1 year;
191
§ 822.2 21 CFR Ch. I (4–1–23 Edition)
(c) The device is intended to be used sion of a plan to us for approval, the
outside a user facility to support or content of the submission, and the con-
sustain life. If you fail to comply with duct and reporting requirements of the
requirements that we order under sec- surveillance.
tion 522 of the Federal Food, Drug, and (e) Human cell, tissue, or cellular or tis-
Cosmetic Act and this part, your de- sue-based product (HCT/P) regulated as a
vice is considered misbranded under device means an HCT/P as defined in
section 502(t)(3) of the Federal Food, § 1271.3(d) of this chapter that does not
Drug, and Cosmetic Act and you are in meet the criteria in § 1271.10(a) and that
violation of section 301(q)(1)(C) of the is also regulated as a device.
Federal Food, Drug, and Cosmetic Act; (f) Investigator means an individual
or who collects data or information in
(d) The device is expected to have support of a postmarket surveillance
significant use in pediatric popu- plan.
lations. (g) Life-supporting or life-sustaining
[67 FR 38887, June 6, 2002, as amended at 88 device used outside a device user facility
FR 16880, Mar. 21, 2023] means that a device is essential to, or
yields information essential to, the res-
§ 822.2 What is the purpose of this toration or continuation of a bodily
part? function important to the continuation
The purpose of this part is to imple- of human life and is used outside a hos-
ment our postmarket surveillance au- pital, nursing home, ambulatory sur-
thority to maximize the likelihood gical facility, or diagnostic or out-
that postmarket surveillance plans will patient treatment facility. A physi-
result in the collection of useful data. cian’s office is not a device user facil-
These data can reveal unforeseen ad- ity.
verse events, the actual rate of antici- (h) Manufacturer means any person,
pated adverse events, or other informa- including any importer, repacker, and/
tion necessary to protect the public or relabeler, who manufactures, pre-
health. pares, propagates, compounds, assem-
bles, processes a device, or engages in
§ 822.3 How do you define the terms any of the activities described in
used in this part? § 807.3(d) of this chapter.
Some of the terms we use in this part (i) Postmarket surveillance means the
are specific to postmarket surveillance active, systematic, scientifically valid
and reflect the language used in the collection, analysis, and interpretation
statute (law). Other terms are more of data or other information about a
general and reflect our interpretation marketed device.
of the law. This section of the part de- (j) Prospective surveillance means that
fines the following terms: the subjects are identified at the begin-
(a) Act means the Federal Food, ning of the surveillance and data or
Drug, and Cosmetic Act, 21 U.S.C. 301 et other information will be collected
seq., as amended. from that time forward (as opposed to
(b) Designated person means the indi- retrospective surveillance).
vidual who conducts or supervises the (k) Serious adverse health consequences
conduct of your postmarket surveil- means any significant adverse experi-
lance. If your postmarket surveillance ence related to a device, including de-
plan includes a team of investigators, vice-related events that are life-threat-
as defined below, the designated person ening or that involve permanent or
is the responsible leader of that team. long-term injuries or illnesses.
(c) Device failure means a device does (l) Specific guidance means guidance
not perform or function as intended, that provides information regarding
and includes any deviation from the de- postmarket surveillance for specific
vice’s performance specifications or in- types or categories of devices or spe-
tended use. cific postmarket surveillance issues.
(d) General plan guidance means agen- This type of guidance may be used to
cy guidance that provides information supplement general guidance and may

about the requirement to conduct address such topics as the type of sur-
postmarket surveillance, the submis- veillance approach that is appropriate
192
for the device and the postmarket sur- (c) The device is intended to be used
veillance question, sample size, or spe- to support or sustain life and to be
cific reporting requirements. used outside a user facility; or
(m) Surveillance question means the (d) The device is expected to have
issue or issues to be addressed by the significant use in pediatric popu-
postmarket surveillance. lations.
(n) Unforeseen adverse event means
any serious adverse health consequence [67 FR 38887, June 6, 2002, as amended at 88
FR 16880, Mar. 21, 2023]
that either is not addressed in the la-
beling of the device or occurs at a rate
higher than anticipated. Subpart B—Notification
(o) Unique device identifier (UDI)
means an identifier that adequately § 822.5 How will I know if I must con-
identifies a device through its distribu- duct postmarket surveillance?
tion and use by meeting the require- We will send you a letter (the
ments of § 830.20 of this chapter. A UDI postmarket surveillance order) noti-
is composed of: fying you of the requirement to con-
(1) A device identifier—a mandatory, duct postmarket surveillance. Before
fixed portion of a UDI that identifies we send the order, or as part of the
the specific version or model of a de- order, we may require that you submit
vice and the labeler of that device; and information about your device that
(2) A production identifier—a condi- will allow us better to define the scope
tional, variable portion of a UDI that of a surveillance order. We will specify
identifies one or more of the following the device(s) subject to the surveil-
when included on the label of the de- lance order and the reason that we are
vice: requiring postmarket surveillance of
(i) The lot or batch within which a the device under section 522 of the act.
device was manufactured; We will also provide you with any gen-
(ii) The serial number of a specific eral or specific guidance that is avail-
device; able to help you develop your plan for
(iii) The expiration date of a specific conducting postmarket surveillance.
device;
(iv) The date a specific device was § 822.6 When will you notify me that I
manufactured. am required to conduct postmarket
(v) For an HCT/P regulated as a de- surveillance?
vice, the distinct identification code We will notify you as soon as we have
required by § 1271.290(c) of this chapter. determined that postmarket surveil-
[67 FR 38887, June 6, 2002, as amended at 78 lance of your device is necessary, based
FR 58823, Sept. 24, 2013] on the identification of a surveillance
question. This may occur during the
§ 822.4 Does this part apply to me? review of a marketing application for
If we have ordered you to conduct your device, as your device goes to
postmarket surveillance of a medical market, or after your device has been
device under section 522 of the Federal marketed for a period of time.
Food, Drug, and Cosmetic Act, this
part applies to you. We have the au- § 822.7 What should I do if I do not
agree that postmarket surveillance
thority to order postmarket surveil- is appropriate?
lance of any class II or class III med-
ical device, including a device reviewed (a) If you do not agree with our deci-
under the licensing provisions of sec- sion to order postmarket surveillance
tion 351 of the Public Health Service for a particular device, you may re-
Act, that meets any of the following quest review of our decision by:
criteria: (1) Requesting a meeting with the Di-
(a) Failure of the device would be rector of the Office that issued the
reasonably likely to have serious ad- order for postmarket surveillance;
verse health consequences; (2) Seeking internal review of the
(b) The device is intended to be im- order under § 10.75 of this chapter;
planted in the human body for more (3) Requesting an informal hearing
than 1 year; under part 16 of this chapter; or
193
§ 822.8 21 CFR Ch. I (4–1–23 Edition)
(4) Requesting review by the Medical § 822.9 What must I include in my sub-
Devices Dispute Resolution Panel of mission?
the Medical Devices Advisory Com- Your submission must include the
mittee. following:
(b) You may obtain guidance docu- (a) Organizational/administrative in-
ments that discuss these mechanisms formation:
from the Center for Devices and Radio- (1) Your name and address;
logical Health’s (CDRH’s) Web site (2) Generic and trade names of your
(http://www.fda.gov/AboutFDA/ device;
CentersOffices/ (3) Name and address of the contact
OfficeofMedicalProductsandTobacco/ person for the submission;
CDRH/CDRHOmbudsman/default.htm.). (4) Premarket application/submission
number and device identifiers for your
[67 FR 38887, June 6, 2002, as amended at 72 device;
FR 17399, Apr. 9, 2007; 78 FR 18233, Mar. 26,
(5) Table of contents identifying the
2013; 85 FR 18843, Apr. 2, 2020; 88 FR 16880,
Mar. 21, 2023]
page numbers for each section of the
submission;
(6) Description of the device (this
Subpart C—Postmarket may be incorporated by reference to
Surveillance Plan the appropriate premarket application/
submission);
§ 822.8 When, where, and how must I (7) Product codes and a list of all rel-
submit my postmarket surveillance evant model numbers; and
plan? (8) Indications for use and claims for
You must submit your plan to con- the device;
duct postmarket surveillance within 30 (b) Postmarket surveillance plan;
days of the date you receive the (c) Designated person information;
postmarket surveillance order. For de- (1) Name, address, and telephone
vices regulated by the Center for Bio- number; and
logics Evaluation and Research, send (2) Experience and qualifications.
your submission to the Food and Drug [67 FR 38887, June 6, 2002, as amended at 78
Administration, Center for Biologics FR 58823, Sept. 24, 2013]
Evaluation and Research, Document
Control Center, 10903 New Hampshire § 822.10 What must I include in my
Ave., Bldg. 71, Rm. G112, Silver Spring, surveillance plan?
MD 20993–0002. For devices regulated by Your surveillance plan must include
the Center for Drug Evaluation and Re- a discussion of:
search, send your submission to the (a) The plan objective(s) addressing
Central Document Room, Center for the surveillance question(s) identified
Drug Evaluation and Research, Food in our order;
and Drug Administration, 5901–B, (b) The subject of the study, e.g., pa-
Ammendale Rd., Beltsville, MD 20705– tients, the device, animals;
1266. For devices regulated by the Cen- (c) The variables and endpoints that
ter for Devices and Radiological will be used to answer the surveillance
question, e.g., clinical parameters or
Health, send your submission to the
outcomes;
Document Mail Center, 10903 New
(d) The surveillance approach or
Hampshire Ave., Bldg. 66, Rm. G609,
methodology to be used;
Silver Spring, MD 20993–0002. When we (e) Sample size and units of observa-
receive your original submission, we tion;
will send you an acknowledgment let- (f) The investigator agreement, if ap-
ter identifying the unique document plicable;
number assigned to your submission. (g) Sources of data, e.g., hospital
You must use this number in any cor- records;
respondence related to this submission. (h) The data collection plan and
[87 FR 17950, Mar. 29, 2022] forms;

(i) The consent document, if applica-
ble;
194
(j) Institutional Review Board infor- isfy the requirements of the act and
mation, if applicable; regulations.
(k) The patient followup plan, if ap- [75 FR 20915, Apr. 22, 2010, as amended at 87
plicable; FR 17950, Mar. 29, 2022]
(l) The procedures for monitoring
conduct and progress of the surveil- § 822.13 [Reserved]
lance;
(m) An estimate of the duration of § 822.14 May I reference information
surveillance; previously submitted instead of
submitting it again?
(n) All data analyses and statistical
tests planned; Yes, you may reference information
(o) The content and timing of re- that you have submitted in premarket
ports. submissions as well as other
postmarket surveillance submissions.
§ 822.11 What should I consider when You must specify the information to be
designing my plan to conduct incorporated and the document number
postmarket surveillance? and pages where the information is lo-
cated.
You must design your surveillance to
address the postmarket surveillance § 822.15 How long must I conduct
question identified in the order you re- postmarket surveillance of my de-
ceived. You should consider what, if vice?
any, patient protection measures
The length of postmarket surveil-
should be incorporated into your plan.
lance will depend on the postmarket
You should also consider the function,
surveillance question identified in our
operating characteristics, and intended order. We may order prospective sur-
use of your device when designing a veillance for a period up to 36 months;
surveillance approach. longer periods require your agreement.
§ 822.12 Do you have any information If we believe that a prospective period
that will help me prepare my sub- of greater than 36 months is necessary
mission or design my postmarket to address the surveillance question,
surveillance plan? and you do not agree, we will use the
Medical Devices Dispute Resolution
Guidance documents that discuss our Panel to resolve the matter. You may
current thinking on preparing a obtain guidance regarding dispute reso-
postmarket surveillance submission lution procedures from the Center for
and designing a postmarket surveil- Devices and Radiological Health’s
lance plan are available on the Center (CDRH’) Web site (http://www.fda.gov/
for Devices and Radiological Health’s AboutFDA/CentersOffices/
website, the Food and Drug Adminis- OfficeofMedicalProductsandTobacco/
tration main website, and from the CDRH/CDRHOmbudsman/default.htm.).
Food and Drug Administration, Center The 36-month period refers to the sur-
for Devices and Radiological Health, veillance period, not the length of time
Office of Policy, Guidance and Policy from the issuance of the order.
Development, Center for Devices and
Radiological Health, Food and Drug [72 FR 17400, Apr. 9, 2007, as amended at 78
Administration, 10903 New Hampshire FR 18233, Mar. 26, 2013]
Ave., Bldg. 66, Rm. 5431, Silver Spring,
MD 20993–0002. They do not establish le- Subpart D—FDA Review and
gally enforceable rights or responsibil- Action
ities and do not legally bind you or
FDA. You may choose to use an ap- § 822.16 What will you consider in the
proach other than the one set forth in review of my submission?
a guidance document, as long as your First, we will determine that the sub-
alternative approach complies with the mission is administratively complete.
relevant statutes (laws) and regula- Then, in accordance with the law, we
tions. If you wish, we will meet with must determine whether the des-
you to discuss whether an alternative ignated person has appropriate quali-
approach you are considering will sat- fications and experience to conduct the
195
§ 822.17 21 CFR Ch. I (4–1–23 Edition)
surveillance and whether the surveil- § 822.18 How will I be notified of your
lance plan will result in the collection decision?
of useful data that will answer the sur-
We will send you a letter notifying
veillance question.
you of our decision and identifying any
§ 822.17 How long will your review of action you must take.
my submission take?
We will review your submission with-
in 60 days of receipt.
§ 822.19 What kinds of decisions may you make?

If your plan: Then we will send you: And you must:
(a) Should result in the collection of useful data An approval order, identifying any Conduct postmarket surveillance of
that will address the postmarket surveillance specific requirements related to your device in accordance with
question your postmarket surveillance the approved plan
(b) Should result in the collection of useful data An approvable letter identifying the Revise your postmarket surveillance
that will address the postmarket surveillance specific revisions or information submission to address the con-
question after specific revisions are made or that must be submitted before cerns in the approvable letter and
specific information is provided your plan can be approved submit it to us within the specified
timeframe. We will determine the
timeframe case-by-case, based on
the types of revisions or informa-
tion that you must submit
(c) Does not meet the requirements specified in A letter disapproving your plan and Revise your postmarket surveillance
this part identifying the reasons for dis- submission and submit it to us
approval within the specified timeframe. We
will determine the timeframe case-
by-case, based on the types of re-
visions or information that you
must submit
(d) Is not likely to result in the collection of useful A letter disapproving your plan and Revise your postmarket surveillance
data that will address the postmarket surveil- identifying the reasons for dis- submission and submit it to us
lance question approval within the specified timeframe. We
will determine the timeframe case-
by-case, based on the types of re-
visions or information that you
must submit
§ 822.20 What are the consequences if I quired to pay civil money penalties, or
fail to submit a postmarket surveil- prosecuted.
lance plan, my plan is disapproved
and I fail to submit a new plan, or I § 822.21 What must I do if I want to
fail to conduct surveillance in ac- make changes to my postmarket
cordance with my approved plan? surveillance plan after you have ap-
The failure to have an approved proved it?
postmarket surveillance plan or failure You must receive our approval in
to conduct postmarket surveillance in writing before making changes in your
accordance with the approved plan con- plan that will affect the nature or va-
stitutes failure to comply with section lidity of the data collected in accord-
522 of the act. Your failure would be a ance with the plan. To obtain our ap-
prohibited act under section proval, you must submit the request to
301(q)(1)(C) of the act, and your device make the proposed change and revised
would be misbranded under section postmarket surveillance plan to the ap-
502(t)(3) of the act. We have the author- plicable address listed in § 822.8. You
ity to initiate actions against products may reference information already
that are adulterated or misbranded, submitted in accordance with § 822.14.
and against persons who commit pro- In your cover letter, you must identify
hibited acts. Adulterated or mis- your submission as a supplement and
branded devices can be seized. Persons cite the unique document number that
who commit prohibited acts can be en- we assigned in our acknowledgment
joined from committing such acts, re- letter for your original submission,
196
specifically identify the changes to the Subpart E—Responsibilities of

plan, and identify the reasons and jus- Manufacturers
tification for making the changes. You
must report changes in your plan that § 822.24 What are my responsibilities
will not affect the nature or validity of once I am notified that I am re-
the data collected in accordance with quired to conduct postmarket sur-
the plan in the next interim report re- veillance?
quired by your approval order. You must submit your plan to con-
[87 FR 17950, Mar. 29, 2022] duct postmarket surveillance to us
within 30 days from receipt of the order
§ 822.22 What recourse do I have if I (letter) notifying you that you are re-
do not agree with your decision? quired to conduct postmarket surveil-
(a) If you disagree with us about the lance of a device. The manufacturer
content of your plan or if we dis- shall commence surveillance not later
approve your plan, or if you believe than 15 months after the day the order
there is a less burdensome approach was issued.
that will answer the surveillance ques- [88 FR 16880, Mar. 21, 2023]
tion, you may request review of our de-
cision by: § 822.25 What are my responsibilities
(1) Requesting a meeting with the in- after my postmarket surveillance
dividual who issued the order for plan has been approved?
postmarket surveillance; After we have approved your plan,
(2) Seeking internal review of the you must conduct the postmarket sur-
order under § 10.75 of this chapter; veillance of your device in accordance
(3) Requesting an informal hearing with your approved plan. This means
under part 16 of this chapter; or that you must ensure that:
(4) Requesting review by the Medical (a) Postmarket surveillance is initi-
Devices Dispute Resolution Panel of ated in a timely manner;
the Medical Devices Advisory Com- (b) The surveillance is conducted
mittee. with due diligence;
(b) You may obtain guidance docu- (c) The data identified in the plan is
ments that discuss these mechanisms collected;
from the Center for Devices and Radio- (d) Any reports required as part of
logical Health’s (CDRH’s) Web site. your approved plan are submitted to us
in a timely manner; and
FR 17400, Apr. 9, 2007; 85 FR 18443, Apr. 2, (e) Any information that we request
2020] prior to your submission of a report or
in response to our review of a report is
§ 822.23 Is the information in my sub- provided in a timely manner.
mission considered confidential?
We consider the content of your sub- § 822.26 If my company changes own-
ership, what must I do?
mission confidential until we have ap-
proved your postmarket surveillance You must notify us within 30 days of
plan. After we have approved your any change in ownership of your com-
plan, the contents of the original sub- pany. Your notification should identify
mission and any amendments, supple- any changes to the name or address of
ments, or reports may be disclosed in the company, the contact person, or
accordance with the Freedom of Infor- the designated person (as defined in
mation Act. We will continue to pro- § 822.3(b)). Your obligation to conduct
tect trade secret and confidential com- postmarket surveillance will generally
mercial information after your plan is transfer to the new owner, unless you
approved. We will not disclose informa- and the new owner have both agreed
tion identifying individual patients. that you will continue to conduct the
You may wish to indicate in your sub- surveillance. If you will continue to
mission which information you con- conduct the postmarket surveillance,

sider trade secret or confidential com- you still must notify us of the change
mercial. in ownership.
197
§ 822.27 21 CFR Ch. I (4–1–23 Edition)
§ 822.27 If I go out of business, what question does not apply to your device
must I do? or does not need to be answered for the
You must notify us within 30 days of device for which you are requesting ex-
the date of your decision to close your emption. Alternatively, you may pro-
business. You should provide the ex- vide information that answers the sur-
pected date of closure and discuss your veillance question for your device, with
plans to complete or terminate supporting documentation, to the ad-
postmarket surveillance of your de- dress in § 822.8.
vice. You must also identify who will
retain the records related to the sur- Subpart G—Records and Reports
veillance (described in subpart G of
this part) and where the records will be § 822.31 What records am I required to
kept. keep?
§ 822.28 If I stop marketing the device You must keep copies of:
subject to postmarket surveillance, (a) All correspondence with your in-
what must I do? vestigators or FDA, including required
You must continue to conduct reports;
postmarket surveillance in accordance (b) Signed agreements from each of
with your approved plan even if you no your investigators, if your surveillance
longer market the device. You may re- plan uses investigators, stating the
quest that we allow you to terminate commitment to conduct the surveil-
postmarket surveillance or modify lance in accordance with the approved
your postmarket surveillance because plan, any applicable FDA regulations,
you no longer market the device. We and any conditions of approval for your
will make these decisions on a case-by- plan, such as reporting requirements;
case basis, and you must continue to (c) Your approved postmarket sur-
conduct the postmarket surveillance veillance plan, with documentation of
unless we notify you that you may stop the date and reason for any deviation
your surveillance study. from the plan;
(d) All data collected and analyses
Subpart F—Waivers and conducted in support of your
Exemptions postmarket surveillance plan; and
(e) Any other records that we require
§ 822.29 May I request a waiver of a to be maintained by regulation or by
specific requirement of this part?
order, such as copies of signed consent
You may request that we waive any documents, evidence of Institutional
specific requirement of this part. You Review Board review and approval, etc.
may submit your request, with sup-
porting documentation, separately or § 822.32 What records are the inves-
as a part of your postmarket surveil- tigators in my surveillance plan re-
lance submission to the address in quired to keep?
§ 822.8. Your investigator must keep copies
§ 822.30 May I request exemption from of:
the requirement to conduct (a) All correspondence between inves-
postmarket surveillance? tigators, FDA, the manufacturer, and
You may request exemption from the the designated person, including re-
requirement to conduct postmarket quired reports.
surveillance for your device or any spe- (b) The approved postmarket surveil-
cific model of that device at any time. lance plan, with documentation of the
You must comply with the require- date and reason for any deviation from
ments of this part unless and until we the plan.
grant an exemption for your device. (c) All data collected and analyses
Your request for exemption must ex- conducted at that site for postmarket
plain why you believe we should ex- surveillance.
empt the device or model from (d) Any other records that we require
postmarket surveillance. You should to be maintained by regulation or by
demonstrate why the surveillance order.
198
§ 822.33 How long must we keep the under contract with you must also
records? produce the records and information
You, the designated person, and your upon our request. This information
investigators must keep all records for must be produced within 72 hours of
a period of 2 years after we have ac- the initiation of the inspection. We
cepted your final report, unless we generally will redact information per-
specify otherwise. taining to individual subjects prior to
copying those records, unless there are
§ 822.34 What must I do with the extenuating circumstances.
records if the sponsor of the plan or
an investigator in the plan § 822.37 Under what circumstances
changes? would you inspect records identi-
If the sponsor of the plan or an inves- fying subjects?
tigator in the plan changes, you must We can inspect and copy records
ensure that all records related to the identifying subjects under the same
postmarket surveillance have been circumstances that we can inspect any
transferred to the new sponsor or in-
records relating to postmarket surveil-
vestigator and notify us within 10
lance. We are likely to be interested in
working days of the effective date of
such records if we have reason to be-
the change. You must provide the
name, address, and telephone number lieve that required reports have not
of the new sponsor or investigator, cer- been submitted, or are incomplete, in-
tify that all records have been trans- accurate, false, or misleading.
ferred, and provide the date of transfer.
§ 822.38 What reports must I submit to
§ 822.35 Can you inspect my manufac- you?
turing site or other sites involved in You must submit interim and final
my postmarket surveillance plan? reports as specified in your approved
We can review your postmarket sur- postmarket surveillance plan. In addi-
veillance programs during regularly tion, we may ask you to submit addi-
scheduled inspections, inspections ini- tional information when we believe
tiated to investigate recalls or other that the information is necessary for
similar actions, and inspections initi- the protection of the public health and
ated specifically to review your implementation of the act. We will also
postmarket surveillance plan. We may state the reason or purpose for the re-
also inspect any other person or site quest and how we will use the informa-
involved in your postmarket surveil- tion.
lance, such as investigators or contrac-
tors. Any person authorized to grant
access to a facility must permit au- PART 830—UNIQUE DEVICE
thorized FDA employees to enter and IDENTIFICATION
inspect any facility where the device is
held or where records regarding Subpart A—General Provisions
postmarket surveillance are held.
830.3 Definitions.
§ 822.36 Can you inspect and copy the
records related to my postmarket Subpart B—Requirements for a Unique
surveillance plan? Device Identifier
We may, at a reasonable time and in Sec.
a reasonable manner, inspect and copy 830.10 Incorporation by reference.
any records pertaining to the conduct 830.20 Requirements for a unique device
of postmarket surveillance that are re- identifier.
quired to be kept by this regulation. 830.40 Use and discontinuation of a device
You must be able to produce records identifier.
and information required by this regu- 830.50 Changes that require use of a new de-
lation that are in the possession of oth- vice identifier.
ers under contract with you to conduct 830.60 Relabeling of a device that is required
the postmarket surveillance. Those to bear a unique device identifier.
who have signed agreements or are
199
§ 830.3 21 CFR Ch. I (4–1–23 Edition)
Subpart C—FDA Accreditation of an Research, depending on which Center

Issuing Agency has been assigned lead responsibility
for the device.
830.100 FDA accreditation of an issuing
agency.
Device package means a package that
830.110 Application for accreditation as an contains a fixed quantity of a par-
issuing agency. ticular version or model of a device.
830.120 Responsibilities of an FDA-accred- Expiration date means the date by
ited issuing agency. which the label of a device states the
830.130 Suspension or revocation of the ac- device must or should be used.
creditation of an issuing agency. FDA, we, or us means the Food and
Drug Administration.
Subpart D—FDA as an Issuing Agency
Federal Food, Drug, and Cosmetic Act
830.200 When FDA will act as an issuing means 21 U.S.C. 321 et seq., as amended.
agency. Finished device means any device or
830.210 Eligibility for use of FDA as an accessory to any device that is suitable
issuing agency. for use or capable of functioning.
830.220 Termination of FDA service as an
Global Unique Device Identification
issuing agency.
Database (GUDID) means the database
Subpart E—Global Unique Device that serves as a repository of informa-
Identification Database tion to facilitate the identification of
medical devices through their distribu-
830.300 Devices subject to device identification and use.
tion data submission requirements. Human cell, tissue, or cellular or tissue-
830.310 Information required for unique de-
vice identification.
based product (HCT/P) regulated as a de-
830.320 Submission of unique device identi- vice means an HCT/P as defined in
fication information. § 1271.3(d) of this chapter that does not
830.330 Times for submission of unique de- meet the criteria in § 1271.10(a) and that
vice identification information. is also regulated as a device.
830.340 Voluntary submission of ancillary Issuing agency means an organization
device identification information. accredited by FDA to operate a system
830.350 Correction of information submitted for the issuance of unique device iden-
to the Global Unique Device Identifica-
tion Database.
tifiers.
830.360 Records to be maintained by the la- Label has the meaning set forth in
beler. section 201(k) of the Federal Food,
AUTHORITY: 21 U.S.C. 321, 331, 352, 353, 360,
360d, 360i, 360j, 371. Labeler means:
(1) Any person who causes a label to
SOURCE: 78 FR 58823, Sept. 24, 2013, unless be applied to a device with the intent
otherwise noted.
that the device will be commercially
distributed without any subsequent re-
Subpart A—General Provisions placement or modification of the label;
and
SOURCE: 78 FR 58825, Sept. 24, 2013, unless (2) Any person who causes the label
otherwise noted. of a device to be replaced or modified
with the intent that the device will be
§ 830.3 Definitions. commercially distributed without any
As used in this part: subsequent replacement or modifica-
Automatic identification and data cap- tion of the label, except that the addi-
ture (AIDC) means any technology that tion of the name of, and contact infor-
conveys the unique device identifier or mation for, a person who distributes
the device identifier of a device in a the device, without making any other
form that can be entered into an elec- changes to the label, is not a modifica-
tronic patient record or other com- tion for the purposes of determining
puter system via an automated proc- whether a person is a labeler.
ess. Lot or batch means one finished device
Center Director means the Director of or more that consist of a single type,
the Center for Devices and Radio- model, class, size, composition, or soft-
logical Health or the Director of the ware version that are manufactured
Center for Biologics Evaluation and under essentially the same conditions
200
and that are intended to have uniform this section, the Food and Drug Admin-
characteristics and quality within istration must publish notice of change
specified limits. in the FEDERAL REGISTER and the ma-
Shipping container means a container terial must be available to the public.
used during the shipment or transpor- All approved material is available for
tation of devices, and whose contents inspection at the Division of Dockets
may vary from one shipment to an- Management (HFA–305), Food and Drug
other. Administration, 5630 Fishers Lane, rm.
Small business means a medical device
1061, Rockville, MD 20852, 301–827–6860,
manufacturer with 500 or fewer em-
and is available from the source listed
ployees, or a medical device relabeler
or repackager with 100 or fewer em- in paragraph (b) of this section. Copies
ployees. are also available for purchase from
Specification means any requirement the American National Standards In-
with which a device must conform. stitute (ANSI), mailing address: ANSI,
Unique device identifier (UDI) means Attn: Customer Service Department, 25
an identifier that adequately identifies West 43rd St., 4th floor, New York, NY
a device through its distribution and 10036, phone: 212–642–4980, and may be
use by meeting the requirements of ordered online at http://
§ 830.20. A UDI is composed of: webstore.ansi.org/. The material is also
(1) A device identifier—a mandatory, available for inspection at the National
fixed portion of a UDI that identifies Archives and Records Administration
the specific version or model of a de- (NARA). For information on the avail-
vice and the labeler of that device; and ability of this material at NARA, call
(2) A production identifier—a condi- 202–741–6030 or go to: http://
tional, variable portion of a UDI that www.archives.gov/federal_register/
identifies one or more of the following code_of_federal_regulations/
when included on the label of the de- ibr_locations.html.
vice:
(b) International Organization for
(i) The lot or batch within which a
Standardization (ISO), mailing address:
device was manufactured;
(ii) The serial number of a specific ISO, Attn: ISO Central Secretariat, 1,
device; ch. de la Voie-Creuse, Case postale 56,
(iii) The expiration date of a specific CH–1211 Geneva 20, Switzerland, phone
device; (dialing from the United States): 011–
(iv) The date a specific device was 41–22–749–0111, and may be ordered on-
manufactured. line at http://www.standardsinfo.net.
(v) For an HCT/P regulated as a de- (1) ISO/IEC 646:1991(E), Information
vice, the distinct identification code technology—ISO 7-bit coded character
required by § 1271.290(c) of this chapter. set for information interchange (third
Universal product code (UPC) means edition; December 15, 1991), into
the product identifier used to identify §§ 830.20(c) and 830.100(b);
an item sold at retail in the United (2) ISO/IEC 15459–2:2006(E), Informa-
States. tion technology—Unique identifiers—
Version or model means all devices Part 2: Registration procedures (second
that have specifications, performance, edition; March 1, 2006), into §§ 830.20(b)
size, and composition, within limits set
and 830.100(b);
by the labeler.
(3) ISO/IEC 15459–4:2008(E), Informa-
tion technology—Unique identifiers—
Subpart B—Requirements for a Part 4: Individual items (second edi-
Unique Device Identifier tion; July 15, 2008), into §§ 830.20(b) and
§ 830.10 Incorporation by reference. 830.100(b);
(4) ISO/IEC 15459–6:2007(E), Informa-
(a) Certain material is incorporated
tion technology—Unique identifiers—
by reference into this part with the ap-
Part 6: Unique identifier for product
proval of the Director of the Federal
groupings (first edition; June 15, 2007),
Register in accordance with 5 U.S.C.

552(a) and 1 CFR part 51. To enforce into §§ 830.20(b) and 830.100(b).
any edition other than that specified in
201
§ 830.20 21 CFR Ch. I (4–1–23 Edition)
§ 830.20 Requirements for a unique de- model, you must assign a new device
vice identifier. identifier to the new version or model.
A unique device identifier (UDI) (b) Whenever you create a new device
must: package, you must assign a new device
(a) Be issued under a system operated identifier to the new device package.
by FDA or an FDA-accredited issuing [78 FR 58825, Sept. 24, 2013]
agency;
(b) Conform to each of the following § 830.60 Relabeling of a device that is
international standards: required to bear a unique device
(1) ISO/IEC 15459–2, which is incor- identifier.
porated by reference at § 830.10; If you relabel a device that is re-
(2) ISO/IEC 15459–4, which is incor- quired to bear a unique device identi-
porated by reference at § 830.10; and fier (UDI), you must:
(3) ISO/IEC 15459–6, which is incor- (a) Assign a new device identifier to
porated by reference at § 830.10. the device, and
(c) Use only characters and numbers (b) Keep a record showing the rela-
from the invariant character set of tionship of the prior device identifier
ISO/IEC 646, which is incorporated by to your new device identifier.
reference at § 830.10. [78 FR 58825, Sept. 24, 2013]
[78 FR 58825, Sept. 24, 2013]
Subpart C—FDA Accreditation of
§ 830.40 Use and discontinuation of a
device identifier. an Issuing Agency
(a) Only one device identifier from § 830.100 FDA accreditation of an
any particular system for the issuance issuing agency.
of unique device identifiers (UDIs) may (a) Eligibility. A private organization
be used to identify a particular version may apply for accreditation as an
or model of a device. A particular issuing agency.
version or model may be identified by (b) Accreditation criteria. FDA may ac-
UDIs from two or more systems for the credit an organization as an issuing
issuance of UDIs. agency, if the system it will operate:
(b) A device identifier shall be used (1) Will employ unique device identi-
to identify only one version or model. fiers (UDIs) that meet the require-
(c) In the event that a version or ments of this part to adequately iden-
model of a device is discontinued, its tify a device through its distribution
device identifier may not be reassigned and use;
to another device. If a discontinued (2) Conforms to each of the following
version or model is re-introduced and international standards:
no changes have been made that would (i) ISO/IEC 15459–2, which is incor-
require the use of a new device identi- porated by reference at § 830.10;
fier, the device identifier that was pre- (ii) ISO/IEC 15459–4, which is incor-
viously in use may be used to identify porated by reference at § 830.10;
the device.
(iii) ISO/IEC 15459–6, which is incor-
(d) In the event that an issuing agen- porated by reference at § 830.10.
cy relinquishes or does not renew its
(3) Uses only characters and numbers
accreditation, you may continue to use
from the invariant character set of
a previously issued UDI until such time
ISO/IEC 646, which is incorporated by
as § 830.50 requires you to assign a new
reference at § 830.10.
device identifier.
(4) Will be available to all users ac-
[78 FR 58825, Sept. 24, 2013] cording to a single set of consistent,
fair, and reasonable terms and condi-
§ 830.50 Changes that require use of a tions.
new device identifier. (5) Will protect against conflicts of
(a) Whenever you make a change to a interest between the issuing agency
device that is required to bear a unique (and its officers, employees, and other
device identifier (UDI) on its label, and agents) and labelers (and their officers,
the change results in a new version or employees, and other agents) seeking
202
to use UDIs that may impede the appli- the applicant’s UDI system, including
cant’s ability to independently operate any appeals process.
a fair and neutral identifier system. (v) Description of the applicant’s
electronic data management system
§ 830.110 Application for accreditation with respect to its review and decision
as an issuing agency. processes and the applicant’s ability to
(a) Application for initial accreditation. provide electronic data in a format
(1) An applicant seeking initial FDA compatible with FDA data systems;
accreditation as an issuing agency (vi) Fee schedules, if any, together
shall notify FDA of its desire to be ac- with an explanation of any fee waivers
credited by sending a notification by or reductions that are available;
email to: [email protected], (vii) Detailed information regarding
or by correspondence to: UDI Regu- any financial or other relationship be-
latory Policy Support, Center for De- tween the applicant and any labeler(s)
vices and Radiological Health, Food or governmental entity(ies); and
and Drug Administration, 10903 New (viii) Other information required by
Hampshire Ave., Bldg. 32, Rm. 3293, Sil- FDA to clarify the application for ac-
ver Spring, MD 20993–0002. creditation.
(2) FDA will provide the applicant (b) Application for renewal of accredita-
with additional information to aid in tion. An accredited issuing agency that
submission of an application for ap- intends to continue to serve as an
proval as an issuing agency, together issuing agency beyond its current term
with an email address for submission of shall apply to FDA for renewal or no-
an application. tify FDA of its plans not to apply for
(3) The applicant shall furnish to renewal in accordance with the fol-
FDA, via email to the email address lowing procedures and schedule:
provided in paragraph (a)(1) of this sec- (1) At least 9 months before the date
tion, an application containing the fol- of expiration of its accreditation, an
lowing information, materials, and issuing agency shall inform FDA, at
supporting documentation: the address given in paragraph (a)(1) of
this section, of its intent to seek re-
(i) Name, address, and phone number
newal.
of the applicant;
(2) FDA will notify the issuing agen-
(ii) Detailed descriptions of any
cy of the relevant information, mate-
standards or criteria the applicant will
rials, and supporting documentation
apply to participating labelers;
that we will require the issuing agency
(iii) A detailed description of the to submit as part of the renewal proce-
guidelines that govern assignment of a dure. We will tailor these requirements
unique device identifier (UDI) to a de- to reflect our experience with the
vice; issuing agency during the current and
(iv) A detailed description of the re- any prior period of accreditation. We
view and decisionmaking process the will limit our request to the types of
applicant will apply when determining the information required by paragraph
whether a particular labeler may use (a)(3) of this section, and we will re-
the applicant’s UDI system, including: quire less information if experience
(A) Copies of the application forms, shows that we need only a subset of
guidelines, instructions, and other ma- that information.
terials the applicant will send to med- (3) At least 6 months before the date
ical device labelers who wish to use the of expiration of its accreditation, an
applicant’s unique device identification issuing agency shall furnish to FDA, at
system; the email address we provide, a copy of
(B) Policies and procedures for noti- a renewal application containing the
fying a labeler of deficiencies in its use information, materials, and supporting
of UDIs; documentation requested by FDA in
(C) Procedures for monitoring a la- accordance with paragraph (b)(2) of
beler’s correction of deficiencies in its this section.
use of UDIs; (4) Any issuing agency that does not

(D) Policies and procedures for sus- plan to renew its accreditation shall so
pending or revoking a labeler’s use of notify FDA at the address given in
203
§ 830.120 21 CFR Ch. I (4–1–23 Edition)
paragraph (a)(1) of this section at least and duties before expiration of the cur-
9 months before the expiration of the rent term of accreditation, shall notify
issuing agency’s term of accreditation all labelers that are using the issuing
and shall include a description of its agency’s UDI system, in a manner and
plans for allowing continued use of time period approved by FDA, of the
UDIs issued prior to the expiration of date that the issuing agency will cease
the current term of accreditation. to serve as an FDA-accredited issuing
(c) FDA action on an application for agency.
initial or renewal accreditation. (1) FDA (f) Term of accreditation. The initial
will conduct a review and evaluation to term of accreditation for an issuing
determine whether the applicant meets agency shall be for a period of 3 years.
the requirements of this subpart and An issuing agency’s term of accredita-
whether the UDI system proposed by tion may be periodically renewed for a
the applicant will meet the require- period of 7 years.
ments of this subpart. [78 FR 58825, Sept. 24, 2013, as amended at 81
(2) Within 60 days of receipt of an ap- FR 11429, Mar. 4, 2016; 85 FR 18443, Apr. 2,
plication for accreditation, FDA will 2020]
notify the applicant of any deficiencies
in its application and will request cor- § 830.120 Responsibilities of an FDA-
rection of those deficiencies within 60 accredited issuing agency.
days. The applicant may request an ex- To maintain its accreditation, an
tension if it needs additional time to issuing agency must:
correct deficiencies in its application. (a) Operate a system for assignment
If the deficiencies are not resolved to of unique device identifiers (UDIs) that
FDA’s satisfaction within the specified meets the requirements of § 830.20;
time period, the application for accred- (b) Make available information con-
itation as an issuing agency may be de- cerning its system for the assignment
nied. of UDIs;
(3) FDA shall notify the applicant (c) Maintain a list of labelers that
whether the application for accredita- use its system for the assignment of
tion has been granted or denied. That UDIs and provide FDA a copy of such
notification shall list any conditions of list in electronic form by December 31
approval or state the reasons for de- of each year;
nial. (d) Upon request, provide FDA with
(4) If FDA denies an application, we information concerning a labeler that
will advise the applicant of the cir- is employing the issuing agency’s sys-
cumstances under which a denied appli- tem for assignment of UDIs; and
cation may be resubmitted. (e) Remain in compliance with the
(5) If FDA does not reach a final deci- eligibility and accreditation criteria
sion on a renewal application before set forth in § 830.100.
the expiration of an issuing agency’s
current accreditation, the approval § 830.130 Suspension or revocation of
will be deemed extended until FDA the accreditation of an issuing
reaches a final decision on the applica- agency.
tion. FDA may suspend or revoke the ac-
(d) Relinquishment of accreditation. If creditation of an issuing agency if FDA
an issuing agency decides to relinquish finds, after providing the issuing agen-
its accreditation before expiration of cy with notice and opportunity for an
the current term of accreditation, it informal hearing in accordance with
shall submit a letter of such intent to part 16 of this chapter, that the issuing
FDA, at the address provided in para- agency or any officer, employee, or
graph (a)(1) of this section, at least 9 other agent of the issuing agency:
months before relinquishing its accred- (a) Has been guilty of misrepresenta-
itation. tion or failure to disclose required in-
(e) Notice of termination of accredita- formation in obtaining accreditation;
tion. An issuing agency that does not (b) Has failed to fulfill the respon-
apply for renewal of its accreditation, sibilities outlined in § 830.120;

is denied renewal of accreditation by (c) Has failed to protect against con-
FDA, or relinquishes its accreditation flicts of interest that may impede the
204
issuing agency’s ability to independ- (b) If FDA has ended our services as
ently operate a fair and neutral identi- an issuing agency, a labeler may con-
fier system; tinue to use a device identifier as-
(d) In the operation of the issuing signed under FDA’s unique device iden-
agency, has engaged in any anti- tification system until such time as
competitive activity to restrain trade; § 830.50 requires the use of a new device
or identifier.
(e) Has violated or aided and abetted
in the violation of any regulation Subpart E—Global Unique Device
issued under section 510(e) or section Identification Database
519(f) of the Federal Food, Drug, and
Cosmetic Act.
SOURCE: 78 FR 58826, Sept. 24, 2013, unless
otherwise noted.
Subpart D—FDA as an Issuing
Agency § 830.300 Devices subject to device
identification data submission re-
quirements.
SOURCE: 78 FR 58826, Sept. 24, 2013, unless
otherwise noted. (a) In general. The labeler of a device
must provide the information required
§ 830.200 When FDA will act as an by this subpart for each version or
issuing agency. model required to bear a unique device
(a) During any period where there is identifier (UDI).
no accredited issuing agency, FDA will (b) Voluntary submission of informa-
act as an issuing agency. tion. If a labeler voluntarily includes a
(b) If FDA determines that a signifi- UDI on the label of a device under
cant number of small businesses would § 801.40, the labeler may also volun-
be substantially and adversely affected tarily submit information concerning
by the fees required by all accredited that device under this part.
issuing agencies, FDA will act as an (c) Exclusions. FDA may reject or re-
issuing agency. move any device identification data
(c) FDA may, in its discretion, act as where:
an issuing agency if we determine it is (1) The device identifier submitted
necessary for us to do so to ensure the does not conform to § 830.20;
continuity or the effectiveness of the (2) The information concerns a device
system for the identification of med- that is neither manufactured in the
ical devices. United States nor in interstate com-
(d) FDA may, in its discretion, act as merce in the United States,
an issuing agency if we determine it is (3) The information concerns a prod-
appropriate for us to do so in order to uct that FDA determines is not a de-
facilitate or implement an alternative vice or a combination product that in-
granted under § 801.55 of this chapter. cludes a device constituent part,
(4) The information concerns a device
§ 830.210 Eligibility for use of FDA as or a combination product that re-
an issuing agency. quires, but does not have, FDA pre-
When FDA acts as an issuing agency, market approval, licensure, or clear-
any labeler will be permitted to use ance;
FDA’s unique device identification sys- (5) A device that FDA has banned
tem, regardless of whether the labeler under section 516 of the Federal Food,
is considered a small business. Drug, and Cosmetic Act; or
(6) FDA has suspended the accredita-
§ 830.220 Termination of FDA service tion of the issuing agency that oper-
as an issuing agency. ates the system used by the labeler.
(a) FDA may end our services as an
issuing agency if we determine that the § 830.310 Information required for
conditions that prompted us to act no unique device identification.
longer exist and that ending our serv- The contact for device identification
ices would not be likely to lead to a redesignated under § 830.320(a) shall pro-
turn of the conditions that prompted vide FDA with the following informa-
us to act. tion concerning each version or model
205
§ 830.320 21 CFR Ch. I (4–1–23 Edition)
of a device required to bear a unique version or model, together with the

device identifier (UDI) on its label: unit of measure, as it appears on the
(a) Concerning the labeler: label of the device;
(1) The name of the labeler; (10) The type of production identi-
(2) A telephone number or email ad- fiers that appear on the label of the de-
dress that will allow FDA to commu- vice;
nicate with the contact for device iden- (11) The FDA premarket submission
tification designated under § 830.320(a); number of a cleared or approved device,
and or a statement that FDA has by regula-
(3) The name of each issuing agency tion exempted the device from pre-
whose system is used by the labeler to market notification;
assign UDIs used by the labeler. (12) The FDA listing number assigned
(b) Concerning each version or model of to the device;
a device with a UDI on its label: (13) The Global Medical Device No-
(1) The device identifier portion of menclature (GMDN) term or code for
the UDI assigned to the version or the device;
model; (14) The total number of individual
(2) When reporting a substitution of a devices contained in the device pack-
new device identifier that will be used age.
in lieu of a previously reported identi-
fier, the device identifier that was pre- § 830.320 Submission of unique device
viously assigned to the version or identification information.
model; (a) Designation of contact for device
(3) If § 801.45 of this chapter requires identification. Each labeler must des-
the device to bear a UDI as a perma- ignate an individual to serve as the
nent marking on the device itself, ei- point of contact with FDA on matters
ther: relating to the identification of med-
(i) A statement that the device iden- ical devices marketed by the labeler.
tifier that appears as a permanent The contact for device information is
marking on the device is identical to responsible for ensuring FDA is pro-
that reported under paragraph (b)(1) of vided with all information required by
this section, or this part. The contact for device infor-
(ii) The device identifier portion of mation may authorize an issuing agen-
the UDI that appears as a permanent cy or any other person to provide infor-
marking on the device; mation to FDA on behalf of the labeler.
(4) The proprietary, trade, or brand (b) Information shall be submitted via
name of the device as it appears on the electronic means. All information re-
label of the device; quired by this subpart shall be sub-
(5) Any version or model number or mitted electronically to FDA’s Global
similar reference that appears on the Unique Device Identification Database
label of the device; (GUDID) in a format that we can proc-
(6) If the device is labeled as sterile, ess, review, and archive, unless the la-
a statement to that effect; beler has obtained a waiver from elec-
(7) If the device is labeled as con- tronic submission of unique device
taining natural rubber latex that con- identifier (UDI) data.
tacts humans, or is labeled as having (c) Waiver from electronic submission.
packaging containing natural rubber (1) A labeler may request a waiver from
latex that contacts humans, as de- electronic submission of UDI data by
scribed by §§ 801.437(b)(1), 801.437(b)(3), submitting a letter addressed to the
and 801.437(f) of this chapter, a state- appropriate Center Director explaining
ment to that effect; why electronic submission is not tech-
(8) Whether a patient may be safely nologically feasible; send the request
exposed to magnetic resonance imag- by email to: [email protected], or by cor-
ing, nuclear magnetic resonance imag- respondence to: UDI Regulatory Policy
ing, or magnetic resonance tomog- Support, Center for Devices and Radio-
raphy while using the device, or while logical Health, Food and Drug Admin-
the device is implanted in patient. istration, 10903 New Hampshire Ave.,

(9) If the device is available in more Bldg. 32, Rm. 3293, Silver Spring, MD
than one size, the size of the particular 20993–0002.
206
(2) If the establishment where the la- of ancillary information that may be
beler is located has obtained a waiver submitted to the GUDID.
from electronic submission of registra- (c) FDA may periodically change the
tion and listing information under sec- types of ancillary information that
tion 510(p) of the Federal Food, Drug, may be submitted to the GUDID. We
and Cosmetic Act, the labeler is will announce any change on the FDA
deemed to have a waiver from elec- Web site at http://www.fda.gov/udi/ at
tronic submission of UDI data. least 60 days before making the change.
(3) A labeler that has a waiver from
electronic submission of UDI data must § 830.350 Correction of information
send a letter containing all of the in- submitted to the Global Unique De-
formation required by § 830.310, as well vice Identification Database.
as any ancillary information permitted (a) If FDA becomes aware that any
to be submitted under § 830.340 that the information submitted to the Global
labeler wishes to submit, within the Unique Device Identification Database
time permitted by § 830.330, addressed (GUDID) appears to be incorrect or po-
to: UDI Regulatory Policy Support, tentially misleading, we may notify
Center for Devices and Radiological the labeler of the specific information
Health, Food and Drug Administration, that appears to be incorrect, and re-
10903 New Hampshire Ave., Bldg. 32, quest that the labeler provide cor-
Rm. 3293, Silver Spring, MD 20993–0002. rected information or explain why the
[78 FR 58826, Sept. 24, 2013, as amended at 85 information is correct. The labeler
FR 18443, Apr. 2, 2020] must provide corrected information or
provide a satisfactory explanation of
§ 830.330 Times for submission of why the information is correct within
unique device identification infor- 30 days of receipt of FDA’s notifica-
mation.
tion.
(a) The labeler shall submit to FDA (b) If the labeler does not respond to
the information required by § 830.310 no FDA’s notification within 30 days of re-
later than the date the label of the de- ceipt, or if FDA determines, at any
vice must bear a unique device identi- time, that any information in the
fier under § 801.20 of this chapter. GUDID is incorrect or could be mis-
(b) The labeler of a device shall sub- leading, we may delete or correct the
mit to FDA an update to the informa- information. Any action taken by FDA
tion required by § 830.310 whenever the under this paragraph does not relieve
information changes. The updated in- the labeler of its responsibility under
formation must be submitted no later paragraph (a) of this section to provide
than the date a device is first labeled
corrected information or an expla-
with the changed information. If the
nation of why the information pre-
information does not appear on the
viously submitted is correct.
label of a device, the updated informa-
tion must be submitted within 10 busi- § 830.360 Records to be maintained by
ness days of the change. the labeler.
§ 830.340 Voluntary submission of an- (a) Each labeler shall retain, and sub-
cillary device identification infor- mit to FDA upon specific request,
mation. records showing all unique device iden-
(a) You may not submit any informa- tifiers (UDIs) used to identify devices
tion to the Global Unique Device Iden- that must bear a UDI on their label,
tification Database (GUDID) other and the particular version or model as-
than that specified by § 830.310, except sociated with each device identifier.
where FDA acts to permit the submis- These records must be retained for 3
sion of specified additional types of in- years from the date the labeler ceases
formation, termed ancillary informa- to market the version or model.
tion. (b) Compliance with this section does
(b) FDA will provide information not relieve the labeler of the need to
through the FDA Web site at http:// comply with recordkeeping require-
www.fda.gov/udi/ concerning the types ments of any other FDA regulation.
207
PART 860—MEDICAL DEVICE SOURCE: 43 FR 32993, July 28, 1978, unless

otherwise noted.
CLASSIFICATION PROCEDURES
EDITORIAL NOTE: Nomenclature changes to
Subpart A—General part 860 appear at 73 FR 35341, June 23, 2008
and at 86 FR 54846, Oct. 5, 2021.
Sec.
860.1 Scope. Subpart A—General
860.3 Definitions.
860.5 Confidentiality and use of data and in- § 860.1 Scope.
formation submitted in connection with
classification and reclassification. (a) This part implements sections 513,
860.7 Determination of safety and effective- 514(b), 515(b), and 520(l) of the Federal
ness. Food, Drug, and Cosmetic Act with re-
860.10 Implants and life-supporting or life- spect to the classification and reclassi-
sustaining devices. fication of devices intended for human
860.15 Exemptions from sections 510, 519, use.
and 520(f) of the Federal Food, Drug, and
Cosmetic Act.
(b) This part prescribes the criteria
and procedures to be used by advisory
Subpart B—Classification committees, including classification
panels, where applicable, in making
860.84 Classification procedures for their recommendations, and by the
‘‘preamendments devices.’’ Commissioner in making the Commis-
860.90 Consultation with panels. sioner’s determinations regarding the
class of regulatory control (class I,
Subpart C—Reclassification
class II, or class III) appropriate for
860.120 General. particular devices. Supplementing the
860.123 Reclassification petition: Content general Food and Drug Administration
and form. procedures governing advisory commit-
860.125 Consultation with panels. tees (part 14 of this chapter), this part
860.130 General procedures under section also provides procedures for manufac-
513(e) of the Federal Food, Drug, and Cos-
turers, importers, and other interested
metic Act.
860.132 Procedures when the Commissioner
persons to participate in proceedings to
initiates a performance standard or pre- classify and reclassify devices. This
market approval proceeding under sec- part also describes the type of data re-
tion 514(b) or 515(b) of the Federal Food, quired for determination of the safety
Drug, and Cosmetic Act. and effectiveness of a device, and the
860.133 Procedures when the Commissioner circumstances under which informa-
initiates a proceeding to require pre- tion submitted to advisory commit-
market approval under section 515(b) of tees, including classification panels, or
the Federal Food, Drug, and Cosmetic
Act.
to the Commissioner in connection
860.134 Procedures for reclassification of with classification and reclassification
‘‘postamendments devices’’ under section proceedings, will be available to the
513(f)(3) of the Federal Food, Drug, and public.
Cosmetic Act.
860.136 Procedures for transitional products
FR 54846, Oct. 5, 2021]
under section 520(l) of the Federal Food,
§ 860.3 Definitions.
Subpart D—De Novo Classification For the purposes of this part:
Class means one of the three cat-
860.200 Purpose and applicability.
egories of regulatory control for med-
860.210 De Novo request format.
860.220 De Novo request content. ical devices, defined as follows:
860.230 Accepting a De Novo request. Class I means the class of devices
860.240 Procedures for review of a De Novo that are subject only to the general
request. controls authorized by or under sec-
860.250 Withdrawal of a De Novo request. tions 501 (adulteration), 502 (mis-
860.260 Granting or declining a De Novo re- branding), 510 (registration), 516
quest. (banned devices), 518 (notification and

AUTHORITY: 21 U.S.C. 321(h), 353(g), 360c, other remedies), 519 (records and re-
360d, 360e, 360i, 360j, 371, 374. ports), and 520 (general provisions) of
208
the Federal Food, Drug, and Cosmetic trols, would provide such assurance,
Act. A device is in class I if: and if, in addition, the device is life-
(1) General controls are sufficient to supporting or life-sustaining, or for a
provide reasonable assurance of the use which is of substantial importance
safety and effectiveness of the device, in preventing impairment of human
or health, or if the device presents a po-
(2) There is insufficient information tential unreasonable risk of illness or
from which to determine that general injury.
controls are sufficient to provide rea- Classification panel means one of the
sonable assurance of the safety and ef- several advisory committees estab-
fectiveness of the device or to establish lished by the Commissioner under sec-
special controls to provide such assur- tion 513 of the Federal Food, Drug, and
ance, but the device is not life-sup-
Cosmetic Act and part 14 of this chap-
porting or life-sustaining, or for a use
ter for the purpose of making rec-
which is of substantial importance in
ommendations to the Commissioner on
preventing impairment of human
the classification and reclassification
health, and which does not present a
potential unreasonable risk of illness of devices and for other purposes pre-
or injury. scribed by the Federal Food, Drug, and
Class II means the class of devices Cosmetic Act or by the Commissioner.
that is or eventually will be subject to Classification regulation means a sec-
special controls. A device is in class II tion under parts 862 through 892 of this
if general controls alone are insuffi- chapter that contains the identifica-
cient to provide reasonable assurance tion (general description and intended
of its safety and effectiveness and there use) and classification (class I, II or III)
is sufficient information to establish of a single device type or more than
special controls, including the promul- one related device type(s).
gation of performance standards, Commissioner means the Commis-
postmarket surveillance, patient reg- sioner of Food and Drugs, Food and
istries, development and dissemination Drug Administration, United States
of guidelines (including guidelines for Department of Health and Human
the submission of clinical data in pre- Services, or the Commissioner’s des-
market notification submissions in ac- ignee.
cordance with section 510(k) of the Fed- De Novo request means any submis-
eral Food, Drug, and Cosmetic Act), sion under section 513(f)(2) of the Fed-
recommendations, and other appro- eral Food, Drug, and Cosmetic Act for
priate actions as the Commissioner a medical device, requesting classifica-
deems necessary to provide such assur- tion into class I or class II, including
ance. For a device that is purported or all information submitted with or in-
represented to be for use in supporting corporated by reference therein.
or sustaining human life, the Commis-
FDA means the Food and Drug Ad-
sioner shall examine and identify the
ministration.
special controls, if any, which are nec-
essary to provide adequate assurance of General controls mean the controls
safety and effectiveness, and describe authorized by or under sections 501
how such controls provide such assur- (adulteration), 502 (misbranding), 510
ance. (registration, listing, and premarket
Class III means the class of devices notification), 516 (banned devices), 518
for which premarket approval is or will (notification and other remedies), 519
be required in accordance with section (records, reports, and unique device
515 of the Federal Food, Drug, and Cos- identification), and 520 (general provi-
metic Act. A device is in class III if in- sions) of the Federal Food, Drug, and
sufficient information exists to deter- Cosmetic Act.
mine that general controls are suffi- Generic type of device means a group-
cient to provide reasonable assurance ing of devices that do not differ signifi-
of its safety and effectiveness, or that cantly in purpose, design, materials,
application of special controls de- energy source, function, or any other

scribed in the definition of ‘‘Class II’’ in feature related to safety and effective-
this section in addition to general con- ness, and for which similar regulatory
209
§ 860.5 21 CFR Ch. I (4–1–23 Edition)
controls are sufficient to provide rea- this section, this provision does not
sonable assurance of safety and effec- apply to data and information exempt
tiveness. from public disclosure in accordance
Implant means a device that is placed with part 20 of this chapter: Such data
into a surgically or naturally formed and information will be available only
cavity of the human body. A device is in accordance with part 20.
regarded as an implant for the purpose (c)(1) Safety and effectiveness data
of this part only if it is intended to resubmitted to classification panels or to
main implanted continuously for a pe- the Commissioner in connection with
riod of 30 days or more, unless the the classification of a device under
Commissioner determines otherwise to § 860.84, which have not been disclosed
protect human health. previously to the public, as described
Life-supporting or life-sustaining device in § 20.81 of this chapter, shall be re-
means a device that is essential to, or garded as confidential if the device is
that yields information that is essen-
classified in to class III. Because the
tial to, the restoration or continuation
classification of a device under § 860.84
of a bodily function important to the
may be ascertained only upon publica-
continuation of human life.
tion of a final regulation, all safety and
Petition means a submission seeking
effectiveness data that have not been
reclassification of a device in accord-
disclosed previously are not available
ance with § 860.123.
Special controls mean the controls for public disclosure unless and until
necessary to provide reasonable assur- the device is classified into class I or
ance of safety and effectiveness for a II, in which case the procedure in para-
generic type of device that is class II. graph (c)(2) of this section applies.
Special controls include performance (2) Thirty days after publication of a
standards, performance testing, final regulation under § 860.84
postmarket surveillance, patient reg- classifying a device into class I or class
istries, development and dissemination II, safety and effectiveness data sub-
of guidelines (including guidelines for mitted for that device that had been
the submission of clinical data in pre- regarded as confidential under para-
market notification submissions in ac- graph (c)(1) of this section will be
cordance with section 510(k) of the Fed- available for public disclosure and
eral Food, Drug, and Cosmetic Act), placed on public display in the office of
recommendations, and other appro- the Division of Dockets Management,
priate actions, as the Commissioner Food and Drug Administration unless,
deems necessary to provide such assur- within that 30-day period, the person
ance. who submitted the data demonstrates
that the data still fall within the ex-
[86 FR 54846, Oct. 5, 2021]
emption for trade secrets and confiden-
§ 860.5 Confidentiality and use of data tial commercial information described
and information submitted in con- in § 20.61 of this chapter. Safety and ef-
nection with classification and re- fectiveness data submitted for a device
classification. that is classified into class III by regu-
(a) This section governs the avail- lation in accordance with § 860.84 will
ability for public disclosure and the use remain confidential and unavailable
by the Commissioner of data and infor- for public disclosure so long as such
mation submitted to classification data have not been disclosed to the
panels or to the Commissioner in con- public as described in § 20.81 of this
nection with the classification or re- chapter.
classification of devices under this (3) Because device classification af-
part. fects generic types of devices, in mak-
(b) In general, data and information ing determinations under § 860.84 con-
submitted to classification panels in cerning the initial classification of a
connection with the classification of device, the classification panels and
devices under § 860.84 will be available the Commissioner may consider safety
immediately for public disclosure upon and effectiveness data developed for
request. However, except as provided another device in the same generic
by the special rules in paragraph (c) of type, regardless of whether such data
210
are regarded currently as confidential the entire contents of the petition will
under paragraph (c)(1) of this section. be available for public disclosure and
(d)(1) The fact of its existence and subject to consideration by classifica-
the contents of a petition for reclassi- tion panels and by the Commissioner in
fication filed in accordance with making a decision on the petition. De-
§ 860.130 or § 860.132 are available for ficient petitions which have not been
public disclosure at the time the peti- corrected within 180 days after notifi-
tion is received by the Food and Drug cation of deficiency will be returned to
Administration. the petitioner and will not be consid-
(2) The fact of the existence of a peti- ered further unless resubmitted.
tion for reclassification filed in accord- (e) The Commissioner may not dis-
ance with § 860.134 or § 860.136 is avail- close, or use as the basis for reclassi-
able for public disclosure at the time fication of a device from class III to
the petition is received by the Food class II, any information reported to or
and Drug Administration. The contents otherwise obtained by the Commis-
of such a petition are not available for sioner under section 513, 514, 515, 516,
public disclosure for the period of time 518, 519, 520(f), 520(g), or 704 of the Fed-
following its receipt (not longer than 30 eral Food, Drug, and Cosmetic Act that
days) during which the petition is re- falls within the exemption described in
viewed for any deficiencies preventing § 20.61 of this chapter for trade secrets
the Commissioner from making a deci- and confidential commercial informa-
sion on it. Once it is determined that tion. The exemption described in § 20.61
the petition contains no deficiencies does not apply to data or information
preventing the Commissioner from contained in a petition for reclassifica-
making a decision on it, the petition tion submitted in accordance with
will be filed with the Division of Dock- § 860.130 or § 860.132, or in a petition sub-
ets Management and its entire con- mitted in accordance with § 860.134 or
tents will be available for public disclo- § 860.136 that has been determined to
sure and subject to consideration by contain no deficiencies that prevent
classification panels and by the Com- the Commissioner from making a deci-
missioner in making a decision on the sion on it. Accordingly, all data and in-
petition. If, during this 30-day period of formation contained in such petitions
time, the petition is found to contain may be disclosed by the Commissioner
deficiencies that prevent the Commis- and used as the basis for reclassifica-
sioner from making a decision on it, tion of a device from class III to class
the petitioner will be so notified and II.
afforded an opportunity to correct the (f) For purposes of this section, safe-
deficiencies. ty and effectiveness data include data
Thirty days after notice to the peti- and results derived from all studies and
tioner of deficiencies in the petition, tests of a device on animals and hu-
the contents of the petition will be mans and from all studies and tests of
available for public disclosure unless, the device itself intended to establish
within that 30 days, the petitioner sub- or determine its safety and effective-
mits supplemental material intended ness.
to correct the deficiencies in the peti- (g) Confidentiality of data and infor-
tion. The Commissioner, in the Com- mation in a De Novo file is as follows:
missioner’s discretion, may allow with- (1) A ‘‘De Novo file’’ includes all data
drawal of a deficient petition during and information from the requester
the 30-day period provided for cor- submitted with or incorporated by ref-
recting deficiencies. Any supplemental erence in the De Novo request, any De
material submitted by the petitioner, Novo supplement, or any other related
together with the material in the origi- submission relevant to the administra-
nal petition, is considered as a new pe- tive file, as defined in § 10.3(a) of this
tition. The new petition is reviewed for chapter. Any record in the De Novo file
deficiencies in the same manner as the will be available for public disclosure
original petition, and the same proce- in accordance with the provisions of
dures for notification and correction of this section and part 20 of this chapter.
deficiencies are followed. Once the pe- (2) The existence of a De Novo file
titioner has corrected the deficiencies, may not be disclosed by FDA before an
211
§ 860.7 21 CFR Ch. I (4–1–23 Edition)
order granting the De Novo request is and effectiveness of a device, the agen-
issued unless it previously has been cy relies upon only valid scientific evi-
publicly disclosed or acknowledged by dence to determine whether there is
the De Novo requester. reasonable assurance that the device is
(3) Before an order granting the De safe and effective. After considering
Novo request is issued, data or infor- the nature of the device and the rules
mation contained in the De Novo file is in this section, the Commissioner will
not available for public disclosure, ex- determine whether the evidence sub-
cept to the extent the existence of the mitted or otherwise available to the
De Novo file is disclosable under para- Commissioner is valid scientific evi-
graph (g)(2) of this section and such dence for the purpose of determining
data or information has been publicly the safety or effectiveness of a par-
disclosed or acknowledged by the De ticular device and whether the avail-
Novo requester. able evidence, when taken as a whole,
(4) After FDA issues an order grant- is adequate to support a determination
ing a De Novo request, the data and in- that there is reasonable assurance that
formation in the De Novo file that are the device is safe and effective for its
not exempt from release under the conditions of use.
Freedom of Information Act, 5 U.S.C. (2) Valid scientific evidence is evi-
552, are immediately available for pub- dence from well-controlled investiga-
lic disclosure. tions, partially controlled studies,
[43 FR 32993, July 28, 1978, as amended at 86 studies and objective trials without
FR 54847, Oct. 5, 2021] matched controls, well-documented
case histories conducted by qualified
§ 860.7 Determination of safety and ef- experts, and reports of significant
fectiveness. human experience with a marketed de-
(a) The classification panels, in re- vice, from which it can fairly and re-
viewing evidence concerning the safety sponsibly be concluded by qualified ex-
and effectiveness of a device and in pre- perts that there is reasonable assur-
paring advice to the Commissioner, and ance of the safety and effectiveness of
the Commissioner, in making deter- a device under its conditions of use.
minations concerning the safety and The evidence required may vary ac-
effectiveness of a device, will apply the cording to the characteristics of the
rules in this section. device, its conditions of use, the exist-
(b) In determining the safety and ef- ence and adequacy of warnings and
fectiveness of a device for purposes of other restrictions, and the extent of ex-
classification, establishment of special perience with its use. Isolated case re-
controls for class II devices, and pre- ports, random experience, reports lack-
market approval of class III devices, ing sufficient details to permit sci-
the Commissioner and the classifica- entific evaluation, and unsubstantiated
tion panels will consider the following, opinions are not regarded as valid sci-
among other relevant factors: entific evidence to show safety or effec-
(1) The persons for whose use the de- tiveness. Such information may be con-
vice is represented or intended; sidered, however, in identifying a de-
(2) The conditions of use for the device with questionable safety or effec-
vice, including conditions of use pre- tiveness.
scribed, recommended, or suggested in (d)(1) There is reasonable assurance
the labeling or advertising of the de- that a device is safe when it can be de-
vice, and other intended conditions of termined, based upon valid scientific
use; evidence, that the probable benefits to
(3) The probable benefit to health health from use of the device for its in-
from the use of the device weighed tended uses and conditions of use, when
against any probable injury or illness accompanied by adequate directions
from such use; and and warnings against unsafe use, out-
(4) The reliability of the device. weigh any probable risks. The valid sci-
(c)(1) Although the manufacturer entific evidence used to determine the
may submit any form of evidence to safety of a device shall adequately

the Food and Drug Administration in demonstrate the absence of unreason-
an attempt to substantiate the safety able risk of illness or injury associated
212
with the use of the device for its in- (a) Provides adequate assurance that
tended uses and conditions of use. the subjects are suitable for the pur-
(2) Among the types of evidence that poses of the study, provides diagnostic
may be required, when appropriate, to criteria of the condition to be treated
determine that there is reasonable as- or diagnosed, provides confirmatory
surance that a device is safe are inves- laboratory tests where appropriate
tigations using laboratory animals, in- and, in the case of a device to prevent
vestigations involving human subjects, a disease or condition, provides evi-
nonclinical investigations, and analyt- dence of susceptibility and exposure to
ical studies for in vitro diagnostic de- the condition against which prophy-
vices. laxis is desired;
(e)(1) There is reasonable assurance (b) Assigns the subjects to test
that a device is effective when it can be groups, if used, in such a way as to
determined, based upon valid scientific minimize any possible bias;
evidence, that in a significant portion (c) Assures comparability between
of the target population, the use of the test groups and any control groups of
device for its intended uses and condi- pertinent variables such as sex, sever-
tions of use, when accompanied by ade- ity or duration of the disease, and use
quate directions for use and warnings of therapy other than the test device;
against unsafe use, will provide clini- (iii) An explanation of the methods of
cally significant results.
observation and recording of results
(2) The valid scientific evidence used
utilized, including the variables meas-
to determine the effectiveness of a de-
ured, quantitation, assessment of any
vice shall consist principally of well-
subject’s response, and steps taken to
controlled investigations, as defined in
minimize any possible bias of subjects
paragraph (f) of this section, unless the
and observers;
Commissioner authorizes reliance upon
other valid scientific evidence which (iv) A comparison of the results of
the Commissioner has determined is treatment or diagnosis with a control
sufficient evidence from which to de- in such a fashion as to permit quan-
termine the effectiveness of a device, titative evaluation. The precise nature
even in the absence of well-controlled of the control must be specified and an
investigations. The Commissioner may explanation provided of the methods
make such a determination where the employed to minimize any possible
requirement of well-controlled inves- bias of the observers and analysts of
tigations in paragraph (f) of this sec- the data. Level and methods of ‘‘blind-
tion is not reasonably applicable to the ing,’’ if appropriate and used, are to be
device. documented. Generally, four types of
(f) The following principles have been comparisons are recognized:
developed over a period of years and (a) No treatments. Where objective
are recognized by the scientific com- measurements of effectiveness are
munity as the essentials of a well-con- available and placebo effect is neg-
trolled clinical investigation. They ligible, comparison of the objective re-
provide the basis for the Commis- sults in comparable groups of treated
sioner’s determination whether there is and untreated patients;
reasonable assurance that a device is (b) Placebo control. Where there may
effective based upon well-controlled in- be a placebo effect with the use of a de-
vestigations and are also useful in as- vice, comparison of the results of use of
sessing the weight to be given to other the device with an ineffective device
valid scientific evidence permitted used under conditions designed to re-
under this section. semble the conditions of use under in-
(1) The plan or protocol for the study vestigation as far as possible;
and the report of the results of a well- (c) Active treatment control. Where an
controlled investigation shall include effective regimen of therapy may be
the following: used for comparison, e.g., the condition
(i) A clear statement of the objec- being treated is such that the use of a
tives of the study; placebo or the withholding of treat-

(ii) A method of selection of the sub- ment would be inappropriate or con-
jects that: trary to the interest of the patient;
213
§ 860.10 21 CFR Ch. I (4–1–23 Edition)
(d) Historical control. In certain cir- eral Food, Drug, and Cosmetic Act. Ac-
cumstances, such as those involving cordingly, the requirement will state
diseases with high and predictable mor- the reason or purpose for such request;
tality or signs and symptoms of pre- will describe the required report or in-
dictable duration or severity, or in the formation as clearly as possible; will
case of prophylaxis where morbidity is not be imposed on a manufacturer, im-
predictable, the results of use of the de- porter, or distributor of a classified de-
vice may be compared quantitatively vice that has been exempted from such
with prior experience historically de- a requirement in accordance with
rived from the adequately documented § 860.95; will prescribe the time for com-
natural history of the disease or condi- pliance with the requirement; and will
tion in comparable patients or popu- prescribe the form and manner in
lations who received no treatment or which the report or information is to
who followed an established effective be provided.
regimen (therapeutic, diagnostic, pro- (4) Required information that has
phylactic). been submitted previously to the Cen-
(v) A summary of the methods of ter for Devices and Radiological
analysis and an evaluation of the data Health, the Center for Biologics Eval-
derived from the study, including any uation and Research, or the Center for
appropriate statistical methods uti- Drug Evaluation and Research, as ap-
lized. plicable, need not be resubmitted, but
(2) To insure the reliability of the re- may be incorporated by reference.
sults of an investigation, a well-con- [43 FR 32993, July 28, 1978, as amended at 53
trolled investigation shall involve the FR 11253, Apr. 6, 1988; 73 FR 49942, Aug. 25,
use of a test device that is standardized 2008; 83 FR 64454, Dec. 17, 2018]
in its composition or design and per-
formance. § 860.10 Implants and life-supporting
(g)(1) It is the responsibility of each or life-sustaining devices.
manufacturer and importer of a device (a) A classification panel will rec-
to assure that adequate, valid sci- ommend classification into class III of
entific evidence exists, and to furnish any implant or life-supporting or life-
such evidence to the Food and Drug sustaining device unless the panel de-
Administration to provide reasonable termines that such classification is not
assurance that the device is safe and necessary to provide reasonable assur-
effective for its intended uses and con- ance of the safety and effectiveness of
ditions of use. The failure of a manu- the device. If the panel recommends
facturer or importer of a device to classification or reclassification of
present to the Food and Drug Adminis- such a device into a class other than
tration adequate, valid scientific evi- class III, it shall set forth in its rec-
dence showing that there is reasonable ommendation the reasons for so doing
assurance of the safety and effective- and an identification of the risks to
ness of the device, if regulated by gen- health, if any, presented by the device.
eral controls alone, or by general con- In the case of such a device being rec-
trols and special controls, may support ommended for classification or reclas-
a determination that the device be sification into class II, the panel shall
classified into class III. describe the special controls that, in
(2) The Commissioner may require addition to general controls, the panel
that a manufacturer, importer, or dis- believes are necessary to provide rea-
tributor make reports or provide other sonable assurance of safety and effec-
information bearing on the classifica- tiveness of the device and how such
tion of a device and indicating whether controls provide such assurance.
there is reasonable assurance of the (b) The Commissioner will classify an
safety and effectiveness of the device implant or life-supporting or life-sus-
or whether it is adulterated or mis- taining device into class III unless the
branded under the Federal Food, Drug, Commissioner determines that such
and Cosmetic Act. classification is not necessary to pro-
(3) A requirement for a report or vide reasonable assurance of the safety

other information under this paragraph and effectiveness of the device. If the
will comply with section 519 of the Fed- Commissioner proposes to classify or
214
reclassify such a device into a class (c) The Commissioner will grant ex-
other than class III, the regulation or emptions under this section only if the
order effecting such classification or Commissioner determines that the re-
reclassification will be accompanied by quirements from which the device is
a full statement of the reasons for so exempted are not necessary to provide
doing. A statement of the reasons for reasonable assurance of the safety and
not classifying or retaining the device effectiveness of the device.
in class III may be in the form of con- [83 FR 64455, Dec. 17, 2018]
currence with the reasons for the rec-
ommendation of the classification
panel, together with supporting docu- Subpart B—Classification
mentation and data satisfying the re- § 860.84 Classification procedures for
quirements of § 860.7 and an identifica- ‘‘preamendments devices.’’
tion of the risks to health, if any, pre-
sented by the device. In the case of (a) This subpart sets forth the proce-
such a device being classified or reclas- dures for the original classification of
sified into class II, the Commissioner a generic type of device that was in
shall describe the special controls that, commercial distribution before May 28,
in addition to general controls, the 1976. Such a device will be classified by
panel believes are necessary to provide regulation into either class I (general
reasonable assurance of safety and ef- controls), class II (special controls) or
fectiveness of the device and how such class III (premarket approval), depend-
controls provide such assurance. ing upon the level of regulatory control
required to provide reasonable assur-
[83 FR 64455, Dec. 17, 2018] ance of the safety and effectiveness of
the device (§ 860.3(c)). This subpart does
§ 860.15 Exemptions from sections 510, not apply to a device that is classified
519, and 520(f) of the Federal Food,
Drug, and Cosmetic Act. into class III by statute under section
513(f)(1) of the Federal Food, Drug, and
(a) A panel recommendation to the Cosmetic Act because the Food and
Commissioner that a device be classi- Drug Administration has determined
fied or reclassified into class I will in- that the device is not ‘‘substantially
clude a recommendation as to whether equivalent’’ to any device subject to
the device should be exempted from this subpart or under section 520(l)(1) of
some or all of the requirements of one the Federal Food, Drug, and Cosmetic
or more of the following sections of the Act because the device was regarded
Federal Food, Drug, and Cosmetic Act: previously as a new drug. In classifying
Section 510 (registration, product list- a preamendments device to which this
ing, and premarket notification), sec- section applies, the Food and Drug Ad-
tion 519 (records and reports) and sec- ministration will follow the procedures
tion 520(f) (good manufacturing prac- described in paragraphs (b) through (g)
tice requirements of the quality sys- of this section.
tem regulation), and, in the case of a (b) The Commissioner refers the de-
recommendation for classification into vice to the appropriate classification
class II, whether the device should be panel organized and operated in accord-
exempted from the premarket notifica- ance with section 513 (b) and (c) of the
tion requirement under section 510. Federal Food, Drug, and Cosmetic Act
(b) A regulation or an order and part 14 of this chapter.
classifying or reclassifying a device (c) In order to make recommenda-
into class I will specify which require- tions to the Commissioner on the class
ments, if any, of sections 510, 519, and of regulatory control (class I, class II,
520(f) of the Federal Food, Drug, and or class III) appropriate for the device,
Cosmetic Act the device is to be ex- the panel reviews the device for safety
empted from or, in the case of a regula- and effectiveness. In so doing, the
tion or an order classifying or reclassi- panel:
fying a device into class II, whether the (1) Considers the factors set forth in
device is to be exempted from the pre- § 860.7 relating to the determination of
market notification requirement under safety and effectiveness;

section 510, together with the reasons (2) Determines the safety and effec-
for such exemption. tiveness of the device on the basis of
215
§ 860.90 21 CFR Ch. I (4–1–23 Edition)
the types of scientific evidence set risks to health, if any, presented by the
forth in § 860.7; and device, in accordance with § 860.10.
(3) Provides, to the maximum extent (e) A panel recommendation is re-
practicable, an opportunity for inter- garded as preliminary until the Com-
ested persons to submit data and views missioner has reviewed it, discussed it
on the classification of the device in with the panel if appropriate, and pub-
accordance with part 14 of this chapter. lished a proposed regulation classifying
(d) Based upon its review of evidence the device. Preliminary panel rec-
of the safety and effectiveness of the ommendations are filed at Dockets
device, and applying the definition of Management Staff upon receipt and are
each class in § 860.3(c), the panel sub- available to the public at https://
mits to the Commissioner a rec- www.regulations.gov.
ommendation regarding the classifica- (f) The Commissioner publishes the
tion of the device. The recommenda- panel’s recommendation in the FED-
tion will include: ERAL REGISTER, together with a pro-
(1) A summary of the reasons for the posed regulation classifying the device,
recommendation; and other devices of that generic type,
(2) A summary of the data upon and provides interested persons an op-
which the recommendation is based; portunity to submit comments on the
(3) An identification of the risks to recommendation and proposed regula-
health (if any) presented by the device; tion.
(4) In the case of a recommendation (g) The Commissioner reviews the
for classification into class I, a rec- comments and issues a final regulation
ommendation as to whether the device classifying the device and other devices
should be exempted from the require- of that generic type. The regulation
ments of one or more of the following will:
sections of the Federal Food, Drug, and (1) If classifying the device into class
Cosmetic Act: Section 510 (registra- I, prescribe which, if any, of the re-
tion, product listing, and premarket quirements of sections 510, 519, and
notification), section 519 (records and 520(f) of the Federal Food, Drug, and
reports), and section 520(f) (good manu- Cosmetic Act will not apply to the de-
facturing practice requirements of the vice and state the reasons for making
quality system regulation) and, in the the requirements inapplicable, in ac-
case of a recommendation for classi- cordance with § 860.95;
fication into class II, whether the de- (2) If classifying the device into class
vice should be exempted from the pre- II, establish the special controls for the
market notification requirement under device and prescribe whether the pre-
section 510, in accordance with § 860.15; market notification requirement will
(5) In the case of a recommendation apply to the device; and
for classification into class II or class (3) If classifying an implant, or a life-
III, to the extent practicable, a rec- supporting or life-sustaining device,
ommendation for the assignment to comply with § 860.10(b).
the device of a priority for the applica-
tion of a performance standard or a [43 FR 32993, July 28, 1978, as amended at 57
premarket approval requirement, and FR 58404, Dec. 10, 1992; 64 FR 404, Jan. 5, 1999;
in the case of classification into class 83 FR 64455, Dec. 17, 2018]
II, a recommendation on the establish-
§ 860.90 Consultation with panels.
ment of special controls and whether
the device should be exempted from (a) When the Commissioner is re-
premarket notification in accordance quired to consult with a panel con-
with § 860.15; and cerning a classification under § 860.84,
(6) In the case of a recommendation the Commissioner will consult with the
for classification of an implant or a panel in one of the following ways:
life-supporting or life-sustaining device (1) Consultation by telephone with at
into class I or class II, a statement of least a majority of current voting
why premarket approval is not nec- panel members and, when possible,
essary to provide reasonable assurance nonvoting panel members in a tele-

of the safety and effectiveness of the phone or video conference call; or
device and an identification of the (2) Discussion at a panel meeting.
216
(b) The method of consultation cho- (2) Section 513(f)(3) (for a device clas-
sen by the Commissioner will depend sified into class III under section
upon the importance and complexity of 513(f)(1) of the Federal Food, Drug, and
the subject matter involved and the Cosmetic Act); or
time available for action. When time (3) Section 520(l)(2) (for a device clas-
and circumstances permit, the Com- sified into class III under section
missioner will consult with a panel 520(l)(1) of the Federal Food, Drug, and
through discussion at a panel meeting. Cosmetic Act).
[83 FR 64456, Dec. 17, 2018] [43 FR 32993, July 28, 1978, as amended at 57
FR 58404, Dec. 10, 1992; 83 FR 64456, Dec. 17,
2018]
Subpart C—Reclassification
§ 860.123 Reclassification petition:
§ 860.120 General. Content and form.
(a) Sections 513(e) and (f), 514(b), (a) Unless otherwise provided in writ-
515(b), and 520(l) of the Federal Food, ing by the Commissioner, any petition
Drug, and Cosmetic Act provide for re- for reclassification of a device, regard-
classification of a device and prescribe less of the section of the Federal Food,
the procedures to be followed to effect Drug, and Cosmetic Act under which it
reclassification. The purposes of sub- is filed, shall include the following:
part C are to: (1) A specification of the type of de-
(1) Set forth the requirements as to vice for which reclassification is re-
form and content of petitions for requested;
classification; (2) A statement of the action re-
(2) Describe the circumstances in quested by the petitioner, e.g., ‘‘It is
which each of the five statutory reclas- requested that _ device(s) be reclassi-
sification provisions applies; and fied from class III to a class II’’;
(3) A statement of the basis for dis-
(3) Explain the procedure for reclassi-
agreement with the present classifica-
fication prescribed in the five statu-
tion status of the device;
tory reclassification provisions.
(4) A full statement of the reasons,
(b) The criteria for determining the together with supporting data satis-
proper class for a device are set forth fying the requirements of § 860.7, why
in § 860.3(c). The reclassification of any the device should not be classified into
device within a generic type of device its present classification and how the
causes the reclassification of all de- proposed classification will provide
vices within that generic type. Accord- reasonable assurance of the safety and
ingly, a petition for the reclassifica- effectiveness of the device;
tion of a specific device will be consid- (5) Representative data and informa-
ered a petition for reclassification of tion known by the petitioner that are
all devices within the same generic unfavorable to the petitioner’s posi-
type. tion;
(c) Any interested person may submit (6) If the petition is based upon new
a petition for reclassification under information under section 513(e), 514(b),
section 513(e), 514(b), or 515(b) of the or 515(b) of the Federal Food, Drug, and
Federal Food, Drug, and Cosmetic Act. Cosmetic Act, a summary of the new
A manufacturer or importer may sub- information;
mit a petition for reclassification (7) Copies of source documents from
under section 513(f) or 520(l) of the Fed- which new information used to support
eral Food, Drug, and Cosmetic Act. The the petition has been obtained (at-
Commissioner may initiate the reclas- tached as appendices to the petition);
sification of a device under the fol- and
lowing sections of the Federal Food, (8) A financial certification or disclo-
Drug, and Cosmetic Act: sure statement or both as required by
(1) Section 513(e) (for a classified depart 54 of this chapter.
vice other than a device classified into (b) Each petition submitted pursuant
class III under section 513(f)(1) or to this section shall be:

520(l)(1) of the Federal Food, Drug, and (1) For devices regulated by the Cen-
Cosmetic Act); ter for Devices and Radiological
217
§ 860.125 21 CFR Ch. I (4–1–23 Edition)
Health, addressed to the Food and Drug panel members and, when possible,
Administration, Center for Devices and nonvoting panel members in a tele-
Radiological Health, Office of Policy phone or video conference call; or
Staff, 10903 New Hampshire Ave., Bldg. (2) Discussion at a panel meeting.
66, Rm. 5445, Silver Spring, MD 20993– (b) The method of consultation cho-
0002; for devices regulated by the Cen- sen by the Commissioner will depend
ter for Biologics Evaluation and Re- upon the importance and complexity of
search, addressed to the Food and Drug the subject matter involved and the
Administration, Center for Biologics time available for action. When time
Evaluation and Research, Document and circumstances permit, the Com-
Control Center, 10903 New Hampshire missioner will consult with a panel
Ave., Bldg. 71, Rm. G112, Silver Spring, through discussion at a panel meeting.
MD 20993–0002; for devices regulated by (c) The Commissioner will consult
the Center for Drug Evaluation and Re- with a classification panel prior to
search, addressed to the Food and Drug changing the classification of a device
Administration, Center for Drug Eval- in a proceeding under section 513(e) of
uation and Research, Central Docu- the Federal Food, Drug, and Cosmetic
ment Control Room, 5901–B Act and § 860.130 upon the Commis-
Ammendale Rd., Beltsville, MD 20705– sioner’s own initiative or upon petition
1266, as applicable. of an interested person, and in the lat-
(2) Marked clearly with the section of ter case, the Commissioner will dis-
the Federal Food, Drug, and Cosmetic tribute a copy of the petition, or its
Act under which the petition is being relevant portions, to each panel mem-
submitted, i.e., ‘‘513(e),’’ ‘‘513(f)(3),’’ ber.
‘‘514(b),’’ ‘‘515(b),’’ or ‘‘520(l) Petition’’; (d) When a petition is submitted
(3) Bound in a volume or volumes, under § 860.134 for a postamendments,
where necessary; and not substantially equivalent, device, if
(4) Submitted in an original and two the Commissioner chooses to consult
copies. with the panel, the Commissioner will
obtain a recommendation that includes
[43 FR 32993, July 28, 1978, as amended at 49 the information described in § 860.84(d).
FR 14505, Apr. 12, 1984; 53 FR 11253, Apr. 6,
In consulting with a panel about a peti-
1988; 55 FR 11169, Mar. 27, 1990; 63 FR 5254,
Feb. 2, 1998; 65 FR 17137, Mar. 31, 2000; 73 FR tion submitted under § 860.130(d),
49942, Aug. 25, 2008; 75 FR 20916, Apr. 22, 2010; § 860.136(a), or received in a proceeding
79 FR 77388, Dec. 24, 2014; 82 FR 39535, Aug. 21, under § 860.133(b), the Commissioner
2017; 83 FR 64456, Dec. 17, 2018; 85 FR 18443, may or may not obtain a formal rec-
Apr. 2, 2020] ommendation.
§ 860.125 Consultation with panels. [43 FR 32993, July 28, 1978, as amended at 83
FR 64456, Dec. 17, 2018]
(a) When the Commissioner chooses
to refer a reclassification petition to a § 860.130 General procedures under
classification panel for its rec- section 513(e) of the Federal Food,
ommendation under § 860.134(b), or the Drug, and Cosmetic Act.
Commissioner is required to consult (a) Section 513(e) of the Federal
with a panel concerning a reclassifica- Food, Drug, and Cosmetic Act applies
tion petition submitted under to reclassification proceedings under
§ 860.130(d) or received in a proceeding the Federal Food, Drug, and Cosmetic
under § 860.133(b), or the Commissioner Act based upon new information.
chooses to consult with a panel with (b) A proceeding to reclassify a de-
regard to the reclassification of a device under section 513(e) may be initi-
vice initiated by the Commissioner ated:
under § 860.134(c) or § 860.136, the Com- (1) On the initiative of the Commis-
missioner will distribute a copy of the sioner alone;
petition, or its relevant portions, if ap- (2) On the initiative of the Commis-
plicable, to each panel member and sioner in response to a request for
will consult with the panel in one of change in classification based upon
the following ways: new information, under section 514(b)

(1) Consultation by telephone with at or 515(b) of the Federal Food, Drug, and
least a majority of current voting Cosmetic Act (see § 860.132); or
218
(3) In response to the petition of an (g) An administrative order under

interested person, based upon new in- this section changing the classification
formation, filed in accordance with of a device to class II may provide that
§ 860.123. such reclassification will not take ef-
(c) By administrative order published fect until the effective date of a per-
under this section, the Commissioner formance standard for the device estab-
may change the classification from: lished under section 514 of the Federal
(1) Class I or class II to class III if the Food, Drug, and Cosmetic Act or other
Commissioner determines that the de- special controls established under the
vice meets the criteria set forth in order. An order under this section
§ 860.3(c)(3) for a class III device; or changing the classification of a device
(2) Class III or class I to class II if the to class II may also establish the spe-
Commissioner determines that the de- cial controls necessary to provide rea-
vice meets the criteria set forth in sonable assurance of the safety and ef-
§ 860.3(c)(2) for a class II device; or fectiveness of the device.
(3) Class III or class II to class I if the [43 FR 32993, July 28, 1978, as amended at 57
Commissioner determines that the de- FR 58404, Dec. 10, 1992; 83 FR 64456, Dec. 17,
vice meets the criteria set forth in 2018]
§ 860.3(c)(1) for a class I device.
(d)(1) The Commissioner shall con- § 860.132 Procedures when the Com-
sult with a classification panel and missioner initiates a performance
may secure a recommendation with re- standard or premarket approval
spect to reclassification of a device proceeding under section 514(b) or
515(b) of the Federal Food, Drug,
from a classification panel. The panel and Cosmetic Act.
will consider reclassification in accord-
ance with the consultation procedures (a) Sections 514(b) and 515(b) of the
of § 860.125. A recommendation sub- Federal Food, Drug, and Cosmetic Act
mitted to the Commissioner by the require the Commissioner to provide,
panel will be published in the FEDERAL by notice in the FEDERAL REGISTER, an
REGISTER when the Commissioner pub- opportunity for interested parties to
lishes an administrative order under petition to change the classification of
this section. a device based upon new information
(2) The Commissioner may change relevant to its classification when the
the classification of a device by admin- Commissioner initiates a proceeding to
istrative order published in the FED- develop a performance standard for the
ERAL REGISTER following publication of device if in class II or to issue an order
a proposed reclassification order in the requiring premarket approval for the
FEDERAL REGISTER, a meeting of a de- device if in class III.
vice classification panel described in (b) If the Commissioner agrees that
section 513(b) of the Federal Food, the new information submitted in re-
Drug, and Cosmetic Act, and consider- sponse to a proposed order to require
ation of comments to a public docket. premarket approval of a device issued
(e) Within 180 days after the filing of under section 515(b) of the Federal
a petition for reclassification under Food, Drug, and Cosmetic Act warrants
this section, the Commissioner will ei- a change in classification, the Commis-
ther deny the petition by order pub- sioner shall follow the administrative
lished in the FEDERAL REGISTER or give order procedures under section 513(e) of
notice of the intent to initiate a the Federal Food, Drug, and Cosmetic
change in the classification of the de- Act and § 860.130 to effect such a
vice. change.
(f) If a device is reclassified under (c) If the Commissioner does not
this section, the administrative order agree that the new information sub-
effecting the reclassification may re- mitted in response to a proposed order
voke any special control or premarket to require premarket approval of a de-
approval requirement that previously vice issued under section 515(b) of the
applied to the device but that is no Federal Food, Drug, and Cosmetic Act
longer applicable because of the change warrants a change in classification, the
in classification. Commissioner will deny the petition.
219
§ 860.133 21 CFR Ch. I (4–1–23 Edition)
(d) The procedures under section § 860.134 Procedures for reclassifica-

514(b) of the Federal Food, Drug, and tion of ‘‘postamendments devices’’
Cosmetic Act are as follows: under section 513(f)(3) of the Fed-
(1) Within 30 days after publication of eral Food, Drug, and Cosmetic Act.
the Commissioner’s notice referred to (a) Section 513(f)(3) of the Federal
in paragraph (a) of this section, an in- Food, Drug, and Cosmetic Act applies
terested person files a petition for re- to proceedings for reclassification of a
classification in accordance with device currently in class III by oper-
§ 860.123. ation of section 513(f)(1) of the Federal
(2) The Commissioner consults with Food, Drug, and Cosmetic Act. This
the appropriate classification panel category includes any device that is to
with regard to the petition in accord- be first introduced or delivered for in-
ance with § 860.125. troduction into interstate commerce
(3) Within 60 days after publication of for commercial distribution after May
the notice referred to in paragraph (a) 28, 1976, unless:
of this section, the Commissioner ei- (1) It is substantially equivalent to
ther denies the petition or gives notice another device that was in commercial
of the intent to initiate a change in distribution before that date and had
classification in accordance with not been regulated before that date as
§ 860.130. a new drug; or
[43 FR 32993, July 28, 1978, as amended at 83 (2) It is substantially equivalent to
FR 64457, Dec. 17, 2018] another device that was not in com-
mercial distribution before such date
§ 860.133 Procedures when the Com- but which has been classified into class
missioner initiates a proceeding to I or class II; or
require premarket approval under (3) The Commissioner has classified
section 515(b) of the Federal Food, the device into class I or class II in re-
sponse to a petition for reclassification
(a) Section 515(b) of the Federal under this section; or
Food, Drug, and Cosmetic Act applies (4) The device is classified under a re-
to proceedings to require premarket quest for De Novo classification under
approval for a class III preamendments section 513(f)(2) of the Federal Food,
device. Drug, and Cosmetic Act.
(b) The Commissioner may require (b) The procedures for effecting re-
premarket approval for a class III classification under section 513(f)(3) of
preamendments device by administra- the Federal Food, Drug, and Cosmetic
tive order published in the FEDERAL Act when initiated by a manufacturer
REGISTER following publication of a or importer are as follows:
proposed order in the FEDERAL REG- (1) The manufacturer or importer of
ISTER, a meeting of a device classifica- the device petitions for reclassification
tion panel described in section 513(b) of of the device in accordance with
the Federal Food, Drug, and Cosmetic § 860.123.
Act, and consideration of comments (2) Within 30 days after the petition
from all affected stakeholders, includ- is filed, the Commissioner notifies the
ing patients, payors, and providers. petitioner of any deficiencies in the pe-
The panel will consider reclassification tition that prevent the Commissioner
petitions received in the proceeding in from making a decision on it and al-
accordance with section 513(e) of the lows the petitioner to supplement a de-
Federal Food, Drug, and Cosmetic and ficient petition. Within 30 days after
the applicable consultation procedures any supplemental material is received,
in § 860.125. A recommendation sub- the Commissioner notifies the peti-
mitted to the Commissioner by the tioner whether the petition, as supple-
panel will be published in the FEDERAL mented, is adequate for review.
REGISTER when the Commissioner pub-
(3) After determining that the peti-
lishes an administrative order under
tion contains no deficiencies pre-

this section.
cluding a decision on it, the Commis-
[83 FR 64457, Dec. 17, 2018] sioner may for good cause shown refer
220
the petition to the appropriate classi- reasonable assurance of the safety and
fication panel for its review and rec- effectiveness of the device and there is
ommendation whether to approve or sufficient information to establish spe-
deny the petition. cial controls to provide such assurance,
(4) Within 90 days after the date the or to class I if the Commissioner deter-
petition is referred to the panel, fol- mines that general controls alone
lowing the review procedures set forth would provide reasonable assurance of
in § 860.84(c) for the original classifica- the safety and effectiveness of the de-
tion of a ‘‘preamendments device’’, the vice. The procedures for the reclassi-
panel submits to the Commissioner its fication proceeding under this para-
recommendation containing the infor- graph (c) are as follows:
mation set forth in § 860.84(d). A panel (1) The Commissioner publishes a
recommendation is regarded as pre- proposed reclassification order in the
liminary until the Commissioner has FEDERAL REGISTER seeking comment
reviewed it, discussed it with the panel, on the proposed reclassification.
if appropriate, and developed a pro- (2) The Commissioner may consult
posed reclassification order. Prelimi- with the appropriate classification
nary panel recommendations are filed panel with respect to the reclassifica-
at Dockets Management Staff upon re- tion of the device. The panel will con-
ceipt and are available to the public sider reclassification in accordance
and posted at https:// with the consultation procedures of
www.regulations.gov. § 860.125.
(5) The panel recommendation is pub-
(3) Following consideration of com-
lished in the FEDERAL REGISTER as
ments to a public docket and any panel
soon as practicable and interested per-
recommendations or comments, the
sons are provided an opportunity to
Commissioner may change the classi-
comment on the recommendation.
fication of a device by final adminis-
(6) Within 90 days after the panel’s
trative order published in the FEDERAL
recommendation is received (and no
REGISTER.
more than 210 days after the date the
petition was filed), the Commissioner (d) An administrative order under
denies or approves the petition by this section changing the classification
order in the form of a letter to the pe- of a device from class III to class II
titioner. If the Commissioner approves may establish the special controls nec-
the petition, the order will classify the essary to provide reasonable assurance
device into class I or class II in accord- of the safety and effectiveness of the
ance with the criteria set forth in device.
§ 860.3(c) and subject to the applicable [43 FR 32993, July 28, 1978, as amended at 57
requirements of § 860.10, relating to the FR 58404, Dec. 10, 1992; 73 FR 34860, June 19,
classification of implants and life-sup- 2008; 83 FR 64457, Dec. 17, 2018]
porting or life-sustaining devices, and
§ 860.15, relating to exemptions from § 860.136 Procedures for transitional
certain requirements of the Federal products under section 520(l) of the
Food, Drug, and Cosmetic Act. Federal Food, Drug, and Cosmetic
Act.
(7) Within a reasonable time after
issuance of an order under this section, (a) Section 520(l)(2) of the Federal
the Commissioner announces the order Food, Drug, and Cosmetic Act applies
by notice published in the FEDERAL to reclassification proceedings initi-
REGISTER. ated by the Commissioner or in re-
(c) By administrative order published sponse to a request by a manufacturer
under section 513(f)(3) of the Federal or importer for reclassification of a de-
Food, Drug, and Cosmetic Act, the vice currently in class III by operation
Commissioner may, on the Commis- of section 520(l)(1). This section applies
sioner’s own initiative, change the only to devices that the Food and Drug
classification from class III under sec- Administration regarded as ‘‘new
tion 513(f)(1) either to class II, if the drugs’’ before May 28, 1976.
Commissioner determines that special (b) The procedures for effecting re-
controls in addition to general controls classification under section 520(l) of the
are necessary and sufficient to provide Federal Food, Drug, and Cosmetic Act
221
§ 860.200 21 CFR Ch. I (4–1–23 Edition)
when initiated by a manufacturer or (2) The Commissioner may consult

importer are as follows: with the appropriate classification
(1) The manufacturer or importer of panel with respect to the reclassifica-
the device files a petition for reclassi- tion of the device. The panel will con-
fication of the device in accordance sider reclassification in accordance
with § 860.123. with the consultation procedures of
(2) Within 30 days after the petition § 860.125.
is filed, the Commissioner notifies the (3) Following consideration of com-
petitioner of any deficiencies in the pe- ments to a public docket and any panel
tition that prevent the Commissioner recommendations or comments, the
from making a decision on it, allowing Commissioner may change the classi-
the petitioner to supplement a defi- fication of a device by final adminis-
cient petition. Within 30 days after any trative order published in the FEDERAL
supplemental material is received, the REGISTER.
Commissioner notifies the petitioner (d) An administrative order under
whether the petition, as supplemented, this section changing the classification
is adequate for review. of a device from class III to class II
(3) The Commissioner consults with may establish the special controls nec-
the appropriate classification panel essary to provide reasonable assurance
with regard to the petition in accord- of the safety and effectiveness of the
ance with § 860.125. device.
(4) Within 180 days after the petition
is filed (where the Commissioner has [43 FR 32993, July 28, 1978, as amended at 83
determined it to be adequate for re- FR 64458, Dec. 17, 2018]
view), the Commissioner, by order in
the form of a letter to the petitioner, Subpart D—De Novo Classification
either denies the petition or classifies
the device into class I or class II in ac- SOURCE: 86 FR 54847, Oct. 5, 2021, unless
cordance with the criteria set forth in otherwise noted.
§ 860.3(c).
(5) Within a reasonable time after § 860.200 Purpose and applicability.
issuance of an order under this section, (a) The purpose of this part is to es-
the Commissioner announces the order tablish an efficient, transparent, and
by notice published in the FEDERAL thorough process to facilitate De Novo
REGISTER. classification into class I or class II for
(c) By administrative order, the Com- devices for which there is no legally
missioner may, on the Commissioner’s marketed device on which to base a re-
own initiative, change the classifica- view of substantial equivalence and
tion from class III under section 520(l) which meet the definition of class I or
of the Federal Food, Drug, and Cos- class II as described in section 513(a)(1)
metic Act either to class II, if the Com- of the Federal Food, Drug, and Cos-
missioner determines that special con- metic Act and § 860.3.
trols in addition to general controls
(b) De Novo requests can be sub-
are necessary and sufficient to provide
mitted for a single device type:
reasonable assurance of the safety and
effectiveness of the device and there is (1) After receiving a not substan-
sufficient information to establish spe- tially equivalent determination in re-
cial controls to provide such assurance, sponse to a premarket notification
or to class I if the Commissioner deter- (510(k)), or
mines that general controls alone (2) If a person determines there is no
would provide reasonable assurance of legally marketed device upon which to
the safety and effectiveness of the de- base a determination of substantial
vice. The procedures for the reclassi- equivalence.
fication proceeding under this para-
graph (c) are as follows: § 860.210 De Novo request format.
(1) The Commissioner publishes a (a) Each De Novo request or informa-
proposed reclassification order in the tion related to a De Novo request pur-

FEDERAL REGISTER seeking comment suant to this part must be formatted in
on the proposed reclassification. accordance with this section. Each De
222
Novo request must be provided as a sin- Drug, and Cosmetic Act; pre-submis-
gle version in electronic format. These sions, or previously submitted De Novo
materials must: requests; or state that there have been
(1)(i) For devices regulated by the no prior submissions.
Center for Devices and Radiological (4) Device name. The generic name of
Health, be sent to the current address the device as well as any proprietary
displayed on the website https:// name or trade name.
www.fda.gov/cdrhsubmissionaddress. (5) Indications for use. A general de-
(ii) For devices regulated by the Cen- scription of the disease or condition
ter for Biologics Evaluation and Re- the device is intended to diagnose,
search, be sent to the current address
treat, prevent, cure or mitigate, or af-
displayed on the website https://
fect the structure or function of the
www.fda.gov/about-fda/center-biologics-
body, including a description of the pa-
evaluation-and-research-cber/regulatory-
tient population for which the device is
submissions-electronic-and-paper.
(2) Be signed by the requester or an intended. The indications for use in-
authorized representative. clude all the labeled patient uses of the
(3) Be designated ‘‘De Novo Request’’ device, including if it is prescription or
in the cover letter. over-the-counter.
(4) Have all content used to support (6) Device description. A complete de-
the request written in, or translated scription of:
into, English. (i) The device, including, where appli-
cable, pictorial representations, device
§ 860.220 De Novo request content. specifications, and engineering draw-
(a) Unless the requester justifies an ings;
omission in accordance with paragraph (ii) Each of the functional compo-
(c) of this section, a De Novo request nents or ingredients of the device, if
must include: the device consists of more than one
(1) Table of contents. A table of con- physical component or ingredient;
tents that specifies the volume (if the (iii) The properties of the device rel-
De Novo request contains more than evant to the diagnosis, treatment, pre-
one volume) and page number for each vention, cure, or mitigation of a dis-
item. ease or condition and/or the effect of
(2) Administrative information. The the device on the structure or function
name, address, phone, and email ad- of the body;
dress of the requester and U.S. rep- (iv) The principles of operation of the
resentative, if applicable. The estab- device; and
lishment registration number, if appli- (v) The relevant FDA assigned ref-
cable, of the owner or operator submit- erence number(s) for any medical de-
ting the De Novo request.
vices (such as accessories or compo-
(3) Regulatory history. Identify any
nents) that are intended to be used
prior submissions to FDA for the de-
with the device and that are already le-
vice, including, but not limited to, any
gally marketed.
premarket notifications (510(k)s) sub-
mitted under part 807 of this chapter; (7) Alternative practices and proce-
applications for premarket approval dures. A description of existing alter-
(PMAs) submitted under part 814 of native practices or procedures that are
this chapter; applications for humani- used in diagnosing, treating, pre-
tarian device exemption (HDE) sub- venting, curing, or mitigating the dis-
mitted under part 814 of this chapter; ease or condition for which the device
applications for investigational device is intended or which similarly affect
exemption (IDEs) submitted under part the structure or function of the body
812 of this chapter; requests for des- and that are known or should reason-
ignation (RFD) under § 3.7 of this chap- ably be known to the requester.
ter; requests for information under sec- (8) Classification summary. (i) For de-
tion 513(g) of the Federal Food, Drug, vices not the subject of a previous sub-
and Cosmetic Act; applications for mission under section 510(k) of the Fed-
emergency use authorization (EUA) eral Food, Drug, and Cosmetic Act, a
under section 564 of the Federal Food, complete description of:
223
§ 860.220 21 CFR Ch. I (4–1–23 Edition)
(A) The searches used to establish (12) Standards. Reference to any pub-
that no legally marketed device of the lished voluntary consensus standards
same type exists. that are relevant to any aspect of the
(B) A list of classification regula- safety or effectiveness of the device
tions, PMAs, HDEs, premarket notifi- and that are known or should reason-
cations (510(k)s), EUAs, and/or product ably be known to the requester. Such
codes regarding devices that are poten- standards include voluntary consensus
tially similar to the subject device. standards whether recognized or not
(C) A rationale explaining how the yet recognized under section 514(c) of
device that is the subject of the De the Federal Food, Drug, and Cosmetic
Novo request is different from the de- Act. Provide adequate information to
vices covered by the classification reg-
demonstrate how the device meets, or
ulations, PMAs, HDEs, 510(k)s, EUAs,
justify any deviation from, the ref-
and/or product codes identified in para-
graph (a)(8)(i)(B) of this section. erenced standard.
(ii) For devices which were the sub- (13) Summary of studies. An abstract
ject of a previous submission under sec- of any information or report described
tion 510(k) of the Federal Food, Drug, in the De Novo request under para-
and Cosmetic Act that were deter- graph (a)(16)(ii) of this section and a
mined not substantially equivalent summary of the results of technical
(NSE), the relevant 510(k) number, data submitted under paragraph (a)(15)
along with a summary of the search of this section. Each such study sum-
performed to confirm the device has mary must include a description of the
not been classified or reclassified since objective of the study, a description of
the date the NSE order was issued by the experimental design of the study, a
FDA pursuant to § 807.100(a) of this brief description of how the data were
chapter. collected and analyzed, and a brief de-
(9) Summary of risks and mitigations. A scription of the results, whether posi-
summary of probable risks to health tive, negative, or inconclusive. This
associated with use of the device that section must also include the fol-
are known or should reasonably be lowing:
known to the requester and the pro- (i) A summary of each nonclinical
posed mitigations, including general
study submitted in the De Novo re-
controls and, if the classification rec-
quest;
ommendation from paragraph (a)(11) of
this section is class II, special controls (ii) A summary of each clinical inves-
for each risk. For each mitigation tigation involving human subjects sub-
measure that involves specific perform- mitted in the De Novo request, includ-
ance testing or labeling, the De Novo ing a discussion of investigation de-
request must provide a reference to the sign, subject selection and exclusion
associated section or pages for the sup- criteria, investigation population, in-
porting information in the De Novo re- vestigation period, safety and effec-
quest. tiveness data, adverse reactions and
(10) Proposed special controls. If the complications, subject discontinuation,
classification recommendation from subject complaints, device failures (in-
paragraph (a)(11) of this section is class cluding unexpected software events, if
II, then the summary must include an applicable) and replacements, results
initial draft proposal for applicable of statistical analyses of the clinical
special controls and a description of investigations, contraindications and
how those special controls provide rea- precautions for use of the device, and
sonable assurance of safety and effec- other information from the clinical in-
tiveness. vestigations as appropriate. Any inves-
(11) Classification recommendation. The tigation conducted under an investiga-
recommended class (I or II) must be tional device exemption (IDE) under
identified and must be supported by a part 812 of this chapter must be identi-
description of why general controls, or
fied as such.
general and special controls, are ade-

quate to provide reasonable assurance (14) Benefit and risk considerations. A
of safety and effectiveness. discussion demonstrating that:
224
(i) The data and information in the tigation, results of statistical analyses
De Novo request constitute valid sci- of the results of the clinical investiga-
entific evidence within the meaning of tions, contraindications, warnings, pre-
§ 860.7(c) and cautions, and other limiting state-
(ii) Pursuant to § 860.7, when subject ments relevant to the use of the device
to general controls, or general and spe- type, and any other appropriate infor-
cial controls, the probable benefit to mation from the clinical investiga-
health from use of the device out- tions. Any investigation conducted
weighs any probable injury or illness under an IDE under part 812 of this
from such use. chapter must be identified as such. In-
(15) Technical sections. The following formation on clinical investigations in-
technical sections, which must contain volving human subjects must include
data and information in sufficient de- the following:
tail to permit FDA to determine (A) For clinical investigations con-
whether to grant or decline the De ducted in the United States, a state-
Novo request: ment with respect to each investiga-
(i) A section containing the results of tion that it either was conducted in
the nonclinical studies of the device, compliance with the institutional re-
including, as appropriate, micro- view board regulations in part 56 of
biological, toxicological, this chapter, or was not subject to the
immunological, biocompatibility, regulations under § 56.104 or § 56.105 of
stress, wear, shelf life, electrical safe- this chapter, and that it was conducted
ty, electromagnetic compatibility, and in compliance with the informed con-
other laboratory or animal tests. Infor- sent regulations in part 50 of this chap-
mation on nonclinical studies must inter; or if the investigation was not con-
clude protocols and complete test re- ducted in compliance with those regu-
ports for each study. For those non- lations, a brief statement of the reason
clinical studies subject to part 58 of for the noncompliance. Failure or in-
this chapter, this section must include ability to comply with these require-
a statement that each such study was ments does not justify failure to pro-
conducted in compliance with such reg- vide information on a relevant clinical
ulations, or, if the study was not con- investigation.
ducted in compliance with part 58 of (B) For clinical investigations con-
this chapter, a brief statement of the ducted in the United States, a state-
reason for the noncompliance. ment that each investigation was con-
(ii) For all devices that incorporate ducted in compliance with part 812 of
software, a section containing all rel- this chapter concerning sponsors of
evant software information and test- clinical investigations and clinical in-
ing, including, but not limited to, ap- vestigators, or if the investigation was
propriate device hazard analysis, hard- not conducted in compliance with
ware, and system information. those regulations, a brief statement of
(iii) A section containing results of the reason for the noncompliance. Fail-
each clinical investigation of the de- ure or inability to comply with these
vice involving human subjects, includ- requirements does not justify failure to
ing clinical protocols, number of inves- provide information on a relevant clin-
tigators and subjects per investigator, ical investigation.
investigation design, subject selection (C) For clinical investigations con-
and exclusion criteria, investigation ducted outside the United States that
population, investigation period, safety are intended to support the De Novo re-
and effectiveness data, adverse reac- quest, the requirements under § 812.28
tions and complications, subject dis- of this chapter apply. If any such inves-
continuation, subject complaints, de- tigation was not conducted in accord-
vice failures (including unexpected ance with good clinical practice (GCP)
software events if applicable) and re- as described in § 812.28(a) of this chap-
placements, tabulations of data from ter, include either a waiver request in
all individual subject report forms and accordance with § 812.28(c) of this chap-
copies of such forms for each subject ter or a brief statement of the reason
who died during a clinical investiga- for not conducting the investigation in
tion or who did not complete the inves- accordance with GCP and a description
225
§ 860.230 21 CFR Ch. I (4–1–23 Edition)
of steps taken to ensure that the data (18) Labeling and advertisements. La-
and results are credible and accurate bels, labeling, and advertisements suf-
and that the rights, safety, and well- ficient to describe the device, its in-
being of subjects have been adequately tended use, and the directions for its
protected. Failure or inability to com- use. Where applicable, photographs or
ply with these requirements does not engineering drawings must be supplied.
justify failure to provide information (19) Other information. Such other in-
on a relevant clinical investigation. formation as is necessary to determine
(D) A statement that each investiga- whether general controls or general
tion has been completed per the pro- and special controls provide reasonable
tocol or a summary of any protocol de- assurance of safety and effectiveness of
viations. the device.
(E) A financial certification or dis- (b) Pertinent information in FDA
closure statement or both as required files specifically referred to by a re-
by part 54 of this chapter. quester may be incorporated into a De
(F) For a De Novo request that relies Novo request by reference. Information
primarily on data from a single investi- submitted to FDA by a person other
gator at one investigation site, a jus- than the requester will not be consid-
tification showing that these data and ered part of a De Novo request unless
other information are sufficient to rea- such reference is authorized in writing
sonably demonstrate the safety and ef- by the person who submitted the infor-
fectiveness of the device when subject mation.
to general controls or general and spe-
(c) If the requester believes that cer-
cial controls, and to ensure that the re-
tain information required under para-
sults from a site are applicable to the
graph (a) of this section to be in a De
intended population.
Novo request is not applicable to the
(G) A discussion of how the investiga-
device that is the subject of the De
tion data represent clinically signifi-
Novo request, and omits any such in-
cant results, pursuant to § 860.7(e).
formation from the De Novo request,
(16) Other information. (i) A bibliog-
the requester must submit a statement
raphy of all published reports not sub-
mitted under paragraph (a)(15) of this that specifies the omitted information
section, whether adverse or supportive, and justifies the omission. The state-
known to or that should reasonably be ment must be submitted as a separate
known to the requester and that con- section in the De Novo request and list-
cern the safety or effectiveness of the ed in the table of contents. If the jus-
device. tification for the omission is not ac-
(ii) An identification, discussion, and cepted by FDA, FDA will so notify the
analysis of any other data, informa- requester.
tion, or report relevant to an evalua- (d) The requester must update the
tion of the safety and effectiveness of pending De Novo request with new
the device known to or that should rea- safety and effectiveness information
sonably be known to the requester learned about the device from ongoing
from any source, foreign or domestic, or completed studies and investiga-
including information derived from in- tions that may reasonably affect an
vestigations other than those in the reevaluation of the safety or effective-
quest and from commercial marketing ness of the device as such information
experience. becomes available.
(iii) Copies of such published reports
or unpublished information in the pos- § 860.230 Accepting a De Novo request.
session of or reasonably obtainable by (a) The acceptance of a De Novo re-
the requester, if requested by FDA. quest means that FDA has made a
(17) Samples. If requested by FDA, one threshold determination that the De
or more samples of the device and its Novo request contains the information
components. If it is impractical to sub- necessary to permit a substantive re-
mit a requested sample of the device, view. Within 15 days after a De Novo
the requester must name the location request is received by FDA, FDA will
at which FDA may examine and test notify the requester whether the De
one or more of the devices. Novo request has been accepted.
226
(b) If FDA does not find that any of § 860.240 Procedures for review of a
the reasons in paragraph (c)(1) of this De Novo request.
section for refusing to accept the De (a) FDA will begin substantive review
Novo request apply or FDA fails to of a De Novo request after the De Novo
complete the acceptance review within request is accepted under § 860.230.
15 days, FDA will accept the De Novo Within 120 days after receipt of a De
request for review and will notify the Novo request or receipt of additional
requester. The notice will include the information that results in the De
De Novo request reference number and Novo request being accepted under
the date FDA accepted the De Novo re- § 860.230, FDA will review the De Novo
quest. The date of acceptance is the request and send the requester an order
date that an accepted De Novo request granting the De Novo request under
was received by FDA. § 860.260(a) or an order declining the De
(c)(1) FDA may refuse to accept a De Novo request under 860.260(b).
Novo request if any of the following ap- (b) A requester may supplement or
plies: amend a pending De Novo request to
(i) The requester has an open or pend- revise existing information or provide
ing premarket submission or reclassi- additional information.
fication petition for the device; (1) FDA may require additional infor-
(ii) The De Novo request is incom- mation regarding the device that is
plete because it does not on its face necessary for FDA to complete the re-
contain all the information required view of the De Novo request.
under section 513(f)(2) of the Federal (2) Additional information submitted
Food, Drug, and Cosmetic Act or does to FDA must include the reference
not contain each of the items required number assigned to the original De
under this part, or a justification for Novo request and, if submitted on the
omission of any item; requester’s own initiative, the reason
for submitting the additional informa-
(iii) The De Novo request is not for-
tion.
matted as required under § 860.210;
(c) Prior to granting or declining a
(iv) The De Novo request is for mul- De Novo request, FDA may inspect rel-
tiple devices and those devices are of evant facilities to help determine:
more than one type; or (1) That clinical or nonclinical data
(v) The requester has not responded were collected in a manner that en-
to, or has failed to provide a rationale sures that the data accurately rep-
for not responding to, deficiencies iden- resents the benefits and risks of the de-
tified by FDA in previous submissions vice; or
for the same device, including those (2) That implementation of Quality
submissions described in § 860.220(a)(3). System Regulation (part 820 of this
(2) If FDA refuses to accept a De chapter) requirements, in addition to
Novo request, FDA will notify the re- other general controls and any speci-
quester of the reasons for the refusal. fied special controls, provide adequate
The notice will identify the defi- assurance that critical and/or novel
ciencies in the De Novo request that manufacturing processes produce de-
prevent accepting and will include the vices that meet specifications nec-
De Novo request reference number. essary to ensure reasonable assurance
(3) If FDA refuses to accept a De of safety and effectiveness.
Novo request, the requester may sub-
mit the additional information nec- § 860.250 Withdrawal of a De Novo re-
essary to comply with the require- quest.
ments of section 513(f)(2) of the Federal (a) FDA considers a De Novo request
Food, Drug, and Cosmetic Act and this to have been withdrawn if:
part. The additional information must (1) The requester fails to provide a
include the De Novo request reference complete response to a request for ad-
number of the original submission. If ditional information pursuant to
the De Novo request is subsequently § 860.240(b)(1) within 180 days after the
accepted, the date of acceptance is the date FDA issues such request;
date FDA receives the additional infor- (2) The requester fails to provide a
mation. complete response to the deficiencies
227
§ 860.260 21 CFR Ch. I (4–1–23 Edition)
identified by FDA pursuant to the Federal Food, Drug, and Cosmetic

§ 860.230(c)(2) within 180 days of the date Act and is not a combination product
notification was issued by FDA; as defined at § 3.2(e) of this chapter;
(3) The requester does not permit an (5) The device is of a type which has
authorized FDA employee an oppor- already been approved in existing ap-
tunity to inspect the facilities, pursu- plications for premarket approval
ant to § 860.240(c), at a reasonable time (PMAs) submitted under part 814 of
and in a reasonable manner, and to this chapter;
have access to copy and verify all (6) The device is of a type that has al-
records pertinent to the De Novo re- ready been classified into class I, class
quest; or II, or class III;
(4) The requester submits a written (7) An inspection of a relevant facil-
notice to FDA that the De Novo re- ity under § 860.240(c) results in a deter-
quest has been withdrawn. mination that general or general and
(b) If a De Novo request is with- special controls would not provide rea-
drawn, the Agency will notify the re- sonable assurance of safety and effec-
quester. The notice will include the De tiveness;
Novo request reference number and the (8) A nonclinical study subject to
date FDA considered the De Novo re- part 58 of this chapter that is described
quest withdrawn. in the De Novo request, and that is es-
sential to show there is reasonable as-
§ 860.260 Granting or declining a De surance of safety, was not conducted in
Novo request. compliance with part 58 of this chapter
(a)(1) FDA will issue to the requester and no reason for the noncompliance is
an order granting a De Novo request if provided or, if a reason is provided, the
none of the reasons in paragraph (c) of practices used in conducting the study
this section for declining the De Novo do not support the validity of the
request applies. study;
(2) If FDA grants a De Novo request, (9) A clinical investigation described
within 30 days after the issuance of an in the De Novo request involving
order granting the De Novo request, human subjects that is subject to the
FDA will publish in the FEDERAL REG- institutional review board regulations
ISTER a notice of the classification in part 56 of this chapter, informed
order, including any special controls. consent regulations in part 50 of this
(b) If FDA declines a De Novo re- chapter, or GCP described in § 812.28(a)
quest, FDA will issue a written order of this chapter, was not conducted in
to the requester. compliance with those regulations such
(c) FDA may decline a De Novo re- that the rights or safety of human sub-
quest if the requester fails to follow jects were not adequately protected or
the requirements of this part or if, the supporting data were determined to
upon the basis of the information sub- be otherwise unreliable;
mitted in the De Novo request or any (10) A clinical or nonclinical study
other information before FDA, FDA de- necessary to demonstrate that general
termines: controls or general and special controls
(1) The device does not meet the cri- provide reasonable assurance of safety
teria under section 513(a)(1) of the Fed- and effectiveness:
eral Food, Drug, and Cosmetic Act and (i) Has not been completed per the
§ 860.3 for classification into class I or study protocol, or
II; (ii) Deficiencies related to the inves-
(2) The De Novo request contains a tigation and identified in any request
false statement of material fact or for additional information under
there is a material omission; § 860.240(b)(1) have not been adequately
(3) The device’s labeling does not addressed; or
comply with the requirements in parts (11) After a De Novo request is ac-
801 and 809 of this chapter, as applica- cepted for review under § 860.230(b), the
ble; requester makes significant unsolicited
(4) The product described in the De changes to the device’s:

Novo request does not meet the defini- (i) Indications for use; or
tion of a device under section 201(h) of (ii) Technological characteristics.
228
(d) An order declining a De Novo re- (2) A class III device which, upon the
quest will inform the requester of the effective date of the standard, is reclas-
deficiencies in the De Novo request, in- sified into class II; and
cluding each applicable ground for de- (3) A class III device, as a condition
clining the De Novo request. to premarket approval under section
(e) FDA will use the criteria specified 515 of the act, to reduce or eliminate a
in § 860.7 to determine the safety and risk or risks associated with such de-
effectiveness of a device in deciding vice.
whether to grant or decline a De Novo (c) References in this part to regu-
request. FDA may use information latory sections of the Code of Federal
other than that submitted by the re- Regulations are to chapter I of title 21
quester in making such determination. unless otherwise noted.
[45 FR 7484, Feb. 1, 1980, as amended at 45 FR
PART 861—PROCEDURES FOR PER- 23686, Apr. 8, 1980; 57 FR 58404, Dec. 10, 1992]
FORMANCE STANDARDS DEVEL- § 861.5 Statement of policy.
OPMENT
In carrying out its duties under this
Subpart A—General section, the Food and Drug Adminis-
tration will, to the maximum extent
Sec. practical:
861.1 Purpose and scope. (a) Use personnel, facilities, and
861.5 Statement of policy. other technical support available in
861.7 Contents of standards.
other Federal agencies;
Subpart B—Procedures for Performance (b) Consult with other Federal agen-
Standards Development and Publication cies concerned with standard setting
and other nationally or internationally
861.20 Summary of standards development recognized standard-setting entities;
process. and
861.24 Existing standard as a proposed (c) Invite participation, through con-
standard. ferences, workshops, or other means,
861.30 Development of standards. by representatives of scientific, profes-
861.34 Amendment or revocation of a stand-
ard.
sional, industry, or consumer organiza-
861.36 Effective dates. tions who can make a significant con-
861.38 Standards advisory committees. tribution.
AUTHORITY: 21 U.S.C. 351, 352, 360c, 360d, § 861.7 Contents of standards.
360gg–360ss, 371, 374; 42 U.S.C. 262, 264.
Any performance standard estab-
SOURCE: 45 FR 7484, Feb. 1, 1980, unless oth- lished under this part will include such
erwise noted.
provisions as the Food and Drug Ad-
ministration determines are necessary
Subpart A—General to provide reasonable assurance of the
safety and effectiveness of the device
§ 861.1 Purpose and scope. or devices for which it is established.
(a) This part implements section 514 Where necessary to provide such assur-
of the Federal Food, Drug, and Cos- ance, a standard will address (but need
metic Act (the act) with respect to the not be limited to):
establishment, amendment, and rev- (a) Performance characteristics of
ocation of performance standards ap- the device;
plicable to devices intended for human (b) The design, construction, compo-
use. nents, ingredients, and properties of
(b) The Food and Drug Administra- the device, and its compatibility with
tion may determine that a performance power systems and connections to such
standard, as described under special systems;
controls for class II devices in § 860.7(b) (c) The manufacturing processes and
of this chapter, is necessary to provide quality control procedures applicable
reasonable assurance of the safety and to the device;
effectiveness of the device. Perform- (d) Testing of the device on either a

ance standards may be established for: sample or a 100-percent basis by the
(1) A class II device; manufacturer, or, if it is determined
229
§ 861.20 21 CFR Ch. I (4–1–23 Edition)
that no other more practical means are (a) The Food and Drug Administra-
available to the Food and Drug Admin- tion (FDA) will publish in the FEDERAL
istration to assure the conformity of REGISTER a notice of proposed rule-
the device to the standard, providing making for the establishment, amend-
for testing by the Food and Drug Ad- ment, or revocation of any perform-
ministration or a third person to en- ance standard for a device.
sure that the device conforms to the (1) A notice of proposed rulemaking
standard; for the establishment or amendment of
(e) The publication of the results of a performance standard for a device
each test or of certain tests of the de- will:
vice to show that the device conforms (i) Set forth a finding, with sup-
to the portions of the standard for porting justification, that the perform-
which the test or tests were required; ance standard is appropriate and nec-
(f) Manufacturers’ certification to essary to provide reasonable assurance
purchasers or to the Food and Drug Ad- of the safety and effectiveness of the
ministration that the device conforms device;
to the applicable performance stand- (ii) Set forth proposed findings with
ard; respect to the risk of illness or injury
(g) Restrictions on the sale and dis- that the performance standard is in-
tribution of the device, but only to the tended to reduce or eliminate;
extent authorized under section 520(e) (iii) Invite interested persons to sub-
of the act; mit to the Food and Drug Administra-
(h) The use, and the form and con- tion, within 30 days of the publication
tent, of labeling for the proper installa- of the notice, requests for changes in
tion, maintenance, operation, and use the classification of the device pursu-
of the device. Among the provisions ant to § 860.132 of this chapter, based on
that may be required in the labeling new information relevant to the classi-
are warnings; storage and transpor- fication; and
tation information; expiration dates; (iv) Invite interested persons to sub-
the date and place of manufacture; the mit an existing performance standard
results that may be expected if the de- for the device, including a draft or pro-
vice is used properly; the ranges of ac- posed performance standard, for con-
curacy of diagnostic information; in- sideration by the Commissioner of
structions regarding the proper care of, Food and Drugs.
and the proper components, acces- (2) A notice of proposed rulemaking
sories, or other equipment to be used for the revocation of a performance
with the device; and statements con- standard will set forth a finding, with
cerning the appropriate patient popu- supporting justification, that the per-
lation, for example, a statement that formance standard is no longer nec-
the device is considered safe and effec- essary to provide reasonable assurance
tive only when used by, or in the treat- of the safety and effectiveness of a de-
ment of, a patient who has been tested vice.
by particular designated procedures
(b) A notice under this section will
and found to have an illness or condi-
provide for a comment period of not
tion for which use of the device is indi-
less than 60 days.
cated by a person skilled in the use of
the device. (c) If, after publication of a notice
under paragraph (a) of this section,
FDA receives a request to change the
Subpart B—Procedures for Per- classification of the device, FDA will,
formance Standards Develop- within 60 days of the publication of the
ment and Publication notice and after consultation with the
appropriate panel under § 860.125 of this
§ 861.20 Summary of standards devel- chapter, either deny the request or give
opment process. notice of its intent to initiate a change
The procedure by which a perform- in the classification under § 860.130.
ance standard for a device may be es- (d) If FDA initiates a rulemaking
tablished, amended, or revoked is as proceeding under paragraph (a) of this
follows: section, FDA will:
230
(1) Complete the proceeding and es- (a) Support its proposed performance
tablish the performance standard for standard by such test data or other
the device in accordance with this part documents or materials as may reason-
and § 10.40 of this chapter; or ably be required;
(2) Terminate the proceeding by pub- (b) Provide interested persons an op-
lishing in the FEDERAL REGISTER a no- portunity to participate in the develop-
tice announcing such termination and ment of the standard by accepting
the reasons therefor and, unless the comments and, where appropriate,
proceeding is terminated because the holding public meetings on issues re-
device is a banned device, initiate a lating to development of the standard.
proceeding in accordance with section Notice of the opportunity to partici-
513(e) of the act to reclassify the de- pate in the development of the stand-
vice; or ard will be furnished in a manner rea-
(3) Take other appropriate action. sonably calculated to reach the major-
[57 FR 58404, Dec. 10, 1992] ity of persons interested in the devel-
opment of the standard. This require-
§ 861.24 Existing standard as a pro- ment shall be satisfied by publishing
posed standard. such a notice in the FEDERAL REG-
(a) The Food and Drug Administra- ISTER. Whenever it is appropriate, FDA
tion may accept an existing standard will use the FEDERAL REGISTER to
or a proposed or draft standard if it in- make announcements about the stand-
cludes: ard development process of standard
(1) A description of the procedures developers other than Federal agen-
used to develop the standard and a list cies.
of the persons and organizations that (c) Maintain records disclosing the
participated in its development, to the course of development of the proposed
extent that such information is avail- standard, the comments and other in-
able or reasonably obtainable; formation submitted by a person in
(2) An identification of the specific connection with such development (in-
portions of the existing standard that cluding comments and information re-
the person submitting the standard be- garding the need for a standard), and
lieves are appropriate for adoption as, such other information as may be re-
or inclusion in, the proposed standard; quired to evaluate the standard.
and
(3) A summary of the test data, or, if [45 FR 7484, Feb. 1, 1980, as amended at 57 FR
requested by the Food and Drug Ad- 58405, Dec. 10, 1992]
ministration, all such data or other in-
formation supporting the specific por- § 861.34 Amendment or revocation of a
tions of the standard identified by the standard.
person submitting the standard. (a) The Food and Drug Administra-
(b) The Food and Drug Administra- tion will provide for periodic evalua-
tion will publish a notice in the FED- tion of performance standards to deter-
ERAL REGISTER stating either that it mine whether such standards should be
has accepted, or accepted with modi- changed to reflect new medical, sci-
fication, as a proposed standard, an ex- entific, or other technological data.
isting standard or one that has been (b) The Food and Drug Administra-
developed, or that an existing standard tion may, on its own initiative or upon
is not acceptable, together with the petition of an interested party, amend
reasons therefor. or revoke by regulation a standard es-
[45 FR 7484, Feb. 1, 1980, as amended at 57 FR tablished under this part.
58405, Dec. 10, 1992] (c) Any petition to amend or revoke
a standard shall:
§ 861.30 Development of standards. (1) Identify the specific device and
The Food and Drug Administration standard for which the amendment or
(FDA), while engaged in the develop- revocation is sought; and

ment of a proposed standard under this (2) Be submitted in accordance with
section will: the requirements of § 10.30.
231
§ 861.36 21 CFR Ch. I (4–1–23 Edition)
(d) Proceedings to amend or revoke a be referred, and these committees shall

performance standard shall be con- consider such referrals in accordance
ducted in accordance with the rule- with this section and part 14 of this
making procedures of § 10.40. In addi- chapter. Such advisory committees,
tion, a notice of proposed rulemaking which may not be classification panels,
to amend or revoke a standard shall set shall be considered ad hoc advisory
forth proposed findings with respect to committees. Their members shall be
the degree of risk or illness to be elimi- selected in accordance with §§ 14.82 and
nated or reduced and the benefit the 14.84, except that no member may be a
public will derive from the proposed regular full-time FDA employee. Each
amendment or revocation. advisory committee established under
this section shall include as nonvoting
§ 861.36 Effective dates. members a representative of consumer
(a) A regulation establishing, amend- interests and a representative of inter-
ing, or revoking a performance stand- ests of the device manufacturing indus-
ard will set forth the date upon which try.
it will take effect. To the extent prac- (b) A proposed regulation to estab-
tical, consistent with the public health lish, amend, or revoke a performance
and safety, such effective date will be standard shall be referred to an advi-
established so as to minimize economic sory committee for a report and rec-
loss to, and disruption or dislocation ommendation with respect to any mat-
of, domestic and international trade. ter involved in the proposed regulation
(b) Except as provided in paragraph which requires the exercise of sci-
(c) of this section, no regulation estab- entific judgment if:
lishing, amending, or revoking a stand- (1) The Food and Drug Administra-
ard may take effect before 1 year after tion determines that such referral is
the date of its publication unless: necessary or appropriate under the cir-
(1) The Food and Drug Administra- cumstances; or
tion determines that an earlier effec- (2) Requested by an interested per-
tive date is necessary to protect the son, in the form of a citizen petition in
public health and safety; or accordance with § 10.30 of this chapter,
(2) The standard has been established which is made within the period pro-
for a device that, by the effective date vided for comment on the proposed reg-
of the standard, has been reclassified ulation and which demonstrates good
from class III to class II. cause for referral.
(c) The Food and Drug Administra- (c) When a proposed regulation is re-
tion may declare a proposed regulation ferred to an advisory committee, the
amending a standard effective on publi- Food and Drug Administration will fur-
cation in the FEDERAL REGISTER if it nish the committee with the data and
determines that making the regulation information upon which the proposed
so effective is in the public interest. A regulation is based. After independ-
proposed amendment of a performance ently reviewing the materials fur-
standard made effective upon publica- nished by the Food and Drug Adminis-
tion may not prohibit the introduction tration and any other available data
or delivery for introduction into inter- and information, the advisory com-
state commerce of a device that con- mittee shall, within 60 days of the re-
forms to the standard without the ferral, submit a report and rec-
change or changes provided in the pro- ommendation on the proposed regula-
posed amendment until the effective tion, together with all underlying data
date of any final action on the pro- and information and a statement of the
posal. reason or basis for the recommenda-
[45 FR 7484, Feb. 1, 1980, as amended at 57 FR tion. A copy of the report and rec-
58405, Dec. 10, 1992] ommendation will be publicly dis-
played in the office of the Division of
§ 861.38 Standards advisory commit- Dockets Management, Food and Drug
tees. Administration.
(a) The Food and Drug Administra- (d) Where appropriate, each proposed
tion will establish advisory commit- regulation establishing a standard pub-
tees to which proposed regulations may lished in the FEDERAL REGISTER will
232
include a call for nominations to the 862.1140 Calcitonin test system.

advisory committee for that particular 862.1145 Calcium test system.
standard. 862.1150 Calibrator.
862.1155 Human chorionic gonadotropin
[45 FR 7484, Feb. 1, 1980, as amended at 57 FR (HCG) test system.
58405, Dec. 10, 1992] 862.1160 Bicarbonate/carbon dioxide test
system.
862.1163 Cardiac allograft gene expression
PART 862—CLINICAL CHEMISTRY profiling test system.
AND CLINICAL TOXICOLOGY 862.1165 Catecholamines (total) test system.
DEVICES 862.1170 Chloride test system.
862.1175 Cholesterol (total) test system.
Subpart A—General Provisions 862.1177 Cholylglycine test system.
862.1180 Chymotrypsin test system.
Sec. 862.1185 Compound S (11-deoxycortisol) test
862.1 Scope. system.
862.2 Regulation of calibrators. 862.1187 Conjugated sulfolithocholic acid
862.3 Effective dates of requirement for pre- (SLCG) test system.
market approval. 862.1190 Copper test system.
862.9 Limitations of exemptions from sec- 862.1195 Corticoids test system.
tion 510(k) of the Federal Food, Drug, 862.1200 Corticosterone test system.
and Cosmetic Act (the act). 862.1205 Cortisol (hydrocortisone and
hydroxycorticosterone) test system.
Subpart B—Clinical Chemistry Test Systems 862.1210 Creatine test system.
862.1215 Creatine phosphokinase/creatine ki-
862.1020 Acid phosphatase (total or pros- nase or isoenzymes test system.
tatic) test system. 862.1220 Acute kidney injury test system.
862.1025 Adrenocorticotropic hormone 862.1225 Creatinine test system.
(ACTH) test system. 862.1230 Cyclic AMP test system.
862.1030 Alanine amino transferase (ALT/ 862.1235 Cyclosporine test system.
SGPT) test system. 862.1240 Cystine test system.
862.1035 Albumin test system. 862.1245 Dehydroepiandrosterone (free and
862.1040 Aldolase test system. sulfate) test system.
862.1045 Aldosterone test system. 862.1250 Desoxycorticosterone test system.
862.1050 Alkaline phosphatase or isoenzymes 862.1255 2,3-Diphosphoglyceric acid test sys-
test system. tem.
862.1055 Newborn screening test system for 862.1260 Estradiol test system.
amino acids, free carnitine, and 862.1265 Estriol test system.
acylcarnitines using tandem mass spec- 862.1270 Estrogens (total, in pregnancy) test
trometry. system.
862.1060 Delta-aminolevulinic acid test sys- 862.1275 Estrogens (total, nonpregnancy)
tem. test system.
862.1065 Ammonia test system. 862.1280 Estrone test system.
862.1070 Amylase test system. 862.1285 Etiocholanolone test system.
862.1075 Androstenedione test system. 862.1290 Fatty acids test system.
862.1080 Androsterone test system. 862.1295 Folic acid test system.
862.1085 Angiotensin I and renin test sys- 862.1300 Follicle-stimulating hormone test
tem. system.
862.1090 Angiotensin converting enzyme 862.1305 Formiminoglutamic acid (FIGLU)
(A.C.E.) test system. test system.
862.1095 Ascorbic acid test system. 862.1310 Galactose test system.
862.1100 Aspartate amino transferase (AST/ 862.1315 Galactose-1-phosphate uridyl trans-
SGOT) test system. ferase test system.
862.1110 Bilirubin (total or direct) test sys- 862.1320 Gastric acidity test system.
tem. 862.1325 Gastrin test system.
862.1113 Bilirubin (total and unbound) in the 862.1330 Globulin test system.
neonate test system. 862.1335 Glucagon test system.
862.1115 Urinary bilirubin and its conjugates 862.1340 Urinary glucose (nonquantitative)
(nonquantitative) test system. test system.
862.1117 B-type natriuretic peptide test sys- 862.1345 Glucose test system.
tem. 862.1350 Continuous glucose monitor sec-
862.1118 Biotinidase test system. ondary alarm system.
862.1120 Blood gases (PCO2PO2) and blood pH 862.1355 Integrated continuous glucose mon-
test system. itoring system.
862.1130 Blood volume test system. 862.1356 Interoperable automated glycemic

862.1135 C-peptides of proinsulin test sys- controller.
tem. 862.1358 Insulin therapy adjustment device.
233
862.1360 Gamma-glutamyl transpeptidase 862.1575 Phospholipid test system.
and isoenzymes test system. 862.1580 Phosphorus (inorganic) test system.
862.1365 Glutathione test system. 862.1585 Human placental lactogen test sys-
862.1370 Human growth hormone test system.
tem. 862.1590 Porphobilinogen test system.
862.1373 Hemoglobin A1c test system. 862.1595 Porphyrins test system.
862.1375 Histidine test system. 862.1600 Potassium test system.
862.1377 Urinary homocystine (nonquantita- 862.1605 Pregnanediol test system.
tive) test system. 862.1610 Pregnanetriol test system.
862.1380 Hydroxybutyric dehydrogenase test 862.1615 Pregnenolone test system.
system. 862.1620 Progesterone test system.
862.1385 17-Hydroxycorticosteroids (17- 862.1622 Prognostic test for assessment of
ketogenic steroids) test system. liver related disease progression.
862.1390 5-Hydroxyindole acetic acid/sero- 862.1625 Prolactin (lactogen) test system.
tonin test system. 862.1630 Protein (fractionation) test system.
862.1395 17-Hydroxyprogesterone test sys- 862.1635 Total protein test system.
tem. 862.1640 Protein-bound iodine test system.
862.1400 Hydroxyproline test system. 862.1645 Urinary protein or albumin (non-
862.1405 Immunoreactive insulin test sys- quantitative) test system.
tem. 862.1650 Pyruvate kinase test system.
862.1410 Iron (non-heme) test system. 862.1655 Pyruvic acid test system.
862.1415 Iron-binding capacity test system. 862.1660 Quality control material (assayed
862.1420 Isocitric dehydrogenase test sys- and unassayed).
tem. 862.1665 Sodium test system.
862.1430 17-Ketosteroids test system. 862.1670 Sorbitol dehydrogenase test sys-
862.1435 Ketones (nonquantitative) test system.
tem. 862.1675 Blood specimen collection device.
862.1440 Lactate dehydrogenase test system. 862.1678 Tacrolimus test system.
862.1445 Lactate dehydrogenase isoenzymes 862.1680 Testosterone test system.
test system. 862.1685 Thyroxine-binding globulin test
862.1450 Lactic acid test system. system.
862.1455 Lecithin/sphingomyelin ratio in 862.1690 Thyroid-stimulating hormone test
amniotic fluid test system. system.
862.1460 Leucine aminopeptidase test sys- 862.1695 Free thyroxine test system.
tem. 862.1700 Total thyroxine test system.
862.1465 Lipase test system. 862.1705 Triglyceride test system.
862.1470 Lipid (total) test system. 862.1710 Total triiodothyronine test system.
862.1715 Triiodothyronine uptake test sys-
862.1475 Lipoprotein test system.
tem.
862.1485 Luteinizing hormone test system.
862.1720 Triose phosphate isomerase test
862.1490 Lysozyme (muramidase) test sys-
system.
tem.
862.1725 Trypsin test system.
862.1495 Magnesium test system.
862.1730 Free tyrosine test system.
862.1500 Malic dehydrogenase test system.
862.1770 Urea nitrogen test system.
862.1505 Mucopolysaccharides (nonquantita-
862.1775 Uric acid test system.
tive) test system.
862.1780 Urinary calculi (stones) test sys-
862.1509 Methylmalonic acid (nonquantita-
tem.
tive) test system. 862.1785 Urinary urobilinogen (nonquantita-
862.1510 Nitrite (nonquantitative) test sys- tive) test system.
tem. 862.1790 Uroporphyrin test system.
862.1515 Nitrogen (amino-nitrogen) test sys- 862.1795 Vanilmandelic acid test system.
tem. 862.1805 Vitamin A test system.
862.1520 5′-Nucleotidase test system. 862.1810 Vitamin B12 test system.
862.1530 Plasma oncometry test system. 862.1815 Vitamin E test system.
862.1535 Ornithine carbamyl transferase test 862.1820 Xylose test system.
system. 862.1825 Vitamin D test system.
862.1540 Osmolality test system. 862.1840 Total 25-hydroxyvitamin D mass
862.1542 Oxalate test system. spectrometry test system.
862.1545 Parathyroid hormone test system.
862.1550 Urinary pH (nonquantitative) test Subpart C—Clinical Laboratory Instruments
system.
862.1555 Phenylalanine test system. 862.2050 General purpose laboratory equip-
862.1560 Urinary phenylketones (non- ment labeled or promoted for a specific
quantitative) test system. medical use.
862.1565 6-Phosphogluconate dehydrogenase 862.2100 Calculator/data processing module
test system. for clinical use.

862.1570 Phosphohexose isomerase test sys- 862.2120 Continuous glucose monitor data
tem. management system.
234
862.2140 Centrifugal chemistry analyzer for 862.3280 Clinical toxicology control mate-
clinical use. rial.
862.2150 Continuous flow sequential mul- 862.3300 Digitoxin test system.
tiple chemistry analyzer for clinical use. 862.3320 Digoxin test system.
862.2160 Discrete photometric chemistry an- 862.3350 Diphenylhydantoin test system.
alyzer for clinical use. 862.3360 Drug metabolizing enzyme
862.2170 Micro chemistry analyzer for clin- genotyping system.
ical use. 862.3380 Ethosuximide test system.
862.2230 Chromatographic separation mate- 862.3450 Gentamicin test system.
rial for clinical use. 862.3520 Kanamycin test system.
862.2250 Gas liquid chromatography system 862.3550 Lead test system.
for clinical use. 862.3555 Lidocaine test system.
862.2260 High pressure liquid chroma- 862.3560 Lithium test system.
tography system for clinical use. 862.3580 Lysergic acid diethylamide (LSD)
862.2265 High throughput genomic sequence test system.
analyzer for clinical use. 862.3590 Meprobamate test system.
862.2270 Thin-layer chromatography system 862.3600 Mercury test system.
for clinical use. 862.3610 Methamphetamine test system.
862.2300 Colorimeter, photometer, or spec- 862.3620 Methadone test system.
trophotometer for clinical use. 862.3630 Methaqualone test system.
862.2310 Clinical sample concentrator. 862.3640 Morphine test system.
862.2320 Beta or gamma counter for clinical 862.3645 Neuroleptic drugs radioreceptor
use. assay test system.
862.2400 Densitometer/scanner (integrating, 862.3650 Opiate test system.
reflectance, TLC, or radiochromatogram) 862.3652 Organophosphate test system.
for clinical use. 862.3660 Phenobarbital test system.
862.2485 Electrophoresis apparatus for clin- 862.3670 Phenothiazine test system.
862.3680 Primidone test system.
ical use.
862.3700 Propoxyphene test system.
862.2500 Enzyme analyzer for clinical use.
862.3750 Quinine test system.
862.2540 Flame emission photometer for
862.3800 Reagents for molecular diagnostic
clinical use.
instrument test systems.
862.2560 Fluorometer for clinical use.
862.3830 Salicylate test system.
862.2570 Instrumentation for clinical multi-
862.3840 Sirolimus test system.
plex test systems. 862.3850 Sulfonamide test system.
862.2680 Microtitrator for clinical use. 862.3870 Cannabinoid test system.
862.2700 Nephelometer for clinical use. 862.3880 Theophylline test system.
862.2720 Plasma oncometer for clinical use. 862.3900 Tobramycin test system.
862.2730 Osmometer for clinical use. 862.3910 Tricyclic antidepressant drugs test
862.2750 Pipetting and diluting system for system.
clinical use. 862.3950 Vancomycin test system.
862.2800 Refractometer for clinical use.
862.2850 Atomic absorption spectrophotom- AUTHORITY: 21 U.S.C. 351, 360, 360c, 360e,
eter for clinical use. 360j, 360l, 371.
862.2860 Mass spectrometer for clinical use. SOURCE: 52 FR 16122, May 1, 1987, unless
862.2900 Automated urinalysis system. otherwise noted.
862.2920 Plasma viscometer for clinical use.
Subpart D—Clinical Toxicology Test part 862 appear at 73 FR 35341, June 23, 2008.
Systems
862.3030 Acetaminophen test system.
862.3035 Amikacin test system. § 862.1 Scope.
862.3040 Alcohol test system.
862.3050 Breath-alcohol test system. (a) This part sets forth the classifica-
862.3080 Breath nitric oxide test system. tion of clinical chemistry and clinical
862.3100 Amphetamine test system. toxicology devices intended for human
862.3110 Antimony test system. use that are in commercial distribu-
862.3120 Arsenic test system. tion.
862.3150 Barbiturate test system. (b) The identification of a device in a
862.3170 Benzodiazepine test system. regulation in this part is not a precise
862.3200 Clinical toxicology calibrator.
862.3220 Carbon monoxide test system.
description of every device that is, or
862.3240 Cholinesterase test system. will be, subject to the regulation. A
862.3250 Cocaine and cocaine metabolite test manufacturer who submits a pre-
system. market notification submission for a
862.3270 Codeine test system. device under part 807 cannot show
235
§ 862.2 21 CFR Ch. I (4–1–23 Edition)
merely that the device is accurately FDA’s issuance of an order approving

described by the section title and iden- an application for premarket approval
tification provisions of a regulation in (PMA) for the device or declaring com-
this part, but shall state why the de- pleted a product development protocol
vice is substantially equivalent to (PDP) for the device.
other devices, as required in § 807.87. (a) Before FDA requires that a device
(c) References in this part to regu- commercially distributed before the
latory sections of the Code of Federal enactment date of the amendments, or
Regulations are to chapter I of title 21 a device that has been found substan-
unless otherwise noted.
tially equivalent to such a device, has
(d) Guidance documents referenced in
an approval under section 515 of the act
this part are available on the Internet
at http://www.fda.gov/MedicalDevices/ FDA must promulgate a regulation
DeviceRegulationandGuidance/ under section 515(b) of the act requir-
GuidanceDocuments/default.htm. ing such approval, except as provided
in paragraph (b) of this section. Such a
[52 FR 16122, May 1, 1987, as amended at 67 regulation under section 515(b) of the
FR 58329, Sept. 16, 2002; 78 FR 18233, Mar. 26,
2013; 79 FR 50552, Aug. 25, 2014]
act shall not be effective during the
grace period ending on the 90th day
§ 862.2 Regulation of calibrators. after its promulgation or on the last
Many devices classified in this part day of the 30th full calendar month
are intended to be used with a cali- after the regulation that classifies the
brator. A calibrator has a reference device into class III is effective, which-
value assigned to it which serves as the ever is later. See section 501(f)(2)(B) of
basis by which test results of patients the act. Accordingly, unless an effec-
are derived or calculated. The cali- tive date of the requirement for pre-
brator for a device may be (a) manufac- market approval is shown in the regu-
tured and distributed separately from lation for a device classified into class
the device with which it is intended to III in this part, the device may be com-
be used, (b) manufactured and distrib- mercially distributed without FDA’s
uted as one of several device compo- issuance of an order approving a PMA
nents, such as in a kit of reagents, or or declaring completed a PDP for the
(c) built-in as an integral part of the device. If FDA promulgates a regula-
device. Because of the central role that tion under section 515(b) of the act re-
a calibrator plays in the measurement quiring premarket approval for a de-
process and the critical effect cali- vice, section 501(f)(1)(A) of the act ap-
brators have on accuracy of test re- plies to the device.
sults, elsewhere in this part, all three (b) Any new, not substantially equiv-
of these types of calibrators (§§ 862.1150 alent, device introduced into commer-
and 862.3200 of this part) are classified cial distribution on or after May 28,
into class II, notwithstanding the clas- 1976, including a device formerly mar-
sification of the device with which it is keted that has been substantially al-
intended to be used. Thus, a device and
tered, is classified by statute (section
its calibrator may have different clas-
513(f) of the act) into class III without
sifications, even if the calibrator is
any grace period and FDA must have
built into the device.
issued an order approving a PMA or de-
§ 862.3 Effective dates of requirement claring completed a PDP for the device
for premarket approval. before the device is commercially dis-
A device included in this part that is tributed unless it is reclassified. If
classified into class III (premarket ap- FDA knows that a device being com-
proval) shall not be commercially dis- mercially distributed may be a ‘‘new’’
tributed after the date shown in the device as defined in this section be-
regulation classifying the device unless cause of any new intended use or other
the manufacturer has an approval reasons, FDA may codify the statutory
under section 515 of the act (unless an classification of the device into class
exemption has been granted under sec- III for such new use. Accordingly, the
tion 520(g)(2) of the act). An approval regulation for such a class III device
under section 515 of the act consists of states that as of the enactment date of
236
the amendments, May 28, 1976, the de- orders, including inborn errors of me-
vice must have an approval under sec- tabolism;
tion 515 of the act before commercial (3) For measuring an analyte that
distribution. serves as a surrogate marker for
screening, diagnosis, or monitoring
§ 862.9 Limitations of exemptions from life-threatening diseases such as ac-
section 510(k) of the Federal Food, quired immune deficiency syndrome
Drug, and Cosmetic Act (the act).
(AIDS), chronic or active hepatitis, tu-
The exemption from the requirement berculosis, or myocardial infarction or
of premarket notification (section to monitor therapy;
510(k) of the act) for a generic type of (4) For assessing the risk of cardio-
class I or II device is only to the extent vascular diseases;
that the device has existing or reason- (5) For use in diabetes management;
ably foreseeable characteristics of (6) For identifying or inferring the
commercially distributed devices with- identity of a microorganism directly
in that generic type or, in the case of from clinical material;
in vitro diagnostic devices, only to the (7) For detection of antibodies to
extent that misdiagnosis as a result of microorganisms other than
using the device would not be associ- immunoglobulin G (IgG) or IgG assays
ated with high morbidity or mortality. when the results are not qualitative, or
Accordingly, manufacturers of any are used to determine immunity, or the
commercially distributed class I or II assay is intended for use in matrices
device for which FDA has granted an other than serum or plasma;
exemption from the requirement of
(8) For noninvasive testing as defined
premarket notification must still sub-
in § 812.3(k) of this chapter; and
mit a premarket notification to FDA
(9) For near patient testing (point of
before introducing or delivering for in-
care).
troduction into interstate commerce
for commercial distribution the device [65 FR 2304, Jan. 14, 2000]
when:
(a) The device is intended for a use Subpart B—Clinical Chemistry Test
different from the intended use of a le- Systems
gally marketed device in that generic
type of device; e.g., the device is in- § 862.1020 Acid phosphatase (total or
tended for a different medical purpose, prostatic) test system.
or the device is intended for lay use
(a) Identification. An acid phosphatase
where the former intended use was by
(total or prostatic) test system is a de-
health care professionals only;
vice intended to measure the activity
(b) The modified device operates
of the acid phosphatase enzyme in plas-
using a different fundamental sci-
ma and serum.
entific technology than a legally mar-
(b) Classification. Class II (special
keted device in that generic type of de-
controls). The device is exempt from
vice; e.g., a surgical instrument cuts
the premarket notification procedures
tissue with a laser beam rather than
in subpart E of part 807 of this chapter
with a sharpened metal blade, or an in
subject to the limitations in § 862.9.
vitro diagnostic device detects or iden-
tifies infectious agents by using [52 FR 16122, May 1, 1987, as amended at 84
deoxyribonucleic acid (DNA) probe or FR 71796, Dec. 30, 2019]
nucleic acid hybridization technology
rather than culture or immunoassay § 862.1025 Adrenocorticotropic hor-
technology; or mone (ACTH) test system.
(c) The device is an in vitro device (a) Identification. An
that is intended: adrenocorticotropic hormone (ACTH)
(1) For use in the diagnosis, moni- test system is a device intended to
toring, or screening of neoplastic dis- measure adrenocorticotropic hormone
eases with the exception of in plasma and serum. ACTH measure-
immunohistochemical devices; ments are used in the differential diag-

(2) For use in screening or diagnosis nosis and treatment of certain dis-
of familial or acquired genetic disorders of the adrenal glands such as
237
§ 862.1030 21 CFR Ch. I (4–1–23 Edition)
Cushing’s syndrome, adrenocortical in- urine. Aldosterone measurements are

sufficiency, and the ectopic ACTH syn- used in the diagnosis and treatment of
drome. primary aldosteronism (a disorder
(b) Classification. Class II. caused by the excessive secretion of
aldosterone by the adrenal gland), hy-
§ 862.1030 Alanine amino transferase pertension caused by primary
(ALT/SGPT) test system.
aldosteronism, selective
(a) Identification. An alanine amino hypoaldosteronism, edematous states,
transferase (ALT/SGPT) test system is and other conditions of electrolyte im-
a device intended to measure the activ- balance.
ity of the enzyme alanine amino trans- (b) Classification. Class II.
ferase (ALT) (also known as a serum
glutamic pyruvic transaminase or § 862.1050 Alkaline phosphatase or
SGPT) in serum and plasma. Alanine isoenzymes test system.
amino transferase measurements are
(a) Identification. An alkaline phos-
used in the diagnosis and treatment of
phatase or isoenzymes test system is a
certain liver diseases (e.g., viral hepa-
device intended to measure alkaline
titis and cirrhosis) and heart diseases.
phosphatase or its isoenzymes (a group
(b) Classification. Class I (general con-
of enzymes with similar biological ac-
trols). The device is exempt from the
tivity) in serum or plasma. Measure-
premarket notification procedures in
ments of alkaline phosphatase or its
subpart E of part 807 of this chapter
isoenzymes are used in the diagnosis
subject to § 862.9.
and treatment of liver, bone, parathy-
[52 FR 16122, May 1, 1987, as amended at 65 roid, and intestinal diseases.
FR 2305, Jan. 14, 2000] (b) Classification. Class II.
§ 862.1035 Albumin test system. § 862.1055 Newborn screening test sys-
(a) Identification. An albumin test tem for amino acids, free carnitine,
system is a device intended to measure and acylcarnitines using tandem
the albumin concentration in serum mass spectrometry.
and plasma. Albumin measurements (a) Identification. A newborn screen-
are used in the diagnosis and treating test system for amino acids, free
ment of numerous diseases involving carnitine, and acylcarnitines using
primarily the liver or kidneys. tandem mass spectrometry is a device
(b) Classification. Class II. that consists of stable isotope internal
standards, control materials, extrac-
§ 862.1040 Aldolase test system.
tion solutions, flow solvents, instru-
(a) Identification. An aldolase test mentation, software packages, and
system is a device intended to measure other reagents and materials. The de-
the activity of the enzyme aldolase in vice is intended for the measurement
serum or plasma. Aldolase measure- and evaluation of amino acids, free car-
ments are used in the diagnosis and nitine, and acylcarnitine concentra-
treatment of the early stages of acute tions from newborn whole blood filter
hepatitis and for certain muscle dis- paper samples. The quantitative anal-
eases such as progressive Duchenne- ysis of amino acids, free carnitine, and
type muscular dystrophy. acylcarnitines and their relationship
(b) Classification. Class I (general con- with each other provides analyte con-
trols). The device is exempt from the centration profiles that may aid in
premarket notification procedures in screening newborns for one or more in-
subpart E of part 807 of this chapter born errors of amino acid, free carni-
subject to § 862.9. tine, and acyl-carnitine metabolism.
[52 FR 16122, May 1, 1987, as amended at 65 (b) Classification. Class II (special
FR 2305, Jan. 14, 2000] controls). The special control is FDA’s
guidance document entitled ‘‘Class II
§ 862.1045 Aldosterone test system. Special Controls Guidance Document:
(a) Identification. An aldosterone test Newborn Screening Test Systems for

system is a device intended to measure Amino Acids, Free Carnitine, and
the hormone aldosterone in serum and Acylcarnitines Using Tandem Mass
238
Spectrometry.’’ See § 862.1(d) for the (b) Classification. Class I (general con-
availability of this guidance document. trols). The device is exempt from the
[69 FR 68255, Nov. 24, 2004]
§ 862.1060 Delta-aminolevulinic acid subject to § 862.9.
test system.
(a) Identification. A delta- FR 2305, Jan. 14, 2000]
aminolevulinic acid test system is a
device intended to measure the level of § 862.1080 Androsterone test system.
delta-aminolevulinic acid (a precursor (a) Identification. An androsterone
of porphyrin) in urine. Delta- test system is a device intended to
aminolevulinic acid measurements are measure the hormone adrosterone in
used in the diagnosis and treatment of serum, plasma, and urine. Andros-
lead poisoning and certain porphyrias
terone measurements are used in the
(diseases affecting the liver, gastro-
diagnosis and treatment of gonadal and
intestinal, and nervous systems that
adrenal diseases.
are accompanied by increased urinary
excretion of various heme compounds (b) Classification. Class I (general con-
including delta-aminolevulinic acid). trols). The device is exempt from the
(b) Classification. Class I (general con- premarket notification procedures in
trols). The device is exempt from pre- subpart E of part 807 of this chapter
market notification procedures in sub- subject to § 862.9.
part E of part 807 of this chapter sub- [52 FR 16122, May 1, 1987, as amended at 65
ject to § 862.9. FR 2305, Jan. 14, 2000]
FR 2305, Jan. 14, 2000] § 862.1085 Angiotensin I and renin test
system.
§ 862.1065 Ammonia test system. (a) Identification. An angiotensin I
(a) Identification. An ammonia test and renin test system is a device in-
system is a device intended to measure tended to measure the level of
ammonia levels in blood, serum, and angiotensin I generated by renin in
plasma, Ammonia measurements are plasma. Angiotensin I measurements
used in the diagnosis and treatment of are used in the diagnosis and treat-
severe liver disorders, such as cir- ment of certain types of hypertension.
rhosis, hepatitis, and Reye’s syndrome. (b) Classification. Class II.
(b) Classification. Class I.
§ 862.1090 Angiotensin converting en-
§ 862.1070 Amylase test system. zyme (A.C.E.) test system.
(a) Identification. An amylase test (a) Identification. An angiotensin con-
system is a device intended to measure verting enzyme (A.C.E.) test system is
the activity of the enzyme amylase in a device intended to measure the activ-
serum and urine. Amylase measure- ity of angiotensin converting enzyme
ments are used primarily for the diag- in serum and plasma. Measurements
nosis and treatment of pancreatitis (in- obtained by this device are used in the
flammation of the pancreas). diagnosis and treatment of diseases
(b) Classification. Class II. such as sarcoidosis, a disease charac-
§ 862.1075 Androstenedione test sys- terized by the formation of nodules in
tem. the lungs, bones, and skin, and
Gaucher’s disease, a hereditary dis-
(a) Identification. An androstenedione order affecting the spleen.
test system is a device intended to
measure androstenedione (a substance
secreted by the testes, ovary, and adre-
nal glands) in serum. Adrostenedione
measurements are used in the diag-
nosis and treatment of females with ex-

cessive levels of androgen (male sex [52 FR 16122, May 1, 1987, as amended at 84
hormone) production. FR 71796, Dec. 30, 2019]
239
§ 862.1095 21 CFR Ch. I (4–1–23 Edition)
§ 862.1095 Ascorbic acid test system. the levels of bilirubin (total and un-
(a) Identification. An ascorbic acid bound) in the blood (serum) of newborn
test system is a device intended to infants to aid in indicating the risk of
measure the level of ascorbic acid (vi- bilirubin encephalopathy (kernicterus).
tamin C) in plasma, serum, and urine. (b) Classification. Class I.
Ascorbic acid measurements are used [54 FR 30206, July 19, 1989]
in the diagnosis and treatment of
ascorbic acid dietary deficiencies. § 862.1115 Urinary bilirubin and its
(b) Classification. Class I (general con- conjugates (nonquantitative) test
trols). The device is exempt from the system.
premarket notification procedures in (a) Identification. A urinary bilirubin
subpart E of part 807 of this chapter and its conjugates (nonquantitative)
subject to § 862.9. test system is a device intended to
[52 FR 16122, May 1, 1987, as amended at 65 measure the levels of bilirubin con-
FR 2305, Jan. 14, 2000] jugates in urine. Measurements of uri-
nary bilirubin and its conjugates (non-
§ 862.1100 Aspartate amino transferase quantitative) are used in the diagnosis
(AST/SGOT) test system. and treatment of certain liver diseases.
(a) Identification. An aspartate amino (b) Classification. Class I (general con-
transferase (AST/SGOT) test system is trols). The device is exempt from the
a device intended to measure the activ- premarket notification procedures in
ity of the enzyme aspartate amino subpart E of part 807 of this chapter
transferase (AST) (also known as a subject to § 862.9.
serum glutamic oxaloacetic transferase
or SGOT) in serum and plasma. FR 2305, Jan. 14, 2000]
Aspartate amino transferase measure-
ments are used in the diagnosis and § 862.1117 B-type natriuretic peptide
treatment of certain types of liver and test system.
heart disease.
(a) Identification. The B-type
natriuretic peptide (BNP) test system
is an in vitro diagnostic device in-
tended to measure BNP in whole blood
and plasma. Measurements of BNP are
used as an aid in the diagnosis of pa-
[52 FR 16122, May 1, 1987, as amended at 84 tients with congestive heart failure.
FR 71796, Dec. 30, 2019] (b) Classification. Class II (special
controls). The special control is ‘‘Class
§ 862.1110 Bilirubin (total or direct)
test system. II Special Control Guidance Document
for B-Type Natriuretic Peptide Pre-
(a) Identification. A bilirubin (total or market Notifications; Final Guidance
direct) test system is a device intended for Industry and FDA Reviewers.’’
to measure the levels of bilirubin (total
or direct) in plasma or serum. Measure- [66 FR 12734, Feb. 28, 2001]
ments of the levels of bilirubin, an or-
ganic compound formed during the nor- § 862.1118 Biotinidase test system.
mal and abnormal distruction of red (a) Identification. The biotinidase test
blood cells, if used in the diagnosis and system is an in vitro diagnostic device
treatment of liver, hemolytic intended to measure the activity of the
hematological, and metabolic dis- enzyme biotinidase in blood. Measure-
orders, including hepatitis and gall ments of biotinidase are used in the
bladder block. treatment and diagnosis of biotinidase
(b) Classification. Class II. deficiency, an inborn error of metabo-
lism in infants, characterized by the
§ 862.1113 Bilirubin (total and un- inability to utilize dietary protein
bound) in the neonate test system. bound vitamin or to recycle endoge-
(a) Identification. A bilirubin (total nous biotin. The deficiency may result
and unbound) in the neonate test sys- in irreversible neurological impair-
tem is a device intended to measure ment.
240
(b) Classification. Class II (special § 862.1140 Calcitonin test system.

controls). The special control is sale,
(a) Identification. A calcitonin test
distribution, and use in accordance system is a device intended to measure
with the prescription device require- the thyroid hormone calcitonin
ments in § 801.109 of this chapter. (thyrocalcitonin) levels in plasma and
[65 FR 16521, Mar. 29, 2000] serum. Calcitonin measurements are
§ 862.1120 Blood gases (PCO2, PO2) and diseases involving the thyroid and
blood pH test system. parathyroid glands, including car-
(a) Identification. A blood gases (PCO2, cinoma and hyperparathyroidism (ex-
cessive activity of the parathyroid
PO2) and blood pH test system is a de-
gland).
vice intended to measure certain gases
(b) Classification. Class II.
in blood, serum, plasma or pH of blood,
serum, and plasma. Measurements of § 862.1145 Calcium test system.
blood gases (PCO2, PO2) and blood pH are
used in the diagnosis and treatment of (a) Identification. A calcium test sys-
life-threatening acid-base disturbances. tem is a device intended to measure
the total calcium level in serum. Cal-
cium measurements are used in the di-
§ 862.1130 Blood volume test system. agnosis and treatment of parathyroid
disease, a variety of bone diseases,
(a) Identification. A blood volume test chronic renal disease and tetany (inter-
system is a device intended to measure mittent muscular contractions or
the circulating blood volume. Blood spasms).
volume measurements are used in the (b) Classification. Class II.
diagnosis and treatment of shock, hem-
orrhage, and polycythemia vera (a dis- § 862.1150 Calibrator.
ease characterized by an absolute in- (a) Identification. A calibrator is a de-
crease in erythrocyte mass and total vice intended for medical purposes for
blood volume). use in a test system to establish points
(b) Classification. Class I (general con- of reference that are used in the deter-
trols). The device is exempt from the mination of values in the measurement
premarket notification procedures in of substances in human specimens. (See
subpart E of part 807 of this chapter also § 862.2 in this part.)
subject to § 862.9. (b) Classification. Class II (special
FR 2305, Jan. 14, 2000]
§ 862.1135 C-peptides of proinsulin test subject to the limitations in § 862.9.
system. [52 FR 16122, May 1, 1987, as amended at 84
(a) Identification. A C-peptides of FR 71796, Dec. 30, 2019]
proinsulin test system is a device in-
§ 862.1155 Human chorionic
tended to measure C-peptides of gonadotropin (HCG) test system.
proinsulin levels in serum, plasma, and
urine. Measurements of C-peptides of (a) Human chorionic gonadotropin
proinsulin are used in the diagnosis (HCG) test system intended for the early
and treatment of patients with abnor- detection of pregnancy—(1) Identification.
mal insulin secretion, including diabe- A human chorionic gonadotropin (HCG)
tes mellitus. test system is a device intended for the
early detection of pregnancy is in-
tended to measure HCG, a placental
trols). The device is exempt from the hormone, in plasma or urine.
(2) Classification. Class II.
(b) Human chorionic gonadotropin
(HCG) test system intended for any uses

[52 FR 16122, May 1, 1987, as amended at 65 other than early detection of pregnancy—
FR 2305, Jan. 14, 2000] (1) Identification. A human chorionic
241
§ 862.1160 21 CFR Ch. I (4–1–23 Edition)
goadotropin (HCG) test system is a de- lar compounds (epinephrine,

vice intended for any uses other than norepinephrine, and dopamine) are
early detection of pregnancy (such as present in urine and plasma.
an aid in the diagnosis, prognosis, and Catecholamine determinations are
management of treatment of persons used in the diagnosis and treatment of
with certain tumors or carcinomas) is adrenal medulla and hypertensive dis-
intended to measure HCG, a placental orders, and for catecholamine-secret-
hormone, in plasma or urine. ing tumors (pheochromo-cytoma, neu-
(2) Classification. Class III. roblastoma, ganglioneuroma, and
(3) Date PMA or notice of completion of retinoblastoma).
a PDP is required. As of the enactment
date of the amendments, May 28, 1976,
an approval under section 515 of the act trols). The device is exempt from the
is required before the device described premarket notification procedures in
in paragraph (b)(1) may be commer- subpart E of part 807 of this chapter
cially distributed. See § 862.3. subject to § 862.9.
§ 862.1160 Bicarbonate/carbon dioxide FR 2305, Jan. 14, 2000]
test system.
(a) Identification. A bicarbonate/car- § 862.1170 Chloride test system.
bon dioxide test system is a device in-
(a) Identification. A chloride test sys-
tended to measure bicarbonate/carbon
dioxide in plasma, serum, and whole tem is a device intended to measure
blood. Bicarbonate/carbon dioxide the level of chloride in plasma, serum,
measurements are used in the diag- sweat, and urine. Chloride measure-
nosis and treatment of numerous po- ments are used in the diagnosis and
tentially serious disorders associated treatment of electrolyte and metabolic
with changes in body acid-base bal- disorders such as cystic fibrosis and di-
ance. abetic acidosis.
(b) Classification. Class II. (b) Classification. Class II.
§ 862.1163 Cardiac allograft gene ex- § 862.1175 Cholesterol (total) test sys-
pression profiling test system. tem.
(a) Identification. A cardiac allograft (a) Identification. A cholesterol (total)
gene expression profiling test system is test system is a device intended to
a device that measures the ribonucleic measure cholesterol in plasma and
acid (RNA) expression level of multiple serum. Cholesterol measurements are
genes and combines this information to used in the diagnosis and treatment of
yield a signature (pattern, classifier, disorders involving excess cholesterol
index, score) to aid in the identifica- in the blood and lipid and lipoprotein
tion of a low probability of acute cel- metabolism disorders.
lular rejection (ACR) in heart trans- (b) Classification. Class I (general con-
plant recipients with stable allograft trols). The device is exempt from the
function. premarket notification procedures in
(b) Classification. Class II (special subpart E of part 807 of this chapter
controls). The special control is FDA’s subject to § 862.9.
Special Controls Guidance Document: [52 FR 16122, May 1, 1987, as amended at 65
Cardiac Allograft Gene Expression FR 2305, Jan. 14, 2000]
Profiling Test Systems.’’ See § 862.1(d)
for the availability of this guidance § 862.1177 Cholylglycine test system.
document. (a) Identification. A cholylglycine test
[74 FR 53885, Oct. 21, 2009] system is a device intended to measure
the bile acid cholylglycine in serum.
§ 862.1165 Catecholamines (total) test Measurements obtained by this device
system. are used in the diagnosis and treat-
(a) Identification. A catecholamines ment of liver disorders, such as cir-

(total) test system is a device intended rhosis or obstructive liver disease.
to determine whether a group of simi- (b) Classification. Class II.
242
§ 862.1180 Chymotrypsin test system. Wilson’s disease (a hereditary disease

(a) Identification. A chymotrypsin primarily of the liver and nervous sys-
test system is a device intended to tem). Test results are also used in mon-
measure the activity of the enzyme itoring patients with Hodgkin’s disease
chymotrypsin in blood and other body (a disease primarily of the lymph sys-
fluids and in feces. Chymotrypsin tem).
measurements are used in the diag- (b) Classification. Class I (general con-
nosis and treatment of pancreatic exo- trols). The device is exempt from the
crine insufficiency. premarket notification procedures in
(b) Classification. Class I (general con- subpart E of part 807 of this chapter
trols). The device is exempt from the subject to the limitations in § 862.9.
premarket notification procedures in [52 FR 16122, May 1, 1987, as amended at 53
subpart E of part 807 of this chapter FR 21449, June 8, 1988; 66 FR 38787, July 25,
subject to § 862.9. 2001]
[52 FR 16122, May 1, 1987, as amended at 65 § 862.1195 Corticoids test system.

FR 2305, Jan. 14, 2000]
(a) Identification. A corticoids test
§ 862.1185 Compound S (11- system is a device intended to measure
deoxycortisol) test system. the levels of corticoids (hormones of
(a) Identification. A compound S (11- the adrenal cortex) in serum and p
dioxycortisol) test system is a device lasma. Measurements of corticoids are
intended to measure the level of com- used in the diagnosis and treatment of
pound S (11-dioxycortisol) in plasma. disorders of the cortex of the adrenal
Compound S is a steroid intermediate glands, especially those associated
in the biosynthesis of the adrenal hor- with hypertension and electrolyte dis-
mone cortisol. Measurements of com- turbances.
pound S are used in the diagnosis and (b) Classification. Class I (general con-
treatment of certain adrenal and pitui- trols). The device is exempt from the
tary gland disorders resulting in clin- premarket notification procedures in
ical symptoms of masculinization and subpart E of part 807 of this chapter
hypertension. subject to § 862.9.
(b) Classification. Class I (general con- [52 FR 16122, May 1, 1987, as amended at 65
trols). The device is exempt from the FR 2305, Jan. 14, 2000]
subpart E of part 807 of this chapter § 862.1200 Corticosterone test system.
subject to § 862.9. (a) Identification. A corticosterone
[52 FR 16122, May 1, 1987, as amended at 65 test system is a device intended to
FR 2305, Jan. 14, 2000] measure corticosterone (a steroid se-
creted by the adrenal gland) levels in
§ 862.1187 Conjugated sulfolithocholic plasma. Measurements of corticos-
acid (SLCG) test system. terone are used in the diagnosis and
(a) Identification. A conjugated treatment of adrenal disorders such as
sulfolithocholic acid (SLCG) test sys- adrenal cortex disorders and blocks in
tem is a device intended to measure cortisol synthesis.
the bile acid SLCG in serum. Measure- (b) Classification. Class I (general con-
ments obtained by this device are used trols). The device is exempt from the
in the diagnosis and treatment of liver premarket notification procedures in
disorders, such as cirrhosis or obstruc- subpart E of part 807 of this chapter
tive liver disease. subject to § 862.9.
(b) Classification. Class II. [52 FR 16122, May 1, 1987, as amended at 65
FR 2305, Jan. 14, 2000]
§ 862.1190 Copper test system.
(a) Identification. A copper test sys- § 862.1205 Cortisol (hydrocortisone
tem is a device intended to measure and hydroxycorticosterone) test
copper levels in plasma, serum, and system.
urine. Measurements of copper are used (a) Identification. A cortisol (hydro-

in the diagnosis and treatment of ane- cortisone and hydroxycorticosterone)
mia, infections, inflammations, and test system is a device intended to
243
§ 862.1210 21 CFR Ch. I (4–1–23 Edition)
measure the cortisol hormones se- (b) Classification. Class II (special

creted by the adrenal gland in plasma controls). The special controls for this
and urine. Measurements of cortisol device are:
are used in the diagnosis and treat- (1) Premarket notification submis-
ment of disorders of the adrenal gland. sions must detail an appropriate end
(b) Classification. Class II. user device training program that will
be offered while marketing the device
§ 862.1210 Creatine test system. as part of your efforts to mitigate the
(a) Identification. A creatine test sys- risk of incorrect interpretation of test
results.
tem is a device intended to measure
(2) As part of the risk management
creatine (a substance synthesized in
activities performed as part of your 21
the liver and pancreas and found in bio-
CFR 820.30 design controls, you must
logical fluids) in plasma, serum, and
document the appropriate end user de-
urine. Measurements of creatine are
vice training program provided in your
premarket notification submission to
muscle diseases and endocrine dis- satisfy special control 21 CFR
orders including hyperthyroidism. 862.1220(b)(1) that will be offered while
(b) Classification. Class I (general con- marketing the device as part of your
trols). The device is exempt from the efforts to mitigate the risk of incorrect
premarket notification procedures in interpretation of test results.
subpart E of part 807 of this chapter (3) Robust clinical data dem-
subject to the limitations in § 862.9. onstrating the positive predictive
[52 FR 16122, May 1, 1987, as amended at 53 value, negative predictive value, sensi-
FR 21449, June 8, 1988; 66 FR 38787, July 25, tivity and specificity of the test in the
2001] intended use population must be sub-
mitted as part of the premarket notifi-
§ 862.1215 Creatine phosphokinase/cre- cation submission.
atine kinase or isoenzymes test sys-
tem. [82 FR 50072, Oct. 30, 2017]
(a) Identification. A creatine § 862.1225 Creatinine test system.

phosphokinase/creatine kinase or
(a) Identification. A creatinine test
isoenzymes test system is a device in- system is a device intended to measure
tended to measure the activity of the creatinine levels in plasma and urine.
enzyme creatine phosphokinase or its Creatinine measurements are used in
isoenzymes (a group of enzymes with the diagnosis and treatment of renal
similar biological activity) in plasma diseases, in monitoring renal dialysis,
and serum. Measurements of creatine and as a calculation basis for meas-
phosphokinase and its isoenzymes are uring other urine analytes.
used in the diagnosis and treatment of (b) Classification. Class II.
myocardial infarction and muscle dis-
eases such as progressive, Duchenne- § 862.1230 Cyclic AMP test system.
type muscular dystrophy. (a) Identification. A cyclic AMP test
(b) Classification. Class II. system is a device intended to measure
the level of adenosine 3′, 5′-
§ 862.1220 Acute kidney injury test sys-
monophosphate (cyclic AMP) in plas-
tem.
ma, urine, and other body fluids. Cyclic
(a) Identification. An acute kidney in- AMP measurements are used in the di-
jury test system is a device that is in- agnosis and treatment of endocrine dis-
tended to measure one or more orders, including hyperparathyroidism
analytes in human samples as an aid in (overactivity of the parathyroid gland).
the assessment of a patient’s risk for Cyclic AMP measurements may also be
developing acute kidney injury. Test used in the diagnosis and treatment of
results are intended to be used in con- Graves’ disease (a disorder of the thy-
junction with other clinical and diag- roid) and in the differentiation of
nostic findings, consistent with profes- causes of hypercalcemia (elevated lev-

sional standards of practice, including els of serum calcium.)
confirmation by alternative methods. (b) Classification. Class II.
244
§ 862.1235 Cyclosporine test system. § 862.1250 Desoxycorticosterone test

system.
(a) Identification. A cyclosporine test
system is a device intended to quan- (a) Identification. A
titatively determine cyclosporine con- desoxycorticosterone test system is a
centrations as an aid in the manage- device intended to measure
ment of transplant patients receiving desoxycorticosterone (DOC) in plasma
and urine. DOC measurements are used
therapy with this drug. This generic
in the diagnosis and treatment of pa-
type of device includes immunoassays
tients with hypermineralocorticoidism
and chromatographic assays for
(excess retention of sodium and loss of
cyclosporine. potassium) and other disorders of the
(b) Classification. Class II (special adrenal gland.
controls). The special control is ‘‘Class (b) Classification. Class I (general con-
II Special Controls Guidance Docu- trols). The device is exempt from the
ment: Cyclosporine and Tacrolimus As- premarket notification procedures in
says; Guidance for Industry and FDA.’’ subpart E of part 807 of this chapter
See § 862.1(d) for the availability of this subject to § 862.9.
guidance document.
[67 FR 58329, Sept. 16, 2002] FR 2306, Jan. 14, 2000]
§ 862.1240 Cystine test system. § 862.1255 2,3-Diphosphoglyceric acid

test system.
(a) Identification. A cystine test sys-
(a) Identification. A 2,3-
diphosphoglyceric acid test system is a
the amino acid cystine in urine. Cys-
device intended to measure 2,3-
tine measurements are used in the di-
diphosphoglyceric acid (2,3-DPG) in
agnosis of cystinuria (occurrence of erythrocytes (red blood cells). Meas-
cystine in urine). Patients with urements of 2,3-diphosphoglyceric acid
cystinuria frequently develop kidney are used in the diagnosis and treat-
calculi (stones). ment of blood disorders that affect the
(b) Classification. Class I (general con- delivery of oxygen by erythrocytes to
trols). The device is exempt from the tissues and in monitoring the quality
premarket notification procedures in of stored blood.
subpart E of part 807 of this chapter (b) Classification. Class I (general con-
subject to § 862.9. trols). The device is exempt from the
FR 2305, Jan. 14, 2000] subpart E of part 807 of this chapter
§ 862.1245 Dehydroepiandrosterone [52 FR 16122, May 1, 1987, as amended at 53
(free and sulfate) test system. FR 21449, June 8, 1988; 66 FR 38787, July 25,
(a) Identification. A 2001]
dehydroepiandrosterone (free and sul- § 862.1260 Estradiol test system.
fate) test system is a device intended
to measure dehydroepiandrosterone (a) Identification. An estradiol test
system is a device intended to measure
(DHEA) and its sulfate in urine, serum,
estradiol, an estrogenic steroid, in
plasma, and amniotic fluid.
plasma. Estradiol measurements are
Dehydroepiandrosterone measurements
are used in the diagnosis and treat- various hormonal sexual disorders and
ment of DHEA-secreting adrenal car- in assessing placental function in com-
cinomas. plicated pregnancy.
(b) Classification. Class I (general con- (b) Classification. Class I (general con-
trols). The device is exempt from the trols). The device is exempt from the
premarket notification procedures in premarket notification procedures in
subpart E of part 807 of this chapter subpart E of part 807 of this chapter
subject to § 862.9. subject to § 862.9.
[52 FR 16122, May 1, 1987, as amended at 65 [52 FR 16122, May 1, 1987, as amended at 65
FR 2306, Jan. 14, 2000] FR 2306, Jan. 14, 2000]
245
§ 862.1265 21 CFR Ch. I (4–1–23 Edition)
§ 862.1265 Estriol test system. subpart E of part 807 of this chapter

(a) Identification. An estriol test sys-
tem is a device intended to measure es- [52 FR 16122, May 1, 1987, as amended at 65
triol, an estrogenic steroid, in plasma, FR 2306, Jan. 14, 2000]
serum, and urine of pregnant females.
§ 862.1280 Estrone test system.
Estriol measurements are used in the
diagnosis and treatment of (a) Identification. An estrone test sys-
fetoplacental distress in certain cases tem is a device intended to measure
of high-risk pregnancy. estrone, an estrogenic steroid, in plas-
(b) Classification. Class I (general con- ma. Estrone measurements are used in
trols). The device is exempt from the the diagnosis and treatment of numer-
premarket notification procedures in ous disorders, including infertility,
subpart E of part 807 of this chapter amenorrhea, differentiation of primary
subject to § 862.9. and secondary ovarian malfunction, es-
trogen secreting testicular and ovarian
[52 FR 16122, May 1, 1987, as amended at 65 tumors, and precocious puberty in fe-
FR 2306, Jan. 14, 2000] males.
§ 862.1270 Estrogens (total, in preg- trols). The device is exempt from the
nancy) test system. premarket notification procedures in
(a) Identification. As estrogens (total, subpart E of part 807 of this chapter
in pregnancy) test system is a device subject to § 862.9.
intended to measure total estrogens in [52 FR 16122, May 1, 1987, as amended at 65
plasma, serum, and urine during preg- FR 2306, Jan. 14, 2000]
nancy. The device primarily measures
estrone plus estradiol. Measurements § 862.1285 Etiocholanolone test system.
of total estrogens are used to aid in the (a) Identification. An etiocholanolone
diagnosis and treatment of test system is a device intended to
fetoplacental distress in certain cases measure etiocholanolone in serum and
of high-risk pregnancy. urine. Etiocholanolone is a metabolic
(b) Classification. Class I (general con- product of the hormone testosterone
trols). The device is exempt from the and is excreted in the urine.
premarket notification procedures in Etiocholanolone measurements are
subpart E of part 807 of this chapter used in the diagnosis and treatment of
subject to § 862.9. disorders of the testes and ovaries.
FR 2306, Jan. 14, 2000] trols). The device is exempt from the
§ 862.1275 Estrogens (total, nonpreg- subpart E of part 807 of this chapter
nancy) test system. subject to § 862.9.
(a) Identification. As estrogens (total, [52 FR 16122, May 1, 1987, as amended at 65
nonpregnancy) test system is a device FR 2306, Jan. 14, 2000]
intended to measure the level of estro-
gens (total estrone, estradiol, and es- § 862.1290 Fatty acids test system.
triol) in plasma, serum, and urine of (a) Identification. A fatty acids test
males and nonpregnant females. Meas- system is a device intended to measure
urement of estrogens (total, nonpreg- fatty acids in plasma and serum. Meas-
nancy) is used in the diagnosis and urements of fatty acids are used in the
treatment of numerous disorders, in- diagnosis and treatment of various dis-
cluding infertility, amenorrhea (ab- orders of lipid metabolism.
sence of menses) differentiation of pri- (b) Classification. Class I (general con-
mary and secondary ovarian malfunc- trols). The device is exempt from the
tion, estrogen secreting testicular and premarket notification procedures in
ovarian tumors, and precocious pu- subpart E of part 807 of this chapter
berty in females. subject to the limitations in § 862.9.
trols). The device is exempt from the FR 21449, June 8, 1988; 66 FR 38787, July 25,
premarket notification procedures in 2001]
246
§ 862.1295 Folic acid test system. disease galactosemia (a disorder of ga-

lactose metabolism) in infants.
(a) Identification. A folic acid test sys-
tem is a device intended to measure (b) Classification. Class I.
the vitamin folic acid in plasma and
§ 862.1315 Galactose-1-phosphate
serum. Folic acid measurements are uridyl transferase test system.
megaloblastic anemia, which is charac- (a) Identification. A galactose-1-phos-
terized by the presence of megaloblasts phate uridyl transferase test system is
(an abnormal red blood cell series) in a device intended to measure the activ-
the bone marrow. ity of the enzyme galactose-1-phos-
(b) Classification. Class II. phate uridyl transferase in
erythrocytes (red blood cells). Meas-
[52 FR 16122, May 1, 1987; 53 FR 11645, Apr. 8,
1988] urements of galactose-1-phosphate
uridyl transferase are used in the diag-
§ 862.1300 Follicle-stimulating hor- nosis and treatment of the hereditary
mone test system. disease galactosemia (disorder of galac-
(a) Identification. A follicle-stimu- tose metabolism) in infants.
lating hormone test system is a device (b) Classification. Class II.
intended to measure follicle-stimu-
lating hormone (FSH) in plasma, § 862.1320 Gastric acidity test system.
serum, and urine. FSH measurements (a) Identification. A gastric acidity
are used in the diagnosis and treat- test system is a device intended to
ment of pituitary gland and gonadal measure the acidity of gastric fluid.
disorders. Measurements of gastric acidity are
(b) Classification. Class I (general con- used in the diagnosis and treatment of
trols). The device is exempt from the patients with peptic ulcer, Zollinger-
premarket notification procedures in Ellison syndrome (peptic ulcer due to
subpart E of part 807 of this chapter gastrin-secreting tumor of the pan-
creas), and related gastric disorders.
[52 FR 16122, May 1, 1987, as amended at 65 (b) Classification. Class I (general con-
FR 2306, Jan. 14, 2000] trols). The device is exempt from the
§ 862.1305 Formiminoglutamic acid
(FIGLU) test system. subpart E of part 807 of this chapter
(a) Identification. A
formiminoglutamic acid (FIGLU) test [52 FR 16122, May 1, 1987, as amended at 53
system is a device intended to measure FR 21449, June 8, 1988; 66 FR 38787, July 25,
formiminolutamic acid in urine. 2001]
FIGLU measurements obtained by this
§ 862.1325 Gastrin test system.
device are used in the diagnosis of
anemias, such as pernicious anemia (a) Identification. A gastrin test sys-
and congenital hemolytic anemia. tem is a device intended to measure
(b) Classification. Class I (general con- the hormone gastrin in plasma and
trols). The device is exempt from the serum. Measurements of gastrin are
premarket notification procedures in used in the diagnosis and treatment of
subpart E of part 807 of this chapter patients with ulcers, pernicious ane-
subject to the limitations in § 862.9. mia, and the Zollinger-Ellison syn-
[52 FR 16122, May 1, 1987, as amended at 53 drome (peptic ulcer due to a gastrin-se-
FR 21449, June 8, 1988; 66 FR 38787, July 25, creting tumor of the pancreas).
2001] (b) Classification. Class I (general con-
§ 862.1310 Galactose test system. premarket notification procedures in
(a) Identification. A galactose test subpart E of part 807 of this chapter
system is a device intended to measure subject to § 862.9.
galactose in blood and urine. Galactose

measurements are used in the diag- [52 FR 16122, May 1, 1987, as amended at 65
FR 2306, Jan. 14, 2000]
nosis and treatment of the hereditary
247
§ 862.1330 21 CFR Ch. I (4–1–23 Edition)
§ 862.1330 Globulin test system. hypoglycemia, and of pancreatic islet

(a) Identification. A globulin test sys- cell carcinoma.
controls). The device, when it is solely
globulins (proteins) in plasma and
intended for use as a drink to test glu-
serum. Measurements of globulin are
cose tolerance, is exempt from the pre-
market notification procedures in sub-
patients with numerous illnesses in-
part E of part 807 of this chapter sub-
cluding severe liver and renal disease,
ject to the limitations in § 862.9.
multiple myeloma, and other disorders
of blood globulins. [52 FR 16122, May 1, 1987, as amended at 84
(b) Classification. Class I (general con- FR 71796, Dec. 30, 2019; 85 FR 18445, Apr. 2,
trols). The device is exempt from the 2020]
§ 862.1350 Continuous glucose monitor
subpart E of part 807 of this chapter secondary alarm system.
(a) Identification. A continuous glu-
[52 FR 16122, May 1, 1987, as amended at 65 cose monitor (CGM) secondary alarm
FR 2306, Jan. 14, 2000] system is identified as a device in-
§ 862.1335 Glucagon test system. tended to be used as a secondary alarm
for a CGM to enable immediate aware-
(a) Identification. A glucagon test sys- ness for potential clinical intervention
tem is a device intended to measure to help assure patient safety.
the pancreatic hormone glucagon in (b) Classification. Class II (special
plasma and serum. Glucagon measure- controls). The device is exempt from
ments are used in the diagnosis and the premarket notification procedures
treatment of patients with various dis- in subpart E of part 807 of this chapter
orders of carbohydrate metabolism, in- subject to the limitations in § 862.9. The
cluding diabetes mellitus, hypo- special controls for this device are:
glycemia, and hyperglycemia. (1) Devices being marketed must in-
(b) Classification. Class I (general conclude appropriate measures to protect
trols). The device is exempt from the against unauthorized access to data
premarket notification procedures in and unauthorized modification of data.
subpart E of part 807 of this chapter (2) The labeling must prominently
subject to § 862.9. and conspicuously display a warning
[52 FR 16122, May 1, 1987, as amended at 65 that states ‘‘Dosing decisions should
FR 2306, Jan. 14, 2000] not be made based on this device. The
user should follow instructions on the
§ 862.1340 Urinary glucose (noncontinuous glucose monitoring sys-
quantitative) test system. tem.’’
(a) Identification. A urinary glucose (3) The labeling for the device must
(nonquantitative) test system is a de- include a statement that reads ‘‘This
vice intended to measure glucosuria device is not intended to replace self-
(glucose in urine). Urinary glucose monitoring practices as advised by a
(nonquantitative) measurements are physician.’’
used in the diagnosis and treatment of [82 FR 13550, Mar. 14, 2017, as amended at 84
carbohydrate metabolism disorders in- FR 71796, Dec. 30, 2019; 86 FR 20283, Apr. 19,
cluding diabetes mellitus, hypo- 2021]
glycemia, and hyperglycemia.
(b) Classification. Class II. § 862.1355 Integrated continuous glu-
cose monitoring system.
§ 862.1345 Glucose test system. (a) Identification. An integrated con-
(a) Identification. A glucose test sys- tinuous glucose monitoring system
tem is a device intended to measure (iCGM) is intended to automatically
glucose quantitatively in blood and measure glucose in bodily fluids con-
other body fluids. Glucose measure- tinuously or frequently for a specified
ments are used in the diagnosis and period of time. iCGM systems are de-
treatment of carbohydrate metabolism signed to reliably and securely trans-

disorders including diabetes mellitus, mit glucose measurement data to
neonatal hypoglycemia, and idiopathic digitally connected devices, including
248
automated insulin dosing systems, and (D) For all iCGM measurements less
are intended to be used alone or in con- than 70 mg/dL, the percentage of iCGM
junction with these digitally connected measurements within ±40 mg/dL of the
medical devices for the purpose of man- corresponding blood glucose value
aging a disease or condition related to must be calculated, and the lower one-
glycemic control. sided 95 percent confidence bound must
(b) Classification. Class II (special exceed 98 percent.
controls). The special controls for this (E) For all iCGM measurements from
device are: 70 mg/dL to 180 mg/dL, the percentage
(1) Design verification and validation of iCGM measurements within ±40 per-
must include the following: cent of the corresponding blood glucose
(i) Robust clinical data dem- value must be calculated, and the
onstrating the accuracy of the device lower one-sided 95 percent confidence
in the intended use population. bound must exceed 99 percent.
(ii) The clinical data must include a (F) For all iCGM measurements
comparison between iCGM values and greater than180 mg/dL, the percentage
blood glucose values in specimens col- of iCGM measurements within ±40 per-
lected in parallel that are measured on cent of the corresponding blood glucose
an FDA-accepted laboratory-based glu- value must be calculated, and the
cose measurement method that is pre- lower one-sided 95 percent confidence
cise and accurate, and that is traceable bound must exceed 99 percent.
to a higher order (e.g., an internation- (G) Throughout the device measuring
ally recognized reference material and/ range, the percentage of iCGM meas-
or method). urements within ±20 percent of the cor-
(iii) The clinical data must be ob- responding blood glucose value must be
tained from a clinical study designed calculated, and the lower one-sided 95
to fully represent the performance of percent confidence bound must exceed
the device throughout the intended use 87 percent.
population and throughout the meas- (H) When iCGM values are less than
uring range of the device. 70 mg/dL, no corresponding blood glu-
(iv) Clinical study results must dem- cose value shall read above 180 mg/dL.
onstrate consistent analytical and clin- (I) When iCGM values are greater
ical performance throughout the sensor than 180 mg/dL, no corresponding blood
wear period. glucose value shall read less than 70
(v) Clinical study results in the adult mg/dL.
population must meet the following (J) There shall be no more than 1 per-
performance requirements: cent of iCGM measurements that indi-
(A) For all iCGM measurements less cate a positive glucose rate of change
than 70 milligrams/deciliter (mg/dL), greater than 1 mg/dL per minute (/min)
the percentage of iCGM measurements when the corresponding true negative
within ±15 mg/dL of the corresponding glucose rate of change is less than ¥2
blood glucose value must be calculated, mg/dL/min as determined by the cor-
and the lower one-sided 95 percent con- responding blood glucose measure-
fidence bound must exceed 85 percent. ments.
(B) For all iCGM measurements from (K) There shall be no more than 1
70 mg/dL to 180 mg/dL, the percentage percent of iCGM measurements that in-
of iCGM measurements within ±15 per- dicate a negative glucose rate of
cent of the corresponding blood glucose change less than ¥1 mg/dL/min when
value must be calculated, and the the corresponding true positive glucose
lower one-sided 95 percent confidence rate of change is greater than 2 mg/dL/
bound must exceed 70 percent. min as determined by the cor-
(C) For all iCGM measurements responding blood glucose measure-
greater than 180 mg/dL, the percentage ments.
of iCGM measurements within ±15 per- (vi) Data demonstrating similar ac-
cent of the corresponding blood glucose curacy and rate of change performance
value must be calculated, and the of the iCGM in the pediatric population
lower one-sided 95 percent confidence as compared to that in the adult popu-
bound must exceed 80 percent. lation, or alternatively a clinical and/
249
§ 862.1356 21 CFR Ch. I (4–1–23 Edition)
or technical justification for why pedi- dL, greater than 180 to 250 mg/dL, and
atric data are not needed, must be pro- greater than 250 mg/dL.
vided and determined by FDA to be ac- (ii) A description of the accuracy of
ceptable and appropriate. positive and negative rate of change
(vii) Data must demonstrate that data.
throughout the claimed sensor life, the (iii) A description of the frequency
device does not allow clinically signifi- and duration of gaps in sensor data.
cant gaps in sensor data availability (iv) A description of the true, false,
that would prevent any digitally con- missed, and correct alert rates and a
nected devices from achieving their in- description of the available glucose
tended use. concentration alert settings, if applica-
(2) Design verification and validation ble.
must include a detailed strategy to en- (v) A description of the observed du-
sure secure and reliable means of iCGM ration of iCGM life for the device.
data transmission to provide real-time [87 FR 9238, Feb. 18, 2022]
glucose readings at clinically meaning-
ful time intervals to devices intended § 862.1356 Interoperable automated
to receive the iCGM glucose data. glycemic controller.
(3) Design verification and validation (a) Identification. An interoperable
must include adequate controls estab- automated glycemic controller is a de-
lished during manufacturing and at vice intended to automatically cal-
product release to ensure the released culate drug doses based on inputs such
product meets the performance speci- as glucose and other relevant physio-
fications as defined in paragraphs (b)(1) logical parameters, and to command
and (b)(2) of this section. the delivery of such drug doses from a
(4) The device must demonstrate connected infusion pump. Interoper-
clinically acceptable performance in able automated glycemic controllers
the presence of clinically relevant lev- are designed to reliably and securely
els of potential interfering substances communicate with digitally connected
that are reasonably present in the in- devices to allow drug delivery com-
tended use population, including but mands to be sent, received, executed,
not limited to endogenous substances and confirmed. Interoperable auto-
and metabolites, foods, dietary supple- mated glycemic controllers are in-
ments, and medications. tended to be used in conjunction with
(5) The device must include appro- digitally connected devices for the pur-
priate measures to ensure that dispos- pose of maintaining glycemic control.
able sensors cannot be used beyond its (b) Classification. Class II (special
claimed sensor wear period. controls). The special controls for this
(6) Design verification and validation device are:
must include results obtained through (1) Design verification and validation
a usability study that demonstrates must include:
that the intended user can use the de- (i) An appropriate, as determined by
vice safely and obtain the expected glu- FDA, clinical implementation strat-
cose measurement accuracy. egy, including data demonstrating ap-
(7) The labeling required under propriate, as determined by FDA, clin-
§ 809.10(b) of this chapter must include ical performance of the device for its
a separate description of the following intended use, including all of its indi-
sensor performance data observed in cations for use.
the clinical study performed in con- (A) The clinical data must be rep-
formance with paragraph (b)(1) of this resentative of the performance of the
section for each intended use popu- device in the intended use population
lation, in addition to separate sensor and in clinically relevant use scenarios
performance data for each different and sufficient to demonstrate appro-
iCGM insertion or use sites (e.g., abdo- priate, as determined by FDA, clinical
men, arm, buttock): performance of the device for its in-
(i) A description of the accuracy in tended use, including all of its indica-
the following blood glucose concentrations for use.

tion ranges: less than 54 mg/dL, 54 mg/ (B) For devices indicated for use with
dL to less than 70 mg/dL, 70 to 180 mg/ multiple therapeutic agents for the
250
same therapeutic effect (e.g., more are digitally connected to the con-
than one type of insulin), data dem- troller.
onstrating performance with each (2) Design verification and validation
product or, alternatively, an appro- documentation must include appro-
priate, as determined by FDA, clinical priate design inputs and design outputs
justification for why such data are not that are essential for the proper func-
needed. tioning of the device that have been
(C) When determined to be necessary documented and include the following:
by FDA, the strategy must include (i) Risk control measures to address
postmarket data collection to confirm device system hazards;
safe real-world use and monitor for (ii) Design decisions related to how
rare adverse events. the risk control measures impact es-
(ii) Results obtained through a sential performance; and
human factors study that dem- (iii) A traceability analysis dem-
onstrates that an intended user can onstrating that all hazards are ade-
safely use the device for its intended quately controlled and that all con-
use. trols have been validated in the final
(iii) A detailed and appropriate, as device design.
determined by FDA, strategy to ensure (3) The device shall include appro-
secure and reliable means of data priate, as determined by FDA, and vali-
dated interface specifications for
transmission with other intended con-
digitally connected devices. These
nected devices.
interface specifications shall, at a min-
(iv) Specifications that are appro-
imum, provide for the following:
priate, as determined by FDA, for con- (i) Secure authentication (pairing) to
nected devices that shall be eligible to connected devices;
provide input to (e.g., specification of (ii) Secure, accurate, and reliable
glucose sensor performance) or accept means of data transmission between
commands from (e.g., specifications for the controller and connected devices;
drug infusion pump performance) the (iii) Sharing of necessary state infor-
controller, and a detailed strategy for mation between the controller and any
ensuring that connected devices meet connected devices (e.g., battery level,
these specifications. reservoir level, sensor use life, pump
(v) Specifications for devices respon- status, error conditions);
sible for hosting the controller, and a (iv) Ensuring that the controller con-
detailed and appropriate, as deter- tinues to operate safely when data is
mined by FDA, strategy for ensuring received in a manner outside the
that the specifications are met by the bounds of the parameters specified;
hosting devices. (v) A detailed process and procedures
(vi) Documentation demonstrating for sharing the controller’s interface
that appropriate, as determined by specification with connected devices
FDA, measures are in place (e.g., vali- and for validating the correct imple-
dated device design features) to ensure mentation of that protocol; and
that safe therapy is maintained when (vi) A mechanism for updating the
communication with digitally con- controller software, including any soft-
nected devices is interrupted, lost, or ware that is required for operation of
re-established after an interruption. the controller in a manner that ensures
Validation testing results must dem- its safety and performance.
onstrate that critical events that occur (4) The device design must ensure
during a loss of communications (e.g., that a record of critical events is
commands, device malfunctions, occlu- stored and accessible for an adequate
sions, etc.) are handled and logged ap- period to allow for auditing of commu-
propriately during and after the inter- nications between digitally connected
ruption to maintain patient safety. devices, and to facilitate the sharing of
(vii) A detailed plan and procedure pertinent information with the respon-
for assigning postmarket responsibil- sible parties for those connected de-
ities including adverse event reporting, vices. Critical events to be stored by

complaint handling, and investigations the controller must, at a minimum, in-
with the manufacturers of devices that clude:
251
§ 862.1358 21 CFR Ch. I (4–1–23 Edition)
(i) Commands issued by the con- this device has been determined to be
troller, and associated confirmations unsafe.
the controller receives from digitally (iii) A prominent statement identi-
connected devices; fying by name the therapeutic agents
(ii) Malfunctions of the controller that are compatible with the con-
and malfunctions reported to the controller, including their identity and
troller by digitally connected devices concentration, as appropriate.
(e.g., infusion pump occlusion, glucose (iv) The identity of those digitally
sensor shut down); connected devices with which the con-
(iii) Alarms and alerts and associated troller can be used, including descrip-
acknowledgements from the controller tions of the specific system configura-
as well as those reported to the con- tions that can be used, per the detailed
troller by digitally connected devices; strategy submitted under paragraph
(b)(1)(iii) of this section.
and
(v) A comprehensive description of
(iv) Connectivity events (e.g., estab- representative clinical performance in
lishment or loss of communications). the hands of the intended user, includ-
(5) The device must only receive glu- ing information specific to use in the
cose input from devices cleared under pediatric use population, as appro-
§ 862.1355 (integrated continuous glu- priate.
cose monitoring system), unless FDA (vi) A comprehensive description of
determines an alternate type of glucose safety of the device, including, for ex-
input device is designed appropriately ample, the incidence of severe hypo-
to allow the controller to meet the spe- glycemia, diabetic ketoacidosis, and
cial controls contained within this sec- other relevant adverse events observed
tion. in a study conducted to satisfy para-
(6) The device must only command graph (b)(1)(i) of this section.
drug delivery from devices cleared (vii) For wireless connection enabled
under § 880.5730 of this chapter (alter- devices, a description of the wireless
nate controller enabled infusion pump), quality of service required for proper
unless FDA determines an alternate use of the device.
type of drug infusion pump device is (viii) For any controller with hard-
designed appropriately to allow the ware components intended for multiple
controller to meet the special controls patient reuse, instructions for safely
contained within this section. reprocessing the hardware components
(7) An appropriate, as determined by between uses.
FDA, training plan must be established [87 FR 14172, Mar. 14, 2022]
for users and healthcare providers to
assure the safety and performance of § 862.1358 Insulin therapy adjustment
the device when used. This may in- device.
clude, but not be limited to, training (a) Identification. An insulin therapy
on device contraindications, situations adjustment device is a device intended
in which the device should not be used, to incorporate biological inputs, in-
notable differences in device cluding glucose measurement data
functionality or features compared to from a continuous glucose monitor, to
similar alternative therapies, and in- recommend insulin therapy adjust-
formation to help prescribers identify ments as an aid in optimizing insulin
suitable candidate patients, as applica- therapy regimens for patients with dia-
ble. betes mellitus.
(8) The labeling required under (b) Classification. Class II (special
§ 809.10(b) of this chapter must include: controls). The special controls for this
(i) A contraindication for use in pedi- device are:
atric populations except to the extent (1) Design verification and validation
clinical performance data or other must include the following:
available information demonstrates (i) A complete description of the re-
that it can be safely used in pediatric quired data inputs, including time-
populations in whole or in part. frame over which data inputs must be

(ii) A prominent statement identi- collected and number of data points re-
fying any populations for which use of quired for accurate recommendations;
252
(ii) A complete description of the § 862.1360 Gamma-glutamyl

types of device outputs and insulin transpeptidase and isoenzymes test
therapy adjustment recommendations, system.
including how the recommendations (a) Identification. A gamma-glutamyl
are generated;
transpeptidase and isoenzymes test
(iii) Robust data demonstrating the
clinical validity of the device outputs system is a device intended to measure
and insulin therapy recommendations; the activity of the enzyme gamma-
(iv) A robust assessment of all input glutamyl transpeptidase (GGTP) in
data specifications, including accuracy plasma and serum. Gamma-glutamyl
requirements for continuous glucose transpeptidase and isoenzymes meas-
monitors and other devices generating urements are used in the diagnosis and
data inputs, to ensure accurate and re- treatment of liver diseases such as al-
liable therapy adjustment rec- coholic cirrhosis and primary and sec-
ommendations. This assessment must ondary liver tumors.
include adequate clinical justification (b) Classification. Class I (general con-
for each specification; trols). The device is exempt from the
(v) A detailed strategy to ensure se- premarket notification procedures in
cure and reliable means of data trans- subpart E of part 807 of this chapter
mission to and from the device, includ- subject to § 862.9.
ing data integrity checks, accuracy
checks, reliability checks, and security [52 FR 16122, May 1, 1987, as amended at 65
measures; FR 2306, Jan. 14, 2000]
(vi) Robust data demonstrating that
users can understand and appropriately § 862.1365 Glutathione test system.
interpret recommendations generated (a) Identification. A glutathione test
by the device; and system is a device intended to measure
(vii) An appropriate mitigation strat- glutathione (the tripeptide of glycine,
egy to minimize the occurrence of dos- cysteine, and glutamic acid) in
ing recommendation errors, and to erythrocytes (red blood cells). Gluta-
mitigate the risk to patients of any re- thione measurements are used in the
sidual dosing recommendation errors diagnosis and treatment of certain
to a clinically acceptable level.
drug-induced hemolytic (erythrocyte
(2) The device must not be intended
destroying) anemias due to an inher-
for use in implementing automated in-
sulin dosing. ited enzyme deficiency.
(3) Your 21 CFR 809.10(b) labeling (b) Classification. Class I (general con-
must include: trols). The device is exempt from the
(i) The identification of specific insu- premarket notification procedures in
lin formulations that have been dem- subpart E of part 807 of this chapter
onstrated to be compatible with use of subject to the limitations in § 862.9
the device; [52 FR 16122, May 1, 1987, as amended at 53
(ii) A detailed description of the spec- FR 21449, June 8, 1988; 66 FR 38787, July 25,
ifications of compatible devices that 2001]
provide acceptable input data (e.g.,
continuous glucose monitors, insulin § 862.1370 Human growth hormone
pumps) used to provide accurate and test system.
reliable therapy adjustment rec-
(a) Identification. A human growth
ommendations;
(iii) A detailed description of all hormone test system is a device in-
types of required data (inputs) and dos- tended to measure the levels of human
ing recommendations (outputs) that growth hormone in plasma. Human
are provided by the device; and growth hormone measurements are
(iv) A description of device limita- used in the diagnosis and treatment of
tions, and instructions to prevent pos- disorders involving the anterior lobe of
sible disruption of accurate therapy ad- the pituitary gland.
justment recommendations (e.g., time (b) Classification. Class I (general con-
zone changes due to travel). trols). The device is exempt from the
[83 FR 54874, Nov. 1, 2018] premarket notification procedures in
253
§ 862.1373 21 CFR Ch. I (4–1–23 Edition)
subpart E of part 807 of this chapter hemoglobin variants with low fre-
subject to § 862.9. quency in the population is observed, a
warning statement must be placed in a
FR 2306, Jan. 14, 2000] black box and must appear in all label-
ing material for these devices describ-
§ 862.1373 Hemoglobin A1c test system. ing the interference and any affected
(a) Identification. A hemoglobin A1c populations.
test system is a device used to measure [79 FR 50551, Aug. 25, 2014]
the percentage concentration of hemo-
globin A1c in blood. Measurement of § 862.1375 Histidine test system.
hemoglobin A1c is used as an aid in the (a) Identification. A histidine test sys-
diagnosis of diabetes mellitus and as an tem is a device intended to measure
aid in the identification of patients at free histidine (an amino acid) in plas-
risk for developing diabetes mellitus. ma and urine. Histidine measurements
(b) Classification. Class II (special are used in the diagnosis and treat-
controls). The special controls for this ment of hereditary histidinemia char-
device are: acterized by excess histidine in the
(1) The device must have initial and blood and urine often resulting in men-
annual standardization verification by tal retardation and disordered speech
a certifying glycohemoglobin standard- development.
ization organization deemed acceptable (b) Classification. Class I (general con-
by FDA. trols). The device is exempt from the
(2) The premarket notification sub-
mission must include performance
testing to evaluate precision, accuracy,
linearity, and interference, including
the following: [52 FR 16122, May 1, 1987, as amended at 65
(i) Performance testing of device pre- FR 2306, Jan. 14, 2000]
cision must, at a minimum, use blood
samples with concentrations near 5.0 § 862.1377 Urinary homocystine (non-
quantitative) test system.
percent, 6.5 percent, 8.0 percent, and 12
percent hemoglobin A1c. This testing (a) Identification. A urinary
must evaluate precision over a min- homocystine (nonquantitative) test
imum of 20 days using at least three system is a device intended to identify
lots of the device and three instru- homocystine (an analogue of the amino
ments, as applicable. acid cystine) in urine. The identifica-
(ii) Performance testing of device action of urinary homocystine is used in
curacy must include a minimum of 120 the diagnosis and treatment of
blood samples that span the measuring homocystinuria (homosystine in
interval of the device and compare re- urine), a heritable metabolic disorder
sults of the new device to results of a which may cause mental retardation.
standardized test method. Results (b) Classification. Class II.
must demonstrate little or no bias
versus the standardized method. § 862.1380 Hydroxybutyric dehydro-
(iii) Total error of the new device genase test system.
must be evaluated using single meas- (a) Identification. A hydroxybutyric
urements by the new device compared dehydrogenase test system is a device
to results of the standardized test intended to measure the activity of the
method, and this evaluation must dem- enzyme alpha-hydroxybutric dehydro-
onstrate a total error less than or genase (HBD) in plasma or serum. HBD
equal to 6 percent. measurements are used in the diag-
(iv) Performance testing must dem- nosis and treatment of myocardial in-
onstrate that there is little to no inter- farction, renal damage (such as rejec-
ference from common hemoglobin tion of transplants), certain
variants, including Hemoglobin C, He- hematological diseases (such as acute
moglobin D, Hemoglobin E, Hemo- leukemias and megaloblastic anemias)
globin A2, and Hemoglobin S. and, to a lesser degree, liver disease.

(3) When assay interference from He- (b) Classification. Class I (general con-
moglobin F or interference with other trols). The device is exempt from the
254
premarket notification procedures in § 862.1395 17-Hydroxyprogesterone

subpart E of part 807 of this chapter test system.
subject to the limitations in § 862.9. (a) Identification. A 17-
[52 FR 16122, May 1, 1987, as amended at 53 hydroxyprogesterone test system is a
FR 21449, June 8, 1988; 66 FR 38787, July 25, device intended to measure 17-
2001] hydroxyprogesterone (a steroid) in
plasma and serum. Measurements of 17-
§ 862.1385 17-Hydroxycorticosteroids hydroxyprogesterone are used in the
(17-ketogenic steroids) test system. diagnosis and treatment of various dis-
(a) Identification. A 17-hydroxy- orders of the adrenal glands or the ova-
corticosteroids (17-ketogenic steroids) ries.
test system is a device intended to (b) Classification. Class I (general con-
measure corticosteroids that possess a trols). The device is exempt from the
dihydroxyacetone premarket notification procedures in
FR 2306, Jan. 14, 2000]
moiety on the steroid nucleus in urine. § 862.1400 Hydroxyproline test system.

Corticosteroids with this chemical con-
figuration include cortisol, cortisone (a) Identification. A hydroxyproline
11-desoxycortisol,
measure the amino acid
desoxycorticosterone, and their
hydroxyproline in urine.
tetrahydroderivatives. This group of
Hydroxyproline measurements are used
hormones is synthesized by the adrenal
in the diagnosis and treatment of var-
gland. Measurements of 17-hydroxy-
ious collagen (connective tissue) dis-
corticosteroids (17-ketogenic steroids)
eases, bone disease such as Paget’s dis-
are used in the diagnosis and treat-
ease, and endocrine disorders such as
ment of various diseases of the adrenal
hyperparathyroidism and hyper-
or pituitary glands and gonadal dis-
thyroidism.
orders.
(b) Classification. Class I (general controls). The device is exempt from the
trols). The device is exempt from the premarket notification procedures in
premarket notification procedures in subpart E of part 807 of this chapter
subpart E of part 807 of this chapter subject to § 862.9.
[52 FR 16122, May 1, 1987; 52 FR 29468, Aug. 7, FR 2306, Jan. 14, 2000]
1987, as amended at 65 FR 2306, Jan. 14, 2000]
§ 862.1405 Immunoreactive insulin test
§ 862.1390 5-Hydroxyindole acetic acid/ system.
serotonin test system.
(a) Identification. An immunoreactive
(a) Identification. A 5-hydroxyindole insulin test system is a device intended
acetic acid/serotonin test system is a to measure immunoreactive insulin in
device intended to measure 5- serum and plasma. Immunoreactive in-
hydroxyindole acetic acid/serotonin in sulin measurements are used in the di-
urine. Measurements of 5- agnosis and treatment of various car-
hydroxyindole acetic acid/serotonin are bohydrate metabolism disorders, in-
used in the diagnosis and treatment of cluding diabetes mellitus, and hypo-
carcinoid tumors of endocrine tissue. glycemia.
FR 2306, Jan. 14, 2000] FR 2306, Jan. 14, 2000]
255
ER01FE93.028</GPH>
§ 862.1410 21 CFR Ch. I (4–1–23 Edition)
§ 862.1410 Iron (non-heme) test system. subpart E of part 807 of this chapter
(a) Identification. An iron (non-heme)
test system is a device intended to [52 FR 16122, May 1, 1987, as amended at 53
measure iron (non-heme) in serum and FR 21449, June 8, 1988; 66 FR 38788, July 25,
plasma. Iron (non-heme) measurements 2001]
§ 862.1430 17-Ketosteroids test system.
ment of diseases such as iron defi-
ciency anemia, hemochromatosis (a (a) Identification. A 17-ketosteroids
disease associated with widespread de- test system is a device intended to
posit in the tissues of two iron-con- measure 17-ketosteroids in urine. Meas-
taining pigments, hemosiderin and urements of 17-ketosteroids are used in
hemofuscin, and characterized by pig- the diagnosis and treatment of dis-
mentation of the skin), and chronic orders of the adrenal cortex and gonads
renal disease. and of other endocrine disorders, in-
(b) Classification. Class I (general concluding hypertension, diabetes, and
trols). The device is exempt from the hypothyroidism.
premarket notification procedures in (b) Classification. Class I (general con-
subpart E of part 807 of this chapter trols). The device is exempt from the
subject to the limitations in § 862.9. premarket notification procedures in
[52 FR 16122, May 1, 1987, as amended at 84 subject to § 862.9.
FR 71796, Dec. 30, 2019]
§ 862.1415 Iron-binding capacity test FR 2307, Jan. 14, 2000]
system.
§ 862.1435 Ketones (nonquantitative)
(a) Identification. An iron-binding ca- test system.
pacity test system is a device intended (a) Identification. A ketones (non-
to measure iron-binding capacity in quantitative) test system is a device
serum. Iron-binding capacity measure- intended to identify ketones in urine
ments are used in the diagnosis and and other body fluids. Identification of
treatment of anemia. ketones is used in the diagnosis and
(b) Classification. Class I (general con- treatment of acidosis (a condition
trols). The device is exempt from the characterized by abnormally high acid-
premarket notification procedures in ity of body fluids) or ketosis (a condi-
subpart E of part 807 of this chapter tion characterized by increased produc-
subject to the limitations in § 862.9. tion of ketone bodies such as acetone)
[52 FR 16122, May 1, 1987, as amended at 84 and for monitoring patients on
FR 71796, Dec. 30, 2019] ketogenic diets and patients with dia-
betes.
§ 862.1420 Isocitric dehydrogenase test (b) Classification. Class I (general con-
system. trols). The device is exempt from the
(a) Identification. An isocitric dehy- premarket notification procedures in
drogenase test system is a device in- subpart E of part 807 of this chapter
tended to measure the activity of the subject to § 862.9.
enzyme isocitric dehydrogenase in [52 FR 16122, May 1, 1987, as amended at 65
serum and plasma. Isocitric dehydro- FR 2307, Jan. 14, 2000]
genase measurements are used in the
diagnosis and treatment of liver dis- § 862.1440 Lactate dehydrogenase test
ease such as viral hepatitis, cirrhosis, system.
or acute inflammation of the biliary (a) Identification. A lactate dehydro-
tract; pulmonary disease such as pul- genase test system is a device intended
monary infarction (local arrest or sud- to measure the activity of the enzyme
den insufficiency of the blood supply to lactate dehydrogenase in serum. Lac-
the lungs), and diseases associated with tate dehydrogenase measurements are
pregnancy. used in the diagnosis and treatment of
(b) Classification. Class I (general con- liver diseases such as acute viral hepa-
trols). The device is exempt from the titis, cirrhosis, and metastatic car-
premarket notification procedures in cinoma of the liver, cardiac diseases
256
such as myocardial infarction, and tu- sphingomyelin ratio in amniotic fluid

mors of the lung or kidneys. are used in evaluating fetal maturity.
(b) Classification. Class II (special (b) Classification. Class II.
the premarket notification procedures § 862.1460 Leucine aminopeptidase
in subpart E of part 807 of this chapter test system.
subject to § 862.9. (a) Identification. A leucine
[52 FR 16122, May 1, 1987, as amended at 63 aminopeptidase test system is a device
FR 59225, Nov. 3, 1998] intended to measure the activity of the
enzyme leucine amino-peptidase in
§ 862.1445 Lactate dehydrogenase serum, plasma, and urine. Leucine
isoenzymes test system. aminopeptidase measurements are used
(a) Identification. A lactate dehydro- in the diagnosis and treatment of liver
genase isoenzymes test system is a de- diseases such as viral hepatitis and ob-
vice intended to measure the activity structive jaundice.
of lactate dehydrogenase isoenzymes (a (b) Classification. Class I (general con-
group of enzymes with similar biologi- trols). The device is exempt from the
cal activity) in serum. Measurements premarket notification procedures in
of lactate dehydrogenase isoenzymes subpart E of part 807 of this chapter
are used in the diagnosis and treat- subject to § 862.9.
ment of liver diseases, such as viral
hepatitis, and myocardial infarction.
FR 2307, Jan. 14, 2000]
controls). The device is exempt from § 862.1465 Lipase test system.
in subpart E of part 807 of this chapter (a) Identification. A lipase test system
subject to the limitations in § 862.9. is a device intended to measure the ac-
tivity of the enzymes lipase in serum.
[52 FR 16122, May 1, 1987, as amended at 84 Lipase measurements are used in diag-
FR 71796, Dec. 30, 2019] nosis and treatment of diseases of the
pancreas such as acute pancreatitis
§ 862.1450 Lactic acid test system.
and obstruction of the pancreatic duct.
(a) Identification. A lactic acid test (b) Classification. Class I (general con-
system is a device intended to measure trols). The device is exempt from the
lactic acid in whole blood and plasma. premarket notification procedures in
Lactic acid measurements that evalu- subpart E of part 807 of this chapter
ate the acid-base status are used in the subject to § 862.9.
diagnosis and treatment of lactic aci-
dosis (abnormally high acidity of the [52 FR 16122, May 1, 1987, as amended at 65
blood). FR 2307, Jan. 14, 2000]
§ 862.1470 Lipid (total) test system.
premarket notification procedures in (a) Identification. A lipid (total) test
subpart E of part 807 of this chapter system is a device intended to measure
subject to § 862.9. total lipids (fats or fat-like substances)
in serum and plasma. Lipid (total)
FR 2307, Jan. 14, 2000] measurements are used in the diag-
nosis and treatment of various diseases
§ 862.1455 Lecithin/sphingomyelin involving lipid metabolism and athero-
ratio in amniotic fluid test system. sclerosis.
(a) Identification. A lecithin/ (b) Classification. Class I (general con-
sphingomyelin ratio in amniotic fluid trols). The device is exempt from the
test system is a device intended to premarket notification procedures in
measure the lecithin/sphingomyelin subpart E of part 807 of this chapter
ratio in amniotic fluid. Lecithin and subject to the limitations in § 862.9.
sphingomyelin are phospholipids (fats [52 FR 16122, May 1, 1987, as amended at 53

or fat-like substances containing phos- FR 21449, June 8, 1988; 66 FR 38788, July 25,
phorus). Measurements of the lecithin/ 2001]
257
§ 862.1475 21 CFR Ch. I (4–1–23 Edition)
§ 862.1475 Lipoprotein test system. ma. Magnesium measurements are used

(a) Identification. A lipoprotein test in the diagnosis and treatment of
system is a device intended to measure hypomagnesemia (abnormally low plas-
lipoprotein in serum and plasma. ma levels of magnesium) and
Lipoprotein measurements are used in hypermagnesemia (abnormally high
the diagnosis and treatment of lipid plasma levels of magnesium).
disorders (such as diabetes mellitus),
atherosclerosis, and various liver and § 862.1500 Malic dehydrogenase test
renal diseases. system.
(a) Identification. A malic dehydro-
genase test system is a device that is
intended to measure the activity of the
enzyme malic dehydrogenase in serum
and plasma. Malic dehydrogenase
[52 FR 16122, May 1, 1987, as amended at 65 measurements are used in the diag-
FR 2307, Jan. 14, 2000] nosis and treatment of muscle and
liver diseases, myocardial infarctions,
§ 862.1485 Luteinizing hormone test
system. cancer, and blood disorders such as
myelogenous (produced in the bone
(a) Identification. A luteinizing hor- marrow) leukemia.
mone test system is a device intended (b) Classification. Class I (general con-
to measure luteinizing hormone in trols). The device is exempt from the
serum and urine. Luteinizing hormone premarket notification procedures in
measurements are used in the diag- subpart E of part 807 of this chapter
nosis and treatment of gonadal dys- subject to § 862.9.
function.
FR 2307, Jan. 14, 2000]
premarket notification procedures in § 862.1505 Mucopolysaccharides (non-
subpart E of part 807 of this chapter quantitative) test system.
subject to § 862.9. (a) Identification. A
[52 FR 16122, May 1, 1987, as amended at 65 mucopolysaccharides (nonquantitative)
FR 2307, Jan. 14, 2000] test system is a device intended to
measure the levels of
§ 862.1490 Lysozyme (muramidase) test mucopolysaccharides in urine.
system. Mucopolysaccharide measurements in
(a) Identification. A lysozyme urine are used in the diagnosis and
(muramidase) test system is a device treatment of various inheritable dis-
intended to measure the activity of the orders that affect bone and connective
bacteriolytic enzyme lysozyme tissues, such as Hurler’s, Hunter’s,
(muramidase) in serum, plasma, leu- Sanfilippo’s, Scheie’s Morquio’s and
kocytes, and urine. Lysozyme measure- Maroteaux-Lamy syndromes.
ments are used in the diagnosis and (b) Classification. Class I (general con-
treatment of monocytic leukemia and trols). The device is exempt from the
kidney disease. premarket notification procedures in
trols). The device is exempt from the subject to § 862.9.
premarket notification procedures in [52 FR 16122, May 1, 1987, as amended at 65
subpart E of part 807 of this chapter FR 2307, Jan. 14, 2000]
[52 FR 16122, May 1, 1987, as amended at 53 § 862.1509 Methylmalonic acid (non-
FR 21449, June 8, 1988; 66 FR 38788, July 25, quantitative) test system.
2001] (a) Identification. A methylmalonic
acid (nonquantitative) test system is a
§ 862.1495 Magnesium test system. device intended to identify
(a) Identification. A magnesium test methylmalonic acid in urine. The iden-

system is a device intended to measure tification of methylmalonic acid in
magnesium levels in serum and plas- urine is used in the diagnosis and
258
treatment of methylmalonic aciduria, (b) Classification. Class I (general con-

a heritable metabolic disorder which, if trols). The device is exempt from the
untreated, may cause mental retarda- premarket notification procedures in
tion. subpart E of part 807 of this chapter
(b) Classification. Class II (special subject to § 862.9.
controls). The device is exempt from [52 FR 16122, May 1, 1987, as amended at 65
the premarket notification procedures FR 2307, Jan. 14, 2000]
subject to the limitations in § 862.9. § 862.1530 Plasma oncometry test sys-
tem.
FR 71796, Dec. 30, 2019] (a) Identification. A plasma
oncometry test system is a device in-
§ 862.1510 Nitrite (nonquantitative) tended to measure plasma oncotic pres-
test system. sure. Plasma oncotic pressure is that
(a) Identification. A nitrite (non- portion of the total fluid pressure con-
quantitative) test system is a device tributed by proteins and other mol-
intended to identify nitrite in urine. ecules too large to pass through a spec-
Nitrite identification is used in the di- ified membrane. Measurements of plas-
agnosis and treatment of uninary tract ma oncotic pressure are used in the di-
infection of bacterial origin. agnosis and treatment of dehydration
(b) Classification. Class I (general con- and circulatory disorders related to
trols). The device is exempt from the low serum protein levels and increased
premarket notification procedures in capillary permeability, such as edema
subpart E of part 807 of this chapter and shock.
subject to § 862.9. (b) Classification. Class I (general con-
FR 2307, Jan. 14, 2000] premarket notification procedures in
§ 862.1515 Nitrogen (amino-nitrogen) subject to § 862.9.
test system. [52 FR 16122, May 1, 1987, as amended at 65
(a) Identification. A nitrogen (amino- FR 2307, Jan. 14, 2000]
nitrogen) test system is a device in-
tended to measure amino acid nitrogen § 862.1535 Ornithine carbamyl trans-
levels in serum, plasma, and urine. Ni- ferase test system.
trogen (amino-nitrogen) measurements (a) Identification. An ornithine
are used in the diagnosis and treat- carbamyl transferase test system is a
ment of certain forms of severe liver device intended to measure the activ-
disease and renal disorders. ity of the enzyme ornithine carbamyl
(b) Classification. Class I (general con- transferase (OCT) in serum. Ornithine
trols). The device is exempt from the carbamyl transferase measurements
premarket notification procedures in are used in the diagnosis and treat-
subpart E of part 807 of this chapter ment of liver diseases, such as infec-
subject to the limitations in § 862.9. tious hepatitis, acute cholecystitis (in-
flammation of the gall bladder), cir-
FR 21449, June 8, 1988; 66 FR 38788, July 25,
rhosis, and liver metastases.
2001] (b) Classification. Class I (general con-
§ 862.1520 5′-Nucleotidase test system. premarket notification procedures in
(a) Identification. A 5′-nucleotidase subpart E of part 807 of this chapter
test system is a device intended to subject to § 862.9.
measure the activity of the enzyme 5′- [52 FR 16122, May 1, 1987, as amended at 65
nucleotidase in serum and plasma. FR 2307, Jan. 14, 2000]
Measurements of 5′-nucleotidase are
used in the diagnosis and treatment of § 862.1540 Osmolality test system.
liver diseases and in the differentia- (a) Identification. An osmolality test
tions between liver and bone diseases system is a device intended to measure
in the presence of elevated serum alka- ionic and nonionic solute concentra-
line phosphatase activity. tion in body fluids, such as serum and
259
§ 862.1542 21 CFR Ch. I (4–1–23 Edition)
urine. Osmolality measurement is used premarket notification procedures in

as an adjunct to other tests in the eval- subpart E of part 807 of this chapter
uation of a variety of diseases, includ- subject to § 862.9.
ing kidney diseases (e.g., chronic pro-
gressive renal failure), diabetes FR 2307, Jan. 14, 2000]
insipidus, other endocrine and meta-
bolic disorders, and fluid imbalances. § 862.1555 Phenylalanine test system.
trols). The device is exempt from the (a) Identification. A phenylalanine
premarket notification procedures in test system is a device intended to
subpart E of part 807 of this chapter measure free phenylalanine (an amino
subject to § 862.9. acid) in serum, plasma, and urine.
Measurements of phenylalanine are
[52 FR 16122, May 1, 1987, as amended at 65 used in the diagnosis and treatment of
FR 2307, Jan. 14, 2000] congenital phenylketonuria which, if
untreated, may cause mental retarda-
§ 862.1542 Oxalate test system.
tion.
(a) Identification. An oxalate test sys- (b) Classification. Class II.
the concentration of oxalate in urine. § 862.1560 Urinary phenylketones
Measurements of oxalate are used to (nonquantitative) test system.
aid in the diagnosis or treatment of (a) Identification. A urinary
urinary stones or certain other meta- phenylketones (nonquantitative) test
bolic disorders. system is a device intended to identify
(b) Classification. Class I (general con- phenylketones (such as phenylpyruvic
trols). The device is exempt from the acid) in urine. The identification of
premarket notification procedures in urinary phenylketones is used in the
subpart E of part 807 of this chapter diagnosis and treatment of congenital
subject to § 862.9. phenylketonuria which, if untreated,
[52 FR 16122, May 1, 1987, as amended at 65 may cause mental retardation.
FR 2307, Jan. 14, 2000] (b) Classification. Class I (general con-
§ 862.1545 Parathyroid hormone test premarket notification procedures in
system.
(a) Identification. A parathyroid hor- subject to § 862.9.
mone test system is a device intended
to measure the levels of parathyroid [52 FR 16122, May 1, 1987, as amended at 65
FR 2307, Jan. 14, 2000]
hormone in serum and plasma. Meas-
urements of parathyroid hormone lev- § 862.1565 6-Phosphogluconate dehy-
els are used in the differential diag- drogenase test system.
nosis of hypercalcemia (abnormally
high levels of calcium in the blood) and (a) Identification. A 6-
hypocalcemia (abnormally low levels of phosphogluconate dehydrogenase test
calcium in the blood) resulting from system is a device intended to measure
disorders of calcium metabolism. the activity of the enzyme 6-
(b) Classification. Class II. phosphogluconate dehydrogenase (6
PGD) in serum and erythrocytes. Meas-
§ 862.1550 Urinary pH (nonquantita- urements of 6-phosphogluconate dehy-
tive) test system. drogenase are used in the diagnosis and
(a) Identification. A urinary pH (non- treatment of certain liver diseases
quantitative) test system is a device (such as hepatitis) and anemias.
intended to estimate the pH of urine. (b) Classification. Class I (general con-
Estimations of pH are used to evaluate trols). The device is exempt from the
the acidity or alkalinity of urine as it premarket notification procedures in
relates to numerous renal and meta- subpart E of part 807 of this chapter
bolic disorders and in the monitoring subject to the limitations in § 862.9.
of patients with certain diets. [52 FR 16122, May 1, 1987, as amended at 53

(b) Classification. Class I (general con- FR 21449, June 8, 1988; 66 FR 38788, July 25,
260
§ 862.1570 Phosphohexose isomerase § 862.1585 Human placental lactogen

test system. test system.
(a) Identification. A phosphohexose (a) Identification. A human placental
isomerase test system is a device in- lactogen test system is a device in-
tended to measure the activity of the tended to measure the hormone human
enzyme phosphohexose isomerase in placental lactogen (HPL), (also known
serum. Measurements of as human chorionic
phosphohexose isomerase are used in somatomammotrophin (HCS)), in ma-
the diagnosis and treatment of muscle ternal serum and maternal plasma.
diseases such as muscular dystrophy, Measurements of human placental
lactogen are used in the diagnosis and
liver diseases such as hepatitis or cir-
clinical management of high-risk preg-
rhosis, and metastatic carcinoma.
nancies involving fetal distress associ-
(b) Classification. Class I (general con- ated with placental insufficiency.
trols). The device is exempt from the Measurements of HPL are also used in
premarket notification procedures in pregnancies complicated by hyper-
subpart E of part 807 of this chapter tension, proteinuria, edema, post-ma-
subject to § 862.9. turity, placental insufficiency, or pos-
[52 FR 16122, May 1, 1987, as amended at 65 sible miscarriage.
§ 862.1575 Phospholipid test system. § 862.1590 Porphobilinogen test sys-

tem.
(a) Identification. A phospholipid test
(a) Identification. A porphobilinogen
phospholipids in serum and plasma.
measure porphobilinogen (one of the
Measurements of phospholipids are
derivatives of hemoglobin which can
used in the diagnosis and treatment of make the urine a red color) in urine.
disorders involving lipid (fat) metabo- Measurements obtained by this device
lism. are used in the diagnosis and treat-
(b) Classification. Class I (general con- ment of porphyrias (primarily inher-
trols). The device is exempt from the ited diseases associated with disturbed
premarket notification procedures in porphyrine metabolism), lead poi-
subpart E of part 807 of this chapter soning, and other diseases character-
subject to the limitations in § 862.9. ized by alterations in the heme path-
way.
FR 21449, June 8, 1988; 66 FR 38788, July 25,
2001] trols). The device is exempt from the
§ 862.1580 Phosphorus (inorganic) test subpart E of part 807 of this chapter
system. subject to § 862.9.
(a) Identification. A phosphorus (inor- [52 FR 16122, May 1, 1987, as amended at 65
ganic) test system is a device intended FR 2307, Jan. 14, 2000]
to measure inorganic phosphorus in
§ 862.1595 Porphyrins test system.
serum, plasma, and urine. Measure-
ments of phosphorus (inorganic) are (a) Identification. A porphyrins test
used in the diagnosis and treatment of system is a device intended to measure
various disorders, including parathy- porphyrins (compounds formed during
roid gland and kidney diseases, and vi- the biosynthesis of heme, a constituent
tamin D imbalance. of hemoglobin, and related compounds)
(b) Classification. Class I (general con- in urine and feces. Measurements ob-
tained by this device are used in the di-
agnosis and treatment of lead poi-
soning, porphyrias (primarily inherited
diseases associated with disturbed por-
phyrin metabolism), and other diseases

[52 FR 16122, May 1, 1987, as amended at 84 characterized by alterations in the
FR 71796, Dec. 30, 2019] heme pathway.
261
§ 862.1600 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class I (general con- synthesis of the adrenal hormone

trols). The device is exempt from the cortisol and adrenal androgen) in
premarket notification procedures in serum and plasma. Measurements ob-
subpart E of part 807 of this chapter tained by this device are used in the di-
subject to § 862.9. agnosis and treatment of diseases of
the adrenal cortex or the gonads.
§ 862.1600 Potassium test system. premarket notification procedures in
(a) Identification. A potassium test subpart E of part 807 of this chapter
potassium in serum, plasma, and urine. [52 FR 16122, May 1, 1987, as amended at 65
Measurements obtained by this device FR 2308, Jan. 14, 2000]
are used to monitor electrolyte balance
in the diagnosis and treatment of dis- § 862.1620 Progesterone test system.
eases conditions characterized by low (a) Identification. A progesterone test
or high blood potassium levels. system is a device intended to measure
(b) Classification. Class II. progesterone (a female hormone) in
serum and plasma. Measurements ob-
§ 862.1605 Pregnanediol test system. tained by this device are used in the di-
(a) Identification. A pregnanediol test agnosis and treatment of disorders of
system is a device intended to measure the ovaries or placenta.
pregnanediol (a major urinary meta- (b) Classification. Class I (general con-
bolic product of progesterone) in urine. trols). The device is exempt from the
Measurements obtained by this device premarket notification procedures in
are used in the diagnosis and treat- subpart E of part 807 of this chapter
ment of disorders of the ovaries or pla- subject to § 862.9.
centa. [52 FR 16122, May 1, 1987, as amended at 65
(b) Classification. Class I (general con- FR 2308, Jan. 14, 2000]
premarket notification procedures in § 862.1622 Prognostic test for assess-
subpart E of part 807 of this chapter ment of liver related disease pro-
subject to § 862.9. gression.
(a) Identification. A prognostic test
FR 2308, Jan. 14, 2000] for assessment of liver related disease
progression is intended to measure one
§ 862.1610 Pregnanetriol test system. or more analytes obtained from human
samples as an aid in assessing progres-
(a) Identification. A pregnanetriol test
sion of liver related disease. This de-
vice is not intended for diagnosis of
pregnanetriol (a precursor in the bio-
any disease, for monitoring the effect
synthesis of the adrenal hormone
of any therapeutic product, for assess-
cortisol) in urine. Measurements ob-
ing progression to hepatocellular car-
cinoma, or for assessing disease pro-
agnosis and treatment of congenital
gression in individuals with viral hepa-
adrenal hyperplasia (congenital en-
titis. It is also not intended for the de-
largement of the adrenal gland). tection of viruses, viral antigens, or
antibodies to viruses.
trols). The device is exempt from the (b) Classification. Class II (special
premarket notification procedures in controls). The special controls for this
subpart E of part 807 of this chapter device are:
subject to § 862.9. (1) Design verification and validation
[52 FR 16122, May 1, 1987, as amended at 65 must include clinical validation data
FR 2308, Jan. 14, 2000] providing:
(i) Information demonstrating clin-
§ 862.1615 Pregnenolone test system. ical performance in a population of pa-
(a) Identification. A pregnenolone test tients with liver disease for the dif-
system is a device intended to measure ferent risk categories (e.g., at lower
pregnenolone (a precursor in the bio- risk, at higher risk) for progression of
262
their disease using well characterized study design determined to be appro-

clinical specimens representing the in- priate by FDA.
tended use population collected from
[88 FR 2519, Jan. 17, 2023]
multiple intended clinical sites, or an
alternative study design determined to § 862.1625 Prolactin (lactogen) test sys-
be appropriate by FDA. tem.
(ii) Information demonstrating that
(a) Identification. A prolactin
the outcomes measured and the length
(lactogen) test system is a device in-
of followup are clinically relevant for
tended to measure the anterior pitui-
the progression of the specified liver
tary polypeptide hormone prolactin in
disease.
serum and plasma. Measurements ob-
(iii) Information demonstrating that
the clinical criteria for determining
agnosis and treatment of disorders of
whether the target disease is present
and that the exclusion and inclusion the anterior pituitary gland or of the
criteria for subjects who have the tar- hypothalamus portion of the brain.
get disease are appropriate. (b) Classification. Class I (general con-
(iv) Information demonstrating test trols). The device is exempt from the
performance of the complete test sys- premarket notification procedures in
tem, including any sample collection subpart E of part 807 of this chapter
and processing steps. subject to § 862.9.
(v) Information, provided or ref- [52 FR 16122, May 1, 1987, as amended at 65
erenced, generated in samples from FR 2308, Jan. 14, 2000]
non-diseased individuals, that dem-
onstrate the upper and lower reference § 862.1630 Protein (fractionation) test
intervals for the output provided by system.
the device. (a) Identification. A protein (fraction-
(2) The labeling required under 21 ation) test system is a device intended
CFR 809.10(b) must include: to measure protein fractions in blood,
(i) A warning statement that test re- urine, cerebrospinal fluid, and other
sults are not intended to diagnose dis- body fluids. Protein fractionations are
ease or for monitoring the effect of any used as an aid in recognizing abnormal
therapeutic product. proteins in body fluids and genetic
(ii) A warning statement that test re- variants of proteins produced in dis-
sults are intended to be used in con- eases with tissue destruction.
junction with other clinical and diag- (b) Classification. Class I (general con-
nostic findings, consistent with profes- trols). The device is exempt from the
sional standards of practice, including premarket notification procedures in
information obtained by alternative subpart E of part 807 of this chapter
methods, and clinical evaluation, as subject to § 862.9.
appropriate.
(iii) A warning statement that de- [52 FR 16122, May 1, 1987, as amended at 65
scribes any limitations on the clinical FR 2308, Jan. 14, 2000]
interpretation(s) of the test results.
§ 862.1635 Total protein test system.
(iv) Detailed information on device
performance, including any limitations (a) Identification. A total protein test
to the data generated in the clinical system is a device intended to measure
study(ies) and information on device total protein(s) in serum or plasma.
performance in relevant subgroups Measurements obtained by this device
(e.g., severity of liver disease at the be- are used in the diagnosis and treat-
ginning of the observation period) ob- ment of a variety of diseases involving
served in the clinical study(ies). the liver, kidney, or bone marrow as
(v) Information on the analytical per- well as other metabolic or nutritional
formance of the device, including dem- disorders.
onstration of reproducibility across (b) Classification. Class II (special

multiple sites and multiple reagent controls). The device is exempt from
lots, or an alternative reproducibility the premarket notification procedures
263
§ 862.1640 21 CFR Ch. I (4–1–23 Edition)
in subpart E of part 807 of this chapter subpart E of part 807 of this chapter
FR 59225, Nov. 3, 1998] FR 2308, Jan. 14, 2000]
§ 862.1640 Protein-bound iodine test § 862.1655 Pyruvic acid test system.

system.
(a) Identification. A pyruvic acid test
(a) Identification. A protein-bound io- system is a device intended to measure
dine test system is a device intended to pyruvic acid (an intermediate com-
measure protein-bound iodine in pound in the metabolism of carbo-
serum. Measurements of protein-bound hydrate) in plasma. Measurements ob-
iodine obtained by this device are used tained by this device are used in the
in the diagnosis and treatment of thy- evaluation of electrolyte metabolism
roid disorders. and in the diagnosis and treatment of
(b) Classification. Class I (general con- acid-base and electrolyte disturbances
trols). The device is exempt from the or anoxia (the reduction of oxygen in
premarket notification procedures in body tissues).
subject to the limitations in § 862.9. trols). The device is exempt from the
[52 FR 16122, May 1, 1987, as amended at 53 premarket notification procedures in
FR 21449, June 8, 1988; 66 FR 38788, July 25, subpart E of part 807 of this chapter
2001] subject to § 862.9.
§ 862.1645 Urinary protein or albumin [52 FR 16122, May 1, 1987, as amended at 65
(nonquantitative) test system. FR 2308, Jan. 14, 2000]
(a) Identification. A urinary protein or § 862.1660 Quality control material (as-

albumin (nonquantitative) test system sayed and unassayed).
is a device intended to identify pro-
(a) Identification. A quality control
teins or albumin in urine. Identifica-
tion of urinary protein or albumin material (assayed and unassayed) for
(nonquantitative) is used in the diag- clinical chemistry is a device intended
nosis and treatment of disease condi- for medical purposes for use in a test
tions such as renal or heart diseases or system to estimate test precision and
thyroid disorders, which are character- to detect systematic analytical devi-
ized by proteinuria or albuminuria. ations that may arise from reagent or
(b) Classification. Class I (general con- analytical instrument variation. A
trols). The device is exempt from the quality control material (assayed and
premarket notification procedures in unassayed) may be used for proficiency
subpart E of part 807 of this chapter testing in interlaboratory surveys.
subject to § 862.9. This generic type of device includes
controls (assayed and unassayed) for
[52 FR 16122, May 1, 1987, as amended at 65 blood gases, electrolytes, enzymes,
FR 2308, Jan. 14, 2000]
multianalytes (all kinds), single (speci-
§ 862.1650 Pyruvate kinase test system. fied) analytes, or urinalysis controls.
(a) Identification. A pyruvate kinase trols). Except when intended for use in
test system is a device intended to donor screening tests, quality control
measure the activity of the enzyme materials (assayed and unassayed) are
pyruvate kinase in erythrocytes (red exempt from the premarket notifica-
blood cells). Measurements obtained by tion procedures in subpart E of part 807
this device are used in the diagnosis of this chapter subject to the limita-
and treatment of various inherited
tions in § 862.9.
anemias due to pyruvate kinase defi-
ciency or of acute leukemias. [52 FR 16122, May 1, 1987, as amended at 65
(b) Classification. Class I (general con- FR 2308, Jan. 14, 2000, 84 FR 71796, Dec. 30,
264
§ 862.1665 Sodium test system. type of device includes immunoassays

and chromatographic assays for
(a) Identification. A sodium test sys-
tacrolimus.
tem is a device intended to measure so-
dium in serum, plasma, and urine.
controls). The special control is ‘‘Class
Measurements obtained by this device
II Special Controls Guidance Docu-
ment: Cyclosporine and Tacrolimus As-
ment of aldosteronism (excessive secre-
says; Guidance for Industry and FDA.’’
tion of the hormone aldosterone), dia-
See § 862.1(d) for the availability of this
betes insipidus (chronic excretion of
guidance document.
large amounts of dilute urine, accom-
panied by extreme thirst), adrenal hy- [67 FR 58329, Sept. 16, 2002]
pertension, Addison’s disease (caused
by destruction of the adrenal glands), § 862.1680 Testosterone test system.
dehydration, inappropriate antidiuretic (a) Identification. A testosterone test
hormone secretion, or other diseases system is a device intended to measure
involving electrolyte imbalance. testosterone (a male sex hormone) in
(b) Classification. Class II. serum, plasma, and urine. Measure-
ment of testosterone are used in the di-
§ 862.1670 Sorbitol dehydrogenase test agnosis and treatment of disorders in-
system. volving the male sex hormones
(a) Identification. A sorbitol dehydro- (androgens), including primary and sec-
genase test system is a device intended ondary hypogonadism, delayed or pre-
to measure the activity of the enzyme cocious puberty, impotence in males
sorbitol dehydrogenase in serum. Meas- and, in females hirsutism (excessive
urements obtained by this device are hair) and virilization (masculinization)
used in the diagnosis and treatment of due to tumors, polycystic ovaries, and
liver disorders such as cirrhosis or adrenogenital syndromes.
acute hepatitis. (b) Classification. Class I.
(b) Classification. Class I (general con- [52 FR 16122, May 1, 1987; 53 FR 11645, Apr. 8,
subpart E of part 807 of this chapter § 862.1685 Thyroxine-binding globulin
subject to the limitations in § 862.9. test system.
[52 FR 16122, May 1, 1987, as amended at 53 (a) Identification. A thyroxine-binding
FR 21449, June 8, 1988; 66 FR 38788, July 25, globulin test system is a device in-
2001] tended to measure thyroxine (thyroid)-
binding globulin (TBG), a plasma pro-
§ 862.1675 Blood specimen collection tein which binds thyroxine, in serum
device. and plasma. Measurements obtained by
(a) Identification. A blood specimen this device are used in the diagnosis
collection device is a device intended and treatment of thyroid diseases.
for medical purposes to collect and to (b) Classification. Class II (special
handle blood specimens and to separate controls). The device is exempt from
serum from nonserum (cellular) compo- the premarket notification procedures
nents prior to further testing. This ge- in subpart E of part 807 of this chapter
neric type device may include blood subject to the limitations in § 862.9.
collection tubes, vials, systems, serum [52 FR 16122, May 1, 1987, as amended at 84
separators, blood collection trays, or FR 71797, Dec. 30, 2019]
vacuum sample tubes.
(b) Classification. Class II. § 862.1690 Thyroid stimulating hor-
mone test system.
§ 862.1678 Tacrolimus test system. (a) Identification. A thyroid stimu-
(a) Identification. A tacrolimus test lating hormone test system is a device
system is a device intended to quan- intended to measure thyroid stimu-
titatively determine tacrolimus con- lating hormone, also known as thyrot-
centrations as an aid in the manage- rophin and thyrotrophic hormone, in

ment of transplant patients receiving serum and plasma. Measurements of
therapy with this drug. This generic thyroid stimulating hormone produced
265
§ 862.1695 21 CFR Ch. I (4–1–23 Edition)
by the anterior pituitary are used in vice intended to measure the hormone
the diagnosis of thyroid or pituitary triiodothyronine in serum and plasma.
disorders. Measurements obtained by this device
(b) Classification. Class II. are used in the diagnosis and treat-
ment of thyroid diseases such as hyper-
§ 862.1695 Free thyroxine test system.
thyroidism.
(a) Identification. A free thyroxine (b) Classification. Class II. This device
test system is a device intended to is exempt from the premarket notifica-
measure free (not protein bound) tion procedures in subpart E of part 807
thyroxine (thyroid hormone) in serum of this chapter subject to the limita-
or plasma. Levels of free thyroxine in tions in § 862.9.
plasma are thought to reflect the
amount of thyroxine hormone avail- [52 FR 16122, May 1, 1987, as amended at 65
able to the cells and may therefore de- FR 62286, Oct. 18, 2000]
termine the clinical metabolic status
of thyroxine. Measurements obtained § 862.1715 Triiodothyronine uptake
by this device are used in the diagnosis test system.
and treatment of thyroid diseases. (a) Identification. A triiodothyronine
(b) Classification. Class II. uptake test system is a device intended
to measure the total amount of binding
§ 862.1700 Total thyroxine test system. sites available for binding thyroid hor-
(a) Identification. A total thyroxine mone on the thyroxine-binding pro-
test system is a device intended to teins, thyroid-binding globulin,
measure total (free and protein bound) thyroxine-binding prealbumin, and al-
thyroxine (thyroid hormone) in serum bumin of serum and plasma. The device
and plasma. Measurements obtained by provides an indirect measurement of
this device are used in the diagnosis thyrkoxine levels in serum and plasma.
and treatment of thyroid diseases. Measurements of triiodothyronine up-
(b) Classification. Class II (special take are used in the diagnosis and
controls). The device is exempt from treatment of thyroid disorders.
the premarket notification procedures (b) Classification. Class II. The device
in subpart E of part 807 of this chapter is exempt from the premarket notifica-
tion procedures in subpart E of part 807
[52 FR 16122, May 1, 1987, as amended at 84 of this chapter subject to the limita-
FR 71797, Dec. 30, 2019] tions in § 862.9.
§ 862.1705 Triglyceride test system. [52 FR 16122, May 1, 1987, as amended at 64
FR 1124, Jan. 8, 1999]
(a) Identification. A triglyceride test
system is a device intended to measure § 862.1720 Triose phosphate isomerase
triglyceride (neutral fat) in serum and test system.
plasma. Measurements obtained by this
device are used in the diagnosis and (a) Identification. A triose phosphate
treatment of patients with diabetes isomerase test system is a device in-
mellitus, nephrosis, liver obstruction, tended to measure the activity of the
other diseases involving lipid metabo- enzyme triose phosphate isomerase in
lism, or various endocrine disorders. erythrocytes (red blood cells). Triose
(b) Classification. Class I (general con- phosphate isomerase is an enzyme im-
trols). The device is exempt from the portant in glycolysis (the energy-yield-
premarket notification procedures in ing conversion of glucose to lactic acid
subpart E of part 807 of this chapter in various tissues). Measurements ob-
subject to § 862.9. tained by this device are used in the di-
[52 FR 16122, May 1, 1987, as amended at 65 agnosis and treatment of congenital
FR 2308, Jan. 14, 2000] triose phosphate isomerase enzyme de-
ficiency, which causes a type of hemo-
§ 862.1710 Total triiodothyronine test lytic anemia.
system.

(a) Identification. A total trols). The device is exempt from the
triiodothyronine test system is a de- premarket notification procedures in
266
subpart E of part 807 subject to the leukemia, psoriasis, starvation or

limitations in § 862.9. other wasting conditions, and of pa-
tients receiving cytotoxic drugs.
FR 21449, June 8, 1988; 66 FR 38788, July 25, (b) Classification. Class I (general con-
2001] trols). The device, when it is solely in-
tended for use as an acid reduction of
§ 862.1725 Trypsin test system. ferric ion test, a phosphotungstate re-
(a) Identification. A trypsin test sys- duction test, a gasometric uricase test,
tem is a device intended to measure an ultraviolet uricase test, or an oxy-
the activity of trypsin (a pancreatic gen rate uricase test, is exempt from
enzyme important in digestion for the the premarket notification procedures
breakdown of proteins) in blood and in subpart E of part 807 of this chapter
other body fluids and in feces. Measure- subject to the limitations in § 862.9.
ments obtained by this device are used [52 FR 16122, May 1, 1987, as amended at 84
in the diagnosis and treatment of pan- FR 71797, Dec. 30, 2019; 85 FR 18445, Apr. 2,
creatic disease. 2020]
trols). The device is exempt from the § 862.1780 Urinary calculi (stones) test
system.
subpart E of part 807 of this chapter (a) Identification. A urinary calculi
subject to § 862.9. (stones) test system is a device in-
tended for the analysis of urinary
calculi. Analysis of urinary calculi is
FR 2308, Jan. 14, 2000]
§ 862.1730 Free tyrosine test system. calculi of the urinary tract.
(a) Identification. A free tyrosine test trols). The device is exempt from the
system is a device intended to measure premarket notification procedures in
free tyrosine (an amono acid) in serum subpart E of part 807 of this chapter
and urine. Measurements obtained by subject to § 862.9.
this device are used in the diagnosis
and treatment of diseases such as con- [52 FR 16122, May 1, 1987, as amended at 65
genital tyrosinemia (a disease that can FR 2308, Jan. 14, 2000]
cause liver/kidney disorders) and as an
§ 862.1785 Urinary urobilinogen (non-
adjunct to the measurement of quantitative) test system.
phenylalanine in detecting congenital
phenylketonuria (a disease that can (a) Identification. A urinary urobi-
cause brain damage). linogen (nonquantitative) test system
(b) Classification. Class I. is a device intended to detect and esti-
mate urobilinogen (a bile pigment deg-
§ 862.1770 Urea nitrogen test system. radation product of red cell hemo-
(a) Identification. A urea nitrogen test globin) in urine. Estimations obtained
system is a device intended to measure by this device are used in the diagnosis
urea nitrogen (an end-product of nitro- and treatment of liver diseases and he-
gen metabolism) in whole blood, molytic (red cells) disorders.
serum, plasma, and urine. Measure- (b) Classification. Class I (general con-
ments obtained by this device are used trols). The device is exempt from the
in the diagnosis and treatment of cer- premarket notification procedures in
tain renal and metabolic diseases. subpart E of part 807 of this chapter
(b) Classification. Class II. subject to § 862.9.
§ 862.1775 Uric acid test system. FR 2308, Jan. 14, 2000]
(a) Identification. A uric acid test sys-
tem is a device intended to measure § 862.1790 Uroporphyrin test system.
uric acid in serum, plasma, and urine. (a) Identification. A uroporphyrin test
Measurements obtained by this device system is a device intended to measure
are used in the diagnosis and treat- uroporphyrin in urine. Measurements

ment of numerous renal and metabolic obtained by this device are used in the
disorders, including renal failure, gout, diagnosis and treatment of porphyrias
267
§ 862.1795 21 CFR Ch. I (4–1–23 Edition)
(primarily inherited diseases associ- § 862.1815 Vitamin E test system.

ated with disturbed porphyrin metabo-
(a) Identification. A vitamin E test
lism), lead poisoning, and other dis-
eases characterized by alterations in
the heme pathway. vitamin E (tocopherol) in serum. Meas-
urements obtained by this device are
infants with vitamin E deficiency syn-
drome.
[52 FR 16122, May 1, 1987, as amended at 65 premarket notification procedures in
FR 2308, Jan. 14, 2000] subpart E of part 807 subject to the
limitations in § 862.9.
§ 862.1795 Vanilmandelic acid test sys-
tem. [52 FR 16122, May 1, 1987, as amended at 53
FR 21449, June 8, 1988; 66 FR 38788, July 25,
(a) Identification. A vanilmandelic
2001]
acid test system is a device intended to
measure vanilmandelic acid in urine. § 862.1820 Xylose test system.
Measurements of vanilmandelic acid
obtained by this device are used in the (a) Identification. A xylose test sys-
diagnosis and treatment of neuro- tem is a device intended to measure
blastoma, pheochromocytoma, and cer- xylose (a sugar) in serum, plasma, and
tain hypertensive conditions. urine. Measurements obtained by this
(b) Classification. Class I (general con- device are used in the diagnosis and
trols). The device is exempt from the treatment of gastrointestinal mal-
premarket notification procedures in absorption syndrome (a group of dis-
subpart E of part 807 of this chapter orders in which there is subnormal ab-
subject to § 862.9. sorption of dietary constituents and
thus excessive loss from the body of
[52 FR 16122, May 1, 1987, as amended at 65 the nonabsorbed substances).
FR 2308, Jan. 14, 2000]
§ 862.1805 Vitamin A test system. trols). The device is exempt from the
(a) Identification. A vitamin A test subpart E of part 807 of this chapter
vitamin A in serum or plasma. Meas-
urements obtained by this device are [52 FR 16122, May 1, 1987, as amended at 65
used in the diagnosis and treatment of FR 2308, Jan. 14, 2000]
vitamin A deficiency conditions, in-
§ 862.1825 Vitamin D test system.
cluding night blindness, or skin, eye, or
intestinal disorders. (a) Identification. A vitamin D test
(b) Classification. Class I (general con- system is a device intended for use in
trols). The device is exempt from the clinical laboratories for the quan-
premarket notification procedures in titative determination of 25-
subpart E of part 807 of this chapter hydroxyvitamin D (25-OH-D) and other
subject to § 862.9. hydroxylated metabolites of vitamin D
in serum or plasma to be used in the
[52 FR 16122, May 1, 1987, as amended at 65 assessment of vitamin D sufficiency.
FR 2308, Jan. 14, 2000]
§ 862.1810 Vitamin B12 test system. controls). Vitamin D test systems must
comply with the following special con-
(a) Identification. A vitamin B12 test trols:
system is a device intended to measure (1) Labeling in conformance with 21
vitamin B12 in serum, plasma, and CFR 809.10 and
urine. Measurements obtained by this
(2) Compliance with existing stand-
device are used in the diagnosis and
ards of the National Committee on
treatment of anemias of gastro-

Clinical Laboratory Standards.
intestinal malabsorption.
(b) Classification. Class II. [63 FR 40366, July 29, 1998]
268
§ 862.1840 Total 25-hydroxyvitamin D Dihydroxyvitamin-D3, 24 (R), 25-

mass spectrometry test system. dihydroxyvitamin-D3, 23 (R), 25-
(a) Identification. A total 25- dihydroxyvitamin-D3 must be de-
hydroxyvitamin D mass spectrometry scribed in the 21 CFR 809.10(b)(7) com-
test system is a device intended for use pliant labeling of the device.
in clinical laboratories for the quan- (3) The 21 CFR 809.10(b) compliant la-
titative determination of total 25- beling must be supported by a ref-
hydroxyvitamin D (25–OH–D) in serum erence range study representative of
or plasma to be used in the assessment the performance of the device. The
of vitamin D sufficiency. study must be conducted using samples
(b) Classification. Class II (special collected from apparently healthy
controls). The device is exempt from male and female adults at least 21
the premarket notification procedures years of age and older from at least 3
in part 807, subpart E, of this chapter distinct climatic regions within the
subject to the limitations in § 862.9. The United States in different weather sea-
device must comply with the following sons. The ethnic, racial, and gender
special controls:
background of this study population
(1) The device must have initial and
must be representative of the U.S. pop-
annual standardization verification by
a certifying vitamin D standardization ulation demographics.
organization deemed acceptable by (4) The results of the device as pro-
FDA. vided in the 21 CFR 809.10(b) compliant
(2) The 21 CFR 809.10(b) compliant la- labeling and any test report generated
beling must include detailed descrip- must be reported as only total 25-
tions of performance testing conducted hydroxyvitamin D.
to evaluate precision, accuracy, lin- [82 FR 51559, Nov. 7, 2017, as amended at 83
earity, interference, including the fol- FR 25914, June 5, 2018]
lowing:
(i) Performance testing of device pre-
cision must, at a minimum, use in- Subpart C—Clinical Laboratory
tended sample type with Vitamin D Instruments
concentrations at medically relevant
decision points. At least one sample in § 862.2050 General purpose laboratory
equipment labeled or promoted for
the precision studies must be an un-
a specific medical use.
modified patient sample. This testing
must evaluate repeatability and repro- (a) Identification. General purpose
ducibility using a protocol from an laboratory equipment labeled or pro-
FDA-recognized standard. moted for a specific medical use is a
(ii) Performance testing of device ac- device that is intended to prepare or
curacy must include a minimum of 115 examine specimens from the human
serum or plasma samples that span the body and that is labeled or promoted
measuring interval of the device and for a specific medical use.
compare results of the new device to (b) Classification. Class I (general con-
results of a reference method or a le- trols). The device is identified in para-
gally marketed standardized mass graph (a) of this section and is exempt
spectrometry based vitamin D assay. from the premarket notification proce-
The results must be described in the 21 dures in subpart E of part 807 of this
CFR 809.10(b)(12) compliant labeling of chapter subject to the limitations in
the device. § 862.9. The device is also exempt from
(iii) Interference from vitamin D the current good manufacturing prac-
analogs and metabolites including vi- tice requirements of the quality sys-
tamin D2, vitamin D3, 1-
tem regulation in part 820 of this chap-
hydroxyvitamin D2, 1-hydroxyvitamin
ter, with the exception of § 820.180, with
D3, 3-Epi-25-Hydroxyvitamin D2, 3-Epi-
respect to general requirements con-
25-Hydroxyvitamin D3, 1,25-
cerning records, and § 820.198, with re-
Dihydroxyvitamin D2, 1,25-
spect to complaint files.
Dihydroxyvitamin D3, 3-Epi-1,25-

Dihydroxyvitamin D2, and 3-Epi-1,25- [52 FR 16122, May 1, 1987, as amended at 66
Dihydroxyvitamin D3, 25, 26- FR 38788, July 25, 2001]
269
§ 862.2100 21 CFR Ch. I (4–1–23 Edition)
§ 862.2100 Calculator/data processing § 862.2150 Continuous flow sequential

module for clinical use. multiple chemistry analyzer for
clinical use.
(a) Identification. A calculator/data
processing module for clinical use is an (a) Identification. A continuous flow
electronic device intended to process sequential multiple chemistry analyzer
laboratory data. for clinical use is a modular analytical
(b) Classification. Class I (general con- instrument intended to simultaneously
trols). The device is exempt from the perform multiple chemical procedures
premarket notification procedures in using the principles of automated con-
subpart E of part 807 of this chapter tinuous flow systems. This device is in-
tended for use in conjunction with cer-
tain materials to measure a variety of
[52 FR 16122, May 1, 1987, as amended at 53 analytes.
2001; 86 FR 20283, Apr. 19, 2021] trols). The device is exempt from the
§ 862.2120 Continuous glucose monitor subpart E of part 807 of this chapter
data management system.
(a) Identification. A continuous glu-
cose monitor data management system
FR 2308, Jan. 14, 2000]
is an electronic device intended to ac-
quire, process, and correlate retrospec- § 862.2160 Discrete photometric chem-
tive data from a continuous glucose istry analyzer for clinical use.
monitoring device. This device is in-
(a) Identification. A discrete photo-
tended to be used by patients or their metric chemistry analyzer for clinical
healthcare providers when determining use is a device intended to duplicate
therapeutic strategies. A continuous manual analytical procedures by per-
glucose monitor data management sys- forming automatically various steps
tem is not a drug dose calculator and such as pipetting, preparing filtrates,
does not provide treatment rec- heating, and measuring color intensity.
ommendations. This device is intended for use in con-
(b) Classification. Class I (general conjunction with certain materials to
trols). The device is exempt from the measure a variety of analytes. Dif-
premarket notification procedures in ferent models of the device incorporate
subpart E of part 807 of this chapter, various instrumentation such as micro
subject to the limitations in § 862.9. analysis apparatus, double beam, sin-
gle, or dual channel photometers, and
[84 FR 57817, Oct. 29, 2019]
bichromatic 2-wavelength
§ 862.2140 Centrifugal chemistry ana- photometers. Some models of the de-
lyzer for clinical use. vice may include reagent-containing
components that may also serve as re-
(a) Identification. A centrifugal chem- action units.
istry analyzer for clinical use is an (b) Classification. Class I (general con-
automatic device intended to cen- trols). The device is exempt from the
trifugally mix a sample and a reagent premarket notification procedures in
and spectrophotometrically measure subpart E of part 807 of this chapter
concentrations of the sample constitu- subject to § 862.9.
ents. This device is intended for use in
conjunction with certain materials to [52 FR 16122, May 1, 1987, as amended at 65
FR 2309, Jan. 14, 2000]
measure a variety of analytes.
(b) Classification. Class I (general con- § 862.2170 Micro chemistry analyzer
trols). The device is exempt from the for clinical use.
(a) Identification. A micro chemistry
analyzer for clinical use is a device in-
tended to duplicate manual analytical

[52 FR 16122, May 1, 1987, as amended at 65 procedures by performing automati-
FR 2308, Jan. 14, 2000] cally various steps such as pipetting,
270
preparing filtrates, heating, and meas- § 862.2260 High pressure liquid chro-
uring color intensity. The distin- matography system for clinical use.
guishing characteristic of the device is (a) Identification. A high pressure liq-
that it requires only micro volume uid chromatography system for clinical
samples obtainable from pediatric pa- use is a device intended to separate one
tients. This device is intended for use or more drugs or compounds from a so-
in conjunction with certain materials lution by processing the mixture of
to measure a variety of analytes. compounds (solutes) through a column
(b) Classification. Class I (general con- packed with materials of uniform size
trols). The device is exempt from the (stationary phase) under the influence
premarket notification procedures in of a high pressure liquid (mobile
subpart E of part 807 of this chapter phase). Separation of the solutes oc-
subject to § 862.9. curs either by absorption, sieving, par-
tition, or selective affinity.
§ 862.2230 Chromatographic separa- premarket notification procedures in
tion material for clinical use. subpart E of part 807 of this chapter
(a) Identification. A chromatographic
separation material for clinical use is a [52 FR 16122, May 1, 1987, as amended at 65
device accessory (e.g., ion exchange FR 2309, Jan. 14, 2000]
absorbents, ion exchagne resins, and
ion papers) intended for use in ion ex- § 862.2265 High throughput genomic
sequence analyzer for clinical use.
change chromatography, a procedure in
which a compound is separated from a (a) Identification. A high throughput
solution. genomic sequence analyzer for clinical
(b) Classification. Class I (general con- use is an analytical instrument system
trols). The device is exempt from the intended to generate, measure and sort
premarket notification procedures in signals in order to analyze nucleic acid
subpart E of part 807 of this chapter sequences in a clinical sample. The de-
vice may include a signal reader unit;
reagent handling, dedicated instrument
[52 FR 16122, May 1, 1987, as amended at 61 control, and other hardware compo-
FR 1119, Jan. 16, 1996; 66 FR 38788, July 25, nents; raw data storage mechanisms;
2001] data acquisition software; and software
to process detected signals.
§ 862.2250 Gas liquid chromatography (b) Classification. Class II (special
system for clinical use.
(a) Identification. A gas liquid chro- the premarket notification procedures
matography system for clinical use is a in subpart E of part 807 of this chapter
device intended to separate one or subject to the limitations in § 862.9. The
more drugs or compounds from a mix- special controls for this device are:
ture. Each of the constituents in a va- (1) The labeling for the instrument
porized mixture of compounds is sepa- system must reference legally mar-
rated according to its vapor pressure. keted pre-analytical and analytical re-
The device may include accessories agents to be used with the instrument
such as columns, gases, column sup- system and include or reference legally
ports, and liquid coating. marketed analytical software that in-
(b) Classification. Class I (general concludes sequence alignment and variant
trols). The device is exempt from the calling functions, to be used with the
premarket notification procedures in instrument system.
subpart E of part 807 of this chapter (2) The labeling for the instrument
subject to § 862.9. system must include a description of
the following information:
(i) The specimen type(s) validated as

FR 2309, Jan. 14, 2000] an appropriate source of nucleic acid
for this instrument.
271
§ 862.2270 21 CFR Ch. I (4–1–23 Edition)
(ii) The type(s) of nucleic acids (e.g., may interfere with the instrument sys-
germline DNA, tumor DNA) validated tem.
with this instrument. (D) If applicable, data demonstrating
(iii) The type(s) of sequence vari- the ability of the system to consist-
ations (e.g. single nucleotide variants, ently generate an accurate result for a
insertions, deletions) validated with given sample across different indexing
this instrument. primer combinations.
(iv) The type(s) of sequencing (e.g., (ix) The upper and lower limit of
targeted sequencing) validated with input nucleic acid that will achieve the
this instrument. claimed accuracy and reproducibility.
Data supporting such claims must also
(v) The appropriate read depth for
be summarized.
the sensitivity claimed and validation
information supporting those claims. [82 FR 13552, Mar. 14, 2017, as amended at 84
(vi) The nucleic acid extraction FR 71797, Dec. 30, 2019]
method(s) validated for use with the in- § 862.2270 Thin-layer chromatography
strument system. system for clinical use.
(vii) Limitations must specify the
(a) Identification. A thin-layer chro-
types of sequence variations that the
matography (TLC) system for clinical
instrument cannot detect with the
use is a device intended to separate one
claimed accuracy and precision (e.g.,
or more drugs or compounds from a
insertions or deletions larger than a mixture. The mixture of compounds is
certain size, translocations). absorbed onto a stationary phase or
(viii) Performance characteristics of thin layer of inert material (e.g., cel-
the instrument system must include: lulose, alumina, etc.) and eluted off by
(A) Reproducibility data generated a moving solvent (moving phase) until
using multiple instruments and mul- equilibrium occurs between the two
tiple operators, and at multiple sites. phases.
Samples tested must include all (b) Classification. Class I (general con-
claimed specimen types, nucleic acid trols). The device is exempt from the
types, sequence variation types, and premarket notification procedures in
types of sequencing. Variants queried subpart E of part 807 of this chapter
shall be located in varying sequence subject to § 862.9. Particular compo-
context (e.g., different chromosomes, nents of TLC systems, i.e., the thin-
GC-rich regions). Device results shall layer chromatography apparatus, TLC
be compared to reference sequence data atomizer, TLC developing tanks, and
with high confidence. TLC ultraviolet light, are exempt from
(B) Accuracy data for all claimed the current good manufacturing prac-
specimen types and nucleic acid types tice requirements of the quality sys-
generated by testing a panel of well tem regulation in part 820 of this chap-
characterized samples to query all ter, with the exception of § 820.180 of
claimed sequence variation types, this chapter, with respect to general
types of sequencing, and sequences lo- requirements concerning records, and
cated in varying sequence context (e.g., § 820.198 of this chapter, with respect to
different chromosomes, GC-rich re- complaint files.
gions). The well-characterized sample [52 FR 16122, May 1, 1987, as amended at 65
panel shall include samples from at FR 2309, Jan. 14, 2000]
least two sources that have highly con-
fident sequence based on well-validated § 862.2300 Colorimeter, photometer, or
sequencing methods. At least one ref- spectrophotometer for clinical use.
erence source shall have sequence gen- (a) Identification. A colorimeter, a
erated independently of the manufac- photometer, or a spectrophotometer
turer with respect to technology and for clinical use is an instrument in-
analysis. Percent agreement and per- tended to measure radiant energy
cent disagreement with the reference emitted, transmitted, absorbed, or re-
sequences must be described for all reflected under controlled conditions.
gions queried by the instrument. The device may include a

(C) If applicable, data describing en- monochromator to produce light of a
dogenous or exogenous substances that specific wavelength.
272
(b) Classification. Class I (general con- the radiochromatogram scanner, by

trols). The device is exempt from the measurement of the distribution of a
premarket notification procedures in specific radio-active element on a
subpart E of part 807 of this chapter radiochromatogram.
[52 FR 16122, May 1, 1987, as amended at 65 trols). The device is exempt from the
FR 2309, Jan. 14, 2000] premarket notification procedures in
§ 862.2310 Clinical sample concen- subject to § 862.9.
trator.
(a) Identification. A clinical sample FR 2309, Jan. 14, 2000]
concentrator is a device intended to
concentrate (by dialysis, evaporation, § 862.2485 Electrophoresis apparatus
etc.) serum, urine, cerebrospinal fluid, for clinical use.
and other body fluids before the fluids (a) Identification. An electrophoresis
are analyzed. apparatus for clinical use is a device
(b) Classification. Class I (general con- intended to separate molecules or par-
trols). The device is exempt from the ticles, including plasma proteins,
premarket notification procedures in lipoproteins, enzymes, and
subpart E of part 807 of this chapter hemoglobulins on the basis of their net
subject to the limitations in § 862.9. charge in specified buffered media.
[52 FR 16122, May 1, 1987, as amended at 60 This device is used in conjunction with
FR 38899, July 28, 1995; 66 FR 38788, July 25, certain materials to measure a variety
2001] of analytes as an aid in the diagnosis
and treatment of certain disorders.
§ 862.2320 Beta or gamma counter for (b) Classification. Class I (general con-
clinical use.
(a) Identification. A beta or gamma premarket notification procedures in
counter for clinical use is a device in- subpart E of part 807 of this chapter
tended to detect and count beta or subject to the limitations in § 862.9.
gamma radiation emitted by clinical
samples. Clinical samples are prepared [52 FR 16122, May 1, 1987, as amended at 60
FR 38900, July 28, 1995; 66 FR 38788, July 25,
by addition of a radioactive reagent to
2001]
the sample. These measurements are
useful in the diagnosis and treatment § 862.2500 Enzyme analyzer for clinical
of various disorders. use.
trols). The device is exempt from the (a) Identification. An enzyme analyzer
premarket notification procedures in for clinical use is a device intended to
subpart E of part 807 of this chapter measure enzymes in plasma or serum
subject to the limitations in § 862.9. by nonkinetic or kinetic measurement
of enzyme-catalyzed reactions. This de-
[52 FR 16122, May 1, 1987, as amended at 60 vice is used in conjunction with certain
FR 38900, July 28, 1995; 66 FR 38788, July 25, materials to measure a variety of en-
2001] zymes as an aid in the diagnosis and
§ 862.2400 Densitometer/scanner (inte- treatment of certain enzyme-related
grating, reflectance, TLC, or disorders.
radiochromatogram) for clinical (b) Classification. Class I (general con-
use. trols). The device is exempt from the
(a) Identification. A densitometer/ premarket notification procedures in
scanner (integrating, reflectance, thin- subpart E of part 807 of this chapter
layer chromatography, or subject to § 862.9.
radiochromatogram) for clinical use is [52 FR 16122, May 1, 1987, as amended at 65
device intended to measure the con- FR 2309, Jan. 14, 2000]
centration of a substance on the sur-
face of a film or other support media § 862.2540 Flame emission photometer
for clinical use.
by either a photocell measurement of

the light transmission through a given (a) Identification. A flame emission
area of the medium or, in the case of photometer for clinical use is a device
273
§ 862.2560 21 CFR Ch. I (4–1–23 Edition)
intended to measure the concentration the premarket notification procedures

of sodium, potassium, lithium, and in subpart E of part 807 of this chapter
other metal ions in body fluids. Abnor- subject to the limitations in § 862.9. The
mal variations in the concentration of special control is FDA’s guidance docu-
these substances in the body are indic- ment entitled ‘‘Class II Special Con-
ative of certain disorders (e.g., electro- trols Guidance Document: Instrumen-
lyte imbalance and heavy metal intoxi- tation for Clinical Multiplex Test Sys-
cation) and are, therefore, useful in di- tems.’’ See § 862.1(d) for the availability
agnosis and treatment of those dis- of this guidance document.
orders. [70 FR 11868, Mar. 10, 2005, as amended at 84
(b) Classification. Class I (general con- FR 71797, Dec. 30, 2019]
premarket notification procedures in § 862.2680 Microtitrator for clinical
subpart E of part 807 of this chapter use.
subject to § 862.9. (a) Identification. A microtitrator for
[52 FR 16122, May 1, 1987, as amended at 65 clinical use is a device intended for use
FR 2309, Jan. 14, 2000] in micronanalysis to measure the con-
centration of a substance by reacting it
§ 862.2560 Fluorometer for clinical use. with a measure ‘‘micro’’ volume of a
(a) Identification. A fluorometer for known standardized solution.
clinical use is a device intended to (b) Classification. Class I (general con-
measure by fluorescence certain trols). The device is exempt from the
analytes. Fluorescence is the property premarket notification procedures in
of certain substances of radiating, subpart E of part 807 of this chapter
when illuminated, a light of a different subject to § 862.9.
wavelength. This device is used in con- [52 FR 16122, May 1, 1987, as amended at 65
junction with certain materials to FR 2309, Jan. 14, 2000]
measure a variety of analytes.
(b) Classification. Class I (general con- § 862.2700 Nephelometer for clinical
trols). The device is exempt from the use.
premarket notification procedures in (a) Identification. A nephelometer for
subpart E of part 807 of this chapter clinical use is a device intended to esti-
subject to § 862.9. mate the concentration of particles in
[52 FR 16122, May 1, 1987, as amended at 65 a suspension by measuring their light
FR 2309, Jan. 14, 2000] scattering properties (the deflection of
light rays by opaque particles in their
§ 862.2570 Instrumentation for clinical path). The device is used in conjunc-
multiplex test systems. tion with certain materials to measure
(a) Identification. Instrumentation for the concentration of a variety of
clinical multiplex test systems is a de- analytes.
vice intended to measure and sort mul- (b) Classification. Class I (general con-
tiple signals generated by an assay trols). The device is exempt from the
from a clinical sample. This instru- premarket notification procedures in
mentation is used with a specific assay subpart E of part 807 of this chapter
to measure multiple similar analytes subject to § 862.9.
that establish a single indicator to aid [52 FR 16122, May 1, 1987, as amended at 65
in diagnosis. Such instrumentation FR 2309, Jan. 14, 2000]
may be compatible with more than one
specific assay. The device includes a § 862.2720 Plasma oncometer for clin-
signal reader unit, and may also inte- ical use.
grate reagent handling, hybridization, (a) Identification. A plasma oncometer
washing, dedicated instrument control, for clinical use is a device intended to
and other hardware components, as measure plasma oncotic pressure,
well as raw data storage mechanisms, which is that portion of the total plas-
data acquisition software, and software ma osmotic pressure contributed by
to process detected signals. protein and other molecules too large

(b) Classification. Class II (special to pass through a specified
controls). The device is exempt from semipermeable membrane. Because
274
variations in plasma oncotic pressure subpart E of part 807 of this chapter

are indications of certain disorders, subject to § 862.9.
measurements of the variations are [52 FR 16122, May 1, 1987, as amended at 65
useful in the diagnosis and treatment FR 2309, Jan. 14, 2000]
of these disorders.
(b) Classification. Class I (general con- § 862.2800 Refractometer for clinical
trols). The device is exempt from the use.
premarket notification procedures in (a) Identification. A refractometer for
subpart E of part 807 of this chapter clinical use is a device intended to de-
subject to the limitations in § 862.9. termine the amount of solute in a solu-
[52 FR 16122, May 1, 1987, as amended at 60 tion by measuring the index of refrac-
FR 38900, July 28, 1995; 66 FR 38788, July 25, tion (the ratio of the velocity of light
2001] in a vacuum to the velocity of light in
the solution). The index of refraction is
§ 862.2730 Osmometer for clinical use. used to measure the concentration of
certain analytes (solutes), such a plas-
(a) Identification. An osmometer for
ma total proteins and urinary total
clinical use is a device intended to
solids. Measurements obtained by this
measure the osmotic pressure of body
device are used in the diagnosis and
fluids. Osmotic pressure is the pressure
treatment of certain conditions.
required to prevent the passage of a so-
lution with a lesser solute concentra-
tion into a solution with greater solute
concentration when the two solutions
are separated by a semipermeable
membrane. The concentration of a so-
lution affects its osmotic pressure, [52 FR 16122, May 1, 1987, as amended at 60
freezing point, and other FR 38900, July 28, 1995; 66 FR 38788, July 25,
physiochemical properties. 2001]
Osmometers determine osmotic pres- § 862.2850 Atomic absorption spectro-
sure by methods such as the measure- photometer for clinical use.
ment of the freezing point. Measure-
ments obtained by this device are used (a) Identification. An atomic absorp-
in the diagnosis and treatment of body tion spectrophotometer for clinical use
fluid disorders. is a device intended to identify and
measure elements and metals (e.g.,
lead and mercury) in human specimens.
The metal elements are identified ac-
cording to the wavelength and inten-
sity of the light that is absorbed when
the specimen is converted to the atom-
[52 FR 16122, May 1, 1987, as amended at 65 ic vapor phase. Measurements obtained
FR 2309, Jan. 14, 2000] by this device are used in the diagnosis
and treatment of certain conditions.
§ 862.2750 Pipetting and diluting sys- (b) Classification. Class I (general con-
tem for clinical use. trols). The device is exempt from the
(a) Identification. A pipetting and di- premarket notification procedures in
luting system for clinical use is a de- subpart E of part 807 of this chapter
vice intended to provide an accurately subject to § 862.9.
measured volume of liquid at a speci- [52 FR 16122, May 1, 1987, as amended at 65
fied temperature for use in certain test FR 2309, Jan. 14, 2000]
procedures. This generic type of device
system includes serial, manual, auto- § 862.2860 Mass spectrometer for clin-
mated, and semi-automated dilutors, ical use.
pipettors, dispensers, and pipetting sta- (a) Identification. A mass spectrom-
tions. eter for clinical use is a device in-
(b) Classification. Class I (general con- tended to identify inorganic or organic

trols). The device is exempt from the compounds (e.g., lead, mercury, and
premarket notification procedures in drugs) in human specimens by ionizing
275
§ 862.2900 21 CFR Ch. I (4–1–23 Edition)
the compound under investigation and measure acetaminophen, an analgestic

separating the resulting ions by means and fever reducing drug, in serum.
of an electrical and magnetic field ac- Measurements obtained by this device
cording to their mass. are used in the diagnosis and treat-
(b) Classification. Class I (general con- ment of acetaminophen overdose.
trols). The device is exempt from the (b) Classification. Class II.
subpart E of part 807 of this chapter § 862.3035 Amikacin test system.
subject to § 862.9. (a) Identification. An amikacin test
[52 FR 16122, May 1, 1987, as amended at 65 system is a device intended to measure
FR 2309, Jan. 14, 2000] amikacin, an aminoglycoside anti-
biotic drug, in serum and plasma.
§ 862.2900 Automated urinalysis sys- Measurements obtained by this device
tem. are used in the diagnosis and treat-
(a) Identification. An automated uri- ment of amikacin overdose and in mon-
nalysis system is a device intended to itoring levels of amikacin to ensure ap-
measure certain of the physical prop- propriate therapy.
erties and chemical constituents of (b) Classification. Class II.
urine by procedures that duplicate
manual urinalysis systems. This device § 862.3040 Alcohol test system.
is used in conjunction with certain ma- (a) Identification. An alcohol test sys-
terials to measure a variety of urinary tem is a device intented to measure al-
analytes. cohol (e.g., ethanol, methanol,
(b) Classification. Class I (general con- isopropanol, etc.) in human body fluids
trols). The device is exempt from the (e.g., serum, whole blood, and urine).
premarket notification procedures in Measurements obtained by this device
subpart E of part 807 of this chapter are used in the diagnosis and treat-
subject to § 862.9. ment of alcohol intoxication and poi-
[52 FR 16122, May 1, 1987, as amended at 65 soning.
§ 862.2920 Plasma viscometer for clin- § 862.3050 Breath-alcohol test system.

ical use. (a) Identification. A breath-alcohol
(a) Identification. A plasma viscom- test system is a device intened to
eter for clinical use is a device in- measure alcohol in the human breath.
tended to measure the viscosity of Measurements obtained by this device
plasma by determining the time period are used in the diagnosis of alcohol in-
required for the plasma to flow a meas- toxication.
ured distance through a calibrated (b) Classification. Class I (general con-
glass tube. Measurements obtained by trols). The device is exempt from the
this device are used to monitor changes premarket notification procedures in
in the amount of solids present in plas- subpart E of part 807 of this chapter
ma in various disorders. subject to the limitations in § 862.9.
trols). The device is exempt from the [52 FR 16122, May 1, 1987, as amended at 84
FR 71797, Dec. 30, 2019]
subpart E of part 807 of this chapter § 862.3080 Breath nitric oxide test sys-
subject to the limitations in § 862.9. tem.
[52 FR 16122, May 1, 1987, as amended at 60 (a) Identification. A breath nitric
FR 38900, July 28, 1995; 66 FR 38788, July 25, oxide test system is a device intended
2001] to measure fractional nitric oxide in
human breath. Measurement of
Subpart D—Clinical Toxicology changes in fractional nitric oxide con-
Test Systems centration in expired breath aids in
evaluating an asthma patient’s re-
§ 862.3030 Acetaminophen test system.
sponse to anti-inflammatory therapy,

(a) Identification. An acetaminophen as an adjunct to established clinical
test system is a device intended to and laboratory assessments of asthma.
276
A breath nitric oxide test system com- § 862.3120 Arsenic test system.
bines chemiluminescence detection of
(a) Identification. An arsenic test sys-
nitric oxide with a pneumotachograph,
tem is a device intended to measure ar-
display, and dedicated software.
senic, a poisonous heavy metal, in
urine, vomitus, stomach contents,
controls). The special control is FDA’s
nails, hair, and blood. Measurements
guidance entitled ‘‘Class II Special
obtained by this device are used in the
Controls Guidance Document: Breath
diagnosis and treatment of arsenic poi-
Nitric Oxide Test System.’’ See
soning.
§ 862.1(d) for the availability of this
guidance document.
[68 FR 40127, July 7, 2003] § 862.3150 Barbiturate test system.
(a) Identification. A barbiturate test
§ 862.3100 Amphetamine test system. system is a device intended to measure
(a) Identification. An amphetamine barbiturates, a class of hypnotic and
test system is a device intended to sedative drugs, in serum, urine, and
measure amphetamine, a central nerv- gastric contents. Measurements ob-
ous system stimulating drug, in plasma tained by this device are used in the di-
and urine. Measurements obtained by agnosis and treatment of barbiturate
this device are used in the diagnosis use or overdose and in monitoring lev-
and treatment of amphetamine use or els of barbiturate to ensure appropriate
overdose and in monitoring levels of therapy.
amphetamine to ensure appropriate (b) Classification. Class II (special
therapy. controls). A barbiturate test system is
(b) Classification. Class II (special not exempt if it is intended for any use
controls). An amphetamine test system other than employment or insurance
is not exempt if it is intended for any testing or is intended for Federal drug
use other than employment or insur- testing programs. The device is exempt
ance testing or is intended for Federal from the premarket notification proce-
drug testing programs. The device is dures in subpart E of part 807 of this
exempt from the premarket notifica- chapter subject to the limitations in
tion procedures in subpart E of part 807 § 862.9, provided the test system is in-
of this chapter subject to the limita- tended for employment and insurance
tions in § 862.9, provided the test sys- testing and includes a statement in the
tem is intended for employment and in- labeling that the device is intended
surance testing and includes a state- solely for use in employment and in-
ment in the labeling that the device is surance testing, and does not include
intended solely for use in employment devices intended for Federal drug test-
and insurance testing, and does not ining programs (e.g., programs run by the
clude devices intended for Federal drug Substance Abuse and Mental Health
testing programs (e.g., programs run by Services Administration (SAMHSA),
the Substance Abuse and Mental the Department of Transportation
Health Services Administration (DOT), and the U.S. military).
(SAMHSA), the Department of Trans- [52 FR 16122, May 1, 1987, as amended at 84
portation (DOT), and the U.S. mili- FR 71797, Dec. 30, 2019]
tary).
[52 FR 16122, May 1, 1987, as amended at 84 § 862.3170 Benzodiazepine test system.
FR 71797, Dec. 30, 2019] (a) Identification. A benzodiazepine
§ 862.3110 Antimony test system. measure any of the benzodiazepine
(a) Identification. An antimony test compounds, sedative and hypnotic
system is a device intended to measure drugs, in blood, plasma, and urine. The
antimony, a heavy metal, in urine, benzodiazepine compounds include
blood, vomitus, and stomach contents. chlordiazepoxide, diazepam, oxazepam,
Measurements obtained by this device chlorzepate, flurazepam, and
are used in the diagnosis and treat- nitrazepam. Measurements obtained by

ment of antimony poisoning. this device are used in the diagnosis
(b) Classification. Class I. and treatment of benzodiazepine use or
277
§ 862.3200 21 CFR Ch. I (4–1–23 Edition)
overdose and in monitoring levels of and treatment of or confirmation of

benzodiazepines to ensure appropriate carbon monoxide poisoning.
therapy. (b) Classification. Class I (general con-
(b) Classification. Class II (special trols). The device is exempt from the
controls). A benzodiazepine test system premarket notification procedures in
is not exempt if it is intended for any subpart E of part 807 of this chapter
use other than employment or insur- subject to the limitations in § 862.9.
ance testing or is intended for Federal
drug testing programs. The device is
FR 71797, Dec. 30, 2019]
exempt from the premarket notifica-
tion procedures in subpart E of part 807 § 862.3240 Cholinesterase test system.
of this chapter subject to the limita-
tions in § 862.9, provided the test sys- (a) Identification. A cholinesterase
tem is intended for employment and in- test system is a device intended to
surance testing and includes a state- measure cholinesterase (an enzyme
ment in the labeling that the device is that catalyzes the hydrolysis of acetyl-
intended solely for use in employment choline to choline) in human speci-
and insurance testing, and does not in- mens. There are two principal types of
clude devices intended for Federal drug cholinesterase in human tissues. True
testing programs (e.g., programs run by cholinesterase is present at nerve
the Substance Abuse and Mental endings and in erythrocytes (red blood
Health Services Administration cells) but is not present in plasma.
(SAMHSA), the Department of Trans- Pseudo cholinesterase is present in
portation (DOT), and the U.S. mili- plasma and liver but is not present in
tary). erythrocytes. Measurements obtained
by this device are used in the diagnosis
and treatment of cholinesterase inhibi-
FR 71797, Dec. 30, 2019]
tion disorders (e.g., insecticide poi-
§ 862.3200 Clinical toxicology cali- soning and succinylcholine poisoning).
brator. (b) Classification. Class I (general con-
(a) Identification. A clinical toxi- trols). The device is exempt from the
cology calibrator is a device intended premarket notification procedures in
for medical purposes for use in a test subpart E of part 807 of this chapter
system to establish points of reference subject to the limitations in § 862.9.
that are used in the determination of [52 FR 16122, May 1, 1987, as amended at 84
values in the measurement of sub- FR 71797, Dec. 30, 2019]
stances in human specimens. A clinical
toxicology calibrator can be a mixture § 862.3250 Cocaine and cocaine me-
of drugs or a specific material for a tabolite test system.
particular drug (e.g., ethanol, lido- (a) Identification. A cocaine and co-
caine, etc.). (See also § 862.2 in this caine metabolite test system is a de-
part.) vice intended to measure cocaine and a
(b) Classification. Class II (special cocaine metabolite (benzoylecgonine)
controls). The device is exempt from in serum, plasma, and urine. Measure-
the premarket notification procedures ments obtained by this device are used
in subpart E of part 807 of this chapter in the diagnosis and treatment of co-
subject to the limitations in § 862.9. caine use or overdose.
FR 71797, Dec. 30, 2019] controls). A cocaine and cocaine me-
tabolite test system is not exempt if it
§ 862.3220 Carbon monoxide test sys- is intended for any use other than em-
tem. ployment or insurance testing or is in-
(a) Identification. A carbon monoxide tended for Federal drug testing pro-
test system is a device intended to grams. The device is exempt from the
measure carbon monoxide or premarket notification procedures in
carboxyhemoglobin (carbon monoxide subpart E of part 807 of this chapter
bound to the hemoglobin in the blood) subject to the limitations in § 862.9,

in blood. Measurements obtained by provided the test system is intended
this device are used in the diagnosis for employment and insurance testing
278
and includes a statement in the label- (b) Classification. Class I (general con-
ing that the device is intended solely trols). The device is exempt from the
for use in employment and insurance premarket notification procedures in
testing, and does not include devices subpart E of part 807 of this chapter
intended for Federal drug testing pro- subject to the limitations in § 862.9.
grams (e.g., programs run by the Sub-
stance Abuse and Mental Health Serv- FR 2309, Jan. 14, 2000, 84 FR 71798, Dec. 30,
ices Administration (SAMHSA), the 2019]
Department of Transportation (DOT),
and the U.S. military). § 862.3300 Digitoxin test system.
[52 FR 16122, May 1, 1987, as amended at 84 (a) Identification. A digitoxin test sys-
FR 71797, Dec. 30, 2019] tem is a device intended to measure
digitoxin, a cardiovascular drug, in
§ 862.3270 Codeine test system. serum and plasma. Measurements ob-
(a) Identification. A codeine test sys- tained by this device are used in the di-
tem is a device intended to measure co- agnosis and treatment of digitoxin
deine (a narcotic pain-relieving drug) overdose and in monitoring levels of
in serum and urine. Measurements ob- digitoxin to ensure appropriate ther-
tained by this device are used in the di- apy.
agnosis and treatment of codeine use (b) Classification. Class II.
or overdose and in monitoring levels of
codeine to ensure appropriate therapy. § 862.3320 Digoxin test system.
(b) Classification. Class II (special (a) Identification. A digoxin test sys-
controls). A codeine test system is not tem is a device intended to measure
exempt if it is intended for any use digoxin, a cardiovascular drug, in
other than employment or insurance serum and plasma. Measurements ob-
testing or is intended for Federal drug tained by this device are used in the di-
testing programs. The device is exempt agnosis and treatment of digoxin over-
from the premarket notification proce- dose and in monitoring levels of dig-
dures in subpart E of part 807 of this oxin to ensure appropriate therapy.
chapter subject to the limitations in (b) Classification. Class II.
§ 862.9, provided the test system is in-
tended for employment and insurance § 862.3350 Diphenylhydantoin test sys-
testing and includes a statement in the tem.
labeling that the device is intended (a) Identification. A diphenylhydan-
solely for use in employment and in- toin test system is a device intended to
surance testing, and does not include measure diphenylhydantoin, an
devices intended for Federal drug test- antiepileptic drug, in human speci-
ing programs (e.g., programs run by the mens. Measurements obtained by this
Substance Abuse and Mental Health device are used in the diagnosis and
Services Administration (SAMHSA), treatment of diphenylhydantoin over-
the Department of Transportation dose and in monitoring levels of di-
(DOT), and the U.S. military). phenylhydantoin to ensure appropriate
[52 FR 16122, May 1, 1987, as amended at 84 therapy.
FR 71798, Dec. 30, 2019] (b) Classification. Class II.
§ 862.3280 Clinical toxicology control § 862.3360 Drug metabolizing enzyme

material. genotyping system.
(a) Identification. A clinical toxi- (a) Identification. A drug metabolizing
cology control material is a device in- enzyme genotyping system is a device
tended to provide an estimation of the intended for use in testing
precision of a device test system and to deoxyribonucleic acid (DNA) extracted
detect and monitor systematic devi- from clinical samples to identify the
ations from accuracy resulting from re- presence or absence of human
agent or instrument defects. This ge- genotypic markers encoding a drug me-
neric type of device includes various tabolizing enzyme. This device is used
single, and multi-analyte control ma- as an aid in determining treatment
terials. choice and individualizing treatment
279
§ 862.3380 21 CFR Ch. I (4–1–23 Edition)
dose for therapeutics that are metabo- § 862.3555 Lidocaine test system.
lized primarily by the specific enzyme (a) Identification. A lidocaine test sys-
about which the system provides tem is a device intended to measure
genotypic information. lidocaine, an antiarrythmic and
(b) Classification. Class II (special anticonvulsant drug, in serum and
controls). The special control is FDA’s plasma. Measurements obtained by this
guidance document entitled ‘‘Class II device are used in the diagnosis and
Special Controls Guidance Document: treatment of lidocaine overdose or in
Drug Metabolizing Enzyme Genotyping monitoring levels of lidocaine to en-
Test System.’’ See § 862.1(d) for the sure appropriate therapy.
availability of this guidance document. (b) Classification. Class II.
[70 FR 11867, Mar. 10, 2005]
§ 862.3560 Lithium test system.
§ 862.3380 Ethosuximide test system. (a) Identification. A lithium test sys-
(a) Identification. An ethosuximide
lithium (from the drug lithium car-
test system is a device intended to bonate) in serum or plasma. Measure-
measure ethosuximide, an antiepileptic ments of lithium are used to assure
drug, in human specimens. Measure- that the proper drug dosage is adminis-
ments obtained by this device are used tered in the treatment of patients with
in the diagnosis and treatment of mental disturbances, such as manic-de-
ethosuximide overdose and in moni- pressive illness (bipolar disorder).
toring levels of ethosuximide to ensure (b) Classification. Class II.
appropriate therapy.
(b) Classification. Class II. § 862.3580 Lysergic acid diethylamide
(LSD) test system.
§ 862.3450 Gentamicin test system. (a) Identification. A lysergic acid
(a) Identification. A gentamicin test diethylamide (LSD) test system is a
system is a device intended to measure device intended to measure lysergic
gentamicin, an antibiotic drug, in acid diethylamide, a hallucinogenic
human specimens. Measurements ob- drug, in serum, urine, and gastric con-
tained by this device are used in the di- tents. Measurements obtained by this
agnosis and treatment of gentamicin device are used in the diagnosis and
overdose and in monitoring levels of treatment of LSD use or overdose.
gentamicin to ensure appropriate ther- (b) Classification. Class II (special
apy. controls). A lysergic acid diethylamide
(b) Classification. Class II. (LSD) test system is not exempt if it is
intended for any use other than em-
§ 862.3520 Kanamycin test system. ployment or insurance testing or is in-
tended for Federal drug testing pro-
(a) Identification. A kanamycin test grams. The device is exempt from the
system is a device intended to measure premarket notification procedures in
kanamycin, an antibiotic drug, in plas- subpart E of part 807 of this chapter
ma and serum. Measurements obtained subject to the limitations in § 862.9,
by this device are used in the diagnosis provided the test system is intended
and treatment of kanamycin overdose for employment and insurance testing
and in monitoring levels of kanamycin and includes a statement in the label-
to ensure appropriate therapy. ing that the device is intended solely
(b) Classification. Class II. for use in employment and insurance
testing, and does not include devices
§ 862.3550 Lead test system. intended for Federal drug testing pro-
(a) Identification. A lead test system grams (e.g., programs run by the Sub-
is a device intended to measure lead, a stance Abuse and Mental Health Serv-
heavy metal, in blood and urine. Meas- ices Administration (SAMHSA), the
urements obtained by this device are Department of Transportation (DOT),
and the U.S. military).

lead poisoning. [52 FR 16122, May 1, 1987, as amended at 84
(b) Classification. Class II. FR 71798, Dec. 30, 2019]
280
§ 862.3590 Meprobamate test system. centrations or to inform dosing adjust-

ment decisions.’’
(a) Identification. A meprobamate test
system is a device intended to measure [83 FR 54876, Nov. 1, 2018]
meprobamate in human specimens.
Measurements obtained by this device § 862.3600 Mercury test system.
are used to detect the presence of me- (a) Identification. A mercury test sys-
probamate to diagnose the use or over- tem is a device intended to measure
dose of meprobamate or structurally- mercury, a heavy metal, in human
related drug compounds (e.g., specimens. Measurements obtained by
prodrugs). this device are used in the diagnosis
(b) Classification. Class II (special and treatment of mercury poisoning.
controls). The special controls for this (b) Classification. Class I.
device are:
(1) Design verification and validation § 862.3610 Methamphetamine test sys-
must include: tem.
(i) Robust data demonstrating the ac- (a) Identification. A methamphet-
curacy of the device when used in the amine test system is a device intended
intended specimen matrix. The accu- to measure methamphetamine, a cen-
racy data must include a comparison tral nervous system stimulating drug,
between the meprobamate test system in serum, plasma, and urine. Measure-
results and meprobamate results that ments obtained by this device are used
are measured on an FDA-accepted in the diagnosis and treatment of
measurement method that is specific methamphetamine use or overdose.
and accurate (e.g., gas or liquid chro- (b) Classification. Class II (special
matography combined with tandem controls). A methamphetamine test
mass spectrometry).
system is not exempt if it is intended
(ii) Robust analytical data dem- for any use other than employment or
onstrating the performance character- insurance testing or is intended for
istics of the device, including, but not Federal drug testing programs. The de-
limited to, specificity, cross-reactivity vice is exempt from the premarket no-
to relevant endogenous and exogenous tification procedures in subpart E of
substances, and the reproducibility of part 807 of this chapter subject to the
analyte detection around the cutoff(s). limitations in § 862.9, provided the test
(2) The intended use of the device system is intended for employment and
must not include an indication for use insurance testing and includes a state-
in monitoring therapeutic drug con- ment in the labeling that the device is
centrations or informing dosing adjust- intended solely for use in employment
ment decisions. and insurance testing, and does not in-
(3) Your 21 CFR 809.10 labeling must clude devices intended for Federal drug
include the following: testing programs (e.g., programs run by
(i) If indicated for use as a screening the Substance Abuse and Mental
test to identify preliminary results for Health Services Administration
further confirmation, the intended use (SAMHSA), the Department of Trans-
must state ‘‘This assay provides only a portation (DOT), and the U.S. mili-
preliminary analytical result. A more tary).
specific alternative chemical confirm-
atory method (e.g., gas or liquid chro- [52 FR 16122, May 1, 1987, as amended at 84
matography and mass spectrometry) FR 71798, Dec. 30, 2019]
must be used to obtain a confirmed an-
alytical result. Clinical consideration § 862.3620 Methadone test system.
and professional judgment must be ex- (a) Identification. A methadone test
ercised with any drug of abuse test, system is a device intended to measure
particularly when the preliminary test methadone, an addictive narcotic pain-
result is positive.’’ relieving drug, in serum and urine.
(ii) A limiting statement that reads Measurements obtained by this device

as follows: ‘‘This test should not be are used in the diagnosis and treat-
used to monitor therapeutic drug con- ment of methadone use or overdose and
281
§ 862.3630 21 CFR Ch. I (4–1–23 Edition)
to determine compliance with regula- portation (DOT), and the U.S. mili-
tions in methadone maintenance treat- tary).
ment. [52 FR 16122, May 1, 1987, as amended at 84
(b) Classification. Class II (special FR 71798, Dec. 30, 2019]
controls). A methadone test system is
not exempt if it is intended for any use § 862.3640 Morphine test system.
other than employment or insurance (a) Identification. A morphine test
testing or is intended for Federal drug system is a device intended to measure
testing programs. The device is exempt morphine, an addictive narcotic pain-
from the premarket notification proce- relieving drug, and its analogs in
dures in subpart E of part 807 of this serum, urine, and gastric contents.
chapter subject to the limitations in Measurements obtained by this device
§ 862.9, provided the test system is in- are used in the diagnosis and treat-
tended for employment and insurance ment of morphine use or overdose and
testing and includes a statement in the in monitoring levels of morphine and
labeling that the device is intended its analogs to ensure appropriate ther-
solely for use in employment and in- apy.
surance testing, and does not include (b) Classification. Class II (special
devices intended for Federal drug test- controls). A morphine test system is
ing programs (e.g., programs run by the not exempt if it is intended for any use
Substance Abuse and Mental Health other than employment or insurance
Services Administration (SAMHSA), testing or is intended for Federal drug
testing programs. The device is exempt
the Department of Transportation
from the premarket notification proce-
(DOT), and the U.S. military).
dures in subpart E of part 807 of this
[52 FR 16122, May 1, 1987, as amended at 84 chapter subject to the limitations in
FR 71798, Dec. 30, 2019] § 862.9, provided the test system is in-
tended for employment and insurance
§ 862.3630 Methaqualone test system. testing and includes a statement in the
(a) Identification. A methaqualone labeling that the device is intended
test system is a device intended to solely for use in employment and in-
measure methaqualone, a hypnotic and surance testing, and does not include
sedative drug, in urine. Measurements devices intended for Federal drug test-
obtained by this device are used in the ing programs (e.g., programs run by the
Substance Abuse and Mental Health
diagnosis and treatment of methaqua-
Services Administration (SAMHSA),
lone use or overdose.
(b) Classification. Class II (special (DOT), and the U.S. military).
controls). A methaqualone test system
is not exempt if it is intended for any [52 FR 16122, May 1, 1987, as amended at 84
use other than employment or insur- FR 71798, Dec. 30, 2019]
ance testing or is intended for Federal § 862.3645 Neuroleptic drugs
drug testing programs. The device is radioreceptor assay test system.
(a) Identification. A neuroleptic drugs
radioceptor assay test system is a de-
vice intended to measure in serum or
tions in § 862.9, provided the test sys- plasma the dopamine receptor blocking
tem is intended for employment and in- activity of neuroleptic drugs and their
surance testing and includes a state- active metabolites. A neuroleptic drug
ment in the labeling that the device is has anti-psychotic action affecting
intended solely for use in employment principally psychomotor activity, is
and insurance testing, and does not in- generally without hypnotic effects, and
clude devices intended for Federal drug is a tranquilizer. Measurements ob-
testing programs (e.g., programs run by tained by this device are used to aid in
the Substance Abuse and Mental determining whether a patient is tak-
Health Services Administration ing the prescribed dosage level of such

(SAMHSA), the Department of Trans- drugs.
282
§ 862.3650 Opiate test system. enced personnel who are trained to

measure and evaluate organophosphate
(a) Identification. An opiate test sys-
exposure and guide public health re-
sponse.
any of the addictive narcotic pain-re-
lieving opiate drugs in blood, serum, (2) Analytical testing must dem-
urine, gastric contents, and saliva. An onstrate the device has appropriate
opiate is any natural or synthetic drug performance characteristics, including
that has morphine-like adequate precision and accuracy across
pharmocological actions. The opiates the measuring range and near medical
include drugs such as morphine, mor- decision points.
phine glucoronide, heroin, codeine, [82 FR 48415, Oct. 18, 2017]
nalorphine, and meperedine. Measure-
ments obtained by this device are used § 862.3660 Phenobarbital test system.
in the diagnosis and treatment of opi- (a) Identification. A phenobarbitol
ate use or overdose and in monitoring test system is a device intended to
the levels of opiate administration to measure phenobarbital, an
ensure appropriate therapy. antiepileptic and sedative-hypnotic
(b) Classification. Class II (special drug, in human specimens. Measure-
controls). An opiate test system is not ments obtained by this device are used
exempt if it is intended for any use in the diagnosis and treatment of phe-
other than employment or insurance nobarbital use or overdose and in moni-
testing or is intended for Federal drug toring levels of phenobarbital to ensure
testing programs. The device is exempt appropriate therapy.
from the premarket notification proce-
chapter subject to the limitations in § 862.3670 Phenothiazine test system.
§ 862.9, provided the test system is in-
tended for employment and insurance (a) Identification. A phenothiazine
testing and includes a statement in the test system is a device intended to
labeling that the device is intended measure any of the drugs of the
solely for use in employment and in- phenothiazine class in human speci-
surance testing, and does not include mens. Measurements obtained by this
devices intended for Federal drug test- device are used in the diagnosis and
ing programs (e.g., programs run by the treatment of phenothiazine use or
Substance Abuse and Mental Health overdose.
Services Administration (SAMHSA), (b) Classification. Class II.
(DOT), and the U.S. military). § 862.3680 Primidone test system.
[52 FR 16122, May 1, 1987, as amended at 84 (a) Identification. A primidone test
FR 71798, Dec. 30, 2019] system is a device intended to measure
primidone, an antiepileptic drug, in
§ 862.3652 Organophosphate test sys- human specimens. Measurements ob-
tem. tained by this device are used in the di-
(a) Identification. An organophosphate agnosis and treatment of primidone
test system is a device intended to overdose and in monitoring levels of
measure organophosphate metabolites primidone to ensure appropriate ther-
quantitatively in human urine from in- apy.
dividuals who have signs and symp- (b) Classification. Class II.
toms consistent with cholinesterase
poisoning. The data obtained by this § 862.3700 Propoxyphene test system.
device is intended to aid in the con- (a) Identification. A propoxyphene
firmation and investigation of test system is a device intended to
organophosphate exposure. measure propoxyphene, a pain-reliev-
(b) Classification. Class II (special ing drug, in serum, plasma, and urine.
controls). The special controls for this Measurements obtained by this device
device are: are used in the diagnosis and treat-

(1) The distribution of these devices ment of propoxyphene use or overdose
is limited to laboratories with experi- or in monitoring levels of
283
§ 862.3750 21 CFR Ch. I (4–1–23 Edition)
propoxyphene to ensure appropriate subpart E of part 807 of this chapter,

therapy. subject to the limitations in § 862.9.
(b) Classification. Class II (special [82 FR 61163, Dec. 27, 2017]
controls). A propoxyphene test system
is not exempt if it is intended for any § 862.3830 Salicylate test system.
use other than employment or insur- (a) Identification. A salicylate test
ance testing or is intended for Federal system is a device intended to measure
drug testing programs. The device is salicylates, a class of analgesic, anti-
exempt from the premarket notifica- pyretic and anti-inflammatory drugs
tion procedures in subpart E of part 807 that includes aspirin, in human speci-
of this chapter subject to the limita- mens. Measurements obtained by this
tions in § 862.9, provided the test sys- device are used in diagnosis and treat-
tem is intended for employment and in- ment of salicylate overdose and in
surance testing and includes a state- monitoring salicylate levels to ensure
ment in the labeling that the device is appropriate therapy.
intended solely for use in employment (b) Classification. Class II.
and insurance testing, and does not in-
§ 862.3840 Sirolimus test system.
clude devices intended for Federal drug
testing programs (e.g., programs run by (a) Identification. A sirolimus test
the Substance Abuse and Mental system is a device intended to quan-
Health Services Administration titatively determine sirolimus con-
(SAMHSA), the Department of Trans- centrations in whole blood. Measure-
ments are used as an aid in manage-
portation (DOT), and the U.S. mili-
ment of transplant patients receiving
tary).
therapy with sirolimus.
FR 71798, Dec. 30, 2019] controls). The special control is FDA’s
§ 862.3750 Quinine test system. Special Controls Guidance Document:
(a) Identification. A quinine test sys- Sirolimus Test Systems.’’ See § 862.1(d)
tem is a device intended to measure for the availability of this guidance
quinine, a fever-reducing and pain-re- document.
lieving drug intended in the treatment [69 FR 58259, Sept. 30, 2004]
of malaria, in serum and urine. Meas-
urements obtained by this device are § 862.3850 Sulfonamide test system.
used in the diagnosis and treatment of (a) Identification. A sulfonamide test
quinine overdose and malaria. system is a device intended to measure
(b) Classification. Class I. sulfonamides, any of the antibacterial
drugs derived from sulfanilamide, in
[52 FR 16122, May 1, 1987, as amended at 53 human specimens. Measurements ob-
FR 21450, June 8, 1988; 65 FR 2310, Jan. 14, tained by this device are used in the di-
2000]
agnosis and treatment of sulfonamide
overdose and in monitoring sul-
§ 862.3800 Reagents for molecular di-
agnostic instrument test systems. fonamide levels to ensure appropriate
therapy.
(a) Identification. Reagents for molec- (b) Classification. Class I.
ular diagnostic test systems are re-
agents other than analyte specific re- FR 21450, June 8, 1988; 65 FR 2310, Jan. 14,
agents used as part of molecular diag- 2000]
nostic test systems, such as
polymerases, nucleotides and nucleo- § 862.3870 Cannabinoid test system.
tide mixes, master mixes in which indi- (a) Identification. A cannabinoid test
vidual reagents are optimized to be system is a device intended to measure
used together, and labeled nucleic acid any of the cannabinoids, hallucino-
molecules. genic compounds endogenous to mari-
(b) Classification. Class I (general con- huana, in serum, plasma, saliva, and
trols). The device is exempt from the urine. Cannabinoid compounds include
premarket notification procedure in delta-9-tetrahydrocannabinol,
284
cannabidiol, cannabinol, and § 862.3910 Tricyclic antidepressant

cannabichromene. Measurements ob- drugs test system.
tained by this device are used in the di- (a) Identification. A tricyclic
agnosis and treatment of cannabinoid antidepressant drugs test system is a
use or abuse and in monitoring levels device intended to measure any of the
of cannabinoids during clinical inves- tricyclic antidepressant drugs in
tigational use. serum. The tricyclic antidepressant
(b) Classification. Class II (special drugs include imipramine,
controls). A cannabinoid test system is desipramine, amitriptyline,
not exempt if it is intended for any use nortriptyline, protriptyline, and
other than employment or insurance doxepin. Measurements obtained by
testing or is intended for Federal drug this device are used in the diagnosis
testing programs. The device is exempt and treatment of chronic depression to
from the premarket notification proce- ensure appropriate therapy.
controls). A tricyclic antidepressant
chapter subject to the limitations in
drugs test system is not exempt if it is
§ 862.9, provided the test system is in- intended for any use other than em-
tended for employment and insurance ployment or insurance testing or is in-
testing and includes a statement in the tended for Federal drug testing pro-
labeling that the device is intended grams. The device is exempt from the
solely for use in employment and in- premarket notification procedures in
surance testing, and does not include subpart E of part 807 of this chapter
devices intended for Federal drug test- subject to the limitations in § 862.9,
ing programs (e.g., programs run by the provided the test system is intended
Substance Abuse and Mental Health for employment and insurance testing
Services Administration (SAMHSA), and includes a statement in the label-
the Department of Transportation ing that the device is intended solely
(DOT), and the U.S. military). for use in employment and insurance
testing, and does not include devices
FR 71799, Dec. 30, 2019]
intended for Federal drug testing pro-
grams (e.g., programs run by the Sub-
§ 862.3880 Theophylline test system. stance Abuse and Mental Health Serv-
ices Administration (SAMHSA), the
(a) Identification. A theophylline test Department of Transportation (DOT),
system is a device intended to measure and the U.S. military).
theophylline (a drug used for stimula-
tion of the muscles in the cardio-
FR 71799, Dec. 30, 2019]
vascular, respiratory, and central nerv-
ous systems) in serum and plasma. § 862.3950 Vancomycin test system.
(a) Identification. A vancomycin test
are used in the diagnosis and treat- system is a device intended to measure
ment of theophylline overdose or in vancomycin, an antibiotic drug, in
monitoring levels of theophylline to serum. Measurements obtained by this
ensure appropriate therapy. device are used in the diagnosis and
(b) Classification. Class II. treatment of vancomycin overdose and
in monitoring the level of vancomycin
§ 862.3900 Tobramycin test system. to ensure appropriate therapy.
(a) Identification. A tobramycin test (b) Classification. Class II.
tobramycin, an aminoglycoside anti- PART 864—HEMATOLOGY AND
biotic drug, in plasma and serum. PATHOLOGY DEVICES
are used in the diagnosis and treat- Subpart A—General Provisions
ment of tobramycin overdose and in
Sec.
monitoring levels of tobramycin to en- 864.1 Scope.

sure appropriate therapy. 864.3 Effective dates of requirement for pre-
(b) Classification. Class II. market approval.
285
864.9 Limitations of exemptions from sec- 864.5425 Multipurpose system for in vitro
tion 510(k) of the Federal Food, Drug, coagulation studies.
and Cosmetic Act (the act). 864.5600 Automated hematocrit instrument.
864.5620 Automated hemoglobin system.
Subpart B—Biological Stains 864.5680 Automated heparin analyzer.
864.5700 Automated platelet aggregation
864.1850 Dye and chemical solution stains. system.
864.1860 Immunohistochemistry reagents 864.5800 Automated sedimentation rate de-
and kits. vice.
864.1865 Cervical intraepithelial neoplasia 864.5850 Automated slide spinner.
(CIN) test system. 864.5950 Blood volume measuring device.
864.1866 Lynch syndrome test systems.
864.1870 Early growth response 1 (EGR1) Subpart G—Manual Hematology Devices
gene fluorescence in-situ hybridization
(FISH) test system for specimen charac- 864.6100 Bleeding time device.
terization. 864.6150 Capillary blood collection tube.
864.6160 Manual blood cell counting device.
Subpart C—Cell and Tissue Culture 864.6400 Hematocrit measuring device.
Products 864.6550 Occult blood test.
864.6600 Osmotic fragility test.
864.2220 Synthetic cell and tissue culture 864.6650 Platelet adhesion test.
media and components. 864.6675 Platelet aggregometer.
864.2240 Cell and tissue culture supplies and 864.6700 Erythrocyte sedimentation rate
equipment. test.
864.2260 Chromosome culture kit.
864.2280 Cultured animal and human cells. Subpart H—Hematology Kits and
864.2360 Mycoplasma detection media and Packages
components.
864.2800 Animal and human sera. 864.7010 Flow cytometric test system for
864.2875 Balanced salt solutions or formula- hematopoietic neoplasms.
tions. 864.7040 Adenosine triphosphate release
assay.
Subpart D—Pathology Instrumentation and 864.7060 Antithrombin III assay.
Accessories 864.7100 Red blood cell enzyme assay.
864.7140 Activated whole blood clotting time
864.3010 Tissue processing equipment. tests.
864.3250 Specimen transport and storage 864.7250 Erythropoietin assay.
container. 864.7275 Euglobulin lysis time tests.
864.3260 OTC test sample collection systems 864.7280 Factor V Leiden DNA mutation de-
for drugs of abuse testing. tection systems.
864.3300 Cytocentrifuge. 864.7290 Factor deficiency test.
864.3400 Device for sealing microsections. 864.7300 Fibrin monomer paracoagulation
864.3600 Microscopes and accessories. test.
864.3700 Whole slide imaging system. 864.7320 Fibrinogen/fibrin degradation prod-
864.3750 Software algorithm device to assist
ucts assay.
users in digital pathology.
864.7340 Fibrinogen determination system.
864.3800 Automated slide stainer.
864.7360 Erythrocytic glucose-6-phosphate
864.3875 Automated tissue processor.
dehydrogenase assay.
864.7375 Glutathione reductase assay.
Subpart E—Specimen Preparation
864.7400 Hemoglobin A2 assay.
Reagents 864.7415 Abnormal hemoglobin assay.
864.4010 General purpose reagent. 864.7425 Carboxyhemoglobin assay.
864.4020 Analyte specific reagents. 864.7440 Electrophoretic hemoglobin anal-
864.4400 Enzyme preparations. ysis system.
864.7455 Fetal hemoglobin assay.
Subpart F—Automated and Semi- 864.7470 Glycosylated hemoglobin assay.
Automated Hematology Devices 864.7490 Sulfhemoglobin assay.
864.7500 Whole blood hemoglobin assays.
864.5200 Automated cell counter. 864.7525 Heparin assay.
864.5220 Automated differential cell 864.7660 Leukocyte alkaline phosphatase
counter. test.
864.5240 Automated blood cell diluting appa- 864.7675 Leukocyte peroxidase test.
ratus. 864.7695 Platelet factor 4
864.5260 Automated cell-locating device. radioimmunoassay.
864.5300 Red cell indices device. 864.7720 Prothrombin consumption test.

864.5350 Microsedimentation centrifuge. 864.7735 Prothrombin-proconvertin test and
864.5400 Coagulation instrument. thrombotest.
286
864.7750 Prothrombin time test. 864.9875 Transfer set.
864.7825 Sickle cell test.
864.7875 Thrombin time test. Subpart K—Products Used In Establish-
864.7900 Thromboplastin generation test. ments That Manufacture Human Cells,
864.7925 Partial thromboplastin time tests. Tissues, and Cellular and Tissue-Based
Products (HCT/Ps)
Subpart I—Hematology Reagents
864.9900 Cord blood processing system and
864.8100 Bothrops atrox reagent. storage container.
864.8150 Calibrator for cell indices.
AUTHORITY: 21 U.S.C. 351, 360, 360c, 360e,
864.8165 Calibrator for hemoglobin or hem-
360j, 360l, 371.
atocrit measurement.
864.8175 Calibrator for platelet counting. EDITORIAL NOTE: Nomenclature changes to
864.8185 Calibrator for red cell and white part 864 appear at 73 FR 35341, June 23, 2008.
cell counting.
864.8200 Blood cell diluent. Subpart A—General Provisions
864.8500 Lymphocyte separation medium.
864.8540 Red cell lysing reagent. § 864.1 Scope.
864.8625 Hematology quality control mix-
ture. (a) This part sets forth the classifica-
864.8950 Russell viper venom reagent. tion of hematology and pathology de-
vices intended for human use that are
Subpart J—Products Used In Establishments in commercial distribution.
That Manufacture Blood and Blood (b) The identification of a device in a
Products regulation in this part is not a precise
description of every device that is, or
864.9050 Blood bank supplies. will be, subject to the regulation. A
864.9100 Empty container for the collection
manufacturer who submits a pre-
and processing of blood and blood compo-
nents.
market notification submission for a
864.9125 Vacuum-assisted blood collection device under part 807 may not show
system. merely that the device is accurately
864.9145 Processing system for frozen blood. described by the section title and iden-
864.9160 Blood group substances of tification provisions of a regulation in
nonhuman origin for in vitro diagnostic this part, but shall state why the de-
use. vice is substantially equivalent to
864.9165 Blood establishment computer soft- other devices, as required by § 807.87.
ware and accessories. (c) References in this part to regu-
864.9175 Automated blood grouping and
latory sections of the Code of Federal
antibody test system.
864.9185 Blood grouping view box. Regulations are to chapter I of title 21,
864.9195 Blood mixing devices and blood unless otherwise noted.
weighing devices. (d) Guidance documents referenced in
864.9205 Blood and plasma warming device. this part are available on the Internet
864.9225 Cell-freezing apparatus and re- at http://www.fda.gov/MedicalDevices/
agents for in vitro diagnostic use. DeviceRegulationandGuidance/
864.9245 Automated blood cell separator. GuidanceDocuments/default.htm.
864.9275 Blood bank centrifuge for in vitro
diagnostic use. [52 FR 17732, May 11, 1987, as amended at 69
864.9285 Automated cell-washing centrifuge FR 12273, Mar. 16, 2004; 78 FR 18233, Mar. 26,
for immuno-hematology. 2013; 79 FR 50552, Aug. 25, 2014]
864.9300 Automated Coombs test systems.
864.9320 Copper sulfate solution for specific § 864.3 Effective dates of requirement
gravity determinations. for premarket approval.
864.9400 Stabilized enzyme solution. A device included in this part that is
864.9550 Lectins and protectins. classified into class III (premarket ap-
864.9575 Environmental chamber for storage proval) shall not be commercially dis-
of platelet concentrate. tributed after the date shown in the
864.9600 Potentiating media for in vitro di-
regulation classifying the device unless
agnostic use.
864.9650 Quality control kit for blood bank- the manufacturer has an approval
ing reagents. under section 515 of the act (unless an
864.9700 Blood storage refrigerator and exemption has been granted under sec-
blood storage freezer. tion 520(g)(2) of the act). An approval
864.9750 Heat-sealing device. under section 515 of the act consists of
287
§ 864.9 21 CFR Ch. I (4–1–23 Edition)
FDA’s issuance of an order approving tion 515 of the act before commercial
an application for premarket approval distribution.
(PMA) for the device or declaring com-
[52 FR 17732, May 11, 1987]
pleted a product development protocol
(PDP) for the device. § 864.9 Limitations of exemptions from
(a) Before FDA requires that a device section 510(k) of the Federal Food,
commercially distributed before the Drug, and Cosmetic Act (the act).
enactment date of the amendments, or
a device that has been found substan- The exemption from the requirement
tially equivalent to such a device, has of premarket notification (section
an approval under section 515 of the act 510(k) of the act) for a generic type of
FDA must promulgate a regulation class I or II device is only to the extent
under section 515(b) of the act requir- that the device has existing or reason-
ing such approval, except as provided ably foreseeable characteristics of
in paragraph (b) of this section. Such a commercially distributed devices with-
regulation under section 515(b) of the in that generic type or, in the case of
act shall not be effective during the in vitro diagnostic devices, only to the
grace period ending on the 90th day extent that misdiagnosis as a result of
after its promulgation or on the last using the device would not be associ-
day of the 30th full calendar month ated with high morbidity or mortality.
after the regulation that classifies the Accordingly, manufacturers of any
device into class III is effective, which- commercially distributed class I or II
ever is later. See section 501(f)(2)(B) of device for which FDA has granted an
the act. Accordingly, unless an effec- exemption from the requirement of
tive date of the requirement for pre-
premarket notification must still sub-
market approval is shown in the regu-
mit a premarket notification to FDA
lation for a device classified into class
before introducing or delivering for in-
III in this part, the device may be com-
mercially distributed without FDA’s troduction into interstate commerce
issuance of an order approving a PMA for commercial distribution the device
or declaring completed a PDP for the when:
device. If FDA promulgates a regula- (a) The device is intended for a use
tion under section 515(b) of the act re- different from the intended use of a le-
quiring premarket approval for a de- gally marketed device in that generic
vice, section 501(f)(1)(A) of the act ap- type of device; e.g., the device is in-
plies to the device. tended for a different medical purpose,
(b) Any new, not substantially equiv- or the device is intended for lay use
alent, device introduced into commer- where the former intended use was by
cial distribution on or after May 28, health care professionals only;
1976, including a device formerly mar- (b) The modified device operates
keted that has been substantially al- using a different fundamental sci-
tered, is classified by statute (section entific technology than a legally mar-
513(f) of the act) into class III without keted device in that generic type of de-
any grace period and FDA must have vice; e.g., a surgical instrument cuts
issued an order approving a PMA or de- tissue with a laser beam rather than
claring completed a PDP for the device with a sharpened metal blade, or an in
before the device is commercially dis-
vitro diagnostic device detects or iden-
tributed unless it is reclassified. If
tifies infectious agents by using
FDA knows that a device being com-
deoxyribonucleic acid (DNA) probe or
mercially distributed may be a ‘‘new’’
device as defined in this section be- nucleic acid hybridization technology
cause of any new intended use or other rather than culture or immunoassay
reasons, FDA may codify the statutory technology; or
classification of the device into class (c) The device is an in vitro device
III for such new use. Accordingly, the that is intended:
regulation for such a class III device (1) For use in the diagnosis, moni-
states that as of the enactment date of toring, or screening of neoplastic dis-

the amendments, May 28, 1976, the de- eases with the exception of
vice must have an approval under sec- immunohistochemical devices;
288
(2) For use in screening or diagnosis § 864.1860 Immunohistochemistry re-

of familial or acquired genetic dis- agents and kits.
orders, including inborn errors of me- (a) Identification.
tabolism; Immunohistochemistry test systems
(3) For measuring an analyte that (IHC’s) are in vitro diagnostic devices
serves as a surrogate marker for
consisting of polyclonal or monoclonal
antibodies labeled with directions for
life-threatening diseases such as ac-
use and performance claims, which
quired immune deficiency syndrome
may be packaged with ancillary re-
(AIDS), chronic or active hepatitis, tu-
agents in kits. Their intended use is to
berculosis, or myocardial infarction or
identify, by immunological techniques,
to monitor therapy;
antigens in tissues or cytologic speci-
(4) For assessing the risk of cardio-
mens. Similar devices intended for use
vascular diseases;
with flow cytometry devices are not
(5) For use in diabetes management;
considered IHC’s.
(6) For identifying or inferring the
identity of a microorganism directly (b) Classification of
from clinical material; immunohistochemistry devices. (1) Class I
(7) For detection of antibodies to (general controls). Except as described
microorganisms other than in paragraphs (b)(2) and (b)(3) of this
immunoglobulin G (IgG) or IgG assays section, these devices are exempt from
when the results are not qualitative, or the premarket notification require-
are used to determine immunity, or the ments in part 807, subpart E of this
assay is intended for use in matrices chapter. This exemption applies to
other than serum or plasma; IHC’s that provide the pathologist with
(8) For noninvasive testing as defined adjunctive diagnostic information that
in § 812.3(k) of this chapter; and may be incorporated into the patholo-
(9) For near patient testing (point of gist’s report, but that is not ordinarily
care). reported to the clinician as an inde-
pendent finding. These IHC’s are used
[65 FR 2310, Jan. 14, 2000] after the primary diagnosis of tumor
(neoplasm) has been made by conven-
Subpart B—Biological Stains tional histopathology using
nonimmunologic histochemical stains,
§ 864.1850 Dye and chemical solution such as hematoxylin and eosin. Exam-
stains. ples of class I IHC’s are differentiation
(a) Identification. Dye and chemical markers that are used as adjunctive
solution stains for medical purposes tests to subclassify tumors, such as
are mixtures of synthetic or natural keratin.
dyes or nondye chemicals in solutions (2) Class II (special control, guidance
used in staining cells and tissues for di- document: ‘‘FDA Guidance for Submis-
agnostic histopathology, sion of Immunohistochemistry Appli-
cytopathology, or hematology. cations to the FDA,’’ Center for De-
(b) Classification. Class I (general con- vices and Radiologic Health, 1998).
trols). These devices are exempt from These IHC’s are intended for the detec-
the premarket notification procedures tion and/or measurement of certain
in subpart E of part 807 of this chapter target analytes in order to provide
subject to the limitations in § 864.9. prognostic or predictive data that are
These devices are also exempt from the not directly confirmed by routine
current good manufacturing practice histopathologic internal and external
requirements of the quality system control specimens. These IHC’s provide
regulation in part 820 of this chapter, the pathologist with information that
with the exception of § 820.180, with re- is ordinarily reported as independent
spect to general requirements con- diagnostic information to the ordering
cerning records, and § 820.198, with re- clinician, and the claims associated
spect to complaint files. with these data are widely accepted
[45 FR 60583, Sept. 12, 1980, as amended at 54 and supported by valid scientific evi-
FR 25044, June 12, 1989; 66 FR 38789, July 25, dence. Examples of class II IHC’s are
2001] those intended for semiquantitative
289
§ 864.1865 21 CFR Ch. I (4–1–23 Edition)
measurement of an analyte, such as (C) If applicable, detailed documenta-

hormone receptors in breast cancer. tion of the device software, including,
(3) Class III (premarket approval). but not limited to, stand-alone soft-
IHC’s intended for any use not de- ware applications and hardware-based
scribed in paragraphs (b)(1) or (b)(2) of devices that incorporate software.
this section. (D) A detailed description of appro-
(c) Date of PMA or notice of completion priate positive and negative controls
of a PDP is required. As of May 28, 1976, that are recommended or provided.
an approval under section 515 of the (E) Detailed specifications for sample
Federal Food, Drug, and Cosmetic Act collection, processing, and storage.
is required for any device described in (F) A detailed description of method-
paragraph (b)(3) of this section before ology and assay procedure.
this device may be commercially dis- (G) A description of the assay cutoff
tributed. See § 864.3. (the medical decision point between
[63 FR 30142, June 3, 1998] positive and negative) or other rel-
evant criteria that distinguishes posi-
§ 864.1865 Cervical intraepithelial neo- tive and negative results, including the
plasia (CIN) test system. rationale for the chosen cutoff or other
(a) Identification. A cervical relevant criteria and results supporting
intraepithelial neoplasia (CIN) test validation of the cutoff.
system is a device used to detect a bio- (H) Detailed specification of the cri-
marker associated with CIN in human teria for test results interpretation and
tissues. The device is indicated as an reporting.
adjunct test and not to be used as a (iv) Detailed information dem-
stand-alone device. The test results onstrating the performance character-
must be interpreted in the context of istics of the device, including:
the patient’s clinical history including, (A) Analytical specificity studies
but not limited to, prior and current such as, but not limited to, antibody
cervical biopsy results, Papanicolaou characterization (e.g., Western Blot,
(Pap) test results, human peptide inhibition analysis), studies
papillomavirus (HPV) test results, and conducted on panels of normal tissues
morphology on hematoxylin and eosin and neoplastic tissues, interference by
(H&E) stained sections. This device is endogenous and exogenous substances
not intended to detect the presence of as well as cross-reactivity, as applica-
HPV. ble.
(b) Classification. Class II (special (B) Device analytical sensitivity data
controls). The special controls for this generated by testing an adequate num-
device are: ber of samples from individuals with
(1) Premarket notification submis- the target condition including limit of
sions must include the following infor- blank, limit of detection, and limit of
mation: quantification, as applicable.
(i) The indications for use must (C) Device precision/reproducibility
specify the biomarker that is intended data to evaluate within-run, between-
to be identified and its adjunct use run, between-day, between-lot, be-
(e.g., adjunct to examination of H&E tween-site, between-reader, within-
stained slides) to improve consistency reader and total precision, as applica-
in the diagnosis of CIN. ble, using a panel of samples covering
(ii) Summary of professional society the device measuring range and/or the
recommendations, as applicable. relevant disease categories (e.g. No
(iii) A detailed device description in- CIN, CIN1, CIN2, CIN3, cervical cancer)
cluding: and testing in replicates across mul-
(A) A detailed description of all test tiple, nonconsecutive days.
components, including all provided re- (D) Device robustness/guardbanding
agents and required, but not provided, studies to assess the tolerance ranges
ancillary reagents. for various critical test and specimen
(B) A detailed description of instru- parameters.
mentation and equipment, including il- (E) Device stability data, including
lustrations or photographs of non- real-time stability and shipping sta-
standard equipment or manuals. bility under various storage times,
290
temperatures, and freeze-thaw condi- that mitigate risks associated with

tions. testing.
(F) Data from a clinical study dem- (2) The device’s 21 CFR 809.10(b) com-
onstrating clinical validity using well- pliant labeling must include a detailed
characterized prospectively or retro- description of the protocol, including
spectively obtained clinical specimens, the information described in paragraph
as appropriate, representative of the (b)(1)(ii) of this section, as applicable,
intended use population. The study and a detailed description of the per-
must evaluate the consistency of the formance studies performed and the
diagnosis of CIN, for example, by com- summary of the results, including
paring the levels of agreements of diag- those that relate to paragraph (b)(1)(ii)
noses rendered by community patholo- of this section, as applicable.
gists to those rendered by a panel of [83 FR 234, Jan. 3, 2018]
expert pathologists. Agreement for
each CIN diagnostic category (e.g., No § 864.1866 Lynch syndrome test sys-
CIN, CIN1, CIN2, CIN3, cancer) and for tems.
alternate diagnostic categories (e.g., (a) Identification. Lynch syndrome
No CIN, low grade squamous test systems are in vitro diagnostic
intraepithelial lesion (LSIL)-histology, tests for use with tumor tissue to iden-
high grade squamous intraepithelial le- tify previously diagnosed cancer pa-
sion (HSIL)-histology, cancer) between tients at risk for having Lynch syn-
reference diagnosis by expert patholo- drome.
gist and community pathologist must (b) Classification. Class II (special
be evaluated, as applicable. In addi- controls). The special controls for this
tion, agreements for CIN binary cat- device are:
egories as ≥CIN2 (i.e., CIN2 or CIN3 or (1) Premarket notification submis-
cancer) and ≤CIN1 (i.e., No CIN or CIN1) sions must include the following infor-
between reference diagnosis by expert mation, as appropriate:
pathologist with H&E staining and (i) A detailed description of all test
community pathologist with H&E components, including all provided re-
staining and agreements for alternate agents, and required but not provided,
CIN binary categories as ≥HSIL-his- ancillary reagents.
tology (i.e., HSIL-histology or cancer) (ii) A detailed description of instru-
and ≤LSIL-histology (i.e., No CIN or mentation and equipment, including il-
LSIL-histology) between reference di- lustrations or photographs of non-
agnosis by an expert pathologist with standard equipment or manuals.
H&E + [biomarker specified in para- (iii) Detailed documentation of the
graph (b)(1)(i) of this section] and a device software, including, but not lim-
community pathologist with H&E + ited to, standalone software applica-
[biomarker specified in paragraph tions and hardware-based devices that
(b)(1)(i) of this section] must be evalu- incorporate software.
ated and compared, as applicable. (iv) A detailed description of quality
(G) The staining performance of the controls including appropriate positive
device as determined by the commu- and negative controls that are rec-
nity pathologists during review of the ommended or provided.
study slides must be evaluated. The (v) Detailed specifications for sample
staining performance criteria assessed collection, processing, and storage.
must include overall staining accept- (vi) A detailed description of method-
ability, background staining accept- ology and assay procedure.
ability, and morphology acceptability, (vii) A description of the assay cut-
as applicable. off (i.e., the medical decision point be-
(H) Appropriate training require- tween positive and negative results) or
ments for users, including interpreta- other relevant criteria that distin-
tion manual, as applicable. guishes positive and negative results,
(I) Identification of risk mitigation or ordinal classes of marker expression,
elements used by the device, including including the rationale for the chosen
a description of all additional proce- cut-off or other relevant criteria and

dures, methods, and practices incor- results supporting validation of the
porated into the instructions for use cut-off.
291
§ 864.1870 21 CFR Ch. I (4–1–23 Edition)
(viii) Detailed specification of the age times, temperatures, and freeze-

criteria for test result interpretation thaw conditions, as appropriate.
and reporting. (H) The staining performance criteria
(ix) Detailed information dem- assessed must include overall staining
onstrating the performance character- acceptability, background staining ac-
istics of the device, including: ceptability, and morphology accept-
(A) Data from an appropriate study ability, as appropriate.
demonstrating clinical accuracy using (I) Appropriate training requirements
well-characterized clinical specimens for users, including interpretation
representative of the intended use pop- manual, as applicable.
ulation (i.e., concordance to (J) Identification of risk mitigation
Deoxyribonucleic Acid (DNA) sequenc- elements used by the device, including
ing results of the Lynch syndrome as- a description of all additional proce-
sociated genes or method comparison dures, methods, and practices incor-
to the predicate device using samples porated into the instructions for use
with known alterations in genes rep- that mitigate risks associated with
resentative of Lynch syndrome). Pre- testing.
specified acceptance criteria must be (2) The device’s § 809.10(b) of this
provided and followed. chapter compliant labeling must in-
(B) Appropriate device reproduc- clude a detailed description of the pro-
ibility data investigating all sources of tocol, including the information de-
variance (e.g., for distributed tests, scribed in paragraphs (b)(1)(i) through
data generated using a minimum of (viii) of this section, as appropriate,
three sites, of which at least two sites and a detailed description of the per-
must be external sites). Each site must formance studies performed and the
perform testing over a minimum of 5 summary of the results, including
nonconsecutive days evaluating a sam- those that relate to paragraph (b)(1)(ix)
ple panel that spans the claimed meas- of this section, as appropriate.
uring range, and includes the clinical
threshold. Pre-specified acceptance cri- [83 FR 8357, Feb. 27, 2018]
teria must be provided and followed.
(C) Data demonstrating reader repro- § 864.1870 Early growth response 1
ducibility, both within-reader and be- (EGR1) gene fluorescence in-situ
hybridization (FISH) test system for
tween-reader, assessed by three readers specimen characterization.
over 3 nonconsecutive days at each
site, including a 2 week washout period (a) Identification. An early growth re-
between reads, as appropriate. sponse 1 (EGR1) gene fluorescence in-
(D) Device precision data using clin- situ hybridization (FISH) test system
ical samples spanning the measuring for specimen characterization is a de-
range and controls to evaluate the vice intended to detect the EGR1 probe
within-lot, between-lot, within-run, be- target on chromosome 5q in bone mar-
tween run, and total variation. row specimens from patients with
(E) Analytical specificity studies in- acute myeloid leukemia (AML) or
cluding as appropriate, western blots, myelodysplastic syndrome (MDS). The
peptide inhibition, testing in normal assay results are intended to be inter-
tissues and neoplastic tissues, interpreted only by a qualified pathologist
ference by endogenous and exogenous or cytogeneticist. These devices do not
substances, and cross-reactivity and include automated systems that di-
cross contamination testing. rectly report results without review
(F) Device analytical sensitivity data and interpretation by a qualified pa-
generated by testing an adequate num- thologist or cytogeneticist. These de-
ber of samples from individuals with vices also do not include any device in-
the target condition such that preva- tended for use to select patient ther-
lence of the biomarker in the target apy, predict patient response to ther-
population is established. apy, or to screen for disease as well as
(G) Device stability data, including any device with a claim for a par-
real-time stability and in-use stability, ticular diagnosis, prognosis, moni-
and stability evaluating various stor- toring, or risk assessment.
292
(b) Classification. Class II (special erature references cited must include

controls). The special controls for this the following elements:
device are: (A) Documentation that the spon-
(1) Premarket notification submis- sor’s probe was used in the literature
sions must also include the following reference,
information: (B) Number and type of specimens,
(i) A detailed description of all (C) Target population studied,
probes included in the kit; (D) Upper reference limit, and
(ii) Purpose of each probe; (E) Range of positive probe results.
(iii) Probe molecular specificity; (2) Your § 809.10(b)(12) of this chapter
(iv) Probe specificity; compliant labeling must include a
(v) Probe limits; statement summarizing the data iden-
(vi) Probe sensitivity; tified in paragraphs (b)(1)(xiii) through
(vii) Specification of required ancil- (xviii) of this section and a description
lary reagents, instrumentation, and of the studies supporting the informa-
equipment; tion, including the pre-specified ac-
(viii) Specification of the specimen ceptance criteria for these performance
collection, processing, storage and studies, justification for the pre-speci-
slide preparation methods; fied acceptance criteria, and whether
(ix) Specification of the assay proce- the pre-specified acceptance criteria
dure; were met.
(x) Specification of control elements (3) Your § 809.10 of this chapter com-
that are incorporated into the rec- pliant labeling must include:
ommended testing procedures; (i) A warning that reads ‘‘The assay
(xi) Specification of risk mitigation results are intended to be interpreted
elements: Description of all additional only by a qualified pathologist or
procedures, methods, and practices in- cytogeneticist.’’
corporated into the directions for use (ii) A warning that reads ‘‘This de-
that mitigate risks associated with vice is not for high-risk uses such as
testing; selecting therapy, predicting thera-
(xii) Specification of the criteria for peutic response or disease screening.’’
test result interpretation and report- (iii) A warning that reads ‘‘The use of
ing; this device for diagnosis, monitoring or
(xiii) Device analytical sensitivity risk assessment has not been estab-
data; lished.’’
(xiv) Device analytical specificity
data; [79 FR 52196, Sept. 3, 2014]
(xv) Device reference limit data;
(xvi) Device precision/reproducibility Subpart C—Cell And Tissue
data; Culture Products
(xvii) Device stability data to in-
clude: § 864.2220 Synthetic cell and tissue
(A) Real-time stability, culture media and components.
(B) Freeze-thaw stability, (a) Identification. Synthetic cell and
(C) Transport and temperature sta- tissue culture media and components
bility, are substances that are composed en-
(D) Post-hybridization signal sta- tirely of defined components (e.g.,
bility, amino acids, vitamins, inorganic salts)
(E) Photostability of probe, and that are essential for the survival and
(xviii) Documentation that dem- development of cell lines of humans
onstrates the clinical validity of the and other animals. This does not in-
device. The documentation must include tissue culture media for human
clude data from clinical studies, a min- ex vivo tissue and cell culture proc-
imum of two peer-reviewed published essing applications as described in
literature references using the specific § 876.5885 of this chapter.
device seeking marketing clearance, or (b) Classification. Class I (general con-

both. Documentation for the clinical trols). The device is exempt from the
studies and peer-reviewed published lit- premarket notification procedures in
293
§ 864.2240 21 CFR Ch. I (4–1–23 Edition)
subpart E of part 807 of this chapter cell lines from the tissue of humans or
subject to the limitations in § 864.9. other animals which are used in var-
ious diagnostic procedures, particu-
FR 25044, June 12, 1989; 66 FR 27024, May 16, larly diagnostic virology and cyto-
2001; 66 FR 38789, July 25, 2001] genetic studies.
§ 864.2240 Cell and tissue culture sup- trols). The device is exempt from the
plies and equipment. premarket notification procedures in
(a) Identification. Cell and tissue cul- subpart E of part 807 of this chapter
ture supplies and equipment are de- subject to § 864.9.
vices that are used to examine, propa- [45 FR 60585, Sept. 12, 1980, as amended at 65
gate, nourish, or grow cells and tissue FR 2310, Jan. 14, 2000]
cultures. These include such articles as
slide culture chambers, perfusion and § 864.2360 Mycoplasma detection
roller apparatus, cell culture suspen- media and components.
sion systems, and tissue culture flasks, (a) Identification. Mycoplasma detec-
disks, tubes, and roller bottles. tion media and components are used to
(b) Classification. Class I (general con- detect and isolate mycoplasma
trols). These devices are exempt from pleuropneumonia-like organisms
the premarket notification procedures (PPLO), a common microbial contami-
in subpart E of part 807 of this chapter nant in cell cultures.
subject to the limitations in § 864.9. If (b) Classification. Class I (general con-
the devices are not labeled or otherwise trols). These devices are exempt from
represented as sterile, they are exempt the premarket notification procedures
from the current good manufacturing in subpart E of part 807 of this chapter
practice requirements of the quality subject to the limitations in § 864.9.
system regulation in part 820 of this
chapter, with the exception of § 820.180, FR 25044, June 12, 1989; 66 FR 38789, July 25,
with respect to general requirements 2001]
concerning records, and § 820.198, with
respect to complaint files. § 864.2800 Animal and human sera.
[45 FR 60584, Sept. 12, 1980, as amended at 54 (a) Identification. Animal and human
FR 25044, June 12, 1989; 66 FR 38789, July 25, sera are biological products, obtained
2001] from the blood of humans or other ani-
mals, that provide the necessary
§ 864.2260 Chromosome culture kit. growth-promoting nutrients in a cell
(a) Identification. A chromosome cul- culture system.
ture kit is a device containing the nec- (b) Classification. Class I (general con-
essary ingredients (e.g., Minimum Es- trols). These devices are exempt from
sential Media (MEM) of McCoy’s 5A the premarket notification procedures
culture media, phytohemagglutinin, in subpart E of part 807 of this chapter
fetal calf serum, antibiotics, and hep- subject to the limitations in § 864.9.
arin) used to culture tissues for diag-
nosis of congenital chromosome abnor- FR 25044, June 12, 1989; 66 FR 38789, July 25,
malities. 2001]
trols). The device is exempt from the § 864.2875 Balanced salt solutions or
premarket notification procedures in formulations.
subpart E of part 807 of this chapter (a) Identification. A balanced salt so-
subject to the limitations in § 864.9. lution or formulation is a defined mix-
[45 FR 60585, Sept. 12, 1980, as amended at 54 ture of salts and glucose in a simple
FR 25044, June 12, 1989; 66 FR 38789, July 25, medium. This device is included as a
2001] necessary component of most cell cul-
ture systems. This media component
§ 864.2280 Cultured animal and human controls for pH, osmotic pressure, en-
cells.
ergy source, and inorganic ions.

(a) Identification. Cultured animal (b) Classification. Class I (general con-
and human cells are in vitro cultivated trols). These devices are exempt from
294
the premarket notification procedures (b) Classification. Class I (general con-

in subpart E of part 807 of this chapter trols). The device is exempt from the
subject to § 864.9. If the device is not la-
FR 25044, June 12, 1989; 66 FR 38789, July 25,
2001] beled or otherwise represented as ster-
ile, it is exempt from the current good
manufacturing practice requirements
Subpart D—Pathology of the quality system regulation in
Instrumentation and Accessories part 820 of this chapter, with the excep-
tion of § 820.180 of this chapter, with re-
§ 864.3010 Tissue processing equip- spect to general requirements con-
ment. cerning records, and § 820.198 of this
(a) Identification. Tissue processing chapter, with respect to complaint
equipment consists of devices used to files.
prepare human tissue specimens for di-
[54 FR 47206, Nov. 13, 1989, as amended at 65
agnostic histological examination by FR 2310, Jan. 14, 2000; 65 FR 18234, Apr. 7,
processing specimens through the var- 2000]
ious stages of decalcifying, infiltrating,
sectioning, and mounting on micro- § 864.3260 OTC test sample collection
scope slides. systems for drugs of abuse testing.
(b) Classification. Class I (general con- (a) Identification. An over-the-counter
trols). These devices are exempt from (OTC) test sample collection system
the premarket notification procedures for drugs of abuse testing is a device
in subpart E of part 807 of this chapter intended to: Collect biological speci-
subject to the limitations in § 864.9. The mens (such as hair, urine, sweat, or sa-
devices are also exempt from the cur- liva), outside of a medical setting and
rent good manufacturing practice re- not on order of a health care profes-
quirements of the quality system regu- sional (e.g., in the home, insurance,
lation in part 820 of this chapter, with sports, or workplace setting); maintain
the exception of § 820.180, with respect the integrity of such specimens during
to general requirements concerning storage and transport in order that the
records, and § 820.198, with respect to matter contained therein can be tested
complaint files. in a laboratory for the presence of
drugs of abuse or their metabolites;
FR 25044, June 12, 1989; 66 FR 38789, July 25, and provide access to test results and
2001] counseling. This section does not apply
to collection, transport, or laboratory
§ 864.3250 Specimen transport and testing of biological specimens for the
storage container. presence of drugs of abuse or their me-
(a) Identification. A specimen trans- tabolites that is performed to develop
port and storage container, which may evidence for law enforcement purposes.
be empty or prefilled, is a device in- (b) Classification. Class I (general con-
tended to contain biological specimens, trols). The device is exempt from the
body waste, or body exudate during premarket notification requirements
storage and transport in order that the in part 807, subpart E of this chapter
matter contained therein can be de- subject to the limitations in § 864.9 if it
stroyed or used effectively for diag- is sold, distributed, and used in accord-
nostic examination. If prefilled, the de- ance with the restrictions set forth in
vice contains a fixative solution or § 809.40 of this chapter. If the device is
other general purpose reagent to pre- not labeled or otherwise represented as
serve the condition of a biological spec- sterile, it is exempt from the current
good manufacturing practice require-
imen added to the container. This sec-
ments of the quality system regulation
tion does not apply to specimen trans-
in part 820 of this chapter, with the ex-
port and storage containers that are
ception of § 820.198 of this chapter with
intended for use as part of an over-the-

respect to complaint files.
counter test sample collection system
for drugs of abuse testing. [65 FR 18234, Apr. 7, 2000]
295
§ 864.3300 21 CFR Ch. I (4–1–23 Edition)
§ 864.3300 Cytocentrifuge. (b) Classification. Class I (general con-

trols). These devices are exempt from
(a) Identification. A cytocentrifuge is
a centrifuge used to concentrate cells
from biological cell suspensions (e.g.,
subject to the limitations in § 864.9. If
cerebrospinal fluid) and to deposit
the device is not labeled or otherwise
these cells on a glass microscope slide
represented as sterile, it is exempt
for cytological examination.
from the current good manufacturing
practice requirements of the quality
trols). This device is exempt from the
chapter, with the exception of § 820.180,
with respect to general requirements
[45 FR 60588, Sept. 12, 1980, as amended at 54 respect to complaint files.
FR 25044, June 12, 1989; 66 FR 38789, July 25,
2001] [45 FR 60590, Sept. 12, 1980, as amended at 54
FR 25044, June 12, 1989; 66 FR 38789, July 25,
§ 864.3400 Device for sealing microsec- 2001]
tions.
§ 864.3700 Whole slide imaging system.
(a) Identification. A device for sealing
(a) Identification. The whole slide im-
microsections is an automated instru-
aging system is an automated digital
ment used to seal stained cells and
slide creation, viewing, and manage-
microsections for histological and
ment system intended as an aid to the
cytological examination.
pathologist to review and interpret dig-
ital images of surgical pathology
slides. The system generates digital
images that would otherwise be appro-
priate for manual visualization by con-
ventional light microscopy.
[45 FR 60589, Sept. 12, 1980, as amended at 54 (b) Classification. Class II (special
FR 25044, June 12, 1989; 66 FR 38789, July 25, controls). The special controls for this
2001] device are:
(1) Premarket notification submis-
§ 864.3600 Microscopes and acces-
sories. sions must include the following infor-
mation:
(a) Identification. Microscopes and ac- (i) The indications for use must
cessories are optical instruments used specify the tissue specimen that is in-
to enlarge images of specimens, prep- tended to be used with the whole slide
arations, and cultures for medical pur- imaging system and the components of
poses. Variations of microscopes and the system.
accessories (through a change in the (ii) A detailed description of the de-
light source) used for medical purposes vice and bench testing results at the
include the following: component level, including for the fol-
(1) Phase contrast microscopes, lowing, as appropriate:
which permit visualization of (A) Slide feeder;
unstained preparations by altering the (B) Light source;
phase relationship of light that passes (C) Imaging optics;
around the object and through the ob- (D) Mechanical scanner movement;
ject. (E) Digital imaging sensor;
(2) Fluorescense microscopes, which (F) Image processing software;
permit examination of specimens (G) Image composition techniques;
stained with fluorochromes that fluo- (H) Image file formats;
resce under ultraviolet light. (I) Image review manipulation soft-
(3) Inverted stage microscopes, which ware;
permit examination of tissue cultures (J) Computer environment; and
or other biological specimens con- (K) Display system.
tained in bottles or tubes with the (iii) Detailed bench testing and re-
light source mounted above the speci- sults at the system level, including for
men. the following, as appropriate:
296
(A) Color reproducibility; (iii) A description of the performance

(B) Spatial resolution; studies and the summary of results, in-
(C) Focusing test; cluding those that relate to paragraph
(D) Whole slide tissue coverage; (b)(1)(iv) of this section, as appropriate.
(E) Stitching error; and (iv) A limiting statement that speci-
fies that pathologists should exercise
(F) Turnaround time.
professional judgment in each clinical
(iv) Detailed information dem- situation and examine the glass slides
onstrating the performance character- by conventional microscopy if there is
istics of the device, including, as ap- doubt about the ability to accurately
propriate: render an interpretation using this de-
(A) Precision to evaluate intra-sys- vice alone.
tem and inter-system precision using a
comprehensive set of clinical speci- [83 FR 22, Jan. 2, 2018]
mens with defined, clinically relevant
§ 864.3750 Software algorithm device
histologic features from various organ to assist users in digital pathology.
systems and diseases. Multiple whole
slide imaging systems, multiple sites, (a) Identification. A software algo-
and multiple readers must be included. rithm device to assist users in digital
(B) Reproducibility data to evaluate pathology is an in vitro diagnostic de-
inter-site variability using a com- vice intended to evaluate acquired
prehensive set of clinical specimens scanned pathology whole slide images.
with defined, clinically relevant The device uses software algorithms to
histologic features from various organ provide information to the user about
systems and diseases. Multiple whole presence, location, and characteristics
slide imaging systems, multiple sites, of areas of the image with clinical im-
and multiple readers must be included. plications. Information from this de-
(C) Data from a clinical study to vice is intended to assist the user in de-
demonstrate that viewing, reviewing, termining a pathology diagnosis.
and diagnosing digital images of sur-
controls). The special controls for this
gical pathology slides prepared from
device are:
tissue slides using the whole slide im-
(1) The intended use on the device’s
aging system is non-inferior to using
label and labeling required under
an optical microscope. The study
§ 809.10 of this chapter must include:
should evaluate the difference in major
(i) Specimen type;
discordance rates between manual dig-
(ii) Information on the device
ital (MD) and manual optical (MO) mo-
input(s) (e.g., scanned whole slide im-
dalities when compared to the ref-
ages (WSI), etc.);
erence (e.g., main sign-out diagnosis).
(iii) Information on the device out-
(D) A detailed human factor engi- put(s) (e.g., format of the information
neering process must be used to evalu- provided by the device to the user that
ate the whole slide imaging system can be used to evaluate the WSI, etc.);
user interface(s). (iv) Intended users;
(2) Labeling compliant with 21 CFR (v) Necessary input/output devices
809.10(b) must include the following: (e.g., WSI scanners, viewing software,
(i) The intended use statement must etc.);
include the information described in (vi) A limiting statement that ad-
paragraph (b)(1)(i) of this section, as dresses use of the device as an adjunct;
applicable, and a statement that reads, and
‘‘It is the responsibility of a qualified (vii) A limiting statement that users
pathologist to employ appropriate pro- should use the device in conjunction
cedures and safeguards to assure the with complete standard of care evalua-
validity of the interpretation of images tion of the WSI.
obtained using this device.’’ (2) The labeling required under
(ii) A description of the technical § 809.10(b) of this chapter must include:
studies and the summary of results, in- (i) A detailed description of the de-
cluding those that relate to paragraphs vice, including the following:

(b)(1)(ii) and (iii) of this section, as ap- (A) Detailed descriptions of the soft-
propriate. ware device, including the detection/
297
§ 864.3750 21 CFR Ch. I (4–1–23 Edition)
analysis algorithm, software design ar- the conditions likely to be encountered

chitecture, interaction with input/out- when used as intended (e.g., fixation
put devices, and necessary third-party type and time, histology slide proc-
software; essing techniques, challenging diag-
(B) Detailed descriptions of the in- nostic cases, multiple sites, patient de-
tended user(s) and recommended train- mographics, etc.);
ing for safe use of the device; and (C) The number of WSI in an inde-
(C) Clear instructions about how to pendent validation dataset must be ap-
resolve device-related issues (e.g., cy- propriate to demonstrate device accu-
bersecurity or device malfunction racy in detecting and localizing ROIs
issues). on scanned WSI, and must include sub-
(ii) A detailed summary of the per- sets clinically relevant to the intended
formance testing, including test meth- use of the device;
ods, dataset characteristics, results, (D) Emergency recovery/backup func-
and a summary of sub-analyses on case tions, which must be included in the
distributions stratified by relevant device design;
confounders, such as anatomical char- (E) System level architecture dia-
acteristics, patient demographics, med- gram with a matrix to depict the com-
ical history, user experience, and scan- munication endpoints, communication
ning equipment, as applicable. protocols, and security protections for
(iii) Limiting statements that indi- the device and its supportive systems,
cate: including any products or services that
(A) A description of situations in are included in the communication
which the device may fail or may not pathway; and
operate at its expected performance (F) A risk management plan, includ-
level (e.g., poor image quality or for ing a justification of how the cyberse-
certain subpopulations), including any curity vulnerabilities of third-party
limitations in the dataset used to software and services are reduced by
train, test, and tune the algorithm dur- the device’s risk management mitiga-
ing device development; tions in order to address cybersecurity
(B) The data acquired using the de- risks associated with key device
vice should only be interpreted by the functionality (such as loss of image, al-
types of users indicated in the intended tered metadata, corrupted image data,
use statement; and degraded image quality, etc.). The risk
(C) Qualified users should employ ap- management plan must also include
propriate procedures and safeguards how the device will be maintained on
(e.g., quality control measures, etc.) to its intended platform (e.g. a general
assure the validity of the interpreta- purpose computing platform, virtual
tion of images obtained using this de- machine, middleware, cloud-based com-
vice. puting services, medical device hard-
(3) Design verification and validation ware, etc.), which includes how the
must include: software integrity will be maintained,
(i) A detailed description of the de- how the software will be authenticated
vice software, including its algorithm on the platform, how any reliance on
and its development, that includes a the platform will be managed in order
description of any datasets used to to facilitate implementation of cyber-
train, tune, or test the software algo- security controls (such as user authen-
rithm. This detailed description of the tication, communication encryption
device software must include: and authentication, etc.), and how the
(A) A detailed description of the device will be protected when the un-
technical performance assessment derlying platform is not updated, such
study protocols (e.g., regions of inter- that the specific risks of the device are
est (ROI) localization study) and re- addressed (such as loss of image, al-
sults used to assess the device out- tered metadata, corrupted image data,
put(s) (e.g., image overlays, image degraded image quality, etc.).
heatmaps, etc.); (ii) Data demonstrating acceptable,
(B) The training dataset must in- as determined by FDA, analytical de-
clude cases representing different pre- vice performance, by conducting ana-
analytical variables representative of lytical studies. For each analytical
298
study, relevant details must be docu- eases, and subsets defined by image
mented (e.g., the origin of the study scanning characteristics, etc.) such
slides and images, reader/annotator that the performance estimates and
qualifications, method of annotation, confidence intervals for these indi-
location of the study site(s), chal- vidual subsets can be characterized.
lenging diagnoses, etc.). The analytical The performance assessment must be
studies must include: based on appropriate diagnostic accu-
(A) Bench testing or technical test- racy measures (e.g., sensitivity, speci-
ing to assess device output, such as lo- ficity, predictive value, diagnostic
calization of ROIs within a pre-speci- likelihood ratio, etc.).
fied threshold. Samples must be rep- (B) [Reserved]
resentative of the entire spectrum of
[88 FR 7009, Feb. 2, 2023]
challenging cases likely to be encoun-
tered when the device is used as in- § 864.3800 Automated slide stainer.
tended; and
(B) Data from a precision study that (a) Identification. An automated slide
demonstrates device performance when stainer is a device used to stain his-
used with multiple input devices (e.g., tology, cytology, and hematology
WSI scanners) to assess total varia- slides for diagnosis.
bility across operators, within-scanner, (b) Classification. Class I (general con-
between-scanner and between-site, trols). This device is exempt from the
using clinical specimens with defined, premarket notification procedures in
clinically relevant, and challenging subpart E of part 807 of this chapter
characteristics likely to be encoun- subject to the limitations in § 864.9.
tered when the device is used as in- [45 FR 60591, Sept. 12, 1980, as amended at 54
tended. Samples must be representa- FR 25044, June 12, 1989; 66 FR 38789, July 25,
tive of the entire spectrum of chal- 2001]
lenging cases likely to be encountered
when the device is used as intended. § 864.3875 Automated tissue processor.
Precision, including performance of the (a) Identification. An automated tis-
device and reproducibility, must be as- sue processor is an automated system
sessed by agreement between rep- used to process tissue specimens for ex-
licates. amination through fixation, dehydra-
(iii) Data demonstrating acceptable, tion, and infiltration.
as determined by FDA, clinical valida- (b) Classification. Class I (general con-
tion must be demonstrated by controls). This device is exempt from the
ducting studies with clinical speci- premarket notification procedures in
mens. For each clinical study, relevant subpart E of part 807 of this chapter
details must be documented (e.g., the subject to the limitations in § 864.9.
origin of the study slides and images,
reader/annotator qualifications, meth- [45 FR 60591, Sept. 12, 1980, as amended at 54
FR 25045, June 12, 1989; 66 FR 38789, July 25,
od of annotation, location of the study
2001]
site(s) (on-site/remote), challenging di-
agnoses, etc.). The studies must in-
clude: Subpart E—Specimen Preparation
(A) A study demonstrating the per- Reagents
formance by the intended users with
and without the software device (e.g., § 864.4010 General purpose reagent.
unassisted and device-assisted reading (a) A general purpose reagent is a
of scanned WSI of pathology slides). chemical reagent that has general lab-
The study dataset must contain suffi- oratory application, that is used to col-
cient numbers of cases from relevant lect, prepare, and examine specimens
cohorts that are representative of the from the human body for diagnostic
scope of patients likely to be encoun- purposes, and that is not labeled or
tered given the intended use of the de- otherwise intended for a specific diag-
vice (e.g., subsets defined by clinically nostic application. It may be either an
relevant confounders, challenging diag- individual substance, or multiple sub-

noses, subsets with potential biopsy ap- stances reformulated, which, when
pearance modifiers, concomitant dis- combined with or used in conjunction
299
§ 864.4020 21 CFR Ch. I (4–1–23 Edition)
with an appropriate analyte specific re- (2) Organizations that use the re-
agent (ASR) and other general purpose agents to make tests for purposes other
reagents, is part of a diagnostic test than providing diagnostic information
procedure or system constituting a fin- to patients and practitioners, e.g., fo-
ished in vitro diagnostic (IVD) test. rensic, academic, research, and other
General purpose reagents are appro- nonclinical laboratories.
priate for combining with one or more (b) Classification. (1) Class I (general
than one ASR in producing such sys- controls). Except as described in para-
tems and include labware or disposable graphs (b)(2) and (b)(3) of this section,
constituents of tests; but they do not these devices are exempt from the pre-
include laboratory machinery, auto- market notification requirements in
mated or powered systems. General part 807, subpart E of this chapter.
purpose reagents include cytological (2) Class II (special controls/guidance
preservatives, decalcifying reagents, documents), when the analyte is used
fixative and adhesives, tissue proc- in blood banking tests that have been
essing reagents, isotonic solutions and classified as class II devices (e.g., cer-
pH buffers. Reagents used in tests for tain cytomegalovirus serological and
more than one individual chemical sub- treponema pallidum nontreponemal
stance or ligand are general purpose retest reagents). Guidance Documents:
agents (e.g., Thermus aquaticus (TAQ) 1. ‘‘Specifications for Immunological Test-
polymerase, substrates for enzyme ing for Infectious Disease; Approved Guide-
immunoassay (EIA)). line,’’ NCCLS Document I/LA18–A, December
(b) Classification. Class I (general con- 1994.
2. ‘‘Assessment of the Clinical Accuracy of
trols). The device is exempt from the Laboratory Tests Using Receiver Operating
premarket notification procedures in Characteristic (ROC) Plots; Tentative Guide-
subpart E of part 807 of this chapter line,’’ NCCLS Document KGP10–T, December
subject to the limitations in § 864.9. If 1993.
the device is not labeled or otherwise 3. ‘‘Review Criteria for Assessment of In
represented as sterile, it is exempt Vitro Diagnostic Devices for Direct Detec-
from the current good manufacturing tion of Mycobacterium spp,’’ FDA, July 6,
1993, and its ‘‘Attachment 1,’’ February 28,
1994.
system regulation in part 820 of this 4. ‘‘Draft Review Criteria for Nucleic Acid
chapter, with the exception of § 820.180, Amplification-Based In Vitro Diagnostic De-
with respect to general requirements vices for Direct Detection of Infectious
concerning records, and § 820.198, with Microorganisms,’’ FDA, July 6, 1993.
respect to complaint files. 5. The Center for Biologics Evaluation and
Research, FDA, ‘‘Points to Consider in the
[45 FR 60592, Sept. 12, 1980, as amended at 54 Manufacture and Clinical Evaluation of In
FR 25045, June 12, 1989; 62 FR 62260, Nov. 21, Vitro Tests to Detect Antibodies to the
1997; 66 FR 38789, July 25, 2001] Human Immunodeficiency Virus, Type I’’ (54
FR 48943, November 28, 1989).
§ 864.4020 Analyte specific reagents.
(3) Class III (premarket approval),
(a) Identification. Analyte specific re- when:
agents (ASR’s) are antibodies, both (i) The analyte is intended as a com-
polyclonal and monoclonal, specific re- ponent in a test intended for use in the
ceptor proteins, ligands, nucleic acid diagnosis of a contagious condition
sequences, and similar reagents which, that is highly likely to result in a fatal
through specific binding or chemical outcome and prompt, accurate diag-
reaction with substances in a speci- nosis offers the opportunity to miti-
men, are intended for use in a diag- gate the public health impact of the
nostic application for identification condition (e.g., human immuno-
and quantification of an individual deficiency virus (HIV/AIDS)or tuber-
chemical substance or ligand in bio- culosis (TB)); or
logical specimens. ASR’s that other- (ii) The analyte is intended as a com-
wise fall within this definition are not ponent in a test intended for use in
within the scope of subpart E of this donor screening for conditions for
part when they are sold to: which FDA has recommended or re-
(1) In vitro diagnostic manufacturers; quired testing in order to safeguard the
or blood supply or establish the safe use
300
of blood and blood products (e.g., tests erythrocyte mean corpuscular volume,
for hepatitis or tests for identifying the mean corpuscular hemoglobin, or
blood groups). the mean corpuscular hemoglobin con-
(c) Date of 510(k), or date of PMA or centration). These devices may use ei-
notice of completion of a product develop- ther an electronic particle counting
ment protocol is required. (1) method or an optical counting method.
Preamendments ASR’s; No effective (b) Classification. Class II (perform-
date has been established for the re- ance standards).
quirement for premarket approval for [45 FR 60593, Sept. 12, 1980]
the device described in paragraph (b)(3)
of this section. See § 864.3. § 864.5220 Automated differential cell
(2) For postamendments ASR’s; No- counter.
vember 23, 1998. (a) Identification. An automated dif-
(d) Restrictions. Restrictions on the ferential cell counter is a device used
sale, distribution and use of ASR’s are to identify one or more of the formed
set forth in § 809.30 of this chapter. elements of the blood. The device may
[62 FR 62260, Nov. 21, 1997] also have the capability to flag, count,
or classify immature or abnormal
§ 864.4400 Enzyme preparations. hematopoietic cells of the blood, bone
(a) Identification. Enzyme prepara- marrow, or other body fluids. These de-
tions are products that are used in the vices may combine an electronic par-
histopathology laboratory for the fol- ticle counting method, optical method,
lowing purposes: or a flow cytometric method utilizing
(1) To disaggregate tissues and cells monoclonal CD (cluster designation)
already in established cultures for markers. The device includes accessory
preparation into subsequent cultures CD markers.
(e.g., trypsin); (b) Classification. Class II (special
(2) To disaggregate fluid specimens controls). The special control for this
for cytological examination (e.g., device is the FDA document entitled
papain for gastric lavage or trypsin for ‘‘Class II Special Controls Guidance
sputum liquefaction); Document: Premarket Notifications for
(3) To aid in the selective staining of Automated Differential Cell Counters
tissue specimens (e.g., diastase for gly- for Immature or Abnormal Blood Cells;
cogen determination). Final Guidance for Industry and FDA.’’
(b) Classification. Class I (general con- [67 FR 1607, Jan. 14, 2002]
premarket notification procedures in § 864.5240 Automated blood cell dilut-
subpart E of part 807 of this chapter ing apparatus.
subject to the limitations in § 864.9. (a) Identification. An automated blood
[45 FR 60592, Sept. 12, 1980, as amended at 54 cell diluting apparatus is a fully auto-
FR 25045, June 12, 1989; 66 FR 38789, July 25, mated or semi-automated device used
2001] to make appropriate dilutions of a
blood sample for further testing.
Subpart F—Automated and Semi- (b) Classification. Class I (general con-
Automated Hematology Devices trols). The device is exempt from the
§ 864.5200 Automated cell counter. subpart E of part 807 of this chapter
(a) Identification. An automated cell subject to § 864.9.
counter is a fully-automated or semi- [45 FR 60596, Sept. 12, 1980, as amended at 65
automated device used to count red FR 2310, Jan. 14, 2000]
blood cells, white blood cells, or blood
platelets using a sample of the pa- § 864.5260 Automated cell-locating de-
tient’s peripheral blood (blood circu- vice.
lating in one of the body’s extremities, (a) Identification. An automated cell-
such as the arm). These devices may locating device is a device used to lo-
also measure hemoglobin or hemato- cate blood cells on a peripheral blood

crit and may also calculate or measure smear, allowing the operator to iden-
one or more of the red cell indices (the tify and classify each cell according to
301
§ 864.5300 21 CFR Ch. I (4–1–23 Edition)
type. (Peripheral blood is blood circu- semiautomated instrument and its as-
lating in one of the body’s extremities, sociated reagents and controls. The
such as the arm.) system is used to perform a series of
(b) Classification. Class II (perform- coagulation studies and coagulation
ance standards). factor assays.
[45 FR 60597, Sept. 12, 1980] (b) Classification. Class II (special
controls). A control intended for use
§ 864.5300 Red cell indices device. with a multipurpose system for in vitro
coagulation studies is exempt from the
(a) Identification. A red cell indices
device, usually part of a larger system,
calculates or directly measures the subpart E of part 807 of this chapter
erythrocyte mean corpuscular volume subject to the limitations in § 864.9.
(MCV), the mean corpuscular hemo- [45 FR 60599, Sept. 12, 1980, as amended at 84
globin (MCH), and the mean corpus- FR 71799, Dec. 30, 2019]
cular hemoglobin concentration
(MCHC). The red cell indices are used § 864.5600 Automated hematocrit in-
for the differential diagnosis of strument.
anemias. (a) Identification. An automated hem-
(b) Classification. Class II (perform- atocrit instrument is a fully auto-
ance standards). mated or semi-automated device which
may or may not be part of a larger sys-
[45 FR 60597, Sept. 12, 1980]
tem. This device measures the packed
§ 864.5350 Microsedimentation cen- red cell volume of a blood sample to
trifuge. distinguish normal from abnormal
(a) Identification. A microsedimenta- states, such as anemia and
tion centrifuge is a device used to sedi- erythrocytosis (an increase in the num-
ment red cells for the microsedimenta- ber of red cells).
tion rate test. (b) Classification. Class II (perform-
(b) Classification. Class I (general con- ance standards).
trols). This device is exempt from the [45 FR 60600, Sept. 12, 1980]
subpart E of part 807 of this chapter § 864.5620 Automated hemoglobin sys-
subject to the limitations in § 864.9. tem.
[45 FR 60598, Sept. 12, 1980, as amended at 59 (a) Identification. An automated he-
FR 63007, Dec. 7, 1994; 66 FR 38789, July 25, moglobin system is a fully automated
2001] or semi-automated device which may
or may not be part of a larger system.
§ 864.5400 Coagulation instrument. The generic type of device consists of
(a) Identification. A coagulation in- the reagents, calibrators, controls, and
strument is an automated or semiauto- instrumentation used to determine the
mated device used to determine the hemoglobin content of human blood.
onset of clot formation for in vitro co- (b) Classification. Class II (perform-
agulation studies. ance standards).
(b) Classification. Class II (special [45 FR 60601, Sept. 12, 1980]
controls). A fibrometer or coagulation
timer intended for use with a coagula- § 864.5680 Automated heparin ana-
tion instrument is exempt from the lyzer.
premarket notification procedures in (a) Identification. An automated hep-
subpart E of part 807 of this chapter arin analyzer is a device used to deter-
subject to the limitations in § 864.9. mine the heparin level in a blood sam-
[45 FR 60598, Sept. 12, 1980, as amended at 84 ple by mixing the sample with prot-
FR 71799, Dec. 30, 2019] amine (a heparin-neutralizing sub-
stance) and determining
§ 864.5425 Multipurpose system for in photometrically the onset of air-acti-
vitro coagulation studies. vated clotting. The analyzer also deter-
(a) Identification. A multipurpose sys- mines the amount of protamine nec-

tem for in vitro coagulation studies is essary to neutralize the heparin in the
a device consisting of one automated or patient’s circulation.
302
(b) Classification. Class II (special § 864.5950 Blood volume measuring de-

controls). vice.
[45 FR 60601, Sept. 12, 1980, as amended at 52 (a) Identification. A blood volume
FR 17733, May 11, 1987; 58 FR 51571, Oct. 4, measuring device is a manual, semi-
1993] automated, or automated system that
is used to calculate the red cell mass,
§ 864.5700 Automated platelet aggrega- plasma volume, and total blood vol-
tion system. ume.
(a) Identification. An automated (b) Classification. Class II (perform-
platelet aggregation system is a device ance standards).
used to determine changes in platelet [45 FR 60603, Sept. 12, 1980]
shape and platelet aggregation fol-
lowing the addition of an aggregating Subpart G—Manual Hematology
reagent to a platelet-rich plasma. Devices
(b) Classification. Class II (perform-
ance standards). § 864.6100 Bleeding time device.
[45 FR 60602, Sept. 12, 1980] (a) Identification. A bleeding time de-
vice is a device, usually employing two
§ 864.5800 Automated sedimentation spring-loaded blades, that produces two
rate device. small incisions in the patient’s skin.
(a) Identification. An automated sedi- The length of time required for the
bleeding to stop is a measure of the ef-
mentation rate device is an instrument
fectiveness of the coagulation system,
that measures automatically the
primarily the platelets.
erythrocyte sedimentation rate in (b) Classification. Class II (special
whole blood. Because an increased sedi- controls). The device is exempt from
mentation rate indicates tissue dam- the premarket notification procedures
age or inflammation, the erythrocyte in subpart E of part 807 of this chapter
sedimentation rate device is useful in subject to § 864.9.
monitoring treatment of a disease.
FR 59225, Nov. 3, 1998]
premarket notification procedures in § 864.6150 Capillary blood collection
subpart E of part 807 of this chapter tube.
subject to the limitations in § 864.9. (a) Identification. A capillary blood
[45 FR 60602, Sept. 12, 1980, as amended at 54 collection tube is a plain or
FR 25045, June 12, 1989; 66 FR 38790, July 25, heparinized glass tube of very small di-
2001] ameter used to collect blood by cap-
illary action.
§ 864.5850 Automated slide spinner. (b) Classification. Class I (general con-
(a) Identification. An automated slide trols). The device is exempt from the
spinner is a device that prepares auto- premarket notification procedures in
matically a blood film on a microscope
slide using a small amount of periph-
eral blood (blood circulating in one of [45 FR 60604, Sept. 12, 1980, as amended at 54
the body’s extremities, such as the FR 25045, June 12, 1989; 65 FR 2310, Jan. 14,
arm). 2000]
(b) Classification. Class I (general con- § 864.6160 Manual blood cell counting
trols). This device is exempt from the device.
(a) Identification. A manual blood cell
subpart E of part 807 of this chapter counting device is a device used to
subject to the limitations in § 864.9. count red blood cells, white blood cells,
[45 FR 60603, Sept. 12, 1980, as amended at 54 or blood platelets.
2001] trols). This device is exempt from the
303
§ 864.6400 21 CFR Ch. I (4–1–23 Edition)
subject to the limitations in § 864.9. subject to the limitations in § 864.9.
[45 FR 60605, Sept. 12, 1980, as amended at 54 [45 FR 60607, Sept. 12, 1980, as amended at 54
FR 25045, June 12, 1989; 66 FR 38790, July 25, FR 25045, June 12, 1989; 66 FR 38790, July 25,
2001] 2001]
§ 864.6400 Hematocrit measuring de- § 864.6650 Platelet adhesion test.

vice.
(a) Identification. A platelet adhesion
(a) Identification. A hematocrit meas- test is a device used to determine in
uring device is a system consisting of vitro platelet function.
instruments, tubes, racks, and a sealer (b) Classification. Class II (perform-
and a holder. The device is used to ance standards).
measure the packed red cell volume in
blood to determine whether the pa- [45 FR 60608, Sept. 12, 1980]
tient’s total red cell volume is normal
§ 864.6675 Platelet aggregometer.
or abnormal. Abnormal states include
anemia (an abnormally low total red (a) Identification. A platelet
cell volume) and erythrocytosis (an ab- aggregometer is a device, used to de-
normally high total red cell mass). The termine changes in platelet shape and
packed red cell volume is produced by platelet aggregation following the ad-
centrifuging a given volume of blood. dition of an aggregating reagent to a
(b) Classification. Class II (special platelet rich plasma.
controls). The device is exempt from (b) Classification. Class II (perform-
the premarket notification procedures ance standards).
[45 FR 60608, Sept. 12, 1980]
[45 FR 60606, Sept. 12, 1980, as amended at 63 § 864.6700 Erythrocyte sedimentation
FR 59225, Nov. 3, 1998] rate test.
(a) Identification. An erythrocyte
§ 864.6550 Occult blood test. sedimentation rate test is a device that
(a) Identification. An occult blood test measures the length of time required
is a device used to detect occult blood for the red cells in a blood sample to
in urine or feces. (Occult blood is blood fall a specified distance or a device
present in such small quantities that it that measures the degree of sedimenta-
can be detected only by chemical tests tion taking place in a given length of
of suspected material, or by micro- time. An increased rate indicates tis-
scopic or spectroscopic examination.) sue damage or inflammation.
(b) Classification. Class II (special (b) Classification. Class I (general con-
controls). A control intended for use trols). This device is exempt from the
with an occult blood test is exempt premarket notification procedures in
from the premarket notification proce- subpart E of part 807 of this chapter
dures in subpart E of part 807 of this subject to the limitations in § 864.9.
chapter subject to the limitations in [45 FR 60608, Sept. 12, 1980, as amended at 54
§ 864.9. FR 25045, June 12, 1989; 66 FR 38790, July 25,
[45 FR 60606, Sept. 12, 1980, as amended at 84 2001]
FR 71799, Dec. 30, 2019]
Subpart H—Hematology Kits and
§ 864.6600 Osmotic fragility test. Packages
(a) Identification. An osmotic fragility
test is a device used to determine the § 864.7010 Flow cytometric test system
resistance of red blood cells to hemol- for hematopoietic neoplasms.
ysis (destruction) in varying con- (a) Identification. A flow cytometric
centrations of hypotonic saline solu- test for hematopoietic neoplasms is a
tions. device that consists of reagents for
(b) Classification. Class I (general con- immunophenotyping of human cells in

trols). This device is exempt from the relation to the level of expression,
premarket notification procedures in antigen density, and distribution of
304
specific cellular markers. These re- markers to a predicate device or data

agents are used as an aid in the dif- collected through a clinical study dem-
ferential diagnosis or monitoring of onstrating clinical validity using well-
hematologically abnormal patients characterized clinical specimens. Sam-
having or suspected of having ples must be representative of the in-
hematopoietic neoplasms. The results tended use population of the device in-
should be interpreted by a pathologist cluding hematologic neoplasms and the
or equivalent professional in conjunc- specific sample types for which the test
tion with other clinical and laboratory is indicated for use.
findings. (B) If applicable, device performance
(b) Classification. Class II (special data from a clinical study dem-
controls). The special controls for this onstrating clinical validity for param-
device are: eters not established in a predicate de-
(1) Premarket notification submis- vice of this generic type using well-
sions must include the following infor- characterized prospectively obtained
mation: clinical specimens including all hem-
(i) The indications for use must indi- atologic neoplasms and the specific
cate the clinical hematopoietic neo- sample types for which the device is in-
plasms for which the assay was dedicated for use.
signed and validated, for example, (C) Device precision data using clin-
chronic leukemia or lymphoma. ical samples to evaluate the within-lot,
(ii) A detailed device description in- between-lot, within-run, between run,
cluding the following: site-to-site and total variation using a
(A) A detailed description of all test minimum of three sites, of which at
components, all required reagents, and least two sites must be external sites.
all instrumentation and equipment, in- Results shall be reported as the stand-
cluding illustrations or photographs of ard deviation and percentage coeffi-
nonstandard equipment or methods. cient of variation for each level tested.
(B) Detailed documentation of the (D) Reproducibility data generated
device software including, but not lim- using a minimum of three lots of re-
ited to, standalone software applica- agents to evaluate mean fluorescence
tions and hardware-based devices that intensity and variability of the recov-
incorporate software. ery of the different markers and/or cell
(C) A detailed description of method- populations.
ology and assay procedure. (E) Data from specimen and reagent
(D) A description of appropriate in- carryover testing performed using well-
ternal and external quality control ma- established methods (e.g., CLSI H26–
terials that are recommended or pro- A2).
vided. The description must identify (F) Specimen and prepared sample
those control elements that are incor- stability data established for each
porated into the testing procedure, if specimen matrix in the anticoagulant
applicable. combinations and storage/use condi-
(E) Detailed specifications for sample tions that will be indicated.
collection, processing, and storage. (G) A study testing anticoagulant
(F) Detailed specification of the cri- equivalency in all claimed specimen
teria for test results interpretation and type/anticoagulant combinations using
reporting including pre-established clinical specimens that are representa-
templates. tive of the intended use population of
(G) If applicable, based on the output the device.
of the results, a description of the spe- (H) Analytic sensitivity data using a
cific number of events to collect, result dilution panel created from clinical
outputs, and analytical sensitivity of samples.
the assay that will be reported. (I) Analytical specificity data, in-
(iii) Information that demonstrates cluding interference and cross-con-
the performance characteristics of the tamination.
test, including: (J) Device stability data, including
(A) Device performance data from ei- real-time stability of reagents under
ther a method comparison study com- various storage times and tempera-
paring the specific lymphocyte cell tures.
305
§ 864.7040 21 CFR Ch. I (4–1–23 Edition)
(K) For devices that include the indications described in paragraph

polyclonal antibodies, Fluorescence (b)(1)(i) of this section.
Minus One (FMO) studies to evaluate
[82 FR 61165, Dec. 27, 2017]
non-specific binding for all polyclonal
antibodies. Each FMO tube is compared § 864.7040 Adenosine triphosphate re-
to reagent reference to demonstrate lease assay.
that no additional population appears
(a) Identification. An adenosine
when one marker is absent. Pre-speci-
triphosphate release assay is a device
fied acceptance criteria must be pro-
that measures the release of adenosine
vided and followed.
triphosphate (ATP) from platelets fol-
(L) For devices indicated for use as a lowing aggregation. This measurement
semi-quantitative test, linearity data is made on platelet-rich plasma using a
using a dilution panel created from photometer and a luminescent firefly
clinical samples. extract. Simultaneous measurements
(M) For devices indicated for use as a of platelet aggregation and ATP re-
semi-quantitative test, clinically rel- lease are used to evaluate platelet
evant analytical sensitivity data, in- function disorders.
cluding limit of blank, limit of detec- (b) Classification. Class I (general con-
tion, and limit of quantification. trols). The device is exempt from the
(iv) Identification of risk mitigation premarket notification procedures in
elements used by the device, including subpart E of part 807 of this chapter
a detailed description of all additional subject to the limitations in § 864.9.
procedures, methods, and practices in-
corporated into the instructions for use FR 71799, Dec. 30, 2019]
that mitigate risks associated with
testing the device. § 864.7060 Antithrombin III assay.
(2) The 21 CFR 809.10 compliant label-
(a) Identification. An antithrombin III
ing must include the following:
assay is a device that is used to deter-
(i) The intended use statement in the mine the plasma level of antithrombin
21 CFR 809.10(a)(2) and (b)(2) compliant III (a substance which acts with the
labeling must include a statement that anticoagulant heparin to prevent co-
the results should be interpreted by a agulation). This determination is used
pathologist or equivalent professional to monitor the administration of hep-
in conjunction with other clinical and arin in the treatment of thrombosis.
laboratory findings. The intended use The determination may also be used in
statement must also include informa- the diagnosis of thrombophilia (a con-
tion on what the device detects and genital deficiency of antithrombin III).
measures, whether the device is quali- (b) Classification. Class II (perform-
tative, semi-quantitative, and/or quan- ance standards).
titative, the clinical indications for
which the device is to be used, and the [45 FR 60609, Sept. 12, 1980]
specific population(s) for which the de-
§ 864.7100 Red blood cell enzyme
vice is intended. assay.
(ii) A detailed description of the per-
formance studies conducted to comply (a) Identification. Red blood cell en-
with paragraph (b)(1)(iii) of this section zyme assay is a device used to measure
and a summary of the results. the activity in red blood cells of clini-
(3) As part of the risk management cally important enzymatic reactions
and their products, such as pyruvate
activities performed under 21 CFR
kinase or 2,3-diphosphoglycerate. A red
820.30 design controls, product labeling
blood cell enzyme assay is used to de-
and instruction manuals must include
termine the enzyme defects responsible
clear examples of all expected
for a patient’s hereditary hemolytic
phenotypic patterns and gating strate-
anemia.
gies using well-defined clinical samples
representative of both abnormal and

ance standards).
normal cellular populations. These
samples must be selected based upon [45 FR 60610, Sept. 12, 1980]
306
§ 864.7140 Activated whole blood clot- ments which include polymerase chain
ting time tests. reaction (PCR) primers, hybridization
(a) Identification. An activated whole matrices, thermal cyclers, imagers,
blood clotting time tests is a device, and software packages. The detection
used to monitor heparin therapy for of the Factor V Leiden mutation aids
the treatment of venous thrombosis or in the diagnosis of patients with sus-
pulmonary embolism by measuring the pected thrombophilia.
coagulation time of whole blood. (b) Classification. Class II (special
(b) Classification. Class II (perform- controls). The special control is FDA’s
ance standards). guidance entitled ‘‘Class II Special
[45 FR 60611, Sept. 12, 1980] Controls Guidance Document: Factor V
Leiden DNA Mutation Detection Sys-
§ 864.7250 Erythropoietin assay. tems.’’ (See § 864.1(d) for the avail-
(a) Identification. A erythropoietin ability of this guidance document.)
assay is a device that measures the
[69 FR 12273, Mar. 16, 2004]
concentration of erythropoietin (an en-
zyme that regulates the production of § 864.7290 Factor deficiency test.
red blood cells) in serum or urine. This
assay provides diagnostic information (a) Identification. A factor deficiency
for the evaluation of erythrocytosis test is a device used to diagnose spe-
(increased total red cell mass) and ane- cific coagulation defects, to monitor
mia. certain types of therapy, to detect co-
(b) Classification. Class II. The special agulation inhibitors, and to detect a
control for this device is FDA’s ‘‘Docu- carrier state (a person carrying both a
ment for Special Controls for Erythro- recessive gene for a coagulation factor
poietin Assay Premarket Notification deficiency such as hemophilia and the
(510(k)s).’’ corresponding normal gene).
[45 FR 60612, Sept. 12, 1980, as amended at 52 (b) Classification. Class II (perform-
FR 17733, May 11, 1987; 65 FR 17144, Mar. 31, ance standards).
2000]
[45 FR 60613, Sept. 12, 1980]
§ 864.7275 Euglobulin lysis time tests.
§ 864.7300 Fibrin monomer
(a) Identification. A euglobulin lysis
paracoagulation test.
time test is a device that measures the
length of time required for the lysis (a) Identification. A fibrin monomer
(dissolution) of a clot formed from paracoagulation test is a device used to
fibrinogen in the euglobulin fraction detect fibrin monomer in the diagnosis
(that fraction of the plasma responsible of disseminated intravascular coagula-
for the formation of plasmin, a clot tion (nonlocalized clotting within a
lysing enzyme). This test evaluates blood vessel) or in the differential diag-
natural fibrinolysis (destruction of a nosis between disseminated
blood clot after bleeding has been ar- intravascular coagulation and primary
rested). The test also will detect accel- fibrinolysis (dissolution of the fibrin in
erated fibrinolysis. a blood clot).
(b) Classification. Class II (special (b) Classification. Class II (special
subject to the limitations in § 864.9. in subpart E of part 807 of this chapter
subject to the limitations in § 864.9. The
[45 FR 60612, Sept. 12, 1980, as amended at 84 special control for this device is FDA’s
FR 71799, Dec. 30, 2019]
‘‘In Vitro Diagnostic Fibrin Monomer
§ 864.7280 Factor V Leiden DNA muta- Paracoagulation Test.’’ See § 864.1(d)
tion detection systems. for information on obtaining this docu-
(a) Identification. Factor V Leiden ment.
deoxyribonucleic acid (DNA) mutation [45 FR 60614, Sept. 12, 1980, as amended at 52
detection systems are devices that con- FR 17733, May 11, 1987; 65 FR 17144, Mar. 31,
sist of different reagents and instru- 2000, 84 FR 71799, Dec. 30, 2019]
307
§ 864.7320 21 CFR Ch. I (4–1–23 Edition)
§ 864.7320 Fibrinogen/fibrin degrada- methemoglobin reduction, catalase in-

tion products assay. hibition, and ultraviolet kinetics.
(a) Identification. A fibrinogen/fibrin (b) Classification. Class II (perform-
degradation products assay is a device ance standards).
used to detect and measure fibrinogen [45 FR 60616, Sept. 12, 1980]
degradation products and fibrin deg-
radation products (protein fragments § 864.7375 Glutathione reductase
produced by the enzymatic action of assay.
plasmin on fibrinogen and fibrin) as an
aid in detecting the presence and de- (a) Identification. A glutathione re-
gree of intravascular coagulation and ductase assay is a device used to deter-
fibrinolysis (the dissolution of the mine the activity of the enzyme gluta-
fibrin in a blood clot) and in moni- thione reductase in serum, plasma, or
toring therapy for disseminated erythrocytes by such techniques as flu-
intravascular coagulation (nonlocal- orescence and photometry. The results
ized clotting in the blood vessels). of this assay are used in the diagnosis
(b) Classification. Class II (perform- of liver disease, glutathione reductase
ance standards). deficiency, or riboflavin deficiency.
[45 FR 60615, Sept. 12, 1980]
§ 864.7340 Fibrinogen determination the premarket notification procedures
system. in subpart E of part 807 of this chapter
(a) Identification. A fibrinogen deter- subject to the limitations in § 864.9.
mination system is a device that con- [45 FR 60616, Sept. 12, 1980, as amended at 84
sists of the instruments, reagents, FR 71799, Dec. 30, 2019]
standards, and controls used to deter-
mine the fibrinogen levels in dissemi- § 864.7400 Hemoglobin A2 assay.
nated intravascular coagulation (non- (a) Identification. A hemoglobin A2
localized clotting within the blood ves- assay is a device used to determine the
sels) and primary fibrinolysis (the dis- hemoglobin A2 content of human blood.
solution of fibrin in a blood clot).
The measurement of hemoglobin A2 is
used in the diagnosis of the
controls). A control or fibrinogen
thalassemias (hereditary hemolytic
standard intended for use with a
anemias characterized by decreased
fibrinogen determination system is ex-
empt from the premarket notification synthesis of one or more types of he-
procedures in subpart E of part 807 of moglobin polypeptide chains).
this chapter subject to the limitations (b) Classification. Class II (perform-
in § 864.9. ance standards).
[45 FR 60615, Sept. 12, 1980, as amended at 84 [45 FR 60617, Sept. 12, 1980]
FR 71799, Dec. 30, 2019]
§ 864.7415 Abnormal hemoglobin assay.
§ 864.7360 Erythrocytic glucose-6-phos- (a) Identification. An abnormal hemo-
phate dehydrogenase assay.
globin assay is a device consisting of
(a) Identification. An erythrocytic the reagents, apparatus, instrumenta-
glucose-6-phosphate dehydrogenase tion, and controls necessary to isolate
assay is a device used to measure the and identify abnormal genetically de-
activity of the enzyme glucose-6-phos- termined hemoglobin types.
phate dehydrogenase or of glucose-6- (b) Classification. Class II (special
phosphate dehydrogenase isoenzymes. controls). A control intended for use
The results of this assay are used in
with an abnormal hemoglobin assay is
the diagnosis and treatment of
nonspherocytic congenital hemolytic
anemia or drug-induced hemolytic ane-
mia associated with a glucose-6-phos-
tions in § 864.9.
phate dehydrogenase deficiency. This

generic device includes assays based on [45 FR 60618, Sept. 12, 1980, as amended at 84
fluorescence, electrophoresis, FR 71799, Dec. 30, 2019]
308
§ 864.7425 Carboxyhemoglobin assay. part 807 of this chapter subject to the

limitations in § 864.9.
(a) Identification. A
carboxyhemoglobin assay is a device [45 FR 60620, Sept. 12, 1980, as amended at 84
used to determine the FR 71799, Dec. 30, 2019]
carboxyhemoglobin (the compound § 864.7470 Glycosylated hemoglobin
formed when hemoglobin is exposed to assay.
carbon monoxide) content of human
(a) Identification. A glycosylated he-
blood as an aid in the diagnosis of car- moglobin assay is a device used to
bon monoxide poisoning. This measure- measure the glycosylated hemoglobins
ment may be made using methods such (A1a, A1b, and A1c) in a patient’s blood
as spectroscopy, colorimetry, by a column chromatographic proce-
spectrophotometry, and gasometry. dure. Measurement of glycosylated he-
(b) Classification. Class II (perform- moglobin is used to assess the level of
ance standards). control of a patient’s diabetes and to
determine the proper insulin dosage for
[45 FR 60619, Sept. 12, 1980]
a patient. Elevated levels of
§ 864.7440 Electrophoretic hemoglobin glycosylated hemoglobin indicate un-
analysis system. controlled diabetes in a patient.
(a) Identification. An electrophoretic ance standards).
hemoglobin analysis system is a device
that electrophoretically separates and [45 FR 60621, Sept. 12, 1980]
identifies normal and abnormal hemo- § 864.7490 Sulfhemoglobin assay.
globin types as an aid in the diagnosis
of anemia or erythrocytosis (increased (a) Identification. A sulfhemoglobin
assay is a device consisting of the re-
total red cell mass) due to a hemo-
agents, calibrators, controls, and in-
globin abnormality.
strumentation used to determine the
(b) Classification. Class II (perform- sulfhemoglobin (a compound of sulfur
ance standards). and hemoglobin) content of human
[45 FR 60620, Sept. 12, 1980] blood as an aid in the diagnosis of
sulfhemoglobinemia (presence of
§ 864.7455 Fetal hemoglobin assay. sulfhemoglobin in the blood due to
drug administration or exposure to a
(a) Identification. A fetal hemoglobin
poison). This measurement may be
assay is a device that is used to deter-
made using methods such as spectros-
mine the presence and distribution of copy, colorimetry, spectrophotometry,
fetal hemoglobin (hemoglobin F) in red or gasometry.
cells or to measure the amount of fetal (b) Classification. Class II (perform-
hemoglobin present. The assay may be ance standards).
used to detect fetal red cells in the ma-
ternal circulation or to detect the ele- [45 FR 60621, Sept. 12, 1980]
vated levels of fetal hemoglobin exhib- § 864.7500 Whole blood hemoglobin as-
ited in cases of hemoglobin abnormali- says.
ties such as thalassemia (a hereditary
(a) Identification. A whole blood he-
hemolytic anemia characterized by a
moglobin assay is a device consisting
decreased synthesis of one or more
or reagents, calibrators, controls, or
types of hemoglobin polypeptide photometric or spectrophotometric in-
chains). The hemoglobin determination strumentation used to measure the he-
may be made by methods such as elec- moglobin content of whole blood for
trophoresis, alkali denaturation, col- the detection of anemia. This generic
umn chromatography, or radial device category does not include auto-
immunodiffusion. mated hemoglobin systems.
(b) Classification. Class II (special (b) Classification. Class II (special
controls). A fetal hemoglobin stain in- controls). An acid hematin intended for
tended for use with a fetal hemoglobin use with whole blood hemoglobin as-
assay is exempt from the premarket says is exempt from the premarket no-
notification procedures in subpart E of tification procedures in subpart E of
309
§ 864.7525 21 CFR Ch. I (4–1–23 Edition)
part 807 of this chapter subject to the activity as evidenced by staining. The
limitations in § 864.9. results of this test are used in the dif-
[45 FR 60622, Sept. 12, 1980, as amended at 84 ferential diagnosis of the leukemias.
FR 71799, Dec. 30, 2019] (b) Classification. Class I (general con-
§ 864.7525 Heparin assay. premarket notification procedures in
(a) Identification. A heparin assay is a subpart E of part 807 of this chapter
device used to determine the level of subject to the limitations in § 864.9.
the anticoagulant heparin in the pa-
tient’s circulation. These assays are FR 63007, Dec. 7, 1994; 66 FR 38790, July 25,
quantitative clotting time procedures 2001]
using the effect of heparin on activated
coagulation factor X (Stuart factor) or § 864.7695 Platelet factor 4
procedures based on the neutralization radioimmunoassay.
of heparin by protamine sulfate (a pro-
tein that neutralizes heparin). (a) Identification. A platelet factor 4
(b) Classification. Class II (perform- radioimmunoassay is a device used to
ance standards). measure the level of platelet factor 4, a
protein released during platelet activa-
[45 FR 60623, Sept. 12, 1980] tion by radioimmunoassay. This device
§ 864.7660 Leukocyte alkaline phos- measures platelet activiation, which
phatase test. may indicate a coagulation disorder,
such as myocardial infarction or coro-
(a) Identification. A leukocyte alka-
line phosphatase test is a device used nary artery disease.
to identify the enzyme leukocyte alka- (b) Classification. Class II (perform-
line phosphatase in neutrophilic ance standards).
granulocytes (granular leukocytes [45 FR 60625, Sept. 12, 1980; 46 FR 14890, Mar.
stainable by neutral dyes). The 3, 1981]
cytochemical identification of alkaline
phosphatase depends on the formation § 864.7720 Prothrombin consumption
of blue granules in cells containing al- test.
kaline phosphatase. The results of this (a) Identification. A prothrombin con-
test are used to differentiate chronic
sumption tests is a device that meas-
granulocytic leukemia (a malignant
ures the patient’s capacity to generate
disease characterized by excessive
thromboplastin in the coagulation
overgrowth of granulocytes in the bone
marrow) and reactions that resemble process. The test also is an indirect in-
true leukemia, such as those occuring dicator of qualitative or quantitative
in severe infections and polycythemia platelet abnormalities. It is a screen-
(increased total red cell mass). ing test for thrombocytopenia (de-
(b) Classification. Class I (general con- creased number of blood platelets) and
trols). This device is exempt from the hemophilia A and B.
premarket notification procedures in (b) Classification. Class II (special
subpart E of part 807 of this chapter controls). The device is exempt from
subject to the limitations in § 864.9. the premarket notification procedures
[45 FR 60623, Sept. 12, 1980, as amended at 59 in subpart E of part 807 of this chapter
FR 63007, Dec. 7, 1994; 66 FR 38790, July 25, subject to the limitations in § 864.9.
2001]
FR 71800, Dec. 30, 2019]
§ 864.7675 Leukocyte peroxidase test.
(a) Identification. A leukocyte peroxi- § 864.7735 Prothrombin-proconvertin
dase test is a device used to distinguish test and thrombotest.
certain myeloid cells derived from the
(a) Identification. The prothrombin-
bone marrow, i.e., neutrophils,
proconvertin test and thrombotest are
eosinophils, and monocytes, from
devices used in the regulation of cou-
lymphoid cells of the lymphatic system

and erythroid cells of the red blood cell marin therapy (administration of a
series on the basis of their peroxidase
310
coumarin anticoagulant such as so- tect and identify coagulation factor de-
dium warfarin in the treatment of ve- ficiencies and coagulation inhibitors.
nous thrombosis and pulmonary embo- (b) Classification. Class I (general con-
lism) and as a diagnostic test in controls). This device is exempt from the
junction with, or in place of, the Quick premarket notification procedures in
prothrombin time test to detect coagu- subpart E of part 807 of this chapter
lation disorders. subject to the limitations in § 864.9.
controls). The device is exempt from FR 63007, Dec. 7, 1994; 66 FR 38790, July 25,
the premarket notification procedures 2001]
subject to the limitations in § 864.9. § 864.7925 Partial thromboplastin time
tests.
FR 71800, Dec. 30, 2019] (a) Identification. A partial thrombo-
plastin time test is a device used for
§ 864.7750 Prothrombin time test. primary screening for coagulation ab-
(a) Identification. A prothrombin time normalities, for evaluation of the ef-
test is a device used as a general fect of therapy on procoagulant dis-
screening procedure for the detection orders, and as an assay for coagulation
of possible clotting factor deficiencies factor deficiencies of the intrinsic co-
in the extrinsic coagulation pathway, agulation pathway.
which involves the reaction between (b) Classification. Class II (perform-
coagulation factors III and VII, and to ance standards).
monitor patients receiving coumarin [45 FR 60629, Sept. 12, 1980]
therapy (the administration of one of
the coumarin anticoagulants in the Subpart I—Hematology Reagents
treatment of venous thrombosis or pul-
monary embolism). § 864.8100 Bothrops atrox reagent.
(a) Identification. A Bothrops atrox
ance standards).
reagent is a device made from snake
[45 FR 60626, Sept. 12, 1980] venom and used to determine blood
fibrinogen levels to aid in the evalua-
§ 864.7825 Sickle cell test. tion of disseminated intravascular co-
(a) Identification. A sickle cell test is agulation (nonlocalized clotting in the
a device used to determine the sickle blood vessels) in patients receiving
cell hemoglobin content of human heparin therapy (the administration of
blood to detect sickle cell trait or sick- the anticoagulant heparin in the treat-
le cell diseases. ment of thrombosis) or as an aid in the
(b) Classification. Class II (perform- classification of dysfibrinogenemia
ance standards). (presence in the plasma of functionally
defective fibrinogen).
[45 FR 60627, Sept. 12, 1980] (b) Classification. Class II (perform-
ance standards).
§ 864.7875 Thrombin time test.
[45 FR 60629, Sept. 12, 1980]
(a) Identification. A thrombin time
test is a device used to measure § 864.8150 Calibrator for cell indices.
fibrinogen concentration and detect
fibrin or fibrinogen split products for (a) Identification. A calibrator for cell
the evaluation of bleeding disorders. indices is a device that approximates
(b) Classification. Class II (perform- whole blood or certain blood cells and
ance standards). that is used to set an instrument in-
tended to measure mean cell volume
[45 FR 60628, Sept. 12, 1980] (MCV), mean corpuscular hemoglobin
(MCH), and mean corpuscular hemo-
§ 864.7900 Thromboplastin generation globin concentration (MCHC), or other
test.
cell indices. It is a suspension of par-

(a) Identification. A thromboplastin ticles or cells whose size, shape, con-
generation test is a device used to de- centration, and other characteristics
311
§ 864.8165 21 CFR Ch. I (4–1–23 Edition)
have been precisely and accurately de- tion, and other characteristics have
termined. been precisely and accurately deter-
(b) Classification. Class II (special mined.
controls). The device is exempt from (b) Classification. Class II (special
the premarket notification procedures controls). The device is exempt from
in subpart E of part 807 of this chapter the premarket notification procedures
FR 71800, Dec. 30, 2019] [45 FR 60634, Sept. 12, 1980, as amended at 84
FR 71800, Dec. 30, 2019]
§ 864.8165 Calibrator for hemoglobin
or hematocrit measurement. § 864.8200 Blood cell diluent.
(a) Identification. A calibrator for he- (a) Identification. A blood cell diluent
moglobin or hematocrit measurement is a device used to dilute blood for fur-
is a device that approximates whole ther testing, such as blood cell count-
blood, red blood cells, or a hemoglobin ing.
derivative and that is used to set in- (b) Classification. Class I (general con-
struments intended to measure hemo- trols). This device is exempt from the
globin, the hematocrit, or both. It is a premarket notification procedures in
material whose characteristics have subpart E of part 807 of this chapter
been precisely and accurately deter- subject to the limitations in § 864.9.
mined. [45 FR 60635, Sept. 12, 1980, as amended at 54
(b) Classification. Class II (special FR 25045, June 12, 1989; 66 FR 38790, July 25,
controls). The device is exempt from 2001]
in subpart E of part 807 of this chapter § 864.8500 Lymphocyte separation me-
subject to the limitations in § 864.9. dium.
[45 FR 60632, Sept. 12, 1980, as amended at 84 (a) Identification. A lymphocyte sepa-
FR 71800, Dec. 30, 2019] ration medium is a device used to iso-
late lymphocytes from whole blood.
§ 864.8175 Calibrator for platelet (b) Classification. Class I (general con-
counting. trols). This device is exempt from the
(a) Identification. A calibrator for premarket notification procedures in
platelet counting is a device that re- subpart E of part 807 of this chapter
sembles platelets in plasma or whole subject to the limitations in § 864.9.
blood and that is used to set a platelet [45 FR 60636, Sept. 12, 1980, as amended at 59
counting instrument. It is a suspension FR 63007, Dec. 7, 1994; 66 FR 38790, July 25,
of particles or cells whose size, shape 2001]
concentration, and other characteris-
tics have been precisely and accurately § 864.8540 Red cell lysing reagent.
determined. (a) Identification. A red cell lysing re-
(b) Classification. Class II (special agent is a device used to lyse (destroy)
controls). The device is exempt from red blood cells for hemoglobin deter-
the premarket notification procedures minations or aid in the counting of
in subpart E of part 807 of this chapter white blood cells.
subject to the limitations in § 864.9. (b) Classification. Class I (general con-
[45 FR 60633, Sept. 12, 1980, as amended at 84 trols). This device is exempt from the
FR 71800, Dec. 30, 2019] premarket notification procedures in
§ 864.8185 Calibrator for red cell and subject to the limitations in § 864.9.
white cell counting.
(a) Identification. A calibrator for red FR 25045, June 12, 1989; 66 FR 38790, July 25,
cell and white cell counting is a device 2001]
that resembles red or white blood cells
and that is used to set instruments in- § 864.8625 Hematology quality control
mixture.
tended to count red cells, white cells,

or both. It is a suspension of particles (a) Identification. A hematology qual-
or cells whose size, shape, concentra- ity control mixture is a device used to
312
ascertain the accuracy and precision of blood and blood components is a device
manual, semiautomated, and auto- intended for medical purposes that is
mated determinations of cell param- an empty plastic bag or plastic or glass
eters such as white cell count (WBC), bottle used to collect, store, or transfer
red cell count (RBC), platelet count blood and blood components for further
(PLT), hemoglobin, hematocrit (HCT), processing.
mean corpuscular volume (MCV), mean (b) Classification. Class II (perform-
corpuscular hemoglobin (MCH), and ance standards).
mean corpuscular hemoglobin con-
centration (MCHC). [45 FR 60638, Sept. 12, 1980]
controls). Except when intended for use § 864.9125 Vacuum-assisted blood col-
lection system.
in blood components, the device is ex-
empt from the premarket notification (a) Identification. A vacuum-assisted
procedures in subpart E of part 807 of blood collection system is a device in-
this chapter subject to the limitations tended for medical purposes that uses a
in § 864.9. vacuum to draw blood for subsequent
reinfusion.
FR 71800, Dec. 30, 2019] (b) Classification. Class I (general con-
trols). The manual device is exempt
§ 864.8950 Russell viper venom rea- from the premarket notification proce-
gent. dures in subpart E of part 807 of this
(a) Identification. Russell viper venom chapter subject to § 864.9.
reagent is a device used to determine [45 FR 60639, Sept. 12, 1980, as amended at 65
the cause of an increase in the pro- FR 2310, Jan. 14, 2000]
thrombin time.
(b) Classification. Class I (general con- § 864.9145 Processing system for fro-
trols). zen blood.
[45 FR 60637, Sept. 12, 1980] (a) Identification. A processing system
for frozen blood is a device used to
Subpart J—Products Used In Es- glycerolize red blood cells prior to
tablishments That Manufac- freezing to minimize hemolysis (disrup-
ture Blood and Blood Prod- tion of the red cell membrane accom-
panied by the release of hemoglobin)
ucts due to freezing and thawing of red
§ 864.9050 Blood bank supplies. blood cells and to deglycerolize and
wash thawed cells for subsequent re-
(a) Identification. Blood bank supplies infusion.
are general purpose devices intended
for in vitro use in blood banking. This
ance standards).
generic type of device includes prod-
ucts such as blood bank pipettes, blood [45 FR 60639, Sept. 12, 1980]
grouping slides, blood typing tubes,
blood typing racks, and cold packs for § 864.9160 Blood group substances of
antisera reagents. The device does not nonhuman origin for in vitro diag-
include articles that are licensed by nostic use.
the Center for Biologics Evaluation (a) Identification. Blood group sub-
and Research of the Food and Drug Ad- stances of nonhuman origin for in vitro
ministration. diagnostic use are materials, such as
(b) Classification. Class I (general con- blood group specific substances pre-
trols). pared from nonhuman sources (e.g.,
[45 FR 60638, Sept. 12, 1980, as amended at 53 pigs, cows, and horses) used to detect,
FR 11253, Apr. 6, 1988] identify, or neutralize antibodies to
various human blood group antigens.
§ 864.9100 Empty container for the col- This generic type of device does not in-
lection and processing of blood and clude materials that are licensed by
blood components.
the Center for Biologics Evaluation

(a) Identification. An empty container and Research of the Food and Drug Ad-
for the collection and processing of ministration.
313
§ 864.9165 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class II (special (e.g., electrical safety, electromagnetic

controls). The device is exempt from compatibility, or wireless coexistence).
[83 FR 23217, June 18, 2018]
subject to § 864.9. § 864.9175 Automated blood grouping
[45 FR 60640, Sept. 12, 1980, as amended at 53 and antibody test system.
FR 11253, Apr. 6, 1988; 63 FR 59225, Nov. 3, (a) Identification. An automated blood
1998] grouping and antibody test system is a
device used to group erythrocytes (red
§ 864.9165 Blood establishment com- blood cells) and to detect antibodies to
puter software and accessories.
blood group antigens.
(a) Identification. Blood establishment (b) Classification. Class II (perform-
computer software (BECS) is a device ance standards).
used in the manufacture of blood and
[45 FR 60641, Sept. 12, 1980]
blood components to assist in the pre-
vention of disease in humans by identi- § 864.9185 Blood grouping view box.
fying ineligible donors, by preventing
the release of unsuitable blood and (a) Identification. A blood grouping
blood components for transfusion or for view box is a device with a glass or
further manufacturing into products plastic viewing surface, which may be
for human treatment or diagnosis, by illuminated and heated, that is used to
performing compatibility testing be- view cell reactions in antigen-antibody
tween donor and recipient, or by per- testing.
forming positive identification of pa- (b) Classification. Class I (general con-
tients and blood components at the trols). The device is exempt from the
point of transfusion to prevent trans- premarket notification procedures in
fusion reactions. This generic type of subpart E of part 807 of this chapter
device may include a BECS accessory, subject to § 864.9.
a device intended for use with BECS to [45 FR 60641, Sept. 12, 1980, as amended at 65
augment the performance of the BECS FR 2310, Jan. 14, 2000]
or to expand or modify its indications
for use. § 864.9195 Blood mixing devices and
(b) Classification. Class II (special blood weighing devices.
controls). The special controls for (a) Identification. A blood mixing de-
these devices are: vice is a device intended for medical
(1) Software performance and func- purposes that is used to mix blood or
tional requirements including detailed blood components by agitation. A
design specifications (e.g., algorithms blood weighing device is a device in-
or control characteristics, alarms, de- tended for medical purposes that is
vice limitations, and safety require- used to weigh blood or blood compo-
ments). nents as they are collected.
(2) Verification and validation test- (b) Classification. Class I (general con-
ing and hazard analysis must be per- trols). The manual device is exempt
formed. from the premarket notification proce-
(3) Labeling must include: dures in subpart E of part 807 of this
(i) Software limitations; chapter subject to § 864.9.
(ii) Unresolved anomalies, annotated [45 FR 60642, Sept. 12, 1980, as amended at 65
with an explanation of the impact on FR 2310, Jan. 14, 2000]
safety or effectiveness;
(iii) Revision history; and § 864.9205 Blood and plasma warming
(iv) Hardware and peripheral speci- device.
fications. (a) Nonelectromagnetic blood or plasma
(4) Traceability matrix must be per- warming device—(1) Identification. A
formed. nonelectromagnetic blood and plasma
(5) Performance testing to ensure the warming device is a device that warms
safety and effectiveness of the system blood or plasma, by means other than
must be performed, including when electromagnetic radiation, prior to ad-
adding new functional requirements ministration.
314
(2) Classification. Class II (perform- erating by Centrifugal or Filtration

ance standards). Separation Principle.’’
(b) Electromagnetic blood and plasma [72 FR 67644, Nov. 30, 2007]
warming device—(1) Identification. An
electromagnetic blood and plasma § 864.9275 Blood bank centrifuge for in
warming device is a device that em- vitro diagnostic use.
ploys electromagnetic radiation (a) Identification. A blood bank cen-
(radiowaves or microwaves) to warm a trifuge for in vitro diagnostic use is a
bag or bottle of blood or plasma prior device used only to separate blood cells
to administration. for further diagnostic testing.
(2) Classfication. Class III (premarket (b) Classification. Class I (general con-
approval). trols). The device is exempt from the
(c) Date PMA or notice of completion of premarket notification procedures in
a PDP is required. No effective date has subpart E of part 807 of this chapter
been established of the requirement for subject to § 864.9.
premarket approval for the device de-
scribed in paragraph (b)(1). See § 864.3.
FR 2310, Jan. 14, 2000]
FR 17733, May 11, 1987] § 864.9285 Automated cell-washing
centrifuge for immuno-hematology.
§ 864.9225 Cell-freezing apparatus and (a) Identification. An automated cell-
reagents for in vitro diagnostic use. washing centrifuge for immuno-hema-
(a) Identification. Cell-freezing appa- tology is a device used to separate and
ratus and reagents for in vitro diag- prepare cells and sera for further in
nostic use are devices used to freeze vitro diagnostic testing.
human red blood cells for in vitro diag- (b) Classification. Class II (perform-
nostic use. ance standards).
(b) Classification. Class I (general con- [45 FR 60646, Sept. 12, 1980]
premarket notification procedures in § 864.9300 Automated Coombs test sys-
subpart E of part 807 of this chapter tems.
subject to § 864.9. (a) Identification. An automated
[45 FR 60643, Sept. 12, 1980, as amended at 65 Coombs test system is a device used to
FR 2310, Jan. 14, 2000] detect and identify antibodies in pa-
tient sera or antibodies bound to red
§ 864.9245 Automated blood cell sepa- cells. The Coombs test is used for the
rator. diagnosis of hemolytic disease of the
(a) Identification. An automated blood newborn, and autoimmune hemolytic
cell separator is a device that uses a anemia. The test is also used in
centrifugal or filtration separation crossmatching and in investigating
principle to automatically withdraw transfusion reactions and drug-induced
whole blood from a donor, separate the red cell sensitization.
whole blood into blood components, (b) Classification. Class II (perform-
collect one or more of the blood compo- ance standards).
nents, and return to the donor the re- [45 FR 60646, Sept. 12, 1980]
mainder of the whole blood and blood
components. The automated blood cell § 864.9320 Copper sulfate solution for
separator device is intended for routine specific gravity determinations.
collection of blood and blood compo- (a) Identification. A copper sulfate so-
nents for transfusion or further manu- lution for specific gravity determina-
facturing use. tions is a device used to determine
(b) Classification. Class II (special whether the hemoglobin content of a
controls). The special control for this potential donor’s blood meets the re-
device is a guidance for industry and quired level (12.5 grams per 100 milli-
FDA staff entitled ‘‘Class II Special liters of blood for women and 13.5
Controls Guidance Document: Auto- grams per 100 milliliters of blood for
mated Blood Cell Separator Device Op- men).
315
§ 864.9400 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class I (general con- § 864.9600 Potentiating media for in

trols). The device is exempt from the vitro diagnostic use.
premarket notification procedures in (a) Identification. Potentiating media
subpart E of part 807 of this chapter for in vitro diagnostic use are media,
subject to § 864.9. such as bovine albumin, that are used
[45 FR 60647, Sept. 12, 1980, as amended at 65 to suspend red cells and to enhance cell
FR 2310, Jan. 14, 2000] reactions for antigen-antibody testing.
§ 864.9400 Stabilized enzyme solution. controls). The device is exempt from
(a) Identification. A stabilized enzyme the premarket notification procedures
solution is a reagent intended for med- in subpart E of part 807 of this chapter
ical purposes that is used to enhance subject to § 864.9.
the reactivity of red blood cells with [45 FR 60649, Sept. 12, 1980, as amended at 63
certain antibodies, including anti- FR 59226, Nov. 3, 1998]
bodies that are not detectable by other
techniques. These enzyme solutions in- § 864.9650 Quality control kit for blood
banking reagents.
clude papain, bromelin, ficin, and
trypsin. (a) Identification. A quality control
(b) Classification. Class II (special kit for blood banking reagents is a de-
controls). The device is exempt from vice that consists of sera, cells, buffers,
the premarket notification procedures and antibodies used to determine the
in subpart E of part 807 of this chapter specificity, potency, and reactivity of
subject to the limitations in § 864.9. the cells and reagents used for blood
banking.
[45 FR 60647, Sept. 12, 1980, as amended at 84 (b) Classification. Class II (perform-
FR 71800, Dec. 30, 2019] ance standards).
§ 864.9550 Lectins and protectins. [45 FR 60649, Sept. 12, 1980]
(a) Identification. Lectins and § 864.9700 Blood storage refrigerator
protectins are proteins derived from and blood storage freezer.
plants and lower animals that cause
(a) Identification. A blood storage re-
cell agglutination in the presence of
frigerator and a blood storage freezer
certain antigens. These substances are
are devices intended for medical pur-
used to detect blood group antigens for
poses that are used to preserve blood
in vitro diagnostic purposes. and blood products by storing them at
(b) Classification. Class II (special cold or freezing temperatures.
controls). The device is exempt from (b) Classification. Class II (special
the premarket notification procedures controls). The device is exempt from
in subpart E of part 807 of this chapter the premarket notification procedures
subject to § 864.9. in subpart E of part 807 of this chapter
[45 FR 60648, Sept. 12, 1980, as amended at 63 subject to § 864.9.
FR 59226, Nov. 3, 1998] [45 FR 60650, Sept. 12, 1980, as amended at 63
FR 59226, Nov. 3, 1998]
§ 864.9575 Environmental chamber for
storage of platelet concentrate. § 864.9750 Heat-sealing device.
(a) Identification. An environmental (a) Identification. A heat-sealing de-
chamber for storage of platelet con- vice is a device intended for medical
centrate is a device used to hold plate- purposes that uses heat to seal plastic
let-rich plasma within a preselected bags containing blood or blood compo-
temperature range. nents.
controls). The device is exempt from trols). The device is exempt from the
the premarket notification procedures premarket notification procedures in
[45 FR 60648, Sept. 12, 1980, as amended at 63 [45 FR 60650, Sept. 12, 1980, as amended at 65
FR 59226, Nov. 3, 1998] FR 2311, Jan. 14, 2000]
316
§ 864.9875 Transfer set. 866.1645 Fully automated short-term incu-

bation cycle antimicrobial susceptibility
(a) Identification. A transfer set is a system.
device intended for medical purposes 866.1655 System for detection of microorga-
that consists of a piece of tubing with nisms and antimicrobial resistance using
suitable adaptors used to transfer reporter expression.
blood or plasma from one container to 866.1700 Culture medium for antimicrobial
another. susceptibility tests.
Subpart C—Microbiology Devices
ance standards).
866.2050 Staphylococcal typing
[45 FR 60651, Sept. 12, 1980]
bacteriophage.
866.2120 Anaerobic chamber.
Subpart K—Products Used In Es- 866.2160 Coagulase plasma.
tablishments That Manufac- 866.2170 Automated colony counter.
866.2180 Manual colony counter.
ture Human Cells, Tissues, and 866.2190 Automated image assessment sys-
Cellular and Tissue-Based tem for microbial colonies on solid cul-
Products (HCT/Ps) ture media.
866.2300 Multipurpose culture medium.
§ 864.9900 Cord blood processing sys- 866.2320 Differential culture medium.
tem and storage container. 866.2330 Enriched culture medium.
866.2350 Microbiological assay culture me-
(a) Identification. A cord blood proc- dium.
essing system and storage container is 866.2360 Selective culture medium.
a device intended for use in the proc- 866.2390 Transport culture medium.
essing and the storage of cord blood. 866.2410 Culture medium for pathogenic
This device is a functionally closed Neisseria spp.
processing system that includes con- 866.2420 Oxidase screening test for gonor-
tainers, other soft goods, and a cen- rhea.
trifugation system for cord blood con- 866.2440 Automated medium dispensing and
stacking device.
centration, and a final container for 866.2450 Supplement for culture media.
the cryopreservation and the storage of 866.2480 Quality control kit for culture
a cord blood product. media.
(b) Classification. Class II (special 866.2500 Microtiter diluting and dispensing
controls). The special control for this device.
device is FDA’s guidance document en- 866.2540 Microbiological incubator.
titled ‘‘Class II Special Controls Guid- 866.2560 Microbial growth monitor.
ance Document: Cord Blood Processing 866.2580 Gas-generating device.
866.2600 Wood’s fluorescent lamp.
System and Storage Container.’’ For
866.2660 Microorganism differentiation and
the availability of this guidance docu- identification device.
ment, see § 864.1(d). 866.2680 Streptococcus spp. nucleic acid-
[72 FR 4638, Feb. 1, 2007] based assay.
866.2850 Automated zone reader.
866.2900 Microbiological specimen collection
PART 866—IMMUNOLOGY AND and transport device.
MICROBIOLOGY DEVICES
Subpart D—Serological Reagents
Subpart A—General Provisions 866.3010 Acinetobacter calcoaceticus sero-
Sec. logical reagents.
866.1 Scope. 866.3020 Adenovirus serological reagents.
866.3 Effective dates of requirement for pre- 866.3035 Arizona spp. serological reagents.
market approval. 866.3040 Aspergillus spp. serological reagents.
866.9 Limitations of exemptions from sec- 866.3045 In vitro diagnostic device for Bacil-
tion 510(k) of the Federal Food, Drug, lus spp. detection.
and Cosmetic Act (the act). 866.3050 Beta-glucan serological assays.
866.3060 Blastomyces dermatitidis serological
Subpart B—Diagnostic Devices reagents.
866.3065 Bordetella spp. serological reagents.
866.1620 Antimicrobial susceptibility test 866.3085 Brucella spp. serological reagents.
disc. 866.3110 Campylobacter fetus serological re-

866.1640 Antimicrobial susceptibility test agents.
powder. 866.3120 Chlamydia serological reagents.
317
866.3125 Citrobacter spp. serological reagents. sistance markers from positive blood cul-
866.3130 Clostridium difficile toxin gene am- tures.
plification assay. 866.3370 Mycobacterium tuberculosis
866.3135 Coccidioides immitis serological re- immunofluorescent reagents.
agents. 866.3372 Nucleic acid-based in vitro diag-
866.3140 Corynebacterium spp. serological re- nostic devices for the detection of
agents. Mycobacterium tuberculosis complex in
866.3145 Coxsackievirus serological re- respiratory specimens.
agents. 866.3373 Nucleic acid-based in vitro diag-
866.3165 Cryptococcus neoformans serological nostic devices for the detection of
reagents. Mycobacterium tuberculosis complex
866.3169 Hepatitis C virus antibody tests. (MTB-complex) and the genetic
866.3170 Nucleic acid-based hepatitis C virus mutations associated with MTB-complex
ribonucleic acid tests. antibiotic resistance in respiratory
866.3175 Cytomegalovirus serological re- specimens.
agents. 866.3375 Mycoplasma spp. serological re-
866.3200 Echinococcus spp. serological reagents.
agents. 866.3380 Mumps virus serological reagents.
866.3205 Echovirus serological reagents. 866.3390 Neisseria spp. direct serological test
866.3210 Endotoxin assay. reagents.
866.3215 Device to detect and measure non- 866.3395 Norovirus serological reagents.
microbial analyte(s) in human clinical 866.3400 Parainfluenza virus serological re-
specimens to aid in assessment of pa- agents.
tients with suspected sepsis. 866.3402 Plasmodium species antigen detec-
866.3220 Entamoeba histolytica serological re- tion assays.
agents. 866.3405 Poliovirus serological reagents.
866.3225 Enterovirus nucleic acid assay. 866.3410 Proteus spp. (Weil-Felix) serological
866.3235 Epstein-Barr virus serological re- reagents.
agents. 866.3415 Pseudomonas spp. serological re-
866.3240 Equine encephalomyelitis virus se- agents.
rological reagents. 866.3460 Rabiesvirus immunofluorescent re-
866.3250 Erysipelothrix rhusiopathiae sero- agents.
logical reagents. 866.3470 Reovirus serological reagents.
866.3255 Escherichia coli serological reagents. 866.3480 Respiratory syncytial virus sero-
866.3270 Flavobacterium spp. serological re- logical reagents.
agents. 866.3490 Rhinovirus serological reagents.
866.3280 Francisella tularensis serological re- 866.3500 Rickettsia serological reagents.
agents. 866.3510 Rubella virus serological reagents.
866.3290 Gonococcal antibody test (GAT). 866.3520 Rubeola (measles) virus serological
866.3300 Haemophilus spp. serological re- reagents.
agents. 866.3550 Salmonella spp. serological reagents.
866.3305 Herpes simplex virus serological as- 866.3600 Schistosoma spp. serological re-
says. agents.
866.3309 Herpes virus nucleic acid-based cu- 866.3630 Serratia spp. serological reagents.
taneous and mucocutaneous lesion panel. 866.3660 Shigella spp. serological reagents.
866.3310 Hepatitis A virus (HAV) serological 866.3680 Sporothrix schenckii serological re-
assays. agents.
866.3320 Histoplasma capsulatum serological 866.3700 Staphylococcus aureus serological re-
reagents. agents.
866.3328 Influenza virus antigen detection 866.3720 Streptococcus spp. exoenzyme re-
test system. agents.
866.3330 Influenza virus serological re- 866.3740 Streptococcus spp. serological re-
agents. agents.
866.3332 Reagents for detection of specific 866.3780 Toxoplasma gondii serological re-
novel influenza A viruses. agents.
866.3336 John Cunningham Virus serological 866.3820 Treponema pallidum nontreponemal
reagents. test reagents.
866.3340 Klebsiella spp. serological reagents. 866.3830 Treponema pallidum treponemal test
866.3350 Leptospira spp. serological reagents. reagents.
866.3355 Listeria spp. serological reagents. 866.3850 Trichinella spiralis serological re-
866.3360 Lymphocytic choriomeningitis agents.
virus serological reagents. 866.3860 Trichomonas vaginalis nucleic acid
866.3361 Mass spectrometer system for clin- assay.
ical use for the identification of micro- 866.3870 Trypanosoma spp. serological re-
organisms. agents.
866.3365 Multiplex nucleic acid assay for 866.3900 Varicella-zoster virus serological
identification of microorganisms and re- reagents.
318
866.3920 Assayed quality control material 866.5080 Alpha-1-antichymotrypsin immuno-
for clinical microbiology assays. logical test system.
866.3930 Vibrio cholerae serological reagents. 866.5090 Antimitochondrial antibody
866.3940 West Nile virus serological re- immunological test system.
agents. 866.5100 Antinuclear antibody immuno-
866.3945 Dengue virus serological reagents. logical test system.
866.3946 Dengue virus nucleic acid amplifi- 866.5110 Antiparietal antibody immuno-
cation test reagents. logical test system.
866.3950 In vitro human immunodeficiency 866.5120 Antismooth muscle antibody
virus (HIV) drug resistance genotype immunological test system.
assay. 866.5130 Alpha-1-antitrypsin immunological
866.3955 Human immunodeficiency virus test system.
(HIV) drug resistance genotyping assay 866.5150 Bence-Jones proteins
using next generation sequencing tech- immunological test system.
nology. 866.5160 Beta-globulin immunological test
866.3956 Human immunodeficiency virus system.
(HIV) serological diagnostic and/or sup- 866.5170 Breast milk immunological test
plemental test. system.
866.3957 Human immunodeficiency virus 866.5180 Fecal calprotectin immunological
(HIV) nucleic acid (NAT) diagnostic and/ test system.
or supplemental test. 866.5200 Carbonic anhydrase B and C
866.3958 Human immunodeficiency virus immunological test system.
(HIV) viral load monitoring test. 866.5210 Ceruloplasmin immunological test
866.3960 Nucleic acid-based device for the system.
amplification, detection, and identifica- 866.5220 Cohn fraction II immunological test
tion of microbial pathogens directly system.
from whole blood specimens. 866.5230 Colostrum immunological test sys-
866.3970 Device to detect and identify micro- tem.
bial pathogen nucleic acids in cerebro- 866.5240 Complement components immuno-
spinal fluid. logical test system.
866.3980 Respiratory viral panel multiplex 866.5250 Complement C1 inhibitor (inact-
nucleic acid assay. ivator) immunological test system.
866.3985 Device to detect and identify micro- 866.5260 Complement C3b inactivator
organisms and associated resistance immunological test system.
marker nucleic acids directly in res- 866.5270 C-reactive protein immunological
piratory specimens. test system.
866.3990 Gastrointestinal microorganism 866.5320 Properidin factor B immunological
multiplex nucleic acid-based assay. test system.
866.5330 Factor XIII, A, S, immunological
Subpart E—Immunology Laboratory test system.
Equipment and Reagents 866.5340 Ferritin immunological test sys-
tem.
866.4070 RNA Preanalytical Systems. 866.5350 Fibrinopeptide A immunological
866.4100 Complement reagent. test system.
866.4500 Immunoelectrophoresis equipment. 866.5360 Cohn fraction IV immunological
866.4520 Immunofluorometer equipment. test system.
866.4540 Immunonephelometer equipment. 866.5370 Cohn fraction V immunological test
866.4600 Ouchterlony agar plate. system.
866.4700 Automated fluorescence in situ hy- 866.5380 Free secretory component immuno-
bridization (FISH) enumeration systems. logical test system.
866.4750 Automated indirect 866.5400 Alpha-globulin immunological test
immunofluorescence microscope and system.
software-assisted system. 866.5420 Alpha-1-glycoproteins immuno-
866.4800 Radial immunodiffusion plate. logical test system.
866.4830 Rocket immunoelectrophoresis 866.5425 Alpha-2-glycoproteins immuno-
equipment. logical test system.
866.4900 Support gel. 866.5430 Beta-2-glycoprotein I immuno-
logical test system.
Subpart F—Immunological Test Systems 866.5440 Beta-2-glycoprotein III immuno-
866.5040 Albumin immunological test sys- 866.5460 Haptoglobin immunological test
tem. system.
866.5060 Prealbumin immunological test 866.5470 Hemoglobin immunological test
system. system.
866.5065 Human allotypic marker immuno- 866.5490 Hemopexin immunological test sys-
logical test system. tem.
319
§ 866.1 21 CFR Ch. I (4–1–23 Edition)
866.5500 Hypersensitivity pneumonitis 866.5910 Quality control material for cystic
immunological test system. fibrosis nucleic acid assays.
866.5510 Immunoglobulins A, G, M, D, and E 866.5930 Newborn screening test for severe
immunological test system. combined immunodeficiency disorder
866.5520 Immunoglobulin G (Fab fragment (SCID).
specific) immunological test system. 866.5940 Autosomal recessive carrier screen-
866.5530 Immunoglobulin G (Fc fragment ing gene mutation detection system.
specific) immunological test system. 866.5950 Genetic health risk assessment sys-
866.5540 Immunoglobulin G (Fd fragment tem.
specific) immunological test system. 866.5960 Human leukocyte antigen typing
866.5550 Immunoglobulin (light chain spe- companion diagnostic test.
cific) immunological test system.
866.5560 Lactic dehydrogenase immuno- Subpart G—Tumor Associated Antigen
logical test system. Immunological Test Systems
866.5570 Lactoferrin immunological test sys-
tem. 866.6010 Tumor associated antigen
866.5580 Alpha-1-lipoprotein immunological immunological test system.
test system. 866.6020 Immunomagnetic circulating can-
866.5590 Lipoprotein X immunological test cer cell selection and enumeration sys-
system. tem.
866.5600 Low-density lipoprotein immuno- 866.6030 AFP-L3% immunological test sys-
logical test system. tem.
866.5620 Alpha-2-macroglobulin immuno- 866.6040 Gene expression profiling test sys-
logical test system. tem for breast cancer prognosis.
866.5630 Beta-2-microglobulin immuno- 866.6050 Ovarian adnexal mass assessment
logical test system. score test system.
866.5640 Infectious mononucleosis immuno- 866.6060 BCR-ABL quantitation test.
logical test system. 866.6080 Next generation sequencing based
866.5660 Multiple autoantibodies immuno- tumor profiling test.
logical test system. AUTHORITY: 21 U.S.C. 351, 360, 360c, 360e,
866.5665 Aquaporin-4 autoantibody 360j, 360l, 371.
immunological test system.
866.5670 Zinc transporter 8 autoantibody SOURCE: 47 FR 50823, Nov. 9, 1982, unless
immunological test system. otherwise noted.
866.5680 Myoglobin immunological test sys- EDITORIAL NOTE: Nomenclature changes to
tem. part 866 appear at 73 FR 35341, June 23, 2008.
866.5700 Whole human plasma or serum
866.5715 Plasminogen immunological test Subpart A—General Provisions
system.
866.5735 Prothrombin immunological test § 866.1 Scope.
system. (a) This part sets forth the classifica-
866.5750 Radioallergosorbent (RAST) tion of immunology and microbiology
immunological test system. devices intended for human use that
866.5760 Tryptase test system.
866.5765 Retinol-binding protein immuno-
are in commercial distribution.
logical test system. (b) The indentification of a device in
866.5775 Rheumatoid factor immunological a regulation in this part is not a pre-
test system. cise description of every device that is,
866.5785 Anti-Saccharomyces cerevisiae (S. or will be, subject to the regulation. A
cerevisiae) antibody (ASCA) test systems. manufacturer who submits a pre-
866.5800 Seminal fluid (sperm) immuno- market notification submission for a
logical test system. device under part 807 may not show
866.5820 Systemic lupus erythematosus
immunological test system. merely that the device is accurately
866.5830 Brain trauma assessment test. described by the section title and iden-
866.5860 Total spinal fluid immunological tification provisions of a regulation in
test system. this part, but shall state why the de-
866.5870 Thyroid autoantibody immuno- vice is substantially equivalent to
logical test system. other devices, as required by § 807.87.
866.5880 Transferrin immunological test sys- (c) To avoid duplicative listings, an
tem.
immunology and microbiology device
866.5890 Inter-alpha trypsin inhibitor
immunological test system. that has two or more types of uses
866.5900 Cystic fibrosis transmembrane con- (e.g., used both as a diagnostic device
ductance regulator (CFTR) gene muta- and as a microbiology device) is listed
tion detection system. only in one subpart.
320
(d) References in this part to regu- proval for a device, section 501(f)(1)(A)
latory sections of the Code of Federal of the act applies to the device.
Regulations are to chapter I of title 21, (b) Any new, not substantially equiv-
unless otherwise noted. alent, device introduced into commer-
(e) Guidance documents referenced in cial distribution on or after May 28,
this part are available on the Internet 1976, including a device formerly mar-
at http://www.fda.gov/MedicalDevices/ keted that has been substantially al-
DeviceRegulationandGuidance/ tered, is classified by statute (section
GuidanceDocuments/default.htm. 513(f) of the act) into class III without
FR 5827, Feb. 5, 2003; 79 FR 50552, Aug. 25, issued an order approving a PMA or de-
2014] claring completed a PDP for the device
§ 866.3 Effective dates of requirement tributed unless it is reclassified. If
for premarket approval. FDA knows that a device being com-
A device included in this part that is mercially distributed may be a ‘‘new’’
classified into class III (Premarket ap- device as defined in this section be-
proval) shall not be commercially dis- cause of any new intended use or other
tributed after the date shown in the reasons, FDA may codify the statutory
regulation classifying the device unless classification of the device into class
the manufacturer has an approval III for such new use. Accordingly, the
under section 515 of the act (unless an regulation for such a class III device
exemption has been granted under sec- states that as of the enactment date of
tion 520(g)(2) of the act). An approval the amendments, May 28, 1976, the de-
under section 515 of the act consists of vice must have an approval under sec-
(PMA) for the device or declaring com- (c) A device identified in a regulation
pleted a product development protocol in this part that is classified into class
(PDP) for the device. III and that is subject to the transi-
(a) Before FDA requires that a device tional provisions of section 520(l) of the
commercially distributed before the act is automatically classified by stat-
enactment date of the amendments, or ute into class III and must have an ap-
a device that has been found substan- proval under section 515 of the act be-
tially equivalent to such a device, has fore being commercially distributed.
an approval under section 515 of the act Accordingly, the regulation for such a
FDA must promulgate a regulation class III transitional device states that
under section 515(b) of the act requir- as of the enactment date of the amend-
ing such approval, except as provided ments, May 28, 1976, the device must
in paragraphs (b) and (c) of this sec- have an approval under section 515 of
tion. Such a regulation under section the act before commercial distribution.
515(b) of the act shall not be effective [52 FR 17733, May 11, 1987; 52 FR 22577, June
during the grace period ending on the 12, 1987]
90th day after its promulgation or on
the last day of the 30th full calendar § 866.9 Limitations of exemptions from
month after the regulation that classi- section 510(k) of the Federal Food,
fies the device into class III is effec- Drug, and Cosmetic Act (the act).
tive, whichever is later. See section The exemption from the requirement
501(f)(2)(B) of the act. Accordingly, un- of premarket notification (section
less an effective date of the require- 510(k) of the act) for a generic type of
ment for premarket approval is shown class I or II device is only to the extent
in the regulation for a device classified that the device has existing or reason-
into class III in this part, the device ably foreseeable characteristics of
may be commercially distributed with- commercially distributed devices with-
out FDA’s issuance of an order approv- in that generic type or, in the case of
ing a PMA or declaring completed a in vitro diagnostic devices, only to the
PDP for the device. If FDA promul- extent that misdiagnosis as a result of
gates a regulation under section 515(b) using the device would not be associ-
of the act requiring premarket ap- ated with high morbidity or mortality.
321
§ 866.1620 21 CFR Ch. I (4–1–23 Edition)
Accordingly, manufacturers of any are used to determine immunity, or the

commercially distributed class I or II assay is intended for use in matrices
device for which FDA has granted an other than serum or plasma;
exemption from the requirement of (8) For noninvasive testing as defined
premarket notification must still sub- in § 812.3(k) of this chapter; and
mit a premarket notification to FDA (9) For near patient testing (point of
before introducing or delivering for in- care).
for commercial distribution the device [65 FR 2311, Jan. 14, 2000]
when:
(a) The device is intended for a use Subpart B—Diagnostic Devices
different from the intended use of a le-
gally marketed device in that generic § 866.1620 Antimicrobial susceptibility
type of device; e.g., the device is in- test disc.
tended for a different medical purpose, (a) Identification. An antimicrobial
or the device is intended for lay use
susceptibility test disc is a device that
where the former intended use was by
consists of antimicrobic-impregnated
health care professionals only;
paper discs used to measure by a disc-
(b) The modified device operates
using a different fundamental sci- agar diffusion technique or a disc-broth
entific technology than a legally mar- elution technique the in vitro suscepti-
keted device in that generic type of de- bility of most clinically important bac-
vice; e.g., a surgical instrument cuts terial pathogens to antimicrobial
tissue with a laser beam rather than agents. In the disc-agar diffusion tech-
with a sharpened metal blade, or an in nique, bacterial susceptibility is
vitro diagnostic device detects or iden- ascertained by directly measuring the
tifies infectious agents by using magnitude of a zone of bacterial inhibi-
deoxyribonucleic acid (DNA) probe or tion around the disc on an agar sur-
nucleic acid hybridization technology face. The disc-broth elution technique
rather than culture or immunoassay is associated with an automated rapid
technology; or susceptibility test system and employs
(c) The device is an in vitro device a fluid medium in which susceptibility
that is intended: is ascertained by photometrically
(1) For use in the diagnosis, moni- measuring changes in bacterial growth
toring, or screening of neoplastic dis- resulting when antimicrobial material
eases with the exception of is eluted from the disc into the fluid
immunohistochemical devices; medium. Test results are used to deter-
(2) For use in screening or diagnosis mine the antimicrobial agent of choice
of familial or acquired genetic dis-
in the treatment of bacterial diseases.
orders, including inborn errors of me-
tabolism;
(3) For measuring an analyte that ance standards).
§ 866.1640 Antimicrobial susceptibility
screening, diagnosis, or monitoring test powder.
life-threatening diseases such as ac-
quired immune deficiency syndrome (a) Identification. An antimicrobial
(AIDS), chronic or active hepatitis, tu- susceptibility test powder is a device
berculosis, or myocardial infarction or that consists of an antimicrobial drug
to monitor therapy; powder packaged in vials in specified
(4) For assessing the risk of cardio- amounts and intended for use in clin-
vascular diseases; ical laboratories for determining in
(5) For use in diabetes management; vitro susceptibility of bacterial patho-
(6) For identifying or inferring the gens to these therapeutic agents. Test
identity of a microorganism directly results are used to determine the anti-
from clinical material; microbial agent of choice in the treat-
(7) For detection of antibodies to ment of bacterial diseases.
microorganisms other than (b) Classification. Class II (perform-

immunoglobulin G (IgG) or IgG assays ance standards).
when the results are not qualitative, or
322
§ 866.1645 Fully automated short-term vice must be cleared in a premarket

incubation cycle antimicrobial sus- submission as a part of this device.
ceptibility system. (3) The labeling required under
(a) Identification. A fully automated § 809.10(b) of this chapter must include:
short-term incubation cycle anti- (i) A detailed description of the de-
microbial susceptibility system is a device, including reagents, instruments,
vice that incorporates concentrations ancillary materials, applicable speci-
of antimicrobial agents into a system men collection and transport device(s)
for the purpose of determining in vitro and control elements, and a detailed
susceptibility of bacterial pathogens explanation of the methodology, in-
isolated from clinical specimens. Test cluding all pre-analytical methods for
results obtained from short-term (less handling and processing of specimens
than 16 hours) incubation are used to and controls to maintain organism via-
determine the antimicrobial agent of bility;
choice to treat bacterial diseases. (ii) Detailed descriptions of the test
(b) Classification. Class II (special procedure, including the preparation
controls). The special control for this and maintenance of quality controls
device is FDA’s guidance document en- and the interpretation of test results;
titled ‘‘Class II Special Controls Guid- (iii) Detailed discussion of the per-
ance Document: Antimicrobial Suscep- formance characteristics of the device
tibility Test (AST) Systems; Guidance for all claimed organisms and specimen
for Industry and FDA.’’ types based on analytical studies, in-
[68 FR 5827, Feb. 5, 2003] cluding evaluation of analytical sensi-
tivity, inclusivity, cross-reactivity, po-
§ 866.1655 System for detection of tentially interfering substances and
microorganisms and antimicrobial microorganisms, contamination, speci-
resistance using reporter expres- men stability, precision, and reproduc-
sion. ibility;
(a) Identification. A system for detec- (iv) Detailed discussion of the per-
tion of microorganisms and anti- formance characteristics of the device
microbial resistance using reporter ex- observed in a clinical study performed
pression is an in vitro diagnostic device on a population that is consistent with
intended for the detection and identi- the intended use population in com-
fication of live microorganisms and the parison to the results obtained by a
detection of associated antimicrobial reference or comparator method deter-
drug susceptibility or resistance in mined to be acceptable by FDA, for mi-
specimens from patients at risk of col- crobial detection, identification, and
onization or suspected of infection. antimicrobial susceptibility testing;
(b) Classification. Class II (special and
controls). The special controls for this (v) A limiting statement indicating
device are: that a negative test result does not
(1) The intended use for the device in preclude colonization or infection with
the labeling required under § 809.10 of organisms that do not express detect-
this chapter must include a detailed able levels of the reporter that is iden-
description of the targets the device tified by the device.
detects, the type of results provided to (4) Design verification and validation
the user, the clinical indications appro- must include:
priate for test use, and the specific pop- (i) A detailed description of the de-
ulation(s) for which the device is in- vice, including an explanation of the
tended. technology, hardware, software, and
(2) Any device used for specimen col- consumables, as well as an explanation
lection and transport must be FDA- of the result algorithms and method(s)
cleared, approved, or -classified as of data processing from signal acquisi-
510(k) exempt (standalone or as part of tion to result assignment;
a test system) for the collection of the (ii) A detailed description of the im-
specimen types claimed by this device pact of any software, including soft-
and for the maintenance of viability of ware applications and hardware-based

the targeted microorganisms; alter- devices that incorporate software, on
natively, the specimen collection de- the device’s functions;
323
§ 866.1700 21 CFR Ch. I (4–1–23 Edition)
(iii) Detailed documentation of the Subpart C—Microbiology Devices

analytical and clinical studies required
in paragraphs (b)(3)(iii) and (iv) of this § 866.2050 Staphylococcal typing
section, including the study protocols bacteriophage.
containing descriptions of the test (a) Identification. A staphylococcal
methods, prescribed methods of data typing bacteriophage is a device con-
analysis and acceptance criteria, final sisting of a bacterial virus intended for
study reports, and data line listings; medical purposes to identify patho-
(iv) Detailed documentation of qual- genic staphylococcal bacteria through
ity control procedures, including an ex- use of the bacteria’s susceptibility to
planation of how quality control mate- destruction by the virus. Test results
rials were selected, the recommended are used principally for the collection
frequency of testing, methods of con- of epidemiological information.
trol preparation, acceptance criteria (b) Classification. Class I (general con-
for performance and the results from trols). The device is exempt from the
quality control testing performed dur- premarket notification procedures in
ing the analytical and clinical studies subpart E of part 807 of this chapter
required under paragraphs (b)(3)(iii) subject to the limitations in § 866.9.
and (iv) of this section;
(v) Detailed documentation of studies [47 FR 50823, Nov. 9, 1982, as amended at 54
performed to establish onboard and in- FR 25045, June 12, 1989; 66 FR 38790, July 25,
use reagent stability, including the 2001]
test method(s), data analysis plans, ac-
§ 866.2120 Anaerobic chamber.
ceptance criteria, final study reports,
and data line listings; (a) Identification. An anaerobic cham-
(vi) Detailed documentation of stud- ber is a device intended for medical
ies to establish reagent shelf-life for purposes to maintain an anaerobic (ox-
the assay kit and each applicable speci- ygen free) environment. It is used to
men collection and transport device, isolate and cultivate anaerobic micro-
including study protocols containing organisms.
descriptions of the test method(s), data (b) Classification. Class I (general con-
analysis plans, and acceptance criteria; trols). The device is exempt from the
and premarket notification procedures in
(vii) Documentation of an appro- subpart E of part 807 of this chapter
priate end user device training pro- subject to the limitations in § 866.9. The
gram that will be offered as part of ef- device is also exempt from the good
forts to assure appropriate conduct of manufacturing practice requirements
the assay and to mitigate the risk as- of the quality system regulation in
sociated with false results, including part 820 of this chapter, with the excep-
failure to use the device correctly or tion of § 820.180, with respect to general
correctly interpret results. requirements concerning records, and
§ 820.198, with respect to complaint
[87 FR 6417, Feb. 4, 2022]
files.
§ 866.1700 Culture medium for anti- [47 FR 50823, Nov. 9, 1982, as amended at 66
microbial susceptibility tests. FR 38790, July 25, 2001]
(a) Identification. A culture medium
for antimicrobial susceptibility tests is § 866.2160 Coagulase plasma.
a device intended for medical purposes (a) Identification. Coagulase plasma is
that consists of any medium capable of a device that consists of freeze-dried
supporting the growth of many of the animal or human plasma that is in-
bacterial pathogens that are subject to tended for medical purposes to perform
antimicrobial susceptibility tests. The coagulase tests primarily on staphy-
medium should be free of components lococcal bacteria. When reconstituted,
known to be antagonistic to the com- the fluid plasma is clotted by the ac-
mon agents for which susceptibility tion of the enzyme coagulase which is
tests are performed in the treatment of produced by pathogenic staphylococci.
disease. Test results are used primarily as an

(b) Classification. Class II (perform- aid in the diagnosis of disease caused
ance standards). by pathogenic bacteria belonging to
324
the genus Staphylococcus and provide § 866.2190 Automated image assess-

epidemiological information on disease ment system for microbial colonies
caused by these microorganisms. on solid culture media.
(b) Classification. Class I (general con- (a) Identification. An automated
trols). The device is exempt from the image assessment system for microbial
premarket notification procedures in colonies on solid culture media is a
subpart E of part 807 of this chapter system that is intended to assess the
subject to the limitations in § 866.9. presence or absence of microbial colo-
[47 FR 50823, Nov. 9, 1982, as amended at 61 nies on solid microbiological culture
FR 1119, Jan. 16, 1996; 66 FR 38790, July 25, medium, and to interpret their num-
2001] ber, and phenotypic and morphologic
characteristics through analysis of two
§ 866.2170 Automated colony counter. dimensional digital images as an aid in
(a) Identification. An automated col- diagnosis of infectious disease.
ony counter is a mechanical device in- (b) Classification. Class II (special
tended for medical purposes to deter- controls). The special controls for this
mine the number of bacterial colonies device are:
present on a bacteriological culture (1) Premarket notification submis-
medium contained in a petri plate. The sions must include a detailed descrip-
number of colonies counted is used in tion of the device, including the tech-
the diagnosis of disease as a measure of nology employed, components and soft-
the degree of bacterial infection. ware modules, as well as a detailed ex-
(b) Classification. Class I (general con- planation of the result algorithms and
trols). The device is exempt from the any expert rules that are used to assess
premarket notification procedures in colony characteristics and enumerate
subpart E of part 807 of this chapter colonies from image capture through
subject to the limitations in § 866.9. end result.
[47 FR 50823, Nov. 9, 1982, as amended at 54 sions must include detailed docu-
FR 25045, June 12, 1989; 66 FR 38790, July 25,
mentation of the analytical studies
2001]
performed to characterize device per-
§ 866.2180 Manual colony counter. formance to support the intended use,
as appropriate.
(a) Identification. A manual colony (3) Premarket notification submis-
counter is a device intended for med- sions must include detailed docu-
ical purposes that consists of a printed mentation from clinical studies per-
grid system superimposed on an illumi- formed on a population that is con-
nated screen. Petri plates containing sistent with the intended use popu-
bacterial colonies to be counted are lation.
placed on the screen for better viewing (i) The clinical studies must estab-
and ease of counting. The number of lish the device performance based on
colonies counted is used in the diag- comparison to results obtained by an
nosis of disease as a measure of the de- acceptable reference method, as appro-
gree of bacterial infection. priate.
(b) Classification. Class I (general con- (ii) The clinical study documentation
trols). The device is exempt from the must include the study protocol with a
premarket notification procedures in predefined statistical analysis plan and
subpart E of part 807 of this chapter the final report documenting support
subject to the limitations in § 866.9. The for the Indications for Use and the re-
device is also exempt from the good sults of the statistical analysis, as ap-
manufacturing practice requirements propriate.
of the quality system regulation in (4) Premarket notification submis-
part 820 of this chapter, with the excep- sions must include detailed docu-
tion of § 820.180, with respect to general mentation for device software, includ-
requirements concerning records, and ing but not limited to software applica-
§ 820.198, with respect to complaint tions and hardware based components
files.
that incorporate software, and any de-

[47 FR 50823, Nov. 9, 1982, as amended at 66 cision-making thresholds used to gen-
FR 38790, July 25, 2001] erate results for the device. If a part of
325
§ 866.2300 21 CFR Ch. I (4–1–23 Edition)
a Total Laboratory Automation Sys- information on diseases caused by

tem, the premarket notification sub- these microorganisms.
mission must include detailed docu- (b) Classification. Class I (general con-
mentation addressing the instrument trols). The device is exempt from the
and software system integration. premarket notification procedures in
(5) Premarket notification submis- subpart E of part 807 of this chapter
sions must include detailed docu- subject to the limitations in § 866.9.
mentation of appropriate instructions [47 FR 50823, Nov. 9, 1982, as amended at 54
for use regarding the intended user’s FR 25046, June 12, 1989; 66 FR 38790, July 25,
device quality control procedures for 2001]
the instrument system and compo-
nents, as appropriate. § 866.2320 Differential culture me-
(6) The 21 CFR 809.10 compliant de- dium.
vice labeling must include: (a) Identification. A differential cul-
(i) Detailed user instructions to miti- ture medium is a device that consists
gate the risk of failure to operate the primarily of liquid biological materials
instrument correctly. intended for medical purposes to cul-
(ii) A detailed explanation of the in- tivate and identify different types of
terpretation of results and limitations pathogenic microorganisms. The iden-
regarding the need for review of cul- tification of these microorganisms is
ture plates by a qualified microbiolo- accomplished by the addition of a spe-
gist, as appropriate. cific biochemical component(s) to the
(iii) A summary of performance data medium. Microorganisms are identified
obtained from the analytical studies by a visible change (e.g., a color
used to support device performance, as change) in a specific biochemical com-
appropriate. ponent(s) which indicates that specific
(iv) A summary of performance data metabolic reactions have occurred.
obtained from clinical studies per- Test results aid in the diagnosis of dis-
formed on a population that is con- ease and also provide epidemiological
sistent with the intended use popu- information on diseases caused by
lation, as appropriate. these microorganisms.
(7) Under 21 CFR 820.30 compliant de- (b) Classification. Class I (general con-
sign control, device manufacturers trols). The device is exempt from the
must, as appropriate: premarket notification procedures in
(i) Conduct human factors/usability subpart E of part 807 of this chapter
validation testing with the final subject to the limitations in § 866.9.
version of the labeling and related ma-
terials to adequately mitigate the risk FR 25046, June 12, 1989; 66 FR 38790, July 25,
of failure to operate the instrument 2001]
correctly.
(ii) Document a device training pro- § 866.2330 Enriched culture medium.
gram that will be offered to the end (a) Identification. An enriched culture
user to adequately mitigate the risk of medium is a device that consists pri-
failure to operate the instrument cor- marily of liquid or solid biological ma-
rectly. terials intended for medical purposes
[82 FR 47969, Oct. 16, 2017] to cultivate and identify fastidious
microorganisms (those having complex
§ 866.2300 Multipurpose culture me- nutritional requirements). The device
dium. consists of a relatively simple basal
(a) Identification. A multipurpose cul- medium enriched by the addition of
ture medium is a device that consists such nutritional components as blood,
primarily of liquid or solid biological blood serum, vitamins, and extracts of
materials intended for medical pur- plant or animal tissues. The device is
poses for the cultivation and identi- used in the diagnosis of disease caused
fication of several types of pathogenic by pathogenic microorganisms and also
microorganisms without the need of provides epidemiological information
additional nutritional supplements. on these diseases.

Test results aid in the diagnosis of dis- (b) Classification. Class I (general con-
ease and also provide epidemiological trols). The device is exempt from the
326
premarket notification procedures in subpart E of part 807 of this chapter

subpart E of part 807 of this chapter subject to the limitations in § 866.9.
subject to the limitations in § 866.9. [47 FR 50823, Nov. 9, 1982, as amended at 54
[47 FR 50823, Nov. 9, 1982, as amended at 54 FR 25046, June 12, 1989; 66 FR 38791, July 25,
FR 25046, June 12, 1989; 66 FR 38791, July 25, 2001]
2001]
§ 866.2390 Transport culture medium.
§ 866.2350 Microbiological assay cul- (a) Identification. A transport culture
ture medium. medium is a device that consists of a
(a) Identification. A microbiological semisolid, usually non-nutrient, me-
assay culture medium is a device that dium that maintains the viability of
consists primarily of liquid or solid bi- suspected pathogens contained in pa-
ological materials intended for medical tient specimens while in transit from
purposes to cultivate selected test the specimen collection area to the
microorganisms in order to measure by laboratory. The device aids in the diag-
microbiological procedures the con- nosis of disease caused by pathogenic
centration in a patient’s serum of cer- microorganisms and also provides epi-
tain substances, such as amino acids, demiological information on these dis-
antimicrobial agents, and vitamins. eases.
The concentration of these substances (b) Classification. Class I (general con-
is measured by their ability to promote trols).
or inhibit the growth of the test orga-
§ 866.2410 Culture medium for patho-
nism in the innoculated medium. Test genic Neisseria spp.
results aid in the diagnosis of disease
resulting from either deficient or ex- (a) Identification. A culture medium
cessive amounts of these substances in for pathogenic Neisseria spp. is a device
a patient’s serum. Tests results may that consists primarily of liquid or
also be used to monitor the effects of solid biological materials used to cul-
the administration of certain anti- tivate and identify pathogenic Neisseria
microbial drugs. spp. The identification aids in the diag-
(b) Classification. Class I (general con- nosis of disease caused by bacteria be-
trols). The device is exempt from the longing to the genus Neisseria, such as
premarket notification procedures in epidemic cerebrospinal meningitis,
subpart E of part 807 of this chapter other meningococcal disease, and gon-
subject to the limitations in § 866.9. orrhea, and also provides epidemiolog-
ical information on these microorga-
[47 FR 50823, Nov. 9, 1982, as amended at 54 nisms.
FR 25046, June 12, 1989; 66 FR 38791, July 25, (b) Classification. Class II (perform-
2001] ance standards).
§ 866.2360 Selective culture medium. § 866.2420 Oxidase screening test for
(a) Identification. A selective culture gonorrhea.
medium is a device that consists pri- (a) Identification. An oxidase screen-
marily of liquid or solid biological ma- ing test for gonorrhea is an in vitro de-
terials intended for medical purposes vice that consists of the articles in-
to cultivate and identify certain patho- tended to identify by chemical reac-
genic microorganisms. The device con- tion, cytochrome oxidase, an oxidizing
tains one or more components that enzyme that is associated with certain
suppress the growth of certain micro- bacteria including Neisseria
organisms while either promoting or gonorrhoeae. A sample of a male’s
not affecting the growth of other urethral discharge is obtained on a
microorganisms. The device aids in the swab which is placed into a wetting
diagnosis of disease caused by patho- agent containing an ingredient that
genic microorganisms and also pro- will react with cytochrome oxidase.
vides epidemiological information on When cytochrome oxidase is present,
these diseases. the swab turns a dark purple color
(b) Classification. Class I (general con- within 3 minutes. Because it is un-

trols). The device is exempt from the likely that cytochrome oxidase-posi-
premarket notification procedures in tive organisms other than Neisseria
327
§ 866.2440 21 CFR Ch. I (4–1–23 Edition)
gonorrhoeae are present in the urethral subpart E of part 807 of this chapter
discharge of males, the identification subject to the limitations in § 866.9.
of cytochrome oxidase with this device
indicates presumptive infection of the FR 25046, June 12, 1989; 66 FR 38791, July 25,
patient with the causative agent of 2001]
gonorrhea.
(b) Classification. Class III (premarket § 866.2480 Quality control kit for cul-
approval) (transitional device). ture media.
(c) Date PMA or notice of completion of (a) Identification. A quality control
a PDP is required. As of May 28, 1976, an kit for culture media is a device that
approval under section 515 of the act is consists of paper discs (or other suit-
required before this device may be able materials), each impregnated with
commercially distributed. See § 866.3. a specified, freeze-dried, viable micro-
[47 FR 50823, Nov. 9, 1982, as amended at 52 organism, intended for medical pur-
FR 17734, May 11, 1987] poses to determine if a given culture
medium is able to support the growth
§ 866.2440 Automated medium dis- of that microorganism. The device aids
pensing and stacking device. in the diagnosis of disease caused by
(a) Identification. An automated me- pathogenic microorganisms and also
dium dispensing and stacking device is provides epidemiological information
a device intended for medical purposes on these diseases.
to dispense a microbiological culture (b) Classification. Class I (general con-
medium into petri dishes and then me- trols). The device is exempt from the
chanically stack the petri dishes. premarket notification procedures in
premarket notification procedures in [47 FR 50823, Nov. 9, 1982, as amended at 54
subpart E of part 807 of this chapter FR 25046, June 12, 1989; 66 FR 38791, July 25,
subject to the limitations in § 866.9. The 2001]
device is also exempt from the good
manufacturing practice requirements § 866.2500 Microtiter diluting and dis-
of the quality system regulation in pensing device.
part 820 of this chapter, with the excep- (a) Identification. A microtiter dilut-
tion of § 820.180, with respect to general ing and dispensing device is a mechan-
requirements concerning records, and ical device intended for medical pur-
§ 820.198, with respect to complaint poses to dispense or serially dilute very
files. small quantities of biological or chem-
ical reagents for use in various diag-
FR 38791, July 25, 2001] nostic procedures.
§ 866.2450 Supplement for culture trols). The device is exempt from the
media. premarket notification procedures in
(a) Identification. A supplement for subpart E of part 807 of this chapter
culture media is a device, such as a vi- subject to the limitations in § 866.9.
tamin or sugar mixture, that is added [47 FR 50823, Nov. 9, 1982, as amended at 54
to a solid or liquid basal culture me- FR 25046, June 12, 1989; 66 FR 38791, July 25,
dium to produce a desired formulation 2001]
and that is intended for medical pur-
poses to enhance the growth of fas- § 866.2540 Microbiological incubator.
tidious microorganisms (those having (a) Identification. A microbiological
complex nutritional requirements). incubator is a device with various
This device aids in the diagnosis of dis- chambers or water-filled compartments
eases caused by pathogenic microorga- in which controlled environmental con-
nisms. ditions, particularly temperature, are
(b) Classification. Class I (general con- maintained. It is intended for medical

trols). The device is exempt from the purposes to cultivate microorganisms
premarket notification procedures in and aid in the diagnosis of disease.
328
(b) Classification. Class I (general con- § 866.2600 Wood’s fluorescent lamp.

trols). The device is exempt from the (a) Identification. A Wood’s fluores-
premarket notification procedures in cent lamp is a device intended for med-
subpart E of part 807 of this chapter ical purposes to detect fluorescent ma-
subject to the limitations in § 866.9. The terials (e.g., fluorescein pigment pro-
device is also exempt from the good duced by certain microorganisms) as
manufacturing practice requirements an aid in the identification of these
of the quality system regulation in microorganisms. The device aids in the
part 820 of this chapter, with the excep- diagnosis of disease.
tion of § 820.180, with respect to general (b) Classification. Class I (general con-
requirements concerning records, and trols). The device is exempt from the
§ 820.198, with respect to complaint premarket notification procedures in
files. subpart E of part 807 of this chapter
[47 FR 50823, Nov. 9, 1982, as amended at 66 subject to the limitations in § 866.9. The
FR 38791, July 25, 2001] device is also exempt from the good
manufacturing practice requirements
§ 866.2560 Microbial growth monitor. of the quality system regulation in
(a) Identification. A microbial growth part 820 of this chapter, with the excep-
monitor is a device intended for med- tion of § 820.180, with respect to general
ical purposes that measures the con- requirements concerning records, and
centration of bacteria suspended in a § 820.198, with respect to complaint
liquid medium by measuring changes files.
in light scattering properties, optical [47 FR 50823, Nov. 9, 1982, as amended at 66
density, electrical impedance, or by FR 38791, July 25, 2001]
making direct bacterial counts. The
device aids in the diagnosis of disease § 866.2660 Microorganism differentia-
caused by pathogenic microorganisms. tion and identification device.
(b) Classification. Class I. With the ex- (a) Identification. A microorganism
ception of automated blood culturing differentiation and identification de-
system devices that are used in testing vice is a device intended for medical
for bacteria, fungi, and other micro- purposes that consists of one or more
organisms in blood and other normally components, such as differential cul-
sterile body fluids, this device is ex- ture media, biochemical reagents, and
empt from the premarket notification paper discs or paper strips impregnated
procedures in subpart E of part 807 of with test reagents, that are usually
this chapter. contained in individual compartments
and used to differentiate and identify
[47 FR 50823, Nov. 9, 1982, as amended at 60 selected microorganisms. The device
FR 38482, July 27, 1995]
aids in the diagnosis of disease.
§ 866.2580 Gas-generating device.
(a) Identification. A gas-generating premarket notification procedures in
device is a device intended for medical subpart E of part 807 of this chapter
purposes that produces predetermined subject to § 866.9.
amounts of selected gases to be used in
a closed chamber in order to establish FR 2311, Jan. 14, 2000]
suitable atmospheric conditions for
cultivation of microorganisms with § 866.2680 Streptococcus spp. nucleic
special atmospheric requirements. The acid-based assay.
device aids in the diagnosis of disease. (a) Identification. A Streptococcus spp.
(b) Classification. Class I (general con- nucleic acid-based assay is a quali-
trols). The device is exempt from the tative in vitro diagnostic device in-
premarket notification procedures in tended to simultaneously detect and
subpart E of part 807 of this chapter identify various Streptococcus spp. nu-
subject to the limitations in § 866.9. cleic acids extracted directly from clin-
[47 FR 50823, Nov. 9, 1982, as amended at 54 ical specimens. The device detects spe-
FR 25046, June 12, 1989; 66 FR 38791, July 25, cific nucleic acid sequences for orga-
2001] nism identification. The identification
329
§ 866.2850 21 CFR Ch. I (4–1–23 Edition)
aids in the diagnosis of diseases caused (8) Premarket notification submis-

by bacteria belonging to the genus sions must include details on an end
Streptococcus and provides epidemiolog- user device training program that will
ical information on these diseases. be offered while marketing the device,
Pathogenic streptococci are associated as appropriate.
with infections, such as sore throat, [82 FR 50074, Oct. 30, 2017]
impetigo (an infection characterized by
small pustules on the skin), urinary § 866.2850 Automated zone reader.
tract infections, rheumatic fever, and
(a) Identification. An automated zone
kidney disease.
reader is a mechanical device intended
for medical purposes to measure zone
diameters of microbial growth inhibi-
device are:
tion (or exhibition), such as those ob-
served on the surface of certain culture
sions must include detailed device de-
media used in disc-agar diffusion anti-
scription documentation, including the
microbial susceptibility tests. The de-
device components, ancillary reagents
vice aids in decisionmaking respecting
required but not provided, and a de-
the treatment of disease.
tailed explanation of the methodology
including primer/probe sequence, de-
trols).
sign, and rationale for sequence selec-
tion. § 866.2900 Microbiological specimen
(2) Premarket notification submis- collection and transport device.
sions must include detailed docu-
(a) Identification. A microbiological
mentation from the following analyt-
specimen collection and transport de-
ical and clinical performance studies:
vice is a specimen collecting chamber
Analytical sensitivity (Limit of Detec-
intended for medical purposes to pre-
tion), reactivity, inclusivity, precision,
serve the viability or integrity of
reproducibility, interference, cross re-
microorganisms in specimens during
activity, carry-over, and cross con-
storage of specimens after their collec-
tamination.
tion and during their transport from
the collecting area to the laboratory.
The device may be labeled or otherwise
mentation from a clinical study. The
represented as sterile. The device aids
study, performed on a study population
in the diagnosis of disease caused by
consistent with the intended use popu-
pathogenic microorganisms.
lation, must compare the device per-
formance to results obtained from
trols). The device, when solely intended
well-accepted reference methods.
for use in the collection of con-
centrated parasites from specimens and
transport, is exempt from the pre-
mentation for device software, includ-
ing, but not limited to, software appli-
cations and hardware-based devices
that incorporate software.
(5) Premarket notification submis- [47 FR 50823, Nov. 9, 1982, as amended at 84
sions must include database implemen- FR 71800, Dec. 30, 2019; 85 FR 18445, Apr. 2,
tation methodology, construction pa- 2020]
rameters, and quality assurance proto-
cols, as appropriate. Subpart D—Serological Reagents
(6) The device labeling must include
limitations regarding the need for cul- § 866.3010 Acinetobacter calcoaceticus
ture confirmation of negative speci- serological reagents.
mens, as appropriate. (a) Identification. Acinetobacter
(7) A detailed explanation of the in- calcoaceticus serological reagents are
terpretation of results and acceptance devices that consist of Acinetobacter
criteria must be included in the de- calcoaceticus antigens and antisera used
vice’s 21 CFR 809.10(b)(9) compliant la- to identify this bacterium from cul-
beling. tured isolates derived from clinical
330
specimens. The identification aids in caused by these microorganisms. Ari-

the diagnosis of disease caused by the zona spp. can cause gastroenteritis
bacterium Acinetobacter calcoaceticus (food poisoning) and sepsis (blood poi-
and provides epidemiological informa- soning).
tion on disease caused by this micro- (b) Classification. Class I (general con-
organism. This organism becomes trols). The device is exempt from the
pathogenic in patients with burns or premarket notification procedures in
with immunologic deficiency, and in- subpart E of part 807 of this chapter
fection can result in sepsis (blood poi- subject to the limitations in § 866.9.
soning).
(b) Classification. Class I (general con- [47 FR 50823, Nov. 9, 1982, as amended at 54
FR 25046, June 12, 1989; 66 FR 38791, July 25,
2001]
subpart E of part 807 of this chapter § 866.3040 Aspergillus spp. serological
subject to the limitations in § 866.9. reagents.
[47 FR 50823, Nov. 9, 1982, as amended at 54 (a) Identification. Aspergillus spp. sero-
FR 25046, June 12, 1989; 66 FR 38791, July 25, logical reagents are devices that con-
2001]
sist of antigens and antisera used in
§ 866.3020 Adenovirus serological re- various serological tests to identify
agents. antibodies to Aspergillus spp. in serum.
The identification aids in the diagnosis
(a) Identification. Adenovirus sero-
of aspergillosis caused by fungi belong-
logical reagents are devices that con-
ing to the genus Aspergillus.
sist of antigens and antisera used in se-
Aspergillosis is a disease marked by in-
rological tests to identify antibodies to
flammatory granulomatous (tumor-
adenovirus in serum. Additionally,
like) lessions in the skin, ear, eyeball
some of these reagents consist of
adenovirus antisera conjugated with a cavity, nasal sinuses, lungs, and occa-
fluorescent dye and are used to identify sionally the bones.
adenoviruses directly from clinical (b) Classification. Class I (general con-
specimens. The identification aids in trols). The device is exempt from the
the diagnosis of disease caused by premarket notification procedures in
adenoviruses and provides epidemiolog- subpart E of part 807 of this chapter
ical information on these diseases. subject to § 866.9.
Adenovirus infections may cause phar- [47 FR 50823, Nov. 9, 1982, as amended at 65
yngitis (inflammation of the throat), FR 2311, Jan. 14, 2000]
acute respiratory diseases, and certain
external diseases of the eye (e.g., con- § 866.3045 In vitro diagnostic device
junctivitis). for Bacillus spp. detection.
(b) Classification. Class I (general con- (a) Identification. An in vitro diag-
trols). The device is exempt from the nostic device for Bacillus species (spp.)
premarket notification procedures in detection is a prescription device used
subpart E of part 807 of this chapter to detect and differentiate among Ba-
subject to the limitations in § 866.9. cillus spp. and presumptively identify
[47 FR 50823, Nov. 9, 1982, as amended at 54 B. anthracis and other Bacillus spp.
FR 25046, June 12, 1989; 66 FR 38791, July 25, from cultured isolates or clinical speci-
2001] mens as an aid in the diagnosis of an-
thrax and other diseases caused by Ba-
§ 866.3035 Arizona spp. serological re- cillus spp. This device may consist of
agents. Bacillus spp. antisera conjugated with a
(a) Identification. Arizona spp. sero- fluorescent dye (immunofluorescent re-
logical reagents are devices that con- agents) used to presumptively identify
sist of antisera and antigens used to bacillus-like organisms in clinical
identify Arizona spp. in cultured iso- specimens; bacteriophage used for dif-
lates derived from clinical specimens. ferentiating B. anthracis from other Ba-
The identification aids in the diagnosis cillus spp. based on susceptibility to
of disease caused by bacteria belonging lysis by the phage; or antigens used to

to the genus Arizona and provides epi- identify antibodies to B. anthracis
demiological information on diseases (anti-toxin and anti-capsular) in
331
§ 866.3050 21 CFR Ch. I (4–1–23 Edition)
serum. Bacillus infections include an- cluding indications, effects, routes,

thrax (cutaneous, inhalational, or gas- methods, and frequency and duration
trointestinal) caused by B. anthracis, of administration and any relevant
and gastrointestinal disease and non- hazards, contraindications, side effects,
gastrointestinal infections caused by and precautions, under which practi-
B. cereus. tioners licensed by law to employ the
(b) Classification. Class II (special device can use the device safely and for
controls). The special controls are set the purposes for which it is intended,
forth in FDA’s special controls guide- including all purposes for which it is
line document entitled ‘‘In Vitro Diag- advertised or represented. This infor-
nostic Devices for Bacillus spp. Detec- mation will not be required on so-
tion; Class II Special Controls Guide- called reminder-piece labeling which
line for Industry and Food and Drug calls attention to the name of the de-
Administration Staff.’’ For availability vice but does not include indications or
of the guideline document, see other use information.
§ 866.1(e). (4) All labeling, except labels and car-
(c) Restriction on Distribution. The dis- tons, bearing information for use of the
tribution of these devices is limited to device also bears the date of the
laboratories that follow public health issuance or the date of the latest revi-
guidelines that address appropriate sion of such labeling.
biosafety conditions, interpretation of
[84 FR 12088, Apr. 1, 2019]
test results, and coordination of find-
ings with public health authorities. § 866.3050 Beta-glucan serological as-
(d) Restriction on Use. The use of this says.
device is restricted to prescription use
(a) Identification. Beta-glucan sero-
and must comply with the following:
logical assays are devices that consist
(1) The device must be in the posses-
of antigens or proteases used in sero-
sion of:
logical assays. The device is intended
(i)(A) A person, or his agents or em-
for use for the presumptive diagnosis of
ployees, regularly and lawfully engaged
fungal infection. The assay is indicated
in the manufacture, transportation,
for use in patients with symptoms of,
storage, or wholesale or retail distribu-
or medical conditions predisposing the
tion of such device; or
patient to invasive fungal infection.
(B) A practitioner, such as a physi-
The device can be used as an aid in the
cian, licensed by law to use or order
diagnosis of deep seated mycoses and
the use of such device; and
fungemias.
(ii) The device must be sold only to
or on the prescription or other order of
such practitioner for use in the course
of his professional practice.
Special Controls Guidance Document:
(2) The label of the device shall bear
Serological Assays for the Detection of
the statement ‘‘Caution: Federal law
Beta-Glucan.’’ See § 866.1(e) for the
restricts this device to sale by or on
availability of this guidance document.
the order of a ____’’, the blank to be
filled with the word ‘‘physician’’ or [69 FR 56936, Sept. 23, 2004]
with the descriptive designation of any
other practitioner licensed by the law § 866.3060 Blastomyces dermatitidis se-
of the State in which he practices to rological reagents.
use or order the use of the device. (a) Identification. Blastomyces
(3) Any labeling, as defined in section dermatitidis serological reagents are de-
201(m) of the Federal Food, Drug, and vices that consist of antigens and
Cosmetic Act, whether or not it is on antisera used in serological tests to
or within a package from which the de- identify antibodies to Blastomyces
vice is to be dispensed, distributed by, determatitidis in serum. The identifica-
or on behalf of the manufacturer, pack- tion aids in the diagnosis of blasto-
er, or distributor of the device, that mycosis caused by the fungus
furnishes or purports to furnish infor- Blastomyces dermatitidis. Blastomycosis

mation for use of the device contains is a chronic granulomatous (tumor-
adequate information for such use, in- like) disease, which may be limited to
332
the skin or lung or may be widely dis- and provides epidemiological informa-
seminated in the body resulting in le- tion on diseases caused by these micro-
sions of the bones, liver, spleen, and organisms.
kidneys. (b) Classification. Class II (special
(b) Classification. Class II (special controls). The device is exempt from
controls). The device is exempt from the premarket notification procedures
the premarket notification procedures in subpart E of part 807 of this chapter
in subpart E of part 807 of this chapter subject to § 866.9.
[47 FR 50823, Nov. 9, 1982, as amended at 63 FR 59226, Nov. 3, 1998]
FR 59226, Nov. 3, 1998]
§ 866.3065 Bordetella spp. serological § 866.3110 Campylobacter fetus sero-

reagents. logical reagents.
(a) Identification. Bordetella spp. sero- (a) Identification. Campylobacter fetus
logical reagents are devices that con- serological reagents are devices that
sist of antigens and antisera, including consist of antisera conjugated with a
antisera conjugated with a fluorescent fluorescent dye used to identify
dye, used in serological tests to iden- Campylobacter fetus from clinical speci-
tify Bordetella spp. from cultured iso- mens or cultured isolates derived from
lates or directly from clinical speci- clinical specimens. The identification
mens. The identification aids in the di- aids in the diagnosis of diseases caused
agnosis of diseases caused by bacteria by this bacterium and provides epide-
belonging to the genus Bordetella and miological information on these dis-
provides epidemiological information eases. Campylobacter fetus is a frequent
on these diseases. Bordetella spp. cause cause of abortion in sheep and cattle
whooping cough (Bordetella pertussis) and is sometimes responsible for endo-
and other similiarly contagious and carditis (inflammation of certain mem-
acute respiratory infections character- branes of the heart) and enteritis (in-
ized by pneumonitis (inflammation of flammation of the intestines) in hu-
the lungs). mans.
trols). The device is exempt from the trols).
subpart E of part 807 of this chapter § 866.3120 Chlamydia serological re-
subject to the limitations in § 866.9. agents.
[47 FR 50823, Nov. 9, 1982, as amended at 54 (a) Identification. Chlamydia sero-
FR 25046, June 12, 1989; 66 FR 38791, July 25, logical reagents are devices that con-
2001]
§ 866.3085 Brucella spp. serological re- rological tests to identify antibodies to
agents. chlamydia in serum. Additionally,
(a) Identification. Brucella spp. sero- some of these reagents consist of
logical reagents are devices that con- chlamydia antisera conjugated with a
sist of antigens and antisera used for fluorescent dye used to identify
serological identification of Brucella chlamydia directly from clinical speci-
spp. from cultured isolates derived mens or cultured isolates derived from
from clinical specimens or to identify clinical specimens. The identification
antibodies to Brucella spp. in serum. aids in the diagnosis of disease caused
Additionally, some of these reagents by bacteria belonging to the genus
consist of antisera conjugated with a Chlamydia and provides epidemiolog-
fluorescent dye (immunofluorescent re- ical information on these diseases.
agents) used to identify Brucella spp. Chlamydia are the causative agents of
directly from clinical specimens or cul- psittacosis (a form of pneumonia),
tured isolates derived from clinical lymphogranuloma venereum (a vene-
specimens. The identification aids in real disease), and trachoma (a chronic
the diagnosis of brucellosis (e.g., undu- disease of the eye and eyelid).
lant fever, Malta fever) caused by bac- (b) Classification. Class I (general con-
teria belonging to the genus Brucella trols).
333
§ 866.3125 21 CFR Ch. I (4–1–23 Edition)
§ 866.3125 Citrobacter spp. serological identification aids in the diagnosis of

reagents. coccidioidomycosis caused by a fungus
(a) Identification. Citrobacter spp. sero- belonging to the genus Coccidioides and
logical reagents are devices that con- provides epidemiological information
sist of antigens and antisera used in se- on diseases caused by this microorga-
rological tests to identify Citrobacter nism. An infection with Coccidioides
spp. from cultured isolates derived immitis produces symptoms varying in
from clinical specimens. The identi- severity from those accompanying the
fication aids in the diagnosis of disease common cold to those of influenza.
caused by bacteria belonging to the
genus Citrobacter and provides epide-
miological information on diseases
caused by these microorganisms.
Citrobacter spp. have occasionally been
associated with urinary tract infec- [47 FR 50823, Nov. 9, 1982, as amended at 63
tions. FR 59226, Nov. 3, 1998]
trols). The device is exempt from the § 866.3140 Corynebacterium spp. sero-
logical reagents.
subpart E of part 807 of this chapter (a) Identification. Corynebacterium spp.
subject to the limitations in § 866.9. serological reagents are devices that
consist of antisera conjugated with a
[47 FR 50823, Nov. 9, 1982, as amended at 54 fluorescent dye used to identify
FR 25046, June 12, 1989; 66 FR 38791, July 25, Corynebacterium spp. from clinical
2001]
specimens. The identification aids in
§ 866.3130 Clostridium difficile toxin the diagnosis of disease caused by bac-
gene amplification assay. teria belonging to the genus
Corynebacterium and provides epidemio-
(a) Identification. A Clostridium logical information on diseases caused
difficile toxin gene amplification assay by these microorganisms. The principal
is a device that consists of reagents for human pathogen of this genus,
the amplification and detection of tar- Corynebacterium diphtheriae, causes
get sequences in Clostridium difficile diphtheria. However, many other types
toxin genes in fecal specimens from pa- of corynebacteria form part of the nor-
tients suspected of having Clostridium mal flora of the human respiratory
difficile infection (CDI). The detection tract, other mucus membranes, and
of clostridial toxin genes, in conjunc- skin, and are either nonpathogenic or
tion with other laboratory tests, aids have an uncertain role.
in the clinical laboratory diagnosis of (b) Classification. Class I (general con-
CDI caused by Clostridium difficile. trols). The device is exempt from the
(b) Classification. Class II (special premarket notification procedures in
controls). The special controls are set subpart E of part 807 of this chapter
forth in FDA’s guideline document en- subject to § 866.9.
titled: ‘‘Class II Special Controls
Guideline: Toxin Gene Amplification [47 FR 50823, Nov. 9, 1982, as amended at 65
FR 2311, Jan. 14, 2000]
Assays for the Detection of Clostridium
difficile; Guideline for Industry and § 866.3145 Coxsackievirus serological
Food and Drug Administration Staff.’’ reagents.
See § 866.1(e) for information on obtain-
(a) Identification. Coxsackievirus se-
ing this document.
rological reagents are devices that con-
[80 FR 51939, Aug. 27, 2015] sist of antigens and antisera used in se-
§ 866.3135 Coccidioides immitis sero- coxsackievirus in serum. Additionally,
logical reagents. some of these reagents consist of
(a) Identification. Coccidioides immitis coxsackievirus antisera conjugated
serological reagents are devices that with a fluorescent dye that are used to
consist of antigens and antisera used in identify coxsackievirus from clinical

serological tests to identify antibodies specimens or from tissue culture iso-
to Coccidioides immitis in serum. The lates derived from clinical specimens.
334
The identification aids in the diagnosis toms of hepatitis and in persons at risk
of coxsackievirus infections and pro- for hepatitis C infection. The test is
vides epidemiological information on not intended for screening blood, plas-
diseases caused by these viruses. ma, cell, or tissue donors.
Coxsackieviruses produce a variety of (b) Classification. Class II (special
infections, including common colds, controls). The special controls for this
meningitis (inflammation of brain and device are:
spinal cord membranes), herpangina (1) The labeling required under
(brief fever accompanied by ulcerated § 809.10(b) of this chapter must include:
lesions of the throat), and (i) A prominent statement that the
myopericarditis (inflammation of heart test is not intended for the screening of
tissue). blood, plasma, and cell or tissue do-
(b) Classification. Class I (general con- nors.
(ii) Limitations, which must be up-
dated to reflect current clinical prac-
tice and disease presentation and man-
agement. The limitations must in-
[47 FR 50823, Nov. 9, 1982, as amended at 65 clude, but are not limited to, state-
FR 2311, Jan. 14, 2000] ments that indicate:
§ 866.3165 Cryptococcus neoformans se- (A) When appropriate, the perform-
rological reagents. ance characteristics of the test have
not been established in populations of
(a) Identification. Cryptococcus immunocompromised or
neoformans serological reagents are de- immunosuppressed patients or, other
vices that consist of antigens used in special populations where test perform-
serological tests to identify antibodies ance may be affected.
to Cryptococcus neoformans in serum.
(B) The detection of HCV antibodies
Additionally, some of these reagents
indicates a present or past infection
consist of antisera conjugated with a
with hepatitis C virus, but does not dif-
fluorescent dye (immunofluorescent re-
agents) and are used to identify ferentiate between acute, chronic, or
Cryptococcus neoformans directly from resolved infection.
clinical specimens or from cultured (C) The specimen types for which the
isolates derived from clinical speci- device has been cleared, and that use of
mens. The identification aids in the di- the test with specimen types other
agnosis of cryptococcosis and provides than those specifically cleared for this
epidemiological information on this device may result in inaccurate test re-
type of disease. Cryptococcosis infec- sults.
tions are found most often as chronic (D) Test results are to be interpreted
meningitis (inflammation of brain by qualified licensed healthcare profes-
membranes) and, if not treated, are sionals in conjunction with the individ-
usually fatal. ual’s clinical presentation, history, and
(b) Classification. Class II (special other laboratory results.
controls). The device is exempt from (E) A non-reactive test result may
the premarket notification procedures occur early during acute infection,
in subpart E of part 807 of this chapter prior to development of a host anti-
subject to § 866.9. body response to infection, or when
analyte levels are below the limit of
FR 59226, Nov. 3, 1998] detection of the test.
(iii) A detailed explanation of the
§ 866.3169 Hepatitis C virus antibody principles of operation and procedures
tests. for performing the test.
(a) Identification. A hepatitis C virus (2) Design verification and validation
(HCV) antibody test is identified as an must include the following:
in vitro diagnostic device intended for (i) A detailed device description, in-
use with human serum, plasma, or cluding all parts that make up the de-
other matrices as a prescription device vice, ancillary reagents required but

that aids in the diagnosis of HCV infec- not provided, an explanation of the de-
tion in persons with signs and symp- vice methodology, and design of the
335
§ 866.3170 21 CFR Ch. I (4–1–23 Edition)
antigen(s) and capture antibody(ies) se- (xi) Detailed documentation of clin-

quences, rationale for the selected ical performance testing from a
epitope(s), degree of amino acid se- multisite clinical study. Performance
quence conservation of the target, and must be analyzed relative to an FDA
the design and nature of all primary, cleared or approved HCV antibody test,
secondary, and subsequent standards or a comparator that FDA has deter-
used for calibration. mined is appropriate. This study must
(ii) Documentation and characteriza- be conducted using appropriate patient
tion (e.g., supplier, determination of samples, with an acceptable number of
identity, and stability) of all critical HCV positive and negative samples in
reagents (including description of the applicable risk categories. Additional
antigen(s) and capture antibody(ies)), relevant patient groups must be vali-
and protocols for maintaining product dated as appropriate. The samples may
integrity throughout its labeled shelf be a combination of fresh and reposi-
life. tory samples, sourced from geographi-
(iii) Risk analysis and management cally diverse areas. The study designs,
strategies, such as Failure Modes Ef- including number of samples tested,
fects Analysis and/or Hazard Analysis must be sufficient to meet the fol-
and Critical Control Points summaries lowing criteria:
and their impact on test performance. (A) Clinical sensitivity of the test
(iv) Final release criteria to be used must have a lower bound of the 95 per-
for manufactured test lots with appro- cent confidence interval of greater
priate evidence that lots released at than or equal to 95 percent.
the extremes of the specifications will (B) Clinical specificity of the test
meet the claimed analytical and clin- must have a lower bound of the 95 per-
ical performance characteristics as cent confidence interval of greater
well as the stability claims. than or equal to 96 percent.
(v) Stability studies for reagents (3) For any HCV antibody test in-
must include documentation of an as- tended for Point of Care (PoC) use, the
sessment of real-time stability for mul- following special controls, in addition
tiple reagent lots using the indicated to those listed in paragraphs (b)(1) and
specimen types and must use accept- (2) of this section, apply:
ance criteria that ensure that analyt- (i) Clinical studies must be conducted
ical and clinical performance charac- at PoC sites.
teristics are met when stability is as- (ii) Additional labeling must include
signed based on the extremes of the ac- a brief summary of the instructions for
ceptance range. use that are appropriate for use in a
(vi) All stability protocols, including PoC environment.
acceptance criteria.
(vii) Final release test results for [86 FR 66176, Nov. 22, 2021]
each lot used in clinical studies.
(viii) Multisite reproducibility study § 866.3170 Nucleic acid-based hepatitis
that includes the testing of three inde- C virus ribonucleic acid tests.
pendent production lots. (a) Identification. A nucleic acid-based
(ix) Analytical performance studies hepatitis C virus (HCV) ribonucleic
and results for determining the limit of acid (RNA) test is identified as an in
blank (LoB), limit of detection (LoD), vitro diagnostic device intended for
cutoff, precision (reproducibility) in- prescription use as an aid in the diag-
cluding lot-to-lot and/or instrument-to- nosis of HCV infection in specified pop-
instrument precision, interference, ulations, and/or as an aid in the man-
cross reactivity, carryover, hook ef- agement of HCV-infected patients in-
fect, seroconversion panel testing, ma- cluding guiding the selection of geno-
trix equivalency, specimen stability, type-specific treatment in individuals
reagent stability, and cross-genotype with chronic HCV infection. The test is
antibody detection sensitivity, when intended for use with human serum or
appropriate. plasma. The test is not intended for use
(x) Analytical sensitivity of the test as a donor screening test for the pres-
is the same or better than that of other ence of HCV antibodies in blood, blood
cleared or approved tests. products, or tissue donors.
336
(b) Classification. Class II (special a standardized reference material that

controls). The special controls for this FDA has determined is appropriate
device are: (e.g., a recognized consensus standard).
(1) For all nucleic acid-based HCV In addition, analytical testing must be
RNA tests, the labeling required under performed following the release of a
§ 809.10(b) of this chapter must include: new lot of the standard material that
(i) A prominent statement that the was used for device clearance or ap-
test is not intended for use as a donor proval, or when there is a transition to
screening test for the presence of HCV a new calibration standard.
RNA from human cells, tissues, and (iii) Documentation and character-
cellular and tissue-based products. ization (e.g., determination of the iden-
(ii) A detailed explanation of the tity, supplier, purity, and stability) of
principles of operation and procedures all critical reagents (including nucleic
for performing the assay. acid sequences for primers and probes)
(iii) A detailed explanation of the in- and protocols for maintaining product
terpretation of results. integrity.
(iv) Limitations, which must be up- (iv) Detailed documentation of ana-
dated to reflect current clinical prac- lytical performance studies conducted
tice and disease presentation and man- as appropriate to the technology, speci-
agement. These limitations must in- men types tested, and intended use of
clude, but are not limited to, state- the device, including, but not limited
ments that indicate: to, limit of detection (LoD), upper and
(A) The specimen types for which the lower limits of quantitation (ULoQ and
device has been cleared and that use of LLoQ, respectively), linearity, preci-
this test kit with specimen types other sion, endogenous and exogenous inter-
than those specifically cleared for this ferences, cross reactivity, carryover,
device may result in inaccurate test re- matrix equivalency, and sample and re-
sults. agent stability. Samples selected for
(B) When applicable, that assay per- use in analytical studies or used to pre-
formance characteristics have not been pare samples for use in analytical stud-
established in populations of ies must be from subjects with clini-
immunocompromised or cally relevant circulating genotypes in
immunosuppressed patients or, other the United States. Cross-reactivity
populations where test performance studies must include samples from
may be affected. HCV RNA negative subjects with other
(C) Test results are to be interpreted causes of liver disease, including auto-
by qualified licensed healthcare profes- immune hepatitis, alcoholic liver dis-
sionals in conjunction with the individ- ease, chronic hepatitis B virus, pri-
ual’s clinical presentation, history, and mary biliary cirrhosis, and non-
other laboratory results. alcoholic steatohepatitis, when appli-
(2) For all nucleic acid-based HCV cable. The effect of each claimed nu-
RNA tests, the design verification and cleic-acid isolation and purification
validation must include: procedure on detection must be evalu-
(i) Detailed device description, in- ated.
cluding the device components, ancil- (v) Risk analysis and management
lary reagents required but not pro- strategies, such as Failure Modes Ef-
vided, and an explanation of the device fects Analysis and/or Hazard Analysis
methodology. Additional information and Critical Control Points summaries
appropriate to the technology must be and their impact on test performance.
included such as design of primers and (vi) Final release criteria to be used
probes, rationale for the selected gene for manufactured test lots with appro-
targets, specifications for amplicon priate evidence that lots released at
size, and degree of nucleic acid se- the extremes of the specifications will
quence conservation. meet the claimed analytical and clin-
(ii) For devices with assay cali- ical performance characteristics as
brators, the design and nature of all well as the stability claims.
primary, secondary, and subsequent (vii) Multisite reproducibility study

quantitation standards used for cali- that includes the testing of three inde-
bration as well as their traceability to pendent production lots.
337
§ 866.3170 21 CFR Ch. I (4–1–23 Edition)
(viii) All stability protocols, includ- technology, specimen types tested, and
ing acceptance criteria. intended use of the device, including
(ix) Final release test results for each but not limited to: LoD, ULoQ and
lot used in clinical studies. LLoQ. LoD, LLoQ, and linearity stud-
(x) Analytical sensitivity and speci- ies must demonstrate acceptable de-
ficity of the test must be the same or vice performance with all HCV
better than that of other cleared or ap- genotypes detected by the device.
proved tests. (B) Detailed documentation of clin-
(xi) Lot-to-lot precision studies, as ical performance testing from either:
appropriate. (1) A multisite clinical study with an
(3) For devices intended for the quali- appropriate number of clinical samples
tative detection of HCV RNA, in addi- from chronically HCV infected patients
tion to the special controls listed in in which the results are compared to
paragraphs (b)(1) and (2) of this section, an FDA-cleared or approved quan-
the design verification and validation titative HCV RNA test, or a com-
must include detailed documentation parator that FDA has determined is ap-
of performance from a multisite clin- propriate. This study must include a
ical study. Performance must be ana- sufficient number of HCV positive sam-
lyzed relative to an FDA cleared or ap- ples containing an analyte concentra-
proved qualitative HCV RNA test, or a tion near the LLoQ to describe per-
comparator that FDA has determined formance at this level. Clinical samples
is appropriate. This study must be con- must cover the full range of the device
ducted using appropriate patient sam- output and must be consistent with the
ples, with appropriate numbers of HCV distribution of these genotypes in the
positive and negative samples in appli- U.S. population. Clinical samples may
cable risk categories. Additional be supplemented with diluted clinical
genotypes must be validated using ap- samples for those viral load concentra-
propriate numbers and types of sam- tions that are not sufficiently covered
ples. The samples may be a combina- by natural clinical specimens, or
tion of fresh and repository samples, (2) A clinical study with prospec-
sourced from within and outside the tively collected samples demonstrating
United States, as appropriate. The clinical validity of the device.
study designs, including number of (C) Detailed documentation of a qual-
samples tested, must be sufficient to itative analysis near the lower end of
meet the following criteria: the measuring range demonstrating ac-
(i) Clinical sensitivity of the test ceptable performance when used as an
must have a lower bound of the 95 per- aid in diagnosis.
cent confidence interval of greater (5) For devices intended for HCV RNA
than or equal to 95 percent. genotyping, in addition to the special
(ii) Clinical specificity of the test controls listed in paragraphs (b)(1) and
must have a lower bound of the 95 per- (2) of this section, design verification
cent confidence interval of greater and validation must include the fol-
than or equal to 96 percent. lowing:
(4) For devices intended for the quan- (i) Detailed documentation of an ana-
titative detection of HCV RNA, the fol- lytical performance study dem-
lowing special controls, in addition to onstrating the LoD for all HCV
those listed in paragraphs (b)(1) and (2) genotypes detected by the device.
of this section, apply: (ii) Detailed documentation, includ-
(i) Labeling required under § 809.10(b) ing results, of a multisite clinical
of this chapter must include a promi- study that assesses genotyping accu-
nent statement that the test is not in- racy (i.e., the proportion of interpret-
tended as a diagnostic test to confirm able results that match with the ref-
the presence of active HCV infection, erence method result) and the
when applicable. genotyping rate (i.e., the proportion of
(ii) Design verification and valida- results that were interpretable).
tion must include the following: (6) For any nucleic acid-based HCV
(A) Detailed documentation of the RNA test intended for Point of Care
following analytical performance stud- (PoC) use, the following special con-
ies conducted as appropriate to the trols, in addition to those listed in
338
paragraphs (b)(1) and (2) of this section, subpart E of part 807 of this chapter
apply: subject to § 866.9.
(i) Clinical studies must be conducted
at PoC sites. FR 2311, Jan. 14, 2000]
(ii) Additional labeling must include
a brief summary of the instructions for § 866.3205 Echovirus serological re-
use that are appropriate for use in a agents.
PoC environment. (a) Identification. Echovirus sero-
[86 FR 66172, Nov. 22, 2021] logical reagents are devices that con-
§ 866.3175 Cytomegalovirus serological rological tests to identify antibodies to
reagents. echovirus in serum. Additionally, some
(a) Identification. Cytomegalovirus se- of these reagents consist of echovirus
rological reagents are devices that con- antisera conjugated with a fluorescent
sist of antigens and antisera used in se- dye used to identify echoviruses from
rological tests to identify antibodies to clinical specimens or from tissue cul-
cytomegalovirus in serum. The identi- ture isolates derived from clinical
fication aids in the diagnosis of dis- specimens. The identification aids in
eases caused by cytomegaloviruses the diagnosis of echovirus infections
(principally cytomegalic inclusion dis- and provides epidemiological informa-
ease) and provides epidemiological in- tion on diseases caused by these vi-
formation on these diseases. ruses. Echoviruses cause illnesses such
Cytomegalic inclusion disease is a gen- as meningitis (inflammation of the
eralized infection of infants and is brain and spinal cord membranes), feb-
caused by intrauterine or early post- rile illnesses (accompanied by fever)
natal infection with the virus. The dis- with or without rash, and the common
ease may cause severe congenital ab- cold.
normalities, such as microcephaly (ab- (b) Classification. Class I (general con-
normal smallness of the head), motor trols). The device is exempt from the
disability, and mental retardation. premarket notification procedures in
Cytomegalovirus infection has also subpart E of part 807 of this chapter
been associated with acquired hemo- subject to the limitations in § 866.9.
lytic anemia, acute and chronic hepa-
titis, and an infectious mononucleosis- [47 FR 50823, Nov. 9, 1982, as amended at 54
like syndrome. FR 25046, June 12, 1989; 66 FR 38791, July 25,
(b) Classification. Class II (perform- 2001]
ance standards).
§ 866.3210 Endotoxin assay.
§ 866.3200 Echinococcus spp. sero- (a) Identification. An endotoxin assay
logical reagents. is a device that uses serological tech-
(a) Identification. Echinococcus spp. se- niques in whole blood. The device is in-
rological reagents are devices that con- tended for use in conjunction with
sist of Echinococcus spp. antigens and other laboratory findings and clinical
antisera used in serological tests to assessment of the patient to aid in the
identify antibodies to Echinococcus spp. risk assessment of critically ill pa-
in serum. The identification aids in the tients for progression to severe sepsis.
diagnosis of echinococcosis, caused by (b) Classification. Class II (special
parasitic tapeworms belonging to the controls). The special control for this
genus Echinococcus and provides epide- device is the FDA guidance entitled
miological information on this disease. ‘‘Class II Special Controls Guidance
Echinococcosis is characterized by the Document: Endotoxin Assay.’’ See
development of cysts in the liver, lung, § 866.1(e) for the availability of this
kidneys, and other organs formed by guidance document.
the larva of the infecting organisms.
(b) Classification. Class I (general con- [68 FR 62008, Oct. 31, 2003. Redesignated at 70
trols). The device is exempt from the FR 53069, Sept. 7, 2005]
339
§ 866.3215 21 CFR Ch. I (4–1–23 Edition)
§ 866.3215 Device to detect and meas- (i) Results must demonstrate ade-
ure non-microbial analyte(s) in quate device performance relative to a
human clinical specimens to aid in well-accepted comparator.
assessment of patients with sus- (ii) Clinical sample results must dem-
pected sepsis. onstrate consistency of device output
(a) Identification. A device to detect throughout the device measuring range
and measure non-microbial analyte(s) likely to be encountered in the In-
in human clinical specimens to aid in tended Use population.
assessment of patients with suspected (iii) Clinical study documentation
sepsis is identified as an in vitro device must include the original study pro-
intended for the detection and quali- tocol (including predefined statistical
tative and/or quantitative measure- analysis plan), study report docu-
ment of one or more non-microbial menting support for the Indications for
analytes in human clinical specimens Use(s), and results of all statistical
to aid in the assessment of patients analyses.
with suspected sepsis when used in con- (5) Premarket notification submis-
junction with clinical signs and symp- sions must include evaluation of the
toms and other clinical and laboratory level of the non-microbial analyte in
findings. asymptomatic patients with demo-
(b) Classification. Class II (special graphic characteristics (e.g., age, ra-
controls). The special controls for this cial, ethnic, and gender distribution)
device are: similar to the Intended Use population.
(1) Premarket notification submis- (6) As part of the risk management
sions must include the device’s de- activities performed under 21 CFR
tailed Indications for Use statement 820.30 design controls, you must docu-
describing what the device detects and ment an appropriate end user device
measures, the results provided to the training program that will be offered
user, whether the measure is quali- as part of your efforts to mitigate the
tative and/or quantitative, the clinical risk of failure to correctly operate the
indications for which the test is to be instrument.
used, and the specific population(s) for (7) A detailed explanation of the in-
which the device use is intended. terpretation of results and acceptance
(2) Premarket notification submis- criteria must be included in the de-
sions must include detailed docu- vice’s 21 CFR 809.10(b)(9) compliant la-
mentation of the device description, in- beling, and a detailed explanation of
cluding (as applicable), all device com- the interpretation of the limitations of
ponents, software, ancillary reagents the samples (e.g., collected on day of
required but not provided, explanation diagnosis) must be included in the de-
of the device principle and method- vice’s 21 CFR 809.10(b)(10) compliant la-
ology, and for molecular devices in- beling.
clude detailed documentation of the [82 FR 49099, Oct. 24, 2017]
primer/probe sequence, design, and ra-
tionale for sequence selection. § 866.3220 Entamoeba histolytica sero-
(3) Premarket notification submis- logical reagents.
sions must include detailed docu- (a) Identification. Entamoeba
mentation of applicable analytical histolytica serological reagents are de-
studies, such as, analytical sensitivity vices that consist of antigens and
(Limit of Detection, Limit of Blank, antisera used in serological tests to
and Limit of Quantitation), precision, identify antibodies to Entamoeba
reproducibility, analytical measuring histolytica in serum. Additionally, some
range, interference, cross-reactivity, of these reagents consist of antisera
and specimen stability. conjugated with a fluorescent dye
(4) Premarket notification submis- (immunofluorescent reagents) used to
sions must include detailed docu- identify Entamoeba histolytica directly
mentation of a prospective clinical from clinical specimens. The identi-
study or, if appropriate, results from fication aids in the diagnosis of amebi-
an equivalent sample set. This detailed asis caused by the microscopic proto-
documentation must include the fol- zoan parasite Entamoeba histolytica and
lowing information: provides epidemiological information
340
on diseases caused by this parasite. (b) Classification. Class I (general con-

The parasite may invade the skin, trols).
liver, intestines, lungs, and diaphragm,
causing disease conditions such as in- § 866.3240 Equine encephalomyelitis
dolent ulcers, an amebic hepatitis, virus serological reagents.
amebic dysentery, and pulmonary le- (a) Identification. Equine
sions. encephalomyelitis virus serological re-
(b) Classification. Class II (special agents are devices that consist of anti-
controls). The device is exempt from gens and antisera used in serological
the premarket notification procedures tests to identify antobodies to equine
in subpart E of part 807 of this chapter encephalomyelitis virus in serum. The
subject to § 866.9. identification aids in the diagnosis of
[47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, diseases caused by equine
1982, as amended at 63 FR 59226, Nov. 3, 1998] encephalomyelitis viruses and provides
epidemiological information on these
§ 866.3225 Enterovirus nucleic acid viruses. Equine encephalomyelitis vi-
assay. ruses are transmitted to humans by
(a) Identification. An enterovirus nu- the bite of insects, such as mosquitos
cleic acid assay is a device that con- and ticks, and may cause encephalitis
sists of primers, probes, enzymes, and (inflammation of the brain), rash,
controls for the amplification and de- acute arthritis, or hepatitis.
tection of enterovirus ribonucleic acid (b) Classification. Class I (general con-
(RNA) in cerebrospinal fluid (CSF) trols). The device is exempt from the
from individuals who have signs and premarket notification procedures in
symptoms consistent with meningitis subpart E of part 807 of this chapter
or meningoencephalitis. The detection subject to § 866.9.
of enterovirus RNA, in conjunction
with other laboratory tests, aids in the [47 FR 50823, Nov. 9, 1982, as amended at 65
clinical laboratory diagnosis of viral FR 2311, Jan. 14, 2000]
meningitis caused by enterovirus.
§ 866.3250 Erysipelothrix rhusiopathiae
(b) Classification. Class II (special serological reagents.
guidance document entitled ‘‘Class II (a) Identification. Erysipelothrix
Special Controls Guidance Document: rhusiopathiae serological reagents are
Nucleic Acid Amplification Assay for devices that consist of antigens and
the Detection of Enterovirus RNA.’’ antisera used in serological tests to
See § 866.1(e) for the availability of this identify Erysipelothrix rhusiopathiae
guidance document. from cultured isolates derived from
clinical specimens. The identification
[74 FR 8, Jan. 2, 2009]
aids in the diagnosis of disease caused
§ 866.3235 Epstein-Barr virus sero- by this bacterium belonging to the
logical reagents. genus Erysipelothrix. This organism is
responsible for a variety of inflamma-
(a) Identification. Epstein-Barr virus
tions of the skin following skin abra-
serological reagents are devices that
consist of antigens and antisera used in sions from contact with fish, shellfish,
serological tests to identify antibodies or poultry.
to Epstein-Barr virus in serum. The (b) Classification. Class I (general con-
identification aids in the diagnosis of trols). The device is exempt from the
Epstein-Barr virus infections and pro- premarket notification procedures in
vides epidemiological information on subpart E of part 807 of this chapter
diseases caused by these viruses. Ep- subject to the limitations in § 866.9.
stein-Barr viruses are thought to cause [47 FR 50823, Nov. 9, 1982, as amended at 54
infectious mononucleosis and have FR 25046, June 12, 1989; 66 FR 38791, July 25,
been associated with Burkitt’s 2001]
lymphoma (a tumor of the jaw in Afri-

can children and young adults) and
postnasal carcinoma (cancer).
341
§ 866.3255 21 CFR Ch. I (4–1–23 Edition)
§ 866.3255 Escherichia coli serological (b) Classification. Class I (general con-

reagents. trols). The device is exempt from the
(a) Identification. Escherichia coli sero- premarket notification procedures in
logical reagents are devices that con- subpart E of part 807 of this chapter
sist of antigens and antisera used in se- subject to the limitations in § 866.9.
rological tests to identify Escherichia [47 FR 50823, Nov. 9, 1982, as amended at 54
coli from cultured isolates derived from FR 25046, June 12, 1989; 66 FR 38792, July 25,
clinical specimens. Additionally, some 2001]
of these reagents consist of Escherichia
coli antisera conjugated with a fluores- § 866.3280 Francisella tularensis sero-
logical reagents.
cent dye used to identify Escherichia
coli directly from clinical specimens or (a) Identification. Francisella tularensis
cultured isolates derived from clinical serological reagents are devices that
specimens. The identification aids in consist of antigens and antisera used in
the diagnosis of diseases caused by this serological tests to identify antibodies
bacterium belonging to the genus Esch- to Francisella tularensis in serum or to
erichia, and provides epidemiological identify Francisella tularensis in cul-
information on diseases caused by this tured isolates derived from clinical
microorganism. Although Escherichia specimens. Additionally, some of these
coli constitutes the greater part of the reagents consist of antisera conjugated
microorganisms found in the intestinal with a fluorescent dye
tract in humans and is usually non- (immunofluorescent reagents) used to
pathogenic, those strains which are identify Francisella tularensis directly
pathogenic may cause urinary tract in- from clinical specimens. The identi-
fections or epidemic diarrheal disease, fication aids in the diagnosis of tula-
especially in children. remia caused by Francisella tularensis
(b) Classification. Class I (general con- and provides epidemiological informa-
trols). The device is exempt from the tion on this disease. Tularemia is a
premarket notification procedures in desease principally of rodents, but may
subpart E of part 807 of this chapter be transmitted to humans through
subject to the limitations in § 866.9. handling of infected animals, animal
products, or by the bites of fleas and
FR 25046, June 12, 1989; 66 FR 38791, July 25,
ticks. The disease takes on several
2001] forms depending upon the site of infec-
tion, such as skin lesions, lymph node
§ 866.3270 Flavobacterium spp. sero- enlargements, or pulmonary infection.
logical reagents. (b) Classification. Class II (special
(a) Identification. Flavobacterium spp. controls). The device is exempt from
serological reagents are devices that the premarket notification procedures
consist of antigens and antisera used in in subpart E of part 807 of this chapter
serological tests to identify subject to § 866.9.
Flavobacteriuim spp. from cultured iso- [47 FR 50823, Nov. 9, 1982, as amended at 63
lates derived from clinical specimens. FR 59226, Nov. 3, 1998]
of disease caused by bacteria belonging § 866.3290 Gonococcal antibody test
to the genus Flavobacterium and pro- (GAT).
vides epidemiological information on (a) Identification. A gonococcal anti-
diseases caused by these microorga- body test (GAT) is an in vitro device
nisms. Most members of this genus are that consists of the reagents intended
found in soil and water and, under cer- to identify by immunochemical tech-
tain conditions, may become patho- niques, such as latex agglutination, in-
genic to humans. Flavobacterium direct fluorescent antibody, or
meningosepticum is highly virulent for radioimmunoassay, antibodies to
the newborn, in whom it may cause Neisseria gonorrhoeae in sera of asymp-
epidemics of septicemia (blood poi- tomatic females at low risk of infec-
soning) and meningitis (inflammation tion. Identification of antibodies with
of the membranes of the brain) and is this device may indicate past or
usually attributable to contaminated present infection of the patient with
hospital equipment. Neisseria gonorrhoeae.
342
(b) Classification. Class III (premarket tions range from common and mild le-
approval) (transitional device). sions of the skin and mucous mem-
(c) Date PMA or notice of completion of branes to a severe form of encephalitis
a PDP is required. As of May 28, 1976, an (inflammation of the brain). Neonatal
approval under section 515 of the act is herpes virus infections range from a
required before this device may be mild infection to a severe generalized
commercially distributed. See § 866.3. disease with a fatal outcome.
[47 FR 50823, Nov. 9, 1982, as amended at 52 (b) Classification. Class II (special
FR 17734, May 11, 1987] controls). The device is classified as
class II (special controls). The special
§ 866.3300 Haemophilus spp. sero- control for the device is FDA’s revised
logical reagents. guidance document entitled ‘‘Class II
(a) Identification. Haemophilus spp. se- Special Controls Guidance Document:
rological reagents are devices that con- Herpes Simplex Virus Types 1 and 2 Se-
sist of antigens and antisera, including rological Assays.’’ For availability of
antisera conjugated with a fluorescent the guidance revised document, see
dye, that are used in serological tests § 866.1(e).
to identify Haemophilus spp. directly [72 FR 15830, Apr. 3, 2007, as amended at 74
from clinical specimens or tissue cul- FR 42775, Aug. 25, 2009; 76 FR 48717, Aug. 9,
ture isolates derived from clinical 2011]
specimens. The identification aids in
the diagnosis of diseases caused by bac- § 866.3309 Herpes virus nucleic acid-
teria belonging to the genus based cutaneous and
Haemophilus and provides epidemiolog- mucocutaneous lesion panel.
ical information on diseases cause by (a) Identification. A herpes virus nu-
these microorganisms. Diseases most cleic acid-based cutaneous and
often caused by Haemophilus spp. in- mucocutaneous lesion panel is a quali-
clude pneumonia, pharyngitis, sinus- tative in vitro diagnostic device in-
itis, vaginitis, chancroid venereal dis- tended for the simultaneous detection
ease, and a contagious form of conjunc- and differentiation of different herpes
tivitis (inflammation of eyelid mem- viruses in cutaneous and
branes). mucocutaneous lesion samples from
(b) Classification. Class II (special symptomatic patients suspected of
controls). The device is exempt from Herpetic infections. Negative results
the premarket notification procedures do not preclude infection and should
in subpart E of part 807 of this chapter not be used as the sole basis for treat-
subject to § 866.9. ment or other patient management de-
[47 FR 50823, Nov. 9, 1982, as amended at 63 cisions. The assay is not intended for
FR 59226, Nov. 3, 1998] use in cerebrospinal fluid samples.
§ 866.3305 Herpes simplex virus sero- controls). The special controls for this
logical assays. device are:
(a) Identification. Herpes simplex (1) Premarket notification submis-
virus serological assays are devices sions must include detailed docu-
that consist of antigens and antisera mentation for the device description,
used in various serological tests to including the device components, an-
identify antibodies to herpes simplex cillary reagents required but not pro-
virus in serum. Additionally, some of vided, and a detailed explanation of the
the assays consist of herpes simplex methodology including primer design
virus antisera conjugated with a fluo- and selection.
rescent dye (immunofluorescent as- (2) Premarket notification submis-
says) used to identify herpes simplex sions must include detailed docu-
virus directly from clinical specimens mentation from the following analyt-
or tissue culture isolates derived from ical and clinical performance studies:
clinical specimens. The identification Analytical sensitivity (Limit of Detec-
aids in the diagnosis of diseases caused tion), reactivity, inclusivity, precision,
by herpes simplex viruses and provides reproducibility, interference, cross re-

epidemiological information on these activity, carry-over, and cross con-
diseases. Herpes simplex viral infec- tamination.
343
§ 866.3310 21 CFR Ch. I (4–1–23 Edition)
(3) Premarket notification submis- (b) Classification. Class II (special

sions must include detailed docu- controls). The special control is
mentation of a clinical study using le- ‘‘Guidance for Industry and FDA Staff:
sion samples in which Herpes Simplex Class II Special Controls Guidance
Virus 1, Herpes Simplex Virus 2, or Document: Hepatitis A Virus Sero-
Varicella Zoster Virus DNA detection logical Assays.’’ See § 866.1(e) for the
was requested. The study must com- availability of this guidance document.
pare the device performance to an ap-
[71 FR 6679, Feb. 9, 2006]
propriate well established reference
method. § 866.3320 Histoplasma capsulatum se-
(4) A detailed explanation of the in- rological reagents.
terpretation of results and acceptance
criteria must be included in the de- (a) Identification. Histoplasma
vice’s 21 CFR 809.10(b)(9) compliant la- capsulatum serological reagents are de-
beling. vices that consist of antigens and
(5) The device labeling must include antisera used in serological tests to
a limitation statement that reads: identify antibodies to Histoplasma
‘‘The device is not intended for use capsulatum in serum. Additionally,
with cerebrospinal fluid or to aid in the some of these reagents consist of
diagnosis of HSV or VZV infections of Histoplasma capsulatum antisera con-
the central nervous system (CNS).’’ jugated with a fluorescent dye
(6) Premarket notification submis- (immunofluorescent reagents) used to
sions must include quality assurance identify Histoplasma capsulatum from
protocols and a detailed documenta- clinical specimens or cultured isolates
tion for device software, including, but derived from clinical specimens. The
not limited to, standalone software ap- identification aids in the diagnosis of
plications and hardware-based devices histoplasmosis caused by this fungus
that incorporate software. belonging to the genus Histoplasma and
(7) The risk management activities provides epidemiological information
performed as part of the manufactur- on the diseases caused by this fungus.
er’s 21 CFR 820.30 design controls must Histoplasmosis usually is a mild and
document an appropriate end user de- often asymptomatic respiratory infec-
vice training program that will be of- tion, but in a small number of infected
fered as part of efforts to mitigate the individuals the lesions may spread to
risk of failure to correctly operate the practically all tissues and organs.
instrument. (b) Classification. Class II (special
[83 FR 52314, Oct. 17, 2018]
§ 866.3310 Hepatitis A virus (HAV) se- in subpart E of part 807 of this chapter
rological assays. subject to § 866.9.
(a) Identification. HAV serological as- [47 FR 50823, Nov. 9, 1982, as amended at 63
says are devices that consist of anti- FR 59227, Nov. 3, 1998]
gens and antisera for the detection of
hepatitis A virus-specific IgM, IgG, or § 866.3328 Influenza virus antigen de-
total antibodies (IgM and IgG), in tection test system.
human serum or plasma. These devices (a) Identification. An influenza virus
are used for testing specimens from in- antigen detection test system is a de-
dividuals who have signs and symp- vice intended for the qualitative detec-
toms consistent with acute hepatitis to tion of influenza viral antigens directly
determine if an individual has been from clinical specimens in patients
previously infected with HAV, or as an with signs and symptoms of res-
aid to identify HAV-susceptible indi- piratory infection. The test aids in the
viduals. The detection of these anti- diagnosis of influenza infection and
bodies aids in the clinical laboratory provides epidemiological information
diagnosis of an acute or past infection on influenza. Due to the propensity of
by HAV in conjunction with other clin- the virus to mutate, new strains
ical laboratory findings. These devices emerge over time which may poten-
are not intended for screening blood or tially affect the performance of these
solid or soft tissue donors. devices. Because influenza is highly
344
contagious and may lead to an acute (2) When performing testing to dem-
respiratory tract infection causing se- onstrate the device meets the require-
vere illness and even death, the accu- ments in paragraph (b)(1) of this sec-
racy of these devices has serious public tion, a currently appropriate and FDA
health implications. accepted comparator method must be
(b) Classification. Class II (special used to establish assay performance in
controls). The special controls for this clinical studies.
device are: (3) Annual analytical reactivity test-
(1) The device’s sensitivity and speci- ing of the device must be performed
ficity performance characteristics or with contemporary influenza strains.
positive percent agreement and nega- This annual analytical reactivity test-
tive percent agreement, for each speci- ing must meet the following criteria:
men type claimed in the intended use (i) The appropriate strains to be test-
of the device, must meet one of the fol- ed will be identified by FDA in con-
lowing two minimum clinical perform- sultation with the Centers for Disease
ance criteria: Control and Prevention (CDC) and
(i) For devices evaluated as compared sourced from CDC or an FDA-des-
to an FDA-cleared nucleic acid based- ignated source. If the annual strains
test or other currently appropriate and are not available from CDC, FDA will
FDA accepted comparator method identify an alternative source for ob-
other than correctly performed viral taining the requisite strains.
culture method: (ii) The testing must be conducted
(A) The positive percent agreement according to a standardized protocol
estimate for the device when testing considered and determined by FDA to
for influenza A and influenza B must be be acceptable and appropriate.
at the point estimate of at least 80 per- (iii) By July 31 of each calendar year,
cent with a lower bound of the 95 per- the results of the last 3 years of annual
cent confidence interval that is greater analytical reactivity testing must be
than or equal to 70 percent. included as part of the device’s label-
(B) The negative percent agreement ing. If a device has not been on the
estimate for the device when testing market long enough for 3 years of an-
for influenza A and influenza B must be nual analytical reactivity testing to
at the point estimate of at least 95 per- have been conducted since the device
cent with a lower bound of the 95 per- received marketing authorization from
cent confidence interval that is greater FDA, then the results of every annual
than or equal to 90 percent. analytical reactivity testing since the
(ii) For devices evaluated as com- device received marketing authoriza-
pared to correctly performed viral cul- tion from FDA must be included. The
ture method as the comparator meth- results must be presented as part of the
od: device’s labeling in a tabular format,
(A) The sensitivity estimate for the which includes the detailed informa-
device when testing for influenza A tion for each virus tested as described
must be at the point estimate of at in the certificate of authentication, ei-
least 90 percent with a lower bound of ther by:
the 95 percent confidence interval that (A) Placing the results directly in the
is greater than or equal to 80 percent. device’s § 809.10(b) of this chapter com-
The sensitivity estimate for the device pliant labeling that physically accom-
when testing for influenza B must be at panies the device in a separate section
the point estimate of at least 80 per- of the labeling where the analytical re-
cent with a lower bound of the 95 per- activity testing data can be found; or
cent confidence interval that is greater (B) In the device’s label or in other
than or equal to 70 percent. labeling that physically accompanies
(B) The specificity estimate for the the device, prominently providing a
device when testing for influenza A and hyperlink to the manufacturer’s public
influenza B must be at the point esti- Web site where the analytical reac-
mate of at least 95 percent with a lower tivity testing data can be found. The
bound of the 95 percent confidence in- manufacturer’s home page, as well as

terval that is greater than or equal to the primary part of the manufacturer’s
90 percent. Web site that discusses the device,
345
§ 866.3330 21 CFR Ch. I (4–1–23 Edition)
must provide a prominently placed taining this information and must

hyperlink to the Web page containing allow unrestricted viewing access.
this information and must allow unre-
[82 FR 3618, Jan. 12, 2017]
stricted viewing access.
(4) If one of the actions listed at sec- § 866.3330 Influenza virus serological
tion 564(b)(1)(A)–(D) of the Federal reagents.
Food, Drug, and Cosmetic Act occurs
with respect to an influenza viral (a) Identification. Influenza virus sero-
strain, or if the Secretary of Health logical reagents are devices that con-
and Human Services (HHS) determines, sist of antigens and antisera used in se-
under section 319(a) of the Public rological tests to identify antibodies to
Health Service Act, that a disease or influenza in serum. The identification
disorder presents a public health emer- aids in the diagnosis of influenza (flu)
gency, or that a public health emer- and provides epidemiological informa-
gency otherwise exists, with respect to tion on influenza. Influenza is an acute
an influenza viral strain: respiratory tract disease, which is
(i) Within 30 days from the date that often epidemic.
FDA notifies manufacturers that char- (b) Classification. Class I (general con-
acterized viral samples are available trols). The device is exempt from the
for test evaluation, the manufacturer premarket notification procedures in
must have testing performed on the de- subpart E of part 807 of this chapter
vice with those viral samples in accord- subject to the limitations in § 866.9.
ance with a standardized protocol con-
sidered and determined by FDA to be FR 25047, June 12, 1989; 66 FR 38792, July 25,
acceptable and appropriate. The proce- 2001]
dure and location of testing may de-
pend on the nature of the emerging § 866.3332 Reagents for detection of
virus. specific novel influenza A viruses.
(ii) Within 60 days from the date that
(a) Identification. Reagents for detec-
FDA notifies manufacturers that char-
tion of specific novel influenza A vi-
acterized viral samples are available
ruses are devices that are intended for
for test evaluation and continuing
use in a nucleic acid amplification test
until 3 years from that date, the re-
to directly detect specific virus RNA in
sults of the influenza emergency ana-
human respiratory specimens or viral
lytical reactivity testing, including the
cultures. Detection of specific virus
detailed information for the virus test-
ed as described in the certificate of au- RNA aids in the diagnosis of influenza
thentication, must be included as part caused by specific novel influenza A vi-
of the device’s labeling in a tabular for- ruses in patients with clinical risk of
mat, either by: infection with these viruses, and also
(A) Placing the results directly in the aids in the presumptive laboratory
device’s § 809.10(b) of this chapter com- identification of specific novel influ-
pliant labeling that physically accom- enza A viruses to provide epidemiolog-
panies the device in a separate section ical information on influenza. These
of the labeling where analytical reac- reagents include primers, probes, and
tivity testing data can be found, but specific influenza A virus controls.
separate from the annual analytical re- (b) Classification. Class II (special
activity testing results; or controls). The special controls are:
(B) In a section of the device’s label (1) FDA’s guidance document entitled
or in other labeling that physically ac- ‘‘Class II Special Controls Guidance
companies the device, prominently pro- Document: Reagents for Detection of
viding a hyperlink to the manufactur- Specific Novel Influenza A Viruses.’’
er’s public Web site where the analyt- See § 866.1(e) for information on obtain-
ical reactivity testing data can be ing this document.
found. The manufacturer’s home page, (2) The distribution of these devices
as well as the primary part of the man- is limited to laboratories with experi-
ufacturer’s Web site that discusses the enced personnel who have training in
device, must provide a prominently standardized molecular testing proce-
placed hyperlink to the Web page con- dures and expertise in viral diagnosis,
346
and appropriate biosafety equipment § 866.3350 Leptospira spp. serological

and containment. reagents.
[71 FR 14379, Mar. 22, 2006] (a) Identification. Leptospira spp. sero-
§ 866.3336 John Cunningham Virus se- sist of antigens and antisera used in se-
rological reagents. rological tests to identify antibodies to
(a) Identification. John Cunningham Leptospira spp. in serum or identify
Virus serological reagents are devices Leptospira spp. from cultured isolates
that consist of antigens and antisera derived from clinical specimens. Addi-
used in serological assays to identify tionally, some of these antisera are
antibodies to John Cunningham Virus conjugated with a fluorescent dye
in serum and plasma. The identifica- (immunofluorescent reagents) and used
tion aids in the risk stratification for to identify Leptospira spp. directly
the development of progressive from clinical specimens. The identi-
multifocal leukoencephalopathy in fication aids in the diagnosis of lepto-
multiple sclerosis and Crohn’s disease spirosis caused by bacteria belonging
patients undergoing natalizumab ther- to the genus Leptospira and provides ep-
apy. These devices are for adjunctive idemiological information on this dis-
use, in the context of other clinical ease. Leptospira infections range from
risk factors for the development of pro- mild fever-producing illnesses to severe
gressive multifocal leukoenceph- liver and kidney involvement pro-
alopathy. ducing hemorrhage and dysfunction of
(b) Classification. Class II (special these organs.
controls). The special control for this (b) Classification. Class II (special
device is the FDA guideline document controls). The device is exempt from
entitled ‘‘Class II Special Controls the premarket notification procedures
Guideline: John Cunningham Virus Se- in subpart E of part 807 of this chapter
rological Reagents.’’ For availability subject to § 866.9.
of the guideline document, see
§ 866.1(e).
FR 59227, Nov. 3, 1998]
[79 FR 3740, Jan. 23, 2014]
§ 866.3355 Listeria spp. serological re-
§ 866.3340 Klebsiella spp. serological agents.
reagents.
(a) Identification. Listeria spp. sero-
(a) Identification. Klebsiella spp. serological reagents are devices that con-
logical reagents are devices that consist of antigens and antisera used in se-
sist of antigens and antisera, including rological tests to identify Listeria spp.
antisera conjugated with a fluorescent from cultured isolates derived from
dye (immunofluorescent reagents), clinical specimens. Additionally, some
that are used in serological tests to of these reagents consist of Listeria spp.
identify Klebsiella spp. from cultured antisera conjugated with a fluorescent
isolates derived from clinical speci- dye (immunofluorescent reagents) used
mens. The identification aids in the di- to identify Listeria spp. directly from
agnosis of diseases caused by bacteria clinical specimens. The identification
belonging to the genus Klebsiella and aids in the diagnosis of listeriosis, a
provides epidemiological information disease caused by bacteria belonging to
on these diseases. These organisms can the genus Listeria, and provides epide-
cause serious urinary tract and pul- miological information on diseases
monary infections, particularly in hos- caused by these microorganisms. Lis-
pitalized patients. teria monocytogenes, the most common
(b) Classification. Class I (general con- human pathogen of this genus, causes
trols). The device is exempt from the meningitis (inflammation of the brain
premarket notification procedures in membranes) and meningoencephalitis
subpart E of part 807 of this chapter (inflammation of the brain and brain
subject to the limitations in § 866.9. membranes) and is often fatal if un-
[47 FR 50823, Nov. 9, 1982, as amended at 54 treated. A second form of human

FR 25047, June 12, 1989; 66 FR 38792, July 25, listeriosis is an intrauterine infection
2001] in pregnant women that results in a
347
§ 866.3360 21 CFR Ch. I (4–1–23 Edition)
high mortality rate for infants before (1) Premarket notification submis-
or after birth. sions must include detailed docu-
(b) Classification. Class I (general con- mentation for device software, includ-
trols). The device is exempt from the ing, but not limited to, standalone
premarket notification procedures in software applications and hardware-
subpart E of part 807 of this chapter based devices that incorporate soft-
subject to § 866.9. ware.
[47 FR 50823, Nov. 9, 1982, as amended at 65 (2) Premarket notification submis-
FR 2311, Jan. 14, 2000] sions must include database implemen-
tation methodology, construction pa-
§ 866.3360 Lymphocytic choriomenin- rameters, and quality assurance proto-
gitis virus serological reagents. cols.
(a) Identification. Lymphocytic cho- (3) A detailed explanation of the in-
riomeningitis virus serological re- terpretation of results and acceptance
agents are devices that consist of anti- criteria must be included in the de-
gens and antisera used in serological vice’s 21 CFR 809.10(b)(9) compliant la-
tests to identify antibodies to beling.
lymphocytic choriomeningitis virus in (4) As part of the risk management
serum. The identification aids in the activities performed as part of your 21
diagnosis of lymphocytic choriomenin- CFR 820.30 design controls, you must
gitis virus infections and provides epi- document an appropriate end user de-
demiological information on diseases vice training program that will be of-
caused by these viruses. Lymphocytic fered as part of your efforts to mitigate
choriomeningitis viruses usually cause the risk of failure to correctly operate
a mild cerebral meningitis (inflamma- the instrument.
tion of membranes that envelop the (5) Premarket notification submis-
brain) and occasionally a mild pneu- sions must include details on the ap-
monia, but in rare instances may propriate end user device training pro-
produce severe and even fatal illnesses gram that will be offered while mar-
due to complications from cerebral keting the device.
meningitis and pneumonia.
(b) Classification. Class I (general con- [82 FR 49101, Oct. 24, 2017]
premarket notification procedures in § 866.3365 Multiplex nucleic acid assay
subpart E of part 807 of this chapter for identification of microorga-
nisms and resistance markers from
positive blood cultures.
(a) Identification. A multiplex nucleic
FR 2311, Jan. 14, 2000]
acid assay for identification of micro-
§ 866.3361 Mass spectrometer system organisms and resistance markers from
for clinical use for the identifica- positive blood cultures is a qualitative
tion of microorganisms. in vitro device intended to simulta-
(a) Identification. A mass spectrom- neously detect and identify microorga-
eter system for clinical use for the nism nucleic acids from blood cultures
identification of microorganisms is a that test positive by Gram stain or
qualitative in vitro diagnostic device other microbiological stains. The de-
intended for the identification of vice detects specific nucleic acid se-
microorganisms cultured from human quences for microorganism identifica-
specimens. The device is comprised of tion as well as for antimicrobial resist-
an ionization source, a mass analyzer, ance. This device aids in the diagnosis
and a spectral database. The device is of bloodstream infections when used in
indicated for use in conjunction with conjunction with other clinical and
other clinical and laboratory findings laboratory findings. However, the de-
to aid in the diagnosis of bacterial and vice does not replace traditional meth-
fungal infections. ods for culture and susceptibility test-
(b) Classification. Class II (special ing.

controls). The special controls for this (b) Classification. Class II (special
device are: controls). The special control for this
348
device is FDA’s guideline document en- ‘‘Class II Special Controls Guideline:

titled ‘‘Class II Special Controls Guide- Nucleic Acid-Based In Vitro Diagnostic
line: Multiplex Nucleic Acid Assay for Devices for the Detection of
Identification of Microorganisms and Mycobacterium tuberculosis Complex in
Resistance Markers from Positive Respiratory Specimens.’’ For avail-
Blood Cultures.’’ For availability of ability of the guideline document, see
the guideline document, see § 866.1(e). § 866.1(e).
[80 FR 30154, May 27, 2015] [79 FR 31027, May 30, 2014]
§ 866.3370 Mycobacterium tuberculosis
immunofluorescent reagents. § 866.3373 Nucleic acid-based in vitro
diagnostic devices for the detection
(a) Identification. Mycobacterium tu- of Mycobacterium tuberculosis com-
berculosis immunofluorescent reagents plex (MTB-complex) and the genetic
are devices that consist of antisera mutations associated with MTB-
conjugated with a fluorescent dye used complex antibiotic resistance in
to identify Mycobacterium tuberculosis respiratory specimens.
directly from clinical specimens. The (a) Identification. Nucleic acid-based
identification aids in the diagnosis of in vitro diagnostic devices for the de-
tuberculosis and provides epidemiolog- tection of Mycobacterium tuberculosis
ical information on this disease. complex (MTB-complex) and the ge-
Mycobacterium tuberculosis is the com- netic mutations associated with MTB-
mon causative organism in human tu- complex antibiotic resistance in res-
berculosis, a chronic infectious disease
piratory specimens are qualitative nu-
characterized by formation of tubercles
cleic acid-based devices that detect the
(small rounded nodules) and tissue ne-
presence of MTB-complex-associated
crosis (destruction), usually occurring
nucleic acid sequences in respiratory
in the lung.
(b) Classification. Class I (general con- samples. These devices are intended to
trols). aid in the diagnosis of pulmonary tu-
berculosis and the selection of an ini-
§ 866.3372 Nucleic acid-based in vitro tial treatment regimen when used in
diagnostic devices for the detection conjunction with clinical findings and
of Mycobacterium tuberculosis com- other laboratory results. These devices
plex in respiratory specimens. do not provide confirmation of anti-
(a) Identification. Nucleic acid-based biotic susceptibility since other mech-
in vitro diagnostic devices for the de- anisms of resistance may exist that
tection of Mycobacterium tuberculosis may be associated with a lack of clin-
complex in respiratory specimens are ical response to treatment other than
qualitative nucleic acid-based in vitro those detected by the device.
diagnostic devices intended to detect (b) Classification. Class II (special
Mycobacterium tuberculosis complex nu- controls). The special controls for this
cleic acids extracted from human res- device are:
piratory specimens. These devices are
(1) The FDA document entitled
non-multiplexed and intended to be
‘‘Class II Special Controls Guideline:
used as an aid in the diagnosis of pul-
Nucleic Acid-Based In Vitro Diagnostic
monary tuberculosis when used in con-
junction with clinical and other labora- Devices for the Detection of
tory findings. These devices do not in- Mycobacterium tuberculosis Complex and
clude devices intended to detect the Genetic Mutations Associated with An-
presence of organism mutations associ- tibiotic Resistance in Respiratory
ated with drug resistance. Respiratory Specimens,’’ which addresses the miti-
specimens may include sputum (in- gation of risks specific to the detection
duced or expectorated), bronchial of MTB-complex. For availability of
specimens (e.g., bronchoalveolar lavage the document, see § 866.1(e).
or bronchial aspirate), or tracheal aspi- (2) The following items, which ad-
rates. dress the mitigation of risks specific to
(b) Classification. Class II (special the detection of the genetic mutations

controls). The special control for this associated with antibiotic resistance of
device is the FDA document entitled MTB-complex:
349
§ 866.3375 21 CFR Ch. I (4–1–23 Edition)
(i) The device must include an exter- complex. The antibiotic resistant
nal positive assay control as appro- strains must be those with well charac-
priate. Acceptable positive assay con- terized genetic mutations associated
trols include MTB-complex isolates with antibiotic resistance.
containing one or more antibiotic-re- (2) Analytical Reactivity (Inclusivity).
sistance associated target sequences Testing must be conducted to evaluate
detected by the device. the ability of the device to detect ge-
(ii) The device must include internal netic mutations associated with anti-
controls as appropriate. An acceptable biotic resistance in a diversity of MTB-
internal control may include human complex strains. Isolates used in test-
nucleic acid co-extracted with MTB- ing must be well characterized. Isolate
complex containing nucleic acid se- strain characterization must be deter-
quences associated with antibiotic re- mined using standardized reference
sistance and primers amplifying human methods recognized by a reputable sci-
housekeeping genes (e.g., RNaseP, b- entific body and appropriate to the
actin). strain lineage.
(iii) The device’s intended use must (3) Within-Laboratory (Repeatability)
include a description of the scope of Precision Testing. Within-laboratory
antibiotic resistance targeted by the precision studies, if appropriate, must
assay, i.e., the specific drugs and/or include at least one antibiotic resist-
drug classes. ant and one antibiotic susceptible
(iv) The specific performance charac- strain of MTB-complex.
teristics section of the device’s label- (4) Between Laboratory Reproducibility
ing must include information regarding Testing. The protocol for the reproduc-
the specificity of the assay ibility study may vary slightly depend-
oligonucleotides for detecting ing on the assay format; however, the
mutations associated with antibiotic panel must include at least one anti-
resistance of MTB-complex, and any biotic resistant and one antibiotic sus-
information indicating the potential ceptible strain of MTB-complex.
for non-specific binding (e.g., BLAST (C) Clinical Studies. Clinical per-
search). formance of the device must be estab-
(v) In demonstrating device perform- lished by conducting prospective clin-
ance you must perform: ical studies that include subjects with
(A) Pre-analytical studies that evalu- culture confirmed active tuberculosis.
ate: Studies must attempt to enroll sub-
(1) Frozen samples. If there is use of jects at risk for antibiotic-resistant
any frozen samples in the device per- MTB-complex; however, it may be nec-
formance studies, or if there is a device essary to include supplemental anti-
claim for the use of frozen samples for biotic resistant retrospective and con-
testing, the effect of freezing samples trived samples. Clinical studies must
prior to testing and the effect of mul- compare device results to both
tiple freeze/thaw cycles on both anti- phenotypic drug susceptibility testing
biotic susceptible and antibiotic resist- and genotypic reference methods. The
ant strains of MTB-complex. genotypic reference method must be a
(2) Nucleic acid extraction methods. Ex- polymerase chain reaction based meth-
traction methods must parallel those od that uses primers different from
used in devices for the detection of those in the experimental device and
MTB-complex nucleic acid and confirm confirmed by bidirectional sequencing.
that the detection of the genetic [79 FR 63036, Oct. 22, 2014]
mutations associated with antibiotic
resistance is not affected. § 866.3375 Mycoplasma spp. serological
(B) Analytical studies that analyze: reagents.
(1) Limit of Detection. Limit of Detec- (a) Identification. Mycoplasma spp. se-
tion must be determined in the most rological reagents are devices that con-
challenging matrix (e.g., sputum) sist of antigens and antisera used in se-
claimed for use with the device. The rological tests to identify antibodies to
Limit of Detection must be determined Mycoplasma spp. in serum. Addition-

using both antibiotic susceptible and ally, some of these reagents consist of
antibiotic resistant strains of MTB- Mycoplasma spp. antisera conjugated
350
with a fluorescent dye that consist of antigens and antisera

(immunofluorescent reagents) used to used in serological tests to identify
identify Mycoplasma spp. directly from Neisseria spp. from cultured isolates.
clinical specimens. The identification Additionally, some of these reagents
aids in the diagnosis of disease caused consist of Neisseria spp. antisera con-
by bacteria belonging to the genus jugated with a fluorescent dye
Mycoplasma and provides epidemiolog- (immunofluorescent reagents) which
ical information on diseases caused by may be used to detect the presence of
these microorganisms. Mycoplasma spp. Neisseria spp. directly from clinical
are associated with inflammatory con- specimens. The identification aids in
ditions of the urinary and respiratory the diagnosis of disease caused by bac-
tracts, the genitals, and the mouth.
teria belonging to the genus Neisseria,
The effects in humans of infection with
such as epidemic cerebrospinal menin-
Mycoplasma pneumoniae range from
gitis, meningococcal disease, and gon-
inapparent infection to mild or severe
upper respiratory disease, ear infec- orrhea, and also provides epidemiolog-
tion, and bronchial pneumonia. ical information on diseases caused by
(b) Classification. Class I (general con- these microorganisms. The device does
trols). The device is exempt from the not include products for the detection
premarket notification procedures in of gonorrhea in humans by indirect
subpart E of part 807 of this chapter methods, such as detection of anti-
subject to § 866.9. bodies or of oxidase produced by gono-
coccal organisms.
FR 2311, Jan. 14, 2000]
ance standards).
§ 866.3380 Mumps virus serological re-
agents. § 866.3395 Norovirus serological re-
agents.
(a) Identification. Mumps virus sero-
logical reagents consist of antigens and (a) Identification. Norovirus sero-
antisera used in serological tests to logical reagents are devices that con-
identify antibodies to mumps virus in sist of antigens and antisera used in se-
serum. Additionally, some of these re- rological tests to detect the presence of
agents consist of antisera conjugated norovirus antigens in fecal samples.
with a fluorescent dye These devices aid in the diagnosis of
(immunofluorescent reagents) used in norovirus infection in the setting of an
serological tests to identify mumps vi- individual patient with symptoms of
ruses from tissue culture isolates de- acute gastroenteritis when the indi-
rived from clinical specimens. The vidual patient is epidemiologically
identification aids in the diagnosis of linked to other patients with symp-
mumps and provides epidemiological toms of acute gastroenteritis and/or
information on mumps. Mumps is an aid in the identification of norovirus as
acute contagious disease, particularly the etiology of an outbreak of acute
in children, characterized by an en- gastroenteritis in the setting of
largement of one or both of the parotid epidemiologically linked patients with
glands (glands situated near the ear), symptoms of acute gastroenteritis.
although other organs may also be in-
volved.
(b) Classification. Class I (general con- controls). The device is exempt from
trols). The device is exempt from the the premarket notification procedures
premarket notification procedures in in subpart E of part 807 of this chapter
subpart E of part 807 of this chapter subject to the limitations in § 866.9. The
subject to § 866.9. special control is FDA’s guidance docu-
ment entitled ‘‘Class II Special Con-
[47 FR 50823, Nov. 9, 1982, as amended at 65 trols Guidance Document: Norovirus
FR 2311, Jan. 14, 2000]
Serological Reagents.’’ See § 866.1(e) for
§ 866.3390 Neisseria spp. direct sero- the availability of this guidance docu-
logical test reagents. ment.
(a) Identification. Neisseria spp. direct [76 FR 14274, Mar. 9, 2012, as amended at 84
serological test reagents are devices FR 71800, Dec. 30, 2019]
351
§ 866.3400 21 CFR Ch. I (4–1–23 Edition)
§ 866.3400 Parainfluenza virus sero- § 866.3405 Poliovirus serological re-

logical reagents. agents.
(a) Identification. Parainfluenza virus (a) Identification. Poliovirus sero-
serological reagents are devices that logical reagents are devices that con-
consist of antigens and antisera used in sist of antigens and antisera used in se-
serological tests to identify antibodies rological tests to identify antibodies to
to parainfluenza virus in serum. The poliovirus in serum. Additionally, some
identification aids in the diagnosis of of these reagents consist of poliovirus
parainfluenza virus infections and pro- antisera conjugated with a fluorescent
vides epidemiological information on dye (immunofluorescent reagents) used
diseases caused by these viruses. to identify polioviruses from clinical
Parainfluenza viruses cause a variety specimens or from tissue culture iso-
of respiratory illnesses ranging from lates derived from clinical specimens.
the common cold to pneumonia. The identification aids in the diagnosis
(b) Classification. Class I (general con- of poliomyelitis (polio) and provides
trols). The device is exempt from the epidemiological information on this
premarket notification procedures in disease. Poliomyelitis is an acute in-
subpart E of part 807 of this chapter fectious disease which in its serious
subject to the limitations in § 866.9. form affects the central nervous sys-
tem resulting in atrophy (wasting
FR 25047, June 12, 1989; 66 FR 38792, July 25,
away) of groups of muscles, ending in
2001] contraction and permanent deformity.
§ 866.3402 Plasmodium species antigen trols). The device is exempt from the
detection assays. premarket notification procedures in
(a) Identification. A Plasmodium spe- subpart E of part 807 of this chapter
cies antigen detection assay is a device subject to § 866.9.
that employs antibodies for the detec- [47 FR 50823, Nov. 9, 1982, as amended at 65
tion of specific malaria parasite anti- FR 2312, Jan. 14, 2000]
gens, including histidine-rich protein-2
(HRP2) specific antigens, and pan ma- § 866.3410 Proteus spp. (Weil-Felix) se-
larial antigens in human whole blood. rological reagents.
These devices are used for testing (a) Identification. Proteus spp. (Weil-
specimens from individuals who have Felix) serological reagents are devices
signs and symptoms consistent with that consist of antigens and antisera,
malaria infection. The detection of including antisera conjugated with a
these antigens aids in the clinical lab- fluorescent dye (immunofluorescent re-
oratory diagnosis of malaria caused by agents), derived from the bacterium
the four malaria species capable of in- Proteus vulgaris used in agglutination
fecting humans: Plasmodium falciparum, tests (a specific type of antigen-anti-
Plasmodium vivax, Plasmodium ovale, body reaction) for the detection of
and Plasmodium malariae, and aids in antibodies to rickettsia (virus-like bac-
the differential diagnosis of Plasmodium teria) in serum. Test results aid in the
falciparum infections from other less diagnosis of diseases caused by bacteria
virulent Plasmodium species. The device belonging to the genus Rickettsiae and
is intended for use in conjunction with provide epidemiological information on
other clinical laboratory findings. these diseases. Rickettsia are generally
(b) Classification. Class II (special transmitted by arthropods (e.g., ticks
controls). The special control is FDA’s and mosquitoes) and produce infections
guidance document entitled ‘‘Class II in humans characterized by rash and
Special Controls Guidance Document: fever (e.g., typhus fever, spotted fever,
Plasmodium species Antigen Detection Q fever, and trench fever).
Assays.’’ See § 866.1(e) for the avail- (b) Classification. Class I (general con-
ability of this guidance document. trols). The device is exempt from the
[73 FR 29054, May 20, 2008] premarket notification procedures in
352
subpart E of part 807 of this chapter § 866.3470 Reovirus serological re-

subject to the limitations in § 866.9. agents.
[47 FR 50823, Nov. 9, 1982, as amended at 54 (a) Identification. Reovirus serological
FR 25047, June 12, 1989; 66 FR 38792, July 25, reagents are devices that consist of
2001] antigens and antisera used in sero-
logical tests to identify antibodies to
§ 866.3415 Pseudomonas spp. sero- reovirus in serum. The identification
logical reagents. aids in the diagnosis of reovirus infec-
(a) Identification. Pseudomonas spp. se- tions and provides epidemiological in-
rological reagents are devices that con- formation on diseases caused by these
sist of antigens and antisera, including viruses. Reoviruses are thought to
antisera conjugated with a fluorescent cause only mild respiratory and gastro-
dye (immunofluorescent reagents), intestinal illnesses.
used to identify Pseudomonas spp. from (b) Classification. Class I (general con-
clinical specimens or from cultured trols). The device is exempt from the
isolates derived from clinical speci- premarket notification procedures in
mens. The identification aids in the di- subpart E of part 807 of this chapter
agnosis of disease caused by bacteria subject to the limitations in § 866.9.
belonging to the genus Pseudomonas.
Pseudomonas aeruginosa is a major
FR 25047, June 12, 1989; 66 FR 38792, July 25,
cause of hospital-acquired infections, 2001]
and has been associated with urinary
tract infections, eye infections, burn § 866.3480 Respiratory syncytial virus
and wound infections, blood poisoning, serological reagents.
abscesses, and meningitis (inflamma- (a) Identification. Respiratory
tion of brain membranes). Pseudomonas syncytial virus serological reagents are
pseudomallei causes melioidosis, a devices that consist of antigens and
chronic pneumonia. antisera used in serological tests to
(b) Classification. Class II (special identify antibodies to respiratory
controls). The device is exempt from syncytial virus in serum. Additionally,
the premarket notification procedures some of these reagents consist of res-
in subpart E of part 807 of this chapter piratory syncytial virus antisera con-
subject to § 866.9. jugated with a fluorescent dye
[47 FR 50823, Nov. 9, 1982, as amended at 63 (immunofluorescent reagents) and used
FR 59227, Nov. 3, 1998] to identify respiratory syncytial vi-
ruses from clinical specimens or from
§ 866.3460 Rabiesvirus immuno- tissue culture isolates derived from
fluorescent reagents. clinical specimens. The identification
(a) Identification. Rabiesvirus aids in the diagnosis of respiratory
immunofluorescent reagents are de- syncytial virus infections and provides
vices that consist of rabiesvirus epidemiological information on dis-
antisera conjugated with a fluorescent eases caused by these viruses. Res-
dye used to identify rabiesvirus in piratory syncytial viruses cause a
specimens taken from suspected rabid number of respiratory tract infections,
animals. The identification aids in the including the common cold, pharyn-
diagnosis of rabies in patients exposed gitis, and infantile bronchopneumonia.
by animal bites and provides epidemio- (b) Classification. Class I (general con-
logical information on rabies. Rabies is trols). The device is exempt from the
an acute infectious disease of the cen- premarket notification procedures in
tral nervous system which, if subpart E of part 807 of this chapter
undiagnosed, may be fatal. The disease subject to § 866.9.
is commonly transmitted to humans by
a bite from a rabid animal. FR 2312, Jan. 14, 2000]

ance standards).
353
§ 866.3490 21 CFR Ch. I (4–1–23 Edition)
§ 866.3490 Rhinovirus serological re- tion aids in the diagnosis of rubella

agents. (German measles) or confirmation of a
(a) Identification. Rhinovirus sero- person’s immune status from past in-
logical reagents are devices that con- fections or immunizations and provides
sist of antigens and antisera used in se- epidemiological information on Ger-
rological tests to identify antibodies to man measles. Newborns infected in the
rhinovirus in serum. The identification uterus with rubella virus may be born
aids in the diagnosis of rhinovirus in- with multiple congenital defects (ru-
fections and provides epidemiological bella syndrome).
information on diseases caused by (b) Classification. Class II. The special
these viruses. Rhinoviruses cause com- controls for this device are:
mon colds. (1) National Committee for Clinical
(b) Classification. Class I (general con- Laboratory Standards’:
trols). The device is exempt from the (i) 1/LA6 ‘‘Detection and Quantita-
premarket notification procedures in tion of Rubella IgG Antibody: Evalua-
subpart E of part 807 of this chapter tion and Performance Criteria for Mul-
subject to the limitations in § 866.9. tiple Component Test Products,
Speciment Handling, and Use of the
[47 FR 50823, Nov. 9, 1982, as amended at 54 Test Products in the Clinical Labora-
FR 25047, June 12, 1989; 66 FR 38792, July 25, tory, October 1997,’’
2001] (ii) 1/LA18 ‘‘Specifications for
Immunological Testing for Infectious
§ 866.3500 Rickettsia serological re-
agents. Diseases, December 1994,’’
(iii) D13 ‘‘Agglutination Characteris-
(a) Identification. Rickettsia sero- tics, Methodology, Limitations, and
logical reagents are devices that con- Clinical Validation, October 1993,’’
sist of antigens and antisera used in se- (iv) EP5 ‘‘Evaluation of Precision
rological tests to identify antibodies to Performance of Clinical Chemistry De-
rickettsia in serum. Additionally, some vices, February 1999,’’ and
of these reagents consist of rickettsial (v) EP10 ‘‘Preliminary Evaluation of
antisera conjugated with a fluorescent the Linearity of Quantitive Clinical
dye (immunofluorescent reagents) used Laboratory Methods, May 1998,’’
to identify rickettsia directly from (2) Centers for Disease Control’s:
clinical specimens. The identification (i) Low Titer Rubella Standard,
aids in the diagnosis of diseases caused (ii) Reference Panel of Well Charac-
by virus-like bacteria belonging to the terized Rubella Sera, and
genus Rickettsiae and provides epide- (3) World Health Organization’s
miological information on these dis- International Rubella Standard.
eases. Rickettsia are generally trans-
mitted by arthropods (e.g., ticks and [47 FR 50823, Nov. 9, 1982, as amended at 52
FR 17734, May 11, 1987; 65 FR 17144, Mar. 31,
mosquitoes) and produce infections in 2000]
humans characterized by rash and
fever (e.g., typhus fever, spotted fever, § 866.3520 Rubeola (measles) virus se-
Q fever, and trench fever). rological reagents.
(b) Classification. Class I (general con- (a) Identification. Rubeola (measles)
trols). The device is exempt from the virus serological reagents are devices
premarket notification procedures in that consist of antigens and antisera
subpart E of part 807 of this chapter used in serological tests to identify
subject to § 866.9. antibodies to rubeola virus in serum.
[47 FR 50823, Nov. 9, 1982, as amended at 65 The identification aids in the diagnosis
FR 2312, Jan. 14, 2000] of measles and provides epidemiolog-
ical information on the disease. Mea-
§ 866.3510 Rubella virus serological re- sles is an acute, highly infectious dis-
agents. ease of the respiratory and
(a) Identification. Rubella virus sero- reticuloendothelial tissues, particu-
logical reagents are devices that con- larly in children, characterized by a
sist of antigens and antisera used in se- confluent and blotchy rash.
rological tests to identify antibodies to (b) Classification. Class I (general con-
rubella virus in serum. The identifica- trols). The device is exempt from the
354

[47 FR 50823, Nov. 9, 1982, as amended at 54 subpart E of part 807 of this chapter
FR 25047, June 12, 1989; 66 FR 38792, July 25, subject to § 866.9.
2001]
§ 866.3550 Salmonella spp. serological FR 2312, Jan. 14, 2000]
reagents.
§ 866.3630 Serratia spp. serological re-
(a) Identification. Salmonella spp. sero- agents.
sist of antigens and antisera used in se- (a) Identification. Serratia spp. sero-
rological tests to identify Salmonella logical reagents are devices that con-
spp. from cultured isolates derived sist of antigens and antisera used in se-
from clinical specimens. Additionally, rological tests to identify Serratia spp.
some of these reagents consist of from cultured isolates. The identifica-
antisera conjugated with a fluorescent tion aids in the diagnosis of disease
dye (immunofluorescent reagents) used caused by bacteria belonging to the
to identify Salmonella spp. directly genus Serratia and provides epidemio-
from clinical specimens or cultured logical information on these diseases.
isolates derived from clinical speci- Serratia spp. are occasionally associ-
mens. The identification aids in the di- ated with gastroenteritis (food poi-
agnosis of salmonellosis caused by bac- soning) and wound infections.
teria belonging to the genus Salmonella
and provides epidemiological informa-
tion on this disease. Salmonellosis is trols). The device is exempt from the
characterized by high grade fever (‘‘en- premarket notification procedures in
teric fever’’), severe diarrhea, and subpart E of part 807 of this chapter
cramps. subject to the limitations in § 866.9.
(b) Classification. Class II (special [47 FR 50823, Nov. 9, 1982, as amended at 54
controls). The device is exempt from FR 25047, June 12, 1989; 66 FR 38792, July 25,
the premarket notification procedures 2001]
subject to § 866.9. § 866.3660 Shigella spp. serological re-
agents.
FR 59227, Nov. 3, 1998] (a) Identification. Shigella spp. sero-
§ 866.3600 Schistosoma spp. serological
reagents. sist of antigens and antisera, including
antisera conjugated with a fluorescent
(a) Identification. Schistosoma spp. se- dye (immunofluorescent reagents),
rological reagents are devices that con- used in serological tests to identify
Shigella spp. from cultured isolates.
Schistosoma spp. in serum. The identi-
fication aids in the diagnosis of schis- of shigellosis caused by bacteria be-
tosomiasis caused by parasitic longing to the genus Shigella and pro-
flatworms of the genus Schistosoma. vides epidemiological information on
Schistosomiasis is characterized by a this disease. Shigellosis is character-
variety of acute and chronic infections. ized by abdominal pain, cramps, diar-
Acute infection is marked by fever, al- rhea, and fever.
lergic symptoms, and diarrhea. Chronic (b) Classification. Class II (special
effects are usually severe and are controls). The device is exempt from
caused by fibrous degeneration of tis- the premarket notification procedures
sue around deposited eggs of the para- in subpart E of part 807 of this chapter
site in the liver, lungs, and central subject to § 866.9.
nervous system. Schistosomes can also
cause schistosome dermatitis (e.g.,

FR 59227, Nov. 3, 1998]
swimmer’s itch), a skin disease marked
by intense itching.
355
§ 866.3680 21 CFR Ch. I (4–1–23 Edition)
§ 866.3680 Sporothrix schenckii sero- caused by bacteria belonging to the

logical reagents. genus Streptococcus and provides epide-
(a) Identification. Sporothrix schenckii miological information on these dis-
serological reagents are devices that eases. Pathogenic streptococci are as-
consist of antigens and antisera used in sociated with infections, such as sore
serological tests to identify antibodies throat, impetigo (an infection charac-
to Sporothrix schenckii in serum. The terized by small pustules on the skin),
identification aids in the diagnosis of urinary tract infections, rheumatic
fever, and kidney disease.
sporothrichosis caused by a fungus be-
longing to the genus Sporothrix and
provides epidemiological information
on this disease. Sporothrichosis is a
chronic tumorlike infection primarily
of the skin.
trols). The device is exempt from the FR 1119, Jan. 16, 1996; 66 FR 38792, July 25,
subpart E of part 807 of this chapter § 866.3740 Streptococcus spp. sero-
subject to § 866.9. logical reagents.
[47 FR 50823, Nov. 9, 1982, as amended at 65 (a) Identification. Streptococcus spp.
FR 2312, Jan. 14, 2000] serological reagents are devices that
consist of antigens and antisera (ex-
§ 866.3700 Staphylococcus aureus sero- cluding streptococcal exoenzyme re-
logical reagents.
agents made from enzymes secreted by
(a) Identification. Staphylococcus streptococci) used in serological tests
aureus serological reagents are devices to identify Streptococcus spp. from cul-
that consist of antigens and antisera tured isolates derived from clinical
used in serological tests to identify specimens. The identification aids in
enterotoxin (toxin affecting the intes- the diagnosis of diseases caused by bac-
tine) producing staphylococci from cul- teria belonging to the genus Strepto-
tured isolates. The identification aids coccus and provides epidemiological in-
in the diagnosis of disease caused by formation on these diseases. Patho-
this bacterium belonging to the genus genic streptococci are associated with
Staphylococcus and provides epidemio- infections, such as sore throat, impe-
logical information on these diseases. tigo (an infection characterized by
Certain strains of Staphylococcus aureus small pustules on the skin), urinary
produce an enterotoxin while growing tract infections, rheumatic fever, and
in meat, dairy, or bakery products. kidney disease.
After ingestion, this enterotoxin is ab- (b) Classification. Class I (general con-
sorbed in the gut and causes destruc- trols). The device is exempt from the
tion of the intestinal lining premarket notification procedures in
(gastroenteritis). subpart E of part 807 of this chapter
(b) Classification. Class I (general con- subject to § 866.9.
trols). The device is exempt from the [47 FR 50823, Nov. 9, 1982, as amended at 65
premarket notification procedures in FR 2312, Jan. 14, 2000]
subject to the limitations in § 866.9. § 866.3780 Toxoplasma gondii sero-
logical reagents.
FR 25047, June 12, 1989; 66 FR 38792, July 25, (a) Identification. Toxoplasma gondii
2001] serological reagents are devices that
consist of antigens and antisera used in
§ 866.3720 Streptococcus spp. exo- serological tests to identify antibodies
enzyme reagents. to Toxoplasma gondii in serum. Addi-
(a) Identification. Streptococcus spp. tionally, some of these reagents consist
exoenzyme reagents are devices used to of antisera conjugated with a fluores-
identify antibodies to Streptococcus spp. cent dye (immunofluorescent reagents)

exoenzyme in serum. The identifica- used to identify Toxoplasma gondii from
tion aids in the diagnosis of disease clinical specimens. The identification
356
aids in the diagnosis of toxoplasmosis (b) Classification. Class II (perform-

caused by the parasitic protozoan ance standards).
Toxoplasma gondii and provides epide-
miological information on this disease. § 866.3850 Trichinella spiralis sero-
Congenital toxoplasmosis is character- logical reagents.
ized by lesions of the central nervous (a) Identification. Trichinella spiralis
system, which if undetected and un- serological reagents are devices that
treated may lead to brain defects, consist of antigens and antisera used in
blindness, and death of an unborn serological tests to identify antibodies
fetus. The disease is characterized in to Trichinella spiralis in serum. The
children by inflammation of the brain identification aids in the diagnosis of
and spinal cord. trichinosis caused by parasitic
(b) Classification. Class II (perform- roundworms belonging to the genus
ance standards). Trichinella and provides epidemiolog-
ical information on trichinosis. Trichi-
§ 866.3820 Treponema pallidum non-
treponemal test reagents. nosis is caused by ingestion of under-
cooked, infested meat, especially pork,
(a) Identification. Treponema pallidum and characterized by fever, muscle
nontreponemal test reagents are de- weakness, and diarrhea.
vices that consist of antigens derived (b) Classification. Class I (general con-
from nontreponemal sources (sources trols). The device is exempt from the
not directly associated with premarket notification procedures in
treponemal organisms) and control subpart E of part 807 of this chapter
sera (standardized sera with which test subject to § 866.9.
results are compared) used in sero-
logical tests to identify reagin, an anti- [47 FR 50823, Nov. 9, 1982, as amended at 65
body-like agent, which is produced FR 2312, Jan. 14, 2000]
from the reaction of treponema micro-
organisms with body tissues. The iden- § 866.3860 Trichomonas vaginalis nu-
tification aids in the diagnosis of cleic acid assay.
syphilis caused by microorganisms be- (a) Identification. A Trichomonas
longing to the genus Treponema and vaginalis nucleic acid assay is a device
provides epidemiological information that consists of primers, probes, en-
on syphilis. zymes, and controls for the amplifi-
(b) Classification. Class II (perform- cation and detection of trichomonas
ance standards). nucleic acids in endocervical swabs,
vaginal swabs, and female urine speci-
§ 866.3830 Treponema pallidum tre- mens, from women symptomatic for
ponemal test reagents. vaginitis, cervicitis, or urethritis and/
(a) Identification. Treponema pallidum or to aid in the diagnosis of trichomo-
treponemal test reagents are devices niasis in asymptomatic women. The de-
that consist of the antigens, antisera tection of trichomonas nucleic acids,
and all control reagents (standardized in conjunction with other laboratory
reagents with which test results are tests, aids in the clinical laboratory di-
compared) which are derived from agnosis of trichomoniasis caused by
treponemal sources and that are used Trichomonas vaginalis.
in the fluorescent treponemal antibody (b) Classification. Class II (special
absorption test (FTA-ABS), the controls). The special controls are set
Treponema pallidum immobilization test forth in FDA’s guideline document en-
(T.P.I.), and other treponemal tests titled: ‘‘Class II Special Controls
used to identify antibodies to Guideline: Nucleic Acid Amplification
Treponema pallidum directly from in- Assays for the Detection of
fecting treponemal organisms in Trichomonas vaginalis; Guideline for In-
serum. The identification aids in the dustry and Food and Drug Administra-
diagnosis of syphilis caused by bacteria tion Staff.’’ See § 866.1(e) for informa-
belonging to the genus Treponema and

tion on obtaining this document.
provides epidemiological information
on syphilis. [80 FR 46192, Aug. 4, 2015]
357
§ 866.3870 21 CFR Ch. I (4–1–23 Edition)
§ 866.3870 Trypanosoma spp. sero- single or multiple microbiological

logical reagents. analytes intended for use with either
(a) Identification. Trypanosoma spp. qualitative or quantitative assays.
serological reagents are devices that (b) Classification. Class II (special
consist of antigens and antisera used in controls). The special controls for this
serological tests to identify antibodies device are:
to Trypanosoma spp. in serum. The (1) Premarket notification submis-
identification aids in the diagnosis of sions must include detailed device de-
trypanosomiasis, a disease caused by scription documentation and informa-
parasitic protozoans belonging to the tion concerning the composition of the
genus Trypanosoma. Trypanosomiasis quality control material, including, as
in adults is a chronic disease charac- appropriate:
terized by fever, chills, headache, and (i) Analyte concentration;
vomiting. Central nervous system in- (ii) Expected values;
volvement produces typical sleeping (iii) Analyte source;
sickness syndrome: physical exhaus- (iv) Base matrix;
tion, inability to eat, tissue wasting, (v) Added components;
and eventual death. Chagas disease, an (vi) Safety and handling information;
acute form of trypanosomiasis in chil- and
dren, most seriously affects the central (vii) Detailed instructions for use.
nervous system and heart muscle. (2) Premarket notification submis-
(b) Classification. Class I (general con- sions must include detailed docu-
trols). mentation, including line data as well
§ 866.3900 Varicella-zoster virus sero- as detailed study protocols and a sta-
logical reagents. tistical analysis plan used to establish
performance, including:
(a) Identification. Varicella-zoster (i) Description of the process for
virus serological reagents are devices value assignment and validation.
that consist of antigens and antisera
(ii) Description of the protocol(s)
used in serological tests to identify
used to establish stability.
antibodies to varicella-zoster in serum.
(iii) Line data establishing precision/
reproducibility.
of diseases caused by varicella-zoster
viruses and provides epidemiological (iv) Where applicable, assessment of
information on these diseases. matrix effects and any significant dif-
Varicella (chicken pox) is a mild, high- ferences between the quality control
ly infectious disease, chiefly of chil- material and typical patient samples
dren. Zoster (shingles) is the recurrent in terms of conditions known to cause
form of the disease, occurring in adults analytical error or affect assay per-
who were previously infected with formance.
varicella-zoster viruses. Zoster is the (v) Where applicable, identify or de-
response (characterized by a rash) of fine traceability or relationship to a
the partially immune host to a reac- domestic or international standard ref-
tivation of varicella viruses present in erence material and/or method.
latent form in the patient’s body. (vi) Where applicable, detailed docu-
(b) Classification. Class II (perform- mentation related to studies for surro-
ance standards). gate controls.
§ 866.3920 Assayed quality control ma- sions must include an adequate mitiga-
terial for clinical microbiology as- tion (e.g., real-time stability program)
says. to the risk of false results due to po-
(a) Identification. An assayed quality tential modifications to the assays
control material for clinical microbi- specified in the device’s 21 CFR 809.10
ology assays is a device indicated for compliant labeling.
use in a test system to estimate test (4) Your 21 CFR 809.10 compliant la-
precision or to detect systematic ana- beling must include the following:
lytical deviations that may arise from (i) The intended use of your 21 CFR
reagent or analytical instrument vari- 809.10(a)(2) and (b)(2) compliant label-
ation. This type of device consists of ing must include the following:
358
(A) Assayed control material consistent with viral meningitis/en-

analyte(s); cephalitis. The detection aids in the
(B) Whether the material is intended clinical laboratory diagnosis of viral
for quantitative or qualitative assays; meningitis/encephalitis caused by West
(C) Stating if the material is a surro- Nile virus.
gate control; and (b) Classification. Class II (special
(D) The system(s), instrument(s), or controls). The special control is FDA’s
test(s) for which the quality control guidance entitled ‘‘Class II Special
material is intended. Controls Guidance Document: Sero-
(ii) The intended use in your 21 CFR logical Reagents for the Laboratory Di-
809.10(a)(2) and (b)(2) compliant label- agnosis of West Nile Virus.’’ See
ing must include the following state- § 866.1(e) for the availability of this
ment: ‘‘This product is not intended to guidance document.
replace manufacturer controls provided
with the device.’’ [68 FR 61745, Oct. 30, 2003]
(iii) A limiting statement that reads
‘‘Quality control materials should be § 866.3945 Dengue virus serological re-
used in accordance with local, state, agents.
federal regulations, and accreditation (a) Identification. Dengue virus sero-
requirements.’’ logical reagents are devices that con-
[82 FR 34850, July 27, 2017] sist of antigens and antibodies for the
detection of dengue virus and dengue
§ 866.3930 Vibrio cholerae serological antibodies in individuals who have
reagents. signs and symptoms of dengue fever or
(a) Identification. Vibrio cholerae sero- dengue hemorrhagic fever. The detec-
logical reagents are devices that are tion aids in the clinical laboratory di-
used in the agglutination (an antigen- agnosis of dengue fever or dengue hem-
antibody clumping reaction) test to orrhagic fever caused by dengue virus.
identify Vibrio cholerae from cultured (b) Classification. Class II (special
isolates derived from clinical speci- controls). The special control is FDA’s
mens. The identification aids in the di- guideline entitled ‘‘Class II Special
agnosis of cholera caused by the bac- Controls Guideline: Dengue Virus Sero-
terium Vibrio cholerae and provides epi- logical Reagents.’’ For availability of
demiological information on cholera. the guideline document, see § 866.1(e).
Cholera is an acute infectious disease
characterized by severe diarrhea with [79 FR 31023, May 30, 2014]
extreme fluid and electrolyte (salts)
§ 866.3946 Dengue virus nucleic acid
depletion, and by vomiting, muscle
amplification test reagents.
cramps, and prostration. If untreated,
the severe dehydration may lead to (a) Identification. Dengue virus nu-
shock, renal failure, cardiovascular cleic acid amplification test reagents
collapse, and death. are devices that consist of primers,
(b) Classification. Class II (special probes, enzymes, and controls for the
controls). The device is exempt from amplification and detection of dengue
the premarket notification procedures virus serotypes 1, 2, 3, or 4 from viral
in subpart E of part 807 of this chapter ribonucleic acid (RNA) in human serum
subject to § 866.9. and plasma from individuals who have
[47 FR 50823, Nov. 9, 1982, as amended at 63 signs and symptoms consistent with
FR 59227, Nov. 3, 1998] dengue (mild or severe). The identifica-
tion of dengue virus serotypes 1, 2, 3, or
§ 866.3940 West Nile virus serological 4 in human serum and plasma (sodium
reagents. citrate) collected from human patients
(a) Identification. West Nile virus se- with dengue provides epidemiologic in-
rological reagents are devices that con- formation for surveillance of circu-
sist of antigens and antisera for the de- lating dengue viruses.
tection of anti-West Nile virus IgM (b) Classification. Class II (special

antibodies, in human serum, from indi- controls). The special control is FDA’s
viduals who have signs and symptoms guideline entitled ‘‘Class II Special
359
§ 866.3950 21 CFR Ch. I (4–1–23 Edition)
Controls Guideline: Dengue Virus Nu- firm the presence of HIV infection, or
cleic Acid Amplification Test Re- for screening donors of blood, plasma,
agents.’’ For availability of the guide- or human cells, tissues, and cellular
line document, see § 866.1(e). and tissue-based products.
[79 FR 53609, Sept. 10, 2014]
(2) The labeling must include:
(i) A detailed device description, in-
§ 866.3950 In vitro human immuno- cluding but not limited to, all proce-
deficiency virus (HIV) drug resist- dures from collection of the patient
ance genotype assay. sample to reporting the final result, all
(a) Identification. The in vitro HIV device components, the control ele-
drug resistance genotype assay is a de- ments incorporated into the test proce-
vice that consists of nucleic acid rea- dure, instrument requirements, and re-
gent primers and probes together with agents required for use but not pro-
software for predicting drug resistance/ vided as part of the device.
susceptibility based on results obtained (ii) Performance characteristics from
with these primers and probes. It is in- analytical studies and all intended
tended for use in detecting HIV specimen types.
genomic mutations that confer resist- (iii) A list of specific mutations de-
ance to specific antiretroviral drugs, as tected.
an aid in monitoring and treating HIV (iv) The name and version of the
infection. standardized database used for se-
(b) Classification. Class II (special quence comparison and results deriva-
controls). The special control for this tion.
device is FDA’s guidance document en- (v) A detailed explanation of the in-
titled ‘‘Class II Special Controls Guid- terpretation of test results, including
ance Document: In Vitro HIV Drug Re- acceptance criteria for evaluating the
sistance Genotype Assay.’’ See § 866.1(e) validity of a test run.
for the availability of this guidance (vi) A limitation statement that the
document. device is intended to be used in con-
[72 FR 44382, Aug. 8, 2007]
junction with clinical history and
other laboratory findings. Results of
§ 866.3955 Human immunodeficiency this test are intended to be interpreted
virus (HIV) drug resistance by a physician or equivalent.
genotyping assay using next gen- (vii) A limitation statement that
eration sequencing technology. lack of detection of drug resistance
(a) Identification. The HIV drug re- mutations does not preclude the possi-
sistance genotyping assay using next bility of genetic mutation.
generation sequencing (NGS) tech- (viii) A limitation statement indi-
nology is a prescription in vitro diag- cating the relevant genetic mutations
nostic device intended for use in de- that are included in the standardized
tecting HIV genomic mutations that database of HIV genomic sequences
confer resistance to specific used for comparison and results deriva-
antiretroviral drugs. The device is in- tion but that are not detected by the
tended to be used as an aid in moni- test.
toring and treating HIV infection. (ix) A limitation statement that de-
(b) Classification. Class II (special tection of a genomic drug resistance
controls). The special controls for this mutation may not correlate with
device are: phenotypic gene expression.
(1) The intended use of the device (x) A limitation statement that the
must: test does not detect all genetic
(i) Specify the analyte (RNA or mutations associated with antiviral
DNA), the genes in which mutations drugs.
are detected, the clinical indications (xi) A limitation statement listing
appropriate for test use, the sample the HIV types for which the test is not
type, and the specific population(s) for intended, if any.
which the device in intended. (3) Device verification and validation
(ii) State that the device in not in- must include:

tended for use as an aid in the diag- (i) Design of primer sequences and ra-
nosis of infection with HIV or to con- tionale for sequence selection.
360
(ii) Computational path from col- (ix) A clear description of the selec-
lected raw data to reported result. tion and use of the standardized data-
(iii) Detailed documentation of ana- base that is used for sequence compari-
lytical studies including, but not lim- son and results derivation.
ited to, characterization of the cutoff, (4) Premarket notification submis-
analytical sensitivity, inclusivity, re- sions must include the information in
producibility, interference, cross reac- paragraphs (b)(3)(i) through (ix) of this
tivity, instrument and method carry- section.
over/cross contamination, sample sta- [85 FR 7217, Feb. 7, 2020]
bility, and handling for all genomic
mutations claimed in the intended use. § 866.3956 Human immunodeficiency
(iv) Precision studies that include all virus (HIV) serological diagnostic
genomic mutations claimed in the in- and/or supplemental test.
tended use. (a) Identification. Human immuno-
(v) Detailed documentation of a deficiency virus (HIV) serological diag-
multisite clinical study evaluating the nostic and supplemental tests are pre-
sensitivity and specificity of the description devices for the qualitative de-
vice. Clinical study subjects must rep- tection of HIV antigen(s) and/or detec-
resent the intended use population and tion of antibodies against HIV in
device results for all targets claimed in human body fluids or tissues. The tests
the intended use must be compared to are intended for use as an aid in the di-
Sanger sequencing or other methods agnosis of infection with HIV and are
found acceptable by FDA. Drug resist- for professional use only. The test re-
ance-associated mutations at or above sults are intended to be interpreted in
the 20 percent frequency level must de- conjunction with other relevant clin-
tect the mutations in greater than 90 ical and laboratory findings. These
percent of at least 10 replicates, for tests are not intended to be used for
each of drug class evaluated. monitoring patient status, or for
(vi) Documentation that variant call- screening donors of blood or blood
ing is performed at a level of coverage products, or human cells, tissues, and
that supports positive detection of all cellular and tissue-based products
genomic mutations claimed in the in- (HCT/Ps).
tended use. (b) Classification. Class II (special
(vii) Detailed documentation of limit controls). The special controls for this
of detection (LoD) studies in which de- device are:
vice performance is evaluated by test- (1) For all HIV serological diagnostic
ing a minimum of 100 HIV-positive and supplemental tests
clinical samples including samples (i) The labeling must include:
with analyte concentrations near the (A) An intended use that states that
clinical decision points and near the the device is not intended for use for
LoD. screening donors of blood or blood
(A) The LoD for the device must be products or HCT/Ps.
determined using a minimum of 10 (B) A detailed explanation of the
HIV–1 group M genotypes if applicable. principles of operation and procedures
A detection rate at 1 × LoD greater used for performing the assay.
than or equal to 95 percent must be (C) A detailed explanation of the in-
demonstrated for mutations with a fre- terpretation of results and rec-
quency greater than 20 percent. ommended actions to take based on re-
(B) The LoD of genetic mutations at sults.
frequency levels less than 20 percent (D) Limitations, which must be up-
must be established. dated to reflect current clinical prac-
(viii) A predefined HIV genotyping tice and disease presentation and man-
bioinformatics analysis pipeline (BAP). agement. The limitations must in-
The BAP must adequately describe the clude, but are not limited to, state-
bioinformatic analysis of the sequenc- ments that indicate:
ing data, including but not limited to (1) The matrices with which the de-
read alignment, variant calling, assem- vice has been cleared, and that use of
bly, genotyping, quality control, and this test kit with specimen types other
final result reporting. than those specifically cleared for this
361
§ 866.3956 21 CFR Ch. I (4–1–23 Edition)
device may result in inaccurate test re- (E) Analytical sensitivity of the test
sults. must be the same as or better than
(2) The test is not intended to be used that of other cleared or approved tests.
to monitor individuals who are under- Samples tested must include appro-
going treatment for HIV infection. priate numbers and types of samples,
(3) A specimen with a reactive result including real clinical samples near the
should be investigated further fol- lower limit of detection. Analytical
lowing current guidelines. specificity of the test must be the same
(4) All test results should be inter- as or better than that of other cleared
preted in conjunction with the individ- or approved tests. Samples must in-
ual’s clinical presentation, history, and clude appropriate numbers and types of
other laboratory results. samples from patients with different
(5) A test result that is nonreactive underlying illnesses or infections and
does not exclude the possibility of ex- from patients with potential endoge-
posure to or infection with HIV. Non- nous interfering substances.
reactive results in this assay may be (F) Detailed documentation of per-
due to analyte levels that are below formance from a multisite clinical
the limit of detection of this assay. study. Performance must be analyzed
(ii) Device verification and validation relative to an FDA-cleared or approved
must include: comparator. This study must be con-
(A) Detailed device description, in- ducted using patient samples, with an
cluding the device components, ancil- appropriate number of HIV positive
lary reagents required but not pro- and HIV negative samples in applicable
vided, and an explanation of the meth- risk categories. Additional subgroups
odology. Additional information appro- or types must be validated using appro-
priate to the technology must be in- priate numbers and types of samples.
cluded, such as the amino acid se- The samples may be a combination of
quence of antigen(s) and design of cap- fresh and repository samples, sourced
ture antibodies. from within and outside the United
(B) For devices with assay cali- States, as appropriate. The study de-
brators, the design of all primary, sec- signs, including number of samples
ondary, and subsequent quantitation tested, must be sufficient to meet the
standards used for calibration as well following criteria:
as their traceability to a reference ma-
(1) Clinical sensitivity of the test
terial. In addition, analytical testing
must have a lower bound of the 95 per-
must be performed following the re-
cent confidence interval of greater
lease of a new lot of the standard mate-
than or equal to 99 percent.
rial that was used for device clearance,
or when there is a transition to a new (2) Clinical specificity of the test
calibration standard. must have a lower bound of the 95 per-
(C) Detailed documentation of ana- cent confidence interval of greater
lytical performance studies conducted than or equal to 99 percent.
as appropriate to the technology, speci- (G) Strategies for detection of new
men types tested, and intended use of strains, types, subtypes, genotypes, and
the device, including, but not limited genetic mutations as they emerge.
to, limit of blank, limit of detection, (H) Risk analysis and management
cutoff determination, precision, endog- strategies, such as Failure Modes Ef-
enous and exogenous interferences, fects Analysis and/or Hazard Analysis
cross reactivity, carryover, quality and Critical Control Points summaries
control, matrix equivalency, and sam- and their impact on test performance.
ple and reagent stability. Samples se- (I) Final release criteria to be used
lected for use in analytical studies or for manufactured test lots with appro-
used to prepare samples for use in ana- priate evidence that lots released at
lytical studies must be from subjects the extremes of the specifications will
with clinically relevant circulating meet the claimed analytical and clin-
genotypes in the United States. ical performance characteristics as
(D) Multisite reproducibility study well as the stability claims.

that includes the testing of three inde- (J) All stability protocols, including
pendent production lots. acceptance criteria.
362
(K) Appropriate and acceptable pro- (A) Detailed documentation of per-

cedure(s) for evaluating customer com- formance from a multisite clinical
plaints and other device information study conducted at appropriate PoC
that determines when to submit a med- sites. Performance must be analyzed
ical device report. relative to an FDA cleared or approved
(L) Premarket notification submis- comparator. This study must be con-
sions must include the information ducted using patient samples, with ap-
contained in paragraph (b)(1)(ii)(A) propriate numbers of HIV positive and
through (K) of this section. HIV negative samples in applicable
(iii) Manufacturers must submit a log risk categories. Additional subgroup or
of all complaints. The log must include type claims must be validated using
the following information regarding appropriate numbers and types of sam-
each complaint if available: The type ples. The samples may be a combina-
of event (e.g., false negative/false non- tion of fresh and repository samples,
reactive or false positive/false reac- sourced from within and outside the
tive), lot, date, population, and wheth- United States, as appropriate. If the
er or not the complaint was reported test is intended solely for PoC use, the
under part 803 of this chapter (Medical test must meet only the performance
Device Reporting). The log must be criteria in paragraphs (b)(2)(v)(A)(1)
submitted annually on the anniversary and (2) of this section and not the cri-
of clearance for 5 years following clear- teria in paragraph (b)(1)(ii)(F) of this
ance of a traditional premarket notifi- section:
cation. (1) Clinical sensitivity of the test
(2) If the test is intended for Point of must have a lower bound of the 95 per-
Care (PoC) use, the following special cent confidence interval of greater
controls, in addition to those listed in than or equal to 98 percent.
paragraph (b)(1) of this section apply: (2) Clinical specificity of the test
(i) The PoC labeling must include a must have a lower bound of the 95 per-
statement that the test is intended for cent confidence interval of greater
PoC use. than or equal to 98 percent.
(ii) The PoC labeling must include (B) Premarket notification submis-
the following information near the sions must include the information
statement of the intended use: contained in paragraph (b)(2)(v)(A) of
(A) That the test is for distribution this section.
to clinical laboratories that have an (3) If the test is intended for supple-
adequate quality assurance program, mental use in addition to use as an aid
including planned systematic activities in initial diagnosis, the following spe-
that provide adequate confidence that cial controls, in addition to those list-
requirements for quality will be met ed in paragraphs (b)(1) and (2) of this
and where there is assurance that oper- section, as appropriate, apply:
ators will receive and use the instruc- (i) The labeling must include a state-
tional materials. ment that the test is intended for use
(B) That the test is for use only by an as an additional test to confirm the
agent of a clinical laboratory. presence of HIV antibodies or antigens
(C) Instructions for individuals to rein specimens found to be repeatedly re-
ceive the ‘‘Subject Information No- active by a diagnostic screening test.
tice’’ prior to specimen collection and (ii) Device validation and verification
appropriate information when test re- for supplemental use must include a
sults are provided. clinical study, including samples that
(iii) PoC labeling must include in- were initially reactive and repeatedly
structions to follow current guidelines reactive on a diagnostic test but were
for informing the individual of the test negative or indeterminate on a dif-
result and its interpretation. ferent confirmatory test. Premarket
(iv) The instructions in the labeling notification submissions must include
must state that reactive results are this information.
considered preliminary and should be (4) If the test is intended solely as a
confirmed following current guidelines. supplemental test, the following spe-

(v) Device verification and validation cial controls, in addition to those list-
for PoC use must include: ed in paragraphs (b)(1) and (2) of this
363
§ 866.3957 21 CFR Ch. I (4–1–23 Edition)
section, except those in paragraphs preted in conjunction with other rel-

(b)(1)(ii)(F) and (b)(2)(v)(A) of this sec- evant clinical and laboratory findings.
tion, as appropriate, apply: These tests are not intended to be used
(i) The labeling must include a state- for monitoring patient status, or for
ment that the test is intended for use screening donors of blood or blood
as an additional test to confirm the products, or human cells, tissues, or
presence of HIV antibodies or antigens cellular or tissue-based products (HCT/
in specimens found to be repeatedly re- Ps).
active by a diagnostic screening test.
(ii) The labeling must clearly state
that the test is not for use for initial controls). The special controls for this
diagnosis or is not intended as a first- device are:
line test. (1) For all HIV NAT diagnostic and/or
(iii) Device validation and supplemental tests
verification must include a clinical (i) The labeling must include:
study including samples that were ini- (A) An intended use that states that
tially reactive and repeatedly reactive the device is not intended for use for
on a diagnostic test but were negative screening donors of blood or blood
or indeterminate on a confirmatory products, or HCT/Ps.
test. Premarket notification submis- (B) A detailed explanation of the
sions must include this information. principles of operation and procedures
(5) If the test is intended to differen- used for performing the assay.
tiate different HIV types, the following (C) A detailed explanation of the in-
special controls, in addition to those terpretation of results and rec-
listed in paragraphs (b)(1) through (4)
ommended actions to take based on re-
of this section, as appropriate, apply:
sults.
(i) The labeling must include the
statement that the test is intended for (D) Limitations, which must be up-
the confirmation of initial results from dated to reflect current clinical prac-
a diagnostic test and differentiation of tice and disease presentation and man-
different HIV types. agement. The limitations must in-
(ii) The results interpretation in the clude, but are not limited to, state-
labeling must include instructions for ments that indicate:
the user on how to interpret the re- (1) The matrices with which the de-
sults, including un-typeable and co-in- vice has been cleared, and that use of
fection results. this test kit with specimen types other
(iii) Device validation and than those specifically cleared for this
verification must include evaluation of device may result in inaccurate test re-
analytical and clinical sensitivity and sults.
specificity for each of the HIV types, (2) The test is not intended to be used
strains, and subtypes of HIV intended to monitor individuals who are under-
to be differentiated. Premarket notifi- going treatment for HIV infection.
cation submissions must include this
(3) A specimen with a reactive result
information.
should be investigated further fol-
[87 FR 29665, May 16, 2022] lowing current guidelines.
(4) All test results should be inter-
§ 866.3957 Human immunodeficiency
virus (HIV) nucleic acid (NAT) diag- preted in conjunction with the individ-
nostic and/or supplemental test. ual’s clinical presentation, history, and
other laboratory results.
(a) Identification. Human immuno-
deficiency virus (HIV) nucleic acid (5) A test result that is nonreactive
(NAT) diagnostic and supplemental does not exclude the possibility of ex-
tests are prescription devices for the posure to or infection with HIV. Non-
qualitative detection of HIV nucleic reactive results in this assay may be
acid in human body fluids or tissues. due to analyte levels that are below
The tests are intended for use as an aid the limit of detection of this assay.
in the diagnosis of infection with HIV (ii) Device verification and validation
and are for professional use only. The must include:
test results are intended to be inter-
364
(A) Detailed device description, in- relative to an FDA cleared or approved

cluding the device components, ancil- comparator. This study must be con-
lary reagents required but not pro- ducted using appropriate patient sam-
vided, and an explanation of the meth- ples, with appropriate numbers of HIV
odology. Additional information appro- positive and negative samples in appli-
priate to the technology must be in- cable risk categories. Additional
cluded, such as design of primers and subtype, strain, or types must be vali-
probes. dated using appropriate numbers and
(B) For devices with assay cali- types of samples. The samples may be
brators, the design and nature of all a combination of fresh and repository
primary, secondary, and subsequent samples, sourced from within and out-
quantitation standards used for cali- side the United States, as appropriate.
bration as well as their traceability to The study designs, including number of
a reference material. In addition, ana- samples tested, must be sufficient to
lytical testing must be performed fol- meet the following criteria:
lowing the release of a new lot of the (1) Clinical sensitivity of the test
standard material that was used for de- must have a lower bound of the 95 per-
vice clearance, or when there is a tran- cent confidence interval of greater
sition to a new calibration standard. than or equal to 99 percent.
(C) Detailed documentation of ana- (2) Clinical specificity of the test
lytical performance studies conducted must have a lower bound of the 95 per-
as appropriate to the technology, speci- cent confidence interval of greater
men types tested, and intended use of than or equal to 99 percent.
the device, including, but not limited (G) Strategies for detection of new
to, limit of blank, limit of detection, strains, types, subtypes, genotypes, and
cutoff determination, precision, endog- genetic mutations as they emerge.
enous and exogenous interferences, (H) Risk analysis and management
cross reactivity, carryover, quality strategies, such as Failure Modes Ef-
control, matrix equivalency, and sam- fects Analysis and/or Hazard Analysis
ple and reagent stability. Samples se- and Critical Control Points summaries
lected for use in analytical studies or and their impact on test performance.
used to prepare samples for use in ana- (I) Final release criteria to be used
lytical studies must be from subjects for manufactured test lots with appro-
with clinically relevant circulating priate evidence that lots released at
genotypes in the United States. The ef- the extremes of the specifications will
fect of each claimed nucleic-acid isola- meet the claimed analytical and clin-
tion and purification procedure on de- ical performance characteristics as
tection must be evaluated. well as the stability claims.
(D) Multisite reproducibility study (J) All stability protocols, including
that includes the testing of three inde- acceptance criteria.
pendent production lots. (K) Appropriate and acceptable pro-
(E) Analytical sensitivity of the test cedure(s) for evaluating customer com-
must be the same as or better than plaints and other device information
that of other cleared or approved tests. that determine when to submit a med-
Samples tested must include appro- ical device report.
priate numbers and types of samples, (L) Premarket notification submis-
including real clinical samples near the sions must include the information
lower limit of detection. Analytical contained in paragraph (b)(1)(ii)(A)
specificity of the test must be as the through (K) of this section.
same as or better than that of other (iii) Manufacturers must submit a log
cleared or approved tests. Samples of all complaints. The log must include
must include appropriate numbers and the following information regarding
types of samples from patients with each complaint, if available: The type
different underlying illnesses or infec- of event (e.g., false negative/false non-
tions and from patients with potential reactive or false positive/false reac-
endogenous interfering substances. tive), lot, date, population, and wheth-
(F) Detailed documentation of per- er or not the complaint was reported

formance from a multisite clinical under part 803 of this chapter (Medical
study. Performance must be analyzed Device Reporting). The log must be
365
§ 866.3957 21 CFR Ch. I (4–1–23 Edition)
submitted annually on the anniversary and (2) of this section and not the cri-
of clearance for 5 years following clear- teria in paragraph (b)(1)(ii)(F) of this
ance of a traditional premarket notifi- section:
cation. (1) Clinical sensitivity of the test
(2) If the test is intended for Point of must have a lower bound of the 95 per-
Care (PoC) use, the following special cent confidence interval of greater
controls, in addition to those listed in than or equal to 98 percent.
paragraph (b)(1) of this section, apply: (2) Clinical specificity of the test
(i) The PoC labeling must include a must have a lower bound of the 95 per-
statement that the test is intended for cent confidence interval of greater
PoC use. than or equal to 98 percent.
(ii) The PoC labeling must include (B) Premarket notification submis-
the following information near the sions must include the information
statement of the intended use: contained in paragraph (b)(2)(v)(A) of
(A) That the test is for distribution this section.
to clinical laboratories that have an (3) If the test is intended for supple-
adequate quality assurance program, mental use in addition to use as an aid
including planned systematic activities in initial diagnosis, the following spe-
that provide adequate confidence that cial controls, in addition to those list-
requirements for quality will be met ed in paragraphs (b)(1) and (2) of this
and where there is assurance that oper- section, as appropriate, apply:
ators will receive and use the instruc- (i) The labeling must include a state-
tional materials. ment that the test is intended for use
(B) That the test is for use only by an as an additional test to confirm the
agent of a clinical laboratory. presence of HIV viral nucleic acid in
(C) Instructions for individuals to re- specimens found to be repeatedly reac-
ceive the ‘‘Subject Information No- tive by a diagnostic screening test.
tice’’ prior to specimen collection and (ii) Device validation and verification
appropriate information when test re- for supplemental use must include a
sults are provided. clinical study, including samples that
(iii) PoC labeling must include in- were initially reactive and repeatedly
structions to follow current guidelines reactive on a diagnostic test but were
for informing the individual of the test negative or indeterminate on a con-
result and its interpretation. firmatory test. Premarket notification
(iv) The instructions in the labeling submissions must include this informa-
must state that reactive results are tion.
considered preliminary and should be (4) If the test is intended solely as a
confirmed following current guidelines. supplemental test, the following spe-
(v) Device verification and validation cial controls, in addition to those list-
for PoC use must include: ed in paragraphs (b)(1) and (2) of this
(A) Detailed documentation from a section, except those in paragraphs
well-conducted multisite clinical study (b)(1)(ii)(F) and (b)(2)(v)(A) of this sec-
conducted at appropriate PoC sites. tion, as appropriate, apply:
Performance must be analyzed relative (i) The labeling must include a state-
to an FDA cleared or approved comment that the test is intended for use
parator. This study must be conducted as an additional test to confirm the
using patient samples, with appro- presence of HIV viral nucleic acid in
priate numbers of HIV positive and specimens found to be repeatedly reac-
HIV negative samples in applicable tive by a diagnostic screening test.
risk categories. Additional subgroup or (ii) The labeling must clearly state
type claims must be validated using that the test is not for use for initial
appropriate numbers and types of sam- diagnosis or is not intended as a first-
ples. The samples may be a combina- line test.
tion of fresh and repository samples, (iii) Device validation and
sourced from within and outside the verification must include a clinical
United States, as appropriate. If the study including samples that were ini-
test is intended solely for PoC use, the tially reactive and repeatedly reactive
test must meet only the performance on a diagnostic test but were negative
criteria in paragraphs (b)(2)(v)(A)(1) or indeterminate on a confirmatory
366
test. Premarket notification submis- (iii) A detailed explanation of the in-

sions must include this information. terpretation of results and that rec-
(5) If the test is intended to differen- ommended actions should be based on
tiate different HIV types, the following current clinical guidelines.
special controls, in addition to those (iv) Limitations, which must be up-
listed in paragraphs (b)(1) through (4) dated to reflect current clinical prac-
of this section, as appropriate, apply: tice and patient management. The lim-
(i) The labeling must include the itations must include, but are not lim-
statement that the test is intended for ited to, statements that indicate:
the confirmation of initial results and (A) The matrices and sample types
differentiation of different HIV types. with which the device has been cleared
(ii) The results interpretation in the and that use of this test with specimen
labeling must include instructions for types other than those specifically
the user on how to interpret the re- cleared for this device may cause inac-
sults, including un-typeable and co-in- curate test results.
fection results. (B) Mutations in highly conserved re-
(iii) Device validation and gions may affect binding of primers
verification must include evaluation of and/or probes resulting in the under-
analytical and clinical sensitivity and quantitation of virus or failure to de-
specificity for each of the types, tect the presence of virus.
strains, and subtypes of HIV intended (C) All test results should be inter-
to be differentiated. Premarket notifi- preted in conjunction with the individ-
cation submissions must include this ual’s clinical presentation, history, and
information. other laboratory results.
[87 FR 29667, May 16, 2022] (2) Device verification and validation
must include:
§ 866.3958 Human immunodeficiency (i) Detailed device description, in-
virus (HIV) viral load monitoring cluding the device components, ancil-
test. lary reagents required but not pro-
(a) Identification. A human immuno- vided, and an explanation of the device
deficiency virus (HIV) viral load moni- methodology. Additional information
toring test is an in vitro diagnostic appropriate to the technology must be
prescription device for the quantita- included, such as detailed information
tion of the amount of HIV ribonucleic on the design of primers and probes.
acid (RNA) in human body fluids. The (ii) For devices with assay cali-
test is intended for use in the clinical brators, the design and nature of all
management of individuals living with primary, secondary, and subsequent
HIV and is for professional use only. quantitation standards used for cali-
The test results are intended to be in- bration as well as their traceability to
terpreted in conjunction with other a reference material. In addition, ana-
relevant clinical and laboratory find- lytical testing must be performed fol-
ings. The test is not intended to be lowing the release of a new lot of the
used as an aid in diagnosis or for standard material that was used for de-
screening donors of blood or blood vice clearance, or when there is a tran-
products or human cells, tissues, or sition to a new calibration standard.
cellular and tissue-based products (iii) Detailed documentation of ana-
(HCT/Ps). lytical performance studies conducted
(b) Classification. Class II (special as appropriate to the technology, speci-
controls). The special controls for this men types tested, and intended use of
device are: the device, including but not limited
(1) The labeling must include: to, limit of blank, limit of detection,
(i) An intended use that states that limit of quantitation, cutoff deter-
the device is not intended for use as an mination, precision, linearity, endoge-
aid in diagnosis or for use in screening nous and exogenous interferences,
donors of blood or blood products, or cross-reactivity, carry-over, quality
HCT/Ps. control, matrix equivalency, sample
(ii) A detailed explanation of the and reagent stability. Samples selected

principles of operation and procedures for use in analytical studies or used to
used for assay performance. prepare samples for use in analytical
367
§ 866.3960 21 CFR Ch. I (4–1–23 Edition)
studies must be from subjects with (vii) Detailed documentation of a sin-

clinically relevant genotypes circu- gle-site analytical method comparison
lating in the United States. study between the device and an FDA-
(iv) Multisite reproducibility study cleared or approved comparator if a
that includes the testing of three inde- multisite clinical study is performed
pendent production lots. under paragraph(b)(2)(vi) of this sec-
(v) Analytical sensitivity of the de- tion. The analytical method compari-
vice must demonstrate acceptable person study must use appropriate num-
formance at current clinically relevant bers and types of samples with analyte
medical decision points. Samples test- concentrations across the measuring
ed to demonstrate analytical sensi- range of the assay, representing clini-
tivity must include appropriate num- cally relevant genotypes. The results
bers and types of samples, including must meet the criteria in paragraphs
real clinical samples near the lower (b)(2)(vi)(B)(1) and (2) of this section.
limit of quantitation and any clini- (viii) Strategies for detection of new
cally relevant medical decision points. strains, types, subtypes, genotypes, and
Analytical specificity of the device genetic mutations as they emerge.
must demonstrate acceptable perform- (ix) Risk analysis and management
ance. Samples tested to demonstrate strategies, such as Failure Modes Ef-
analytical specificity must include ap- fects Analysis and/or Hazard Analysis
propriate numbers and types of sam- and Critical Control Points summaries
ples from patients with different under- and their impact on test performance.
lying illnesses and infection and from (x) Final release criteria to be used
for manufactured device lots with an
patients with potential interfering sub-
appropriate justification that lots re-
stances.
leased at the extremes of the specifica-
(vi) Detailed documentation of per-
tions will meet the claimed analytical
formance from a multisite clinical and clinical performance characteris-
study or a multisite analytical method tics as well as the stability claims.
comparison study. (xi) All stability protocols, including
(A) For devices evaluated in a acceptance criteria.
multisite clinical study, the study (xii) Appropriate and acceptable pro-
must use specimens from individuals cedure(s) for addressing complaints and
living with HIV being monitored for other device information that deter-
changes in viral load, and the test re- mines when to submit a medical device
sults must be compared to the clinical report.
status of the patients. (xiii) Premarket notification submis-
(B) For tests evaluated in a multisite sions must include the information
analytical method comparison study, contained in paragraphs (b)(2)(i)
the performance of the test must be through (xii) of this section.
compared to an FDA-cleared or ap-
[87 FR 66548, Nov. 4, 2022]
proved comparator. The multisite
method comparison study must include § 866.3960 Nucleic acid-based device
appropriate numbers and types of sam- for the amplification, detection, and
ples with analyte concentrations identification of microbial patho-
across the measuring range of the gens directly from whole blood
assay, representing clinically relevant specimens.
genotypes. The multisite method com- (a) Identification. A nucleic acid-based
parison study design, including number device for the amplification, detection,
of samples tested, must be sufficient to and identification of microbial patho-
meet the following criteria: gens directly from whole blood speci-
(1) Agreement between the two tests mens is a qualitative in vitro device in-
across the measuring range of the as- tended for the amplification, detection,
says must have an r2 of greater than or and identification of microbial-associ-
equal to 0.95. ated nucleic acid sequences from pa-
(2) The bias between the test and tients with suspected bloodstream in-
comparator assay, as determined by fections. This device is intended to aid

difference plots, must be less than or in the diagnosis of bloodstream infec-
equal to 0.5 log copies/mL. tion when used in conjunction with
368
clinical signs and symptoms and other the risk of failure to correctly operate
laboratory findings. the instrument.
(b) Classification. Class II (special [82 FR 47967, Oct. 16, 2017]
device are: § 866.3970 Device to detect and iden-
(1) Premarket notification submis- tify microbial pathogen nucleic
sions must include detailed device de- acids in cerebrospinal fluid.
scription documentation, including the (a) Identification. A device to detect
device components, ancillary reagents and identify microbial pathogen nu-
required but not provided, and a de- cleic acids in cerebrospinal fluid is a
tailed explanation of the methodology, qualitative in vitro device intended for
including primer/probe sequence, de- the detection and identification of mi-
sign, and rationale for sequence selec- crobial-associated nucleic acid se-
tion. quences from patients suspected of
(2) Premarket notification submis- meningitis or encephalitis. A device to
sions must include detailed docu- detect and identify microbial pathogen
mentation from the following analyt- nucleic acids in cerebrospinal fluid is
ical and clinical performance studies: intended to aid in the diagnosis of men-
Analytical sensitivity (limit of detec- ingitis or encephalitis when used in
tion), reactivity, inclusivity, precision, conjunction with clinical signs and
reproducibility, interference, cross re- symptoms and other clinical and lab-
activity, carryover, and cross contami- oratory findings.
nation. (b) Classification. Class II (special
(3) Premarket notification submis- controls). The special controls for this
sions must include detailed docu- device are:
mentation from a clinical study. The (1) Premarket notification submis-
study, performed on a study population sions must include detailed device de-
consistent with the intended use popu- scription documentation, including the
lation, must compare the device per- device components, ancillary reagents
formance to results obtained from required but not provided, and a de-
well-accepted reference methods. tailed explanation of the methodology,
including primer/probe sequence, de-
sign, and rationale for sequence selec-
tion.
mentation for device software, includ-
ing, but not limited to, software appli- (2) Premarket notification submis-
cations and hardware-based devices
mentation from the following analyt-
that incorporate software.
ical studies: Analytical sensitivity
(5) The device labeling must include (limit of detection), inclusivity, repro-
limitations regarding the need for cul- ducibility, interference, cross reac-
ture confirmation of negative speci- tivity, and specimen stability.
mens, as appropriate. (3) Premarket notification submis-
(6) A detailed explanation of the in- sions must include detailed docu-
terpretation of results and acceptance mentation from a clinical study. The
criteria must be included in the de- study, performed on a study population
vice’s 21 CFR 809.10(b)(9) compliant la- consistent with the intended use popu-
beling. lation, must compare the device per-
(7) Premarket notification submis- formance to results obtained from
sions must include details on an end well-accepted comparator methods.
user device training program that will (4) Premarket notification submis-
be offered while marketing the device, sions must include detailed docu-
as appropriate. mentation for device software, includ-
(8) As part of the risk management ing, but not limited to, software appli-
activities performed as part of your 21 cations and hardware-based devices
CFR 820.30 design controls, you must that incorporate software.
document an appropriate end user de- (5) The Intended Use statement in
vice training program that will be of- the device labeling must include a
fered as part of your efforts to mitigate statement that the device is intended
369
§ 866.3980 21 CFR Ch. I (4–1–23 Edition)
to be used in conjunction with stand- (6) Rhinovirus; and

ard of care culture. (7) Adenovirus.
(6) A detailed explanation of the in- (b) Classification. Class II (special
terpretation of results and acceptance controls). The special controls are:
criteria must be included in the de- (1) FDA’s guidance document entitled
vice’s 21 CFR 809.10(b)(9) compliant la- ‘‘Class II Special Controls Guidance
beling. Document: Respiratory Viral Panel
(7) The device labeling must include Multiplex Nucleic Acid Assay;’’
a limitation stating that the negative (2) For a device that detects and
results do not preclude the possibility identifies Human Metapneumovirus,
of central nervous system infection. FDA’s guidance document entitled
(8) The device labeling must include
‘‘Class II Special Controls Guidance
a limitation stating that device results
Document: Testing for Human
are not intended to be used as the sole
Metapneumovirus (hMPV) Using Nu-
basis for diagnosis, treatment, or other
cleic Acid Assays;’’ and
patient management decisions.
(9) The device labeling must include (3) For a device that detects and dif-
a limitation stating that positive re- ferentiates Influenza A subtype H1 and
sults do not mean that the organism subtype H3, FDA’s guidance document
detected is infectious or is the causa- entitled ‘‘Class II Special Controls
tive agent for clinical symptoms. Guidance Document: Testing for Detec-
(10) As part of the risk management tion and Differentiation of Influenza A
activities performed as part of your 21 Virus Subtypes Using Multiplex Nu-
CFR 820.30 design controls, you must cleic Acid Assays.’’ See § 866.1(e) for the
document an appropriate end user de- availability of these guidance docu-
vice training program that will be of- ments.
fered as part of your efforts to mitigate [74 FR 52138, Oct. 9, 2009]
the risk of failure to correctly operate
the instrument. § 866.3985 Device to detect and iden-
tify microorganisms and associated
[82 FR 48763, Oct. 20, 2017] resistance marker nucleic acids di-
rectly in respiratory specimens.
§ 866.3980 Respiratory viral panel mul-
tiplex nucleic acid assay. (a) Identification. A device to detect
(a) Identification. A respiratory viral and identify microorganisms and asso-
panel multiplex nucleic acid assay is a ciated resistance marker nucleic acids
qualitative in vitro diagnostic device directly from respiratory specimens is
intended to simultaneously detect and an in vitro diagnostic device intended
identify multiple viral nucleic acids ex- for the detection and identification of
tracted from human respiratory speci- microorganisms and associated resist-
mens or viral culture. The detection ance markers in respiratory specimens
and identification of a specific viral collected from patients with signs or
nucleic acid from individuals exhib- symptoms of respiratory infection. The
iting signs and symptoms of res- device is intended to aid in the diag-
piratory infection aids in the diagnosis nosis of respiratory infection in con-
of respiratory viral infection when used junction with clinical signs and symp-
in conjunction with other clinical and toms and other laboratory findings.
laboratory findings. The device is in- These devices do not provide confirma-
tended for detection and identification tion of antibiotic susceptibility since
of a combination of the following vi- mechanisms of resistance may exist
ruses: other than those detected by the de-
(1) Influenza A and Influenza B; vice.
(2) Influenza A subtype H1 and Influ- (b) Classification. Class II (special
enza A subtype H3; controls). The special controls for this
(3) Respiratory Syncytial Virus device are:
subtype A and Respiratory Syncytial (1) The intended use for the 21 CFR
Virus subtype B; 809.10 labeling must include a detailed
(4) Parainfluenza 1, Parainfluenza 2, description of what the device detects,

and Parainfluenza 3 virus; the type of results provided to the user,
(5) Human Metapneumovirus; the clinical indications appropriate for
370
test use, and the specific population(s) do not indicate susceptibility of de-
for which the device is intended. tected microorganisms.
(2) The 21 CFR 809.10(b) labeling must (4) Design verification and validation
include: must include:
(i) A detailed device description, in- (i) Performance characteristics from
cluding all device components, control clinical studies that include prospec-
elements incorporated into the test tive (sequential) samples and, if appro-
procedure, instrument requirements, priate, additional characterized sam-
ancillary reagents required but not ples. The study must be performed on a
provided, and a detailed explanation of study population consistent with the
the methodology, including all pre-an- intended use population and compare
alytical methods for processing of the device performance to results ob-
specimens. tained from an FDA accepted reference
(ii) Performance characteristics from method and/or FDA accepted com-
analytical studies, including, but not parator method, as appropriate. Re-
limited to, limit of detection, sults from the clinical studies must in-
inclusivity, reproducibility, cross reac- clude the clinical study protocol (in-
tivity, interfering substances, competi- cluding predefined statistical analysis
tive inhibition, carryover/cross con- plan, if applicable), clinical study re-
tamination, specimen stability, and port, and results of all statistical anal-
linearity, as applicable. yses.
(iii) A limiting statement that the (ii) A detailed device description in-
device is intended to be used in concluding the following:
junction with clinical history, signs (A) Thorough description of the assay
and symptoms, and results of other di- methodology including, but not limited
agnostic tests, including culture and to, primer/probe sequences, primer/
antimicrobial susceptibility testing. probe design, and rationale for target
(iv) A detailed explanation of the in- sequence selection, as applicable.
terpretation of test results for clinical (B) Algorithm used to generate a
specimens and acceptance criteria for final result from raw data (e.g., how
any quality control testing. raw signals are converted into a re-
(v) A limiting statement that nega- ported result).
tive results for microorganisms do not (iii) A detailed description of device
preclude the possibility of infection, software, including, but not limited to,
and should not be used as the sole basis validation activities and outcomes.
for diagnosis, treatment, or other pa- (iv) As part of the risk management
tient management decisions. activities, an appropriate end user de-
(vi) If applicable, a limiting state- vice training program must be offered
ment that detected microorganisms as an effort to mitigate the risk of fail-
may not be the cause of lower res- ure from user error.
piratory tract infection and may be in- [84 FR 9228, Mar. 14, 2019]
dicative of colonizing or normal res-
piratory flora. § 866.3990 Gastrointestinal microorga-
(vii) If applicable, a limiting state- nism multiplex nucleic acid-based
ment that detection of resistance assay.
markers cannot be definitively linked (a) Identification. A gastrointestinal
to specific microorganisms and that microorganism multiplex nucleic acid-
the source of a detected resistance based assay is a qualitative in vitro di-
marker may be an organism not de- agnostic device intended to simulta-
tected by the assay, including colo- neously detect and identify multiple
nizing flora. gastrointestinal microbial nucleic
(viii) If applicable, a limiting state- acids extracted from human stool
ment that detection of antibiotic re- specimens. The device detects specific
sistance markers may not correlate nucleic acid sequences for organism
with phenotypic gene expression. identification as well as for deter-
(3) The 21 CFR 809.10(b) labeling and mining the presence of toxin genes.
any test report generated by the device The detection and identification of a
must include a limiting statement that specific gastrointestinal microbial nu-
negative results for resistance markers cleic acid from individuals exhibiting
371
§ 866.4070 21 CFR Ch. I (4–1–23 Edition)
signs and symptoms of gastrointestinal (b) Classification. Class I (general con-

infection aids in the diagnosis of gas- trols). The device is exempt from the
trointestinal infection when used in premarket notification procedures in
conjunction with clinical evaluation subpart E of part 807 of this chapter
and other laboratory findings. A gas- subject to the limitations in § 866.9.
trointestinal microorganism multiplex [47 FR 50823, Nov. 9, 2001, as amended at 66
nucleic acid-based assay also aids in FR 38792, July 25, 2001]
the detection and identification of
acute gastroenteritis in the context of § 866.4500 Immunoelectrophoresis
outbreaks. equipment.
(b) Classification. Class II (special (a) Identification.
controls). The special controls are set Immunoelectrophoresis equipment for
forth in FDA’s guideline document en- clinical use with its electrical power
titled: ‘‘Class II Special Controls supply is a device used for separating
Guideline: Gastrointestinal Microorga- protein molecules.
nism Multiplex Nucleic Acid-Based As- Immunoelectrophoresis is a procedure
says for Detection and Identification of in which a complex protein mixture is
Microorganisms and Toxin Genes from placed in an agar gel and the various
Human Stool Specimens.’’ For avail- proteins are separated on the basis of
ability of the guideline document, see their relative mobilities under the in-
§ 866.1(e). fluence of an electric current. The sep-
arated proteins are then permitted to
[80 FR 67314, Nov. 2, 2015]
diffuse through the agar toward a
multispecific antiserum, allowing pre-
Subpart E—Immunology Labora- cipitation and visualization of the sep-
tory Equipment and Re- arate complexes.
agents (b) Classification. Class I (general con-
§ 866.4070 RNA Preanalytical Systems. premarket notification procedures in
(a) Identification. RNA Preanalytical subpart E of part 807 of this chapter
Systems are devices intended to col- subject to the limitations in § 866.9.
lect, store, and transport patient speci- [47 FR 50823, Nov. 9, 1982, as amended at 54
mens, and stabilize intracellular RNA FR 25047, June 12, 1989; 66 FR 38792, July 25,
from the specimens, for subsequent iso- 2001]
lation and purification of the
intracellular RNA for RT–PCR used in § 866.4520 Immunofluorometer equip-
ment.
in vitro molecular diagnostic testing.
(b) Classification. Class II (special (a) Identification. Immunofluorometer
controls). The special control is FDA’s equipment for clinical use with its
guidance document entitled ‘‘Class II electrical power supply is a device used
Special Controls Guidance Document: to measure the fluorescence of
RNA Preanalytical Systems (RNA Col- fluorochrome-labeled antigen-antibody
lection, Stabilization and Purification complexes. The concentration of these
System for RT–PCR Used in Molecular complexes may be measured by means
Diagnostic Testing).’’ See § 866.1(e) for of reflected light. A beam of light is
the availability of this guidance docu- passed through a solution in which a
ment. fluorochrome has been selectively at-
tached to serum protein antibody mol-
[70 FR 49863, Aug. 25, 2005] ecules in suspension. The amount of
light emitted by the fluorochrome
§ 866.4100 Complement reagent. label is detected by a photodetector,
(a) Identification. A complement rea- which converts light energy into elec-
gent is a device that consists of com- trical energy. The amount of electrical
plement, a naturally occurring serum energy registers on a readout system
protein from any warm-blooded animal such as a digital voltmeter or a record-
such as guinea pigs, that may be ining chart. This electrical readout is
cluded as a component part of sero- called the fluorescence value and is

logical test kits used in the diagnosis used to measure the concentration of
of disease. antigen-antibody complexes.
372
FR 25047, June 12, 1989; 66 FR 38792, July 25,
subject to the limitations in § 866.9. 2001]
FR 25047, June 12, 1989; 66 FR 38792, July 25, § 866.4700 Automated fluorescence in
2001] situ hybridization (FISH) enumera-
tion systems.
§ 866.4540 Immunonephelometer (a) Identification. An automated FISH
equipment.
enumeration system is a device that
(a) Identification. consists of an automated scanning mi-
Immunonephelometer equipment for croscope, image analysis system, and
clinical use with its electrical power customized software applications for
supply is a device that measures light FISH assays. This device is intended
scattering from antigen-antibody com- for in vitro diagnostic use with FISH
plexes. The concentration of these assays as an aid in the detection,
complexes may be measured by means counting and classification of cells
of reflected light. A beam of light based on recognition of cellular color,
passed through a solution is scattered size, and shape, and in the detection
by the particles in suspension. The and enumeration of FISH signals in
amount of light is detected by a interphase nuclei of formalin-fixed,
photodetector, which converts light en- paraffin-embedded human tissue speci-
ergy into electrical energy. The mens.
amount of electrical energy registers
on a readout system such as a digital
voltmeter or a recording chart. This
electrical readout is called the light-
scattering value and is used to measure Special Controls Guidance Document:
the concentration of antigen-antibody Automated Fluorescence in situ Hy-
complexes. This generic type of device bridization (FISH) Enumeration Sys-
includes devices with various kinds of tems.’’ See § 866.1(e) for the availability
light sources, such as laser equipment. of this guidance document.
(b) Classification. Class I (general con- [70 FR 14534, Mar. 23, 2005]
premarket notification procedures in § 866.4750 Automated indirect
subpart E of part 807 of this chapter immunofluorescence microscope
subject to the limitations in § 866.9. and software-assisted system.
[47 FR 50823, Nov. 9, 1982, as amended at 54 (a) Identification. An automated indi-
FR 25047, June 12, 1989; 66 FR 38792, July 25, rect immunofluorescence microscope
2001] and software assisted system is a de-
vice that acquires, analyzes, stores,
§ 866.4600 Ouchterlony agar plate. and displays digital images of indirect
(a) Identification. An ouchterlony immunofluorescent slides. It is in-
agar plate for clinical use is a device tended to be used as an aid in the de-
containing an agar gel used to examine termination of antibody status in clin-
antigen-antibody reactions. In ical samples. The device may include a
immunodiffusion, antibodies and anti- fluorescence microscope with light
gens migrate toward each other source, a motorized microscope stage,
through gel which originally contained dedicated instrument controls, a cam-
neither of these reagents. As the re- era, a computer, a sample processor, or
agents come in contact with each other hardware components. The de-
other, they combine to form a precipi- vice may use fluorescent signal acqui-
tate that is trapped in the gel matrix sition and processing software, data
and is immobilized. storage and transferring mechanisms,
(b) Classification. Class I (general con- or assay specific algorithms to suggest

trols). The device is exempt from the results. A trained operator must con-
premarket notification procedures in firm results generated with the device.
373
§ 866.4750 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class II (special and the differential diagnosis popu-

controls). The special controls for this lation. For all samples, the diagnostic
device are: clinical criteria and the demographic
(1) The labeling for the device must information must be collected and pro-
reference legally marketed assays in- vided. Clinical validation must be
tended for use with the device. based on the determination of clinical
(2) Premarket notification submis- sensitivity and clinical specificity
sions must include the following infor- using the test results (e.g., antibody
mation: status based on fluorescence to include
(i) A detailed description of the de- pattern and titer, if applicable) com-
vice that includes: pared to the clinical diagnosis of the
(A) A detailed description of instru- subject from whom the clinical sample
mentation and equipment, and illustra- was obtained. The data must be sum-
tions or photographs of non-standard marized in tabular format comparing
equipment or methods, if applicable; the result generated by automated,
(B) Detailed documentation of the manual, and digital only interpretation
software, including, but not limited to, to the disease status;
stand-alone software applications and (C) Device precision/reproducibility
hardware-based devices that incor- data generated from within-run, be-
porate software, if applicable; tween-run, between-day, between-lot,
(C) A detailed description of appro- between-operator, between-instru-
priate internal and external quality ments, between-site, and total preci-
controls that are recommended or pro- sion for multiple nonconsecutive days
vided. The description must identify (as applicable) using multiple opera-
those control elements that are incor- tors, multiple instruments and at mul-
porated into the recommended testing tiple sites. A well-characterized panel
procedures; of patient samples or pools from the as-
(D) Detailed description and speci- sociated assay specific intended use
fications for sample preparation, proc- population must be used;
essing, and storage, if applicable; (D) Device linearity data generated
(E) Methodology and protocols for de- from patient samples covering the
tecting fluorescence and visualizing re- assay measuring range, if applicable;
sults; and
(E) Device analytical sensitivity
(F) Detailed specification of the cri-
data, including limit of blank, limit of
teria for test results interpretation and
detection, and limit of quantitation, if
reporting.
applicable;
(ii) Data demonstrating the perform-
(F) Device assay specific cutoff, if ap-
ance characteristics of the device,
plicable;
which must include:
(A) A comparison study of the results (G) Device analytical specificity
obtained with the conventional manual data, including interference by endoge-
method (i.e., reference standard), the nous and exogenous substances, if ap-
device, and the reading of the digital plicable;
image without aid of the software, (H) Device instrument carryover
using the same set of patient samples data, if applicable;
for each. The study must use a legally (I) Device stability data including
marketed assay intended for use with real-time stability under various stor-
the device. Patient samples must be age times and temperatures, if applica-
from the assay-specific intended use ble; and
population and differential diagnosis (J) Information on traceability to a
population. Samples must also cover reference material and description of
the assay measuring range, if applica- value assignment of calibrators and
ble; controls, if applicable.
(B) Device clinical performance es- (iii) Identification of risk mitigation
tablished by comparing device results elements used by the device, including
at multiple U.S. sites to the clinical di- description of all additional proce-
agnostic standard used in the United dures, methods, and practices, incor-
States, using patient samples from the porated into the directions for use that
assay-specific intended use population mitigate risks associated with testing.
374
(3) Your 21 CFR 809.10 compliant la- (b) Classification. Class I (general con-
beling must include: trols). The device is exempt from the
(i) A warning statement that reads premarket notification procedures in
‘‘The device is for use by a trained op- subpart E of part 807 of this chapter
erator in a clinical laboratory setting’’; subject to the limitations in § 866.9.
(ii) A warning statement that reads
‘‘All software-aided results must be
FR 25047, June 12, 1989; 66 FR 38792, July 25,
confirmed by the trained operator’’; 2001]
(iii) A warning statement that reads
‘‘This device is only for use with re- § 866.4900 Support gel.
agents that are indicated for use with
the device’’; and (a) Identification. A support gel for
(iv) A description of the protocol and clinical use is a device that consists of
performance studies performed in ac- an agar or agarose preparation that is
cordance with paragraph (b)(2)(ii) of used while measuring various kinds of,
this section and a summary of the re- or parts of, protein molecules by var-
sults, if applicable. ious immunochemical techniques, such
as immunoelectrophoresis,
[82 FR 52648, Nov. 14, 2017, as amended at 86 immunodiffusion, or chromatography.
FR 20283, Apr. 19, 2021]
§ 866.4800 Radial immunodiffusion trols). The device is exempt from the
plate. premarket notification procedures in
(a) Identification. A radial subpart E of part 807 of this chapter
immunodiffusion plate for clinical use subject to the limitations in § 866.9.
is a device that consists of a plastic [47 FR 50823, Nov. 9, 1982, as amended at 54
plate to which agar gel containing FR 25047, June 12, 1989; 66 FR 38792, July 25,
antiserum is added. In radial 2001]
immunodiffusion, antigens migrate
through gel which originally contains Subpart F—Immunological Test
specific antibodies. As the reagents Systems
come in contact with each other, they
combine to form a precipitate that is § 866.5040 Albumin immunological test
trapped in the gel matrix and immo- system.
bilized.
(a) Identification. An albumin
immunological test system is a device
premarket notification procedures in that consists of the reagents used to
subpart E of part 807 of this chapter measure by immunochemical tech-
subject to the limitations in § 866.9. niques the albumin (a plasma protein)
in serum and other body fluids. Meas-
[47 FR 50823, Nov. 9, 1982, as amended at 66 urement of albumin aids in the diag-
FR 38792, July 25, 2001] nosis of kidney and intestinal diseases.
§ 866.4830 Rocket immunoelectro- (b) Classification. Class II (special
phoresis equipment. controls). The device is exempt from
(a) Identification. Rocket in subpart E of part 807 of this chapter
immunoelectrophoresis equipment for subject to § 866.9.
clinical use is a device used to perform
a specific test on proteins by using a [47 FR 50823, Nov. 9, 1982, as amended at 63
procedure called rocket FR 59227, Nov. 3, 1998]
immunoelectrophoresis. In this proce-
dure, an electric current causes the § 866.5060 Prealbumin immunological
protein in solution to migrate through test system.
agar gel containing specific antisera. (a) Identification. A prealbumin
The protein precipitates with the immunological test system is a device
antisera in a rocket-shaped pattern, that consists of the reagents used to
giving the name to the device. The measure by immunochemical tech-
height of the peak (or the area under niques the prealbumin (a plasma pro-
the peak) is proportional to the con- tein) in serum and other body fluids.
centration of the protein. Measurement of prealbumin levels in
375
§ 866.5065 21 CFR Ch. I (4–1–23 Edition)
serum may aid in the assessment of the of liver tissue) and chronic active hepa-
patient’s nutritional status. titis (inflammation of the liver).
(b) Classification. Class I (general con- (b) Classification. Class II (perform-
trols). The device is exempt from the ance standards).
subpart E of part 807 of this chapter § 866.5100 Antinuclear antibody
subject to § 866.9. immunological test system.
[47 FR 50823, Nov. 9, 1982, as amended at 65 (a) Identification. An antinuclear
FR 2312, Jan. 14, 2000] antibody immunological test system is
a device that consists of the reagents
§ 866.5065 Human allotypic marker used to measure by immunochemical
immunological test system. techniques the autoimmune antibodies
(a) Identification. A human allotypic in serum, other body fluids, and tissues
marker immunological test system is a that react with cellular nuclear con-
device that consists of the reagents stituents (molecules present in the nu-
used to identify by immunochemical cleus of a cell, such as ribonucleic acid,
techniques the inherited human pro- deoxyribonucleic acid, or nuclear pro-
tein allotypic markers (such as nGm, teins). The measurements aid in the di-
nA2 m, and Km allotypes) in serum and agnosis of systemic lupus
other body fluids. The identification erythematosus (a multisystem auto-
may be used while studying population immune disease in which antibodies at-
genetics. tack the victim’s own tissues), hepa-
(b) Classification. Class I (general con- titis (a liver disease), rheumatoid ar-
trols). The device is exempt from the thritis, Sjögren’s syndrome (arthritis
premarket notification procedures in with inflammation of the eye, eyelid,
subpart E of part 807 of this chapter and salivary glands), and systemic scle-
subject to § 866.9. rosis (chronic hardening and shrinking
of many body tissues).
FR 2312, Jan. 14, 2000] (b) Classification. Class II (perform-
ance standards).
§ 866.5080 Alpha-1-antichymotrypsin
immunological test system. § 866.5110 Antiparietal antibody
(a) Identification. An alpha-1-
antichymotrypsin immunological test (a) Identification. An antiparietal
system is a device that consists of the antibody immunological test system is
reagents used to measure by a device that consists of the reagents
immunochemical techniques alpha-1- used to measure by immunochemical
antichymotrypsin (a protein) in serum, techniques the specific antibody for
other body fluids, and tissues. Alpha-1- gastric parietal cells in serum and
antichymotrypsin helps protect tissues other body fluids. Gastric parietal cells
against proteolytic (protein-splitting) are those cells located in the stomach
enzymes released during infection. that produce a protein that enables vi-
(b) Classification. Class II (perform- tamin B12 to be absorbed by the body.
ance standards). The measurements aid in the diagnosis
of vitamin B12 deficiency (or pernicious
§ 866.5090 Antimitochondrial antibody anemia), atrophic gastritis (inflamma-
immunological test system. tion of the stomach), and autoimmune
(a) Identification. An connective tissue diseases (diseases re-
antimitochondrial antibody sulting when the body produces anti-
immunological test system is a device bodies against its own tissues).
that consists of the reagents used to (b) Classification. Class II (perform-
measure by immunochemical tech- ance standards).
niques the antimitochondrial anti-
bodies in human serum. The measure- § 866.5120 Antismooth muscle antibody
ments aid in the diagnosis of diseases immunological test system.
that produce a spectrum of (a) Identification. An antismooth mus-
autoantibodies (antibodies produced cle antibody immunological test sys-

against the body’s own tissue), such as tem is a device that consists of the re-
primary biliary cirrhosis (degeneration agents used to measure by
376
immunochemical techniques the kemia (cancer of the blood-forming or-

antismooth muscle antibodies (anti- gans), and lymphoma (cancer of the
bodies to nonstriated, involuntary lymphoid tissue).
muscle) in serum. The measurements (b) Classification. Class II (perform-
aid in the diagnosis of chronic hepa- ance standards).
titis (inflammation of the liver) and
autoimmune connective tissue diseases § 866.5160 Beta-globulin immunolog-
(diseases resulting from antibodies pro- ical test system.
duced against the body’s own tissues). (a) Identification. A beta-globulin
(b) Classification Class II (perform- immunological test system is a device
ance standards). that consists of reagents used to meas-
ure by immunochemical techniques
§ 866.5130 Alpha-1-antitrypsin beta globulins (serum protein) in serum
immunological test system. and other body fluids. Beta-globulin
(a) Identification. An alpha-1- proteins include beta-lipoprotein,
antitrypsin immunological test system transferrin, glycoproteins, and com-
is a device that consists of the reagents plement, and are rarely associated with
used to measure by immunochemical specific pathologic disorders.
techniques the alpha-1-antitrypsin (a (b) Classification. Class I (general con-
plasma protein) in serum, other body trols). The device is exempt from the
fluids, and tissues. The measurements premarket notification procedures in
aid in the diagnosis of several condi- subpart E of part 807 of this chapter
tions including juvenile and adult cir- subject to § 866.9.
rhosis of the liver. In addition, alpha-1- [47 FR 50823, Nov. 9, 1982, as amended at 65
antitrypsin deficiency has been associ- FR 2312, Jan. 14, 2000]
ated with pulmonary emphysema.
(b) Classification. Class II (perform- § 866.5170 Breast milk immunological
ance standards). test system.
(a) Identification. A breast milk
§ 866.5150 Bence-Jones proteins immunological test system is a device
immunological test system. that consists of the reagents used to
(a) Identification. A Bence-Jones pro- measure by immunochemical tech-
teins immunological test system is a niques the breast milk proteins.
device that consists of the reagents (b) Classification. Class I (general con-
used to measure by immunochemical trols). The device is exempt from the
techniques the Bence-Jones proteins in premarket notification procedures in
urine and plasma. Immunoglobulin subpart E of part 807 of this chapter
molecules normally consist of pairs of subject to the limitations in § 866.9.
polypeptide chains (subunits) of un- [47 FR 50823, Nov. 9, 1982, as amended at 59
equal size (light chains and heavy FR 63007, Dec. 7, 1994; 66 FR 38793, July 25,
chains) bound together by several di- 2001]
sulfide bridges. In some cancerous con-
ditions, there is a proliferation of one § 866.5180 Fecal calprotectin
plasma cell (antibody-producing cell) immunological test system.
with excess production of light chains (a) Identification. A fecal calprotectin
of one specific kind (monoclonal light immunological test system is an in
chains). These free homogeneous light vitro diagnostic device that consists of
chains not associated with an reagents used to quantitatively meas-
immunoglobulin molecule can be found ure, by immunochemical techniques,
in urine and plasma, and have been fecal calprotectin in human stool
called Bence-Jones proteins. Measure- specimens. The device is intended forin
ment of Bence-Jones proteins and de- vitro diagnostic use as an aid in the di-
termination that they are monoclonal agnosis of inflammatory bowel diseases
aid in the diagnosis of multiple (IBD), specifically Crohn’s disease and
myeloma (malignant proliferation of ulcerative colitis, and as an aid in dif-
plasma cells), Waldenstrom’s ferentiation of IBD from irritable
macroglobulinemia (increased produc- bowel syndrome.

tion of large immunoglobulins by (b) Classification. Class II (special
spleen and bone marrow cells), leu- controls). The special control for these
377
§ 866.5200 21 CFR Ch. I (4–1–23 Edition)
devices is FDA’s guidance document fication of IgG subclasses, and to re-

entitled ‘‘Class II Special Controls duce nonspecific adsorption of plasma
Guidance Document: Fecal proteins in immunoassay techniques.
Calprotectin Immunological Test Sys- Measurement of these proteins aids in
tems.’’ For the availability of this the diagnosis of any disease concerned
guidance document, see § 866.1(e). with abnormal levels of IgG gamma
[71 FR 42598, July 27, 2006]
globulins such as agammaglobulinemia
or multiple myeloma.
§ 866.5200 Carbonic anhydrase B and (b) Classification. Class I (general con-
C immunological test system. trols). The device is exempt from the
(a) Identification. A carbonic anhy- premarket notification procedures in
drase B and C immunological test sys- subpart E of part 807 of this chapter
tem is a device that consists of the re- subject to the limitations in § 866.9.
agents used to measure by [47 FR 50823, Nov. 9, 1982, as amended at 59
immunochemical techniques specific FR 63007, Dec. 7, 1994; 66 FR 38793, July 25,
carbonic anhydrase protein molecules 2001]
in serum and other body fluids. Meas-
urements of carbonic anhydrase B and § 866.5230 Colostrum immunological
test system.
C aid in the diagnosis of abnormal he-
moglobin metabolism. (a) Identification. A colostrum
(b) Classification. Class I (general con- immunological test system is a device
trols). The device is exempt from the that consists of the reagents used to
premarket notification procedures in measure by immunochemical tech-
subpart E of part 807 of this chapter niques the specific proteins in colos-
subject to § 866.9. trum. Colostrum is a substance ex-
creted by the mammary glands during
FR 2312, Jan. 14, 2000]
pregnancy and until production of
breast milk begins 1 to 5 days after
§ 866.5210 Ceruloplasmin immunolog- childbirth.
ical test system. (b) Classification. Class I (general con-
(a) Identification. A ceruloplasmin trols). The device is exempt from the
immunological test system is a device premarket notification procedures in
that consists of the reagents used to subpart E of part 807 of this chapter
measure by immunochemical tech- subject to the limitations in § 866.9.
niques the ceruloplasmin (copper- [47 FR 50823, Nov. 9, 1982, as amended at 59
transporting serum protein) in serum, FR 63007, Dec. 7, 1994; 66 FR 38793, July 25,
other body fluids, or tissues. Measure- 2001]
ments of ceruloplasmin aid in the diag-
nosis of copper metabolism disorders. § 866.5240 Complement components
(b) Classification. Class II (special immunological test system.
controls). The device is exempt from (a) Identification. A complement com-
the premarket notification procedures ponents immunological test system is
in subpart E of part 807 of this chapter a device that consists of the reagents
subject to the limitations in § 866.9. used to measure by immunochemical
techniques complement components
FR 71800, Dec. 30, 2019]
C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and
C9, in serum, other body fluids, and tis-
§ 866.5220 Cohn fraction II immunolog- sues. Complement is a group of serum
ical test system. proteins which destroy infectious
(a) Identification. A Cohn fraction II agents. Measurements of these proteins
immunological test system is a device aids in the diagnosis of immunologic
that consists of the reagents that con- disorders, especially those associated
tain or are used to measure that frac- with deficiencies of complement com-
tion of plasma containing protein ponents.
gamma globulins, predominantly of the (b) Classification. Class II (perform-
ance standards).
IgG class. The device may be used as a

coprecipitant in radioimmunoassay [47 FR 50823, Nov. 9, 1982, as amended at 53
methods, as raw material for the puri- FR 11253, Apr. 6, 1988]
378
§ 866.5250 Complement C1 inhibitor niques properdin factor B in serum and

(inactivator) immunological test other body fluids. The deposition of
system. properdin factor B in body tissues or a
(a) Identification. A complement C1 corresponding depression in the
inhibitor (inactivator) immunological amount of properdin factor B in serum
test system is a device that consists of and other body fluids is evidence of the
the reagents used to measure by involvement of the alternative to the
immunochemical techniques the com- classical pathway of activation of com-
plement C1 inhibitor (a plasma protein) plement (a group of plasma proteins
in serum. Complement C1 inhibitor oc- which cause the destruction of cells
curs normally in plasma and blocks the which are foreign to the body). Meas-
action of the C1 component of com- urement of properdin factor B aids in
plement (a group of serum proteins the diagnosis of several kidney dis-
which destroy infectious agents). Meas- eases, e.g., chronic glomerulonephritis
urement of complement C1 inhibitor (inflammation of the glomeruli of the
aids in the diagnosis of hereditary kidney), lupus nephritis (kidney dis-
angioneurotic edema (increased blood ease associated with a multisystem
vessel permeability causing swelling of autoimmune disease, systemic lupus
tissues) and a rare form of angioedema erythematosus), as well as several skin
associated with lymphoma (lymph node diseases, e.g., dermititis herpetiformis
cancer). (presence of vesicles on the skin that
(b) Classification. Class II (perform- burn and itch), and pemphigus vulgaris
ance standards). (large vesicles on the skin). Other dis-
eases in which the alternate pathway
§ 866.5260 Complement C3b inactivator of complement activation has been im-
immunological test system. plicated include rheumatoid arthritis,
(a) Identification. A complement C3b sickle cell anemia, and gram-negative
inactivator immunological test system bacteremia.
is a device that consists of the reagents (b) Classification. Class II (special
used to measure by immunochemical controls). The device is exempt from
techniques the complement C3b the premarket notification procedures
inactivator (a plasma protein) in in subpart E of part 807 of this chapter
serum. Complement is a group of serum subject to § 866.9.
proteins that destroy infectious agents. [47 FR 50823, Nov. 9, 1982, as amended at 63
Measurement of complement C3b FR 59227, Nov. 3, 1998]
inactivator aids in the diagnosis of in-
herited antibody dysfunction. § 866.5330 Factor XIII, A, S, immuno-
(b) Classification. Class II (perform- logical test system.
ance standards). (a) Identification. A factor XIII, A, S,
§ 866.5270 C-reactive protein immuno- immunological test system is a device
logical test system. that consists of the reagents used to
measure by immunochemical tech-
(a) Identification. A C-reactive protein
niques the factor XIII (a bloodclotting
factor), in platelets (A) or serum (S).
that consists of the reagents used to
Measurements of factor XIII, A, S, aid
in the diagnosis and treatment of cer-
niques the C-reactive protein in serum
tain bleeding disorders resulting from a
and other body fluids. Measurement of
deficiency of this factor.
C-reactive protein aids in evaluation of
the amount of injury to body tissues.
(b) Classification. Class II (perform- trols). The device is exempt from the
ance standards). premarket notification procedures in
§ 866.5320 Properdin factor B immuno- subject to § 866.9. This exemption does
logical test system. not apply to factor deficiency tests
(a) Identification. A properdin factor classified under § 864.7290 of this chap-
ter.
B immunological test system is a de-

vice that consists of the reagents used [47 FR 50823, Nov. 9, 1982, as amended at 65
to measure by immunochemical tech- FR 2312, Jan. 14, 2000]
379
§ 866.5340 21 CFR Ch. I (4–1–23 Edition)
§ 866.5340 Ferritin immunological test § 866.5370 Cohn fraction V immuno-

system. logical test system.
(a) Identification. A ferritin (a) Identification. A Cohn fraction V
immunological test system is a device immunological test system is a device
that consists of the reagents used to that consists of or measures that frac-
measure by immunochemical tech- tion of plasma containing predomi-
niques the ferritin (an iron-storing pro- nantly albumin (a plasma protein).
tein) in serum and other body fluids. This test aids in the diagnosis of dis-
Measurements of ferritin aid in the di- eases where albumin levels may be de-
agnosis of diseases affecting iron me- pressed, e.g., nephrosis (disease of the
tabolism, such as hemochromatosis kidney), proteinuria (protein in the
(iron overload) and iron deficiency urine), gastroenteropathy (disease of
amemia. the stomach and small intestine), rheu-
matoid arthritis, and viral hepatitis.
ance standards). (b) Classification. Class I (general con-
§ 866.5350 Fibrinopeptide A immuno- premarket notification procedures in
logical test system. subpart E of part 807 of this chapter
(a) Identification. A fibrinopeptide A
immunological test system is a device [47 FR 50823, Nov. 9, 1982, as amended at 59
that consists of the reagents used to FR 63007, Dec. 7, 1994; 66 FR 38793, July 25,
measure by immunochemical tech- 2001]
niques the fibrinopeptide A (a blood-
§ 866.5380 Free secretory component
clotting factor) in plasma and other immunological test system.
body fluids. Measurement of
fibrinopeptide A may aid in the diag- (a) Identification. A free secretory
nosis and treatment of certain blood- component immunological test system
clotting disorders. is a device that consists of the reagents
used to measure by immunochemical
techniques free secretory component
ance standards).
(normally a portion of the secretory
§ 866.5360 Cohn fraction IV immuno- IgA antibody molecule) in body fluids.
logical test system. Measurement of free secretory compo-
nent (protein molecules) aids in the di-
(a) Identification. A Cohn fraction IV agnosis or repetitive lung infections
immunological test system is a device and other hypogammaglobulinemic
that consists of or measures that frac- conditions (low antibody levels).
tion of plasma proteins, predominantly (b) Classification. Class II (special
alpha- and beta- globulins, used as a controls). The device is exempt from
raw material for the production of pure the premarket notification procedures
alpha- or beta- globulins. Measurement in subpart E of part 807 of this chapter
of specific alpha- or beta- globulins aids subject to § 866.9.
in the diagnosis of many diseases, such
as Wilson’s disease (an inherited dis- [47 FR 50823, Nov. 9, 1982, as amended at 63
FR 59227, Nov. 3, 1998]
ease affecting the liver and brain),
Tangier’s disease (absence of alpha-1- § 866.5400 Alpha-globulin immuno-
lipoprotein), malnutrition, iron defi- logical test system.
ciency anemia, red blood cell disorders,
and kidney disease. (a) Identification. An alpha-globulin
premarket notification procedures in niques the alpha-globulin (a serum pro-
subpart E of part 807 of this chapter tein) in serum and other body fluids.
subject to the limitations in § 866.9. Measurement of alpha-globulin may
[47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, aid in the diagnosis of inflammatory
1982, as amended at 59 FR 63007, Dec. 7, 1994; lesions, infections, severe burns, and a
66 FR 38793, July 25, 2001] variety of other conditions.
380
(b) Classification. Class I (general con- § 866.5430 Beta-2-glycoprotein I

trols). The device is exempt from the immunological test system.
premarket notification procedures in (a) Identification. A beta-2-
subpart E of part 807 of this chapter glycoprotein I immunological test sys-
subject to § 866.9. tem is a device that consists of the re-
[47 FR 50823, Nov. 9, 1982, as amended at 65 agents used to measure by
FR 2312, Jan. 14, 2000] immunochemical techniques the beta-2-
glycoprotein I (a serum protein) in
§ 866.5420 Alpha-1-glycoproteins serum and other body fluids. Measure-
immunological test system. ment of beta-2-glycoprotein I aids in
(a) Identification. An alpha-1- the diagnosis of an inherited deficiency
glycoproteins immunological test sys- of this serum protein.
tem is a device that consists of the re- (b) Classification. Class I (general con-
agents used to measure by trols). The device is exempt from the
immunochemical techniques alpha-1- premarket notification procedures in
glycoproteins (a group of plasma pro- subpart E of part 807 of this chapter
teins found in the alpha-1 group when
subjected to electrophoresis) in serum [47 FR 50823, Nov. 9, 1982, as amended at 65
and other body fluids. Measurement of FR 2312, Jan. 14, 2000]
specific alpha-1-glycoproteins may aid
in the diagnosis of collagen (connective § 866.5440 Beta-2-glycoprotein III
tissue) disorders, tuberculosis, infec-
tions, extensive malignancy, and diabe- (a) Identification. A beta-2-
tes. glycoprotein III immunological test
(b) Classification. Class I (general con- system is a device that consists of the
trols). The device is exempt from the reagents used to measure by
premarket notification procedures in immunochemical techniques the beta-2-
subpart E of part 807 of this chapter glycoprotein III (a serum protein) in
subject to § 866.9. serum and other body fluids. Measure-
ment of beta-2-glycoprotein III aids in
[47 FR 50823, Nov. 9, 1982, as amended at 65 the diagnosis of an inherited deficiency
FR 2312, Jan. 14, 2000] of this serum protein and a variety of
other conditions.
§ 866.5425 Alpha-2-glycoproteins (b) Classification. Class I (general con-
immunological test system. trols). The device is exempt from the
(a) Identification. An alpha-2- premarket notification procedures in
glycoproteins immunolgical test sys- subpart E of part 807 of this chapter
tem is a device that consists of the re- subject to § 866.9.
agents used to measure by [47 FR 50823, Nov. 9, 1982, as amended at 65
immunochemical techniques the alpha- FR 2312, Jan. 14, 2000]
2-glycoproteins (a group of plasma pro-
teins found in the alpha-2 group when § 866.5460 Haptoglobin immunological
subjected to electrophoresis) in serum test system.
and other body fluids. Measurement of (a) Identification. A haptoglobin
alpha-2-glycoproteins aids in the diag- immunological test system is a device
nosis of some cancers and genetically that consists of the reagents used to
inherited deficiencies of these plasma measure by immunochemical tech-
proteins. niques the haptoglobin (a protein that
(b) Classification. Class I (general con- binds hemoglobin, the oxygen-carrying
trols). The device is exempt from the pigment in red blood cells) in serum.
premarket notification procedures in Measurement of haptoglobin may aid
subpart E of part 807 of this chapter in the diagnosis of hemolytic diseases
subject to § 866.9. (diseases in which the red blood cells
rupture and release hemoglobin) re-
[47 FR 50823, Nov. 9, 1982, as amended at 65 lated to the formation of hemoglobin-

FR 2312, Jan. 14, 2000] haptoglobin complexes and certain kid-
ney diseases.
381
§ 866.5470 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class II (special § 866.5500 Hypersensitivity pneumo-

controls). The device is exempt from nitis immunological test system.
the premarket notification procedures (a) Identification. A hypersensitivity
in subpart E of part 807 of this chapter pneumonitis immunological test sys-
subject to § 866.9. tem is a device that consists of the re-
[47 FR 50823, Nov. 9, 1982, as amended at 63 agents used to measure by
FR 59227, Nov. 3, 1998] immunochemical techniques the
immunoglobulin antibodies in serum
§ 866.5470 Hemoglobin immunological which react specifically with organic
test system. dust derived from fungal or animal pro-
(a) Indentification. A hemoglobin tein sources. When these antibodies
immunological test system is a device react with such dusts in the lung, im-
mune complexes precipitate and trig-
ger an inflammatory reaction (hyper-
sensitivity pneumonitis). Measurement
niques the different types of free hemo-
of these immunoglobulin G antibodies
globin (the oxygen-carrying pigment in
aids in the diagnosis of hyper-
red blood cells) in blood, urine, plasma,
sensitivity pneumonitis and other al-
or other body fluids. Measurements of
lergic respiratory disorders.
free hemoglobin aid in the diagnosis of
various hematologic disorders, such as
ance standards).
sickle cell anemia, Fanconi’s anemia (a
rare inherited disease), aplastic anemia § 866.5510 Immunoglobulins A, G, M, D,
(bone marrow does not produce enough and E immunological test system.
blood cells), and leukemia (cancer of (a) Identification. An
the blood-forming organs). immunoglobulins A, G, M, D, and E
(b) Classification. Class II (special immunological test system is a device
controls). The device is exempt from that consists of the reagents used to
the premarket notification procedures measure by immunochemical tech-
in subpart E of part 807 of this chapter niques the immunoglobulins A, G, M,
subject to the limitations in § 866.9. D, an E (serum antibodies) in serum.
[47 FR 50823, Nov. 9, 1982, as amended at 84 Measurement of these
FR 71800, Dec. 30, 2019] immunoglobulins aids in the diagnosis
of abnormal protein metabolism and
§ 866.5490 Hemopexin immunological the body’s lack of ability to resist in-
test system. fectious agents.
(a) Indentification. A hemopexin (b) Classification. Class II (perform-
immunological test system is a device ance standards).
that consists of the reagents used to § 866.5520 Immunoglobulin G (Fab
measure by immunochemical tech- fragment specific) immunological
niques the hemopexin (a serum protein test system.
that binds heme, a component of hemo-
(a) Identification. An immunoglobulin
globin) in serum. Measurement of
G (Fab fragment specific)
hemopexin aids in the diagnosis of var-
ious hematologic disorders, such as he-
molytic anemia (anemia due to short-
ened in vivo survival of mature red
niques the Fab antigen-binding frag-
blood cells and inability of the bone
ment resulting from breakdown of
marrow to compensate for their de-
immunoglobulin G antibodies in urine,
creased life span) and sickle cell ane-
serum, and other body fluids. Measure-
mia.
ment of Fab fragments of
(b) Classification. Class II (special immunoglobulin G aids in the diag-
controls). The device is exempt from nosis of lymphoproliferative disorders,
the premarket notification procedures such as multiple myeloma (tumor of
in subpart E of part 807 of this chapter bone marrow cells), Waldenstrom’s
macroglobulinemia (increased
[47 FR 50823, Nov. 9, 1982, as amended at 63 immunoglobulin production by the
FR 59227, Nov. 3, 1998] spleen and bone marrow cells), and
382
lymphoma (tumor of the lymphoid tis- subpart E of part 807 of this chapter
sues). subject to the limitations in § 866.9.
trols). The device is exempt from the FR 63007, Dec. 7, 1994; 66 FR 38793, July 25,
subject to the limitations in § 866.9. § 866.5550 Immunoglobulin (light
chain specific) immunological test
[47 FR 50823, Nov. 9, 1982, as amended at 61 system.
FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, (a) Identification. An immunoglobulin
2001] (light chain specific) immunological
test system is a device that consists of
§ 866.5530 Immunoglobulin G (Fc frag-
the reagents used to measure by
ment specific) immunological test
system. immunochemical techniques both
kappa and lambda types of light chain
(a) Identification. An immunoglobulin portions of immunoglobulin molecules
G (Fc fragment specific) in serum, other body fluids, and tis-
immunological test system is a device sues. In some disease states, an excess
that consists of the reagents used to of light chains are produced by the
measure by immunochemical tech- antibody-forming cells. These free
niques the Fc (carbohydrate con- light chains, unassociated with gamma
taining) fragment of immunoglobulin globulin molecules, can be found in a
G (resulting from breakdown of patient’s body fluids and tissues. Meas-
immunoglobulin G antibodies) in urine, urement of the various amounts of the
serum, and other body fluids. Measure- different types of light chains aids in
ment of immunoglobulin G Fc frag- the diagnosis of multiple myeloma
ments aids in the diagnosis of plasma (cancer of antibody-forming cells),
cell antibody-forming abnormalities, lymphocytic neoplasms (cancer of
e.g., gamma heavy chain disease. lymphoid tissue), Waldenstrom’s
macroglobulinemia (increased produc-
tion of large immunoglobulins), and
connective tissue diseases such as
premarket notification procedures in rheumatoid arthritis or systemic lupus
subpart E of part 807 of this chapter erythematosus.
subject to the limitations in § 866.9. (b) Classification. Class II (perform-
[47 FR 50823, Nov. 9, 1982, as amended at 61 ance standards).
FR 1119, Jan. 16, 1996; 66 FR 38793, July 25,
2001] § 866.5560 Lactic dehydrogenase
§ 866.5540 Immunoglobulin G (Fd frag- (a) Identification. A lactic dehydro-
ment specific) immunological test genase immunological test system is a
system. device that consists of the reagents
(a) Identification. An immunoglobulin used to measure by immunochemical
G (Fd fragment specific) techniques the activity of the lactic
immunological test system is a device dehydrogenase enzyme in serum. In-
that consists of the reagents used to creased levels of lactic dehydrogenase
measure by immunochemical tech- are found in a variety of conditions, in-
cluding megaloblastic anemia (de-
niques the amino terminal (antigen-
crease in the number of mature red
binding) end (Fd fragment) of the
blood cells), myocardial infarction
heavy chain (a subunit) of the (heart disease), and some forms of leu-
immunoglobulin antibody molecule in kemia (cancer of the blood-forming or-
serum. Measurement of gans). However, the diagnostic useful-
immunoglobulin G Fd fragments aids ness of this device is limited because of
in the diagnosis of plasma antibody- the many conditions known to cause
forming cell abnormalities. increased lactic dehydrogenase levels.
383
§ 866.5570 21 CFR Ch. I (4–1–23 Edition)
[47 FR 50823, Nov. 9, 1982, as amended at 65 [47 FR 50823, Nov. 9, 1982, as amended at 65
FR 2312, Jan. 14, 2000] FR 2313, Jan. 14, 2000]
§ 866.5570 Lactoferrin immunological § 866.5600 Low-density lipoprotein

test system. immunological test system.
(a) Identification. A lactoferrin (a) Identification. A low-density
immunological test system is a device lipoprotein immunological test system
that consists of the reagents used to is a device that consists of the reagents
measure by immunochemical tech- used to measure by immunochemical
niques the lactoferrin (an iron-binding techniques the low-density lipoprotein
protein with the ability to inhibit the in serum and other body fluids. Meas-
growth of bacteria) in serum, breast urement of low-density lipoprotein in
milk, other body fluids, and tissues. serum may aid in the diagnosis of dis-
Measurement of lactoferrin may aid in orders of lipid (fat) metabolism and
the diagnosis of an inherited deficiency help to identify young persons at risk
of this protein. from cardiovascular diseases.
subpart E of part 807 of this chapter § 866.5620 Alpha-2-macroglobulin
subject to § 866.9. immunological test system.

(a) Identification. An alpha-2-
FR 2312, Jan. 14, 2000] macroglobulin immunological test sys-
tem is a device that consists of the re-
§ 866.5580 Alpha-1-lipoprotein agents used to measure by
immunological test system. immunochemical techniques the alpha-
(a) Identification. An alpha-1- 2-macroglobulin (a serum protein) in
lipoprotein immunological test system plasma. Measurement of alpha-2-
is a device that consists of the reagents macroglobulin may aid in the diagnosis
used to measure by immunochemical of blood-clotting or clot lysis disorders.
techniques the alpha-1-lipoprotein (b) Classification. Class II (special
(high-density lipoprotein) in serum and controls). The device is exempt from
plasma. Measurement of alpha-1- the premarket notification procedures
lipoprotein may aid in the diagnosis of in subpart E of part 807 of this chapter
Tangier disease (a hereditary disorder subject to the limitations in § 866.9.
of fat metabolism). [47 FR 50823, Nov. 9, 1982, as amended at 84
(b) Classification. Class II (perform- FR 71800, Dec. 30, 2019]
ance standards).
§ 866.5630 Beta-2-microglobulin
§ 866.5590 Lipoprotein X immunolog- immunological test system.
ical test system. (a) Identification. A beta-2-microglob-
(a) Identification. A lipoprotein X ulin immunological test system is a de-
immunological test system is a device vice that consists of the reagents used
that consists of the reagents used to to measure by immunochemical tech-
measure by immunochemical techniques beta-2-microglobulin (a protein
niques lipoprotein X (a high-density molecule) in serum, urine, and other
lipoprotein) in serum and other body body fluids. Measurement of beta-2-
fluids. Measurement of lipoprotein X microglobulin aids in the diagnosis of
aids in the diagnosis of obstructive active rheumatoid arthritis and kidney
liver disease. disease.
(b) Classification. Class I (general con- (b) Classification. Class II (special
trols). The device is exempt from the controls). The device is exempt from
premarket notification procedures in the premarket notification procedures
384
in subpart E of part 807 of this chapter (1) Premarket notification submis-

subject to the limitations in § 866.9. sions must include the following infor-
mation:
FR 71800, Dec. 30, 2019] (i) A detailed device description in-
cluding:
§ 866.5640 Infectious mononucleosis (A) A detailed description of all com-
immunological test system. ponents including all required ancil-
(a) Identification. An infectious mono- lary reagents in the test;
nucleosis immunological test system is (B) If applicable, a detailed descrip-
a device that consists of the reagents tion of instrumentation and equip-
used to measure by immunochemical ment, including illustrations or photo-
techniques heterophile antibodies fre- graphs of non-standard equipment or
quently associated with infectious manuals;
mononucleosis in serum, plasma, and (C) If applicable, detailed documenta-
other body fluids. Measurements of tion of the device software, including,
these antibodies aid in the diagnosis of but not limited to, standalone software
infectious mononucleosis. applications and hardware-based de-
(b) Classification. Class II (perform- vices that incorporate software;
ance standards). (D) A detailed description of appro-
[47 FR 50823, Nov. 9, 1982; 47 FR 56846, Dec. 21, priate internal and external quality
1982] controls that are recommended or pro-
vided. The description must identify
§ 866.5660 Multiple autoantibodies those control elements that are incor-
immunological test system. porated into the specified testing pro-
(a) Identification. A multiple cedures;
autoantibodies immunological test sys- (E) Detailed specifications for sample
tem is a device that consists of the re- collection, processing, and storage;
agents used to measure by (F) A detailed description of method-
immunochemical techniques the ology and assay procedure;
autoantibodies (antibodies produced (G) A description of how the assay
against the body’s own tissues) in cutoff (the medical decision point be-
serum and other body fluids. Measure- tween positive and negative) was estab-
ment of multiple autoantibodies aids lished and validated as well as sup-
in the diagnosis of autoimmune dis- porting data; and
orders (disease produced when the (H) Detailed specification of the cri-
body’s own tissues are injured by
teria for test results interpretation and
autoantibodies).
reporting.
ance standards). (ii) Detailed information dem-
onstrating the performance character-
§ 866.5665 Aquaporin-4 autoantibody istics of the device, including:
immunological test system. (A) Device precision/reproducibility
(a) Identification. An Aquaporin-4 data generated from within-run, be-
autoantibody immunological test sys- tween-run, between-day, between-lot,
tem is a device that consists of re- between-site, and total precision for
agents used to measure by multiple nonconsecutive days, as appli-
immunochemical techniques cable. A well characterized panel of pa-
autoantibodies in human serum sam- tient samples or pools from the indi-
ples that react with Aquaporin-4 cated population that covers the device
(AQP4Ab). The measurements aid in measuring range must be used.
the diagnosis of neuromyelitis optica (B) Device linearity data generated
(NMO) and neuromyelitis optica spec- from samples covering the device
trum disorders (NMOSD) in conjunc- measuring range, if applicable.
tion with other clinical, laboratory, (C) Information on traceability to a
and radiological (e.g., magnetic reso- reference material and description of
nance imaging) findings. value assignment of calibrators and
(b) Classification. Class II (special controls, if applicable.

controls). The special controls for this (D) Device analytical sensitivity
device are: data, including limit of blank, limit of
385
§ 866.5665 21 CFR Ch. I (4–1–23 Edition)
detection, and limit of quantitation, if (3) Diagnosis of diseases or conditions

applicable. for the differential or non-target dis-
(E) Device analytical specificity ease groups must be based on estab-
data, including interference by endoge- lished diagnostic criteria and clinical
nous and exogenous substances, as well evaluation.
as cross-reactivity with samples de- (4) For all samples, the diagnostic
rived from patients with other auto- clinical criteria and the demographic
immune diseases or conditions. information must be collected and pro-
(F) Device instrument carryover vided.
data, when applicable.
(5) The clinical validation results
(G) Device stability data, including
must demonstrate clinical sensitivity
real-time stability under various stor-
age times and temperatures. and clinical specificity for the test val-
(H) Specimen stability data, includ- ues based on the presence or absence of
ing stability under various storage NMO and NMOSD.
times, temperatures, freeze-thaw, and (6) The data must be summarized in
transport conditions, where appro- tabular format comparing the interpre-
priate. tation of results to the disease status.
(I) Method comparison data gen- (L) Expected/reference values gen-
erated by comparison of the results ob- erated by testing an adequate number
tained with the device to those ob- of samples from apparently healthy
tained with a legally marketed predi- normal individuals.
cate device with similar indications of (iii) Identification of risk mitigation
use. A well-characterized panel of pa- elements used by the device, including
tient samples from the indicated popu- description of all additional proce-
lation covering the device measuring dures, methods, and practices incor-
range must be used. porated into the directions for use that
(J) Specimen matrix comparison mitigate risks associated with testing.
data, if more than one specimen type (2) The device’s 21 CFR 809.10(b) com-
or anticoagulant can be tested with the pliant labeling must include warnings
device. Samples used for comparison
relevant to the device including:
must be from well-characterized pa-
tient samples covering the device (i) A warning statement that reads
measuring range. ‘‘The device is for use by laboratory
(K) Clinical performance must be es- professionals in a clinical laboratory
tablished by comparing data generated setting’’; and
by testing samples from the indicated (ii) A warning statement that reads
population and the differential diag- ‘‘The device is not to be used as a
nosis or non-target disease groups with stand-alone device but as an adjunct to
the device to the clinical diagnostic other clinical information. A diagnosis
standard. of Neuromyelitis Optica (NMO) and
(1) The diagnosis of NMO and NMOSD Neuromyelitis Optica Spectrum Dis-
must be based on clinical findings, lab- orders (NMOSD) should not be made on
oratory tests (e.g., serological tests), a single test result. The clinical symp-
and radiological tests (e.g., magnetic toms, results from physical examina-
resonance imaging). tion, laboratory tests (e.g., serological
(2) The differential diagnosis or non- tests), and radiological tests (e.g. Mag-
target disease group must include the netic Resonance Imaging), when appro-
applicable diseases or conditions, in- priate, should always be taken into ac-
cluding but not be limited to the fol- count when considering the diagnosis
lowing: Multiple sclerosis, stroke, of NMO and NMOSD.’’
Lyme disease, shingles, syphilis, (3) The device’s 21 CFR 809.10(b) com-
human immunodeficiency virus, hepa- pliant labeling must include a detailed
titis B, tuberculosis, Srgen’s syndrome, description of the protocol and per-
systemic lupus erythematous, systemic formance studies performed in accord-
vasculitis, sarcoidosis, Graves’ disease, ance with paragraph (b)(1)(ii) of this
Hashimoto’s disease, Type I diabetes,

section and a summary of the results.
rheumatoid arthritis, Addison’s dis-
ease, and myasthenia gravis. [82 FR 50076, Oct. 30, 2017]
386
§ 866.5670 Zinc transporter 8 sion for multiple nonconsecutive days

autoantibody immunological test as applicable. A well characterized
system. panel of patient samples or pools from
(a) Identification. A zinc transporter 8 the intended use population that cov-
autoantibody immunological test sys- ers the device measuring range must be
tem is a device that consists of reused;
agents used to measure, by (B) Device linearity data generated
immunochemical techniques, the from patient samples covering the
autoantibodies in human serum sam- assay measuring range if applicable;
ples that react with Zinc Transporter 8 (C) Information on traceability to a
(ZnT8). The measurements aid in the reference material and description of
diagnosis of Type 1 diabetes mellitus value assignment of calibrators and
(autoimmune mediated diabetes) in controls if applicable;
conjunction with other clinical and (D) Device analytical sensitivity
laboratory findings. data, including limit of blank, limit of
(b) Classification. Class II (special detection and limit of quantitation if
controls). The special controls for this applicable;
device are: (E) Device analytical specificity
(1) Premarket notification submis- data, including interference by endoge-
sions must include the following infor- nous and exogenous substances, as well
mation: as cross-reactivity with samples de-
(i) A detailed description of the derived from patients with other auto-
vice that includes: immune diseases or conditions;
(A) A detailed description of all com- (F) Device instrument carryover data
ponents in the test system, including a when applicable;
description of the assay components in (G) Device stability data including
the kit and all required ancillary re- real-time stability under various stor-
agents; age times and temperatures;
(B) A detailed description of instru- (H) Specimen stability data, includ-
mentation and equipment, and illustra- ing stability under various storage
tions or photographs of non-standard times, temperatures, freeze-thaw, and
equipment or methods if applicable; transport conditions where appro-
(C) Detailed documentation of the de- priate;
vice software, including, but not lim- (I) Method comparison data gen-
ited to, standalone software applica- erated by comparison of the results ob-
tions and hardware-based devices that tained with the device to those ob-
incorporate software where applicable; tained with a legally marketed predi-
(D) A detailed description of appro- cate device with similar indication of
priate internal and external quality use. Patient samples from the intended
controls that are recommended or pro- use population covering the device
vided. The description must identify measuring range must be used;
those control elements that are incor- (J) Specimen matrix comparison data
porated into the recommended testing if more than one specimen type or anti-
procedures; coagulant can be tested with the de-
(E) Detailed specifications for sample vice. Samples used for comparison
collection, processing, and storage; must be from patient samples covering
(F) A detailed description of method- the device measuring range;
ology and assay procedure; and (K) A description of how the assay
(G) Detailed specification of the cri- cut-off (the medical decision point be-
teria for test results interpretation and tween positive and negative) was estab-
reporting. lished and validated as well as sup-
(ii) Information that demonstrates porting data;
the performance characteristics of the (L) Clinical performance must be es-
device, including: tablished by comparing data generated
(A) Device precision/reproducibility by testing samples from the intended
data generated from within-run, be- use population and the differential di-
tween-run, between-day, between-lot, agnosis groups with the device to the

between-operator, between-instru- clinical diagnostic standard. The diag-
ments, between-site, and total preci- nosis of Type 1 diabetes mellitus must
387
§ 866.5680 21 CFR Ch. I (4–1–23 Edition)
be based on clinical history, physical sults on physical examination, and lab-

examination, and laboratory tests, oratory tests (e.g., serological tests),
such as one or more pancreatic or insu- when appropriate, should always be
lin autoantibody test. Because the in- taken into account when considering
tended use population for Type 1 diabe- the diagnosis of Type 1 diabetes
tes mellitus includes subjects less than mellitus and Type 2 diabetes mellitus’’;
18 years old, samples from representa- (iii) A warning statement that reads,
tive numbers of these subjects must be ‘‘Absence of Zinc T8 autoantibody does
included. Representative numbers of not rule out a diagnosis of Type 1 dia-
samples from all age strata must also betes mellitus’’; and
be included. The differential diagnosis
(iv) A warning statement that reads,
groups must include, but not be limited
to the following: Type 2 diabetes ‘‘The assay has not been demonstrated
mellitus; metabolic syndrome; latent to be effective for monitoring the stage
autoimmune diabetes in adults; other of disease or its response to treat-
autoimmune diseases such as celiac ment.’’
disease (without a concomitant diag- (3) Your 21 CFR 809.10(b) compliant
nosis of Type 1 diabetes mellitus), sys- labeling must include a description of
temic lupus erythematosus, rheu- the protocol and performance studies
matoid arthritis, and Hashimoto’s thy- performed in accordance with para-
roiditis; infection; renal disease; and graph (b)(1)(ii) of this section and a
testicular cancer. Diseases for the dif- summary of the results.
ferential groups must be based on es-
[82 FR 49103, Oct. 20, 2017]
tablished diagnostic criteria and clin-
ical evaluation. For all samples, the di- § 866.5680 Myoglobin immunological
agnostic clinical criteria and the demo- test system.
graphic information must be collected
and provided. The clinical validation (a) Identification. A myoglobin
results must demonstrate clinical sen- immunological test system is a device
sitivity and clinical specificity for the that consists of the reagents used to
test values based on the presence or ab- measure by immunochemical tech-
sence of Type 1 diabetes mellitus. The niques the myoglobin (an oxygen stor-
data must be summarized in tabular age protein found in muscle) in serum
format comparing the interpretation of and other body fluids. Measurement of
results to the disease status; and myoglobin aids in the rapid diagnosis
(M) Expected/reference values gen- of heart or renal disease.
erated by testing an adequate number (b) Classification. Class II (perform-
of samples from apparently healthy ance standards).
normal individuals.
(iii) Identification of risk mitigation § 866.5700 Whole human plasma or
elements used by the device, including serum immunological test system.
description of all additional proce-
(a) Identification. A whole human
dures, methods, and practices incor-
plasma or serum immunological test
porated into the directions for use that
mitigate risks associated with testing. system is a device that consists of re-
(2) Your 21 CFR 809.10(a) compliant agents used to measure by
label and 21 CFR 809.10(b) compliant la- immunochemical techniques the pro-
beling must include warnings relevant teins in plasma or serum. Measure-
to the assay including: ments of proteins in plasma or serum
(i) A warning statement that reads, aid in the diagnosis of any disease con-
‘‘The device is for use by laboratory cerned with abnormal levels of plasma
professionals in a clinical laboratory or serum proteins, e.g., agammaglobu-
setting’’; linemia, allergies, multiple myeloma,
(ii) A warning statement that reads, rheumatoid vasculitis, or hereditary
‘‘The test is not a stand-alone test but angioneurotic edema.
an adjunct to other clinical informa- (b) Classification. Class I (general con-
tion. A diagnosis of Type 1 diabetes trols). The device is exempt from the
mellitus should not be made on a single premarket notification procedures in
test result. The clinical symptoms, re-
388
subpart E of part 807 of this chapter bodies) prothrombin aid in the diag-
subject to the limitations in § 866.9. nosis of blood-clotting disorders.
[47 FR 50823, Nov. 9, 1982, as amended at 59 (b) Classification. Class I (general con-
FR 63007, Dec. 7, 1994; 66 FR 38793, July 25, trols). The device is exempt from the
2001] premarket notification procedures in
§ 866.5715 Plasminogen immunological subject to § 866.9. This exemption does
test system. not apply to multipurpose systems for
(a) Identification. A plasminogen in vitro coagulation studies classified
immunological test system is a device under § 864.5425 of this chapter or pro-
that consists of the reagents used to thrombin time tests classified under
measure by immunochemical tech- § 864.7750 of this chapter.
niques the plasminogen (an inactive
substance from which plasmin, a blood- [47 FR 50823, Nov. 9, 1982, as amended at 65
clotting factor, is formed) in serum, FR 2313, Jan. 14, 2000]
other body fluids, and tissues. Measure-
§ 866.5750 Radioallergosorbent (RAST)
ment of plasminogen levels may aid in immunological test system.
the diagnosis of fibrinolytic (blood-
clotting) disorders. (a) Identification. A
(b) Classification. Class I (general con- radioallergosorbent immunological
trols). The device is exempt from the test system is a device that consists of
premarket notification procedures in the reagents used to measure by
subpart E of part 807 of this chapter immunochemical techniques the aller-
subject to § 866.9. gen antibodies (antibodies which cause
an allergic reaction) specific for a
FR 2313, Jan. 14, 2000] given allergen. Measurement of specific
allergen antibodies may aid in the di-
§ 866.5735 Prothrombin immunological agnosis of asthma, allergies, and other
test system. pulmonary disorders.
(a) Identification. A prothrombin (b) Classification. Class II (special
immunological test system is a device controls). The device, when intended to
that consists of the reagents used to detect any of the allergens included in
measure by immunochemical tech- Table 1 in this paragraph, is exempt
niques the prothrombin (clotting factor from the premarket notification proce-
II) in serum. Measurements of the dures in subpart E of part 807 of this
amount of antigenically competent chapter subject to the limitations in
(ability to react with protein anti- § 866.9.
TABLE 1—CLASS II EXEMPT ALLERGENS UNDER § 866.5750—RADIOALLERGOSORBENT (RAST)
IMMUNOLOGICAL TEST SYSTEMS
Source
Allergen code Allergen product (taxonomical name)
Grass Pollens
g1 ........................ Sweet vernal grass ..................................................... Anthoxanthum odoratum.

g3 ........................ Cocksfoot grass, Orchard grass ................................. Dactylis glomerata.
g4 ........................ Meadow fescue ........................................................... Festuca elatior.
g5 ........................ Rye-grass (perennial rye grass) ................................. Lolium perenne.
g7 ........................ Common reed (common reed grass) ......................... Phragmites communis.
g8 ........................ Meadow grass, Kentucky blue (June grass) .............. Poa pratensis.
g9 ........................ Redtop, Bentgrass ...................................................... Agrostis stolonifera, Agrostis gigantea (Agrostis
alba).
g11 ...................... Brome grass ............................................................... Bromus inermis.
g12 ...................... Cultivated rye (cultivated rye grass) ........................... Secale cereale.
g13 ...................... Velvet grass ................................................................ Holcus lanatus.
g14 ...................... Cultivated oat (cultivated oat grass) ........................... Avena sativa.
g15 ...................... Cultivated wheat (cultivated wheat grass) .................. Triticum aestivum (Triticum spp.).
g16 ...................... Meadow foxtail (meadow foxtail grass) ...................... Alopecurus pratensis.
g17 ...................... Bahia grass ................................................................. Paspalum notatum.
g24 ...................... Wheat grass, Western ................................................ Agropyron smithii (Elymus smithii).
g30 ...................... Bluegrass, annual ....................................................... Poa annua.

g70 ...................... Wild rye grass ............................................................. Elymus triticoides Elymus condensatus.
g71 ...................... Canary grass .............................................................. Phalaris arundinacea.
389
§ 866.5750 21 CFR Ch. I (4–1–23 Edition)

IMMUNOLOGICAL TEST SYSTEMS—Continued
Source
g201 .................... Barley, cultivated ........................................................ Hordeum vulgare.

g202 .................... Maize, corn (cultivated corn) ...................................... Zea mays.
g203 .................... Salt grass .................................................................... Distichlis spicata.
g204 .................... False oat-grass ........................................................... Arrhenatherum elatius.
g216 .................... Cyn d 1 ....................................................................... Cynodon dactylon.
g701 .................... Phl p 1.0102, Phl p 5.0101 ......................................... Phleum pratense.
g702 .................... Phl p 7.0101 ............................................................... Phleum pratense.
g703 .................... Phl p 12.0101 ............................................................. Phleum pratense.
Weed Pollens
w2 ....................... Western ragweed ........................................................ Ambrosia psilostachya.

w4 ....................... False ragweed ............................................................ Ambrosia acanthicarpa (Franseria acanthicarpa).
w5 ....................... Wormwood .................................................................. Artemisia absinthium Artemisia annua.
w6 ....................... Mugwort ...................................................................... Artemisia vulgaris.
w7 ....................... Marguerite, ox-eye daisy ............................................ Chrysanthemum leucanthemum.
w8 ....................... Dandelion .................................................................... Taraxacum vulgare, Taraxacum officinale.
w9 ....................... Plantain (English), Ribwort ......................................... Plantago lanceolata.
w10 ..................... Goosefoot, lamb’s quarters ........................................ Chenopodium album.
w11 ..................... Saltwort (prickly), Russian thistle ............................... Salsola kali (Salsola pestifer).
w12 ..................... Goldenrod ................................................................... Solidago virgaurea (Solidago spp.).
w13 ..................... Cocklebur, common .................................................... Xanthium commune.
w14 ..................... Common pigweed (rough pigweed) ........................... Amaranthus retroflexus.
w15 ..................... Scale, Lenscale .......................................................... Atriplex lentiformis.
w16 ..................... Rough marsh elder ..................................................... Iva ciliate, Iva annua.
w17 ..................... Firebush (Kochia) ....................................................... Kochia scoparia.
w18 ..................... Sheep sorrel ............................................................... Rumex acetosella.
w19 ..................... Wall pellitory ............................................................... Parietaria officinalis.
w20 ..................... Nettle (Common stinging nettle) ................................. Urtica dioica.
w21 ..................... Wall pellitory ............................................................... Parietaria judaica.
w22 ..................... Japanese hop (careless weed) .................................. Humulus japonicas (Humulus scandens).
w23 ..................... Yellow dock, Yellow dockweed .................................. Rumex crispus.
w24 ..................... Spiny pigweed ............................................................ Amaranthus spinosus.
w27 ..................... Carnation .................................................................... Dianthus spp.
w28 ..................... Rose ............................................................................ Rosa rugosa.
w33 ..................... Clover .......................................................................... Trifolium pratense.
w35 ..................... Mexican tea ................................................................ Chenopodium ambrosioides.
w36 ..................... Rabbit bush ................................................................. Ambrosia deltoidea (Franseria deltoides).
w37 ..................... Salt bush, annual ........................................................ Atriplex wrightii.
w39 ..................... Water hemp, Western ................................................. Amaranthus rudis (Acnida tamariscina).
w41 ..................... Burrobrush .................................................................. Hymenoclea salsola.
w42 ..................... Poverty weed .............................................................. Baccharis neglecta.
w43 ..................... Common sagebrush ................................................... Artemisia tridentata.
w45 ..................... Alfalfa .......................................................................... Medicago sativa.
w46 ..................... Dog fennel .................................................................. Eupatorium capillifolium.
w53 ..................... Geranium .................................................................... Geranium spp.
w67 ..................... Groundsel bush .......................................................... Baccharis halimifolia.
w69 ..................... Iodine bush ................................................................. Allenrolfea occidentalis.
w70 ..................... Ragweed, slender ....................................................... Ambrosia confertiflora.
w75 ..................... Wing scale (wingscale) ............................................... Atriplex canescens.
w82 ..................... Careless weed ............................................................ Amaranthus palmeri, Amaranthus hybridus.
w90 ..................... Japanese hop ............................................................. Humulus japonicas (Humulus scandens).
w203 ................... Rape (rape pollen) ...................................................... Brassica napus.
w204 ................... Sunflower .................................................................... Helianthus annuus.
w206 ................... Camomile .................................................................... Matricaria chamomilla.
w207 ................... Lupin ........................................................................... Lupinus spp.
w210 ................... Sugar-beet .................................................................. Beta vulgaris.
w211 ................... Par j 2.0101 ................................................................ Parietaria judaica.
w231 ................... Art v 1 ......................................................................... Artemisia vulgaris (Mugwort).
w232 ................... Sal k 1 ......................................................................... Salsola kali.
w233 ................... Art v 3 ......................................................................... Artemisa vulgaris (LTP, Mugwort).
w234 ................... Pla l 1 .......................................................................... Plantago lanceolata.
w235 ................... Che a 1.0101 .............................................................. Chenopodium album.
w236 ................... Mer a 1.0101 .............................................................. Mercurialis annua.
a753 .................... Art v 1 ......................................................................... Artemisia vulgaris (Mugwort weed).
Tree Pollens
t1 ......................... Box-elder (Maple) ....................................................... Acer negundo, Acer saccharum.

t2 ......................... Gray alder, speckled alder (alder) .............................. Alnus incana.
390

Source
t4 ......................... Hazel, hazelnut ........................................................... Corylus avellana, Corylus americana.

t5 ......................... American beech (beech) ............................................ Fagus grandifolia (Fagus americana).
t6 ......................... Mountain juniper, Mountain cedar .............................. Juniperus ashei (Juniperus sabinoides).
t8 ......................... Elm .............................................................................. Ulmus americana.
t9 ......................... Olive ............................................................................ Olea europaea.
t10 ....................... Walnut ......................................................................... Juglans californica, Juglans nigra.
t11 ....................... Maple leaf sycamore, London plane, Plane tree ....... Platanus acerifolia.
t61 ....................... Sycamore .................................................................... Platanus occidentalis.
t12 ....................... Willow .......................................................................... Salix caprea, Salix nigra.
t14 ....................... Cottonwood (Eastern Cottonwood/Black Cottonwood) Populus deltoides.
t15 ....................... White ash .................................................................... Fraxinus americana.
t16 ....................... White pine ................................................................... Pinus strobus.
t18 ....................... Eucalyptus, gum-tree .................................................. Eucalyptus globulus (Eucalyptus spp.).
t19/t26 ................. Acacia ......................................................................... Acacia longifolia (Acacia spp.).
t20 ....................... Mesquite ..................................................................... Prosopis glandulosa/Prosopis juliflora.
t21 ....................... Melaleuca, cajeput tree .............................................. Melaleuca quinquenervia (Melaleuca leucadendron).
t22 ....................... Pecan, hickory ............................................................ Carya illinoinensis (Carya pecan).
t23 ....................... Italian/Mediterranean/funeral cypress ......................... Cupressus sempervirens.
t24 ....................... Japanese cypress ....................................................... Chamaecyparis obtusa (Chamaecyparis spp.).
t25 ....................... Ash .............................................................................. Fraxinus excelsior.
t27 ....................... Maple, red ................................................................... Acer rubrum.
t29 ....................... Acacia ......................................................................... Acacia spp.
t30 ....................... Birch, white ................................................................. Betula populifolia.
t32 ....................... Willow, black ............................................................... Salix nigra.
t33 ....................... Ash, Arizona ............................................................... Fraxinus velutina.
t35 ....................... Cedar, salt .................................................................. Tamarix gallica.
t37 ....................... Bald cypress (white bald cypress) .............................. Taxodium distichum.
t38 ....................... Elm, Chinese/Siberian ................................................ Ulmus pumila.
t40 ....................... Hazelnut tree .............................................................. Corylus americana.
t41 ....................... White hickory .............................................................. Carya alba (Carya tomentosa).
t42 ....................... Oak, red ...................................................................... Quercus rubra.
t43 ....................... Loblolly pine ................................................................ Pinus taeda.
t44 ....................... Hackberry .................................................................... Celtis occidentalis.
t45 ....................... Cedar elm ................................................................... Ulmus crassifolia.
t47 ....................... Juniper, one seed ....................................................... Juniperus monosperma.
t48 ....................... Pine, lodgepole ........................................................... Pinus contorta.
t49 ....................... Pine, ponderosa .......................................................... Pinus ponderosa.
t50 ....................... Beech, European ........................................................ Fagus sylvatica.
t51 ....................... Tree of Heaven ........................................................... Ailanthus altissima.
t52 ....................... Western white pine ..................................................... Pinus monticola.
t54 ....................... Russian olive .............................................................. Elaeagnus angustifolia.
t55 ....................... Scotch broom .............................................................. Cytisus scoparius.
t56 ....................... Bayberry ...................................................................... Myrica cerifera.
t57 ....................... Red cedar ................................................................... Juniperus virginiana.
t60 ....................... Western juniper ........................................................... Juniperus occidentalis.
t61 ....................... Sycamore .................................................................... Platanus occidentalis.
t70 ....................... Mulberry (white mulberry) ........................................... Morus alba.
t71 ....................... Red mulberry .............................................................. Morus rubra.
t72 ....................... Queen palm ................................................................ Arecastrum romanzoffiamon.
t73 ....................... Australian pine ............................................................ Casuarina equisetifolia.
t77 ....................... Oak mix (red, white, black) ......................................... Quercus spp.
t80 ....................... Japanese cypress ....................................................... Chamaecyparis obtusa.
t81 ....................... Japanese alder ........................................................... Alnus japonica.
t83 ....................... Mango tree .................................................................. Mangifera indica.
t90 ....................... Walnut, black .............................................................. Juglans nigra.
t96 ....................... Poplar, white (poplar) ................................................. Populus alba.
t103/t218 ............. Virginia live oak (live oak) .......................................... Quercus virginiana.
t105 ..................... Pepper tree ................................................................. Schinus molle.
t110 ..................... Orange tree ................................................................. Citrus sinensis.
t201 ..................... Spruce, Norway spruce .............................................. Picea abies (Picea excelsa).
t202 ..................... Alder, smooth .............................................................. Alnus incana spp. Rugosa (Alnus rugosa).
t203 ..................... Horse chestnut ............................................................ Aesculus hippocastanum.
t205 ..................... Elder ............................................................................ Sambucus nigra.
t206 ..................... Chestnut ...................................................................... Castanea sativa.
t207 ..................... Douglas fir ................................................................... Pseudotsuga menziesii (Pseudotsuga taxifolia).
t208 ..................... Linden ......................................................................... Tilia cordata.
t209 ..................... Horn beam .................................................................. Carpinus betulus.

t210 ..................... Privet ........................................................................... Ligustrum vulgare.
t211 ..................... Sweet gum .................................................................. Liquidambar styraciflua.
t212 ..................... Cedar .......................................................................... Libocedrus decurrens.
391
§ 866.5750 21 CFR Ch. I (4–1–23 Edition)

Source
t213 ..................... Pine ............................................................................. Pinus radiata.

t214 ..................... Date palm ................................................................... Phoenix canariensis.
t215 ..................... Lilac ............................................................................. Syringa vulgaris.
t217 ..................... Pepper tree ................................................................. Schinus molle.
t217 ..................... Red alder .................................................................... Alnus rubra.
t218 ..................... Virginia live oak .......................................................... Quercus virginiana.
t218 ..................... Bayberry (bayberry/sweet gale) .................................. Myrica gale.
t219 ..................... Palo verde ................................................................... Cercidium floridum.
t219 ..................... Red cedar ................................................................... Juniperus virginiana.
t220 ..................... Bet v 4 ........................................................................ Betula verrucosa (Birch).
t221 ..................... Bet v 2.0101, Bet v 4 .................................................. Betula verrucosa (Birch).
t222 ..................... Cypress (Arizona cypress) ......................................... Cupressus arizonica.
t223 ..................... Oil palm ....................................................................... Elaeis guineensis.
t224 ..................... Ole e 1 ........................................................................ Olea europaea.
t225 ..................... Bet v 6 ........................................................................ Betula verrucosa (Birch).
t226 ..................... Cup a 1 ....................................................................... Cupressus arizonica.
t227 ..................... Ole e 7 ........................................................................ Olea Europaea.
t228 ..................... Aspen, quaking ........................................................... Populus tremuloides.
t229 ..................... Eastern hemlock ......................................................... Tsuga canadensis.
t230 ..................... Redwood (sequoia) ..................................................... Sequoia sempervirens.
t232 ..................... Pussy willow ............................................................... Salix discolor.
t240 ..................... Ole e 9.0101 ............................................................... Olea Europaea.
t241 ..................... Pla a 1.0101 ............................................................... Platanus acerifolia.
t242 ..................... Pla a 2 ........................................................................ Platanus acerifolia.
t243 ..................... Pla a 3.0101 ............................................................... Platanus acerifolia.
t244 ..................... Cor a 1.0103 ............................................................... Corylus avellana.
t245 ..................... Aln g 1.0101 ............................................................... Alnus glutinosa.
t246 ..................... Cry j 1 ......................................................................... Cryptomeria japonica.
t280 ..................... Locust tree .................................................................. Robinia pseudoacacia.
t401 ..................... Brazilian peppertree .................................................... Schinus terebinthifolius.
t402 ..................... Mastic tree .................................................................. Pistacia lentiscus.
t404 ..................... Tree of heaven ........................................................... Ailanthus altissima.
t406 ..................... Date palm ................................................................... Phoenix dactylifera.
a482 .................... Ole e 1 ........................................................................ Olea europaea (Olive Oil).
Mites
d207 .................... Blo t 5.0101 ................................................................ Blomia tropicalis.

d208 .................... Lep d 2.0101 ............................................................... Lepidoglyphus destructor.
Microorganisms, Molds, Yeast
m1 ....................... Penicillium chrysogenum (Penicillium notatum) ......... Penicillium chrysogenum (Penicillium notatum).
m2 ....................... Cladosporium herbarum (Hormodendrum) ................. Cladosporium herbarum (Hormodendrum).
m3 ....................... Aspergillus fumigatus .................................................. Aspergillus fumigatus.
m4 ....................... Mucor racemosus ....................................................... Mucor racemosus.
m5 ....................... Candida albicans ........................................................ Candida albicans.
m7 ....................... Botrytis cinerea ........................................................... Botrytis cinerea.
m8 ....................... Drechslera halodes (Setomelanomma rostrata, Drechslera halodes (Setomelanomma rostrata,
Helminthosporium halodes, Helminthosporium Helminthosporium halodes.
interseminatum).
m9 ....................... Fusarium moniliforme (Fusarium proliferatum) .......... Fusarium moniliforme (Fusarium proliferatum).
m10 ..................... Stemphylium botryosum ............................................. Stemphylium herbarum (Stemphylium botryosum).
m11 ..................... Rhizopus nigricans ..................................................... Rhizopus nigricans.
m12 ..................... Aureobasidium pullulans ............................................. Aureobasidium pullulans.
m13 ..................... Phoma betae .............................................................. Phoma betae.
m14 ..................... Epicoccum purpurascens ........................................... Epicoccum purpurascens (Epicoccum nigrum).
m15 ..................... Trichoderma viride ...................................................... Trichoderma viride.
m16 ..................... Curvularia lunata ......................................................... Curvularia lunata, Curvularia specifera (K923044).
m17 ..................... Cladosporium fulvum .................................................. Cladosporium fulvum.
m18 ..................... Fusarium culmorum .................................................... Fusarium culmorum.
m19 ..................... Aspergillus versicolor .................................................. Aspergillus versicolor.
m20 ..................... Mucor mucedo ............................................................ Mucor mucedo.
m21 ..................... Aspergillus clavatus .................................................... Aspergillus clavatus.
m22 ..................... Micropolyspora faeni ................................................... Saccharopolyspora rectivirgula (Micropolyspora
faeni).
m23 ..................... Thermoactinomyces vulgaris ...................................... Thermoactinomyces vulgaris.
m24 ..................... Stachybotrys atra ........................................................ Stachybotrys chartarum (Stachybotrys atra).

m24 ..................... Paecilomyces spp ....................................................... Paecilomyces spp.
m25 ..................... Aspergillus versicolor .................................................. Aspergillus versicolor.
392

Source
m25 ..................... Penicillium brevicompactum ....................................... Penicillium brevicompactum.

m26 ..................... Cladosporium cladosporioides .................................... Cladosporium cladosporioides.
m26 ..................... Penicillium citrinum ..................................................... Penicillium citrinum.
m27 ..................... Penicillium spp ............................................................ Penicillium spp.
m29 ..................... Aspergillus repens ...................................................... Aspergillus repens.
m30 ..................... Penicillium roqueforti .................................................. Penicillium roqueforti.
m32 ..................... Cladosporium cladosporioides .................................... Cladosporium cladosporioides.
m34 ..................... Serpula lacrymans ...................................................... Serpula lacrymans.
m36 ..................... Aspergillus terreus ...................................................... Aspergillus terreus.
m37 ..................... Trichophyton mentagrophytes .................................... Trichophyton mentagrophytes.
m40 ..................... Aspergillus amstelodami ............................................. Aspergillus amstelodami.
m43 ..................... Saccharomyces Carlsberg .......................................... Saccharomyces carlsbergensis.
m44 ..................... Saccharomyces cerevisiae ......................................... Saccharomyces cerevisiae.
m45 ..................... Hormodendrum hordei ................................................ Hormodendrum hordei.
m46 ..................... Bipolaris spicifera ........................................................ Bipolaris spicifera.
m47 ..................... Aspergillus nidulans .................................................... Aspergillus nidulans.
m48 ..................... Aspergillus oryzae ...................................................... Aspergillus oryzae.
m49 ..................... Fusarium oxysporum .................................................. Fusarium oxysporum.
m50 ..................... Micropolyspora faeni ................................................... Saccharopolyspora rectivirgula (Micropolyspora
faeni).
m51 ..................... Thermoactinomyces vulgaris ...................................... Thermoactinomyces vulgaris.
m53 ..................... Microspora canis ......................................................... Microsporum canis (Microspora canis).
m54 ..................... Aspergillus flavus ........................................................ Aspergillus flavus.
m63 ..................... Helminthosporium intersemin ..................................... Helminthosporium intersemin.
m66 ..................... Mucor plumbeus ......................................................... Mucor plumbeus.
m67 ..................... Mycogone ................................................................... Mycogone perniciosa.
m68 ..................... Nigrospora oryzae ...................................................... Nigrospora oryzae.
m69 ..................... Rhodotorula ................................................................ Rhodotorula rubra (Rhodotorula mucilaginosa).
m70 ..................... Malassezia furfur (Pityrosporum orbiculare) ............... Malassezia furfur (Pityrosporum orbiculare).
m71 ..................... Spondylocladium ......................................................... Spondylocladium spp.
m72 ..................... Epidermophyton .......................................................... Epidermophyton floccosum.
m73 ..................... Epicoccum nigrum ...................................................... Epicoccum purpurascens (Epicoccum nigrum).
m80 ..................... Staphylococcal enterotoxin A (Sta a SEA) ................. Staphylococcus aureus.
m80 ..................... Helminthosporium spp ................................................ Helminthosporium spp.
m81 ..................... Staphylococcal enterotoxin B (Sta a SEB) ................. Staphylococcus aureus.
m88 ..................... Stemphylium solani ..................................................... Stemphylium solani.
m93 ..................... Gliocladium fimbriatum ............................................... Gliocladium fimbriatum.
m94 ..................... Phycomyces blakesleeanus ....................................... Phycomyces blakesleeanus.
m201 ................... Tilletia tritici (Ustilago nuda, Ustilago tritici) (Barley Tilletia tritici (Ustilago nuda, Ustilago tritici).
smut).
m202 ................... Acremonium kiliense (Cephalosporium acremonium) Acremonium kiliense (Cephalosporium acremonium).
m203 ................... Trichosporon pullulans ................................................ Trichosporon pullulans.
m204 ................... Ulocladium chartarum ................................................. Ulocladium chartarum.
m205 ................... Trichophyton rubrum ................................................... Trichophyton rubrum.
m207 ................... Aspergillus niger ......................................................... Aspergillus niger.
m208 ................... Chaetomium globosum ............................................... Chaetomium globosum.
m209 ................... Penicillium frequentans ............................................... Penicillium glabrum (Penicillium frequentans).
m209 ................... Stachybotrys chartarum .............................................. Stachybotrys chartarum (Stachybotrys atra).
m210 ................... Trichophyton mentagrophytes var. goetzii ................. Trichophyton mentagrophytes var. goetzii.
m211 ................... Trichophyton mentagrophytes var. interdigitale ......... Trichophyton mentagrophytes var. interdigitale.
m211 ................... Oat smut ..................................................................... Ustilago avenae.
m212 ................... Micropolyspora faeni ................................................... Saccharopolyspora rectivirgula (Micropolyspora
faeni).
m212 ................... Geotrichum candidum ................................................. Geotrichum candidum.
m213 ................... Bermuda grass smut .................................................. Ustilago cynodontis.
m214 ................... Johnson grass smut ................................................... Sphacelotheca cruenta.
m215 ................... Corn smut ................................................................... Ustilago maydis.
m218 ................... Asp f 1.0101 ............................................................... Aspergillus fumigatus.
a3050 .................. Asp r 1 ........................................................................ Aspergillus restrictus.
m219 ................... Asp f 2 ........................................................................ Aspergillus fumigatus.
m221 ................... Asp f 4 ........................................................................ Aspergillus fumigatus.
m223 ................... Staphylococcal enterotoxin C (Sta a SEC) ................ Staphylococcus aureus.
m224 ................... Staphylococcal enterotoxin D (Sta a SED) ................ Staphylococcus aureus.
m226 ................... Staphylococcal enterotoxin TSST (Sta a TSST) ........ Staphylococcus aureus.
m227 ................... Malassezia spp. (Pityrosporum spp.) ......................... Malassezia spp. (Pityrosporum spp.).
m228 ................... Aspergillus flavus..
m229 ................... Alt a 1.0101 ................................................................ Alternaria alternata (Alternaria tenuis).
m230 ................... Alt a 6.0101 ................................................................ Alternaria alternata (Alternaria tenuis).
393
§ 866.5750 21 CFR Ch. I (4–1–23 Edition)

Source
m231 ................... Cla h 8.0101 ............................................................... Cladosporium herbarum (Hormodendrum).

m300 ................... Eurotium spp ............................................................... Eurotium spp.
m304 ................... Aspergillus oryzae ...................................................... Aspergillus oryzae.
m305 ................... Penicillium brevicompactum ....................................... Penicillium brevicompactum.
m309 ................... Aspergillus terreus ...................................................... Aspergillus terreus.
m310 ................... Aspergillus nidulans .................................................... Aspergillus nidulans.
m311 ................... Aspergillus flavus ........................................................ Aspergillus flavus.
m312 ................... Aspergillus clavatus .................................................... Aspergillus clavatus.
Epidermal & Animal
e6 ........................ Guinea pig epithelium ................................................. Cavia porcellus.

e7 ........................ Pigeon droppings ........................................................ Columba palumbus, Columba livia.
e25 ...................... Chicken serum ............................................................ Gallus domesticus (Gallus gallus domesticus; Gallus
spp.).
e26 ...................... Parrot serum ............................................................... Psittacoidea spp.
e62 ...................... Camel .......................................................................... Camelus dromedaries.
e70 ...................... Goose feathers ........................................................... Anser anser.
e71 ...................... Mouse epithelium ........................................................ Mus musculus (Mus spp.).
e73 ...................... Rat epithelium ............................................................. Rattus norvegicus.
e74 ...................... Rat urine proteins ....................................................... Rattus norvegicus, Rattus rattus.
e75 ...................... Rat serum proteins ..................................................... Rattus norvegicus, Rattus rattus.
e76 ...................... Mouse serum proteins ................................................ Mus musculus (Mus spp.).
e77 ...................... Budgerigar droppings ................................................. Melopsittacus undulatus.
e78 ...................... Budgerigar feathers .................................................... Melopsittacus undulatus.
e79 ...................... Budgerigar serum proteins ......................................... Melopsittacus undulatus.
e80 ...................... Goat epithelium ........................................................... Capra hircus.
e81 ...................... Sheep epithelium ........................................................ Ovis aries (Ovis spp.).
e82 ...................... Rabbit epithelium ........................................................ Oryctolagus cuniculus (Oryctolagus spp.).
e83 ...................... Swine epithelium ......................................................... Sus scrofa (Sus scrofa domesticus; Sus spp.).
e84 ...................... Hamster epithelium ..................................................... Cricetus cricetus, Mesocricetus auratus, and
Phodopus sungorus.
e85 ...................... Chicken feathers ......................................................... Gallus domesticus (Gallus gallus domesticus; Gallus
spp.).
e86 ...................... Duck feathers .............................................................. Anas platyrhynchos.
e87 ...................... Rat epithelium, serum proteins, and urine proteins ... Rattus norvegicus Rattus rattus.
e88 ...................... Mouse epithelium, serum proteins, and urine pro- Mus musculus (Mus spp.).
teins (mouse).
e89 ...................... Turkey feathers ........................................................... Meleagris gallopavo.
e90 ...................... Budgerigar serum proteins, feathers, and droppings Melopsittacus undulatus.
e91 ...................... Pigeon serum proteins, feathers, and droppings ....... Streptopelia roseogrisea, Psittacidae spp.
e92 ...................... Parrot serum proteins, feathers, and droppings ......... Ara spp.
e93 ...................... Pigeon serum proteins ................................................ Streptopelia roseogrisea.
e94 ...................... Fel d 1.0101 ................................................................ Felis domesticus.
a345 .................... Fel d 1 ......................................................................... Felis domesticus.
e98 ...................... Parrot droppings ......................................................... Psittacoidea spp.
e101 .................... Can f 1.0101 ............................................................... Canis familiaris (Canis domesticus).
a174 .................... Can f 1 ........................................................................ Canis familiaris (Canis domesticus).
e102 .................... Can f 2.0101 ............................................................... Canis familiaris (Canis domesticus).
e196 .................... Parakeet feathers ....................................................... Nymphicus hollandicus.
e197 .................... Parakeet droppings ..................................................... Nymphicus hollandicus.
e198 .................... Parakeet serum .......................................................... Nymphicus hollandicus.
e199 .................... Canary bird serum ...................................................... Serinus canarius.
e200 .................... Canary bird droppings ................................................ Serinus canarius.
e201 .................... Canary bird feathers (Canary feathers) ...................... Serinus canarius.
e202 .................... Reindeer epithelium .................................................... Rangifer tarandus.
e203 .................... Mink epithelium ........................................................... Mustela spp.
e204 .................... Bos d 6 ....................................................................... Bos domesticus (Bos taurus; Bos spp.).
e205 .................... Horse, serum proteins ................................................ Equus caballus (Equus spp.).
e206 .................... Rabbit, serum proteins ............................................... Oryctolagus cuniculus (Oryctolagus spp.).
e208 .................... Chinchilla epithelium ................................................... Chinchilla laniger.
e209 .................... Gerbil epithelium ......................................................... Meriones unguiculatus.
e210 .................... Fox epithelium ............................................................ Vulpes vulpes.
e211 .................... Rabbit, urine proteins ................................................. Oryctolagus cuniculus (Oryctolagus spp.).
e212 .................... Swine, urine proteins .................................................. Sus scrofa (Sus scrofa domesticus; Sus spp.).
e213 .................... Parrot feathers ............................................................ Ara spp.
e214 .................... Finch feathers ............................................................. Lonchura domestica.
e215 .................... Pigeon feathers ........................................................... Streptopelia roseogrisea (Streptopelia spp.), Colum-
bia spp.
e216 .................... Deer epithelium ........................................................... Dama dama.
394

Source
e217 .................... Ferret epithelium ......................................................... Mustela putorius.

e218 .................... Chicken droppings ...................................................... Gallus domesticus (Gallus gallus domesticus; Gallus
spp.).
e219 .................... Chicken, serum proteins ............................................. Gallus domesticus (Gallus gallus domesticus; Gallus
spp.).
e220 .................... Fel d 2, Cat serum albumin ........................................ Felis domesticus.
e221 .................... Can f 3 ........................................................................ Canis familiaris (Canis domesticus) (Dog serum al-
bumin).
e222 .................... Swine serum albumin (Sus s PSA) ............................ Sus scrofa (Sus scrofa domesticus; Sus spp.).
e225 .................... Lovebird feathers ........................................................ Psittacoidea agapomis.
e226 .................... Can f 5.0101 ............................................................... Canis familiaris.
e227 .................... Equ c 1.0101 .............................................................. Equus caballus.
e228 .................... Fel d 4.0101 ................................................................ Felis domesticus.
e230 .................... Equ c 3 ....................................................................... Equus caballus.
e231 .................... Mus m 1 ...................................................................... Mus musculus.
Food
f9 ......................... Rice ............................................................................. Oryza sativa.

f12 ....................... Pea (green pea) .......................................................... Pisum sativum.
f15 ....................... White bean .................................................................. Phaseolus vulgaris.
f19 ....................... Cayenne pepper ......................................................... Capsicum frutescens (Capsicum annum).
f21 ....................... Sugar cane ................................................................. Saccharum officinarum.
f22 ....................... Raspberry ................................................................... Rubus idaeus.
f26 ....................... Pork ............................................................................. Sus scrofa (Sus scrofa domesticus; Sus spp.).
f29 ....................... Watermelon ................................................................. Citrullus lanatus (Citrullus vulgaris).
f31 ....................... Carrot .......................................................................... Daucus carota.
f32 ....................... Oyster mushroom ....................................................... Pleurotus ostreatus.
f33 ....................... Orange ........................................................................ Citrus sinensis.
f35 ....................... Potato .......................................................................... Solanum tuberosum.
f43 ....................... Mother’s milk ............................................................... Homo sapiens.
f44 ....................... Strawberry ................................................................... Fragaria vesca (Fragaria spp.).
f45 ....................... Yeast, baker’s ............................................................. Saccharomyces cerevisiae.
f46 ....................... Pepper, Red ................................................................ Capsicum annuum.
f47 ....................... Garlic ........................................................................... Allium sativum.
f48 ....................... Onion .......................................................................... Allium cepa.
f49 ....................... Apple ........................................................................... Malus x domestica (Malus spp.).
f51 ....................... Bamboo shoot ............................................................. Phyllostachys pubescens.
f52 ....................... Cacao/chocolate ......................................................... Theobroma cacao.
f54 ....................... Sweet potato ............................................................... Ipomoea batatas.
f55 ....................... Common millet ............................................................ Panicum miliaceum.
f56 ....................... Foxtail millet ................................................................ Setaria italica.
f57 ....................... Japanese millet ........................................................... Echinochloa crus-galli.
f58 ....................... Pacific squid ................................................................ Todarodes pacificus.
f59 ....................... Octopus ....................................................................... Octopus vulgaris (Octopus spp.).
f63 ....................... Kefir ............................................................................. NA.
f67 ....................... Parmesan cheese ....................................................... NA.
f81 ....................... Cheese, cheddar type ................................................ NA.
f82 ....................... Cheese, mold type ...................................................... NA.
f83 ....................... Chicken ....................................................................... Gallus domesticus (Gallus gallus domesticus; Gallus
spp.).
f86 ....................... Parsley ........................................................................ Petroselinum crispum.
f87 ....................... Melon .......................................................................... Cucumis melo Cucumis melo + Citrullus lanatus.
f88 ....................... Mutton (lamb) .............................................................. Ovis aries (Ovis spp.).
f90 ....................... Malt ............................................................................. Hordeum vulgare.
f92 ....................... Banana ........................................................................ Musa spp.
f93 ....................... Cacao .......................................................................... Theobroma cacao.
f94 ....................... Pear ............................................................................ Pyrus communis (Pyrus spp.).
f97 ....................... Yam ............................................................................. Dioscorea spp. Dioscorea opposita.
f97 ....................... Chamomile tea ............................................................ Matricaria chamomilla.
f98 ....................... Gliadin ......................................................................... Triticum aestivum (Triticum spp.).
f102 ..................... Cantaloupe .................................................................. Cucumis melo var. cantalupensis.
f105 ..................... Chocolate .................................................................... Theobroma cacao.
f109 ..................... Cottonseed .................................................................. Gossypium hirsutum.
f110 ..................... Giant radish ................................................................ Raphanus sativus.
f118 ..................... Zucchini ....................................................................... Cucurbita pepo.
f119 ..................... Radish ......................................................................... Raphanus sativus.
f120 ..................... Venison ....................................................................... Capreolus capeolus.

f121 ..................... Pinto bean ................................................................... Phaseolus vulgaris.
f122 ..................... Cheese, American ...................................................... NA.
395
§ 866.5750 21 CFR Ch. I (4–1–23 Edition)

Source
f127 ..................... Black-eyed pea ........................................................... Vigna unguiculata.

f131 ..................... Black Olive .................................................................. Olea europaea.
f136 ..................... Red beet ..................................................................... Beta vulgaris var. conditiva.
f139 ..................... Goat’s Cheese ............................................................ Capra aegagrus.
f140 ..................... Bran ............................................................................ NA.
f141 ..................... Corn (vegetables) ....................................................... Zea mays.
f152 ..................... Green bell pepper ....................................................... Capsicum annuum.
f155 ..................... Brewer’s yeast ............................................................ Saccharomyces carlsbergensis.
f157 ..................... Duck ............................................................................ Anas domesticus.
f158 ..................... Goose ......................................................................... Anser anser.
f160 ..................... Camembert cheese .................................................... NA.
f162 ..................... Nectarine ..................................................................... Prunus persica var. nucipersica.
f163 ..................... Kohlrabi ....................................................................... Brassica oleracea var. gongylodes.
f65 ....................... Perch.
f166 ..................... Leek ............................................................................ Allium porrum.
f170 ..................... Cheese (Switzerland) (Swiss cheese) ........................ NA.
f174 ..................... Fig ............................................................................... Ficus carica.
f177 ..................... Cranberry .................................................................... Vaccinium macrocarpon.
f179 ..................... Raisin .......................................................................... Vitis spp.
f182 ..................... Lima bean ................................................................... Phaseolus lunatus.
f198 ..................... Flaxseed (bruised grain) ............................................. Linum usitatissimum.
f199 ..................... Untreated native milk .................................................. Bos domesticus (Bos taurus; Bos spp.).
f208 ..................... Lemon ......................................................................... Citrus limon.
f209 ..................... Grapefruit .................................................................... Citrus paradisi.
f210 ..................... Pineapple .................................................................... Ananas comosus.
f211 ..................... Blackberry ................................................................... Rubus fruticosus.
f212 ..................... Mushroom (champignon) ............................................ Agaricus hortensis (Agaricus spp.).
f213 ..................... Rabbit .......................................................................... Oryctolagus cuniculus (Oryctolagus spp.).
f214 ..................... Spinach ....................................................................... Spinacia oleracea.
f215 ..................... Lettuce ........................................................................ Lactuca sativa.
f216 ..................... Cabbage ..................................................................... Brassica oleracea var. capitata.
f217 ..................... Brussels sprouts ......................................................... Brassica oleracea var. gem.
f218 ..................... Paprika, sweet pepper ................................................ Capsicum annuum.
f219 ..................... Fennel seed ................................................................ Foeniculum vulgare.
f219 ..................... Sage ............................................................................ Salvia officinalis.
f220 ..................... Cinnamon .................................................................... Cinnamomum spp.
f221 ..................... Coffee ......................................................................... Coffea spp.
f222 ..................... Tea .............................................................................. Camellia sinensis.
f223 ..................... Green olive ................................................................. Olea europaea.
f225 ..................... Summer squash, pumpkin .......................................... Cucurbita pepo.
f225 ..................... Pumpkin ...................................................................... Cucurbita maxima.
f226 ..................... Pumpkin seed ............................................................. Cucurbita pepo.
f227 ..................... Sugar-beet seed ......................................................... Beta vulgaris.
f229 ..................... Safflower Seed ........................................................... Carthamus tinctorius.
f231 ..................... Milk, boiled .................................................................. Bos domesticus (Bos taurus; Bos spp.).
f234 ..................... Vanilla ......................................................................... Vanilla planifolia.
f237 ..................... Apricot ......................................................................... Prunus armeniaca.
f241 ..................... Gouda cheese ............................................................ NA.
f242 ..................... Cherry ......................................................................... Prunus avium.
f244 ..................... Cucumber ................................................................... Cucumis sativus.
f246 ..................... Guar, guar gum .......................................................... Cyamopsis tetragonoloba.
f247 ..................... Honey .......................................................................... NA.
f248 ..................... Rosemary .................................................................... Rosmarinus officinalis.
f254 ..................... Plaice .......................................................................... Pleuronectes platessa.
f255 ..................... Plum ............................................................................ Prunus domestica, Prunus americana.
f258 ..................... Squid ........................................................................... Loligo spp.
f259 ..................... Grape .......................................................................... Vitis vinifera (Vitis spp.).
f260 ..................... Broccoli ....................................................................... Brassica oleracea var. italica (Brassica oleracea var.
cultivar).
f261 ..................... Asparagus ................................................................... Asparagus officinalis.
f262 ..................... Aubergine, eggplant .................................................... Solanum melongena.
f263 ..................... Green pepper .............................................................. Piper nigrum, Capsicum annuum.
f264 ..................... Eel ............................................................................... Anguilla anguilla.
f265 ..................... Caraway ...................................................................... Carum carvi.
f265 ..................... Cumin .......................................................................... Cuminum cyminum.
f266 ..................... Mace ........................................................................... Myristica fragrans.
f267 ..................... Cardamon ................................................................... Elettaria cardamomum.

f268 ..................... Clove ........................................................................... Syzygium aromaticum.
f269 ..................... Basil ............................................................................ Ocimum basilicum.
f270 ..................... Ginger ......................................................................... Zingiber officinale.
396

Source
f271 ..................... Anise ........................................................................... Pimpinella anisum.

f272 ..................... Tarragon ..................................................................... Artemisia dracunculus.
f273 ..................... Thyme ......................................................................... Thymus vulgaris.
f274 ..................... Marjoram ..................................................................... Origanum majorana.
f275 ..................... Lovage ........................................................................ Levisticum officinale.
f276 ..................... Fennel, fresh ............................................................... Foeniculum vulgare.
f277 ..................... Dill ............................................................................... Anethum graveolens.
f278 ..................... Bay leaf ....................................................................... Laurus nobilis.
f279 ..................... Chili pepper ................................................................. Capsicum frutescens.
f280 ..................... Black pepper ............................................................... Piper nigrum.
f281 ..................... Curry (Santa Maria) .................................................... NA.
f282 ..................... Nutmeg ....................................................................... Myristica fragrans.
f283 ..................... Oregano ...................................................................... Origanum vulgare.
f284 ..................... Turkey meat ................................................................ Meleagris gallopavo.
f285 ..................... Elk/moose meat .......................................................... Alces spp.
f286 ..................... Mare’s milk .................................................................. Equus caballus (Equus spp.).
f287 ..................... Red kidney bean ......................................................... Phaseolus vulgaris.
f288 ..................... Blueberry ..................................................................... Vaccinium myrtillus (Vaccinium spp.).
f289 ..................... Date ............................................................................ Phoenix dactylifera.
f291 ..................... Cauliflower .................................................................. Brassica oleracea var. botrytis.
f292 ..................... Guava ......................................................................... Psidium guajava.
f293 ..................... Papaya ........................................................................ Carica papaya.
f294 ..................... Passion fruit, Maracuja ............................................... Passiflora edulis (Passiflora spp.).
f295 ..................... Carambola .................................................................. Averrhoa carambola.
f296 ..................... Carob .......................................................................... Ceratonia siliqua.
f297 ..................... Gum Arabic ................................................................. Acacia senegal (Acacia spp.).
f298 ..................... Tragacanth .................................................................. Astragalus spp.
f299 ..................... Sweet chestnut (chestnut) .......................................... Castanea sativa.
f300 ..................... Pinto bean ................................................................... Phaseolus spp.
f301 ..................... Persimmon (kaki fruit, sharon) ................................... Diospyros kaki.
f302 ..................... Mandarin (tangerine, clementine, satsumas) ............. Citrus reticulata.
f305 ..................... Fenugreek ................................................................... Trigonella foenum-graecum.
f306 ..................... Lime ............................................................................ Citrus aurantifolia.
f307 ..................... Hake ............................................................................ Merluccius merluccius.
f308 ..................... Sardine (pilchard) ....................................................... Sardina pilchardus.
f310 ..................... Blue vetch ................................................................... Lathyrus sativus.
f311 ..................... Megrim ........................................................................ Lepidorhombus whiffiagonis.
f315 ..................... Green bean ................................................................. Phaseolus vulgaris.
f316 ..................... Rape seed .................................................................. Brassica napus.
f317 ..................... Coriander .................................................................... Coriandrum sativum.
f318 ..................... Jack fruit ..................................................................... Artocarpus heterophyllus.
f319 ..................... Beetroot ...................................................................... Beta vulgaris.
f320 ..................... Crayfish ....................................................................... Astacus astacus.
f321 ..................... Horse meat ................................................................. Equus caballus (Equus spp.).
f322 ..................... Red currant ................................................................. Ribes sylvestre.
f324 ..................... Hop (fruit cone) ........................................................... Humulus lupulus.
f325 ..................... Saffron ........................................................................ Colchicum autumnale.
f329 ..................... Watermelon ................................................................. Citrullus lanatus.
f330 ..................... Rose hip ...................................................................... Rosa spp.
f331 ..................... Saffron ........................................................................ Crocus sativus.
f332 ..................... Mint ............................................................................. Mentha piperita.
f333 ..................... Linseed ....................................................................... Linum usitatissimum.
f336 ..................... Jujube ......................................................................... Ziziphus jujuba.
f336 ..................... Wine vinegar ............................................................... Vitis vinifera (Vitis spp.).
f337 ..................... Sole ............................................................................. Solea solea.
f337 ..................... English sole ................................................................ Parophrys vetulus.
f338 ..................... Wine, white ................................................................. Vitis vinifera (Vitis spp.).
f339 ..................... Allspice ........................................................................ Pimenta dioica.
f339 ..................... Wine, red .................................................................... Vitis vinifera (Vitis spp.).
f341 ..................... Cranberry .................................................................... Vaccinium oxycoccus, Vaccinium macrocarpon.
f342 ..................... Olive (black, fresh) ...................................................... Olea europaea.
f343 ..................... Raspberry ................................................................... Rubus idaeus.
f344 ..................... Sage ............................................................................ Salvia officinalis.
f346 ..................... Chives ......................................................................... Allium schoenoprasum.
f347 ..................... Quinoa ........................................................................ Chenopodium quinoa.
f348 ..................... Litchi ............................................................................ Litchi chinensis.

f349 ..................... Chum salmon roe ....................................................... Oncorhynchus keta.
f358 ..................... Artichoke ..................................................................... Cynara scolymus.
f360 ..................... Yogurt ......................................................................... NA.
397
§ 866.5750 21 CFR Ch. I (4–1–23 Edition)

Source
f368 ..................... Black bass .................................................................. Micropterus dolomieu (Micropterus dolomieui).

f374 ..................... Karaya gum ................................................................ Sterculia urens.
f375 ..................... Horseradish ................................................................. Armoracia rusticana.
f377 ..................... Maple syrup ................................................................ NA.
f379 ..................... Okra ............................................................................ Abelmoschus esculentus.
f382 ..................... Beet, sugar ................................................................. Beta vulgaris var. altissima.
f401 ..................... Loquat ......................................................................... Eriobotrya japonica.
f403 ..................... Brewer’s yeast ............................................................ Saccharomyces cerevisiae.
f405 ..................... Mint ............................................................................. Mentha spp.
f406 ..................... Arugula ........................................................................ Eruca vesicaria.
House Dust
h1 ........................ Greer Labs., Inc .......................................................... NA.

h2 ........................ Hollister-Stier Labs ..................................................... NA.
h6 ........................ Japan .......................................................................... NA.
Venoms & Insects
i7 ......................... Midge .......................................................................... Chironomus yoshimatsui.

i8 ......................... Moth ............................................................................ Bombyx mori, Heterocera spp.
i47 ....................... Water flea ................................................................... Daphnia spp.
i49 ....................... Deer fly ....................................................................... Chrysops spp.
i51 ....................... Black ant ..................................................................... Camponotus pennsylvanicus.
i54 ....................... Flea mix (dog/cat), common flea ................................ Ctenocephalides spp.
i71 ....................... Mosquito ..................................................................... Aedes communis, Aedes spp. and Culex spp.
i72 ....................... Green nimitti ............................................................... Cladotanytarsus lewisi.
i73 ....................... Blood worm ................................................................. Chironomus thummi, Chironomusri parius,
Chironomus spp.
i75 ....................... European hornet ......................................................... Vespa crabro.
i76 ....................... Berlin beetle ................................................................ Trogoderma angustum.
i77 ....................... European paper wasp ................................................ Polistes dominulus.
i78 ....................... Fly ............................................................................... Musca domestica.
i80 ....................... Bumblebee .................................................................. Bombus pennsylvanicus.
i201 ..................... Horse bot fly ............................................................... Gasterophilus intestinalis.
i202 ..................... Grain weevil ................................................................ Sitophilus granarius.
i203 ..................... Mediterranean flour moth ........................................... Ephestia kuehniella (Anagasta kuehniella).
i204 ..................... Horse fly ...................................................................... Tabanus spp.
i205 ..................... Bumblebee .................................................................. Bombus terrestris.
i208 ..................... Api m 1.0101 .............................................................. Apis mellifera.
a45 ...................... Api m 1 ....................................................................... Apis mellifera.
i209 ..................... Ves v 5.0101 ............................................................... Vespula vulgaris.
a670 .................... Ves v 5 ........................................................................ Vespula vulgaris.
i210 ..................... Pol d 5.0101 ............................................................... Polistes dominulus.
i211 ..................... Ves v 1.0101 ............................................................... Vespula vulgaris.
i213 ..................... Api m 4 ....................................................................... Apis mellifera.
i217 ..................... Api m 10 ..................................................................... Apis mellifera.
i220 ..................... Bla g 1.0101 ............................................................... Blattella germanica.
i223 ..................... Bla g 7 ........................................................................ Blattella germanica.
a46 ...................... Api m 2 ....................................................................... Apis mellifera.
Miscellaneous
o1 ........................ Cotton, crude fibers .................................................... Gossypium spp.

o3 ........................ Cotton (treated) ........................................................... Gossypium spp.
o70 ...................... Seminal fluid ............................................................... Homo sapiens.
o71 ...................... Staphylococcus aureus ............................................... Staphylococcus aureus.
o72 ...................... Pichia pastoris crude extract customer specific ......... Pichia pastoris.
o72 ...................... Sperm-sediment .......................................................... Homo sapiens.
o73 ...................... Pichia pastoris crude extr. vector customer specific .. Pichia pastoris.
o74 ...................... Pichia pastoris with vector customer specific ............. Pichia pastoris.
o201 .................... Tobacco leaf, tobacco dust ........................................ Nicotiana tabacum.

o202 .................... Artemia salina, fish feed ............................................. Artemia salina.
o203 .................... Tetramin, fish feed ...................................................... NA.
398

Source
o207 .................... Daphnia, fish feed ....................................................... Daphnia spp.

o211 .................... Mealworm ................................................................... Tenebrio molitor.
o212 .................... Streptavidin ................................................................. Streptomyces avidini.
o213 .................... MBP (maltose binding protein) ................................... Escherichia coli.
o214 .................... CCD; MUXF3 from bromelain .................................... Ananas comosus.
o72 ...................... Enterotoxin A (Sta a SEA) .......................................... Staphylococcus aureus.
o73 ...................... Enterotoxin B (Sta a SEB) .......................................... Staphylococcus aureus.
Parasites
p1 ........................ Ascaris ........................................................................ Ascaris suum.

p2 ........................ Echinococcus .............................................................. Echinococcus granulosus.
p3 ........................ Schistosoma ............................................................... Schistosoma mansoni.
p4 ........................ Anisakis (Herring Worm) ............................................ Anisakis simplex (Anisakis spp.).
p5 ........................ Toxocara canis ........................................................... Toxocara canis.
p10 ...................... Ani s 3.0101 ................................................................ Anisakis simplex (Anisakis spp.).
p11 ...................... Ani s 1 ......................................................................... Anisakis simplex (Anisakis spp.).
Occupational
k4 ........................ Threshing dust ............................................................ NA.

k5 ........................ Flax ............................................................................. NA.
k7 ........................ Hay Dust ..................................................................... NA.
k8 ........................ Hop (hops) .................................................................. Humulus lupulus.
k12 ...................... Grain mill dust ............................................................. NA.
k14 ...................... Kapok .......................................................................... NA.
k20 ...................... Sheep’s wool (treated) (wool) ..................................... Ovis aries (Ovis spp.).
k21 ...................... Sheep’s wool (Untreated) ........................................... Ovis aries (Ovis spp.).
k23 ...................... Straw Dust .................................................................. NA.
k33 ...................... Oak ............................................................................. NA.
k70 ...................... Green coffee bean ...................................................... Coffea spp.
k71 ...................... Castor bean ................................................................ Ricinus communis.
k72 ...................... Ispaghula .................................................................... Plantago psyllium/Plantago ovata.
k73 ...................... Silk waste .................................................................... NA.
k74 ...................... Silk .............................................................................. Bombyx mori.
k75 ...................... Isocyanate TDI (Toluene diisocyanate) ...................... NA.
k76 ...................... Isocyanate MDI (Diphenylmethane diisocyanate) ...... NA.
k77 ...................... Isocyanate HDI (Hexamethylen diisocyanate) ........... NA.
k78 ...................... Ethylene oxide ............................................................ NA.
k79 ...................... Phthalic anhydride ...................................................... NA.
k80 ...................... Formaldehyde/Formalin .............................................. NA.
k81 ...................... Ficus ........................................................................... Ficus benjamina (Ficus spp.).
k83 ...................... Cotton seed ................................................................ Gossypium hirsutum.
k84 ...................... Sunflower seed ........................................................... Helianthus annuus.
k85 ...................... Chloramin T ................................................................ NA.
k86 ...................... Trimellitic anhydride, TMA .......................................... NA.
k87 ...................... Asp o 21, alpha-amylase ............................................ Aspergillus oryzae.
k89 ...................... Orris root ..................................................................... Iris florentina.
k99 ...................... HSA (Human Serum Albumin) (Hom s HSA) ............. Homo sapiens.
k201 .................... Car p 1, Papain .......................................................... Carica papaya.
k202 .................... Ana c 2, Bromelain ..................................................... Ananas comosus.
k204 .................... Maxatase .................................................................... Bacillus licheniformis.
k205 .................... Alcalase ...................................................................... Bacillus spp.
k206 .................... Savinase, Protease 1 (Bac l Subtilisin) ...................... Bacillus spp.
k208 .................... Gal d 4, Lysozyme ...................................................... Gallus domesticus (Gallus gallus domesticus; Gallus
spp.).
k209 .................... Hexahydrophtalic anhydrid ......................................... NA.
k210 .................... Maleic anhydride ......................................................... NA.
k211 .................... Methyltetrahydrophtalic anhydrid ................................ NA.
k212 .................... Abachi wood dust ....................................................... Triplochiton scleroxylon.
k213 .................... Pepsin (Sus s Pepsin) ................................................ Sus scrofa (Sus scrofa domesticus; Sus spp.).
k213 .................... TCPA .......................................................................... NA.
k214 .................... Bougainvillea ............................................................... Bougainvillea spp.
k225 .................... Horse radish peroxidase (Arm r HRP) ....................... Armoracia rusticana.
k226 .................... Ascorbate oxidase (Cuc p ascorbate oxidase) .......... Cucurbita pepo.
k301 .................... Flour dust .................................................................... Triticum spp.
k501 .................... Savinase customer specific ........................................ Proprietary knowledge of customer.
k502 .................... Lipolase customer specific ......................................... Proprietary knowledge of customer.

k503 .................... Termamyl customer specific ....................................... Proprietary knowledge of customer.
k504 .................... Clazinase customer specific ....................................... Proprietary knowledge of customer.
399
§ 866.5760 21 CFR Ch. I (4–1–23 Edition)
[47 FR 50823, Nov. 9, 1982, as amended at 84 FR 71800, Dec. 30, 2019]
§ 866.5760 Tryptase test system. § 866.5785 Anti-Saccharomyces

cerevisiae (S. cerevisiae) antibody
(a) Identification. A tryptase test sys- (ASCA) test systems.
tem is a device that aids in the diag-
nosis of systemic mastocytosis. It is in- (a) Identification. The Anti-Saccharo-
tended for in vitro diagnostic use as an myces cerevisiae (S. cerevisiae) antibody
aid in the clinical diagnosis of patients (ASCA) test system is an in vitro diag-
with a suspicion of systemic nostic device that consists of the re-
mastocytosis in conjunction with other agents used to measure, by
immunochemical techniques, anti-
clinical and laboratory findings.
bodies to S. cerevisiae (baker’s or brew-
er’s yeast) in human serum or plasma.
Detection of S. cerevisiae antibodies
guideline entitled ‘‘Class II Special may aid in the diagnosis of Crohn’s dis-
Controls Guideline: Tryptase Test Sys- ease.
tem as an Aid in the Diagnosis of Sys- (b) Classification. Class II (special
temic Mastocytosis.’’ For availability controls). The special control is FDA’s
of the document, see § 866.1(e). ‘‘Guidance for Industry and FDA Re-
[79 FR 56010, Sept. 18, 2014] viewers: Class II Special Control Guid-
ance Document for Anti-Saccharomyces
§ 866.5765 Retinol-binding protein cerevisiae (S. cerevisiae) Antibody
immunological test system. (ASCA) Premarket Notifications.’’
(a) Identification. A retinol-binding [65 FR 70307, Nov. 22, 2000]
protein immunological test system is a
device that consists of the reagents § 866.5800 Seminal fluid (sperm)
used to measure by immunochemical immunological test system.
techniques the retinol-binding protein (a) Identification. A seminal fluid
that binds and transports vitamin A in (sperm) immunological test system is a
serum and urine. Measurement of this device that consists of the reagents
protein may aid in the diagnosis of kid- used for legal purposes to identify and
ney disease and in monitoring patients differentiate animal and human semen.
with kidney transplants. The test results may be used as court
(b) Classification. Class I (general con- evidence in alleged instances of rape
trols). The device is exempt from the and other sex-related crimes.
subject to § 866.9. premarket notification procedures in
[47 FR 50823, Nov. 9, 1982, as amended at 65 subject to the limitations in § 866.9.
FR 2313, Jan. 14, 2000]
§ 866.5775 Rheumatoid factor immuno- FR 38793, July 25, 2001]
§ 866.5820 Systemic lupus erythema-
(a) Identification. A rheumatoid factor tosus immunological test system.
that consists of the reagents used to (a) Identification. A systemic lupus
measure by immunochemical tech- erythematosus (SLE) immunological
niques the rheumatoid factor (anti- test system is a device that consists of
bodies to immunoglobulins) in serum, the reagents used to measure by
other body fluids, and tissues. Measure- immunochemical techniques the auto-
ment of rheumatoid factor may aid in immune antibodies in serum and other
body fluids that react with cellular nu-
the diagnosis of rheumatoid arthritis.
clear double-stranded deoxyribonucleic
acid (DNA) or other nuclear constitu-

ance standards). ents that are specifically diagnostic of
SLE. Measurement of nuclear double-
400
stranded DNA antibodies aids in the di- for determination of severity of trau-
agnosis of SLE (a multisystem automatic brain injury (TBI).
immune disease in which tissues are (B) Study must be performed using
attacked by the person’s own anti- the operators and in settings that are
bodies). representative of the types of operators
(b) Classification. Class II (perform- and settings for which the device is in-
ance standards). tended to be used.
(C) All eligible subjects must meet
§ 866.5830 Brain trauma assessment
test. the well-defined study inclusion and
exclusion criteria that define the in-
(a) Identification. A brain trauma as- tended use population. The prevalence
sessment test is a device that consists of diseased or injured subjects in the
of reagents used to detect and measure study population must reflect the prev-
brain injury biomarkers in human alence of the device’s intended use pop-
specimens. The measurements aid in ulation, or alternatively, statistical
the evaluation of patients with sus- measures must be used to account for
pected mild traumatic brain injury in any bias due to enrichment of sub-
conjunction with other clinical infor- populations of the intended use popu-
mation to assist in determining the lation.
need for head imaging per current (D) All eligible subjects must have
standard of care.
undergone a head computerized tomog-
raphy (CT) scan or other appropriate
clinical diagnostic standard used to de-
device are:
termine the presence of an intracranial
(1) The 21 CFR 809.10(b) compliant la-
lesion as part of standard of care and
beling must include detailed descrip-
must also be evaluated by the subject
tions of and results from performance
device. All clinical diagnostic stand-
testing conducted to evaluate preci-
ards used in the clinical study must
sion, accuracy, linearity, analytical
follow standard clinical practice in the
sensitivity, interference, and cross-re-
United States.
activity. This information must in-
clude the following: (E) Relevant demographic variables
(i) Performance testing of device pre- and baseline characteristics including
cision must, at minimum, use one un- medical history and neurological his-
modified clinical specimen from the in- tory. In addition, head injury charac-
tended use population with concentra- teristics, neurological assessments, and
tion of the brain injury biomarker(s) physical evidence of trauma must be
near the medical decision point. Con- provided for each subject. This infor-
trived specimens that have been gen- mation includes but is not limited to
erated from pooling of multiple sam- the following: Time since head injury,
ples or spiking of purified analyte to time from head injury to CT scan, time
cover the measuring range may be from head injury to blood draw, GCS
used, but the contrived samples must score or equivalent, experience of loss
be prepared to mimic clinical speci- of consciousness, presence of confusion,
mens as closely as possible. This test- episodes of vomiting, post-traumatic
ing must evaluate repeatability and re- amnesia characteristics, presence of
producibility using a protocol from an post-traumatic seizures, drug or alco-
FDA-recognized standard. hol intoxication, mechanism of injury,
(ii) Device performance data must be acute intracranial lesion type,
demonstrated through a clinical study neurosurgical lesion, and cranial frac-
and must include the following: ture.
(A) Data demonstrating clinical va- (F) Each CT scan or other imaging
lidity including the clinical sensitivity result must be independently evaluated
and specificity, and positive and nega- in a blinded manner by at least two
tive predictive value of the test in the board-certified radiologists to deter-
intended use population of patients mine whether it is positive or negative
with suspected mild traumatic brain as defined by the presence or absence of

injury (i.e., Glasgow Coma Score (GCS) acute intracranial lesions. This inde-
of 13–15), or equivalent standard of care pendent review must be conducted
401
§ 866.5860 21 CFR Ch. I (4–1–23 Edition)
without access to test results of the de- § 866.5860 Total spinal fluid immuno-
vice. Prior to conducting the review, logical test system.
the criteria and procedures to be fol- (a) Identification. A total spinal fluid
lowed for scoring the images must be
established, including the mechanism
for determining consensus.
(G) All the clinical samples must be
niques the total protein in cerebro-
tested with the subject device blinded
spinal fluid. Measurement of spinal
to the TBI status and the neurological-
fluid proteins may aid in the diagnosis
lesion-status of the subject.
of multiple sclerosis and other diseases
(H) Details on how missing values in
of the nervous system.
data are handled must be provided.
(I) For banked clinical samples, de-
tails on storage conditions and storage trols). The device is exempt from the
period must be provided. In addition, a premarket notification procedures in
specimen stability study must be con- subpart E of part 807 of this chapter
ducted for the duration of storage to subject to the limitations in § 866.9.
demonstrate integrity of archived clin- [47 FR 50823, Nov. 9, 1982, as amended at 61
ical samples. The samples evaluated in FR 1119, Jan. 16, 1996; 66 FR 38793, July 25,
the assay test development must not 2001]
be used to establish the clinical valid-
ity of the assays. § 866.5870 Thyroid autoantibody
(iii) Performance testing of device immunological test system.
analytical specificity must include the (a) Identification. A thyroid
most commonly reported concomitant autoantibody immunological test sys-
medications present in specimens from tem is a device that consists of the re-
the intended use population. Addition- agents used to measure by
ally, potential cross-reacting endoge- immunochemical techniques the thy-
nous analytes must be evaluated at the roid autoantibodies (antibodies pro-
highest concentration reported in duced against the body’s own tissues).
specimens from the intended use popu- Measurement of thyroid autoantibodies
lation. may aid in the diagnosis of certain thy-
(iv) Expected/reference values gen- roid disorders, such as Hashimoto’s dis-
erated by testing a statistically appro- ease (chronic lymphocytic thyroiditis),
priate number of samples from appar- nontoxic goiter (enlargement of thy-
ently healthy normal individuals. roid gland), Grave’s disease (enlarge-
(2) The 21 CFR 809.10(a) and (b) comment of the thyroid gland with protru-
pliant labeling must include the fol- sion of the eyeballs), and cancer of the
lowing limitations: thyroid.
(i) A limiting statement that this de- (b) Classification. Class II (perform-
vice is not intended to be used a stand- ance standards).
alone device but as an adjunct to other
clinical information to aid in the eval- § 866.5880 Transferrin immunological
uation of patients who are being con- test system.
sidered for standard of care (a) Identification. A transferrin
neuroimaging. immunological test system is a device
(ii) A limiting statement that reads that consists of the reagents used to
‘‘A negative result is generally associ- measure by immunochemical tech-
ated with the absence of acute niques the transferrin (an iron-binding
intracranial lesions. An appropriate and transporting serum protein) in
neuroimaging method is required for serum, plasma, and other body fluids.
diagnosis of acute intracranial le- Measurement of transferrin levels aids
sions.’’ in the diagnosis of malnutrition, acute
(iii) As applicable, a limiting state- inflammation, infection, and red blood
ment that reads ‘‘This device is for use cell disorders, such as iron deficiency
by laboratory professionals in a clin-
anemia.
ical laboratory setting.’’
[83 FR 27701, June 14, 2018] ance standards).
402
§ 866.5890 Inter-alpha trypsin inhib- type of device includes recombinant,

itor immunological test system. synthetic, and cell line-based DNA con-
(a) Identification. An inter-alpha trols.
trypsin inhibitor immunological test (b) Classification. Class II (special
system is a device that consists of the controls). The device is exempt from
reagents used to measure by the premarket notification procedures
immunochemical techniques the inter- in subpart E of part 807 of this chapter
alpha trypsin inhibitor (a protein) in subject to the limitations in § 866.9. The
serum and other body fluids. Measure- special control is FDA’s guidance docu-
ment of inter-alpha trypsin inhibitor ment entitled ‘‘Class II Special Con-
may aid in the diagnosis of acute bac- trols Guidance Document: Quality Con-
terial infection and inflammation. trol Material for Cystic Fibrosis Nu-
(b) Classification. Class I (general con- cleic Acid Assays.’’ See § 866.1(e) for the
trols). The device is exempt from the availability of this guidance document.
premarket notification procedures in [72 FR 1176, Jan. 10, 2007, as amended at 84
subpart E of part 807 of this chapter FR 71811, Dec. 30, 2019]
§ 866.5930 Newborn screening test for
[47 FR 50823, Nov. 9, 1982, as amended at 53 severe combined immunodeficiency
FR 11253, Apr. 6, 1988; 65 FR 2313, Jan. 14, disorder (SCID).
2000]
(a) Identification. A newborn screen-
§ 866.5900 Cystic fibrosis ing test for SCID is a prescription de-
transmembrane conductance regu- vice intended to measure T-cell recep-
lator (CFTR) gene mutation detector excision circle (TREC) DNA ob-
tion system. tained from dried blood spot specimens
(a) Identification. The CFTR gene mu- on filter paper using a polymerase
tation detection system is a device chain reaction based test as an aid in
used to simultaneously detect and screening newborns for SCID. Presump-
identify a panel of mutations and tive positive results must be followed
variants in the CFTR gene. It is in- up by diagnostic confirmatory testing.
tended as an aid in confirmatory diag- This test is not intended for use as a
nostic testing of individuals with sus- diagnostic test, or for screening of
pected cystic fibrosis (CF), carrier SCID-like syndromes, such as DiGeorge
identification, and newborn screening. syndrome or Omenn syndrome. It is
This device is not intended for stand- also not intended to screen for less
alone diagnostic purposes, prenatal di- acute SCID syndromes, such as leaky
agnostic, pre-implantation, or popu- SCID or variant SCID.
lation screening. (b) Classification. Class II (special
(b) Classification. Class II (special controls). The special controls for this
controls). The special control is FDA’s device are:
guidance document entitled ‘‘Class II (1) Premarket notification submis-
Special Controls Guidance Document: sions must include the following infor-
CFTR Gene Mutation Detection Sys- mation:
tem.’’ See § 866.1(e) for the availability (i) The intended use must indicate:
of this guidance document. (A) The test is not intended for diag-
[70 FR 61738, Oct. 26, 2005] nostic use, or for screening of SCID-
like syndromes, such as DiGeorge syn-
§ 866.5910 Quality control material for drome or Omenn syndrome; and
cystic fibrosis nucleic acid assays. (B) The test is not intended to screen
(a) Identification. Quality control ma- for less acute SCID syndromes, such as
terial for cystic fibrosis nucleic acid leaky SCID or variant SCID.
assays. A quality control material for (ii) A detailed description of all com-
cystic fibrosis nucleic acid assays is a ponents in the test that includes:
device intended to help monitor reli- (A) A detailed description of the test
ability of a test system by detecting components, all required reagents, in-
analytical deviations such as those strumentation and equipment, includ-

that may arise from reagent or instru- ing illustrations or photographs of non-
ment variation in genetic testing. This standard equipment or methods;
403
§ 866.5930 21 CFR Ch. I (4–1–23 Edition)
(B) Detailed documentation of the that are characterized by other dis-

device software including, but not lim- orders that can be found by screening
ited to, standalone software applica- specimens that have low or absent
tions and hardware-based devices that TREC (e.g., other T-cell lymphopenic
incorporate software; disorders) to supplement the range of
(C) Specifications for the filter paper, results. The clinical validation study
which must be appropriately labeled must have a pre-specified clinical deci-
for in vitro diagnostic use, to be used sion point (i.e., cutoff to distinguish
in specimen collection and how it will positive and negative results). Results
be used in specimen collection valida- must be summarized in tabular format
tion. These specifications must in- comparing interpretation of results to
clude: descriptive characteristics of the the reference method. Point estimates
filter paper, instructions on how a lab together with two-sided 95 percent con-
should choose the appropriate filter fidence intervals must be provided for
paper, chemical properties of the filter the positive percent agreement, nega-
paper, interference concerns associated tive percent agreement, and overall
with the chemicals in the filter paper, percent agreement. Data must include
absorption properties of the filter the retest rate, the false positive rate
paper, punch size, absorption capacity, before retest, the final false positive
testing for homogeneity of punches, di- rate, and the false negative rate;
ameter of the circle for the dried blood (B) Device reproducibility data gen-
spot aliquot, absorption time, physical erated, using a minimum of three sites
composition, and number and size of of which at least two must be external
punches to be tested; sites, with two operators at each site.
(D) Methodology and protocols for Each site must conduct a minimum of
detection of T-cell receptor excision five runs per operator over five non-
circles and methods for determination consecutive days evaluating a min-
of results. The cutoff must be selected imum of six different relevant TREC
before conducting clinical and analyt- concentrations that span and are well
ical studies; distributed over the measuring range
(E) A description of the result out- and include the clinical cutoff. Speci-
puts along with sample reports. Sample mens must include cord blood and cord
reports must include the scale used in blood diluted with ABO matched adult
reporting of results (e.g., TREC copies/ blood specimens. Identical specimens
μL) and the range of values that will be from the same sample panel must be
reported out; and tested at each site. Each specimen
(F) A description of appropriate in- must be run in triplicate and include
ternal and external controls that are controls run in triplicate. Results must
recommended or provided. The descrip- be reported as the standard deviation
tion must identify those control ele- and percentage coefficient of variation
ments that are incorporated into the for each level tested. Results must also
testing procedure. be displayed as a dichotomous variable
(iii) Information that demonstrates around the cutoff. Total variation
the performance characteristics of the must be partitioned into the sum of
test, including: within-lab and between-lab variations
(A) Data that demonstrates the clin- with pre-specified acceptance criteria
ical validity of the device, using well and 95 percent confidence intervals for
characterized prospectively or retro- all data. Pre-specified acceptance cri-
spectively obtained clinical specimens teria must be provided and followed;
representative of the intended use pop- (C) Device precision data using clin-
ulation. A minimum of 10 to 15 con- ical samples to evaluate the within-lot,
firmed positive specimens must be ob- between-lot, within-run, between run,
tained from more than 1 site, including and total variation. A range of TREC
relevant annotation, and, at 1 year or levels of the specimen must include
beyond, a SCID diagnosis by flow samples within the measuring range,
cytometry or clinically meaningful in- samples above and below the meas-
formation regarding the status of the uring range, as well as with samples
subject must be obtained. Additional very near above and below the cutoff
specimens should have been obtained value. At least three replicates of each
404
specimen must be tested with controls summarized providing the mean, stand-
and calibrator(s) according to the de- ard deviation, and percentage coeffi-
vice instructions for use. The precision cient of variation in a tabular format.
study must use well characterized sam- Data must be calculated for within-
ples using different lots, instruments, run, between-run, within-lot, and be-
and operators. Results must be summa- tween-lot. Data demonstrating the con-
rized in tabular format. Pre-specified cordance between results across dif-
acceptance criteria must be provided ferent filter papers must be provided.
and followed; Study acceptance criteria must be pro-
(D) Linearity of the test must be vided and followed; and
demonstrated using a dilution panel (I) If applicable, a thermocycler re-
from clinical samples. The range of di- producibility study must be performed
lution samples must include samples using thermocyclers from three inde-
within the measuring range, samples pendent thermocyler manufacturers.
above and below the measuring range, The sample panel must consist of speci-
as well as with samples very near mens with a range of TREC levels and
above and below the cutoff value. Re- must include samples within the meas-
sults of the regression analysis must be uring range, samples above and below
summarized in tabular format and the measuring range, and samples very
fitted into a linear regression model near above and below the cutoff value.
with the individual measurement re- The study must be done using three fil-
sults against the dilution factors. Pre- ter paper lots and conducted over five
specified acceptance criteria must be nonconsecutive days. Results of the
provided and followed; thermocycler reproducibility study
(E) Device analytic sensitivity data, must be summarized providing the
including limit of blank, limit of detec- mean, standard deviation, and percent-
tion, and limit of quantification; age coefficient of variance in a tabular
(F) Device specificity data, including format. Data must be calculated for
interference, carryover, cross-contami- the within-run, between-run, within-
nation, and in silico analysis of poten- lot, between-lot, and between
tial off-target genomic sequences; thermocycler manufacturer study re-
(G) Device stability data, including sults. Study acceptance criteria must
real-time stability of samples under be provided and followed.
various storage times, temperatures,
(iv) Identification of risk mitigation
and freeze-thaw conditions. A separate
elements used by your device, includ-
shipping stability study must be per-
ing a description of all additional pro-
formed;
cedures, methods, and practices incor-
(H) Lot-to-lot reproducibility study
of each filter paper that will be vali- porated into the directions for use that
dated with the test. The lot-to-lot mitigate risks associated with testing.
study must include a minimum of (2) Your § 809.10 compliant labeling
three lots of each blood spot card that must include:
will be validated with the test and be (i) A warning statement that reads
conducted over five nonconsecutive ‘‘This test is not intended for diag-
days. The sample panel must consist of nostic use, preimplantation or prenatal
specimens with a range of TREC levels testing, or for screening of SCID-like
and include samples within the meas- syndromes, such as DiGeorge syndrome
uring range, samples above and below or Omenn syndrome. It is also not in-
the measuring range, and samples very tended to screen for less acute SCID
near above and below the cutoff value. syndromes, such as leaky SCID or vari-
Multiple punches must be obtained ant SCID.’’;
from each card for demonstration of (ii) A warning statement that reads
homogeneity of the analyte across the ‘‘Test results are intended to be used in
dried blood spot. Comparability of the conjunction with other clinical and di-
test performance for each filter paper agnostic findings, consistent with pro-
must be demonstrated. Stability and fessional standards of practice, includ-
storage of TREC DNA on each blood ing confirmation by alternative meth-

spot card must be demonstrated. Re- ods and clinical evaluation, as appro-
sults of the lot-to-lot study must be priate.’’;
405
§ 866.5940 21 CFR Ch. I (4–1–23 Edition)
(iii) A description of the performance Web site or testing using the device
studies listed in paragraph (b)(1)(iii) can be ordered from the Web site, the
and a summary of the results; and same information must be found on the
(iv) A description of the filter paper Web page for ordering the device or
specifications required for the test. provided in a prominently placed and
[82 FR 50079, Oct. 30, 2017] publicly accessible hyperlink on the
Web page for ordering the device. Any
§ 866.5940 Autosomal recessive carrier changes to the device that could sig-
screening gene mutation detection nificantly affect safety or effectiveness
system. would require new data or information
(a) Identification. Autosomal reces- in support of such changes, which
sive carrier screening gene mutation would also have to be posted on the
detection system is a qualitative in manufacturer’s Web site. The informa-
vitro molecular diagnostic system used tion must include:
for genotyping of clinically relevant (i) A detailed device description in-
variants in genomic DNA isolated from cluding:
human specimens intended for pre- (A) Gene (or list of the genes if more
scription use or over-the-counter use. than one) and variants the test detects
The device is intended for autosomal (using standardized nomenclature,
recessive disease carrier screening in Human Genome Organization (HUGO)
adults of reproductive age. The device nomenclature, and coordinates).
is not intended for copy number vari- (B) Scientifically established clinical
ation, cytogenetic, or biochemical test- validity of each variant detected and
ing. reported by the test, which must be
(b) Classification. Class II (special well-established in peer-reviewed jour-
controls). The device is exempt from nal articles, authoritative summaries
the premarket notification procedures of the literature such as Genetics
in subpart E of part 807 of this chapter Home Reference (http://ghr.nlm.nih.gov/
subject to the limitations in § 866.9, ex- ), GeneReviews (http://
cept § 866.9(c)(2). Autosomal recessive www.ncbi.nlm.nih.gov/books/NBK1116/),
carrier screening gene mutation detec- or similar summaries of valid scientific
tion system must comply with the fol- evidence, and/or professional society
lowing special controls: recommendations, including:
(1) If the device is offered over-the- (1) Genotype-phenotype information
counter, the device manufacturer must for the reported mutations.
provide information to a potential pur- (2) Relevant American College of
chaser or actual test report recipient Medical Genetics (ACMG) or American
about how to obtain access to a board- Congress of Obstetricians and Gyne-
certified clinical molecular geneticist cologists (ACOG) guideline recom-
or equivalent to assist in pre- and post- mending testing of the specific gene(s)
test counseling. and variants the test detects and rec-
(2) The device must use a collection ommended populations, if available. If
device that is FDA cleared, approved, not available, a statement stating that
or classified as 510(k) exempt, with an professional guidelines currently do
indication for in vitro diagnostic use in not recommend testing for this specific
DNA testing. gene(s) and variants.
(3) The device’s labeling must include (3) Table of expected prevalence of
a prominent hyperlink to the manufac- carrier status in major ethnic and ra-
turer’s public Web site where the man- cial populations and the general popu-
ufacturer shall make the information lation.
identified in this section publicly (C) The specimen type (e.g., saliva,
available. The manufacturer’s home whole blood), matrix, and volume.
page, as well as the primary part of the (D) Assay steps and technology used.
manufacturer’s Web site that discusses (E) Specification of required ancil-
the device, must provide a prominently lary reagents, instrumentation, and
placed hyperlink to the Web page con- equipment.
taining this information and must (F) Specification of the specimen col-
allow unrestricted viewing access. If lection, processing, storage, and prepa-
the device can be purchased from the ration methods.
406
(G) Specification of risk mitigation percent agreement (NPA), must be

elements and description of all addi- measured; accuracy point estimates
tional procedures, methods, and prac- must be greater than 99 percent (both
tices incorporated into the directions per reported variant and overall) and
for use that mitigate risks associated uncertainty of the point estimate must
with testing. be presented using the 95 percent con-
(H) Information pertaining to the fidence interval. Clinical specimens
probability of test failure (e.g., failed must include both homozygous wild
quality control) based on data from type and heterozygous genotypes. The
clinical samples, description of sce- number of clinical specimens for each
narios in which a test can fail (i.e., low variant reported that must be included
sample volume, low DNA concentra- in the accuracy study must be based on
tion, etc.), how customers will be noti- the variant prevalence. Common
fied, and followup actions to be taken. variants (greater than 0.1 percent allele
(I) Specification of the criteria for frequency in ethnically relevant popu-
test result interpretation and report- lation) must have at least 20 unique
ing. heterozygous clinical specimens tested.
(ii) Information that demonstrates Rare variants (less than or equal to 0.1
the performance characteristics of the percent allele frequency in ethnically
device, including: relevant population) shall have at least
(A) Accuracy (method comparison) of three unique mutant heterozygous
study results for each claimed speci- specimens tested. Any no calls (i.e., ab-
men type. sence of a result) or invalid calls (e.g.,
(1) Accuracy of the device shall be failed quality control) in the study
evaluated with fresh clinical specimens must be included in accuracy study re-
collected and processed in a manner sults and reported separately. Variants
consistent with the device’s instruc- that have a point estimate for PPA or
tions for use. If this is impractical, NPA of less than 99 percent (incorrect
fresh clinical samples may be sub- test results as compared to
stituted or supplemented with archived bidirectional sequencing or other
clinical samples. Archived samples methods identified as appropriate by
shall have been collected previously in FDA) must not be incorporated into
accordance with the device’s instruc- test claims and reports. Accuracy
tions for use, stored appropriately, and measures generated from clinical speci-
randomly selected. In some instances, mens versus contrived samples or cell
use of contrived samples or human cell lines must be presented separately. Re-
line samples may also be appropriate; sults must be summarized and pre-
the contrived or human cell line sam- sented in tabular format, by sample
ples shall mimic clinical specimens as and by genotype. Point estimate of
much as is feasible and provide an un- PPA should be calculated as the num-
biased evaluation of the device’s accu- ber of positive results divided by the
racy. number of specimens known to harbor
(2) Accuracy must be evaluated as variants (mutations) without ‘‘no
compared to bidirectional sequencing calls’’ or invalid calls. The point esti-
or other methods identified as appro- mate of NPA should be calculated as
priate by FDA. Performance criteria the number of negative results divided
for both the comparator method and by the number of wild type specimens
device must be predefined and appro- tested without ‘‘no calls’’ or invalid
priate to the test’s intended use. De- calls, for each variant that is being re-
tailed appropriate study protocols ported. Point estimates should be cal-
must be provided. culated along with 95 percent two-sided
(3) Information provided shall in- confidence intervals.
clude the number and type of speci- (4) Information shall be reported on
mens, broken down by clinically rel- the clinical positive predictive value
evant variants, that were compared to (PPV) and negative predictive value
bidirectional sequencing or other (NPV) for carrier status (and where
methods identified as appropriate by possible, for each variant) in each pop-

FDA. The accuracy, defined as positive ulation. Specifically, to calculate PPV
percent agreement (PPA) and negative and NPV, estimate test coverage (TC)
407
§ 866.5940 21 CFR Ch. I (4–1–23 Edition)
and the percent of persons with vari- more than one laboratory, different
ant(s) included in the device among all laboratories must be included in the
carriers: PPV = (PPA * TC * π)/(PPA * precision study (and reproducibility
TC * π + (1 ¥ NPA) * (1 ¥ π)) and NPV must be evaluated). The percentage of
= (NPA * (1 ¥ π))/(NPA *(1 ¥ π) + (1 ¥ ‘‘no calls’’ or invalid calls, if any, in
PPA*TC) * π) where PPA and NPA de- the study must be provided as a part of
scribed either in paragraph the precision (reproducibility) study
(b)(3)(ii)(A)(4)(i) or in paragraph results.
(b)(3)(ii)(A)(4)(ii) of this section and π is (C) Analytical specificity data: Data
prevalence of carriers in the population must be generated evaluating the ef-
(pre-test risk to be a carrier for the dis- fect on test performance of potential
ease). endogenous and exogenous interfering
(i) For the point estimates of PPA substances relevant to the specimen
and NPA less than 100 percent, use the type, evaluation of cross-reactivity of
calculated estimates in the PPV and known cross-reactive alleles and
NPV calculations. pseudogenes, and assessment of cross-
(ii) Point estimates of 100 percent contamination.
may have high uncertainty. If these (D) Analytical sensitivity data: Data
variants are measured using highly must be generated demonstrating the
multiplexed technology, calculate the minimum amount of DNA that will en-
random error rate for the overall de- able the test to perform accurately in
vice and incorporate that rate in the 95 percent of runs.
estimation of the PPA and NPA as cal- (E) Device stability data: The manu-
culated previously. Then use these cal- facturer must establish upper and
culated estimates in the PPV and NPV lower limits of input nucleic acid and
calculations. This type of accuracy sample stability that will achieve the
study is helpful in determining that claimed accuracy and reproducibility.
there is no systematic error in such de- Data supporting such claims must be
vices. described.
(B) Precision (reproducibility): Preci- (F) Specimen type and matrix com-
sion data must be generated using mul- parison data: Specimen type and ma-
tiple instruments and multiple opera- trix comparison data must be gen-
tors, on multiple non-consecutive days, erated if more than one specimen type
and using multiple reagent lots. The or anticoagulant can be tested with the
sample panel must include specimens device, including failure rates for the
with claimed sample type (e.g. saliva different specimen types.
samples) representing different (iii) If the device is offered over-the-
genotypes (i.e., wild type, counter, including cases in which the
heterozygous). Performance criteria test results are provided direct-to-con-
must be predefined. A detailed study sumer, the manufacturer must conduct
protocol must be created in advance of a study that assesses user comprehen-
the study and then followed. The sion of the device’s labeling and test
‘‘failed quality control’’ rate must be process and provide a concise summary
indicated. It must be clearly docu- of the results of the study. The fol-
mented whether results were generated lowing items must be included in the
from clinical specimens, contrived user study:
samples, or cell lines. The study results (A) The test manufacturer must per-
shall state, in a tabular format, the form pre- and post-test user com-
variants tested in the study and the prehension studies to assess user abil-
number of replicates for each variant, ity to understand the possible results
and what testing conditions were stud- of a carrier test and their clinical
ied (i.e., number of runs, days, instru- meaning. The comprehension test ques-
ments, reagent lots, operators, speci- tions must directly evaluate the mate-
mens/type, etc). The study must in- rial being presented to the user in the
clude all nucleic acid extraction steps test reports.
from the claimed specimen type or ma- (B) The test manufacturer must pro-
trix, unless a separate extraction study vide a carrier testing education module
for the claimed sample type is per- to potential and actual test report re-
formed. If the device is to be used at cipients. The module must define
408
terms that are used in the test reports education module and test reports are
and explain the significance of carrier adequate for over-the-counter use.
status. (D) A summary of the user com-
(C) The user study must meet the fol- prehension study must be provided and
lowing criteria: include the following:
(1) The study participants must be (1) Results regarding reports that are
comprised of a statistically justified provided for each gene/variant/eth-
and demographically diverse popu- nicity tested.
lation (determined using methods such (2) Statistical methods used to ana-
as quota-based sampling) that is rep- lyze all data sets.
resentative of the intended user popu- (3) Completion rate, non-responder
lation. Furthermore, the users must be rate, and reasons for non-response/data
comprised of a diverse range of age and exclusion, as well as a summary table
educational levels that have no prior
of comprehension rates regarding com-
experience with the test or its manu-
prehension concepts (purpose of test,
facturer. These factors shall be well-de-
test results, test limitations, ethnicity
fined in the inclusion and exclusion
relevance for the test results, etc.) for
criteria.
each study report.
(2) All sources of bias (e.g., non-re-
sponders) must be predefined and ac- (4) Your 21 CFR 809.10 compliant la-
counted for in the study results with beling and any test report generated
regard to both responders and non-re- must include the following warning
sponders. and limitation statements, as applica-
(3) The testing must follow a format ble:
where users have limited time to com- (i) A warning that reads ‘‘The test is
plete the studies (such as an onsite sur- intended only for autosomal recessive
vey format and a one-time visit with a carrier screening in adults of reproduc-
cap on the maximum amount of time tive age.’’
that a participant has to complete the (ii) A statement accurately dis-
tests). closing the genetic coverage of the test
(4) Users must be randomly assigned in lay terms, including, as applicable,
to study arms. Test reports given to information on variants not queried by
users must: Define the condition being the test, and the proportion of incident
tested and related symptoms; explain disease that is not related to the
the intended use and limitations of the gene(s) tested. For example, where ap-
test; explain the relevant ethnicities plicable, the statement would have to
regarding the variant tested; explain include a warning that the test does
carrier status and relevance to the not or may not detect all genetic
user’s ethnicity; and provide links to variants related to the genetic disease,
additional information pertaining to and that the absence of a variant test-
situations where the user is concerned ed does not rule out the presence of
about their test results or would like other genetic variants that may be dis-
followup information as indicated in ease-related. Or, where applicable, the
test labeling. The study shall assess statement would have to include a
participants’ ability to understand the warning that the basis for the disease
following comprehension concepts: The for which the genetic carrier status is
test’s limitations, purpose, and results. being tested is unknown or believed to
(5) Study participants must be un- be non-heritable in a substantial num-
trained, naive to the test subject of the ber of people who have the disease, and
study, and be provided only the mate- that a negative test result cannot rule
rials that will be available to them out the possibility that any offspring
when the test is marketed. may be affected with the disease. The
(6) The user comprehension study statement would have to include any
must meet the predefined primary end- other warnings needed to accurately
point criteria, including a minimum of convey to consumers the degree to
a 90 percent or greater overall com- which the test is informative for car-
prehension rate (i.e. selection of the rier status.

correct answer) for each comprehen- (iii) For prescription use tests, the
sion concept to demonstrate that the following warnings that read:
409
§ 866.5950 21 CFR Ch. I (4–1–23 Edition)
(A) ‘‘The results of this test are in- (5) The testing done to comply with
tended to be interpreted by a board- paragraph (b)(3) of this section must
certified clinical molecular geneticist show the device meets or exceeds each
or equivalent and should be used in of the following performance specifica-
conjunction with other available lab- tions:
oratory and clinical information.’’ (i) The accuracy must be shown to be
(B) ‘‘This device is not intended for equal to or greater than 99 percent for
disease diagnosis, prenatal testing of both PPA and NPA. Variants that have
fetuses, risk assessment, prognosis or a point estimate for PPA or NPA of
pre-symptomatic testing, suscepti- less than 99 percent (incorrect test re-
bility testing, or newborn screening.’’ sults as compared to bidirectional se-
(iv) For over-the-counter tests, a quencing or other methods identified
statement that reads ‘‘This test is not as appropriate by FDA) must not be in-
intended to diagnose a disease, or tell corporated into test claims and re-
you anything about your risk for devel- ports.
oping a disease in the future. On its (ii) Precision (reproducibility) per-
own, this test is also not intended to formance must meet or exceed 99 per-
tell you anything about the health of cent for both positive and negative re-
your fetus, or your newborn child’s sults.
risk of developing a particular disease (iii) The user comprehension study
later on in life.’’ must obtain values of 90 percent or
(v) For over-the-counter tests, the greater user comprehension for each
following warnings that read: comprehension concept.
(A) ‘‘This test is not a substitute for (6) The distribution of this device, ex-
visits to a healthcare provider. It is cluding the collection device described
recommended that you consult with a in paragraph (b)(2) of this section, shall
healthcare provider if you have any be limited to the manufacturer, the
questions or concerns about your remanufacturer’s subsidiaries, and lab-
sults.’’ oratories regulated under the Clinical
(B) ‘‘The test does not diagnose any Laboratory Improvement Amend-
health conditions. Results should be ments.
used along with other clinical informa-
tion for any medical purposes.’’ [80 FR 65630, Oct. 27, 2015, as amended at 82
(C) ‘‘The laboratory may not be able FR 51570, Nov. 7, 2017]
to process your sample. The prob-
§ 866.5950 Genetic health risk assess-
ability that the laboratory cannot ment system.
process your saliva sample can be up to
[actual probability percentage].’’ (a) Identification. A genetic health
(D) ‘‘Your ethnicity may affect how risk assessment system is a qualitative
your genetic health results are inter- in vitro molecular diagnostic system
preted.’’ used for detecting variants in genomic
(vi) For a positive result in an over- deoxyribonucleic acid (DNA) isolated
the-counter test when the positive pre- from human specimens that will pro-
dictive value for a specific population vide information to users about their
is less than 50 percent and more than 5 genetic risk of developing a disease to
percent, a warning that reads ‘‘The inform lifestyle choices and/or con-
positive result you obtained may false- versations with a health care profes-
ly identify you as a carrier. Consider sional. This assessment system is for
genetic counseling and followup test- over-the-counter use. This device does
ing.’’ not determine the person’s overall risk
(vii) For a positive result in an over- of developing a disease.
the-counter test when the positive pre- (b) Classification. Class II (special
dictive value for a specific population controls). The genetic health risk as-
is less than 5 percent, a warning that sessment system device, when it has
reads ‘‘The positive result you obtained previously received a first-time FDA
is very likely to be incorrect due to the marketing authorization (e.g., 510(k)

rarity of this variant. Consider genetic clearance) for the genetic health risk
counseling and followup testing.’’ assessment system (a ‘‘one-time FDA
410
reviewed genetic health risk assess- agnose a disease, tell you anything
ment system’’), is exempt from the pre- about your current state of health, or
market notification procedures in part be used to make medical decisions, in-
807, subpart E, of this chapter subject cluding whether or not you should take
to the limitations in § 866.9. The device a medication or how much of a medica-
must comply with the following special tion you should take.
controls: (G) A limiting statement explaining
(1) The 21 CFR 809.10 compliant label- that the laboratory may not be able to
ing and any prepurchase page and test process a sample, and a description of
report generated, unless otherwise the next steps to be taken by the man-
specified, must include: ufacturer and/or the customer, as ap-
(i) A section addressed to users with plicable.
the following information: (ii) A section in your 21 CFR 809.10 la-
(A) The limiting statement explain- beling and any test report generated
ing that this test provides genetic risk that is for health care professionals
information based on assessment of who may receive the test results from
specific genetic variants but does not their patients with the following infor-
report on a user’s entire genetic pro- mation:
file. This test [does not/may not, as ap- (A) The limiting statement explain-
propriate] detect all genetic variants ing that this test is not intended to di-
related to a given disease, and the ab- agnose a disease, determine medical
sence of a variant tested does not rule treatment, or tell the user anything
out the presence of other genetic about their current state of health.
variants that may be related to the dis- (B) The limiting statement explain-
ease. ing that this test is intended to provide
(B) The limiting statement explain- users with their genetic information to
ing that other companies offering a ge- inform lifestyle decisions and con-
netic risk test may be detecting dif- versations with their doctor or other
ferent genetic variants for the same health care professional.
disease, so the user may get different (C) The limiting statement explain-
results using a test from a different ing that any diagnostic or treatment
company. decisions should be based on testing
(C) The limiting statement explain- and/or other information that you de-
ing that other factors such as environ- termine to be appropriate for your pa-
mental and lifestyle risk factors may tient.
affect the risk of developing a given (2) The genetic test must use a sam-
disease. ple collection device that is FDA-
(D) The limiting statement explain- cleared, -approved, or -classified as
ing that some people may feel anxious 510(k) exempt, with an indication for in
about getting genetic test health re- vitro diagnostic use in over-the-
sults. This is normal. If the potential counter DNA testing.
user feels very anxious, such user (3) The device’s labeling must include
should speak to his or her doctor or a hyperlink to the manufacturer’s pub-
other health care professional prior to lic Web site where the manufacturer
collection of a sample for testing. This shall make the information identified
test is not a substitute for visits to a in paragraph (b)(3) of this section pub-
doctor or other health care profes- licly available. The manufacturer’s
sional. Users should consult with their home page, as well as the primary part
doctor or other health care profes- of the manufacturer’s Web site that
sional if they have any questions or discusses the device, must provide a
concerns about the results of their test hyperlink to the Web page containing
or their current state of health. this information and must allow unre-
(E) Information about how to obtain stricted viewing access. If the device
access to a genetic counselor, board- can be purchased from the Web site or
certified clinical molecular geneticist, testing using the device can be ordered
or equivalent health care professional from the Web site, the same informa-
about the results of a user’s test. tion must be found on the Web page for
(F) The limiting statement explain- ordering the device or provided in a
ing that this test is not intended to di- publicly accessible hyperlink on the
411
§ 866.5950 21 CFR Ch. I (4–1–23 Edition)
Web page for ordering the device. Any the risk of a life-threatening or irre-
changes to the device that could sig- versibly debilitating disease or condi-
nificantly affect safety or effectiveness tion for which there are few or no op-
would require new data or information tions to prevent, treat, or cure the dis-
in support of such changes, which ease, a user opt-in section must be pro-
would also have to be posted on the vided. This opt-in page must be pro-
manufacturer’s Web site. The informa- vided for each disease that falls into
tion must include: this category and must provide specific
(i) An index of the material being information relevant to each test re-
provided to meet the requirements in sult. The opt-in page must include:
paragraph (b)(3) of this section and its (i) An option to accept or decline to
location. receive this specific test result;
(ii) A section that highlights sum- (ii) Specification of the risk involved
mary information that allows the user if the user is found to have the specific
to understand how the test works and genetic test result;
how to interpret the results of the test. (iii) Professional guidelines that rec-
This section must, at a minimum, be ommend when genetic testing for the
written in plain language understand- associated target condition is or is not
able to a lay user and include: recommended; and
(A) Consistent explanations of the (iv) A recommendation to speak with
risk of disease associated with all a health care professional, genetic
variants included in the test. If there counselor, or equivalent professional
are different categories of risk, the before getting the results of the test.
manufacturer must provide literature (3) Frequently asked questions (FAQ)
references that support the different page: This page must provide informa-
risk categories. If there will be mul- tion that is specific for each variant/
tiple test reports and multiple disease pair that is reported. Informa-
variants, the risk categories must be tion provided in this section must be
defined similarly among them. For ex- scientifically valid and supported by
ample, ‘‘increased risk’’ must be de- corresponding publications. The FAQ
fined similarly between different test page must explain the health condi-
reports and different variant combination/disease being tested, the purpose
tions. of the test, the information the test
(B) Clear context for the user to un- will and will not provide, the relevance
derstand the context in which the cited of race and ethnicity to the test re-
clinical performance data support the sults, information about the popu-
risk reported. This includes, but is not lation to which the variants in the test
limited to, any risks that are influ- is most applicable, the meaning of the
enced by ethnicity, age, gender, envi- result(s), other risk factors that con-
ronment, and lifestyle choices. tribute to disease, appropriate followup
(C) Materials that explain the main procedures, how the results of the test
concepts and terminology used in the may affect the user’s family, including
test that include: children, and links to resources that
(1) Definitions: Scientific terms that provide additional information.
are used in the test reports. (iii) A technical information section
(2) Prepurchase page: This page must containing the following information:
contain information that informs the (A) Gene(s) and variant(s) the test de-
user about what information the test tects using standardized nomenclature,
will provide. This includes, but is not Human Genome Organization nomen-
limited to, variant information, the clature and coordinates as well as Sin-
condition or disease associated with gle Nucleotide Polymorphism Database
the variant(s), professional guideline (dbSNP) reference SNP numbers (rs#).
recommendations for general genetic (B) Scientifically established disease-
risk testing, the limitations associated risk association of each variant de-
with the test (e.g., test does not detect tected and reported by the test. This
all variants related to the disease) and risk association information must in-
any precautionary information about clude:

the test the user should be aware of be- (1) Genotype-phenotype information
fore purchase. When the test reports for the reported variants.
412
(2) Table of expected frequency and samples may be substituted or supple-

risks of developing the disease in rel- mented with archived clinical samples.
evant ethnic populations and the gen- Archived samples shall have been col-
eral population. lected previously in accordance with
(3) A statement about the current the instructions for use, stored appro-
professional guidelines for testing priately, and randomly selected. In
these specific gene(s) and variant(s). some limited circumstances, use of
(i) If professional guidelines are contrived samples or human cell line
available, provide the recommenda- samples may also be appropriate and
tions in the professional guideline for used as an acceptable alternative. The
the gene, variant, and disease, for when contrived or human cell line samples
genetic testing should or should not be shall mimic clinical specimens as much
performed, and cautionary information as is feasible and provide an unbiased
that should be communicated when a evaluation of the device accuracy.
particular gene and variant is detected. (ii) Accuracy must be evaluated by
(ii) If professional guidelines are not comparison to bidirectional Sanger se-
available, provide a statement that the quencing or other methods identified
professional guidelines are not avail- as appropriate by FDA. Performance
able for these specific gene(s) and vari- criteria for both the comparator meth-
ant(s). od and the device must be predefined
(C) The specimen type (e.g., saliva, and appropriate to the device’s in-
capillary whole blood). tended use. Detailed study protocols
(D) Assay steps and technology used. must be provided.
(E) Specification of required ancil- (iii) Test specimens must include all
lary reagents, instrumentation, and genotypes that will be included in the
equipment. tests and reports. The number of sam-
(F) Specification of the specimen col- ples tested in the accuracy study for
lection, processing, storage, and prepa- each variant reported must be based on
ration methods. the variant frequency using either the
(G) Specification of risk mitigation minimum numbers of samples identi-
elements and description of all addi- fied in this paragraph or, when deter-
tional procedures, methods, and prac- mined appropriate and identified by
tices incorporated into the directions FDA, a minimum number of samples
for use that mitigate risks associated determined using an alternative meth-
with testing. od. When appropriate, the same sam-
(H) Information pertaining to the ples may be used in testing to dem-
probability of test failure (i.e., percent- onstrate the accuracy of testing for
age of tests that failed quality control) multiple genotypes by generating se-
based on data from clinical samples, a quence information at multiple rel-
description of scenarios in which a test evant genetic locations. At least 20
can fail (i.e., low sample volume, low unique samples representing the wild-
DNA concentration, etc.), how users type genotype must be tested. To test
will be notified of a test failure, and samples that are heterozygous for the
the nature of followup actions on a reported variant(s), common variants
failed test to be taken by the user and (>0.1 percent variant frequency in the
the manufacturer. relevant population) must be tested
(I) Specification of the criteria for with at least 20 unique samples. Rare
test result interpretation and report- variants (≤0.1 percent variant fre-
ing. quency in the relevant population)
(J) Information that demonstrates must be tested with at least three
the performance characteristics of the unique samples. To test samples that
test, including: are homozygous for the reported vari-
(1) Accuracy of study results for each ant(s), variants with ≥2 percent variant
claimed specimen type. frequency in a relevant population
(i) Accuracy of the test shall be eval- must be tested with at least 20 unique
uated with fresh clinical specimens col- samples. Variants with a frequency in
lected and processed in a manner con- the relevant population <2 percent and
sistent with the test’s instructions for ≥0.5 percent must be tested with at
use. If this is impractical, fresh clinical least 10 unique samples. Variants with
413
§ 866.5950 21 CFR Ch. I (4–1–23 Edition)
a frequency in the relevant population bidirectional Sanger sequencing or

<0.5 percent must be tested with at other methods identified as appro-
least three unique samples. If variants priate by FDA. This information must
with a frequency of <0.5 percent are not either be reported in tabular format
found within the relevant population and arranged by clinically relevant
and homozygous samples are not test- variants or reported using another
ed, then the test results for this method identified as appropriate by
homozygous rare variant must not be FDA. As an example, for samples with
reported to the user. different genotypes DD, Dd, and dd, the
(iv) Information about the accuracy following table represents data from
study shall include the number and the accuracy study presented in tab-
type of samples that were compared to ular format:
(v) The accuracy represents the de- calls’ or ‘invalid calls.’ Calculate the
grees of agreement between the device rate of ‘no calls’ and ‘invalid calls’ for
results and the comparator results. each comparator output as %Inv(DD) =
The accuracy must be evaluated by A4/NDD, %Inv(Dd) = B4/NDd, %Inv(dd) =
measuring different percent agree- C4/Ndd. If ‘no calls’ or ‘invalid calls’ are
ments (PA) of device results with the required to be retested according to the
comparator results and percent of ‘no device instructions for use, the percent
414
ER07NO17.001</GPH>
of final ‘no calls’ or ‘invalid calls’ must C4)/(NDD + NDd + Ndd) and provide a 95
be provided. In the table presenting the percent two-sided confidence interval.
results of the accuracy study, use only The percent of final ‘no calls’ or ‘in-
the final results (i.e., after retesting valid calls’ must be clinically accept-
the initial ‘no calls’ or ‘invalid calls’, if able.
required according to the instructions (vi) Point estimates of percent agree-
for use). Samples that resulted in a ‘no ment for each genotype must be cal-
call’ or ‘invalid call’ after retesting culated as the number of correct calls
must not be included in the final cal- for that genotype divided by the num-
culations of agreement. If the percent- ber of samples known to contain that
ages of ‘no calls’ or ‘invalid calls’ for genotype excluding ‘no calls’ or ‘in-
each comparator output are similar, valid calls’. The calculations must be
combine these estimates as (A4 + B4 + performed as follows:
(vii) For percent agreements for DD, (viii) Information must be reported
Dd and dd (PA(DD|DD), PA(Dd|Dd) and on the Technical Positive Predictive
PA(dd|dd)) as described in paragraph Value (TPPV) related to the analytical
(b)(3)(iii)(J)(1)(vi) of this section, the 95 (technical) performance of the device
percent two-sided confidence intervals for genotypes in each relevant sub-
must be provided. The accuracy point population (e.g., ethnicity, gender, age,
estimates for percent agreements for geographical location, etc.). TPPV is
DD, Dd and dd must be ≥99 percent per the percentage of individuals with the
reported variant and overall. Any genotype truly present among individ-
variants that have a point estimate for uals whose test reports indicate that
either PA(DD|DD), PA(Dd|Dd), or this genotype is present. The TPPV de-
pends on the accuracy measures of per-
PA(dd|dd) of <99 percent compared to
cent agreements and on the frequency
bidirectional sequencing or other
of the genotypes in the subpopulation
methods identified as appropriate by being studied. The f(DD) is the fre-
FDA must not be incorporated into quency of DD and f(Dd) is the fre-
test claims and reports. Accuracy re- quency of Dd in the subpopulation
sults generated from clinical specimens being studied; TPPV must be cal-
versus contrived samples or cell lines culated as described in paragraphs
must be presented separately. Results (b)(3)(iii)(J)(1)(ix) through (xi) of this
must be summarized and presented in section.
tabular format by sample type and by (ix) For variants where the point esti-
genotype or must be reported using an- mates of PA(DD|DD), PA(Dd|Dd) and
other method identified as appropriate PA(dd|dd) are less than 100 percent, use
by FDA (see paragraph these point estimates in TPPV calcula-
(b)(3)(iii)(J)(1)(iv) of this section). tions.
415
ER07NO17.002</GPH>
§ 866.5950 21 CFR Ch. I (4–1–23 Edition)
(x) Point estimates of 100 percent in is no systematic error in such devices.

the accuracy study may have high un- In those cases, incorporate that rate in
certainty about performance of the the estimation of the percent agree-
test in the population. If these variants ments as calculated in paragraph
are measured using highly multiplexed (b)(3)(iii)(J)(1)(vi) of this section and in-
technology, calculate the random error clude it in TPPV calculations.
rate for the overall device. The accu- (xi) The TPPV for subpopulations
racy study described in paragraph with genotype frequencies of f(dd),
(b)(3)(iii)(J) of this section in those f(Dd) and f(DD) = 1¥f(dd)¥f(Dd) in the
cases is more to determine that there subpopulation is calculated as:
(2) Precision and reproducibility data lines. The study results shall report
must be provided using multiple in- the variants tested in the study and
struments and multiple operators, on the number of replicates for each vari-
multiple non-consecutive days, and ant, and what conditions were tested
using multiple reagent lots. The sam- (i.e., number of runs, days, instru-
ple panel must either include speci- ments, reagent lots, operators, speci-
mens from the claimed sample type mens/type, etc.). Results must be eval-
(e.g., saliva) representing all genotypes uated and presented in tabular format
for each variant (e.g., wild type, and stratified by study parameter (e.g.,
heterozygous, and homozygous) or, if by site, instrument(s), reagent lot, op-
an alternative panel composition of erator, and sample variant). The study
specimens is identified by FDA as ap- must include all extraction steps from
propriate, a panel composed of those the claimed specimen type or matrix,
specimens FDA identified as appro- unless a separate extraction reproduc-
priate. A detailed study protocol must ibility study for the claimed sample
be created in advance of the study and type is performed. If the device is to be
must include predetermined accept- used at more than one laboratory, dif-
ance criteria for performance results. ferent laboratories must be included in
The percentage of samples that failed the reproducibility study and reproduc-
quality control must be indicated (i.e., ibility across sites must be evaluated.
the total number of sample replicates Any no calls or invalid calls in the
for which a sequence variant cannot be study must be listed as a part of the
called (no calls) or that fail sequencing precision and reproducibility study re-
quality control criteria divided by the sults.
total number of replicates tested). It (3) Analytical specificity data: Data
must be clearly documented whether must be provided that evaluates the ef-
results were generated from clinical fect of potential endogenous and exoge-
specimens, contrived samples, or cell nous interferents on test performance,
416
ER07NO17.003</GPH>
including specimen extraction and var- performance section to support clinical

iant detection. Interferents tested performance for the risk category (e.g.,
must include those reasonably likely not at risk, increased risk). For each
to be potentially relevant to the sam- variant combination, a summary of
ple type used for the device. key results must be provided in tabular
(4) Interfering variant data: Nucleotide format or using another method identi-
mutations that can interfere with the fied as appropriate by FDA to include
technology must be cited and evalu- the appropriate information regarding
ated. Data must be provided to dem- variant type, data source, definition of
onstrate the effect of the interfering the target condition (e.g., disease),
variant(s) on the performance of the clinical criteria for determining wheth-
correct calls. Alternatively, for each er the target disease is present or ab-
suspected interfering mutation for sent, description of subjects with the
which data is not provided dem- target disease present and target dis-
onstrating the effect of the interfering ease absent (exclusion or inclusion cri-
variant, the manufacturer must iden- teria), and technical method for
tify the suspected interfering variants genotyping. When available, informa-
in the labeling and indicate that the tion on the effect of the variant on risk
impact that the interfering variants must be provided as the risk of a dis-
may have on the assay’s performance ease (lifetime risk or lifetime
has not been studied by providing a incidences) for an individual compared
statement that reads ‘‘It is possible with the general population risk.
that the presence of [insert clearly
(i) If odds ratios are available, using
identifying information for the sus-
information about the genotype dis-
pected interfering variant] in a sample
tribution either among individuals
may interfere with the performance of
this test. However, its effect on the with the target disease absent, or in
performance of this test has not been the general population, or information
studied.’’ about the risk variant frequency and
(5) Analytical sensitivity data: Data odds ratios, the likelihood ratios for
must be provided demonstrating the the corresponding device results along
minimum amount of DNA that will en- with 95 percent confidence intervals
able the test to perform correctly in 95 must be calculated. Using information
percent of runs. about pretest risk (π), an estimate of
(6) Reagent stability: The manufac- likelihood ratio (LR), and a relation-
turer must evaluate reagent stability ship between post-test risk R as R/
using wild-type, heterozygous, and (1¥R) = LR·π/(1¥π), the post-test risk
homozygous samples. Reagent stability R must be calculated.
data must demonstrate that the re- (ii) When available, likelihood ratios
agents maintain the claimed accuracy (LR) for different test results must be
and reproducibility. Data supporting presented in a tabular format along
such claims must be provided. with references to the source data or
(7) Specimen type and matrix compari- using another method identified as ap-
son data: Specimen type and matrix propriate by FDA as stated in para-
comparison data must be generated if graph (b)(3)(iii)(K)(2) of this section.
more than one specimen type can be When these values are not directly
tested with this device, including fail- available in published literature, like-
ure rates for the different specimens. lihood ratios can be separately cal-
(K) Clinical performance summary. culated along with the 95 percent con-
(1) Information to support the clin- fidence interval with references to the
ical performance of each variant re- source data. Note that a minimum re-
ported by the test must be provided. quirement for the presence of the
(2) Manufacturers must organize invariant’s effect on the risk is that a
formation by the specific variant com- corresponding LR is statistically high-
bination as appropriate (e.g., wild type, er than 1 (a lower bound of 95 percent
heterozygous, homozygous, compound two-sided confidence interval is larger
heterozygous, hemizygous genotypes). than 1). It means that the post-test

For each variant combination, infor- risk is statistically higher than the
mation must be provided in the clinical pretest risk (an observed value of the
417
§ 866.5950 21 CFR Ch. I (4–1–23 Edition)
difference between the post-test and is most applicable, the meaning of the
pretest risks). result(s), other risks factors that con-
(L) Materials that explain the main tribute to disease, appropriate followup
concepts and terminology used in the procedures, how the results of the test
test that includes, but is not limited may affect the user’s family, including
to: children, and links to resources that
(1) Definitions: Scientific terms that provide additional information.
are used in the test reports. (M) User comprehension study: Infor-
(2) Prepurchase page: This page must mation on a study that assesses com-
contain information that informs the prehension of the test process and re-
user about what the test will provide.
sults by potential users of the test
This includes, but is not limited to,
must be provided.
variant information, the condition or
disease associated with the variant(s), (1) The test manufacturer must pro-
professional guideline recommenda- vide a genetic risk education module to
tions for general genetic risk testing, naı̈ve user comprehension study par-
the limitations associated with the ticipants prior to their participation in
test (e.g., test does not detect all the user comprehension study. The
variants related to the disease) and any module must define terms that are
precautionary information about the used in the test reports and explain the
test the user should be aware of before significance of genetic risk reports.
purchase. When the test reports the (2) The test manufacturer must per-
risk of a life-threatening or irrevers- form pre- and post-test user com-
ibly debilitating disease or condition prehension studies. The comprehension
for which there are few or no options to test questions must include directly
prevent, treat, or cure the disease, a evaluating a representative sample of
user opt-in section must be provided. the material being presented to the
This opt-in page must be provided for user as described in paragraph (b)(3)(ii)
each disease that falls into this cat- of this section.
egory and must provide specific infor- (3) The manufacturer must provide a
mation relevant to each test result.
justification from a physician and/or
The opt-in page must include:
genetic counselor that identifies the
(i) An option to accept or decline to
receive this specific test result; appropriate general and variant-spe-
(ii) Specification of the risk involved cific concepts contained within the ma-
if the user is found to have the specific terial being tested in the user com-
genetic test result; prehension study to ensure that all rel-
(iii) Professional guidelines that rec- evant concepts are incorporated in the
ommend when genetic testing for the study.
associated target condition is or is not (4) The user study must meet the fol-
recommended; and lowing criteria:
(iv) A recommendation to speak with (i) The study participants must com-
a health care professional, genetic prise a statistically sufficient sample
counselor, or equivalent professional size and demographically diverse popu-
before getting the results of the test. lation (determined using methods such
(3) Frequently asked questions (FAQ) as quota-based sampling) that is rep-
page: This page must provide informa- resentative of the intended user popu-
tion that is specific for each variant/ lation. Furthermore, the study partici-
disease pair that is reported. Informa- pants must comprise a diverse range of
tion provided in this section must be age and educational levels and have no
scientifically valid and supported by prior experience with the test or its
corresponding publications. The FAQ manufacturer. These factors shall be
page must explain the health condi-
well defined in the inclusion and exclu-
tion/disease being tested, the purpose
sion criteria.
of the test, the information the test
will and will not provide, the relevance (ii) All sources of bias must be
predefined and accounted for in the
of race and ethnicity on the test re-

sults, information about the popu- study results with regard to both re-
lation to which the variants in the test sponders and non-responders.
418
(iii) The testing must follow a format (ii) Determining predisposition for
where users have limited time to com- cancer where the result of the test may
plete the studies (such as an onsite sur- lead to prophylactic screening, con-
vey format and a one-time visit with a firmatory procedures, or treatments
cap on the maximum amount of time that may incur morbidity or mortality
that a participant has to complete the to the patient;
tests). (iii) Assessing the presence of genetic
(iv) Users must be randomly assigned variants that impact the metabolism,
to study arms. Test reports in the user exposure, response, risk of adverse
comprehension study given to users events, dosing, or mechanisms of pre-
must define the target condition being scription or over-the-counter medica-
tested and related symptoms, explain tions; or
the intended use and limitations of the (iv) Assessing the presence of deter-
test, explain the relevant ethnicities in ministic autosomal dominant variants.
regard to the variant tested, explain [82 FR 51561, Nov. 7, 2017, as amended at 83
genetic health risks and relevance to FR 25914, June 5, 2018]
the user’s ethnicity, and assess partici-
pants’ ability to understand the fol- § 866.5960 Human leukocyte antigen
lowing comprehension concepts: The typing companion diagnostic test.
test’s limitations, purpose, appropriate (a) Identification. A human leukocyte
action, test results, and other factors antigen (HLA) typing companion diag-
that may have an impact on the test nostic (CDx) test is a prescription
results. genotyping or phenotyping in vitro di-
(v) Study participants must be un- agnostic product intended for use as an
trained, be naı̈ve to the test subject of aid in identifying patients who have
the study, and be provided the labeling specific HLA allele(s) or express spe-
prior to the start of the user com- cific HLA antigen(s) and may benefit
prehension study. from treatment with a corresponding
(vi) The user comprehension study therapeutic product or are likely to be
must meet the predefined primary end- at increased risk for serious adverse re-
point criteria, including a minimum of actions as a result of treatment with a
a 90 percent or greater overall com- corresponding therapeutic product.
prehension rate (i.e., selection of the (b) Classification. Class II (special
correct answer) for each comprehen- controls). The special controls for this
sion concept. Other acceptance criteria device are:
may be acceptable depending on the (1) The intended use of the device
concept being tested. Meeting or ex- must specify the target HLA allele(s)
ceeding this overall comprehension or antigen(s), the patient population(s),
rate demonstrates that the materials and the corresponding therapeutic
presented to the user are adequate for product(s).
over-the-counter use. (2) Design verification and validation
(vii) The analysis of the user com- must include:
prehension results must include results (i) Detailed documentation of an ana-
regarding reports that are provided for lytical accuracy study that uses well-
each gene/variant/ethnicity tested, sta- characterized samples including clin-
tistical methods used to analyze all ical samples from intended use popu-
data sets, and completion rate, non-relation(s) focusing on the target
sponder rate, and reasons for non- allele(s) needed for patient selection;
response/data exclusion. A summary (ii) Detailed documentation of preci-
table of comprehension rates regarding sion studies (repeatability, reproduc-
comprehension concepts (e.g., purpose ibility) that evaluate possible sources
of test, test results, test limitations, of variation that may affect test re-
ethnicity relevance for the test results, sults;
etc.) for each study report must be in- (iii) Detailed documentation of a
cluded. study determining range of input sam-
(4) The intended use of the device ple concentrations that meet perform-
must not include the following indica- ance specifications;

tions for use: (iv) Detailed description of the ambi-
(i) Prenatal testing; guity resolution method, if applicable;
419
§ 866.6010 21 CFR Ch. I (4–1–23 Edition)
(v) For a sequencing-based assay, Subpart G—Tumor Associated

documentation of coverage and Antigen immunological Test
predefined coverage threshold of target Systems
genomic regions, pertinent variant
types, and sequence contexts; § 866.6010 Tumor-associated antigen
(vi) For multiplex assays, docu- immunological test system.
mentation of a risk assessment and de- (a) Identification. A tumor-associated
sign specifications that are in place to antigen immunological test system is a
prevent incorrect reactivity assign- device that consists of reagents used to
ment; qualitatively or quantitatively meas-
(vii) Description of a plan on how to ure, by immunochemical techniques,
ensure the performance of the device tumor-associated antigens in serum,
does not change when new HLA alleles plasma, urine, or other body fluids.
are identified, and/or when reactivity This device is intended as an aid in
assignments are changed; and monitoring patients for disease
(viii) Detailed description of device progress or response to therapy or for
software including standalone soft- the detection of recurrent or residual
ware, or software and bioinformatics disease.
analysis pipeline, if applicable, incor- (b) Classification. Class II (special
porated in the instruments, and docu- controls). Tumor markers must comply
mentation of software including the with the following special controls: (1)
level of concern and associated risks, A guidance document entitled ‘‘Guid-
software requirement specifications, ance Document for the Submission of
software design specifications (e.g., al- Tumor Associated Antigen Premarket
gorithms, alarms and device limita- Notifications (510(k)s) to FDA,’’ and (2)
tions), hazard analysis, traceability voluntary assay performance standards
matrix, verification and validation issued by the National Committee on
testing, unresolved anomalies, hard- Clinical Laboratory Standards.
ware requirements, and effective cyber- [62 FR 66005, Dec. 17, 1997]
security management.
(3) Clinical validity data (which may § 866.6020 Immunomagnetic circu-
include summary reports from clinical lating cancer cell selection and enu-
trials, comparison studies using clin- meration system.
ical samples, or through an alternative (a) Identification. An
approach determined to be appropriate immunomagnetic circulating cancer
by FDA), demonstrating the following, cell selection and enumeration system
as applicable: is a device that consists of biological
(i) Which patients identified by the probes, fluorochromes, and other re-
HLA CDx test are most likely to ben- agents; preservation and preparation
efit from the corresponding thera- devices; and a semiautomated analyt-
peutic product; and ical instrument to select and count cir-
(ii) Which patients identified by the culating cancer cells in a prepared
HLA CDx test are likely to be at in- sample of whole blood. This device is
creased risk for serious adverse reac- intended for adjunctive use in moni-
tions as a result of treatment with the toring or predicting cancer disease pro-
corresponding therapeutic product. gression, response to therapy, and for
(4) If the HLA test used in the clin- the detection of recurrent disease.
ical trials is different from the HLA (b) Classification. Class II (special
CDx test in the premarket notification controls). The special control for this
submission, the submission must in- device is FDA’s guidance document en-
clude results of a bridging study, or an titled ‘‘Class II Special Controls Guid-
alternative approach determined to be ance Document: Immunomagnetic Cir-
appropriate by FDA. culating Cancer Cell Selection and
Enumeration System.’’ See § 866.1(e) for
[87 FR 79252, Dec. 27, 2022] availability of this guidance document.

[69 FR 26038, May 11, 2004]
420
§ 866.6030 AFP-L3% immunological test Special Controls Guidance Document:

system. Gene Expression Profiling Test System
(a) Identification. An AFP-L3% for Breast Cancer Prognosis.’’ See
immunological test system is an in § 866.1(e) for the availability of this
vitro device that consists of reagents guidance document.
and an automated instrument used to [72 FR 26291, May 9, 2007]
quantitatively measure, by
immunochemical techniques, AFP and § 866.6050 Ovarian adnexal mass as-
AFP-L3 subfraction in human serum. sessment score test system.
The device is intended for in vitro diag-
nostic use as an aid in the risk assess- (a) Identification. An ovarian/adnexal
ment of patients with chronic liver dis- mass assessment test system is a de-
ease for development of hepatocellular vice that measures one or more pro-
carcinoma, in conjunction with other teins in serum or plasma. It yields a
laboratory findings, imaging studies, single result for the likelihood that an
and clinical assessment. adnexal pelvic mass in a woman, for
(b) Classification. Class II (special whom surgery is planned, is malignant.
controls). The special control is FDA’s The test is for adjunctive use, in the
guidance document entitled ‘‘Class II context of a negative primary clinical
Special Controls Guidance Document: and radiological evaluation, to aug-
AFP-L3% Immunological Test Sys- ment the identification of patients
tems.’’ See § 866.1(e) for the availability whose gynecologic surgery requires on-
of this guidance document. cology expertise and resources.
[70 FR 57749, Oct. 4, 2005]
controls). The special control for this
§ 866.6040 Gene expression profiling device is FDA’s guidance document en-
test system for breast cancer prog- titled ‘‘Class II Special Controls Guid-
nosis. ance Document: Ovarian Adnexal Mass
(a) Identification. A gene expression Assessment Score Test System.’’ For
profiling test system for breast cancer the availability of this guidance docu-
prognosis is a device that measures the ment, see § 866.1(e).
ribonucleic acid (RNA) expression level (c) Black box warning. Under section
of multiple genes and combines this in- 520(e) of the Federal Food, Drug, and
formation to yield a signature (pattern Cosmetic Act these devices are subject
or classifier or index) to aid in prog- to the following restriction: A warning
nosis of previously diagnosed breast statement must be placed in a black
cancer. box and must appear in all advertising,
(b) Classification. Class II (special labeling, and promotional material for
controls). The special control is FDA’s these devices. That warning statement
guidance document entitled ‘‘Class II must read:
421
ER30DE11.007</GPH>
§ 866.6060 21 CFR Ch. I (4–1–23 Edition)
[76 FR 16294, Mar. 23, 2011, as amended at 76 vice of this generic type, device per-
FR 82131, Dec. 30, 2011] formance data from either a method
comparison study to the predicate de-
§ 866.6060 BCR-ABL quantitation test.
vice or through a clinical study dem-
(a) Identification. A BCR–ABL quan- onstrating clinical validity using well-
titation test is identified as a reverse characterized prospectively or retro-
transcription-quantitative polymerase spectively obtained clinical specimens,
chain reaction (RT-qPCR) test for the as appropriate, representative of the
quantitation of BCR–ABL1 expressed intended use population;
on the International Scale (IS) and (B) For indications for use based on a
control transcripts in total RNA from threshold not established in a predicate
whole blood of diagnosed t(9;22) posi- device of this generic type, device per-
tive chronic myeloid leukemia (CML) formance data from a clinical study
patients during monitoring of treat- demonstrating clinical validity using
ment with tyrosine kinase inhibitors. well-characterized prospectively or ret-
This test is not intended for the diag- rospectively obtained clinical speci-
nosis of CML. mens, as appropriate, representative of
(b) Classification. Class II (special the intended use population;
controls). The special controls for this (C) Device reproducibility data gen-
device are:
erated, using a minimum of three sites,
of which at least two sites must be ex-
sions must include the following infor-
ternal sites, with two operators at each
mation:
site. Each site must conduct a min-
(i) The indication for use must indi-
imum of three runs per operator over
cate the variant(s) for which the assay
non-consecutive days evaluating a min-
was designed and validated, for exam-
imum of five different BCR–ABL con-
ple BCR–ABL e13a2 and/or e14a2.
centrations that span and are well dis-
(ii) A detailed description of all com-
tributed over the measuring range and
ponents in the test, including the fol-
include MR3 (0.1 percent IS). Results
lowing:
shall be reported as the standard devi-
(A) A detailed description of the test
ation and percentage coefficient of var-
components, all required reagents, in-
iation for each level tested.
strumentation and equipment, includ-
Prespecified acceptance criteria must
ing illustrations or photographs of non-
be provided and followed;
standard equipment or methods;
(B) Detailed documentation of the (D) Device precision data using clin-
device software including, but not lim- ical samples to evaluate the within-lot,
ited to, standalone software applica- between-lot, within-run, between run,
tions and hardware-based devices that and total variation;
incorporate software; (E) Device linearity data using a di-
(C) Methodology and protocols for lution panel created from clinical sam-
control procedures for the assay to ples;
allow reporting on the International (F) Device analytic sensitivity data,
Scale; including limit of blank, limit of detec-
(D) A description of the result out- tion, and limit of quantification;
puts, analytical sensitivity of the (G) Device specificity data, including
assay, and the range of values that will interference and cross-contamination;
be reported; and and
(E) A description of appropriate in- (H) Device stability data, including
ternal and external controls that are real-time stability of samples under
recommended or provided. The descrip- various storage times, temperatures,
tion must identify those control ele- and freeze-thaw conditions.
ments that are incorporated into the (iv) Identification of risk mitigation
testing procedure. elements used by your device, includ-
(iii) Information that demonstrates ing a detailed description of all addi-
the performance characteristics of the tional procedures, methods, and prac-
test, including: tices incorporated into the instructions

(A) For indications for use based on a for use that mitigate risks associated
threshold established in a predicate de- with testing using your device.
422
(2) Your 21 CFR 809.10 compliant la- (B) The intended specimen type(s)
beling must include the following: and matrix (e.g., formalin-fixed, par-
(i) The intended use in your 21 CFR affin-embedded tumor tissue).
809.10(a)(2) and (b)(2) complaint label- (C) The mutation types (e.g., single
ing must include an indication for use nucleotide variant, insertion, deletion,
statement that reads ‘‘This test is not copy number variation or gene rear-
intended for the diagnosis of CML’’; rangement) for which validation data
and has been provided.
(ii) A detailed description of the per- (D) The name of the testing facility
formance studies conducted to comply or facilities, as applicable.
with paragraph (b)(1)(iii) of this section (iii) A detailed device description in-
and a summary of the results. cluding the following:
(3) Your device output must include (A) A description of the test in terms
results on the International Scale (IS) of genomic coverage, as follows:
and your assay must include (1) Tabulated summary of all
multipoint calibration controls trace- mutations reported, grouped according
able to a relevant international ref- to gene and target region within each
erence panel (e.g., the World Health Or- gene, along with the specific cDNA and
ganization International Genetic Ref- amino acid positions for each muta-
erence Panel for quantitation of BCR– tion.
ABL mRNA). (2) A description of any within-gene
[82 FR 50532, Nov. 1, 2017] targeted regions that cannot be re-
ported and the data behind such con-
§ 866.6080 Next generation sequencing clusion.
based tumor profiling test. (B) Specifications for specimen re-
(a) Identification. A next generation quirements including any specimen
sequencing (NGS) based tumor collection devices and preservatives,
profiling test is a qualitative in vitro specimen volume, minimum tumor
diagnostic test intended for NGS anal- content, specimen handling, DNA ex-
ysis of tissue specimens from malig- traction, and criteria for DNA quality
nant solid neoplasms to detect somatic and quantity metrics that are pre-
mutations in a broad panel of targeted requisite to performing the assay.
genes to aid in the management of pre- (C) A detailed description of all test
viously diagnosed cancer patients by components, reagents, instrumenta-
qualified health care professionals. tion, and software required. Detailed
(b) Classification. Class II (special documentation of the device software
controls). The special controls for this including but not limited to, software
device are: applications and hardware-based de-
(1) Premarket notification submis- vices that incorporate software.
sions must include the following infor- (D) A detailed description of the
mation: methodology and protocols for each
(i) A detailed description of all so- step of the test, including description
matic mutations that are intended to of the quality metrics, thresholds, and
be detected by the test and that are filters at each step of the test that are
adequately supported in accordance implemented for final result reporting
with paragraph (b)(1)(v) of this section and a description of the metrics for
and reported in the test results in ac- run-failures, specimen-failures, inva-
cordance with paragraph (b)(2)(iv) of lids, as applicable.
this section, including: (E) A list of links provided by the de-
(A) A listing of mutations that are vice to the user or accessed by the de-
cancer mutations with evidence of clin- vice for internal or external informa-
ical significance. tion (e.g., decision rules or databases)
(B) As appropriate, a listing of supporting clinical significance of test
mutations that are cancer mutations results for the panel or its elements in
with potential clinical significance. accordance with paragraphs (b)(1)(v)
(ii) The indications for use must and (b)(2)(vi) of this section.
specify the following: (F) A description of internal and ex-

(A) The test is indicated for pre- ternal controls that are recommended
viously diagnosed cancer patients. or provided and control procedures.
423
§ 866.6080 21 CFR Ch. I (4–1–23 Edition)
The description must identify those clinical significance and that are based
control elements that are incorporated on evidence established in the intended
into the testing procedure. specimen type (e.g., tumor tissues) but
(iv) Information demonstrating ana- for a different analyte type (e.g., pro-
lytical validity of the device according tein, RNA) and/or a measurement (e.g.,
to analytical performance characteris- incorporating a score or copy number)
tics, evaluated either specifically for and/or with an alternative technology
each gene/mutation or, when clinically (e.g., IHC, RT-qPCR, FISH), evidence of
and practically justified, using a rep- accuracy must include clinically ade-
resentative approach based on other quate concordance between results for
mutations of the same type, including: the mutation and the medically estab-
(A) Data that adequately supports lished biomarker test (e.g., evidence
the intended specimen type (e.g., for- generated from an appropriately sized
malin-fixed, paraffin-embedded tumor method comparison study using clin-
tissue), specimen handling protocol, ical specimens from the target popu-
and nucleic acid purification for spe- lation).
cific tumor types or for a pan-tumor (3) For qualitative DNA mutations
claim. not described in paragraph
(B) A summary of the empirical evi- (b)(1)(iv)(G)(2) of this section, accuracy
dence obtained to demonstrate how the studies must include both mutation-
analytical quality metrics and thresh- positive and wild-type results.
olds were optimized. (H) Adequate device stability infor-
(C) Device precision data using clin- mation.
ical samples to adequately evaluate (v) Information that adequately sup-
intra-run, inter-run, and total varia- ports the clinical significance of the
bility. The samples must cover all mu- panel must include:
tation types tested (both positive and (A) Criteria established on what
negative samples) and include samples types and levels of evidence will clini-
near the limit of detection of the de- cally validate a mutation as a cancer
vice. Precision must be assessed by mutation with evidence of clinical sig-
agreement within replicates on the nificance versus a cancer mutation
assay final result for each representa- with potential clinical significance.
tive mutation, as applicable, and also (B) For representative mutations of
supported by sequencing quality those designated as cancer mutations
metrics for targeted regions across the with evidence of clinical significance, a
panel. description of the clinical evidence as-
(D) Description of the protocols and/ sociated with such mutations, such as
or data adequately demonstrating the clinical evidence presented in profes-
interchangeability of reagent lots and sional guidelines, as appropriate, with
multiplexing barcodes. method comparison performance data
(E) A description of the nucleic acid as described in paragraph (b)(1)(iv)(G)
assay input concentration range and of this section.
the evidence to adequately support the (C) For all other mutations des-
range. ignated as cancer mutations with po-
(F) A description of the data ade- tential clinical significance, a descrip-
quately supporting the limit of detection of the rationale for reporting.
tion of the device. (2) The 21 CFR 809.10 compliant label-
(G) A description of the data to ade- ing and any product information and
quately support device accuracy using test report generated, must include the
clinical specimens representing the in- following, as applicable:
tended specimen type and range of (i) The intended use statement must
tumor types, as applicable. specify the following:
(1) Clinical specimens tested to sup- (A) The test is indicated for pre-
port device accuracy must adequately viously diagnosed cancer patients.
represent the list of cancer mutations (B) The intended specimen type(s)
with evidence of clinical significance and matrix (e.g., formalin-fixed, par-
to be detected by the device. affin-embedded tumor tissue).

(2) For mutations that are designated (C) The mutation types (e.g., single
as cancer mutations with evidence of nucleotide variant, insertion, deletion,
424
copy number variation or gene rear- PART 868—ANESTHESIOLOGY

rangement) for which validation data DEVICES
has been provided.
(D) The name of the testing facility Subpart A—General Provisions
or facilities, as applicable.
Sec.
(ii) A description of the device and 868.1 Scope.
summary of the results of the perform- 868.3 Effective dates of requirement for pre-
ance studies performed in accordance market approval.
with paragraphs (b)(1)(iii), (b)(1)(iv), 868.9 Limitations of exemptions from sec-
and (b)(1)(v) of this section. tion 510(k) of the Federal Food, Drug,
and Cosmetic Act (the act).
(iii) A description of applicable test
limitations, including, for device spe- Subpart B—Diagnostic Devices
cific mutations validated with method
comparison data to a medically estab- 868.1030 Manual algesimeter.
868.1040 Powered algesimeter.
lished test in the same intended speci- 868.1075 Argon gas analyzer.
men type, appropriate description of 868.1100 Arterial blood sampling kit.
the level of evidence and/or the dif- 868.1120 Indwelling blood oxyhemoglobin
ferences between next generation se- concentration analyzer.
quencing results and results from the 868.1150 Indwelling blood carbon dioxide
partial pressure (PCO2) analyzer.
medically established test (e.g., as de- 868.1170 Indwelling blood hydrogen ion con-
scribed in professional guidelines). centration (pH) analyzer.
(iv) A listing of all somatic 868.1200 Indwelling blood oxygen partial
mutations that are intended to be de- pressure (PO2) analyzer.
tected by the device and that are re- 868.1400 Carbon dioxide gas analyzer.
868.1430 Carbon monoxide gas analyzer.
ported in the test results under the fol- 868.1500 Enflurane gas analyzer.
lowing two categories or equivalent 868.1505 Ventilatory electrical impedance
designations, as appropriate: ‘‘cancer tomograph.
mutations panel with evidence of clin- 868.1575 Gas collection vessel.
ical significance’’ or ‘‘cancer 868.1620 Halothane gas analyzer.
868.1640 Helium gas analyzer.
mutations panel with potential clinical
868.1670 Neon gas analyzer.
significance.’’ 868.1690 Nitrogen gas analyzer.
(v) For mutations reported under the 868.1700 Nitrous oxide gas analyzer.
category of ‘‘cancer mutations panel 868.1720 Oxygen gas analyzer.
with potential clinical significance,’’ a 868.1730 Oxygen uptake computer.
868.1750 Pressure plethysmograph.
limiting statement that states ‘‘For
868.1760 Volume plethysmograph.
the mutations listed in [cancer 868.1780 Inspiratory airway pressure meter.
mutations panel with potential clinical 868.1800 Rhinoanemometer.
significance or equivalent designation], 868.1840 Diagnostic spirometer.
the clinical significance has not been 868.1850 Monitoring spirometer.
demonstrated [with adequate clinical 868.1860 Peak-flow meter for spirometry.
868.1870 Gas volume calibrator.
evidence (e.g., by professional guide- 868.1880 Pulmonary-function data calcu-
lines) in accordance with paragraph lator.
(b)(1)(v) of this section] or with this 868.1890 Predictive pulmonary-function
test.’’ value calculator.
(vi) For mutations under the cat- 868.1900 Diagnostic pulmonary-function in-
terpretation calculator.
egory of ‘‘cancer mutations panel with
868.1910 Esophageal stethoscope.
evidence of clinical significance,’’ or 868.1920 Esophageal stethoscope with elec-
equivalent designation, link(s) for phy- trical conductors.
sicians to access internal or external 868.1930 Stethoscope head.
information concerning decision rules 868.1965 Switching valve (ploss).
or conclusions about the level of evi- 868.1975 Water vapor analyzer.
dence for clinical significance that is Subpart C—Monitoring Devices
associated with the marker in accord-
ance with paragraph (b)(1)(v) of this 868.2025 Ultrasonic air embolism monitor.
section. 868.2300 Bourdon gauge flowmeter.

868.2320 Uncompensated thorpe tube flow-
[83 FR 28995, June 22, 2018] meter.
425
868.2340 Compensated thorpe tube flow- 868.5450 Respiratory gas humidifier.
meter. 868.5454 High flow humidified oxygen deliv-
868.2350 Gas calibration flowmeter. ery device.
868.2375 Breathing frequency monitor. 868.5460 Therapeutic humidifier for home
868.2377 Apnea monitor. use.
868.2380 Nitric oxide analyzer. 868.5470 Hyperbaric chamber.
868.2385 Nitrogen dioxide analyzer. 868.5480 Isocapnic ventilation device.
868.2450 Lung water monitor. 868.5530 Flexible laryngoscope.
868.2480 Cutaneous carbon dioxide (PcCO2) 868.5540 Rigid laryngoscope.
monitor. 868.5550 Anesthetic gas mask.
868.2500 Cutaneous oxygen (PcO2) monitor. 868.5560 Gas mask head strap.
868.2550 Pneumotachometer. 868.5570 Nonrebreathing mask.
868.2600 Airway pressure monitor. 868.5580 Oxygen mask.
868.2610 Gas pressure gauge. 868.5590 Scavenging mask.
868.2620 Gas pressure calibrator. 868.5600 Venturi mask.
868.2700 Pressure regulator. 868.5620 Breathing mouthpiece.
868.2775 Electrical peripheral nerve stimu- 868.5630 Nebulizer.
lator. 868.5640 Medicinal nonventilatory nebulizer
868.2875 Differential pressure transducer. (atomizer).
868.2885 Gas flow transducer. 868.5650 Esophageal obturator.
868.2900 Gas pressure transducer. 868.5655 Portable liquid oxygen unit.
868.5665 Powered percussor.
Subparts D–E [Reserved] 868.5675 Rebreathing device.
868.5690 Incentive spirometer.
Subpart F—Therapeutic Devices 868.5700 Nonpowered oxygen tent.
868.5710 Electrically powered oxygen tent.
868.5090 Emergency airway needle. 868.5720 Bronchial tube.
868.5095 Retrograde intubation device. 868.5730 Tracheal tube.
868.5100 Nasopharyngeal airway. 868.5740 Tracheal/bronchial differential ven-
868.5105 External negative pressure airway tilation tube.
aid. 868.5750 Inflatable tracheal tube cuff.
868.5110 Oropharyngeal airway. 868.5760 Cuff spreader.
868.5115 Device to relieve acute upper air- 868.5770 Tracheal tube fixation device.
way obstruction. 868.5780 Tube introduction forceps.
868.5120 Anesthesia conduction catheter. 868.5790 Tracheal tube stylet.
868.5130 Anesthesia conduction filter. 868.5795 Tracheal tube cleaning brush.
868.5140 Anesthesia conduction kit. 868.5800 Tracheostomy tube and tube cuff.
868.5150 Anesthesia conduction needle. 868.5810 Airway connector.
868.5160 Gas machine for anesthesia or anal- 868.5820 Dental protector.
gesia. 868.5830 Autotransfusion apparatus.
868.5165 Nitric oxide administration appa- 868.5860 Pressure tubing and accessories.
ratus. 868.5870 Nonrebreathing valve.
868.5170 Laryngotracheal topical anesthesia 868.5880 Anesthetic vaporizer.
applicator. 868.5895 Continuous ventilator.
868.5180 Rocking bed. 868.5905 Noncontinuous ventilator (IPPB).
868.5220 Blow bottle. 868.5915 Manual emergency ventilator.
868.5240 Anesthesia breathing circuit. 868.5925 Powered emergency ventilator.
868.5250 Breathing circuit circulator. 868.5935 External negative pressure venti-
868.5260 Breathing circuit bacterial filter. lator.
868.5270 Breathing system heater. 868.5955 Intermittent mandatory ventila-
868.5273 Positive airway pressure delivery tion attachment.
system. 868.5965 Positive end expiratory pressure
868.5280 Breathing tube support. breathing attachment.
868.5300 Carbon dioxide absorbent. 868.5975 Ventilator tubing.
868.5310 Carbon dioxide absorber. 868.5995 Tee drain (water trap).
868.5320 Reservoir bag.
868.5330 Breathing gas mixer. Subpart G—Miscellaneous
868.5340 Nasal oxygen cannula.
868.5350 Nasal oxygen catheter. 868.6100 Anesthetic cabinet, table, or tray.
868.5365 Posture chair for cardiac or pul- 868.6175 Cardiopulmonary emergency cart.
monary treatment. 868.6225 Nose clip.
868.5375 Heat and moisture condenser (arti- 868.6250 Portable air compressor.
ficial nose). 868.6400 Calibration gas.
868.5400 Electroanesthesia apparatus. 868.6700 Anesthesia stool.
868.5420 Ether hook. 868.6810 Tracheobronchial suction catheter.

868.5430 Gas-scavenging apparatus. 868.6820 Patient position support.
868.5440 Portable oxygen generator. 868.6885 Medical gas yoke assembly.
426
AUTHORITY: 21 U.S.C. 351, 360, 360c, 360e, an application for premarket approval
360j, 360l, 371. (PMA) for the device or declaring com-
SOURCE: 47 FR 31142, July 16, 1982, unless pleted a product development protocol
otherwise noted. (PDP) for the device.
EDITORIAL NOTE: Nomenclature changes to (a) Before FDA requires that a device
part 868 appear at 73 FR 35341, June 23, 2008. commercially distributed before the
Subpart A—General Provisions a device that has been found substan-
tially equivalent to such a device, has
§ 868.1 Scope. an approval under section 515 of the act
(a) This part sets forth the classifica- FDA must promulgate a regulation
tion of anesthesiology devices intended under section 515(b) of the act requir-
for human use that are in commercial ing such approval, except as provided
distribution. in paragraph (b) of this section. Such a
(b) The identification of a device in a regulation under section 515(b) of the
regulation in this part is not a precise act shall not be effective during the
description of every device that is, or grace period ending on the 90th day
will be, subject to the regulation. A after its promulgation or on the last
manufacturer who submits a pre- day of the 30th full calendar month
market notification submission for a after the regulation that classifies the
device under part 807 may not show device into class III is effective, which-
merely that the device is accurately ever is later. See section 501(f)(2)(B) of
described by the section title and iden- the act. Accordingly, unless an effec-
tification provisions of a regulation in tive date of the requirement for pre-
this part, but shall state why the de- market approval is shown in the regu-
vice is substantially equivalent to
lation for a device classified into class
other devices, as required by § 807.87.
III in this part, the device may be com-
(c) To avoid duplicative listings, an
mercially distributed without FDA’s
anesthesiology device that has two or
more types of uses (e.g., used both as a issuance of an order approving a PMA
diagnostic device and as a therapeutic or declaring completed a PDP for the
device) is listed only in one subpart. device. If FDA promulgates a regula-
(d) References in this part to regu- tion under section 515(b) of the act re-
latory sections of the Code of Federal quiring premarket approval for a de-
Regulations are to chapter I of title 21, vice, section 501(f)(1)(A) of the act ap-
unless otherwise noted. plies to the device.
(e) Guidance documents referenced in (b) Any new, not substantially equiv-
this part are available on the Internet alent, device introduced into commer-
at http://www.fda.gov/MedicalDevices/ cial distribution on or after May 28,
DeviceRegulationandGuidance/ 1976, including a device formerly mar-
GuidanceDocuments/default.htm. keted that has been substantially al-
[52 FR 17734, May 11, 1987, as amended at 67 tered, is classified by statute (section
FR 76681, Dec. 13, 2002; 78 FR 18233, Mar. 26, 513(f) of the act) into class III without
2013] any grace period and FDA must have
issued an order approving a PMA or de-
§ 868.3 Effective dates of requirement claring completed a PDP for the device
for premarket approval. before the device is commercially dis-
A device included in this part that is tributed unless it is reclassified. If
classified into class III (premarket ap- FDA knows that a device being com-
proval) shall not be commercially dis- mercially distributed may be a ‘‘new’’
tributed after the date shown in the device as defined in this section be-
regulation classifying the device unless cause of any new intended use or other
the manufacturer has an approval reasons, FDA may codify the statutory
under section 515 of the act (unless an classification of the device into class
exemption has been granted under sec- III for such new use. Accordingly, the
tion 520(g)(2) of the act). An approval

regulation for such a class III device
under section 515 of the act consists of
states that as of the enactment date of
FDA’s issuance of an order approving
427
§ 868.9 21 CFR Ch. I (4–1–23 Edition)
the amendments, May 28, 1976, the de- (2) For use in screening or diagnosis
vice must have an approval under sec- of familial or acquired genetic dis-
tion 515 of the act before commercial orders, including inborn errors of me-
distribution. tabolism;
[52 FR 17734, May 11, 1987] (3) For measuring an analyte that
§ 868.9 Limitations of exemptions from screening, diagnosis, or monitoring
section 510(k) of the Federal Food, life-threatening diseases such as ac-
Drug, and Cosmetic Act (the act). quired immune deficiency syndrome
The exemption from the requirement (AIDS), chronic or active hepatitis, tu-
of premarket notification (section berculosis, or myocardial infarction or
510(k) of the act) for a generic type of to monitor therapy;
class I or II device is only to the extent (4) For assessing the risk of cardio-
that the device has existing or reason- vascular diseases;
ably foreseeable characteristics of (5) For use in diabetes management;
commercially distributed devices with- (6) For identifying or inferring the
in that generic type or, in the case of identity of a microorganism directly
in vitro diagnostic devices, only to the from clinical material;
extent that misdiagnosis as a result of (7) For detection of antibodies to
using the device would not be associ- microorganisms other than
ated with high morbidity or mortality.
immunoglobulin G (IgG) or IgG assays
Accordingly, manufacturers of any
when the results are not qualitative, or
commercially distributed class I or II
device for which FDA has granted an are used to determine immunity, or the
exemption from the requirement of assay is intended for use in matrices
premarket notification must still sub- other than serum or plasma;
mit a premarket notification to FDA (8) For noninvasive testing as defined
before introducing or delivering for in- in § 812.3(k) of this chapter; and
troduction into interstate commerce (9) For near patient testing (point of
for commercial distribution the device care).
when: [65 FR 2313, Jan. 14, 2000]
(a) The device is intended for a use
gally marketed device in that generic Subpart B—Diagnostic Devices
type of device; e.g., the device is in-
§ 868.1030 Manual algesimeter.
tended for a different medical purpose,
or the device is intended for lay use (a) Identification. A manual algesim-
where the former intended use was by eter is a mechanical device intended to
health care professionals only; determine a patient’s sensitivity to
(b) The modified device operates pain after administration of an anes-
using a different fundamental sci- thetic agent, e.g., by pricking with a
entific technology than a legally mar- sharp point.
keted device in that generic type of de- (b) Classification. Class I (general con-
vice; e.g., a surgical instrument cuts trols). The device is exempt from the
tissue with a laser beam rather than premarket notification procedures in
with a sharpened metal blade, or an in subpart E of part 807 of this chapter
vitro diagnostic device detects or iden- subject to the limitations in § 868.9. The
tifies infectious agents by using device is also exempt from the current
deoxyribonucleic acid (DNA) probe or good manufacturing practice require-
ments of the quality system regulation
rather than culture or immunoassay
technology; or
ception of § 820.180, with respect to gen-
(c) The device is an in vitro device
eral requirements concerning records,
that is intended:
and § 820.198, with respect to complaint
(1) For use in the diagnosis, moni-
files.
toring, or screening of neoplastic dis-

eases with the exception of [54 FR 25048, June 12, 1989, as amended at 66
immunohistochemical devices; FR 38793, July 25, 2001]
428
§ 868.1040 Powered algesimeter. for any indwelling blood

(a) Identification. A powered algesim- oxyhemoglobin concentration analyzer
eter is a device using electrical stimu- that was in commercial distribution
lation intended to determine a pa- before May 28, 1976, or that has, on or
tient’s sensitivity to pain after admin- before September 21, 2004, been found
istration of an anesthetic agent. to be substantially equivalent to an in-
(b) Classification. Class II (special dwelling blood oxyhemoglobin con-
controls). The device is exempt from centration analyzer that was in com-
the premarket notification procedures mercial distribution before May 28,
in subpart E of part 807 of this chapter 1976. Any other indwelling blood
subject to the limitations in § 868.9. oxyhemoglobin concentration analyzer
[47 FR 31142, July 16, 1982, as amended at 84 shall have an approved PMA or de-
FR 71811, Dec. 30, 2019] clared completed PDP in effect before
being placed in commercial distribu-
§ 868.1075 Argon gas analyzer. tion.
(a) Identification. An argon gas ana- [47 FR 31142, July 16, 1982, as amended at 52
lyzer is a device intended to measure FR 17735, May 11, 1987; 52 FR 22577, June 12,
the concentration of argon in a gas 1987; 69 FR 34920, June 23, 2004]
mixture to aid in determining the pa-
tient’s ventilatory status. The device § 868.1150 Indwelling blood carbon di-
may use techniques such as mass spec- oxide partial pressure (P2CO2) ana-
trometry or thermal conductivity. lyzer.
(b) Classification. Class II (perform- (a) Identification. An indwelling blood
ance standards). carbon dioxide partial pressure PCO2
§ 868.1100 Arterial blood sampling kit. analyzer is a device that consists of a
catheter-tip PCO2 transducer (e.g., PCO2
(a) Identification. An arterial blood electrode) and that is used to measure,
sampling kit is a device, in kit form,
in vivo, the partial pressure of carbon
used to obtain arterial blood samples
dioxide in blood to aid in determining
from a patient for blood gas determina-
tions. The kit may include a syringe, the patient’s circulatory, ventilatory,
needle, cork, and heparin. and metabolic status.
(b) Classification. Class I (general con- (b) Classification. Class II (special
trols). The device is exempt from the controls). The special control for this
premarket notification procedures in device is FDA’s ‘‘Class II Special Con-
subpart E of part 807 of this chapter trols Guidance Document: Indwelling
subject to the limitations in § 868.9. Blood Gas Analyzers; Final Guidance
for Industry and FDA.’’
FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, [47 FR 31142, July 16, 1982; 47 FR 40410, Sept.
2001] 14, 1982, as amended at 52 FR 17735, May 11,
1987; 66 FR 57368, Nov. 15, 2001]
§ 868.1120 Indwelling blood
oxyhemoglobin concentration ana- § 868.1170 Indwelling blood hydrogen
lyzer. ion concentration (pH) analyzer.
(a) Identification. An indwelling blood
(a) Identification. An indwelling blood
oxyhemoglobin concentration analyzer
hydrogen ion concentration (pH) ana-
is a photoelectric device used to meas-
lyzer is a device that consists of a cath-
ure, in vivo, the oxygen-carrying ca-
pacity of hemoglobin in blood to aid in eter-tip pH electrode and that is used
determining the patient’s physiological to measure, in vivo, the hydrogen ion
status. concentration (pH) in blood to aid in
(b) Classification. Class III (premarket determining the patient’s acid-base
approval). balance.
(c) Date PMA or notice of completion (b) Classification. Class II (special
of PDP is required. A PMA or notice of controls). The special control for this
completion of a PDP is required to be device is FDA’s ‘‘Class II Special Con-

filed with the Food and Drug Adminis- trols Guidance Document: Indwelling
tration on or before September 21, 2004,
429
§ 868.1200 21 CFR Ch. I (4–1–23 Edition)
Blood Gas Analyzers; Final Guidance ure the concentration of enflurane an-
for Industry and FDA.’’ esthetic in a gas mixture.
[47 FR 31142, July 16, 1982, as amended at 52 (b) Classification. Class II (perform-
FR 17735, May 11, 1987; 66 FR 57368, Nov. 15, ance standards).
2001]
§ 868.1505 Ventilatory electrical im-
§ 868.1200 Indwelling blood oxygen pedance tomograph.
partial pressure (PO2) analyzer. (a) Identification. A ventilatory elec-
(a) Identification. An indwelling blood trical impedance tomograph is a pre-
oxygen partial pressure (PO2) analyzer scription non-invasive, non-radio-
is a device that consists of a catheter- logical ventilatory device that provides
tip PO2 transducer (e.g., PO2 electrode) an assessment of local impedance vari-
and that is used to measure, in vivo, ation within a cross-section of a pa-
the partial pressure of oxygen in blood tient’s thorax.
to aid in determining the patient’s cir- (b) Classification. Class II (special
culatory, ventilatory, and metabolic controls). The special controls for this
status. device are:
(b) Classification. Class II (special (1) The patient-contacting compo-
controls). The special control for this nents of the device must be dem-
device is FDA’s ‘‘Class II Special Con- onstrated to be biocompatible.
trols Guidance Document: Indwelling (2) Non-clinical performance testing
Blood Gas Analyzers; Final Guidance must demonstrate that the device per-
for Industry and FDA.’’ forms as intended under anticipated
[47 FR 31142, July 16, 1982; 47 FR 40410, Sept. conditions of use, including the fol-
14, 1982, as amended at 52 FR 17735, May 11, lowing:
1987; 66 FR 57368, Nov. 15, 2001] (i) Characterization of device param-
eters, including signal-to-noise ratio,
§ 868.1400 Carbon dioxide gas ana-
lyzer. voltage accuracy, drift, reciprocity ac-
curacy, amplitude response, position
(a) Identification. A carbon dioxide error, and ringing;
gas analyzer is a device intended to (ii) Real time evaluation of local im-
measure the concentration of carbon pedance variation;
dioxide in a gas mixture to aid in de- (iii) Plethysmogram accuracy test-
termining the patient’s ventilatory, ing; and
circulatory, and metabolic status. The
(iv) Use life testing of reusable com-
device may use techniques such as
ponents.
chemical titration, absorption of infra-
red radiation, gas chromatography, or (3) Performance data must validate
mass spectrometry. reprocessing instructions for any reus-
(b) Classification. Class II (perform- able components of the device.
ance standards). (4) Performance data must dem-
onstrate the electrical, thermal, and
§ 868.1430 Carbon monoxide gas ana- mechanical safety and the electro-
lyzer. magnetic compatibility of the device.
(a) Identification. A carbon monoxide (5) Software verification, validation,
gas analyzer is a device intended to and hazard analysis must be performed.
measure the concentration of carbon (6) Labeling must include the fol-
monoxide in a gas mixture to aid in de- lowing:
termining the patient’s ventilatory (i) Guidance for interpretation of the
status. The device may use techniques images generated;
such as infrared absorption or gas chro- (ii) A warning that the device should
matography. be removed before use of a
(b) Classification. Class II (perform- defibrillator, or defibrillator inter-
ance standards). action information based on
defibrillator performance testing with
§ 868.1500 Enflurane gas analyzer.
the device;
(a) Identification. An enflurane gas (iii) A use life for any reusable com-
analyzer is a device intended to meas- ponents; and
430
(iv) Instructions for reprocessing any may use techniques such as gas chro-
reusable components. matography or mass spectrometry.
[84 FR 15098, Apr. 15, 2019] (b) Classification. Class II (perform-
ance standards).
§ 868.1575 Gas collection vessel.
§ 868.1700 Nitrous oxide gas analyzer.
(a) Identification. A gas collection
vessel is a container-like device in- (a) Identification. A nitrous oxide gas
tended to collect a patient’s exhaled analyzer is a device intended to meas-
gases for subsequent analysis. It does ure the concentration of nitrous oxide
not include a sampling pump. anesthetic in a gas mixture. The device
(b) Classification. Class I (general con- may use techniques such as infrared
trols). The device is exempt from the absorption or mass spectrometry.
premarket notification procedures in (b) Classification. Class II (perform-
subpart E of part 807 of this chapter ance standards).
§ 868.1720 Oxygen gas analyzer.
FR 1119, Jan. 16, 1996; 66 FR 38793, July 25, (a) Identification. An oxygen gas ana-
2001] lyzer is a device intended to measure
the concentration of oxygen in res-
§ 868.1620 Halothane gas analyzer. piratory gases by techniques such as
(a) Identification. A halothane gas an- mass spectrometry, polarography,
alyzer is a device intended to measure thermal conductivity, or gas chroma-
the concentration of halothane anes- tography. This generic type of device
thetic in a gas mixture. The device also includes paramagnetic analyzers.
may use techniques such as mass spec- (b) Classification. Class II (perform-
trometry or absorption of infrared or ance standards).
ultraviolet radiation.
(b) Classification. Class II (perform- § 868.1730 Oxygen uptake computer.
ance standards).
(a) Identification. An oxygen uptake
§ 868.1640 Helium gas analyzer. computer is a device intended to com-
pute the amount of oxygen consumed
(a) Identification. A helium gas ana-
by a patient and may include compo-
lyzer is a device intended to measure
nents for determining expired gas vol-
the concentration of helium in a gas
mixture during pulmonary function ume and composition.
testing. The device may use techniques (b) Classification. Class II (perform-
such as thermal conductivity, gas chro- ance standards).
matography, or mass spectrometry.
§ 868.1750 Pressure plethysmograph.
ance standards). (a) Identification. A pressure
plethysmograph is a device used to de-
§ 868.1670 Neon gas analyzer. termine a patient’s airway resistance
(a) Identification. A neon gas analyzer and lung volumes by measuring pres-
is a device intended to measure the sure changes while the patient is in an
concentration of neon in a gas mixture airtight box.
exhaled by a patient. The device may (b) Classification. Class II (perform-
use techniques such as mass spectrom- ance standards).
etry or thermal conductivity.
(b) Classification. Class II (perform- § 868.1760 Volume plethysmograph.
ance standards). (a) Identification. A volume
§ 868.1690 Nitrogen gas analyzer. plethysmograph is an airtight box, in
which a patient sits, that is used to de-
(a) Identification. A nitrogen gas ana- termine the patient’s lung volume
lyzer is a device intended to measure changes.
the concentration of nitrogen in res- (b) Classification. Class II (perform-

piratory gases to aid in determining a ance standards).
patient’s ventilatory status. The device
431
§ 868.1780 21 CFR Ch. I (4–1–23 Edition)
§ 868.1780 Inspiratory airway pressure premarket notification procedures in

meter. subpart E of part 807 of this chapter
(a) Identification. An inspiratory air- subject to the limitations in § 868.9.
way pressure meter is a device used to [47 FR 31142, July 16, 1982, as amended at 61
measure the amount of pressure pro- FR 1119, Jan. 16, 1996; 66 FR 38793, July 25,
duced in a patient’s airway during 2001]
maximal inspiration.
(b) Classification. Class II (perform- § 868.1880 Pulmonary-function data
ance standards). calculator.
(a) Identification. A pulmonary-func-
§ 868.1800 Rhinoanemometer. tion data calculator is a device used to
(a) Identification. A rhinoanemometer calculate pulmonary-function values
is a device used to quantify the amount based on actual physical data obtained
of nasal congestion by measuring the during pulmonary-function testing.
airflow through, and differential pres- (b) Classification. Class II (perform-
sure across, a patient’s nasal passages. ance standards).
ance standards). § 868.1890 Predictive pulmonary-func-
tion value calculator.
§ 868.1840 Diagnostic spirometer. (a) Identification. A predictive pul-
(a) Identification. A diagnostic spi- monary-function value calculator is a
rometer is a device used in pulmonary device used to calculate normal pul-
function testing to measure the volume monary-function values based on em-
of gas moving in or out of a patient’s pirical equations.
lungs. (b) Classification. Class II (perform-
(b) Classification. Class II (performance standards).
ance standards). § 868.1900 Diagnostic pulmonary-func-
§ 868.1850 Monitoring spirometer. tion interpretation calculator.
(a) Identification. A monitoring spi- (a) Identification. A diagnostic pul-
rometer is a device used to measure monary-function interpretation calcu-
continuously a patient’s tidal volume lator is a device that interprets pul-
(volume of gas inhaled by the patient monary study data to determine clin-
during each respiration cycle) or ical significance of pulmonary-function
minute volume (the tidal volume mul- values.
tiplied by the rate of respiration for 1 (b) Classification. Class II (perform-
minute) for the evaluation of the pa- ance standards).
tient’s ventilatory status. § 868.1910 Esophageal stethoscope.
ance standards). (a) Identification. An esophageal
stethoscope is a nonpowered device
§ 868.1860 Peak-flow meter for that is inserted into a patient’s esoph-
spirometry. agus to enable the user to listen to
(a) Identification. A peak-flow meter heart and breath sounds.
for spirometry is a device used to (b) Classification. Class I (general con-
measure a patient’s maximum venti- trols). The device is exempt from the
latory flow rate. premarket notification procedures in
(b) Classification. Class II (perform- subpart E of part 807 of this chapter
ance standards). subject to § 868.9.
§ 868.1870 Gas volume calibrator. FR 2313, Jan. 14, 2000]
(a) Identification. A gas volume cali-
brator is a device that is intended for § 868.1920 Esophageal stethoscope
medical purposes and that is used to with electrical conductors.
calibrate the output of gas volume (a) Identification. An esophageal
measurement instruments by deliv- stethoscope with electrical conductors
ering a known gas volume. is a device that is inserted into the

(b) Classification. Class I (general con- esophagus to listen to a patient’s heart
trols). The device is exempt from the and breath sounds and to monitor
432
electrophysiological signals. The de- subpart E of part 807 of this chapter

vice may also incorporate a thermistor subject to the limitations in § 868.9.
for temperature measurement.
(b) Classification. Class II (perform- FR 1119, Jan. 16, 1996; 66 FR 38793, July 25,
ance standards). 2001]
§ 868.1930 Stethoscope head.
Subpart C—Monitoring Devices
(a) Identification. A stethoscope head
is a weighted chest piece used during § 868.2025 Ultrasonic air embolism
anesthesia to listen to a patient’s monitor.
heart, breath, and other physiological
(a) Identification. An ultrasonic air
sounds.
embolism monitor is a device used to
detect air bubbles in a patient’s blood
stream. It may use Doppler or other ul-
subpart E of part 807 of this chapter trasonic principles.
subject to the limitations in § 868.9. (b) Classification. Class II (perform-
ance standards).
FR 25048, June 12, 1989; 66 FR 38793, July 25, § 868.2300 Bourdon gauge flowmeter.
2001]
(a) Identification. A bourdon gauge
§ 868.1965 Switching valve (ploss). flowmeter is a device intended for med-
ical purposes that is used in conjunc-
(a) Identification. A switching valve
tion with respiratory equipment to
(ploss) is a three-way valve located be-
sense gas pressure. The device is cali-
tween a stethoscope placed over the
heart, a blood pressure cuff, and an ear- brated to indicate gas flow rate when
piece. The valve allows the user to the outflow is open to the atmosphere.
eliminate one sound channel and listen (b) Classification. Class I (general con-
only to a patient’s heart or korotkoff trols). The device is exempt from the
(blood pressure) sounds through the premarket notification procedures in
other channel. subpart E of part 807 of this chapter
(b) Classification. Class I (general con- subject to the limitations in § 868.9.
trols). The device is exempt from the [47 FR 31142, July 16, 1982, as amended at 61
premarket notification procedures in FR 1119, Jan. 16, 1996; 66 FR 38794, July 25,
subpart E of part 807 of this chapter 2001]
device is also exempt from the current § 868.2320 Uncompensated thorpe tube
good manufacturing practice require- flowmeter.
ments of the quality system regulation (a) Identification. An uncompensated
thorpe tube flowmeter is a device in-
ception of § 820.180, with respect to gen-
tended for medical purposes that is
eral requirements concerning records,
and § 820.198, with respect to complaint used to indicate and control gas flow
files. rate accurately. The device includes a
vertically mounted tube and is cali-
[47 FR 31142, July 16, 1982, as amended at 54 brated when the outlet of the flow-
FR 25048, June 12, 1989; 66 FR 38793, July 25, meter is open to the atmosphere.
2001]
§ 868.1975 Water vapor analyzer. trols). The device is exempt from the
(a) Identification. A water vapor ana- subpart E of part 807 of this chapter
lyzer is a device intended to measure subject to the limitations in § 868.9.
the concentration of water vapor in a
patient’s expired gases by using tech- [47 FR 31142, July 16, 1982, as amended at 61
niques such as mass spectrometry. FR 1119, Jan. 16, 1996; 66 FR 38794, July 25,
(b) Classification. Class I (general con- 2001]

433
§ 868.2340 21 CFR Ch. I (4–1–23 Edition)
§ 868.2340 Compensated thorpe tube tion such as monitoring of heart rate

flowmeter. and other physiological parameters
(a) Identification. A compensated linked to the presence or absence of
thorpe tube flowmeter is a device inadequate respiration.
tended for medical purposes that is (b) Classification. Class II (special
used to control and measure gas flow controls). The special control for this
rate accurately. The device includes a device is the FDA guidance document
vertically mounted tube, with the out- entitled ‘‘Class II Special Controls
let of the flowmeter calibrated to a ref- Guidance Document: Apnea Monitors;
erence pressure. Guidance for Industry and FDA.’’
(b) Classification. Class I (general con- [67 FR 46852, July 17, 2002]
premarket notification procedures in § 868.2380 Nitric oxide analyzer.
subpart E of part 807 of this chapter (a) Identification. The nitric oxide an-
subject to the limitations in § 868.9. alyzer is a device intended to measure
[47 FR 31142, July 16, 1982, as amended at 61 the concentration of nitric oxide in res-
FR 1119, Jan. 16, 1996; 66 FR 38794, July 25, piratory gas mixtures during adminis-
2001] tration of nitric oxide.
(b) Classification. Class II. The special
§ 868.2350 Gas calibration flowmeter. control for this device is FDA’s ‘‘Guid-
(a) Identification. A gas calibration ance Document for Premarket Notifi-
flowmeter is a device intended for med- cation Submissions for Nitric Oxide
ical purposes that is used to calibrate Administration Apparatus, Nitric
flowmeters and accurately measure gas Oxide Analyzer, and Nitrogen Dioxide
flow. Analyzer.’’
(b) Classification. Class I (general con- [65 FR 14465, Mar. 3, 2000]
premarket notification procedures in § 868.2385 Nitrogen dioxide analyzer.
subpart E of part 807 of this chapter (a) Identification. The nitrogen diox-
subject to the limitations in § 868.9. ide analyzer is a device intended to
[47 FR 31142, July 16, 1982, as amended at 61 measure the concentration of nitrogen
FR 1119, Jan. 16, 1996; 66 FR 38794, July 25, dioxide in respiratory gas mixtures
2001] during administration of nitric oxide.
§ 868.2375 Breathing frequency mon- controls). The device, when it is a
itor. standalone nitrogen dioxide analyzer
(a) Identification. A breathing (venti- and not those that are components of
latory) frequency monitor is a device nitric oxide delivery systems intended
intended to measure or monitor a pa- to monitor nitrogen dioxide levels dur-
tient’s respiratory rate. The device ing inhaled nitric oxide therapy, is ex-
may provide an audible or visible empt from the premarket notification
alarm when the respiratory rate, aver- procedures in subpart E of part 807 of
aged over time, is outside operator this chapter subject to the limitations
settable alarm limits. This device does in § 868.9. The special control is FDA’s
not include the apnea monitor classi- ‘‘Guidance Document for Premarket
fied in § 868.2377. Notification Submissions for Nitric
(b) Classification. Class II (perform- Oxide Administration Apparatus, Ni-
ance standards). tric Oxide Analyzer, and Nitrogen Di-
oxide Analyzer.’’ See § 868.1(e) for the
FR 46852, July 17, 2002] availability of this guidance document.
[65 FR 11465, Mar. 3, 2000, as amended at 84
§ 868.2377 Apnea monitor. FR 71811, Dec. 30, 2019]
(a) Identification. An apnea monitor is
a complete system intended to alarm § 868.2450 Lung water monitor.
primarily upon the cessation of breath- (a) Identification. A lung water mon-
ing timed from the last detected itor is a device used to monitor the
breath. The apnea monitor also in- trend of fluid volume changes in a pa-
cludes indirect methods of apnea detec- tient’s lung by measuring changes in
434
thoracic electrical impedance (resist- (b) Classification. Class II (special

ance to alternating current) by means controls). The device is exempt from
of electrodes placed on the patient’s the premarket notification procedures
chest. in subpart E of part 807 of this chapter
(b) Classification. Class III (premarket subject to the limitations in § 868.9. The
approval). special control is FDA’s ‘‘Class II Spe-
(c) Date PMA or notice of completion of cial Controls Guidance Document: Cu-
a PDP is required. A PMA or a notice of taneous Carbon Dioxide (PcCO2) and
completion of a PDP for a device is re- Oxygen (PcO2) Monitors; Guidance for
quired to be filed with the Food and Industry and FDA.’’ See § 868.1(e) for
Drug Administration on or before July the availability of this guidance docu-
12, 2000, for any lung water monitor ment.
that was in commercial distribution
before May 28, 1976, or that has, on or [67 FR 76681, Dec. 13, 2002, as amended at 84
FR 71811, Dec. 30, 2019]
before July 12, 2000, been found to be
substantially equivalent to a lung § 868.2550 Pneumotachometer.
water monitor that was in commercial
distribution before May 28, 1976. Any (a) Identification. A
other lung water monitor device shall pneumotachometer is a device intended
have an approved PMA or declared for medical purposes that is used to de-
completed PDP in effect before being termine gas flow by measuring the
placed in commercial distribution. pressure differential across a known re-
sistance. The device may use a set of
FR 17735, May 11, 1987; 65 FR 19834, Apr. 13,
capillaries or a metal screen for the re-
2000] sistive element.
§ 868.2480 Cutaneous carbon dioxide controls). The device is exempt from
(PcCO2) monitor. the premarket notification procedures
(a) Identification. A cutaneous carbon in subpart E of part 807 of this chapter
dioxide (PcCO2) monitor is a subject to the limitations in § 868.9.
noninvasive heated sensor and a pH- [47 FR 31142, July 16, 1982, as amended at 84
sensitive glass electrode placed on a FR 71811, Dec. 30, 2019]
patient’s skin, which is intended to
monitor relative changes in a § 868.2600 Airway pressure monitor.
hemodynamically stable patient’s cu-
(a) Identification. An airway pressure
taneous carbon dioxide tension as an
adjunct to arterial carbon dioxide ten- monitor is a device used to measure
sion measurement. the pressure in a patient’s upper air-
way. The device may include a pressure
gauge and an alarm.
controls). The special control for this
device is FDA’s ‘‘Class II Special Con- (b) Classification. Class II (perform-
trols Guidance Document: Cutaneous ance standards).
Carbon Dioxide (PcCO2) and Oxygen
§ 868.2610 Gas pressure gauge.
(PcO2) Monitors; Guidance for Industry
and FDA.’’ See § 868.1(e) for the avail- (a) Identification. A gas pressure
ability of this guidance document. gauge (e.g., bourdon tube pressure
gauge) is a device intended for medical
FR 76681, Dec. 13, 2002]
purposes that is used to measure gas
pressure in a medical gas delivery sys-
§ 868.2500 Cutaneous oxygen (PcO2) tem.
monitor. (b) Classification. Class I (general con-
(a) Identification. A cutaneous oxygen trols). The device is exempt from the
(PcO2) monitor is a noninvasive, heat- premarket notification procedures in
ed sensor (e.g., a Clark-type subpart E of part 807 of this chapter
polargraphic electrode) placed on the subject to the limitations in § 868.9.
patient’s skin that is intended to mon- [47 FR 31142, July 16, 1982, as amended at 61
itor relative changes in the cutaneous FR 1119, Jan. 16, 1996; 66 FR 38794, July 25,
oxygen tension. 2001]
435
§ 868.2620 21 CFR Ch. I (4–1–23 Edition)
§ 868.2620 Gas pressure calibrator. (b) Classification. Class I (general con-

(a) Identification. A gas pressure cali-
brator is a device intended for medical
purposes that is used to calibrate pres-
sure-measuring instruments by gener-
ating a known gas pressure. [47 FR 31142, July 16, 1982, as amended at 61
(b) Classification. Class I (general con- FR 1119, Jan. 16, 1996; 66 FR 38794, July 25,
subpart E of part 807 of this chapter § 868.2885 Gas flow transducer.
subject to the limitations in § 868.9. (a) Identification. A gas flow trans-
ducer is a device intended for medical
FR 1119, Jan. 16, 1996; 66 FR 38794, July 25,
purposes that is used to convert gas
2001] flow rate into an electrical signal for
subsequent display or processing.
§ 868.2700 Pressure regulator. (b) Classification. Class I (general con-
(a) Identification. A pressure regu-
lator is a device, often called a pres-
sure-reducing valve, that is intended
for medical purposes and that is used
to convert a medical gas pressure from [47 FR 31142, July 16, 1982, as amended at 61
a high variable pressure to a lower, FR 1119, Jan. 16, 1996; 66 FR 38794, July 25,
more constant working pressure. This 2001]
device includes mechanical oxygen reg-
ulators. § 868.2900 Gas pressure transducer.
(b) Classification. Class I (general con- (a) Identification. A gas pressure
trols). The device is exempt from the transducer is a device intended for
premarket notification procedures in medical purposes that is used to con-
subpart E of part 807 of this chapter vert gas pressure into an electrical sig-
subject to the limitations in § 868.9. nal for subsequent display or proc-
essing.
FR 1119, Jan. 16, 1996; 66 FR 38794, July 25, (b) Classification. Class I. The device
2001] is exempt from the premarket notifica-
§ 868.2775 Electrical peripheral nerve of this chapter.
stimulator.
(a) Identification. An electrical pe- FR 1120, Jan. 16, 1996]
ripheral nerve stimulator (neuro-
muscular blockade monitor) is a device Subparts D–E [Reserved]
used to apply an electrical current to a
patient to test the level of pharma-
cological effect of anesthetic drugs and Subpart F—Therapeutic Devices
gases.
§ 868.5090 Emergency airway needle.
ance standards). (a) Identification. An emergency air-
way needle is a device intended to
§ 868.2875 Differential pressure trans- puncture a patient’s cricothyroid mem-
ducer. brane to provide an emergency airway
(a) Identification. A differential pres- during upper airway obstruction.
sure transducer is a two-chambered de- (b) Classification. Class II (perform-
vice intended for medical purposes that ance standards).
is often used during pulmonary func-
tion testing. It generates an electrical § 868.5095 Retrograde intubation de-
signal for subsequent display or proc- vice.
essing that is proportional to the dif- (a) Identification. A retrograde

ference in gas pressures in the two intubation device is a prescription de-
chambers. vice used to perform retrograde
436
intubation via the cricothyroid mem- § 868.5105 External negative pressure

brane. The device may contain or be la- airway aid.
beled for use with guidewires and
(a) Identification. An external nega-
intubating catheters, in addition to
tive pressure airway aid is a prescrip-
needles (§ 868.5090), syringe (§ 880.5860 of
tion device that applies negative pres-
this chapter), and hemostats (§ 878.4800
of this chapter). sure to a patient’s neck to aid in pro-
(b) Classification. Class II (special viding a patent airway during proce-
controls). The special controls for this dures requiring anesthesia.
device are: (b) Classification. Class II (special
(1) Non-clinical performance testing controls). The special controls for this
must demonstrate that the device per- device are:
forms as intended under anticipated (1) Clinical performance testing must
conditions of use, including the fol- document any adverse events observed
lowing: during clinical use, including impaired
(i) Wire guide tensile, flex, fracture, blood flow, and demonstrate that the
and corrosion testing; device performs as intended under an-
(ii) Catheter tensile strength testing ticipated conditions.
at likely points of failure; (2) Non-clinical performance testing
(iii) Catheter kink radius testing; must demonstrate that the device per-
(iv) Compatibility of device compo- forms as intended under anticipated
nents that interact, including compat- patient positions, does not fail during
ibility in connection, disconnection, use, and does not lose negative pres-
and ability to transfer fluids; sure capability. The following testing
(v) Dimensional validation; should be performed:
(vi) Accuracy testing of markings; (i) Ability of the device to maintain a
and seal during various patient positions;
(vii) Validation of the maximum air- (ii) Device leakage testing to dem-
way pressure. onstrate the device maintains vacuum;
(2) Performance data must support (iii) Drop testing to ensure the device
the shelf life of the device by dem- does not incur functional damage after
onstrating continued sterility, package dropping the device; and
integrity, and device functionality (iv) Functional testing after high and
over the identified shelf life. low storage temperature.
(3) The device must be demonstrated (3) All patient contacting compo-
to be biocompatible. nents must be demonstrated to be bio-
(4) Labeling must include: compatible.
(i) Instructions for use; and (4) Labeling must include:
(ii) Package labels that clearly iden- (i) A summary of clinical testing re-
tify the minimum compatible size of sults, including any adverse events and
endotracheal tube. evidence that effectiveness has been
[86 FR 73678, Dec. 28, 2021] achieved.
(ii) Technical specifications of the
§ 868.5100 Nasopharyngeal airway. device, including collar sizes, max-
(a) Identification. A nasopharyngeal imum duration of use, operating tem-
airway is a device used to aid breathing perature, and storage temperature
by means of a tube inserted into a pa- range.
tient’s pharynx through the nose to (iii) Technical specifications of the
provide a patent airway. vacuum source, including maximum
(b) Classification. Class I (general con- vacuum level and operational vacuum
trols). The device is exempt from the level.
premarket notification procedures in (iv) Instructions for use that includes
subpart E of part 807 of this chapter how to place the device, determination
subject to the limitations in § 868.9. of size, verification of suction, ref-
[47 FR 31142, July 16, 1982, as amended at 61 erence to training materials, and infor-
FR 1120, Jan. 16, 1996; 66 FR 38794, July 25, mation on troubleshooting the device if
2001] it does not attach properly.
437
§ 868.5110 21 CFR Ch. I (4–1–23 Edition)
(v) A warning to screen patients for § 868.5130 Anesthesia conduction fil-

carotid artery disease due to the prob- ter.
able risk of the device to dislodge arte- (a) Identification. An anesthesia con-
rial plaques in the carotid artery. duction filter is a microporous filter
(vi) A warning to exclude patients used while administering to a patient
with anatomical abnormalities. injections of local anesthetics to mini-
(vii) A warning not to use the device mize particulate (foreign material)
during medical procedures involving contamination of the injected fluid.
medications that contain propofol. (b) Classification. Class II (perform-
ance standards).
[82 FR 60867, Dec. 26, 2017]
§ 868.5140 Anesthesia conduction kit.
§ 868.5110 Oropharyngeal airway. (a) Identification. An anesthesia con-
(a) Identification. An oropharyngeal duction kit is a device used to admin-
airway is a device inserted into a pa- ister to a patient conduction, regional,
tient’s pharynx through the mouth to or local anesthesia. The device may
provide a patent airway. contain syringes, needles, and drugs.
premarket notification procedures in § 868.5150 Anesthesia conduction nee-
subpart E of part 807 of this chapter dle.
(a) Identification. An anesthesia con-
[47 FR 31142, July 16, 1982, as amended at 61 duction needle is a device used to in-
FR 1120, Jan. 16, 1996; 66 FR 38794, July 25, ject local anesthetics into a patient to
2001] provide regional anesthesia.
§ 868.5115 Device to relieve acute ance standards).
upper airway obstruction.
(a) Identification. The device is a § 868.5160 Gas machine for anesthesia
or analgesia.
raised, rounded pad that, in the event
of choking on a foreign body, can be (a) Gas machine for anesthesia—(1)
applied to the abdomen and pushed up- Identification. A gas machine for anes-
ward to generate expulsion pressure to thesia is a device used to administer to
remove the obstruction to relieve acute a patient, continuously or intermit-
tently, a general inhalation anesthetic
upper airway obstruction.
and to maintain a patient’s ventila-
tion. The device may include a gas
controls) (‘‘Class II Special Control flowmeter, vaporizer, ventilator,
Guidance Document for Acute Upper breathing circuit with bag, and emer-
Airway Obstruction Devices’’). The de- gency air supply.
vice is exempt from the premarket no- (2) Classification. Class II (perform-
tification procedures in subpart E of ance standards).
part 807 of this chapter, subject to (b) Gas machine for analgesia—(1)
§ 868.9. Identification. A gas machine for anal-
[65 FR 39099, June 23, 2000; 65 FR 47669, Aug.
gesia is a device used to administer to
3, 2000] a patient an analgesic agent, such as a
nitrous oxide-oxygen mixture (max-
§ 868.5120 Anesthesia conduction cath- imum concentration of 70 percent ni-
eter. trous oxide).
(2) Classification. Class II (perform-
(a) Identification. An anesthesia con- ance standards).
duction catheter is a flexible tubular
device used to inject local anesthetics § 868.5165 Nitric oxide administration
into a patient and to provide contin- apparatus.
uous regional anesthesia. (a) Identification. The nitric oxide ad-
(b) Classification. Class II (perform- ministration apparatus is a device used

ance standards). to add nitric oxide to gases that are to
be breathed by a patient. The nitric
438
oxide administration apparatus is to be concerning records, and § 820.198, with

used in conjunction with a ventilator respect to complaint files.
or other breathing gas administration
system. FR 25048, June 12, 1989; 66 FR 38794, July 25,
(b) Classification. Class II. The special 2001]
control for this device is FDA’s ‘‘Guid-
ance Document for Premarket Notifi- § 868.5240 Anesthesia breathing cir-
cation Submissions for Nitric Oxide cuit.
Administration Apparatus, Nitric (a) Identification. An anesthesia
Oxide Analyzer, and Nitrogen Dioxide breathing circuit is a device that is in-
Analyzer.’’ tended to administer medical gases to
[65 FR 11465, Mar. 3, 2000] a patient during anesthesia. It provides
both an inhalation and exhalation
§ 868.5170 Laryngotracheal topical an- route and may include a connector,
esthesia applicator. adaptor, and Y-piece.
(a) Identification. A laryngotracheal (b) Classification. Class I (general con-
topical anesthesia applicator is a de- trols). The device is exempt from the
vice used to apply topical anesthetics premarket notification procedures in
to a patient’s laryngotracheal area. subpart E of part 807 of this chapter
(b) Classification. Class II (perform- subject to the limitations in § 868.9.
ance standards).
FR 1120, Jan. 16, 1996; 66 FR 38794, July 25,
§ 868.5180 Rocking bed.
2001]
(a) Identification. A rocking bed is a
device intended for temporary use to § 868.5250 Breathing circuit circulator.
help patient ventilation (breathing) by (a) Identification. A breathing circuit
repeatedly tilting the patient, thereby circulator is a turbine device that is
using the weight of the abdominal con- attached to a closed breathing circuit
tents to move the diaphragm. and that is intended to circulate anes-
(b) Classification. Class II (special thetic gases continuously by maintain-
controls). The device is exempt from ing the unidirectional valves in an
the premarket notification procedures open position and reducing mechanical
in subpart E of part 807 of this chapter dead space and resistance in the
subject to the limitations in § 868.9. breathing circuit.
[47 FR 31142, July 16, 1982, as amended at 84 (b) Classification. Class II (perform-
FR 71811, Dec. 30, 2019] ance standards).
§ 868.5220 Blow bottle. § 868.5260 Breathing circuit bacterial
(a) Identification. A blow bottle is a filter.
device that is intended for medical pur- (a) Identification. A breathing circuit
poses to induce a forced expiration bacterial filter is a device that is in-
from a patient. The patient blows into tended to remove microbiological and
the device to move a column of water particulate matter from the gases in
from one bottle to another. the breathing circuit.
subpart E of part 807 of this chapter § 868.5270 Breathing system heater.
subject to the limitations in § 868.9. If (a) Identification. A breathing system
the device is not labeled or otherwise heater is a device that is intended to
represented as sterile, it is exempt warm breathing gases before they enter
from the current good manufacturing a patient’s airway. The device may in-
clude a temperature controller.

ance standards).
439
§ 868.5273 21 CFR Ch. I (4–1–23 Edition)
§ 868.5273 Positive airway pressure de- (6) Labeling must include the fol-
livery system. lowing:
(a) Identification. A positive airway (i) Therapy pressure range;
pressure delivery system is a prescrip- (ii) Use life and replacement schedule
tion noninvasive ventilatory device for all components;
that delivers expiratory positive air- (iii) Cleaning instructions; and
way pressure for patients suffering (iv) Instructions for assembly and
from obstructive sleep apnea. The sys- connection of device components.
tem also provides positive airway pres-
sure during incipient apnea. The sys- [83 FR 52966, Oct. 19, 2018]
tem may include a dedicated flow gen-
§ 868.5280 Breathing tube support.
erator and a patient interface.
(b) Classification. Class II (special (a) Identification. A breathing tube
controls). The special controls for this support is a device that is intended to
device are: support and anchor a patient’s breath-
(1) The patient-contacting compo- ing tube(s).
nents of the device must be dem- (b) Classification. Class I (general con-
onstrated to be biocompatible. trols). The device is exempt from the
(2) Non-clinical performance testing premarket notification procedures in
must demonstrate that the device per- subpart E of part 807 of this chapter
forms as intended under anticipated subject to the limitations in § 868.9.
conditions of use, including the fol-
lowing: [47 FR 31142, July 16, 1982, as amended at 54
(i) Waveform testing must simulate FR 25048, June 12, 1989; 66 FR 38794, July 25,
breathing conditions and evaluate pres- 2001]
sure and airflow response over a range
and combination of high and low § 868.5300 Carbon dioxide absorbent.
breath rates and tidal volumes. (a) Identification. A carbon dioxide ab-
(ii) Use life testing must demonstrate sorbent is a device intended for med-
adequate device performance over the ical purposes that consists of an ab-
labeled use life of the device. sorbent material (e.g., soda lime) that
(iii) Device integrity testing must is intended to remove carbon dioxide
demonstrate that the device can with- from the gases in the breathing circuit.
stand typical forces expected during (b) Classification. Class I (general con-
use. trols). The device is exempt from the
(iv) Carbon dioxide rebreathing test- premarket notification procedures in
ing must be performed.
(v) System flow rate, maximum ex-
piratory pressure, inhalation pressure,
and intra-mask static pressure testing [47 FR 31142, July 16, 1982, as amended at 61
must be performed. FR 1120, Jan. 16, 1996; 66 FR 38794, July 25,
(vi) Air bolus testing must dem- 2001]
onstrate that the device can withstand
worst-case scenario air pressures. § 868.5310 Carbon dioxide absorber.
(vii) Maximum limited pressure test- (a) Identification. A carbon dioxide ab-
ing of the flow generator in single fault sorber is a device that is intended for
condition must be performed. medical purposes and that is used in a
(viii) Maximum output temperature breathing circuit as a container for
testing of delivered gas, if humidified, carbon dioxide absorbent. It may in-
must be performed. clude a canister and water drain.
(3) Performance data must validate
reprocessing instructions for any reus-
able components of the device.
(4) Performance data must dem- premarket notification procedures in
onstrate the electrical, thermal, and subpart E of part 807 of this chapter
mechanical safety and the electro- subject to the limitations in § 868.9.
magnetic compatibility of the device. [47 FR 31142, July 16, 1982, as amended at 61
(5) Software verification, validation, FR 1120, Jan. 16, 1996; 66 FR 38794, July 25,
and hazard analysis must be performed. 2001]
440
§ 868.5320 Reservoir bag. device intended to assist in the reha-

(a) Identification. A reservoir bag is a bilitation and mobilization of patients
device, usually made of conductive rub- with chronic heart or lung disease.
ber, intended for use in a breathing cir- (b) Classification. Class I (general con-
cuit as a reservoir for breathing gas trols). The device is exempt from the
and to assist, control, or monitor a pa- premarket notification procedures in
tient’s ventilation. subpart E of part 807 of this chapter
trols). The device is exempt from the [47 FR 31142, July 16, 1982, as amended at 54
premarket notification procedures in FR 25048, June 12, 1989; 66 FR 38794, July 25,
§ 868.5375 Heat and moisture con-
[47 FR 31142, July 16, 1982, as amended at 61 denser (artificial nose).
FR 1120, Jan. 16, 1996; 66 FR 38794, July 25,
2001] (a) Identification. A heat and moisture
condenser (artificial nose) is a device
§ 868.5330 Breathing gas mixer. intended to be positioned over a tra-
(a) Identification. A breathing gas cheotomy (a surgically created opening
mixer is a device intended for use in in the throat) or tracheal tube (a tube
conjunction with a respiratory support inserted into the trachea) to warm and
apparatus to control the mixing of humidify gases breathed in by a pa-
gases that are to be breathed by a patient.
tient. (b) Classification. Class I (general con-
§ 868.5340 Nasal oxygen cannula. subject to the limitations in § 868.9.
(a) Identification. A nasal oxygen [47 FR 31142, July 16, 1982, as amended at 61
cannula is a two-pronged device used to FR 1120, Jan. 16, 1996; 66 FR 38795, July 25,
administer oxygen to a patient through 2001]
both nostrils.
(b) Classification. Class I (general con- § 868.5400 Electroanesthesia appa-
trols). The device is exempt from the ratus.
premarket notification procedures in (a) Identification. An
subpart E of part 807 of this chapter electroanesthesia apparatus is a device
subject to the limitations in § 868.9. used for the induction and mainte-
[47 FR 31142, July 16, 1982, as amended at 59 nance of anesthesia during surgical
FR 63007, Dec. 7, 1994; 66 FR 38794, July 25, procedures by means of an alternating
2001] or pulsed electric current that is
passed through electrodes fixed to a pa-
§ 868.5350 Nasal oxygen catheter. tient’s head.
(a) Identification. A nasal oxygen (b) Classification. Class III (premarket
catheter is a device intended to be in- approval).
serted through a patient’s nostril to (c) Date PMA or notice of completion of
administer oxygen. a PDP is required. A PMA or notice of
(b) Classification. Class I (general con- completion of a PDP is required to be
trols). The device is exempt from the filed with the Food and Drug Adminis-
premarket notification procedures in tration on or before December 26, 1996
subpart E of part 807 of this chapter for any electroanesthesia apparatus
subject to the limitations in § 868.9. that was in commercial distribution
[47 FR 31142, July 16, 1982, as amended at 59 before May 28, 1976, or that has, on or
FR 63007, Dec. 7, 1994; 66 FR 38794, July 25, before December 26, 1996 been found to
2001] be substantially equivalent to an
electroanesthesia apparatus that was
§ 868.5365 Posture chair for cardiac or in commercial distribution before May
pulmonary treatment.
28, 1976. Any other electroanesthesia

(a) Identification. A posture chair for apparatus shall have an approved PMA
cardiac or pulmonary treatment is a or a declared completed PDP in effect
441
§ 868.5420 21 CFR Ch. I (4–1–23 Edition)
before being placed in commercial dis- heated, and prefilled humidifiers are
tribution. included in this generic type of device.
FR 17735, May 11, 1987; 61 FR 50706, Sept. 27,
ance standards).
1996]
§ 868.5454 High flow humidified oxy-
gen delivery device.
§ 868.5420 Ether hook.
(a) Identification. A high flow humidi-
(a) Identification. An ether hook is a
fied oxygen delivery device is a pre-
device that fits inside a patient’s
scription device that delivers high flow
mouth and that is intended to deliver
oxygen with humidification for pa-
vaporized ether.
tients who are suffering from res-
(b) Classification. Class I (general con- piratory distress and/or hypoxemia.
premarket notification procedures in controls). The special controls for this
subpart E of part 807 of this chapter device are:
subject to the limitations in § 868.9. If
(1) The patient-contacting compo-
the device is not labeled or otherwise
nents of the device must be dem-
represented as sterile, it is exempt
onstrated to be biocompatible.
(2) Non-clinical performance testing
must demonstrate that the device per-
forms as intended under anticipated
conditions for use, including the fol-
lowing:
(i) Alarm testing must be performed;
respect to complaint files.
(ii) Continuous use thermal stability
[47 FR 31142, July 16, 1982, as amended at 54 testing must be performed;
FR 25048, June 12, 1989; 66 FR 38795, July 25, (iii) Humidity output testing must be
2001] performed; and
(iv) Blender performance testing
§ 868.5430 Gas-scavenging apparatus.
must evaluate fraction of inspired oxy-
(a) Identification. A gas-scavenging gen (FiO2) blending accuracy.
apparatus is a device intended to col- (3) Performance data must validate
lect excess anesthetic, analgesic, or cleaning instructions for any reusable
trace gases or vapors from a patient’s components of the device.
breathing system, ventilator, or (4) Electrical safety, thermal safety,
extracorporeal pump-oxygenator, and mechanical safety, electromagnetic
to conduct these gases out of the area compatibility, and radiofrequency
by means of an exhaust system. identification testing must be per-
(b) Classification. Class II (perform- formed.
ance standards). (5) Software verification, validation,
and hazard analysis must be performed.
§ 868.5440 Portable oxygen generator. (6) Labeling must include:
(a) Identification. A portable oxygen (i) A description of available FiO2
generator is a device that is intended ranges for different flowrates and inlet
to release oxygen for respiratory ther- gas pressures;
apy by means of either a chemical re- (ii) Instructions for applicable
action or physical means (e.g., a molec- flowrates for all intended populations;
ular sieve). (iii) A warning that patients on high
(b) Classification. Class II (perform- flow oxygen are acute and require ap-
ance standards). propriate monitoring, to include pulse
oximetry;
§ 868.5450 Respiratory gas humidifier. (iv) A warning regarding the risk of
condensation at low set temperatures
(a) Identification. A respiratory gas
and certain flows; and
humidifier is a device that is intended
(v) A description of all alarms and
to add moisture to, and sometimes to

their functions.
warm, the breathing gases for adminis-
tration to a patient. Cascade, gas, [83 FR 54007, Oct. 26, 2018]
442
§ 868.5460 Therapeutic humidifier for (ii) Airway pressure delivery accu-

home use. racy testing;
(a) Identification. A therapeutic hu- (iii) Supplemental O2 flowrate accu-
midifier for home use is a device that racy testing;
adds water vapor to breathing gases (iv) Alarm testing; and
and that is intended for respiratory (v) Use life testing.
therapy or other medical purposes. The (2) The patient-contacting compo-
vapor produced by the device pervades nents of the device must be dem-
the area surrounding the patient, who onstrated to be biocompatible.
breathes the vapor during normal res- (3) Labeling must include the fol-
piration. lowing:
(b) Classification. Class I (general con- (i) Instructions for use;
trols). The device is exempt from the (ii) A precaution that monitoring of
premarket notification procedures in capnography is necessary during treat-
subpart E of part 807 of this chapter ment with non-spontaneously breath-
subject to the limitations in § 868.9. ing patients; and
(iii) Use life specification.
[47 FR 31142, July 16, 1982; 47 FR 40410, Sept.
14, 1982, as amended at 61 FR 1120, Jan. 16, [86 FR 68397, Dec. 2, 2021]
1996; 66 FR 38795, July 25, 2001]
§ 868.5530 Flexible laryngoscope.
§ 868.5470 Hyperbaric chamber. (a) Identification. A flexible laryn-
(a) Identification. A hyperbaric cham- goscope is a fiberoptic device used to
ber is a device that is intended to in- examine and visualize a patient’s upper
crease the environmental oxygen pres- airway and aid placement of a tracheal
sure to promote the movement of oxy- tube.
gen from the environment to a pa- (b) Classification. Class I (general con-
tient’s tissue by means of pressuriza- trols). The device is exempt from the
tion that is greater than atmospheric premarket notification procedures in
pressure. This device does not include subpart E of part 807 of this chapter
topical oxygen chambers for extrem- subject to the limitations in § 868.9.
ities (§ 878.5650). [47 FR 41107, Sept. 17, 1982, as amended at 61
(b) Classification. Class II (perform- FR 1120, Jan. 16, 1996; 66 FR 38795, July 25,
ance standards). 2001]
§ 868.5480 Isocapnic ventilation device. § 868.5540 Rigid laryngoscope.

(a) Identification. An isocapnic ven- (a) Identification. A rigid laryn-
tilation device is a prescription device goscope is a device used to examine
used to administer a blend of carbon di- and visualize a patient’s upper airway
oxide and oxygen gases to a patient to and aid placement of a tracheal tube.
induce hyperventilation. This device (b) Classification. Class I (general con-
may be labeled for use with breathing trols). The device is exempt from the
circuits made of reservoir bags premarket notification procedures in
(§ 868.5320), oxygen cannulas (§ 868.5340), subpart E of part 807 of this chapter
masks (§ 868.5550), valves (§ 868.5870), re- subject to the limitations in § 868.9
suscitation bags (§ 868.5915), and/or tub- [47 FR 41107, Sept. 17, 1982, as amended at 61
ing (§ 868.5925). FR 1120, Jan. 16, 1996; 66 FR 38795, July 25,
(b) Classification. Class II (special 2001]
device are: § 868.5550 Anesthetic gas mask.
(1) Nonclinical performance testing (a) Identification. An anesthetic gas
data must demonstrate that the device mask is a device, usually made of con-
performs as intended under anticipated ductive rubber, that is positioned over
conditions of use, including the fol- a patient’s nose or mouth to direct an-
lowing performance characteristics: esthetic gases to the upper airway.
(i) Gas concentration accuracy test- (b) Classification. Class I (general con-
ing for the range of intended controls). The device is exempt from the
centrations; premarket notification procedures in
443
§ 868.5560 21 CFR Ch. I (4–1–23 Edition)
subject to the limitations in § 868.9. trols). The device is exempt from the
FR 1120, Jan. 16, 1996; 66 FR 38795, July 25, subpart E of part 807 of this chapter
2001] subject to the limitations in § 868.9.
§ 868.5560 Gas mask head strap. FR 1120, Jan. 16, 1996; 66 FR 38795, July 25,
(a) Identification. A gas mask head 2001]
strap is a device used to hold an anes-
thetic gas mask in position on a pa- § 868.5600 Venturi mask.
tient’s face. (a) Identification. A venturi mask is a
(b) Classification. Class I (general con- device containing an air-oxygen mixing
trols). The device is exempt from the mechanism that dilutes 100 percent ox-
premarket notification procedures in ygen to a predetermined concentration
subpart E of part 807 of this chapter and delivers the mixed gases to a pa-
subject to the limitations in § 868.9. tient.
FR 25048, June 12, 1989; 66 FR 38795, July 25, trols). The device is exempt from the
2001] premarket notification procedures in
§ 868.5570 Nonrebreathing mask. subject to the limitations in § 868.9.
(a) Identification. A nonrebreathing [47 FR 31142, July 16, 1982, as amended at 61
mask is a device fitting over a pa- FR 1120, Jan. 16, 1996; 66 FR 38795, July 25,
tient’s face to administer oxygen. It 2001]
utilizes one-way valves to prevent the
patient from rebreathing previously ex- § 868.5620 Breathing mouthpiece.
haled gases. (a) Identification. A breathing mouth-
(b) Classification. Class I (general con- piece is a rigid device that is inserted
trols). The device is exempt from the into a patient’s mouth and that con-
premarket notification procedures in nects with diagnostic or therapeutic
subpart E of part 807 of this chapter respiratory devices.
subject to the limitations in § 868.9. (b) Classification. Class I (general con-
[47 FR 31142, July 16, 1982, as amended at 61 trols). The device is exempt from the
FR 1120, Jan. 16, 1996; 66 FR 38795, July 25, premarket notification procedures in
2001] subpart E of part 807 of this chapter
§ 868.5580 Oxygen mask.
(a) Identification. An oxygen mask is FR 2313, Jan. 14, 2000]
a device placed over a patient’s nose,
mouth, or tracheostomy to administer § 868.5630 Nebulizer.
oxygen or aerosols. (a) Identification. A nebulizer is a de-
(b) Classification. Class I (general con- vice intended to spray liquids in aer-
trols). The device is exempt from the osol form into gases that are delivered
premarket notification procedures in directly to the patient for breathing.
subpart E of part 807 of this chapter Heated, ultrasonic, gas, venturi, and
subject to the limitations in § 868.9. refillable nebulizers are included in
[47 FR 31142, July 16, 1982, as amended at 61 this generic type of device.
FR 1120, Jan. 16, 1996; 66 FR 38795, July 25, (b) Classification. Class II (perform-
2001] ance standards).
§ 868.5590 Scavenging mask. § 868.5640 Medicinal nonventilatory
(a) Identification. A scavenging mask nebulizer (atomizer).
is a device positioned over a patient’s (a) Identification. A medicinal non-
nose to deliver anesthetic or analgesic ventilatory nebulizer (atomizer) is a
gases to the upper airway and to re- device that is intended to spray liquid
move excess and exhaled gas. It is usu- medication in aerosol form into the air
ally used during dentistry. that a patient will breathe.
444
trols). The device is exempt from the subject to § 868.9.
premarket notification procedures in [47 FR 31142, July 16, 1982, as amended at 65
subpart E of part 807 of this chapter FR 2313, Jan. 14, 2000]
§ 868.5690 Incentive spirometer.
FR 2313, Jan. 14, 2000] (a) Identification. An incentive spi-
rometer is a device that indicates a pa-
§ 868.5650 Esophageal obturator. tient’s breathing volume or flow and
that provides an incentive to the pa-
(a) Identification. An esophageal obtu-
tient to improve his or her ventilation.
rator is a device inserted through a pa-
tient’s mouth to aid ventilation of the
ance standards).
patient during emergency resuscitation
by occluding (blocking) the esophagus, § 868.5700 Nonpowered oxygen tent.
thereby permitting positive pressure (a) Identification. A nonpowered oxy-
ventilation through the trachea. The gen tent is a device that encloses a pa-
device consists of a closed-end tient’s head and upper body to contain
semirigid esophageal tube that is at- oxygen delivered to the patient for
tached to a face mask. breathing. This generic type of device
(b) Classification. Class II (perform- includes infant oxygen hoods.
ance standards). (b) Classification. Class I (general con-
§ 868.5655 Portable liquid oxygen unit. premarket notification procedures in
(a) Identification. A portable liquid subpart E of part 807 of this chapter
oxygen unit is a portable, thermally in- subject to § 868.9.
sulated container of liquid oxygen that [47 FR 31142, July 16, 1982, as amended at 65
is intended to supplement gases to be FR 2313, Jan. 14, 2000]
inhaled by a patient, is sometimes ac-
companied by tubing and an oxygen § 868.5710 Electrically powered oxygen
mask. An empty portable liquid oxygen tent.
unit is a device, while the oxygen con- (a) Identification. An electrically pow-
tained therein is a drug. ered oxygen tent is a device that en-
(b) Classification. Class II (perform- closes a patient’s head and, by means
ance standards). of an electrically powered unit, admin-
isters breathing oxygen and controls
§ 868.5665 Powered percussor. the temperature and humidity of the
breathing gases. This generic type de-
(a) Identification. A powered percussor
vice includes the pediatric aerosol
is a device that is intended to transmit
tent.
vibration through a patient’s chest
wall to aid in freeing mucus deposits in
ance standards).
the lung in order to improve bronchial
drainage and that may be powered by § 868.5720 Bronchial tube.
electricity or compressed gas.
(a) Identification. A bronchial tube is
(b) Classification. Class II (perform- a device used to differentially intubate
ance standards). a patient’s bronchus (one of the two
main branches of the trachea leading
§ 868.5675 Rebreathing device.
directly to the lung) in order to isolate
(a) Identification. A rebreathing de- a portion of lung distal to the tube.
vice is a device that enables a patient (b) Classification. Class II (perform-
to rebreathe exhaled gases. It may be ance standards).
used in conjunction with pulmonary
function testing or for increasing § 868.5730 Tracheal tube.
minute ventilation. (a) Identification. A tracheal tube is a
(b) Classification. Class I (general con- device inserted into a patient’s trachea
trols). The device is exempt from the via the nose or mouth and used to
premarket notification procedures in maintain an open airway.
445
§ 868.5740 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class II (perform- § 868.5780 Tube introduction forceps.

ance standards). (a) Identification. Tube introduction
§ 868.5740 Tracheal/bronchial differen- forceps (e.g., Magill forceps) are a
tial ventilation tube. right-angled device used to grasp a tra-
cheal tube and place it in a patient’s
(a) Identification. A tracheal/bron- trachea.
chial differential ventilation tube is a (b) Classification. Class I (general con-
device used to isolate the left or the trols). The device is exempt from the
right lung of a patient for anesthesia
or pulmonary function testing.
ance standards).
§ 868.5750 Inflatable tracheal tube FR 1120, Jan. 16, 1996; 66 FR 38795, July 25,
cuff. 2001]
(a) Identification. An inflatable tra-
§ 868.5790 Tracheal tube stylet.
cheal tube cuff is a device used to pro-
vide an airtight seal between a tra- (a) Identification. A tracheal tube sty-
cheal tube and a patient’s trachea. let is a device used temporarily to
(b) Classification. Class II (perform- make rigid a flexible tracheal tube to
ance standards). aid its insertion into a patient.
§ 868.5760 Cuff spreader. trols). The device is exempt from the
(a) Identification. A cuff spreader is a premarket notification procedures in
device used to install tracheal tube subpart E of part 807 of this chapter
cuffs on tracheal or tracheostomy subject to the limitations in § 868.9.
tubes. [47 FR 31142, July 16, 1982, as amended at 61
(b) Classification. Class I (general con- FR 1120, Jan. 16, 1996; 66 FR 38795, July 25,
subpart E of part 807 of this chapter § 868.5795 Tracheal tube cleaning
subject to the limitations in § 868.9. If brush.
the device is not labeled or otherwise (a) Identification. A tracheal tube
represented as sterile, it is exempt cleaning brush is a device consisting of
from the current good manufacturing a brush with plastic bristles intended
practice requirements of the quality to clean tracheal cannula devices after
system regulation in part 820 of this their removal from patients.
chapter, with the exception of § 820.180, (b) Classification. Class I (general con-
with respect to general requirements trols). The device is exempt from the
concerning records, and § 820.198, with premarket notification procedures in
respect to complaint files. subpart E of part 807 of this chapter
[47 FR 31142, July 16, 1982, as amended at 54 subject to the limitations in § 868.9. If
FR 25048, June 12, 1989; 66 FR 38795, July 25, the device is not labeled or otherwise
2001] represented as sterile, it is exempt
§ 868.5770 Tracheal tube fixation de- practice requirements of the quality
vice. system regulation in part 820 of this
(a) Identification. A tracheal tube fix- chapter, with the exception of § 820.180,
ation device is a device used to hold a with respect to general requirements
tracheal tube in place, usually by concerning records, and § 820.198, with
means of straps or pinch rings. respect to complaint files.
trols). The device is exempt from the FR 38795, July 25, 2001]
subpart E of part 807 of this chapter § 868.5800 Tracheostomy tube and tube
subject to the limitations in § 868.9. cuff.
[47 FR 31142, July 16, 1982, as amended at 61 (a) Identification. A tracheostomy

FR 1120, Jan. 16, 1996; 66 FR 38795, July 25, tube and tube cuff is a device intended
2001] to be placed into a surgical opening of
446
the trachea to facilitate ventilation to (b) Classification. Class I (general con-

the lungs. The cuff may be a separate trols). The device is exempt from the
or integral part of the tracheostomy premarket notification procedures in
tube and is, when inflated, intended to subpart E of part 807 of this chapter
establish a seal between the tracheal subject to the limitations in § 868.9.
wall and the tracheostomy tube. The [47 FR 31142, July 16, 1982, as amended at 61
cuff is used to prevent the patient’s as- FR 1120, Jan. 16, 1996; 66 FR 38796, July 25,
piration of substances, such as blood or 2001]
vomit, or to provide a means for posi-
tive-pressure ventilation of the pa- § 868.5870 Nonrebreathing valve.
tient. This device is made of either (a) Identification. A nonrebreathing
stainless steel or plastic. valve is a one-way valve that directs
(b) Classification. Class II. breathing gas flow to the patient and
[51 FR 40389, Nov. 6, 1986]
vents exhaled gases into the atmos-
phere.
§ 868.5810 Airway connector. (b) Classification. Class II (perform-
ance standards).
(a) Identification. An airway con-
nector is a device intended to connect § 868.5880 Anesthetic vaporizer.
a breathing gas source to a tracheal (a) Identification. An anesthetic va-
tube, tracheostomy tube, or mask. porizer is a device used to vaporize liq-
(b) Classification. Class I (general con- uid anesthetic and deliver a controlled
trols). The device is exempt from the amount of the vapor to the patient.
§ 868.5895 Continuous ventilator.
FR 1120, Jan. 16, 1996; 66 FR 38795, July 25, (a) Identification. A continuous venti-
2001] lator (respirator) is a device intended
to mechanically control or assist pa-
§ 868.5820 Dental protector. tient breathing by delivering a pre-
(a) Identification. A dental protector determined percentage of oxygen in the
is a device intended to protect a pa- breathing gas. Adult, pediatric, and
tient’s teeth during manipulative pro- neonatal ventilators are included in
cedures within a patient’s oral cavity. this generic type of device.
§ 868.5905 Noncontinuous ventilator
subpart E of part 807 of this chapter (IPPB).
(a) Identification. A noncontinuous
[47 FR 31142, July 16, 1982, as amended at 61 ventilator (intermittent positive pres-
FR 1120, Jan. 16, 1996; 66 FR 38795, July 25, sure breathing-IPPB) is a device in-
2001]
tended to deliver intermittently an
§ 868.5830 Autotransfusion apparatus. aerosol to a patient’s lungs or to assist
a patient’s breathing.
(a) Identification. An autotransfusion (b) Classification. Class II (perform-
apparatus is a device used to collect ance standards).
and reinfuse the blood lost by a patient
due to surgery or trauma. § 868.5915 Manual emergency venti-
(b) Classification. Class II (perform- lator.
ance standards). (a) Identification. A manual emer-
gency ventilator is a device, usually in-
§ 868.5860 Pressure tubing and acces- corporating a bag and valve, intended
sories. to provide emergency respiratory sup-
(a) Identification. Pressure tubing and port by means of a face mask or a tube
accessories are flexible or rigid devices inserted into a patient’s airway.

intended to deliver pressurized medical (b) Classification. Class II (perform-
gases. ance standards).
447
§ 868.5925 21 CFR Ch. I (4–1–23 Edition)
§ 868.5925 Powered emergency venti- subpart E of part 807 of this chapter

lator. subject to the limitations in § 868.9.
(a) Identification. A powered emer- [47 FR 31142, July 16, 1982, as amended at 61
gency ventilator is a demand valve or FR 1120, Jan. 16, 1996; 66 FR 38796, July 25,
inhalator intended to provide emer- 2001]
gency respiratory support by means of
§ 868.5995 Tee drain (water trap).
a face mask or a tube inserted into a
patient’s airway. (a) Identification. A tee drain (water
(b) Classification. Class II (perform- trap) is a device intended to trap and
ance standards). drain water that collects in ventilator
tubing during respiratory therapy,
§ 868.5935 External negative pressure thereby preventing an increase in
ventilator. breathing resistance.
(a) Identification. An external nega- (b) Classification. Class I (general con-
tive pressure ventilator (e.g., iron lung, trols). The device is exempt from the
cuirass) is a device chamber that is in-
tended to support a patient’s ventila-
tion by alternately applying and re-
leasing external negative pressure over [47 FR 31142, July 16, 1982, as amended at 61
the diaphragm and upper trunk of the FR 1120, Jan. 16, 1996; 66 FR 38796, July 25,
patient. 2001]
ance standards). Subpart G—Miscellaneous
§ 868.5955 Intermittent mandatory § 868.6100 Anesthetic cabinet, table, or
ventilation attachment. tray.
(a) Identification. An intermittent (a) Identification. An anesthetic cabi-
mandatory ventilation (IMV) attach- net, table, or tray is a device intended
ment is a device attached to a mechan- to store anesthetic equipment and
ical ventilator that allows spontaneous drugs. The device is usually con-
breathing by a patient while providing structed to eliminate build-up of static
mechanical ventilation at a preset electrical charges.
rate. (b) Classification. Class I (general con-
ance standards).
§ 868.5965 Positive end expiratory subject to the limitations in § 868.9.
pressure breathing attachment. [47 FR 31142, July 16, 1982, as amended at 54
(a) Identification. A positive end ex- FR 25048, June 12, 1989; 66 FR 38796, July 25,
piratory pressure (PEEP) breathing at- 2001]
tachment is a device attached to a ven- § 868.6175 Cardiopulmonary emer-
tilator that is used to elevate pressure gency cart.
in a patient’s lungs above atmospheric
pressure at the end of exhalation. (a) Identification. A cardiopulmonary
emergency cart is a device intended to
store and transport resuscitation sup-
ance standards).
plies for emergency treatment. The de-
§ 868.5975 Ventilator tubing. vice does not include any equipment
used in cardiopulmonary resuscitation.
(a) Identification. Ventilator tubing is (b) Classification. Class I (general con-
a device intended for use as a conduit trols). The device is exempt from the
for gases between a ventilator and a premarket notification procedures in
patient during ventilation of the pa- subpart E of part 807 of this chapter
tient. subject to the limitations in § 868.9. The
(b) Classification. Class I (general con- device is also exempt from the current
trols). The device is exempt from the good manufacturing practice require-
premarket notification procedures in ments of the quality system regulation
448
in part 820 of this chapter, with the ex- subpart E of part 807 of this chapter
ception of § 820.180, with respect to gen- subject to the limitations in § 868.9.
eral requirements concerning records, [47 FR 31142, July 16, 1982, as amended at 61
and § 820.198, with respect to complaint FR 1121, Jan. 16, 1996; 66 FR 38796, July 25,
files. 2001]
[47 FR 31142, July 16, 1982, as amended at 54 § 868.6700 Anesthesia stool.
FR 25048, June 12, 1989; 66 FR 38796, July 25,
2001] (a) Identification. An anesthesia stool
is a device intended for use as a stool
§ 868.6225 Nose clip. for the anesthesiologist in the oper-
ating room.
(a) Identification. A nose clip is a de- (b) Classification. Class I (general con-
vice intended to close a patient’s exter- trols). The device is exempt from the
nal nares (nostrils) during diagnostic premarket notification procedures in
or therapeutic procedures. subpart E of part 807 of this chapter
premarket notification procedures in FR 25049, June 12, 1989; 66 FR 38796, July 25,
device is also exempt from the current § 868.6810 Tracheobronchial suction
good manufacturing practice require- catheter.
ments of the quality system regulation (a) Identification. A tracheobronchial
in part 820 of this chapter, with the ex- suction catheter is a device used to as-
ception of § 820.180, with respect to gen- pirate liquids or semisolids from a pa-
eral requirements concerning records, tient’s upper airway.
and § 820.198, with respect to complaint (b) Classification. Class 1 (general con-
files. trols). The device is exempt from the
[47 FR 31142, July 16, 1982, as amended at 54 subpart E of part 807 of this chapter
FR 25048, June 12, 1989; 66 FR 38796, July 25, subject to § 868.9.
2001]
§ 868.6250 Portable air compressor. FR 2314, Jan. 14, 2000]
(a) Identification. A portable air com- § 868.6820 Patient position support.

pressor is a device intended to provide (a) Identification. A patient position
compressed air for medical purposes, support is a device intended to main-
e.g., to drive ventilators and other res- tain the position of an anesthetized pa-
piratory devices. tient during surgery.
controls). The device is exempt from trols). The device is exempt from the
the premarket notification procedures premarket notification procedures in
[47 FR 31142, July 16, 1982, as amended at 84 [47 FR 31142, July 16, 1982, as amended at 61
FR 71811, Dec. 30, 2019] FR 1121, Jan. 16, 1996; 66 FR 38796, July 25,
2001]
§ 868.6400 Calibration gas.
§ 868.6885 Medical gas yoke assembly.
(a) Identification. A calibration gas is
(a) Identification. A medical gas yoke
a device consisting of a container of
assembly is a device intended to con-
gas of known concentration intended nect medical gas cylinders to regu-
to calibrate medical gas concentration lators or needle valves to supply gases
measurement devices. for anesthesia or respiratory therapy.
(b) Classification. Class I (general con- The device may include a particulate
trols). The device is exempt from the filter.

449
premarket notification procedures in 870.1405 Interventional cardiovascular im-

subpart E of part 807 of this chapter plant simulation software device.
subject to the limitations in § 868.9. 870.1415 Coronary vascular physiologic sim-
ulation software device.
[47 FR 31142, July 16, 1982, as amended at 61 870.1420 Coronary artery disease risk indi-
FR 1121, Jan. 16, 1996; 66 FR 38796, July 25, cator using acoustic heart signals.
2001] 870.1425 Programmable diagnostic com-
puter.
870.1435 Single-function, preprogrammed di-
PART 870—CARDIOVASCULAR agnostic computer.
DEVICES 870.1450 Densitometer.
870.1650 Angiographic injector and syringe.
Subpart A—General Provisions 870.1660 Indicator injector.
870.1670 Syringe actuator for an injector.
Sec. 870.1750 External programmable pacemaker
870.1 Scope. pulse generator.
870.3 Effective dates of requirement for pre- 870.1800 Withdrawal-infusion pump.
market approval. 870.1875 Stethoscope.
870.9 Limitations of exemptions from sec- 870.1915 Thermodilution probe.
tion 510(k) of the Federal Food, Drug,
and Cosmetic Act (the act). Subpart C—Cardiovascular Monitoring
Devices
Subpart B—Cardiovascular Diagnostic
Devices 870.2050 Biopotential amplifier and signal
conditioner.
870.1025 Arrhythmia detector and alarm (in- 870.2060 Transducer signal amplifier and sig-
cluding ST-segment measurement and nal conditioner.
alarm). 870.2100 Cardiovascular blood flowmeter.
870.1100 Blood pressure alarm. 870.2120 Extravascular blood flow probe.
870.1110 Blood pressure computer. 870.2200 Adjunctive cardiovascular status
870.1120 Blood pressure cuff. indicator.
870.1130 Noninvasive blood pressure meas- 870.2210 Adjunctive predictive cardio-
urement system. vascular indicator.
870.1140 Venous blood pressure manometer. 870.2220 Adjunctive hemodynamic indicator
870.1200 Diagnostic intravascular catheter. with decision point.
870.1210 Continuous flush catheter. 870.2300 Cardiac monitor (including
870.1220 Electrode recording catheter or cardiotachometer and rate alarm).
870.2310 Apex cardiograph
electrode recording probe.
(vibrocardiograph).
870.1230 Fiberoptic oximeter catheter.
870.2320 Ballistocardiograph.
870.1240 Flow-directed catheter.
870.2330 Echocardiograph.
870.1250 Percutaneous catheter.
870.2340 Electrocardiograph.
870.1251 Temporary catheter for embolic 870.2345 Electrocardiograph software for
protection during transcatheter over-the-counter use.
intracardiac procedures. 870.2350 Electrocardiograph lead switching
870.1252 Percutaneous catheter for creation adaptor.
of an arteriovenous fistula for hemo- 870.2360 Electrocardiograph electrode.
dialysis access. 870.2370 Electrocardiograph surface elec-
870.1255 Balloon aortic valvuloplasty cath- trode tester.
eter. 870.2390 Phonocardiograph.
870.1270 Intracavitary phonocatheter sys- 870.2400 Vectorcardiograph.
tem. 870.2450 Medical cathode-ray tube display.
870.1280 Steerable catheter. 870.2600 Signal isolation system.
870.1290 Steerable catheter control system. 870.2620 Line isolation monitor.
870.1300 Catheter cannula. 870.2640 Portable leakage current alarm.
870.1310 Vessel dilator for percutaneous 870.2675 Oscillometer.
catheterization. 870.2700 Oximeter.
870.1330 Catheter guide wire. 870.2710 Ear oximeter.
870.1340 Catheter introducer. 870.2750 Impedance phlebograph.
870.1342 Reverse central venous recanaliza- 870.2770 Impedance plethysmograph.
tion system. 870.2780 Hydraulic, pneumatic, or photo-
870.1345 Intravascular bleed monitor. electric plethysmographs.
870.1350 Catheter balloon repair kit. 870.2785 Software for optical camera-based
870.1360 Trace microsphere. measurement of pulse rate, heart rate,
870.1370 Catheter tip occluder. breathing rate, and/or respiratory rate.

870.1380 Catheter stylet. 870.2786 Hardware and software for optical
870.1390 Trocar. camera-based measurement of pulse rate,
450
heart rate, breathing rate, and/or res- Subpart E—Cardiovascular Surgical
piratory rate. Devices
870.2790 Photoplethysmograph analysis soft-
ware for over-the-counter use. 870.4075 Endomyocardial biopsy device.
870.2800 Medical magnetic tape recorder. 870.4100 Extracorporeal circuit and acces-
870.2810 Paper chart recorder. sories for long-term respiratory/
870.2840 Apex cardiographic transducer. cardiopulmonary failure.
870.2850 Extravascular blood pressure trans- 870.4150 Extracorporeal system for carbon
ducer. dioxide removal.
870.2855 Implantable Intra-aneurysm Pres- 870.4200 Cardiopulmonary bypass accessory
sure Measurement System. equipment.
870.2860 Heart sound transducer. 870.4205 Cardiopulmonary bypass bubble de-
870.2870 Catheter tip pressure transducer. tector.
870.2880 Ultrasonic transducer. 870.4210 Cardiopulmonary bypass vascular
870.2890 Vessel occlusion transducer. catheter, cannula, or tubing.
870.2900 Patient transducer and electrode 870.4220 Cardiopulmonary bypass heart-lung
cable (including connector). machine console.
870.2910 Radiofrequency physiological sig- 870.4230 Cardiopulmonary bypass defoamer.
nal transmitter and receiver. 870.4240 Cardiopulmonary bypass heat ex-
870.2920 Telephone electrocardiograph changer.
transmitter and receiver. 870.4250 Cardiopulmonary bypass tempera-
ture controller.
Subpart D—Cardiovascular Prosthetic 870.4260 Cardiopulmonary bypass arterial
Devices line blood filter.
870.4270 Cardiopulmonary bypass cardi-
870.3250 Vascular clip. otomy suction line blood filter.
870.3260 Vena cava clip. 870.4280 Cardiopulmonary prebypass filter.
870.3300 Vascular embolization device.
870.4290 Cardiopulmonary bypass adaptor,
870.3375 Cardiovascular intravascular filter. stopcock, manifold, or fitting.
870.3450 Vascular graft prosthesis. 870.4300 Cardiopulmonary bypass gas con-
870.3460 Endovascular suturing system. trol unit.
870.3470 Intracardiac patch or pledget made 870.4310 Cardiopulmonary bypass coronary
of polypropylene, polyethylene pressure gauge.
terephthalate, or polytetrafluoro-
870.4320 Cardiopulmonary bypass pulsatile
ethylene.
flow generator.
870.3535 Intra-aortic balloon and control
870.4330 Cardiopulmonary bypass on-line
system.
blood gas monitor.
870.3545 Ventricular bypass (assist) device.
870.4340 Cardiopulmonary bypass level sens-
870.3600 External pacemaker pulse gener-
ing monitor and/or control.
ator.
870.4350 Cardiopulmonary bypass
870.3605 Pacing system analyzer.
oxygenator.
870.3610 Implantable pacemaker pulse gen-
erator. 870.4360 Nonroller-type blood pump.
870.3620 Pacemaker lead adaptor. 870.4370 Roller-type cardiopulmonary by-
870.3630 Pacemaker generator function ana- pass blood pump.
lyzer. 870.4380 Cardiopulmonary bypass pump
870.3640 Indirect pacemaker generator func- speed control.
tion analyzer. 870.4390 Cardiopulmonary bypass pump tub-
870.3650 Pacemaker polymeric mesh bag. ing.
870.3670 Pacemaker charger. 870.4400 Cardiopulmonary bypass blood res-
870.3680 Cardiovascular permanent or tem- ervoir.
porary pacemaker electrode. 870.4410 Cardiopulmonary bypass in-line
870.3690 Pacemaker test magnet. blood gas sensor.
870.3700 Pacemaker programmers. 870.4420 Cardiopulmonary bypass cardi-
870.3710 Pacemaker repair or replacement otomy return sucker.
material. 870.4430 Cardiopulmonary bypass
870.3720 Pacemaker electrode function intracardiac suction control.
tester. 870.4450 Vascular clamp.
870.3730 Pacemaker service tools. 870.4475 Surgical vessel dilator.
870.3800 Annuloplasty ring. 870.4500 Cardiovascular surgical instru-
870.3850 Carotid sinus nerve stimulator. ments.
870.3925 Replacement heart valve. 870.4510 Apical closure device.

870.3935 Prosthetic heart valve holder. 870.4875 Intraluminal artery stripper.
870.3945 Prosthetic heart valve sizer. 870.4885 External vein stripper.
451
§ 870.1 21 CFR Ch. I (4–1–23 Edition)
Subpart F—Cardiovascular Therapeutic (e) Guidance documents referenced in

Devices this part are available on the Internet
at http://www.fda.gov/MedicalDevices/
870.5050 Patient care suction apparatus.
870.5100 Percutaneous Transluminal Coro- DeviceRegulationandGuidance/
nary Angioplasty (PTCA) Catheter. GuidanceDocuments/default.htm..
870.5150 Embolectomy catheter.
870.5175 Septostomy catheter.
870.5200 External cardiac compressor. FR 61344, Oct. 28, 2003; 78 FR 18233, Mar. 26,
870.5210 Cardiopulmonary resuscitation 2013]
(CPR) aid.
870.5225 External counter-pulsating device. § 870.3 Effective dates of requirement
870.5300 DC-defibrillator (including paddles). for premarket approval.
870.5310 Automated external defibrillator A device included in this part that is
system.
870.5325 Defibrillator tester. classified into class III (premarket ap-
870.5550 External transcutaneous cardiac proval) shall not be commercially dis-
pacemaker (noninvasive). tributed after the date shown in the
870.5700 Steerable cardiac ablation catheter regulation classifying the device unless
remote control system. the manufacturer has an approval
870.5800 Compressible limb sleeve.
under section 515 of the act (unless an
870.5900 Thermal regulating system.
870.5910 Esophageal thermal regulation de- exemption has been granted under sec-
vice. tion 520(g)(2) of the act). An approval
870.5925 Automatic rotating tourniquet. under section 515 of the act consists of
AUTHORITY: 21 U.S.C. 351, 360, 360c, 360e, FDA’s issuance of an order approving
360j, 360l, 371. an application for premarket approval
(PMA) for the device or declaring com-
SOURCE: 45 FR 7907, Feb. 5, 1980, unless oth-
erwise noted. pleted a product development protocol
(PDP) for the device.
part 870 appear at 73 FR 35341, June 23, 2008.
(a) Before FDA requires that a device
commercially distributed before the
Subpart A—General Provisions a device that has been found substan-
§ 870.1 Scope. tially equivalent to such a device, has
an approval under section 515 of the act
(a) This part sets forth the classifica-
FDA must promulgate a regulation
tion of cardiovascular devices intended
under section 515(b) of the act requir-
for human use that are in commercial
ing such approval, except as provided
distribution.
in paragraph (b) of this section. Such a
(b) The identification of a device in a
regulation in this part is not a precise regulation under section 515(b) of the
description of every device that is, or act shall not be effective during the
will be, subject to the regulation. A grace period ending on the 90th day
manufacturer who submits a pre- after its promulgation or on the last
market notification submission for a day of the 30th full calendar month
device under part 807 may not show after the regulation that classifies the
merely that the device is accurately device into class III is effective, which-
described by the section title and iden- ever is later. See section 501(f)(2)(B) of
tification provisions of a regulation in the act. Accordingly, unless an effec-
this part, but shall state why the de- tive date of the requirement for pre-
vice is substantially equivalent to market approval is shown in the regu-
other devices, as required by § 807.87. lation for a device classified into class
(c) To avoid duplicative listings, a III in this part, the device may be com-
cardiovascular device that has two or mercially distributed without FDA’s
more types of uses (e.g., used both as a issuance of an order approving a PMA
diagnostic device and as a therapeutic or declaring completed a PDP for the
device) is listed only in one subpart. device. If FDA promulgates a regula-
(d) References in this part to regu- tion under section 515(b) of the act re-
latory sections of the Code of Federal quiring premarket approval for a de-
Regulations are to chapter I of title 21, vice, section 501(f)(1)(A) of the act ap-
unless otherwise noted. plies to the device.
452
(b) Any new, not substantially equiv- type of device; e.g., the device is in-
alent, device introduced into commer- tended for a different medical purpose,
cial distribution on or after May 28, or the device is intended for lay use
1976, including a device formerly mar- where the former intended use was by
keted that has been substantially al- health care professionals only;
tered, is classified by statute (section (b) The modified device operates
513(f) of the act) into class III without using a different fundamental sci-
any grace period and FDA must have entific technology than a legally mar-
issued an order approving a PMA or de- keted device in that generic type of de-
claring completed a PDP for the device vice; e.g., a surgical instrument cuts
before the device is commercially dis- tissue with a laser beam rather than
tributed unless it is reclassified. If with a sharpened metal blade, or an in
FDA knows that a device being com- vitro diagnostic device detects or iden-
mercially distributed may be a ‘‘new’’ tifies infectious agents by using
device as defined in this section be- deoxyribonucleic acid (DNA) probe or
cause of any new intended use or other nucleic acid hybridization technology
reasons, FDA may codify the statutory rather than culture or immunoassay
classification of the device into class technology; or
III for such new use. Accordingly, the (c) The device is an in vitro device
regulation for such a class III device that is intended:
states that as of the enactment date of (1) For use in the diagnosis, moni-
the amendments, May 28, 1976, the de- toring, or screening of neoplastic dis-
vice must have an approval under sec- eases with the exception of
tion 515 of the act before commercial immunohistochemical devices;
distribution.
(2) For use in screening or diagnosis
[52 FR 17735, May 11, 1987] of familial or acquired genetic dis-
orders, including inborn errors of me-
§ 870.9 Limitations of exemptions from tabolism;
section 510(k) of the Federal Food,
(3) For measuring an analyte that
Drug, and Cosmetic Act (the act).
The exemption from the requirement screening, diagnosis, or monitoring
of premarket notification (section life-threatening diseases such as ac-
510(k) of the act) for a generic type of quired immune deficiency syndrome
class I or II device is only to the extent (AIDS), chronic or active hepatitis, tu-
that the device has existing or reason- berculosis, or myocardial infarction or
ably foreseeable characteristics of to monitor therapy;
commercially distributed devices with- (4) For assessing the risk of cardio-
in that generic type or, in the case of vascular diseases;
in vitro diagnostic devices, only to the (5) For use in diabetes management;
extent that misdiagnosis as a result of (6) For identifying or inferring the
using the device would not be associ- identity of a microorganism directly
ated with high morbidity or mortality. from clinical material;
Accordingly, manufacturers of any (7) For detection of antibodies to
commercially distributed class I or II microorganisms other than
device for which FDA has granted an immunoglobulin G (IgG) or IgG assays
exemption from the requirement of when the results are not qualitative, or
premarket notification must still sub- are used to determine immunity, or the
mit a premarket notification to FDA assay is intended for use in matrices
before introducing or delivering for in- other than serum or plasma;
(8) For noninvasive testing as defined
for commercial distribution the device
in § 812.3(k) of this chapter; and
when:
(a) The device is intended for a use
care).
gally marketed device in that generic [65 FR 2314, Jan. 14, 2000]
453
§ 870.1025 21 CFR Ch. I (4–1–23 Edition)
Subpart B—Cardiovascular vice that provides a signal from which

Diagnostic Devices systolic, diastolic, mean, or any com-
bination of the three pressures can be
§ 870.1025 Arrhythmia detector and derived through the use of tranducers
alarm (including ST-segment meas- placed on the surface of the body.
urement and alarm). (b) Classification. Class II (perform-
(a) Identification. The arrhythmia de- ance standards).
tector and alarm device monitors an
electrocardiogram and is designed to § 870.1140 Venous blood pressure ma-
produce a visible or audible signal or nometer.
alarm when atrial or ventricular ar- (a) Identification. A venous blood
rhythmia, such as premature contrac- pressure manometer is a device at-
tion or ventricular fibrillation, occurs. tached to a venous catheter to indicate
(b) Classification. Class II (special manometrically the central or periph-
controls). The guidance document enti- eral venous pressure.
tled ‘‘Class II Special Controls Guid- (b) Classification. Class II (perform-
ance Document: Arrhythmia Detector ance standards).
and Alarm’’ will serve as the special
control. See § 870.1 for the availability § 870.1200 Diagnostic intravascular
of this guidance document. catheter.
[68 FR 61344, Oct. 28, 2003] (a) Identification. An intravascular di-
agnostic catheter is a device used to
§ 870.1100 Blood pressure alarm. record intracardiac pressures, to sam-
(a) Identification. A blood pressure ple blood, and to introduce substances
alarm is a device that accepts the sig- into the heart and vessels. Included in
nal from a blood pressure transducer this generic device are right-heart
amplifier, processes the signal, and catheters, left-heart catheters, and
emits an alarm when the blood pres- angiographic catheters, among others.
sure falls outside a pre-set upper or (b) Classification. Class II (perform-
lower limit. ance standards).
§ 870.1210 Continuous flush catheter.
ance standards).
(a) Identification. A continuous flush
§ 870.1110 Blood pressure computer. catheter is an attachment to a cath-
(a) Identification. A blood pressure eter-transducer system that permits
computer is a device that accepts the continuous intravascular flushing at a
electrical signal from a blood pressure slow infusion rate for the purpose of
transducer amplifier and indicates the eliminating clotting, back-leakage,
systolic, diastolic, or mean pressure and waveform damping.
based on the input signal. (b) Classification. Class II (perform-
ance standards).
§ 870.1220 Electrode recording cath-
§ 870.1120 Blood pressure cuff. eter or electrode recording probe.
(a) Identification. A blood pressure (a) Identification. An electrode record-
cuff is a device that has an inflatable ing catheter or an electrode recording
bladder in an inelastic sleeve (cuff) probe is a device used to detect an
with a mechanism for inflating and de- intracardiac electrocardiogram, or to
flating the bladder. The cuff is used in detect cardiac output or left-to-right
conjunction with another device to de- heart shunts. The device may be
termine a subject’s blood pressure. unipolar or multipolar for electro-
(b) Classification. Class II (perform- cardiogram detection, or may be a
ance standards). platinum-tipped catheter which senses
the presence of a special indicator for
§ 870.1130 Noninvasive blood pressure cardiac output or left-to-right heart
measurement system.
shunt determinations.
(a) Identification. A noninvasive blood (b) Classification. Class II (perform-
pressure measurement system is a de- ance standards).
454
§ 870.1230 Fiberoptic oximeter cath- ment and retrieval forces, and proce-
eter. dural time; and
(a) Identification. A fiberoptic oxim- (B) Device compatibility and lack of
eter catheter is a device used to esti- interference with the transcatheter
mate the oxygen saturation of the intracardiac procedure and device.
blood. It consists of two fiberoptic bun- (ii) Tensile strengths of joints and
dles that conduct light at a desired components, tip flexibility, torque
wavelength through blood and detect strength, torque response, and kink re-
the reflected and scattered light at the sistance.
distal end of the catheter. (iii) Flow characteristics.
(b) Classification. Class II (perform- (A) The ability of the filter to not
ance standards). impede blood flow.
(B) The amount of time the filter can
§ 870.1240 Flow-directed catheter. be deployed in position and/or retrieved
(a) Identification. A flow-directed from its location without disrupting
catheter is a device that incorporates a blood flow.
gas-filled balloon to help direct the (iv) Characterization and verification
catheter to the desired position. of all dimensions.
(b) Classification. Class II (perform- (2) Animal testing must demonstrate
ance standards). that the device performs as intended
under anticipated conditions of use.
§ 870.1250 Percutaneous catheter. The following performance characteris-
(a) Identification. A percutaneous tics must be assessed:
catheter is a device that is introduced (i) Delivery, deployment, and re-
into a vein or artery through the skin trieval, including quantifying proce-
using a dilator and a sheath (intro- dural time.
ducer) or guide wire. (ii) Device compatibility and lack of
(b) Classification. Class II (perform- interference with the transcatheter
ance standards). intracardiac procedure and device.
(iii) Flow characteristics.
§ 870.1251 Temporary catheter for em-
bolic protection during (A) The ability of the filter to not
transcatheter intracardiac proce- impede blood flow.
dures. (B) The amount of time the filter can
be deployed in position and/or retrieved
(a) Identification. This device is a sin-
from its location without disrupting
gle use percutaneous catheter system
blood flow.
that has (a) blood filter(s) at the distal
end. This device is indicated for use (iv) Gross pathology and
while performing transcatheter histopathology assessing vascular in-
intracardiac procedures. The device is jury and downstream embolization.
used to filter blood in a manner that (3) All patient contacting compo-
may prevent embolic material (throm- nents of the device must be dem-
bus/debris) from the transcatheter onstrated to be biocompatible.
intracardiac procedure from traveling (4) Performance data must dem-
towards the cerebral circulation. onstrate the sterility of the device
(b) Classification. Class II (special components intended to be provided
controls). The special controls for this sterile.
device are: (5) Performance data must support
(1) Non-clinical performance testing the shelf life of the device by dem-
must demonstrate that the device per- onstrating continued sterility, package
forms as intended under anticipated integrity, and device functionality
conditions of use. The following per- over the identified shelf life.
formance characteristics must be test- (6) Labeling for the device must in-
ed: clude:
(i) Simulated-use testing in a clini- (i) Instructions for use;
cally relevant bench anatomic model (ii) Compatible transcatheter
to assess the following: intracardiac procedure devices;

(A) Delivery, deployment, and re- (iii) A detailed summary of the clin-
trieval, including quantifying deploy- ical testing conducted; and
455
§ 870.1252 21 CFR Ch. I (4–1–23 Edition)
(iv) A shelf life and storage condi- (v) Gross pathology and
tions. histopathology assessing vascular in-
(7) Clinical performance testing must jury and downstream embolization.
demonstrate: (3) Non-clinical performance testing
(i) The ability to safely deliver, de- must demonstrate that the device per-
ploy, and remove the device; forms as intended under anticipated
(ii) The ability of the device to filter conditions of use. The following per-
embolic material while not impeding formance characteristics must be test-
blood flow; ed:
(iii) Secure positioning and stability (i) Simulated-use testing in a clini-
of the position throughout the cally relevant bench anatomic model
transcatheter intracardiac procedure; to assess the delivery, deployment, ac-
and tivation, and retrieval of the device;
(ii) Tensile strengths of joints and
(iv) Evaluation of all adverse events
components;
including death, stroke, and vascular
(iii) Accurate positioning and align-
injury.
ment of the device to achieve fistula
[83 FR 4140, Jan. 30, 2018] creation; and
(iv) Characterization and verification
§ 870.1252 Percutaneous catheter for of all dimensions.
creation of an arteriovenous fistula (4) Electrical performance, electrical
for hemodialysis access. safety, and electromagnetic compat-
(a) Identification. This device is a sin- ibility (EMC) testing must be per-
gle use percutaneous catheter system formed for devices with electrical com-
that creates an arteriovenous fistula in ponents.
the arm of patients with chronic kid- (5) Software verification, validation,
ney disease who need hemodialysis. and hazard analysis must be performed
(b) Classification. Class II (special for devices that use software.
controls). The special controls for this (6) All patient-contacting compo-
device are: nents of the device must be dem-
(1) Clinical performance testing must onstrated to be biocompatible.
evaluate: (7) Performance data must dem-
onstrate the sterility of the device
(i) The ability to safely deliver, de-
components intended to be provided
ploy, and remove the device;
sterile.
(ii) The ability of the device to create
(8) Performance data must support
an arteriovenous fistula;
the shelf life of the device by dem-
(iii) The ability of the arteriovenous onstrating continued sterility, package
fistula to attain a blood flow rate and integrity, and device functionality
diameter suitable for hemodialysis; over the identified shelf life.
(iv) The ability of the fistula to be (9) Labeling for the device must in-
used for vascular access for hemo- clude:
dialysis; (i) Instructions for use;
(v) The patency of the fistula; and (ii) Identification of system compo-
(vi) The rates and types of all adverse nents and compatible devices;
events. (iii) Expertise needed for the safe use
(2) Animal testing must demonstrate of the device;
that the device performs as intended (iv) A detailed summary of the clin-
under anticipated conditions of use. ical testing conducted and the patient
The following performance characteris- population studied; and
tics must be assessed: (v) A shelf life and storage condi-
(i) Delivery, deployment, and re- tions.
trieval of the device; [87 FR 9241, Feb. 18, 2022]
(ii) Compatibility with other devices
labeled for use with the device; § 870.1255 Balloon aortic valvuloplasty
(iii) Patency of the fistula; catheter.
(iv) Characterization of blood flow at (a) Identification. A balloon aortic

the time of the fistula creation proce- valvuloplasty catheter is a catheter
dure and at chronic followup; and with a balloon at the distal end of the
456
shaft, which is intended to treat ste- § 870.1300 Catheter cannula.

nosis in the aortic valve when the bal-
(a) Identification. A catheter cannula
loon is expanded.
(b) Classification. Class II (special is a hollow tube which is inserted into
controls). The special controls for this a vessel or cavity; this device provides
device are: a rigid or semirigid structure which
(1) The device must be demonstrated can be connected to a tube or con-
to be biocompatible. nector.
(2) Sterility and shelf life testing (b) Classification. Class II (perform-
must demonstrate the sterility of pa- ance standards).
tient-contacting components and the
shelf life of these components. § 870.1310 Vessel dilator for
percutaneous catheterization.
(3) Non-clinical performance evalua-
tion must demonstrate that the device (a) Identification. A vessel dilator for
performs as intended under anticipated percutaneous catheterization is a de-
conditions of use, including device device which is placed over the guide wire
livery, inflation, deflation, and re- to enlarge the opening in the vessel,
moval. and which is then removed before slid-
(4) In vivo evaluation of the device ing the catheter over the guide wire.
must demonstrate device performance, (b) Classification. Class II (perform-
including the ability of the device to ance standards).
treat aortic stenosis.
(5) Labeling must include a detailed § 870.1330 Catheter guide wire.
summary of the device-related and pro- (a) Identification. A catheter guide
cedure-related complications pertinent wire is a coiled wire that is designed to
to the use of the device. fit inside a percutaneous catheter for
[82 FR 34852, July 27, 2017] the purpose of directing the catheter
through a blood vessel.
§ 870.1270 Intracavitary phonocatheter (b) Classification. Class II (special
system. controls). The device, when it is a
(a) Identification. An intracavitary torque device that is manually oper-
phonocatheter system is a system that ated, non-patient contacting, and in-
includes a catheter with an acoustic tended to manipulate non-cerebral vas-
transducer and the associated device cular guide wires, is exempt from the
that processes the signal from the premarket notification procedures in
transducer; this device records bio- subpart E of part 807 of this chapter
acoustic phenomena from a transducer subject to the limitations in § 870.9.
placed within the heart, blood vessels,
or body cavities. [45 FR 7907, Feb. 5, 1980, as amended at 84 FR
71811, Dec. 30, 2019]
ance standards). § 870.1340 Catheter introducer.
§ 870.1280 Steerable catheter. (a) Identification. A catheter intro-
(a) Identification. A steerable catheter ducer is a sheath used to facilitate
is a catheter used for diagnostic and placing a catheter through the skin
monitoring purposes whose movements into a vein or artery.
are directed by a steering control unit. (b) Classification. Class II (perform-
ance standards).
§ 870.1342 Reverse central venous re-
§ 870.1290 Steerable catheter control canalization system.
system. (a) Identification. A reverse central
(a) Identification. A steerable catheter venous recanalization system is a pre-
control system is a device that is con- scription device for obtaining central
nected to the proximal end of a steer- venous access to facilitate catheter in-
able guide wire that controls the mo- sertion into the central venous system.
tion of the steerable catheter. Reverse recanalization involves the

(b) Classification. Class II (perform- initiation of an access path from with-
ance standards). in the vein and then progressing to the
457
§ 870.1345 21 CFR Ch. I (4–1–23 Edition)
skin for patients with upper body ve- § 870.1345 Intravascular bleed mon-
nous occlusions or other conditions itor.
that preclude central venous access by (a) Identification. An intravascular
other methods. bleed monitor is a probe, catheter, or
(b) Classification. Class II (special catheter introducer that measures
controls). The special controls for this changes in bioimpedance and uses an
device are: algorithm to detect or monitor pro-
(1) Clinical performance testing must
gression of potential internal bleeding
fulfill the following:
complications.
(i) Demonstrate the ability to safely
deliver, deploy, and remove the device;
and
(ii) Evaluate all adverse events in- device are:
cluding death, bleeding, damage to (1) In vivo animal performance test-
non-target tissue and organs, blood ing must demonstrate that the device
vessel perforation or rupture, and he- performs as intended under anticipated
matoma. conditions of use and evaluate the fol-
(2) Non-clinical performance testing lowing:
must demonstrate that the device per- (i) Device performance characteris-
forms as intended under anticipated tics;
conditions of use. The following per- (ii) Adverse effects, including gross
formance characteristics must be test- necropsy and histopathology; and
ed: (iii) Device usability, including de-
(i) Simulated-use testing in a clini- vice preparation, device handling, and
cally relevant bench anatomic model user interface.
to assess the delivery, deployment, and (2) Non-clinical performance testing
retrieval of the system; data must demonstrate that the device
(ii) Compatibility with other devices performs as intended under anticipated
labeled for use with the device; conditions of use. The following per-
(iii) Tensile strengths of joints and formance characteristics must be test-
components; ed:
(iv) Kink resistance of system com- (i) Tensile testing of joints and mate-
ponents; rials;
(v) Radiopacity of components used (ii) Mechanical integrity testing;
to monitor procedure under fluoros- (iii) Friction testing;
copy; (iv) Flush testing;
(vi) Characterization and verification
(v) Air leakage and liquid leakage
of all dimensions; and
testing;
(vii) Leakage of air or fluid.
(3) All patient contacting compo- (vi) Latching and unlatching testing;
nents of the device must be dem- (vii) Kink and bend testing;
onstrated to be biocompatible. (viii) Insertion force testing;
(4) Performance data must dem- (ix) Torque testing;
onstrate the sterility of the device (x) Corrosion testing; and
components intended to be provided (xi) Dimensional tolerance testing.
sterile. (3) Performance data must support
(5) Performance data must support the sterility and pyrogenicity of the
the shelf life of the device by dem- device components intended to be pro-
onstrating continued sterility, package vided sterile.
integrity, and device functionality (4) Performance data must support
over the identified shelf life. the shelf life of the device by dem-
(6) Labeling for the device must in- onstrating continued sterility, package
clude: integrity, and device functionality
(i) Instructions for use, including a over the identified shelf life.
description of compatible devices; (5) The patient contacting compo-
(ii) A detailed summary of the clin- nents of the device must be dem-
ical testing conducted and;
onstrated to be biocompatible.
(iii) Shelf life and storage conditions. (6) Software verification, validation,
[87 FR 26991, May 6, 2022] and hazard analysis must be performed.
458
(7) Performance data must dem- filed with the Food and Drug Adminis-
onstrate electromagnetic compat- tration on or before December 26, 1996
ibility (EMC), electrical safety, ther- for any trace microsphere that was in
mal safety, and mechanical safety. commercial distribution before May 28,
(8) Human factors performance eval- 1976, or that has, on or before Decem-
uation must demonstrate that the user ber 26, 1996 been found to be substan-
can correctly use the device, based tially equivalent to a trace micro-
solely on reading the directions for use. sphere that was in commercial dis-
(9) Labeling must include: tribution before May 28, 1976. Any
(i) Instructions for use; other trace microsphere shall have an
(ii) A shelf life and storage condi- approved PMA or a declared completed
tions; PDP in effect before being placed in
(iii) Compatible procedures; commercial distribution.
(iv) A sizing table; and
(v) Quantification of blood detected. 17736, May 11, 1987; 61 FR 50706, Sept. 27, 1996]
[87 FR 34778, June 8, 2022]
§ 870.1370 Catheter tip occluder.
§ 870.1350 Catheter balloon repair kit. (a) Identification. A catheter tip
(a) Identification. A catheter balloon occluder is a device that is inserted
repair kit is a device used to repair or into certain catheters to prevent flow
replace the balloon of a balloon cath- through one or more orifices.
eter. The kit contains the materials, (b) Classification. Class II (perform-
such as glue and balloons, necessary to ance standards).
effect the repair or replacement.
(b) Classification. Class III (premarket § 870.1380 Catheter stylet.
approval). (a) Identification. A catheter stylet is
(c) Date PMA or notice of completion of a wire that is run through a catheter or
a PDP is required. A PMA or notice of cannula to render it stiff.
completion of a PDP is required to be (b) Classification. Class II (perform-
filed with the Food and Drug Adminis- ance standards).
tration on or before December 26, 1996
for any catheter balloon repair kit that § 870.1390 Trocar.
was in commercial distribution before (a) Identification. A trocar is a sharp-
May 28, 1976, or that has, on or before pointed instrument used with a
December 26, 1996 been found to be sub- cannula for piercing a vessel or cham-
stantially equivalent to a catheter bal- ber to facilitate insertion of the
loon repair kit that was in commercial cannula.
distribution before May 28, 1976. Any (b) Classification. Class II (special
other catheter balloon repair kit shall controls). Except for trocars that are
have an approved PMA or a declared reprocessed for multiple use, the device
completed PDP in effect before being is exempt from the premarket notifica-
placed in commercial distribution. tion procedures in subpart E of part 807
[45 FR 7907, Feb. 5, 1980, as amended at 52 FR of this chapter subject to the limita-
17736, May 11, 1987; 61 FR 50706, Sept. 27, 1996] tions in § 870.9.
§ 870.1360 Trace microsphere.
71811, Dec. 30, 2019]
(a) Identification. A trace microsphere
is a radioactively tagged nonbiodegrad- § 870.1405 Interventional cardio-
able particle that is intended to be in- vascular implant simulation soft-
jected into an artery or vein and ware device.
trapped in the capillary bed for the (a) Identification. An interventional
purpose of studying blood flow within cardiovascular implant simulation
or to an organ. software device is a prescription device
(b) Classification. Class III (premarket that provides a computer simulation of
approval). an interventional cardiovascular im-
(c) Date PMA or notice of completion of plant device inside a patient’s cardio-
a PDP is required. A PMA or notice of vascular anatomy. It performs com-
completion of a PDP is required to be putational modeling to predict the
459
§ 870.1415 21 CFR Ch. I (4–1–23 Edition)
interaction of the interventional car- uation, and a description must be pro-

diovascular implant device with the vided for the computations and statis-
patient-specific anatomical environ- tical analyses used to evaluate the
ment. data.
(b) Classification. Class II (special (4) Human factors evaluation must be
controls). The special controls for this performed to evaluate the ability of
device are: the user interface and labeling to allow
(1) Software verification, validation, for intended users to correctly use the
and hazard analysis, with identifica- device and interpret the provided infor-
tion of appropriate mitigations, must mation.
be performed, including a full (5) Device labeling must be provided
verification and validation of the soft- that describes the following:
ware according to the predefined soft- (i) Warnings that identify anatomy
ware specifications. and image acquisition factors that may
(2) Computational modeling impact simulation results and provide
verification and validation activities cautionary guidance for interpretation
must be performed to establish the pre- of the provided simulation results;
dictive capability of the device for its (ii) Device simulation inputs and out-
indications for use. puts, and key assumptions made in the
(3) Performance validation testing simulation and determination of simu-
must be provided to demonstrate the lated outputs; and
accuracy and clinical relevance of the (iii) The computational modeling
modeling methods for the intended im- performance of the device for presented
plantation simulations, including the simulation outputs, and the supporting
following: evidence for this performance.
(i) Computational modeling results
must be compared to clinical data sup- [87 FR 79803, Dec. 28, 2022]
porting the indications for use to dem-
§ 870.1415 Coronary vascular physio-
onstrate accuracy and clinical mean- logic simulation software device.
ingfulness of the simulations;
(ii) Agreement between computa- (a) Identification. A coronary vascular
tional modeling results and clinical physiologic simulation software device
data must be assessed and dem- is a prescription device that provides
onstrated across the full intended oper- simulated functional assessment of
ating range (e.g., full range of patient blood flow in the coronary vascular
population, implant device sizes and system using data extracted from med-
patient anatomic morphologies). Any ical device imaging to solve algorithms
selection criteria or limitations of the and yield simulated metrics of physio-
samples must be described and justi- logic information (e.g., blood flow, cor-
fied; onary flow reserve, fractional flow re-
(iii) Endpoints (e.g., performance serve, myocardial perfusion). A coro-
goals) and sample sizes established nary vascular physiologic simulation
must be justified as to how they were software device is intended to generate
determined and why they are clinically results for use and review by a quali-
meaningful; and fied clinician.
(iv) Validation must be performed (b) Classification. Class II (special
and controls implemented to charac- controls). The special controls for this
terize and ensure consistency (i.e., re- device are:
peatability and reproducibility) of (1) Adequate software verification
modeling outputs: and validation based on comprehensive
(A) Testing must be performed using hazard analysis, with identification of
multiple qualified operators and using appropriate mitigations, must be per-
the procedure that will be implemented formed, including:
under anticipated conditions of use; (i) Full characterization of the tech-
and nical parameters of the software, in-
(B) The factors (e.g., medical imaging cluding:
dataset, operator) must be identified (A) Any proprietary algorithm(s)

regarding which were held constant used to model the vascular anatomy;
and which were varied during the eval- and
460
(B) Adequate description of the ex- (vi) Sensitivity and specificity must
pected impact of all applicable image be characterized across the range of
acquisition hardware features and available measurements;
characteristics on performance and any (vii) Agreement of the simulated
associated minimum specifications; measure(s) with clinically acceptable
(ii) Adequate consideration of pri- measure(s) must be assessed across the
vacy and security issues in the system full range of measurements;
design; and (viii) Comparison of the measure-
(iii) Adequate mitigation of the im- ment performance must be provided
pact of failure of any subsystem com- across the range of intended image ac-
ponents (e.g., signal detection and anal- quisition hardware; and
ysis, data storage, system communica- (ix) If the device uses a cutoff thresh-
tions and cybersecurity) with respect old or operates across a spectrum of
to incorrect patient reports and oper- disease, it must be established prior to
ator failures.
validation, and it must be justified as
(2) Adequate non-clinical perform- to how it was determined and clinically
ance testing must be provided to dem- validated;
onstrate the validity of computational
(4) Adequate validation must be per-
modeling methods for flow measure-
ment; and formed and controls implemented to
characterize and ensure consistency
(3) Clinical data supporting the pro-
(i.e., repeatability and reproducibility)
posed intended use must be provided,
of measurement outputs:
including the following:
(i) Acceptable incoming image qual-
(i) Output measure(s) must be com-
ity control measures and the resulting
pared to a clinically acceptable method
and must adequately represent the image rejection rate for the clinical
simulated measure(s) the device pro- data must be specified, and
vides in an accurate and reproducible (ii) Data must be provided within the
manner; clinical validation study or using
(ii) Clinical utility of the device equivalent datasets demonstrating the
measurement accuracy must be dem- consistency (i.e., repeatability and re-
onstrated by comparison to that of producibility) of the output that is rep-
other available diagnostic tests (e.g., resentative of the range of data quality
from literature analysis); likely to be encountered in the in-
(iii) Statistical performance of the tended use population and relevant use
device within clinical risk strata (e.g., conditions in the intended use environ-
age, relevant comorbidities, disease ment;
stability) must be reported; (A) Testing must be performed using
(iv) The dataset must be adequately multiple operators meeting planned
representative of the intended use pop- qualification criteria and using the
ulation for the device (e.g., patients, procedure that will be implemented in
range of vessel sizes, imaging device the production use of the device, and
models). Any selection criteria or limi- (B) The factors (e.g., medical imaging
tations of the samples must be fully de- dataset, operator) must be identified
scribed and justified; regarding which were held constant
(v) Statistical methods must consider and which were varied during the eval-
the predefined endpoints: uation, and a description must be pro-
(A) Estimates of probabilities of in- vided for the computations and statis-
correct results must be provided for tical analyses used to evaluate the
each endpoint, data;
(B) Where multiple samples from the (5) Human factors evaluation and val-
same patient are used, statistical anal- idation must be provided to dem-
ysis must not assume statistical inde- onstrate adequate performance of the
pendence without adequate justifica- user interface to allow for users to ac-
tion, and curately measure intended parameters,
(C) The report must provide appro- particularly where parameter settings
priate confidence intervals for each that have impact on measurements re-
performance metric; quire significant user intervention; and
461
§ 870.1420 21 CFR Ch. I (4–1–23 Edition)
(6) Device labeling must be provided tery disease, as an aid in cardiac anal-
that adequately describes the fol- ysis and diagnosis.
lowing: (b) Classification. Class II (special
(i) The device’s intended use, includ- controls). The special controls for this
ing the type of imaging data used, device are:
what the device measures and outputs (1) Clinical performance testing must
to the user, whether the measure is fulfill the following:
qualitative or quantitative, the clin- (i) Testing must include a discussion
ical indications for which it is to be of the patient population and any sta-
used, and the specific population for tistical techniques used for analyzing
which the device use is intended; the data; and
(ii) Appropriate warnings specifying (ii) Testing must be representative of
the intended patient population, iden- the intended use population for the de-
tifying anatomy and image acquisition vice. Any selection criteria or sample
factors that may impact measurement limitations must be fully described and
results, and providing cautionary guid- justified.
ance for interpretation of the provided (2) Acoustic performance testing
measurements; must evaluate microphone sensitivity,
(iii) Key assumptions made in the sound acquisition bandwidth, and am-
calculation and determination of simu- plitude accuracy. The acoustic sensor
lated measurements; specifications and mechanism used to
(iv) The measurement performance of capture heart sounds must be de-
the device for all presented param- scribed.
eters, with appropriate confidence in- (3) A scientific justification for the
tervals, and the supporting evidence validity of the algorithm(s) must be
for this performance. Per-vessel clin- provided. This justification must fulfill
ical performance, including where ap- the following:
plicable localized performance accord- (i) All inputs and outputs of the algo-
ing to vessel and segment, must be in- rithm must be fully described;
cluded as well as a characterization of (ii) The procedure for segmenting,
the measurement error across the ex- characterizing, and classifying the
pected range of measurement for key acoustic signal must be fully described;
parameters based on the clinical data; and
(v) A detailed description of the pa- (iii) This justification must include
tients studied in the clinical validation verification of the algorithm calcula-
(e.g., age, gender, race or ethnicity, tions and validation using an inde-
clinical stability, current treatment pendent data set.
regimen) as well as procedural details (4) The patient-contacting compo-
of the clinical study (e.g., scanner rep- nents of the device must be dem-
resentation, calcium scores, use of onstrated to be biocompatible.
beta-blockers or nitrates); and (5) Software verification, validation,
and hazard analysis must be performed.
(vi) Where significant human inter-
(6) Human factors/usability testing
face is necessary for accurate analysis,
must demonstrate that the user can
adequately detailed description of the
correctly use the device, including de-
analysis procedure using the device and
vice placement, based solely on reading
any data features that could affect ac-
the directions for use.
curacy of results.
(7) Performance data must dem-
[80 FR 63673, Oct. 21, 2015] onstrate the electromagnetic compat-
ibility and electrical safety of the de-
§ 870.1420 Coronary artery disease vice.
risk indicator using acoustic heart (8) Labeling must include the fol-
signals. lowing:
(a) Identification. A coronary artery (i) A description of what the device
disease risk indicator using acoustic measures and outputs to the user;
heart signals is a device that records (ii) Instructions for proper placement
heart sounds including murmurs and of the device;

vibrations to calculate a patient-spe- (iii) Instructions on care and clean-
cific risk of presence of coronary ar- ing of the device;
462
(iv) Warnings identifying sensor ac- within the balloon, is exempt from the
quisition factors that may impact premarket notification procedures in
measurement results and instructions subpart E of part 807 of this chapter
for mitigating these factors; and subject to the limitations in § 870.9.
(v) The expected performance of the
device for all intended use populations 71811, Dec. 30, 2019]
and environments.
[87 FR 32990, June 1, 2022] § 870.1660 Indicator injector.
(a) Identification. An indicator injec-
§ 870.1425 Programmable diagnostic tor is an electrically or gas-powered
computer.
device designed to inject accurately an
(a) Identification. A programmable di- indicator solution into the blood
agnostic computer is a device that can stream. This device may be used in
be programmed to compute various conjuction with a densitometer or
physiologic or blood flow parameters thermodilution device to determine
based on the output from one or more cardiac output.
electrodes, transducers, or measuring (b) Classification. Class II (perform-
devices; this device includes any asso- ance standards).
ciated commercially supplied pro-
grams. § 870.1670 Syringe actuator for an in-
(b) Classification. Class II (perform- jector.
ance standards). (a) Identification. A syringe actuator
§ 870.1435 Single-function, for an injector is an electrical device
preprogrammed diagnostic com- that controls the timing of an injection
puter. by an angiographic or indicator injec-
tor and synchronizes the injection with
(a) Identification. A single-function,
the electrocardiograph signal.
preprogrammed diagnostic computer is
a hard-wired computer that calculates
ance standards).
a specific physiological or blood-flow
parameter based on information ob- § 870.1750 External programmable
tained from one or more electrodes, pacemaker pulse generator.
transducers, or measuring devices.
(b) Classification. Class II (perform- (a) Identification. An external pro-
ance standards). grammable pacemaker pulse genera-
tors is a device that can be pro-
§ 870.1450 Densitometer. grammed to produce one or more
pulses at preselected intervals; this de-
(a) Identification. A densitometer is a
vice is used in electrophysiological
device used to measure the trans-
studies.
mission of light through an indicator
in a sample of blood. (b) Classification. Class II (perform-
ance standards). § 870.1800 Withdrawal-infusion pump.
§ 870.1650 Angiographic injector and (a) Identification. A withdrawal-infu-
syringe. sion pump is a device designed to inject
(a) Identification. An angiographic in- accurately drugs into the bloodstream
jector and syringe is a device that con- and to withdraw blood samples for use
sists of a syringe and a high-pressure in determining cardiac output.
injector which are used to inject con- (b) Classification. Class II (perform-
trast material into the heart, great ance standards).
vessels, and coronary arteries to study
the heart and vessels by x-ray photog- § 870.1875 Stethoscope.
raphy. (a) Manual stethoscope—(1) Identifica-
(b) Classification. Class II (special tion. A manual stethoscope is a me-
controls). The device, when it is a non- chanical device used to project the
patient contacting balloon inflation sounds associated with the heart, arte-
syringe intended only to inflate/deflate ries, and veins and other internal or-
balloon catheters and monitor pressure gans.
463
§ 870.1915 21 CFR Ch. I (4–1–23 Edition)
(2) Classification. Class I (general con- gizes the transducer and processes and
trols). The device is exempt from the displays the blood flow signal.
(b) Electronic stethoscope—(1) Identi- § 870.2120 Extravascular blood flow
fication. An electronic stethoscope is an probe.
electrically amplified device used to (a) Identification. An extravascular
project the sounds associated with the blood flow probe is an extravascular ul-
heart, arteries, and veins and other in- trasonic or electromagnetic probe used
ternal organs. in conjunction with a blood flowmeter
(2) Classification. Class II (special con- to measure blood flow in a chamber or
trols). The device, when it is a lung vessel.
sound monitor, is exempt from the pre-
ance standards).
ject to the limitations in § 870.9. § 870.2200 Adjunctive cardiovascular
[45 FR 7907, Feb. 5, 1980, as amended at 59 FR status indicator.
63007, Dec. 7, 1994; 66 FR 38796, July 25, 2001; (a) Identification. The adjunctive car-
84 FR 71811, Dec. 30, 2019]
diovascular status indicator is a pre-
§ 870.1915 Thermodilution probe. scription device based on sensor tech-
nology for the measurement of a phys-
(a) Identification. A thermodilution ical parameter(s). This device is in-
probe is a device that monitors cardiac tended for adjunctive use with other
output by use of thermodilution tech- physical vital sign parameters and pa-
niques; this device is commonly at-
tient information and is not intended
tached to a catheter that may have one
to independently direct therapy.
or more probes.
(b) Classification. Class II (perform- (b) Classification. Class II (special
ance standards). controls). The special controls for this
device are:
(1) Software description, verification,
Subpart C—Cardiovascular and validation based on comprehensive
Monitoring Devices hazard analysis must be provided, in-
§ 870.2050 Biopotential amplifier and cluding:
signal conditioner. (i) Full characterization of technical
parameters of the software, including
(a) Identification. A biopotential am-
any proprietary algorithm(s);
plifier and signal conditioner is a de-
vice used to amplify or condition an (ii) Description of the expected im-
electrical signal of biologic origin. pact of all applicable sensor acquisi-
(b) Classification. Class II (perform- tion hardware characteristics on per-
ance standards). formance and any associated hardware
specifications;
§ 870.2060 Transducer signal amplifier (iii) Specification of acceptable in-
and conditioner. coming sensor data quality control
(a) Identification. A transducer signal measures; and
amplifier and conditioner is a device (iv) Mitigation of impact of user
used to provide the excitation energy error or failure of any subsystem com-
for the transducer and to amplify or ponents (signal detection and analysis,
condition the signal emitted by the data display, and storage) on accuracy
transducer. of patient reports.
(b) Classification. Class II (perform- (2) Scientific justification for the va-
ance standards). lidity of the status indicator algo-
rithm(s) must be provided. Verification
§ 870.2100 Cardiovascular blood flow- of algorithm calculations and valida-
meter. tion testing of the algorithm using a
(a) Identification. A cardiovascular data set separate from the training

blood flowmeter is a device that is con- data must demonstrate the validity of
nected to a flow transducer that ener- modeling.
464
(3) Usability assessment must be pro- § 870.2210 Adjunctive predictive car-

vided to demonstrate that risk of mis- diovascular indicator.
interpretation of the status indicator (a) Identification. The adjunctive pre-
is appropriately mitigated. dictive cardiovascular indicator is a
(4) Clinical data must be provided in prescription device that uses software
support of the intended use and include
algorithms to analyze cardiovascular
the following:
vital signs and predict future cardio-
(i) Output measure(s) must be com-
vascular status or events. This device
pared to an acceptable reference meth-
is intended for adjunctive use with
od to demonstrate that the output
other physical vital sign parameters
measure(s) represent(s) the predictive
and patient information and is not in-
measure(s) that the device provides in
tended to independently direct ther-
an accurate and reproducible manner;
(ii) The data set must be representa- apy.
tive of the intended use population for (b) Classification. Class II (special
the device. Any selection criteria or controls). The special controls for this
limitations of the samples must be device are:
fully described and justified; (1) A software description and the re-
(iii) Agreement of the measure(s) sults of verification and validation
with the reference measure(s) must be testing based on a comprehensive haz-
assessed across the full measurement ard analysis and risk assessment must
range; and be provided, including:
(iv) Data must be provided within the (i) A full characterization of the soft-
clinical validation study or using ware technical parameters, including
equivalent datasets to demonstrate the algorithms;
consistency of the output and be rep- (ii) A description of the expected im-
resentative of the range of data sources pact of all applicable sensor acquisi-
and data quality likely to be encoun- tion hardware characteristics and asso-
tered in the intended use population ciated hardware specifications;
and relevant use conditions in the in- (iii) A description of sensor data
tended use environment. quality control measures;
(5) Labeling must include the fol- (iv) A description of all mitigations
lowing: for user error or failure of any sub-
(i) The type of sensor data used, in- system components (including signal
cluding specification of compatible detection, signal analysis, data display,
sensors for data acquisition; and storage) on output accuracy;
(ii) A description of what the device (v) A description of the expected time
measures and outputs to the user; to patient status or clinical event for
(iii) Warnings identifying sensor all expected outputs, accounting for
reading acquisition factors that may differences in patient condition and en-
impact measurement results; vironment; and
(iv) Guidance for interpretation of (vi) The sensitivity, specificity, posi-
the measurements, including warn- tive predictive value, and negative pre-
ing(s) specifying adjunctive use of the dictive value in both percentage and
measurements; number form.
(v) Key assumptions made in the cal- (2) A scientific justification for the
culation and determination of meas- validity of the predictive cardio-
urements; vascular indicator algorithm(s) must
(vi) The measurement performance of be provided. This justification must in-
the device for all presented param- clude verification of the algorithm cal-
eters, with appropriate confidence in- culations and validation using an inde-
tervals, and the supporting evidence pendent data set.
for this performance; and (3) A human factors and usability en-
(vii) A detailed description of the pa- gineering assessment must be provided
tients studied in the clinical validation that evaluates the risk of misinter-
(e.g., age, gender, race/ethnicity, clin- pretation of device output.
ical stability) as well as procedural de-
(4) A clinical data assessment must

tails of the clinical study. be provided. This assessment must ful-
[82 FR 35067, July 28, 2017] fill the following:
465
§ 870.2220 21 CFR Ch. I (4–1–23 Edition)
(i) The assessment must include a adjunctively along with other moni-
summary of the clinical data used, in- toring and patient information.
cluding source, patient demographics, (b) Classification. Class II (special
and any techniques used for annotating controls). The special controls for this
and separating the data. device are:
(ii) The clinical data must be rep- (1) Software description, verification,
resentative of the intended use popu- and validation based on comprehensive
lation for the device. Any selection cri- hazard analysis and risk assessment
teria or sample limitations must be must be provided, including:
fully described and justified. (i) Full characterization of technical
(iii) The assessment must dem- parameters of the software, including
onstrate output consistency using the algorithm(s);
expected range of data sources and (ii) Description of the expected im-
data quality encountered in the in- pact of all applicable sensor acquisi-
tended use population and environ- tion hardware characteristics on per-
ment. formance and any associated hardware
(iv) The assessment must evaluate specifications;
how the device output correlates with (iii) Specification of acceptable in-
the predicted event or status. coming sensor data quality control
(5) Labeling must include: measures;
(i) A description of what the device (iv) Mitigation of impact of user
measures and outputs to the user; error or failure of any subsystem com-
(ii) Warnings identifying sensor ac- ponents (signal detection and analysis,
quisition factors that may impact data display, and storage) on output
measurement results; accuracy; and
(iii) Guidance for interpretation of (v) The sensitivity, specificity, posi-
the measurements, including a state- tive predictive value, and negative pre-
ment that the output is adjunctive to dictive value in both percentage and
other physical vital sign parameters number form for clinically meaningful
and patient information; pre-specified time windows consistent
(iv) A specific time or a range of with the device output.
times before the predicted patient sta- (2) Scientific justification for the va-
tus or clinical event occurs, accounting lidity of the hemodynamic indicator
for differences in patient condition and algorithm(s) must be provided.
environment; Verification of algorithm calculations
(v) Key assumptions made during cal- and validation testing of the algorithm
culation of the output; must use an independent data set.
(vi) The type(s) of sensor data used, (3) Usability assessment must be pro-
including specification of compatible vided to demonstrate that risk of mis-
sensors for data acquisition; interpretation of the status indicator
(vii) The expected performance of the is appropriately mitigated.
device for all intended use populations (4) Clinical data must support the in-
and environments; and tended use and include the following:
(viii) Relevant characteristics of the (i) The assessment must include a
patients studied in the clinical valida- summary of the clinical data used, in-
tion (including age, gender, race or eth- cluding source, patient demographics,
nicity, and patient condition) and a and any techniques used for annotating
summary of validation results. and separating the data;
[87 FR 8191, Feb. 14, 2022] (ii) Output measure(s) must be com-
pared to an acceptable reference meth-
§ 870.2220 Adjunctive hemodynamic in- od to demonstrate that the output rep-
dicator with decision point. resents the measure(s) that the device
(a) Identification. An adjunctive provides in an accurate and reproduc-
hemodynamic indicator with decision ible manner;
point is a device that identifies and (iii) The data set must be representa-
monitors hemodynamic condition(s) of tive of the intended use population for
interest and provides notifications at a the device. Any selection criteria or

clinically meaningful decision point. limitations of the samples must be
This device is intended to be used fully described and justified;
466
(iv) Where continuous measurement and to produce a visual display of the

variables are displayed, agreement of motion of the heart; this device also
the output with the reference meas- provides any excitation energy re-
ure(s) must be assessed across the full quired by the transducer.
measurement range; and (b) Classification. Class II (perform-
(v) Data must be provided within the ance standards).
clinical validation study or using
equivalent datasets to demonstrate the § 870.2320 Ballistocardiograph.
consistency of the output and be rep- (a) Identification. A
resentative of the range of data sources ballistocardiograph is a device, includ-
and data quality likely to be encoun- ing a supporting structure on which
tered in the intended use population the patient is placed, that moves in re-
and relevant use conditions in the in- sponse to blood ejection from the
tended use environment. heart. The device often provides a vis-
(5) Labeling must include the fol- ual display.
lowing:
(i) The type of sensor data used, in-
ance standards).
cluding specification of compatible
sensors for data acquisition, and a § 870.2330 Echocardiograph.
clear description of what the device
measures and outputs to the user; (a) Identification. An echocardiograph
(ii) Warnings identifying factors that is a device that uses ultrasonic energy
may impact output results; to create images of cardiovascular
(iii) Guidance for interpretation of structures. It includes phased arrays
the outputs, including warning(s) and two-dimensional scanners.
specifying adjunctive use of the meas- (b) Classification. Class II (perform-
urements; ance standards).
(iv) Key assumptions made in the cal-
culation and determination of meas- § 870.2340 Electrocardiograph.
urements; and (a) Identification. An electrocardio-
(v) A summary of the clinical valida- graph is a device used to process the
tion data, including details of the pa- electrical signal transmitted through
tient population studied (e.g., age, gen- two or more electrocardiograph elec-
der, race/ethnicity), clinical study pro- trodes and to produce a visual display
tocols, and device performance with of the electrical signal produced by the
confidence intervals for all intended heart.
use populations. (b) Classification. Class II (perform-
[87 FR 79254, Dec. 27, 2022] ance standards).
§ 870.2300 Cardiac monitor (including § 870.2345 Electrocardiograph soft-

cardiotachometer and rate alarm). ware for over-the-counter use.
(a) Identification. A cardiac monitor (a) Identification. An electrocardio-
(including cardiotachometer and rate graph software device for over-the-
alarm) is a device used to measure the counter use creates, analyzes, and dis-
heart rate from an analog signal pro- plays electrocardiograph data and can
duced by an electrocardiograph, provide information for identifying
vectorcardiograph, or blood pressure cardiac arrhythmias. This device is not
monitor. This device may sound an intended to provide a diagnosis.
alarm when the heart rate falls outside (b) Classification. Class II (special
preset upper and lower limits. controls). The special controls for this
(b) Classification. Class II (perform- device are:
ance standards). (1) Clinical performance testing
under anticipated conditions of use
§ 870.2310 Apex cardiograph must demonstrate the following:
(vibrocardiograph). (i) The ability to obtain an electro-
(a) Identification. An apex cardio- cardiograph of sufficient quality for
graph (vibrocardiograph) is a device display and analysis; and

used to amplify or condition the signal (ii) The performance characteristics
from an apex cardiographic transducer of the detection algorithm as reported
467
§ 870.2350 21 CFR Ch. I (4–1–23 Edition)
by sensitivity and either specificity or (b) Classification. Class II (special

positive predictive value. controls). The device is exempt from
(2) Software verification, validation, the premarket notification procedures
and hazard analysis must be performed. in subpart E of part 807 of this chapter
Documentation must include a charac- subject to the limitations in § 870.9. The
terization of the technical specifica- special control for this device is the
tions of the software, including the de- FDA guidance document entitled
tection algorithm and its inputs and ‘‘Class II Special Controls Guidance
outputs. Document: Electrocardiograph Elec-
(3) Non-clinical performance testing trodes.’’ See § 870.1(e) for availability
must validate detection algorithm per- information of guidance documents.
formance using a previously adju-
dicated data set. [45 FR 7907, Feb. 5, 1980, as amended at 76 FR
43585, July 21, 2011]
(4) Human factors and usability test-
ing must demonstrate the following: § 870.2370 Electrocardiograph surface
(i) The user can correctly use the de- electrode tester.
vice based solely on reading the device
labeling; and (a) Identification. An electrocardio-
(ii) The user can correctly interpret graph surface electrode tester is a de-
the device output and understand when vice used to test the function and ap-
to seek medical care. plication of electrocardiograph elec-
(5) Labeling must include: trodes.
(i) Hardware platform and operating (b) Classification. Class II (perform-
system requirements; ance standards).
(ii) Situations in which the device
may not operate at an expected per- § 870.2390 Phonocardiograph.
formance level; (a) Identification. A phonocardiograph
(iii) A summary of the clinical per- is a device used to amplify or condition
formance testing conducted with the the signal from a heart sound trans-
device; ducer. This device furnishes the exci-
(iv) A description of what the device tation energy for the transducer and
measures and outputs to the user; and provides a visual or audible display of
(v) Guidance on interpretation of any the heart sounds.
results. (b) Classification. Class I (general con-
[86 FR 2549, Jan. 18, 2022] trols). The device is exempt from the
§ 870.2350 Electrocardiograph lead subpart E of part 807 of this chapter
switching adaptor. subject to the limitations in § 870.9.
(a) Identification. An electrocardio-
graph lead switching adaptor is a pas- 1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001]
sive switching device to which electro-
cardiograph limb and chest leads may § 870.2400 Vectorcardiograph.
be attached. This device is used to con-
nect various combinations of limb and (a) Identification. A vectorcardiograph
chest leads to the output terminals in is a device used to process the elec-
order to create standard lead combina- trical signal transmitted through elec-
tions such as leads I, II, and III. trocardiograph electrodes and to
(b) Classification. Class II (perform- produce a visual display of the mag-
ance standards). nitude and direction of the electrical
signal produced by the heart.
§ 870.2360 Electrocardiograph elec- (b) Classification. Class II (perform-
trode. ance standards).
(a) Identification. An electrocardio-
graph electrode is the electrical con- § 870.2450 Medical cathode-ray tube
ductor which is applied to the surface display.
of the body to transmit the electrical (a) Identification. A medical cathode-
signal at the body surface to a proc- ray tube display is a device designed
essor that produces an electrocardio- primarily to display selected biological
gram or vectorcardiogram. signals. This device often incorporates
468
special display features unique to a (b) Classification. Class II (special

specific biological signal. controls). The device is exempt from
(b) Classification. Class II (perform- the premarket notification procedures
ance standards). in subpart E of part 807 of this chapter
§ 870.2600 Signal isolation system.
(a) Identification. A signal isolation 71812, Dec. 30, 2019]
system is a device that electrically iso-
lates the patient from equipment con- § 870.2700 Oximeter.
nected to the commercial power supply (a) Identification. An oximeter is a de-
received from a utility company. This vice used to transmit radiation at a
isolation may be accomplished, for ex- known wavelength(s) through blood
ample, by transformer coupling, acous- and to measure the blood oxygen satu-
tic coupling, or optical coupling. ration based on the amount of reflected
(b) Classification. Class I (general con- or scattered radiation. It may be used
trols). The device is exempt from the alone or in conjunction with a
premarket notification procedures in fiberoptic oximeter catheter.
subpart E of part 807 of this chapter (b) Classification. Class II (perform-
subject to the limitations in § 870.9. ance standards).
1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001] § 870.2710 Ear oximeter.
(a) Identification. An ear oximeter is
§ 870.2620 Line isolation monitor. an extravascular device used to trans-
(a) Identification. A line isolation mit light at a known wavelength(s)
monitor is a device used to monitor the through blood in the ear. The amount
electrical leakage current from a of reflected or scattered light as indi-
power supply electrically isolated from cated by this device is used to measure
the commercial power supply received the blood oxygen saturation.
from a utility company. (b) Classification. Class II (perform-
(b) Classification. Class I (general con- ance standards).
premarket notification procedures in § 870.2750 Impedance phlebograph.
subpart E of part 807 of this chapter (a) Identification. An impedance
subject to the limitations in § 870.9. phlebograph is a device used to provide
[45 FR 7907, Feb. 5, 1980, as amended at 61 FR a visual display of the venous pulse or
1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001] drainage by measuring electrical im-
pedance changes in a region of the
§ 870.2640 Portable leakage current body.
alarm. (b) Classification. Class II (perform-
(a) Identification. A portable leakage ance standards).
current alarm is a device used to meas-
ure the electrical leakage current be- § 870.2770 Impedance plethysmograph.
tween any two points of an electrical (a) Identification. An impedance
system and to sound an alarm if the plethysmograph is a device used to es-
current exceeds a certain threshold. timate peripheral blood flow by meas-
(b) Classification. Class I (general con- uring electrical impedance changes in
trols). The device is exempt from the a region of the body such as the arms
premarket notification procedures in and legs.
subpart E of part 807 of this chapter (b) Classification. Class II (special
subject to the limitations in § 870.9. controls). The device, when it is a body
[45 FR 7907, Feb. 5, 1980, as amended at 61 FR composition analyzer which is not in-
1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001] tended to diagnose or treat any med-
ical condition, is exempt from the pre-
§ 870.2675 Oscillometer. market notification procedures in sub-
(a) Identification. An oscillometer is a part E of part 807 of this chapter sub-
device used to measure physiological

oscillations of any kind, e.g., changes [45 FR 7907, Feb. 5, 1980, as amended at 84 FR
in the volume of arteries. 71812, Dec. 30, 2019]
469
§ 870.2780 21 CFR Ch. I (4–1–23 Edition)
§ 870.2780 Hydraulic, pneumatic, or teria or sample limitations must be

photoelectric plethysmographs. fully described and justified.
(a) Identification. A hydraulic, pneu- (ii) The assessment must dem-
matic, or photoelectric onstrate output consistency using the
plethysmograph is a device used to es- expected range of data sources and
timate blood flow in a region of the data quality encountered in the in-
body using hydraulic, pneumatic, or tended use population and environ-
photoelectric measurement techniques. ment.
(iii) The assessment must compare
device output with a clinically accu-
ance standards).
rate patient-contacting relevant com-
§ 870.2785 Software for optical camera- parator device in an accurate and re-
based measurement of pulse rate, producible manner.
heart rate, breathing rate, and/or (3) A human factors and usability en-
respiratory rate. gineering assessment must be provided
that evaluates the risk of improper
(a) Identification. The device uses
measurement.
software algorithms to analyze video
(4) Labeling must include:
signal and estimate pulse rate, heart
(i) A description of what the device
rate, breathing rate, and/or respiratory
measures and outputs to the user;
rate. This device is not intended to
(ii) Warnings identifying sensor ac-
independently direct therapy.
quisition factors or subject conditions
(b) Classification. Class II (special or characteristics (garment types/tex-
controls). The special controls for this tures, motion, etc.) that may impact
device are: measurement results;
(1) A software description and the re- (iii) Guidance for interpretation of
sults of verification and validation the measurements, including a state-
testing based on a comprehensive haz- ment that the output is adjunctive to
ard analysis and risk assessment must other physical vital sign parameters
include: and patient information;
(i) A full characterization of the soft- (iv) The expected performance of the
ware technical parameters, including device for all intended use populations
algorithms; and environments; and
(ii) If required image acquisition (v) Robust instructions to ensure cor-
hardware is not included with the de- rect system setup.
vice, full specifications of the hardware
[88 CFR 6167, Jan. 31, 2023]
requirements and testing to dem-
onstrate the specified hardware ensures § 870.2786 Hardware and software for
adequate data for validated and accu- optical camera-based measurement
rate measurements; of pulse rate, heart rate, breathing
(iii) A description of the expected im- rate, and/or respiratory rate.
pact of all applicable sensor acquisi- (a) Identification. The device uses an
tion hardware characteristics and asso- optical sensor system and software al-
ciated hardware specifications; gorithms to obtain and analyze video
(iv) A description of all mitigations signal and estimate pulse rate, heart
for user error or failure of any sub- rate, breathing rate, and/or respiratory
system components (including signal rates. This device is not intended to
detection, signal analysis, data display, independently direct therapy.
and storage) on output accuracy; and (b) Classification. Class II (special
(v) Software documentation must in- controls). The special controls for this
clude a cybersecurity vulnerability and device are:
management process to assure software (1) A software description and the re-
functionality. sults of verification and validation
(2) Clinical data must be provided. testing based on a comprehensive haz-
This assessment must fulfill the fol- ard analysis and risk assessment must
lowing: include:
(i) The clinical data must be rep- (i) A full characterization of the soft-
resentative of the intended use popu- ware technical parameters, including
lation for the device. Any selection cri- algorithms;
470
(ii) A description of all mitigations § 870.2790 Photoplethysmograph anal-

for user error or failure of any sub- ysis software for over-the-counter
system components (including signal use.
detection, signal analysis, data display, (a) Identification. A
and storage) on output accuracy; and photoplethysmograph analysis soft-
(iii) Software documentation must ware device for over-the-counter use
include a cybersecurity vulnerability analyzes photoplethysmograph data
and management process to assure and provides information for identi-
software functionality. fying irregular heart rhythms. This de-
(2) Performance testing must dem- vice is not intended to provide a diag-
onstrate the safety of any illuminating nosis.
optics.
(3) Clinical data must be provided. device are:
This assessment must fulfill the fol- (1) Clinical performance testing must
lowing: demonstrate the performance charac-
(i) The clinical data must be rep- teristics of the detection algorithm
resentative of the intended use popu- under anticipated conditions of use.
lation for the device. Any selection cri- (2) Software verification, validation,
teria or sample limitations must be and hazard analysis must be performed.
fully described and justified. Documentation must include a charac-
(ii) The assessment must dem- terization of the technical specifica-
onstrate output consistency using the tions of the software, including the de-
expected range of data sources and tection algorithm and its inputs and
data quality encountered in the in- outputs.
tended use population and environ- (3) Non-clinical performance testing
must demonstrate the ability of the de-
ment.
vice to detect adequate
(iii) The assessment must compare photoplethysmograph signal quality.
device output with a clinically accu- (4) Human factors and usability test-
rate patient-contacting relevant coming must demonstrate the following:
parator device in an accurate and re- (i) The user can correctly use the de-
producible manner. vice based solely on reading the device
(4) A human factors and usability en- labeling; and
gineering assessment must be provided (ii) The user can correctly interpret
that evaluates the risk of improper the device output and understand when
measurement. to seek medical care.
(5) Labeling must include: (5) Labeling must include:
(i) A description of what the device (i) Hardware platform and operating
measures and outputs to the user; system requirements;
(ii) Situations in which the device
(ii) Warnings identifying sensor ac-
may not operate at an expected per-
quisition factors or subject conditions
formance level;
or characteristics (garment types/tex-
(iii) A summary of the clinical per-
tures, motion, etc.) that may impact formance testing conducted with the
measurement results; device;
(iii) Guidance for interpretation of (iv) A description of what the device
the measurements, including a state- measures and outputs to the user; and
ment that the output is adjunctive to (v) Guidance on interpretation of any
other physical vital sign parameters results.
and patient information;
[87 FR 6419, Feb. 4, 2022]
(iv) The expected performance of the
device for all intended use populations § 870.2800 Medical magnetic tape re-
and environments; and corder.
(v) Robust instructions to ensure cor- (a) Identification. A medical magnetic
rect system setup. tape recorder is a device used to record
[88 FR 976, Jan. 6, 2023]

and play back signals from, for exam-
ple, physiological amplifiers, signal
conditioners, or computers.
471
§ 870.2810 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class II (perform- Measurement System.’’ See § 870.1 (e)

ance standards). for the availability of this guidance
document.
§ 870.2810 Paper chart recorder.
[71 FR 7871, Feb. 15, 2006]
(a) Identification. A paper chart re-
corder is a device used to print on § 870.2860 Heart sound transducer.
paper, and create a permanent record
of the signal from, for example, a phys- (a) Identification. A heart sound
iological amplifier, signal conditioner, transducer is an external transducer
or computer. that exhibits a change in mechanical
(b) Classification. Class I (general con- or electrical properties in relation to
trols). The device is exempt from the sounds produced by the heart. This de-
premarket notification procedures in vice may be used in conjunction with a
subpart E of part 807 of this chapter phonocardiograph to record heart
subject to the limitations in § 870.9. sounds.
[45 FR 7907, Feb. 5, 1980, as amended at 61 FR ance standards).
1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001]
§ 870.2870 Catheter tip pressure trans-
§ 870.2840 Apex cardiographic transducer.
ducer.
(a) Identification. A catheter tip pres-
(a) Identification. An apex cardio-
sure transducer is a device incor-
graphic transducer is a device used to
porated into the distal end of a cath-
detect motion of the heart (accelera-
eter. When placed in the bloodstream,
tion, velocity, or displacement) by
its mechanical or electrical properties
changes in the mechanical or electrical
change in relation to changes in blood
properties of the device.
pressure. These changes are trans-
mitted to accessory equipment for
ance standards).
processing.
§ 870.2850 Extravascular blood pres- (b) Classification. Class II (perform-
sure transducer. ance standards).
(a) Identification. An extravascular § 870.2880 Ultrasonic transducer.
blood pressure transducer is a device
used to measure blood pressure by (a) Identification. An ultrasonic trans-
changes in the mechanical or electrical ducer is a device applied to the skin to
properties of the device. The proximal transmit and receive ultrasonic energy
end of the transducer is connected to a that is used in conjunction with an
pressure monitor that produces an ana- echocardiograph to provide imaging of
log or digital electrical signal related cardiovascular structures. This device
to the electrical or mechanical changes includes phased arrays and two-dimen-
produced in the transducer. sional scanning transducers.
(b) Classification. Class II (perform- (b) Classification. Class II (perform-
ance standards). ance standards).
§ 870.2855 Implantable Intra-aneurysm § 870.2890 Vessel occlusion transducer.

Pressure Measurement System. (a) Identification. A vessel occlusion
(a) Identification. Implantable intra- transducer is a device used to provide
aneurysm pressure measurement sys- an electrical signal corresponding to
tem is a device used to measure the sounds produced in a partially occluded
intra-sac pressure in a vascular aneu- vessel. This device includes motion,
rysm. The device consists of a pressure sound, and ultrasonic transducers.
transducer that is implanted into the (b) Classification. Class II (perform-
aneurysm and a monitor that reads the ance standards).
pressure from the transducer.
(b) Classification. Class II (special § 870.2900 Patient transducer and elec-
controls). The special control is FDA’s trode cable (including connector).
guidance document entitled ‘‘Class II (a) Identification. A patient trans-

Special Controls Guidance Document: ducer and electrode cable (including
Implantable Intra-Aneurysm Pressure connector) is an electrical conductor
472
used to transmit signals from, or power § 870.3300 Vascular embolization de-

or excitation signals to, patient-con- vice.
nected electrodes or transducers. (a) Identification. A vascular
(b) Classification. Class II (perform- embolization device is an intravascular
ance standards). implant intended to control hem-
§ 870.2910 Radiofrequency physio- orrhaging due to aneurysms, certain
logical signal transmitter and re- types of tumors (e.g., nephroma,
ceiver. hepatoma, uterine fibroids), and
arteriovenous malformations. This
(a) Identification. A radiofrequency
physiological signal transmitter and does not include cyanoacrylates and
receiver is a device used to condition a other embolic agents, which act by po-
physiological signal so that it can be lymerization or precipitation.
transmitted via radiofrequency from Embolization devices used in neuro-
one location to another, e.g., a central vascular applications are also not in-
monitoring station. The received signal cluded in this classification, see
is reconditioned by the device into its § 882.5950 of this chapter.
original format so that it can be dis- (b) Classification. Class II (special
played. controls.) The special control for this
(b) Classification. Class II (perform- device is the FDA guidance document
ance standards). entitled ‘‘Class II Special Controls
Guidance Document: Vascular and
§ 870.2920 Telephone electrocardio- Neurovascular Embolization Devices.’’
graph transmitter and receiver. For availability of this guidance docu-
(a) Identification. A telephone electro- ment, see § 870.1(e).
cardiograph transmitter and receiver is [69 FR 77899, Dec. 29, 2004]
a device used to condition an electro-
cardiograph signal so that it can be § 870.3375 Cardiovascular
transmitted via a telephone line to an- intravascular filter.
other location. This device also in- (a) Identification. A cardiovascular
cludes a receiver that reconditions the intravascular filter is an implant that
received signal into its original format is placed in the inferior vena cava for
so that it can be displayed. The device the purpose of preventing pulmonary
includes devices used to transmit and thromboemboli (blood clots generated
receive pacemaker signals. in the lower limbs and broken loose
(b) Classification. Class II (perform- into the blood stream) from flowing
ance standards). into the right side of the heart and the
pulmonary circulation.
Subpart D—Cardiovascular (b) Classification. Class II. The special
Prosthetic Devices controls for this device are:
(1) ‘‘Use of International Standards
§ 870.3250 Vascular clip. Organization’s ISO 10993 ‘Biological
(a) Identification. A vascular clip is an Evaluation of Medical Devices Part I:
implanted extravascular device de- Evaluation and Testing,’ ’’ and
signed to occlude, by compression, (2) FDA’s:
blood flow in small blood vessels other (i) ‘‘510(k) Sterility Review Guidance
than intracranial vessels. and Revision of 2/12/90 (K90–1)’’ and
(b) Classification. Class II (perform- (ii) ‘‘Guidance for Cardiovascular
ance standards). Intravascular Filter 510(k) Submis-
sions.’’
§ 870.3260 Vena cava clip. [45 FR 7907, Feb. 5, 1980, as amended at 52 FR
(a) Identification. A vena cava clip is 17736, May 11, 1987; 65 FR 17144, Mar. 31, 2000]
an implanted extravascular device de-
signed to occlude partially the vena § 870.3450 Vascular graft prosthesis.
cava for the purpose of inhibiting the (a) Identification. A vascular graft
flow of thromboemboli through that prosthesis is an implanted device in-
vessel. tended to repair, replace, or bypass sec-

(b) Classification. Class II (perform- tions of native or artificial vessels, ex-
ance standards). cluding coronary or cerebral
473
§ 870.3460 21 CFR Ch. I (4–1–23 Edition)
vasculature, and to provide vascular detailed summary of the non-clinical

access. It is commonly constructed of and clinical evaluations pertinent to
materials such as polyethylene use of the device.
terephthalate and polytetrafluoro-
[77 FR 8119, Feb. 14, 2012]
ethylene, and it may be coated with a
biological coating, such as albumin or § 870.3470 Intracardiac patch or pledg-
collagen, or a synthetic coating, such et made of polypropylene, poly-
as silicone. The graft structure itself is ethylene terephthalate, or poly-
not made of materials of animal origin, tetrafluoroethylene.
including human umbilical cords. (a) Identification. An intracardiac
(b) Classification. Class II (special patch or pledget made of poly-
controls). The special control for this propylene, polyethylene terephthalate,
device is the FDA guidance document or polytetrafluoroethylene is a fabric
entitled ‘‘Guidance Document for Vas- device placed in the heart that is used
cular Prostheses 510(k) Submissions.’’ to repair septal defects, for patch graft-
[66 FR 18542, Apr. 10, 2001] ing, to repair tissue, and to buttress su-
tures.
§ 870.3460 Endovascular Suturing Sys- (b) Classification. Class II (perform-
tem. ance standards).
(a) Identification. An endovascular su-
turing system is a medical device in- § 870.3535 Intra-aortic balloon and
tended to provide fixation and sealing control system.
between an endovascular graft and the (a) Identification. An intra-aortic bal-
native artery. The system is comprised loon and control system is a prescrip-
of the implant device and an tion device that consists of an inflat-
endovascular delivery device used to able balloon, which is placed in the
implant the endovascular suture. aorta to improve cardiovascular func-
(b) Classification. Class II (special tioning during certain life-threatening
controls). The special controls for this emergencies, and a control system for
device are: regulating the inflation and deflation
(1) The device should be dem- of the balloon. The control system,
onstrated to be biocompatible; which monitors and is synchronized
(2) Sterility and shelf life testing with the electrocardiogram, provides a
should demonstrate the sterility of pa- means for setting the inflation and de-
tient-contacting components and the flation of the balloon with the cardiac
shelf-life of these components; cycle.
(3) Non-clinical and clinical perform- (b) Classification. (1) Class II (special
ance testing should demonstrate sub- controls) when the device is indicated
stantial equivalence in safety and ef- for acute coronary syndrome, cardiac
fectiveness, including durability, com- and non-cardiac surgery, or complica-
patibility, migration resistance, corro- tions of heart failure. The special con-
sion resistance, and delivery and de- trols for this device are:
ployment; (i) Appropriate analysis and non-clin-
(4) Non-clinical testing should evalu- ical testing must be conducted to vali-
ate the compatibility of the device in date electromagnetic compatibility
an magnetic resonance (MR) environ- and electrical safety of the device;
ment; (ii) Software verification, validation,
(5) Appropriate analysis and non-clin- and hazard analysis must be performed;
ical testing should validate electro- (iii) The device must be dem-
magnetic compatibility (EMC) and onstrated to be biocompatible;
electrical safety; (iv) Sterility and shelf-life testing
(6) The sale, distribution, and use of must demonstrate the sterility of pa-
the device are restricted to prescrip- tient-contacting components and the
tion use in accordance with 21 CFR shelf life of these components;
801.109 of this chapter; and (v) Non-clinical performance evalua-
(7) Labeling must bear all information of the device must demonstrate
tion required for the safe and effective mechanical integrity, durability, and
use of the device as outlined in reliability to support its intended pur-
§ 801.109(c) of this chapter, including a pose; and
474
(vi) Labeling must include a detailed PDP in effect before being placed in
summary of the device- and procedure- commercial distribution.
related complications pertinent to use
of the device. 17736, May 11, 1987; 76 FR 50666, Aug. 16, 2011]
(2) Class III (premarket approval)
when the device is indicated for septic § 870.3600 External pacemaker pulse
shock and pulsatile flow generation. generator.
(c) Date premarket approval application (a) Identification. An external pace-
(PMA) or notice of completion of product maker pulse generator (EPPG) is a pre-
development protocol (PDP) is required. A scription device that has a power sup-
PMA or notice of completion of a PDP ply and electronic circuits that
is required to be filed with the Food produce a periodic electrical pulse to
and Drug Administration on or before stimulate the heart. This device, which
March 31, 2014, for any intra-aortic bal- is used outside the body, is used as a
loon and control system indicated for temporary substitute for the heart’s
septic shock or pulsatile flow genera- intrinsic pacing system until a perma-
tion that was in commercial distribu- nent pacemaker can be implanted, or
tion before May 28, 1976, or that has, on to control irregular heartbeats in pa-
or before March 31, 2014, been found to tients following cardiac surgery or a
be substantially equivalent to any myocardial infarction. The device may
intra-aortic balloon and control system have adjustments for impulse strength,
indicated for septic shock or pulsatile duration, R-wave sensitivity, and other
flow generation that was in commer- pacing variables.
cial distribution before May 28, 1976. (b) Classification. Class II (special
Any other intra-aortic balloon and con- controls). The special controls for this
trol system indicated for septic shock device are:
or pulsatile flow generation shall have (1) Appropriate analysis/testing must
an approved PMA or declared com- validate electromagnetic compatibility
pleted PDP in effect before being (EMC) within a hospital environment.
placed in commercial distribution. (2) Electrical bench testing must
demonstrate device safety during in-
[78 FR 79303, Dec. 31, 2013]
tended use. This must include testing
§ 870.3545 Ventricular bypass (assist) with the specific power source (i.e., bat-
device. tery power, AC mains connections, or
both).
(a) Identification. A ventricular by- (3) Non-clinical performance testing
pass (assist) device is a device that as- data must demonstrate the perform-
sists the left or right ventricle in main- ance characteristics of the device.
taining circulatory blood flow. The de- Testing must include the following:
vice is either totally or partially im- (i) Testing must demonstrate the ac-
planted in the body. curacy of monitoring functions,
(b) Classification. Class III (premarket alarms, measurement features, thera-
approval). peutic features, and all adjustable or
(c) Date PMA or notice of completion of programmable parameters as identified
PDP is required. A PMA or notice of in labeling;
completion of a PDP is required to be (ii) Mechanical bench testing of ma-
filed with the Food and Drug Adminis- terial strength must demonstrate that
tration on or before November 21, 2011, the device and connection cables will
for any ventricular bypass (assist) de- withstand forces or conditions encoun-
vice that was in commercial distribu- tered during use;
tion before May 28, 1976, or that has, on (iii) Simulated use analysis/testing
or before November 21, 2011, been found must demonstrate adequate user inter-
to be substantially equivalent to any face for adjustable parameters, per-
ventricular bypass (assist) device that formance of alarms, display screens,
was in commercial distribution before interface with external devices (e.g.
May 28, 1976. Any other ventricular by- data storage, printing), and indi-
pass (assist) device shall have an ap- cator(s) functionality under intended
proved PMA or declared completed use conditions; and
475
§ 870.3605 21 CFR Ch. I (4–1–23 Edition)
(iv) Methods and instructions for tery power, AC mains connections, or

cleaning the pulse generator and con- both).
nection cables must be validated. (3) Non-clinical performance testing
(4) Appropriate software verification, data must demonstrate the perform-
validation, and hazard analysis must ance characteristics of the device.
be performed. Testing must include the following:
(5) Labeling must include the fol- (i) Testing must demonstrate the ac-
lowing: curacy of monitoring functions,
(i) The labeling must clearly state alarms, measurement features, thera-
that these devices are intended for use
peutic features, and all adjustable or
in a hospital environment and under
programmable parameters as identified
the supervision of a clinician trained in
in labeling;
their use;
(ii) Connector terminals should be (ii) Mechanical bench testing of ma-
clearly, unambiguously marked on the terial strength must demonstrate that
outside of the EPPG device. The mark- the device and connection cables will
ings should identify positive (+) and withstand forces or conditions encoun-
negative (¥) polarities. Dual chamber tered during use;
devices should clearly identify atrial (iii) Simulated use analysis/testing
and ventricular terminals; must demonstrate adequate user inter-
(iii) The labeling must list all pacing face for adjustable parameters, per-
modes available in the device; formance of alarms, display screens,
(iv) Labeling must include a detailed interface with external devices (e.g.
description of any special capabilities data storage, printing), and indi-
(e.g., overdrive pacing or automatic cator(s) functionality under intended
mode switching); and use conditions; and
(v) Appropriate electromagnetic com- (iv) Methods and instructions for
patibility information must be in- cleaning the pulse generator and con-
cluded. nection cables must be validated.
[81 FR 22529, Apr. 18, 2016] (4) Appropriate software verification,
validation, and hazard analysis must
§ 870.3605 Pacing system analyzer. be performed.
(a) Identification. A pacing system an- (5) Labeling must include the fol-
alyzer (PSA) is a prescription device lowing:
that combines the functionality of a (i) The labeling must clearly state
pacemaker electrode function tester that these devices are intended for use
(§ 870.3720) and an external pacemaker in a hospital environment and under
pulse generator (EPPG) (§ 870.3600). It is the supervision of a clinician trained in
connected to a pacemaker lead and their use;
uses a power supply and electronic cir- (ii) Connector terminals should be
cuits to supply an accurately cali- clearly, unambiguously marked on the
brated, variable pacing pulse for meas- outside of the PSA. The markings
uring the patient’s pacing threshold should identify positive (+) and nega-
and intracardiac R-wave potential. A
tive (¥) polarities. Dual chamber de-
PSA may be a single, dual, or triple
vices should clearly identify atrial and
chamber system and can simulta-
ventricular terminals. Triple chamber
neously deliver pacing therapy while
devices should clearly identify atrial,
testing one or more implanted pacing
right ventricular, and left ventricular
leads.
(b) Classification. Class II (special terminals;
controls). The special controls for this (iii) The labeling must list all pacing
device are: modes available in the device;
(1) Appropriate analysis/testing must (iv) Labeling must include a detailed
validate electromagnetic compatibility description of any special capabilities
(EMC) within a hospital environment. (e.g., overdrive pacing or automatic
(2) Electrical bench testing must mode switching);
demonstrate device safety during in- (v) Labeling must limit the use of ex-
tended use. This must include testing ternal pacing to the implant procedure;
with the specific power source (i.e., bat- and
476
(vi) Appropriate electromagnetic § 870.3630 Pacemaker generator func-

compatibility information must be in- tion analyzer.
cluded. (a) Identification. A pacemaker gener-
[81 FR 22350, Apr. 18, 2016] ator function analyzer is a device that
is connected to a pacemaker pulse gen-
§ 870.3610 Implantable pacemaker erator to test any or all of the genera-
pulse generator.
tor’s parameters, including pulse dura-
(a) Identification. An implantable tion, pulse amplitude, pulse rate, and
pacemaker pulse generator is a device sensing threshold.
that has a power supply and electronic (b) Classification. Class II (perform-
circuits that produce a periodic elec- ance standards).
trical pulse to stimulate the heart.
This device is used as a substitute for § 870.3640 Indirect pacemaker gener-
the heart’s intrinsic pacing system to ator function analyzer.
correct both intermittent and contin-
(a) Identification. An indirect pace-
uous cardiac rhythm disorders. This
maker generator function analyzer is
device may include triggered, inhib-
an electrically powered device that is
ited, and asynchronous modes and is
implanted in the human body. used to determine pacemaker function
(b) Classification. Class III (premarket or pacemaker battery function by peri-
approval). odically monitoring an implanted pace-
(c) Date PMA or notice of completion of maker’s pulse rate and pulse width.
PDP is required. A PMA or notice of The device is noninvasive, and it de-
completion of a PDP is required to be tects pacemaker pulse rate and width
filed with the Food and Drug Adminis- via external electrodes in contact with
tration on or before September 20, 2012, the patient’s skin.
for any implantable pacemaker pulse (b) Classification. Class II (perform-
generator device that was in commer- ance standards).
cial distribution before May 28, 1976, or
that has, on or before September 20, § 870.3650 Pacemaker polymeric mesh
2012, been found to be substantially bag.
equivalent to any implantable pace- (a) Identification. A pacemaker poly-
maker pulse generator device that was meric mesh bag is an implanted device
in commercial distribution before May used to hold a pacemaker pulse gener-
28, 1976. Any other implantable pace- ator. The bag is designed to create a
maker pulse generator device shall stable implant environment for the
have an approved PMA or declared pulse generator.
completed PDP in effect before being (b) Classification. Class I (general con-
placed in commercial distribution. trols). The device is exempt from the
[45 FR 7907, Feb. 5, 1980, as amended at 52 FR premarket notification procedures in
17736, May 11, 1987; 77 FR 37576, June 22, 2012] subpart E of part 807 of this chapter
§ 870.3620 Pacemaker lead adaptor.
(a) Identification. A pacemaker lead 1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001]
adaptor is a device used to adapt a
pacemaker lead so that it can be con- § 870.3670 Pacemaker charger.
nected to a pacemaker pulse generator
produced by a different manufacturer. (a) Identification. A pacemaker charg-
(b) Classification. Class II (special er is a device used transcutaneously to
controls). The special control for this recharge the batteries of a recharge-
device is the FDA guidance document able pacemaker.
entitled ‘‘Guidance for the Submission (b) Classification. Class I (general con-
of Research and Marketing Applica- trols). The device is exempt from the
tions for Permanent Pacemaker Leads premarket notification procedures in
and for Pacemaker Lead Adaptor 510(k) subpart E of part 807 of this chapter
Submissions.’’ subject to the limitations in § 870.9.
[45 FR 7907, Feb. 5, 1980, as amended at 52 FR [45 FR 7907, Feb. 5, 1980, as amended at 61 FR
17736, May 11, 1987; 66 FR 18542, Apr. 10, 2001] 1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001]
477
§ 870.3680 21 CFR Ch. I (4–1–23 Edition)
§ 870.3680 Cardiovascular permanent (b) Classification. Class I (general con-

or temporary pacemaker electrode. trols). The device is exempt from the
(a) Temporary pacemaker electrode—(1) premarket notification procedures in
Identification. A temporary pacemaker subpart E of part 807 of this chapter
electrode is a device consisting of flexi- subject to the limitations in § 870.9.
ble insulated electrical conductors [45 FR 7907, Feb. 5, 1980, as amended at 61 FR
with one end connected to an external 1121, Jan. 16, 1996; 66 FR 38796, July 25, 2001]
pacemaker pulse generator and the
other end applied to the heart. The de- § 870.3700 Pacemaker programmers.
vice is used to transmit a pacing elec-
trical stimulus from the pulse gener- (a) Identification. A pacemaker pro-
ator to the heart and/or to transmit grammer is a device used to
the electrical signal of the heart to the noninvasively change one or more of
pulse generator. the electrical operating characteristics
(2) Classification. Class II (perform- of a pacemaker.
ance standards). (b) Classification. Class III (premarket
(b) Permanent pacemaker electrode—(1) approval).
Identification. A permanent pacemaker (c) Date PMA or notice of completion of
electrode is a device consisting of flexi- PDP is required. A PMA or notice of
ble insulated electrical conductors completion of a PDP is required to be
with one end connected to an filed with the Food and Drug Adminis-
implantable pacemaker pulse gener- tration on or before September 20, 2012,
ator and the other end applied to the for any pacemaker programmer that
heart. The device is used to transmit a was in commercial distribution before
pacing electrical stimulus from the May 28, 1976, or that has, on or before
pulse generator to the heart and/or to September 20, 2012, been found to be
transmit the electrical signal of the substantially equivalent to any pace-
heart to the pulse generator. maker programmer that was in com-
(2) Classification. Class III (premarket mercial distribution before May 28,
approval). 1976. Any other pacemaker programmer
(c) Date PMA or notice of completion of shall have an approved PMA or de-
PDP is required. A PMA or notice of
clared completed PDP in effect before
completion of a PDP is required to be
filed with the Food and Drug Adminis-
tration on or before October 4, 2012, for tion.
any permanent pacemaker electrode [45 FR 7907, Feb. 5, 1980, as amended at 52 FR
device that was in commercial dis- 17736, May 11, 1987; 77 FR 37573, June 22, 2012]
tribution before May 28, 1976, or that
has, on or before October 4, 2012, been § 870.3710 Pacemaker repair or re-
found to be substantially equivalent to placement material.
any permanent pacemaker electrode (a) Identification. A pacemaker repair
device that was in commercial dis- or replacement material is an adhesive,
tribution before May 28, 1976. Any a sealant, a screw, a crimp, or any
other pacemaker repair or replacement other material used to repair a pace-
material device shall have an approved maker lead or to reconnect a pace-
PMA or declared completed PDP in ef-
maker lead to a pacemaker pulse gen-
fect before being placed in commercial
erator.
distribution.
(b) Classification. Class III (premarket
[45 FR 7907, Feb. 5, 1980, as amended at 52 FR approval).
17736, May 11, 1987; 77 FR 39927, July 6, 2012] (c) Date PMA or notice of completion of
§ 870.3690 Pacemaker test magnet. PDP is required. A PMA or notice of
completion of a PDP is required to be
(a) Identification. A pacemaker test filed with the Food and Drug Adminis-
magnet is a device used to test an in- tration on or before November 21, 2011,
hibited or triggered type of pacemaker for any pacemaker repair or replace-
pulse generator and cause an inhibited

ment material device that was in com-
or triggered generator to revert to
mercial distribution before May 28,
asynchronous operation.
478
1976, or that has, on or before Novem- vice used to decrease arterial pressure
ber 21, 2011, been found to be substan- by stimulating Hering’s nerve at the
tially equivalent to any pacemaker re- carotid sinus.
pair or replacement material device (b) Classification. Class III (premarket
that was in commercial distribution approval).
before May 28, 1976. Any other pace- (c) Date PMA or notice of completion of
maker repair or replacement material a PDP is required. A PMA or a notice of
device shall have an approved PMA or completion of a PDP is required to be
declared completed PDP in effect be- filed with the Food and Drug Adminis-
fore being placed in commercial dis- tration on or before December 26, 1996
tribution. for any carotid sinus nerve stimulator
[45 FR 7907, Feb. 5, 1980, as amended at 52 FR that was in commercial distribution
17736, May 11, 1987; 76 FR 50666, Aug. 16, 2011] before May 28, 1976, or that has, on or
before December 26, 1996 been found to
§ 870.3720 Pacemaker electrode func- be substantially equivalent to a carotid
tion tester. sinus nerve stimulator that was in
(a) Identification. A pacemaker elec- commercial distribution before May 28,
trode function tester is a device which 1976. Any other carotid sinus nerve
is connected to an implanted pace- stimulator shall have an approved
maker lead that supplies an accurately PMA or a declared completed PDP in
calibrated, variable pacing pulse for effect before being placed in commer-
measuring the patient’s pacing thresh- cial distribution.
old and intracardiac R-wave potential.
(b) Classification. Class II (perform- [45 FR 7907, Feb. 5, 1980, as amended at 52 FR
17736, May 11, 1987; 61 FR 50706, Sept. 27, 1996]
ance standards).
§ 870.3730 Pacemaker service tools. § 870.3925 Replacement heart valve.
(a) Identification. Pacemaker service (a) Identification. A replacement
tools are devices such as screwdrivers heart valve is a device intended to per-
and Allen wrenches, used to repair a form the function of any of the heart’s
pacemaker lead or to reconnect a pace- natural valves. This device includes
maker lead to a pacemaker generator. valves constructed of prosthetic mate-
(b) Classification. Class I (general con- rials, biologic valves (e.g., porcine
trols). The device is exempt from the valves), or valves constructed of a com-
premarket notification procedures in bination of prosthetic and biologic ma-
subpart E of part 807 of this chapter terials.
subject to the limitations in § 870.9. (b) Classification. Class III (premarket
approval).
25049, June 12, 1989; 66 FR 38797, July 25, 2001] (c) Date premarket approval application
(PMA) or notice of completion of a prod-
§ 870.3800 Annuloplasty ring. uct development protocol (PDP) is re-
(a) Identification. An annuloplasty quired. A PMA or a notice of comple-
ring is a rigid or flexible ring im- tion of a PDP is required to be filed
planted around the mitral or tricuspid with the Food and Drug Administra-
heart valve for reconstructive treat- tion on or before December 9, 1987 for
ment of valvular insufficiency. any replacement heart valve that was
(b) Classification. Class II (special in commercial distribution before May
controls). The special control for this 28, 1976, or that has on or before De-
device is the FDA guidance document cember 9, 1987 been found to be sub-
entitled ‘‘Guidance for Annuloplasty stantially equivalent to a replacement
Rings 510(k) Submissions.’’ heart valve that was in commercial
distribution before May 28, 1976. Any
other replacement heart valve shall
17736, May 11, 1987; 66 FR 18542, Apr. 10, 2001]
have an approved PMA or a declared
§ 870.3850 Carotid sinus nerve stimu- completed PDP in effect before being
lator. placed in commercial distribution.
(a) Identification. A carotid sinus [45 FR 7907, Feb. 5, 1980, as amended at 52 FR

nerve stimulator is an implantable de- 18163, May 13, 1987; 52 FR 23137, June 17, 1987]
479
§ 870.3935 21 CFR Ch. I (4–1–23 Edition)
§ 870.3935 Prosthetic heart valve hold- not limited to, the console (hardware),
er. software, and disposables, including,
(a) Identification. A prosthetic heart but not limited to, an oxygenator,
valve holder is a device used to hold a blood pump, heat exchanger, cannulae,
replacement heart valve while it is tubing, filters, and other accessories
being sutured into place. (e.g., monitors, detectors, sensors, con-
(b) Classification. Class I. The device nectors).
is exempt from the premarket notifica- (b) Classification—Class II (special
tion procedures in subpart E of part 807 controls). The special controls for this
of this chapter. device are:
(1) The technological characteristics
[45 FR 7907, Feb. 5, 1980, as amended at 61 FR of the device must ensure that the ge-
1121, Jan. 16, 1996] ometry and design parameters are con-
sistent with the intended use, and that
§ 870.3945 Prosthetic heart valve sizer.
the devices and accessories in the cir-
(a) Identification. A prosthetic heart cuit are compatible;
valve sizer is a device used to measure (2) The devices and accessories in the
the size of the natural valve opening to circuit must be demonstrated to be bio-
determine the size of the appropriate compatible;
replacement heart valve. (3) Sterility and shelf-life testing
(b) Classification. Class I (general con- must demonstrate the sterility of any
trols). The device is exempt from the patient-contacting devices and acces-
premarket notification procedures in sories in the circuit and the shelf life of
subpart E of part 807 of this chapter these devices and accessories;
subject to the limitations in § 870.9. (4) Non-clinical performance evalua-
[45 FR 7907, Feb. 5, 1980, as amended at 61 FR tion of the devices and accessories in
1121, Jan. 16, 1996; 66 FR 38797, July 25, 2001] the circuit must demonstrate substan-
tial equivalence of the performance
Subpart E—Cardiovascular characteristics on the bench, mechan-
ical integrity, electromagnetic com-
Surgical Devices patibility (where applicable), software,
§ 870.4075 Endomyocardial biopsy de- durability, and reliability;
vice. (5) In vivo evaluation of the devices
and accessories in the circuit must
(a) Identification. An endomyocardial
demonstrate their performance over
biopsy device is a device used in a cath-
the intended duration of use, including
eterization procedure to remove sam-
a detailed summary of the clinical
ples of tissue from the inner wall of the
evaluation pertinent to the use of the
heart.
devices and accessories to demonstrate
their effectiveness if a specific indica-
ance standards).
tion (patient population and/or condi-
§ 870.4100 Extracorporeal circuit and tion) is identified; and
accessories for long-term res- (6) Labeling must include a detailed
piratory/cardiopulmonary failure. summary of the non-clinical and in
(a) Identification. An extracorporeal vivo evaluations pertinent to use of the
circuit and accessories for long-term devices and accessories in the circuit
respiratory/cardiopulmonary support and adequate instructions with respect
(>6 hours) is a system of devices and to anticoagulation, circuit setup, per-
accessories that provides assisted formance characteristics with respect
extracorporeal circulation and physio- to compatibility among different de-
logic gas exchange of the patient’s vices and accessories in the circuit, and
blood in patients with acute res- maintenance during a procedure.
piratory failure or acute [81 FR 7451, Feb. 12, 2016]
cardiopulmonary failure, where other
available treatment options have § 870.4150 Extracorporeal system for
failed, and continued clinical deterio- carbon dioxide removal.
ration is expected or the risk of death (a) Identification. An extracorporeal

is imminent. The main devices and ac- system for carbon dioxide removal is a
cessories of the system include, but are system of devices and accessories that
480
provides assisted extracorporeal carbon vice functionality over the identified

dioxide removal from the patient’s shelf life.
blood in patients with acute res- (9) Labeling must include the fol-
piratory failure, where other available lowing:
treatment options have failed, and con- (i) A detailed summary of the non-
tinued clinical deterioration is ex- clinical and in vivo evaluations perti-
pected or the risk of death is imminent to use of the device and acces-
nent. The main devices and accessories sories in the circuit;
of the system include, but are not lim- (ii) Adequate instructions with re-
ited to, the console (hardware), soft- spect to circuit setup, performance
ware, and disposables, including, but characteristics with respect to compat-
not limited to, a gas exchanger, blood ibility among different devices and ac-
pump, cannulae, tubing, filters, and cessories in the circuit, and mainte-
other accessories (e.g., monitors, detec- nance during a procedure; and
tors, sensors, connectors). (iii) A shelf life.
(b) Classification. Class II (special [87 FR 80039, Dec. 29, 2022]
device are: § 870.4200 Cardiopulmonary bypass ac-
(1) In vivo evaluation, which may in- cessory equipment.
clude animal testing and clinical data, (a) Identification. Cardiopulmonary
of the devices and accessories in the bypass accessory equipment is a device
circuit must demonstrate their per- that has no contact with blood and
formance over the intended duration of that is used in the cardiopulmonary
use, including a detailed summary of bypass circuit to support, adjoin, or
the in vivo evaluation pertinent to the connect components, or to aid in the
use of the devices and accessories to setup of the extracorporeal line, e.g.,
demonstrate their effectiveness. an oxygenator mounting bracket or
(2) The technological characteristics system-priming equipment.
of the device must ensure that the ge- (b) Classification. (1) Class I. The de-
ometry and design parameters are con- vice is classified as class I if it does not
sistent with the intended use, and that involve an electrical connection to the
the devices and accessories in the cir- patient. The device is exempt from the
cuit are compatible. premarket notification procedures in
(3) Non-clinical performance testing subpart E of part 807 of this chapter
of the devices and accessories in the subject to § 870.9.
circuit must demonstrate that the de- (2) Class II (special controls). The de-
vice performs as intended under antici- vice is classified as class II if it in-
pated conditions of use. The following volves an electrical connection to the
performance characteristics must be patient. The special controls are as fol-
tested: lows:
(i) Mechanical integrity; (i) The performance standard under
(ii) Durability; and part 898 of this chapter, and
(iii) Reliability. (ii) The guidance document entitled
(4) All patient contacting compo- ‘‘Guidance on the Performance Stand-
nents of the device must be dem- ard for Electrode Lead Wires and Pa-
onstrated to be biocompatible. tient Cables.’’ The device is exempt
(5) Performance testing must dem- from the premarket notification proce-
onstrate the electrical safety and elec- dures in subpart E of part 807 of this
tromagnetic compatibility (EMC) of chapter subject to § 870.9.
any electrical components. [65 FR 19319, Apr. 11, 2000]
(6) Software validation, verification,
and hazard analysis must be performed. § 870.4205 Cardiopulmonary bypass
(7) Performance testing must dem- bubble detector.
onstrate the sterility of all patient- (a) Identification. A cardiopulmonary
contacting components. bypass bubble detector is a device used
(8) Performance testing must support to detect bubbles in the arterial return
the shelf life of the device by dem- line of the cardiopulmonary bypass cir-
onstrating continued sterility and de- cuit.
481
§ 870.4210 21 CFR Ch. I (4–1–23 Edition)
(b) Classification. Class II (perform- § 870.4250 Cardiopulmonary bypass

ance standards). temperature controller.
(a) Identification. A cardiopulmonary
§ 870.4210 Cardiopulmonary bypass
vascular catheter, cannula, or tub- bypass temperature controller is a de-
ing. vice used to control the temperature of
the fluid entering and leaving a heat
(a) Identification. A cardiopulmonary exchanger.
bypass vascular catheter, cannula, or (b) Classification. Class II (perform-
tubing is a device used in ance standards).
cardiopulmonary surgery to cannulate
the vessels, perfuse the coronary arte- § 870.4260 Cardiopulmonary bypass ar-
ries, and to interconnect the catheters terial line blood filter.
and cannulas with an oxygenator. The (a) Identification. A cardiopulmonary
device includes accessory bypass equip- bypass arterial line blood filter is a de-
ment. vice used as part of a gas exchange
(b) Classification. Class II (perform- (oxygenator) system to filter nonbio-
ance standards). logic particles and emboli (blood clots
or pieces of foreign material flowing in
§ 870.4220 Cardiopulmonary bypass the bloodstream which will obstruct
heart-lung machine console. circulation by blocking a vessel) out of
(a) Identification. A cardiopulmonary the blood. It is used in the arterial re-
bypass heart-lung machine console is a turn line.
device that consists of a control panel (b) Classification. Class II (special
and the electrical power and control controls). The special control for this
circuitry for a heart-lung machine. The device is the FDA guidance document
console is designed to interface with entitled ‘‘Guidance for
the basic units used in a gas exchange Cardiopulmonary Bypass Arterial Line
system, including the pumps, Blood Filter 510(k) Submissions.’’
oxygenator, and heat exchanger. [45 FR 7907, Feb. 5, 1980, as amended at 52 FR
(b) Classification. Class II (perform- 17737, May 11, 1987; 66 FR 18542, Apr. 10, 2001]
ance standards).
§ 870.4230 Cardiopulmonary bypass cardiotomy suction line blood filter.
defoamer. (a) Identification. A cardiopulmonary
(a) Identification. A cardiopulmonary bypass cardiotomy suction line blood
bypass defoamer is a device used in filter is a device used as part of a gas
conjunction with an oxygenator during exchange (oxygenator) system to filter
cardiopulmonary bypass surgery to re- nonbiologic particles and emboli (a
move gas bubbles from the blood. blood clot or a piece of foreign mate-
(b) Classification. Class II (special rial flowing in the bloodstream which
controls). The special control for this will obstruct circulation by blocking a
device is the FDA guidance document vessel) out of the blood. This device is
entitled ‘‘Guidance for Extracorporeal intended for use in the cardiotomy suc-
Blood Circuit Defoamer 510(k) Submis- tion line.
sions.’’ (b) Classification. Class II (perform-
ance standards).
17737, May 11, 1987; 66 FR 18542, Apr. 10, 2001] § 870.4280 Cardiopulmonary prebypass
filter.
§ 870.4240 Cardiopulmonary bypass (a) Identification. A cardiopulmonary
heat exchanger.
prebypass filter is a device used during
(a) Identification. A cardiopulmonary priming of the oxygenator circuit to
bypass heat exchanger is a device, con- remove particulates or other debris
sisting of a heat exchange system used from the circuit prior to initiating by-
in extracorporeal circulation to warm pass. The device is not used to filter
or cool the blood or perfusion fluid blood.
flowing through the device. (b) Classification. Class II (special

(b) Classification. Class II (perform- controls). The device is exempt from
ance standards). the premarket notification procedures
482
in subpart E of part 807 of this chapter for any cardiopulmonary bypass

subject to the limitations in § 870.9. pulsatile flow generator that was in
commercial distribution before May 28,
71812, Dec. 30, 2019] 1976, or that has, on or before Sep-
tember 21, 2004, been found to be sub-
§ 870.4290 Cardiopulmonary bypass stantially equivalent to any
adaptor, stopcock, manifold, or fit- cardiopulmonary bypass pulsatile flow
ting. generator that was in commercial dis-
(a) Identification. A cardiopulmonary tribution before May 28, 1976. Any
bypass adaptor, stopcock, manifold, or other cardiopulmonary bypass
fitting is a device used in cardio- pulsatile flow generator shall have an
vascular diagnostic, surgical, and approved PMA or declared completed
therapeutic applications to inter- PDP in effect before being placed in
connect tubing, catheters, or other de- commercial distribution.
vices.
(b) Classification. Class II (special [45 FR 7907, Feb. 5, 1980, as amended at 52 FR
17737, May 11, 1987; 69 FR 34920, June 23, 2004]
the premarket notification procedures § 870.4330 Cardiopulmonary bypass
in subpart E of part 807 of this chapter on-line blood gas monitor.
[45 FR 7907, Feb. 5, 1980, as amended at 84 FR bypass on-line blood gas monitor is a
71812, Dec. 30, 2019]
device used in conjunction with a blood
§ 870.4300 Cardiopulmonary bypass gas sensor to measure the level of gases
gas control unit. in the blood.
(a) Identification. A cardiopulmonary (b) Classification. Class II (perform-
bypass gas control unit is a device used ance standards).
to control and measure the flow of gas
into the oxygenator. The device is cali- § 870.4340 Cardiopulmonary bypass
level sensing monitor and/or con-
brated for a specific gas. trol.
ance standards). (a) Identification. A cardiopulmonary
bypass level sensing monitor and/or
§ 870.4310 Cardiopulmonary bypass control is a device used to monitor and/
coronary pressure gauge. or control the level of blood in the
(a) Identification. A cardiopulmonary blood reservoir and to sound an alarm
bypass coronary pressure gauge is a de- when the level falls below a predeter-
vice used in cardiopulmonary bypass mined value.
surgery to measure the pressure of the (b) Classification. Class II (special
blood perfusing the coronary arteries. controls). The device is exempt from
pulsatile flow generator. [45 FR 7907, Feb. 5, 1980, as amended at 84 FR
71812, Dec. 30, 2019]
bypass pulsatile flow generator is an
electrically and pneumatically oper- oxygenator.
ated device used to create pulsatile
blood flow. The device is placed in a (a) Identification. A cardiopulmonary
cardiopulmonary bypass circuit down- bypass oxygenator is a device used to
stream from the oxygenator. exchange gases between blood and a
(b) Classification. Class III (premarket gaseous environment to satisfy the gas
approval). exchange needs of a patient during
(c) Date PMA or notice of completion open-heart surgery.
of PDP is required. A PMA or notice of (b) Classification. Class II (special
completion of a PDP is required to be controls). The special control for this

filed with the Food and Drug Adminis- device is the FDA guidance document
tration on or before September 21, 2004, entitled ‘‘Guidance for
483
§ 870.4360 21 CFR Ch. I (4–1–23 Edition)
Cardiopulmonary Bypass Oxygenators ticipated hemodynamic instability due

510(k) Submissions.’’ to immediately reversible alterations
in ventricular myocardial function re-
17737, May 11, 1987; 66 FR 18542, Apr. 10, 2001] sulting from mechanical or physiologic
causes. Duration of use would be less
§ 870.4360 Nonroller-type blood pump. than 6 hours.
(a) Nonroller-type cardiopulmonary and (2) Classification. Class III (premarket
circulatory bypass blood pump—(1) Iden- approval).
tification. A nonroller-type (c) Date premarket approval application
cardiopulmonary and circulatory by- (PMA) or notice of completion of product
pass blood pump is a prescription de- development protocol (PDP) is required. A
vice that uses a method other than re- PMA or notice of completion of a PDP
volving rollers to pump the blood is required to be filed with FDA on or
through an extracorporeal circuit for before September 8, 2015, for any non-
periods lasting less than 6 hours for the roller-type temporary ventricular sup-
purpose of providing either: port blood pump that was in commer-
(i) Full or partial cardiopulmonary cial distribution before May 28, 1976, or
bypass (i.e., circuit includes an that has, on or before September 8,
oxygenator) during open surgical pro- 2015, been found to be substantially
cedures on the heart or great vessels; equivalent to any nonroller-type tem-
or porary ventricular support blood pump
(ii) Temporary circulatory bypass for that was in commercial distribution
diversion of flow around a planned dis- before May 28, 1976. Any other non-
ruption of the circulatory pathway roller-type temporary ventricular sup-
necessary for open surgical procedures port blood pump shall have an ap-
on the aorta or vena cava. proved PMA or declared completed
(2) Classification—Class II (special PDP in effect before being placed in
controls). The special controls for this commercial distribution.
device are: [80 FR 32311, June 8, 2015]
(i) Non-clinical performance testing
must perform as intended over the in- § 870.4370 Roller-type
tended duration of use and dem- cardiopulmonary bypass blood
onstrate the following: Operating pa- pump.
rameters, dynamic blood damage, heat (a) Identification. A roller-type
generation, air entrapment, mechan- cardiopulmonary bypass blood pump is
ical integrity, and durability/reli- a device that uses a revolving roller
ability; mechanism to pump the blood through
(ii) The patient-contacting compo- the cardiopulmonary bypass circuit
nents of the device must be dem- during bypass surgery.
onstrated to be biocompatible; (b) Classification. Class II (perform-
(iii) Sterility and shelf life testing ance standards).
must demonstrate the sterility of pa-
tient-contacting components and the § 870.4380 Cardiopulmonary bypass
shelf life of these components; and pump speed control.
(iv) Labeling must include informa- (a) Identification. A cardiopulmonary
tion regarding the duration of use, and bypass pump speed control is a device
a detailed summary of the device- and used that incorporates an electrical
procedure-related complications perti- system or a mechanical system, or
nent to use of the device. both, and is used to control the speed
(b) Nonroller-type temporary ventric- of blood pumps used in
ular support blood pump—(1) Identifica- cardiopulmonary bypass surgery.
tion. A nonroller-type temporary ven- (b) Classification. Class II (perform-
tricular support blood pump is a pre- ance standards).
scription device that uses any method
resulting in blood propulsion to provide § 870.4390 Cardiopulmonary bypass
the temporary ventricular assistance pump tubing.
required for support of the systemic (a) Identification. A cardiopulmonary

and/or pulmonary circulations during bypass pump tubing is polymeric tub-
periods when there is ongoing or an- ing which is used in the blood pump
484
head and which is cyclically com- device which provides the vacuum and
pressed by the pump to cause the blood control for a cardiotomy return sucker.
to flow through the cardiopulmonary (b) Classification. Class II (special
bypass circuit. controls). The device is exempt from
blood reservoir. [45 FR 7907, Feb. 5, 1980, as amended at 84 FR
(a) Identification. A cardiopulmonary 71812, Dec. 30, 2019]
bypass blood reservoir is a device used
in conjunction with short-term § 870.4450 Vascular clamp.
extracorporeal circulation devices to (a) Identification. A vascular clamp is
hold a reserve supply of blood in the a surgical instrument used to occlude a
bypass circulation. blood vessel temporarily.
(b) Classification. Class II (special (b) Classification. Class II (perform-
controls), except that a reservoir that ance standards).
contains a defoamer or filter is classi-
fied into the same class as the § 870.4475 Surgical vessel dilator.
defoamer or filter. The device, when it
is a cardiopulmonary bypass blood res- (a) Identification. A surgical vessel di-
ervoir that does not contain defoamers lator is a device used to enlarge or cali-
or blood filters, is exempt from the pre- brate a vessel.
market notification procedures in sub- (b) Classification. Class II (perform-
part E of part 807 of this chapter sub- ance standards).
§ 870.4500 Cardiovascular surgical in-
[45 FR 7907, Feb. 5, 1980, as amended at 84 FR struments.
71812, Dec. 30, 2019]
(a) Identification. Cardiovascular sur-
§ 870.4410 Cardiopulmonary bypass in- gical instruments are surgical instru-
line blood gas sensor. ments that have special features for
(a) Identification. A cardiopulmonary use in cardiovascular surgery. These
bypass in-line blood gas sensor is a devices include, e.g., forceps, retrac-
transducer that measures the level of tors, and scissors.
gases in the blood. (b) Classification. Class I (general con-
§ 870.4420 Cardiopulmonary bypass subject to the limitations in § 870.9.
cardiotomy return sucker.
(a) Identification. A cardiopulmonary [45 FR 7907, Feb. 5, 1980, as amended at 54 FR
25049, June 12, 1989; 66 FR 38797, July 25, 2001]
bypass cardiotomy return sucker is a
device that consists of tubing, a con- § 870.4510 Apical closure device.
nector, and a probe or tip that is used
to remove blood from the chest or (a) Identification. An apical closure
heart during cardiopulmonary bypass device is a prescription device con-
surgery. sisting of a delivery system and im-
(b) Classification. Class II (special plant component that is used for soft
controls). The device is exempt from tissue approximation of cardiac apical
the premarket notification procedures tissue during transcatheter valve re-
in subpart E of part 807 of this chapter placement procedures.
subject to the limitations in § 870.9. (b) Classification. Class II (special
[45 FR 7907, Feb. 5, 1980, as amended at 84 FR controls). The special controls for this
71812, Dec. 30, 2019] device are:
(1) The patient contacting materials
§ 870.4430 Cardiopulmonary bypass must be evaluated to be biocompatible.
intracardiac suction control.
(2) Performance data must validate

(a) Identification. A cardiopulmonary the sterility of the patient-contacting
bypass intracardiac suction control is a components of the device.
485
§ 870.4875 21 CFR Ch. I (4–1–23 Edition)
(3) Performance data must support fluid from the chest during the recov-
the shelf life of the device by dem- ery period following surgery.
onstrating continued sterility, package (b) Classification. Class II (perform-
integrity, and device functionality ance standards).
over the labeled shelf life.
(4) Non-clinical performance testing § 870.5100 Percutaneous Transluminal
data must demonstrate that the device Coronary Angioplasty (PTCA) Cath-
performs as intended under anticipated eter.
conditions of use. The following per- (a) Standard PTCA Catheter—(1) Iden-
formance characteristics must be test- tification. A PTCA catheter is a device
ed: that operates on the principle of hy-
(i) Consistent and reliable implant draulic pressurization applied through
deployment; an inflatable balloon attached to the
(ii) Assessment of implant pull-out distal end. A PTCA balloon catheter
force; and has a single or double lumen shaft. The
(iii) Sheath size compatibility with catheter features a balloon of appro-
implant. priate compliance for the clinical ap-
(5) In vivo evaluation of the device plication, constructed from a polymer.
must demonstrate device performance, The balloon is designed to uniformly
including device operation resulting in expand to a specified diameter and
closure of the myocardial wound. length at a specific pressure as labeled,
(6) Labeling must include the fol- with well characterized rates of infla-
lowing: tion and deflation and a defined burst
(i) Detailed information explaining pressure. The device generally features
how the device operates; a type of radiographic marker to facili-
(ii) Sheath size that device can ac- tate fluoroscopic visualization of the
commodate; balloon during use. A PTCA catheter is
(iii) Identification of the minimum intended for balloon dilatation of a
myocardial wall thickness to ensure hemodynamically significant coronary
optimal device function; and artery or bypass graft stenosis in pa-
(iv) A shelf life. tients evidencing coronary ischemia
for the purpose of improving myocar-
[81 FR 71371, Oct. 17, 2016]
dial perfusion. A PTCA catheter may
§ 870.4875 Intraluminal artery strip- also be intended for the treatment of
per. acute myocardial infarction; treatment
of in-stent restenosis (ISR) and/or post-
(a) Identification. An intraluminal ar- deployment stent expansion.
tery stripper is a device used to per- (2) Classification. Class II (special con-
form an endarterectomy (removal of trols). The special control for this de-
plaque deposits from arterisclerotic ar- vice is ‘‘Class II Special Controls Guid-
teries.) ance Document for Certain
(b) Classification. Class II (perform- Percutaneous Transluminal Coronary
ance standards). Angioplasty (PTCA) Catheters.’’ See
§ 870.4885 External vein stripper. § 870.1(e) for the availability of this
guidance document.
(a) Identification. An external vein (b) Cutting/scoring PTCA Catheter—(1)
stripper is an extravascular device used Identification. A cutting/scoring PTCA
to remove a section of a vein. catheter is a balloon-tipped catheter
(b) Classification. Class II (perform- with cutting/scoring elements at-
ance standards). tached, which is used in those cir-
cumstances where a high pressure bal-
Subpart F—Cardiovascular loon resistant lesion is encountered. A
Therapeutic Devices cutting/scoring PTCA catheter is in-
tended for the treatment of
§ 870.5050 Patient care suction appa- hemodynamically significant coronary
ratus. artery stenosis for the purpose of im-
(a) Identification. A patient care suc- proving myocardial perfusion. A cut-

tion apparatus is a device used with an ting/scoring PTCA catheter may also
intrathoracic catheter to withdraw be indicated for use in complex type C
486
lesions or for the treatment of in-stent (i) The clinical training necessary for
restenosis. the safe use of this device;
(2) Classification. Class III (premarket (ii) Adjunctive use only indication
approval). As of May 28, 1976, an ap- prominently displayed on labels phys-
proval under section 515 of the act is ically placed on the device and in any
required before this device may be device manuals or other labeling;
commercially distributed. See § 870.3. (iii) Information on the patient popu-
lation for which the device has been
[75 FR 54496, Sept. 8, 2010] demonstrated to be effective (including
patient size and/or age limitations, e.g.,
§ 870.5150 Embolectomy catheter.
adult, pediatric and/or infant); and
(a) Identification. An embolectomy (iv) Information on the time nec-
catheter is a balloon-tipped catheter essary to deploy the device as dem-
that is used to remove thromboemboli, onstrated in the performance testing.
i.e., blood clots which have migrated in (3) For devices that incorporate elec-
blood vessels from one site in the vas- trical components, appropriate anal-
cular tree to another. ysis and testing must demonstrate that
(b) Classification. Class II (perform- the device is electrically safe and elec-
ance standards). tromagnetically compatible in its in-
tended use environment.
§ 870.5175 Septostomy catheter. (4) Human factors testing and anal-
(a) Identification. A septostomy cath- ysis must validate that the device de-
eter is a special balloon catheter that sign and labeling are sufficient for ef-
is used to create or enlarge the atrial fective use by the intended user, in-
septal defect found in the heart of cer- cluding an evaluation for the time nec-
tain infants. essary to deploy the device.
(b) Classification. Class II (perform- (5) For devices containing software,
ance standards). software verification, validation, and
hazard analysis must be performed.
§ 870.5200 External cardiac com- (6) Components of the device that
pressor. come into human contact must be dem-
(a) Identification. An external cardiac onstrated to be biocompatible.
compressor is an externally applied [81 FR 33133, May 25, 2016]
prescription device that is electrically,
pneumatically, or manually powered § 870.5210 Cardiopulmonary resuscita-
and is used to compress the chest peri- tion (CPR) aid.
odically in the region of the heart to (a) CPR aid without feedback—(1) Iden-
provide blood flow during cardiac ar- tification. A CPR aid without feedback
rest. External cardiac compressor de- is a device that performs a simple func-
vices are used as an adjunct to manual tion such as proper hand placement
cardiopulmonary resuscitation (CPR) and/or simple prompting for rate and/or
when effective manual CPR is not pos- timing of compressions/breathing for
sible (e.g., during patient transport or the professionally trained rescuer, but
extended CPR when fatigue may pro- offers no feedback related to the qual-
hibit the delivery of effective/con- ity of the CPR being provided. These
sistent compressions to the victim, or devices are intended for use by persons
when insufficient EMS personnel are professionally trained in CPR to assure
available to provide effective CPR). proper use and the delivery of optimal
(b) Classification. Class II (special CPR to the victim.
controls). The special controls for this (2) Classification. Class I (general con-
device are: trols). The device is exempt from the
(1) Nonclinical performance testing premarket notification procedures in
under simulated physiological condi- subpart E of part 807 of this chapter
tions must demonstrate the reliability subject to the limitations in § 870.9.
of the delivery of specific compression (b) CPR aid with feedback—(1) Identi-
depth and rate over the intended dura- fication. A CPR Aid device with feed-
tion of use. back is a device that provides real-time

(2) Labeling must include the fol- feedback to the rescuer regarding the
lowing: quality of CPR being delivered to the
487
§ 870.5225 21 CFR Ch. I (4–1–23 Edition)
victim, and provides either audio and/ this section, subject to the limitations
or visual information to encourage the of exemptions in § 870.9.
rescuer to continue the consistent ap-
[81 FR 33134, May 25, 2016]
plication of effective manual CPR in
accordance with current accepted CPR § 870.5225 External counter-pulsating
guidelines (to include, but not be lim- device.
ited to, parameters such as compres-
(a) Identification. An external
sion rate, compression depth, ventila-
counter-pulsating device is a
tion, recoil, instruction for one or mul-
noninvasive, prescription device used
tiple rescuers, etc.). These devices may
to assist the heart by applying positive
also perform a coaching function to aid
or negative pressure to one or more of
rescuers in the sequence of steps nec-
the body’s limbs in synchrony with the
essary to perform effective CPR on a
heart cycle.
victim.
(b) Classification. (1) Class II (special
(2) Classification. Class II (special con-
controls) when the device is intended
trols). The special controls for this de- for the treatment of chronic stable an-
vice are: gina that is refractory to optimal anti-
(i) Nonclinical performance testing anginal medical therapy and without
under simulated physiological or use options for revascularization. The spe-
conditions must demonstrate the accu- cial controls for this device are:
racy and reliability of the feedback to (i) Nonclinical performance evalua-
the user on specific compression rate, tion of the device must demonstrate a
depth and/or respiration over the in- reasonable assurance of safety and ef-
tended duration, and environment of fectiveness for applied pressure, syn-
use. chronization of therapy with the appro-
(ii) Labeling must include the clin- priate phase of the cardiac cycle, and
ical training, if needed, for the safe use functionality of alarms during a device
of this device and information on the malfunction or an abnormal patient
patient population for which the device condition;
has been demonstrated to be effective (ii) Reliabilities of the mechanical
(including patient size and/or age limi- and electrical systems must be estab-
tations, e.g., adult, pediatric and/or in- lished through bench testing under
fant). simulated use conditions and matched
(iii) For devices that incorporate by appropriate maintenance schedules;
electrical components, appropriate (iii) Software design and verification
analysis and testing must demonstrate and validation must be appropriately
that the device is electrically safe and documented;
electromagnetically compatible in its (iv) The skin-contacting components
intended use environment. of the device must be demonstrated to
(iv) For devices containing software, be biocompatible;
software verification, validation, and (v) Appropriate analysis and testing
hazard analysis must be performed. must be conducted to verify electrical
(v) Components of the device that safety and electromagnetic compat-
come into human contact must be dem- ibility of the device; and
onstrated to be biocompatible. (vi) Labeling must include a detailed
(vi) Human factors testing and anal- summary of the device-related and pro-
ysis must validate that the device de- cedure-related complications pertinent
sign and labeling are sufficient for ef- to use of the device.
fective use by the intended user. (2) Class III (premarket approval) for
(3) Premarket notification. The CPR the following intended uses: Unstable
Aid with feedback device is exempt angina pectoris; acute myocardial in-
from the premarket notification proce- farction; cardiogenic shock; congestive
dures in subpart E of part 807 of this heart failure; postoperative treatment
chapter if it does not contain software of patients who have undergone coro-
(e.g., is mechanical or electro-mechan- nary artery bypass surgery; peripheral

ical) and is in compliance with the spe- arterial disease associated with
cial controls under paragraph (b)(2) of ischemic ulcers rest pain or
488
claudication, threatened gangrene, in- of energy that are used in pediatric

sufficient blood supply at an amputa- defibrillation or in cardiac surgery.
tion site, persisting ischemia after The device may either synchronize the
embolectomy or bypass surgery, and/or shock with the proper phase of the
pre- and post-arterial reconstruction to electrocardiogram or may operate
improve runoff; diabetes complicated asynchronously. The device delivers
by peripheral arterial disease or other the electrical shock through paddles
conditions possibly related to arterial placed either directly across the heart
insufficiency including nocturnal leg or on the surface of the body.
cramps and/or necrobiosis (2) Classification. Class II (perform-
diabeticorum; venous diseases, includ- ance standards).
ing prophylaxis of deep vein
(b) High-energy DC-defibrillator—(1)
thrombophlebitis, edema (e.g., chronic
Identification. A high-energy DC-
lymphedema) and/or induration (e.g.,
stasis dermatitis) associated with defibrillator is a device that delivers
chronic venous stasis, venous stasis ul- into a 50 ohm test load an electrical
cers, and/or thrombophlebitis; athletic shock of greater than 360 joules of en-
injuries, including Charley horses, ergy used for defibrillating the atria or
pulled muscles and/or edematous mus- ventricles of the heart or to terminate
cles; necrotizing cellulitis. other cardiac arrhythmias. The device
(c) Date premarket approval application may either synchronize the shock with
(PMA) or notice of completion of product the proper phase of the electrocardio-
development protocol (PDP) is required. A gram or may operate asynchronously.
PMA or notice of completion of a PDP The device delivers the electrical shock
is required to be filed with FDA on or through paddles placed either directly
before March 31, 2014, for any external across the heart or on the surface of
counter-pulsating device, with an in- the body.
tended use described in paragraph (b)(2) (2) Classification. Class III (premarket
of this section, that was in commercial approval).
distribution before May 28, 1976, or that (c) Date PMA or notice of completion of
has, on or before March 31, 2014, been a PDP is required. A PMA or a notice of
found to be substantially equivalent to completion of a PDP is required to be
any external counter-pulsating device, filed with the Food and Drug Adminis-
with an intended use described in para- tration on or before December 26, 1996
graph (b)(2) of this section, that was in for any DC-defibrillator (including pad-
commercial distribution before May 28, dles) described in paragraph (b)(1) of
1976. Any other external counter-pul- this section that was in commercial
sating device with an intended use de- distribution before May 28, 1976, or that
scribed in paragraph (b)(2) of this sec-
has, on or before December 26, 1996
tion shall have an approved PMA or de-
been found to be substantially equiva-
clared completed PDP in effect before
lent to a DC-defibrillator (including
paddles) described in paragraph (b)(1)
tion.
of this section that was in commercial
[78 FR 79307, Dec. 30, 2013] distribution before May 28, 1976. Any
other DC-defibrillator (including pad-
§ 870.5300 DC-defibrillator (including dles) described in paragraph (b)(1) of
paddles).
this section shall have an approved
(a) Low-energy DC-defibrillator—(1) PMA or declared completed PDP in ef-
Identification. A low-energy DC- fect before being placed in commercial
defibrillator is a device that delivers distribution.
into a 50 ohm test load an electrical
shock of a maximum of 360 joules of en- [45 FR 7907, Feb. 5, 1980, as amended at 52 FR
ergy used for defibrillating (restoring 17737, May 11, 1987; 61 FR 50706, Sept. 27, 1996]
normal heart rhythm) the atria or ven-
tricles of the heart or to terminate § 870.5310 Automated external
other cardiac arrhythmias. This ge- defibrillator system.
neric type of device includes low en- (a) Identification. An automated ex-
ergy defibrillators with a maximum ternal defibrillator (AED) system con-
electrical output of less than 360 joules sists of an AED and those accessories
489
§ 870.5325 21 CFR Ch. I (4–1–23 Edition)
necessary for the AED to detect and in- a periodic electrical pulse intended to
terpret an electrocardiogram and de- pace the heart. The pulse from the de-
liver an electrical shock (e.g., battery, vice is usually applied to the surface of
pad electrode, adapter, and hardware the chest through electrodes such as
key for pediatric use). An AED system defibrillator paddles.
analyzes the patient’s electrocardio- (b) Classification. Class II. The special
gram, interprets the cardiac rhythm, controls for this device are:
and automatically delivers an elec- (1) ‘‘American National Standards In-
trical shock (fully automated AED), or stitute/American Association for Med-
advises the user to deliver the shock ical Instrumentation’s DF–21 ‘Cardiac
(semi-automated or shock advisory Defibrillator Devices’ ’’ 2d ed., 1996, and
AED) to treat ventricular fibrillation (2) ‘‘The maximum pulse amplitude
or pulseless ventricular tachycardia. should not exceed 200 milliamperes.
(b) Classification. Class III (premarket The maximum pulse duration should
approval) not exceed 50 milliseconds.’’
(c) Date PMA or notice of completion of
PDP is required. A PMA will be required 17737, May 11, 1987; 65 FR 17144, Mar. 31, 2000]
to be submitted to the Food and Drug
Administration by April 29, 2015, for § 870.5700 Steerable cardiac ablation
any AED that was in commercial dis- catheter remote control system.
tribution before May 28, 1976, or that (a) Identification. A steerable cardiac
has, by April 29, 2015, been found to be ablation catheter remote control sys-
substantially equivalent to any AED tem is a prescription device that is ex-
that was in commercial distribution ternal to the body and interacts with
before May 28, 1976. A PMA will be re- the manual handle of a steerable car-
quired to be submitted to the Food and diac ablation catheter to remotely con-
Drug Administration by April 29, 2015, trol the advancement, retraction, rota-
for any AED accessory described in tion, and deflection of a compatible,
paragraph (a) that was in commercial steerable ablation catheter used for the
distribution before May 28, 1976, or that treatment of cardiac arrhythmias in
has, by April 29, 2015, been found to be the right side of the heart. The device
substantially equivalent to any AED allows reversion to manual control of
accessory described in paragraph (a) the steerable cardiac ablation catheter
that was in commercial distribution without withdrawal of the catheter and
before May 28, 1976. Any other AED and interruption of the procedure.
AED accessory described in paragraph (b) Classification. Class II (special
(a), shall have an approved PMA or de- controls). The special controls for this
clared completed PDP in effect before device are:
being placed in commercial distribu- (1) Non-clinical mechanical perform-
tion. ance testing must demonstrate that
[68 FR 61344, Oct. 28, 2003; 69 FR 10615, Mar. the device performs as intended under
8, 2004, as amended at 80 FR 5682, Feb. 3, 2015] anticipated conditions of use. The fol-
lowing performance testing must be
§ 870.5325 Defibrillator tester. performed:
(a) Identification. A defibrillator (i) Mechanical performance of the
tester is a device that is connected to system (without catheter connected);
the output of a defibrillator and is used (ii) Mechanical performance of the
to measure the energy delivered by the system with compatible catheters con-
defibrillator into a standard resistive nected to verify that the system does
load. Some testers also provide wave- not impact catheter function or per-
form information. formance. Assessments must include
(b) Classification. Class II (perform- the following:
ance standards). (A) Side-by-side remote control and
manual comparisons of catheter ma-
§ 870.5550 External transcutaneous nipulation (including all ranges of mo-
cardiac pacemaker (noninvasive). tion of catheter deflection and tip curl)
(a) Identification. An external trans- for all compatible catheters; must in-
cutaneous cardiac pacemaker clude testing for worst-case conditions,
(noninvasive) is a device used to supply and
490
(B) Evaluation of the accuracy and (iii) Efficacy: Assess ablation success
function of all device control safety in comparison to literature and/or a
features; and manual comparison group for compat-
(iii) Simulated-use testing in a bench ible ablation catheters to support the
anatomic model or animal model. indications for use; and
(2) Non-clinical electrical testing (iv) User assessment of device remote
must include validation of electro- controls and safety features.
magnetic compatibility (EMC), elec- (4) Post-market surveillance (PMS)
trical safety, thermal safety, and elec- must be conducted and completed in
trical system performance. The fol- accordance with FDA agreed upon PMS
lowing performance testing must be protocol.
performed: (5) A training program must be in-
(i) Electrical performance of the sys- cluded with sufficient educational ele-
tem with compatible catheters con- ments that, upon completion of the
nected to verify that the system does training program, the clinician and
not impact catheter function or per- supporting staff can:
formance. Assessments must include (i) Identify the safe environments for
the following: device use,
(A) Side-by-side remote control and (ii) Use all safety features of device,
manual comparisons of catheter ma- and
nipulation (including all ranges of mo- (iii) Operate the device in simulated
tion of catheter deflection and tip curl) or actual use environments representa-
for all compatible catheters; must in- tive of indicated environments and use
clude testing for worst-case conditions, for the indication of compatible cath-
and eters.
(B) Evaluation of the accuracy and (6) Performance data must dem-
function of all device control safety onstrate the sterility of the sterile dis-
features; and posable components of the system.
(ii) Electrical safety between the de- (7) Performance data must support
vice and ablation catheter system and shelf life by demonstrating continued
with other electrical equipment ex- sterility of the device (of the sterile
pected in the catheter lab or operating disposable components), package integ-
room. rity, and device functionality over the
(3) In vivo testing must demonstrate requested shelf life.
that the device performs as intended (8) Labeling must include the fol-
under anticipated conditions of use, in- lowing:
cluding an assessment of the system (i) Appropriate instructions, warn-
impact on the functionality and per- ings, cautions, limitations, and infor-
formance of compatible catheters, and mation related to the intended patient
documentation of the adverse event population, compatible ablation cath-
profile associated with clinical use. eters, and the device safeguards for the
Evidence must be submitted to address safe use of the device;
the following: (ii) Specific instructions and the clin-
(i) Manipulation and Positioning: ical training needed for the safe use of
Ability to manipulate compatible cath- the device, which includes:
eters to pre-specified cardiac locations (A) Instructions on assembling the
and confirm proper anatomic place- device in all available configurations,
ment and tissue contact, in accordance including installation and removal of
with the system indications for use and compatible catheters;
the compatible catheter indications for (B) Instructions and explanation of
use; all controls, inputs, and outputs;
(ii) Safety: Assess device-related (C) Instructions on all available
complication rate and major proce- modes or states of the device;
dural complication rate (regardless of (D) Instructions on all safety fea-
device relatedness) in comparison to tures of the device; and
literature and/or a manual comparison (E) Validated methods and instruc-

group for compatible ablation cath- tions for reprocessing/disinfecting any
eters to support the indications for use; reusable components;
491
§ 870.5800 21 CFR Ch. I (4–1–23 Edition)
(iii) A detailed summary of the me- (b) Classification. Class II (perform-

chanical compatibility testing includ- ance standards).
ing:
(A) A table with a complete list of § 870.5900 Thermal regulating system.
compatible catheters tested (manufac- (a) Identification. A thermal regu-
turer trade name and model number), lating system is an external system
and consisting of a device that is placed in
(B) A table with detailed test results, contact with the patient and a tem-
including type of test, acceptance cri- perature controller for the device. The
teria, and test results (i.e., pass for system is used to regulate patient tem-
meeting acceptance criteria); perature.
(iv) A detailed summary of the in (b) Classification. Class II (perform-
vivo testing including: ance standards).
(A) A table with a complete list of
compatible catheters used during test- § 870.5910 Esophageal thermal regula-
ing (manufacturer trade name and tion device.
model number); (a) Identification. An esophageal ther-
(B) Adverse events encountered perti- mal regulation device is a prescription
nent to use of the device under use con- device used to apply a specified tem-
ditions; perature to the endoluminal surface of
(C) A detailed summary of the the esophagus via an external con-
device- and procedure-related com- troller. This device may incorporate a
plications; and mechanism for gastric decompression
(D) A summary of study outcomes and suctioning. The device is used to
and endpoints. Information pertinent regulate patient temperature.
to the fluoroscopy times/exposure for (b) Classification. Class II (special
the procedure, patient, and operator controls). The special controls for this
fluoroscopic exposure; device are:
(v) Other labeling items: (1) The patient contacting materials
(A) A detailed summary of pertinent must be demonstrated to be biocompat-
non-clinical testing information: EMC, ible.
mechanical, electrical, and steriliza- (2) Non-clinical performance evalua-
tion of device and components; tion must demonstrate that the device
(B) A detailed summary of the device performs as intended under anticipated
technical parameters; and conditions of use. The following per-
(C) An expiration date/shelf life and formance characteristics must be test-
storage conditions for the sterile acces- ed:
sories; and (i) Mechanical integrity testing.
(vi) When available, and according to (ii) Testing to determine tempera-
the timeframe included in the PMS ture change rate(s).
protocol agreed upon with FDA, pro- (iii) Testing to demonstrate compat-
vide a detailed summary of the PMS ibility with the indicated external con-
data including: troller.
(A) Updates to the labeling to accu- (iv) Shelf life testing.
rately reflect outcomes or necessary (3) Animal testing must demonstrate
modifications based upon data col- that the device does not cause esopha-
lected during the PMS experience, and geal injury and that body temperature
(B) Inclusion of results and adverse remains within appropriate boundaries
events associated with utilization of under anticipated conditions of use.
the device during the PMS. (4) Labeling must include the fol-
lowing:
[80 FR 58606, Sept. 30, 2015] (i) Detailed insertion instructions.
(ii) Warning against attaching the
§ 870.5800 Compressible limb sleeve. device to unintended connections, such
(a) Identification. A compressible limb as external controllers for which the
sleeve is a device that is used to pre- device is not indicated, or pressurized
vent pooling of blood in a limb by in- air outlets instead of vacuum outlets
flating periodically a sleeve around the for those devices, including gastric suc-
limb. tion.
492
(iii) The operating parameters, name, 872.3200 Resin tooth bonding agent.
and model number of the indicated ex- 872.3220 Facebow.
ternal controller. 872.3240 Dental bur.
872.3250 Calcium hydroxide cavity liner.
(iv) The intended duration of use. 872.3260 Cavity varnish.
[80 FR 49896, Aug. 18, 2015] 872.3275 Dental cement.
872.3285 Preformed clasp.
§ 870.5925 Automatic rotating tour- 872.3300 Hydrophilic resin coating for den-
niquet. tures.
872.3310 Coating material for resin fillings.
(a) Identification. An automatic rotat- 872.3330 Preformed crown.
ing tourniquet is a device that prevents 872.3350 Gold or stainless steel cusp.
blood flow in one limb at a time, which 872.3360 Preformed cusp.
temporarily reduces the total blood 872.3400 Karaya and sodium borate with or
volume, thereby reducing the normal without acacia denture adhesive.
workload of the heart. 872.3410 Ethylene oxide homopolymer and/or
carboxymethylcellulose sodium denture
(b) Classification. Class II (perform- adhesive.
ance standards). 872.3420 Carboxymethylcellulose sodium
and cationic polyacrylamide polymer
PART 872—DENTAL DEVICES denture adhesive.
872.3450 Ethylene oxide homopolymer and/or
Subpart A—General Provisions karaya denture adhesive.
872.3480 Polyacrylamide polymer (modified
Sec. cationic) denture adhesive.
872.1 Scope. 872.3490 Carboxymethylcellulose sodium
872.3 Effective dates of requirement for pre- and/or polyvinylmethylether maleic acid
market approval. calcium-sodium double salt denture ad-
872.9 Limitations of exemptions from sec- hesive.
tion 510(k) of the Federal Food, Drug, 872.3500 Polyvinylmethylether maleic anhy-
and Cosmetic Act (the act). dride (PVM-MA), acid copolymer, and
carboxymethylcellulose sodium
Subpart B—Diagnostic Devices (NACMC) denture adhesive.
872.3520 OTC denture cleanser.
872.1500 Gingival fluid measurer. 872.3530 Mechanical denture cleaner.
872.1720 Pulp tester. 872.3540 OTC denture cushion or pad.
872.1730 Electrode gel for pulp testers. 872.3560 OTC denture reliner.
872.1740 Caries detection device. 872.3570 OTC denture repair kit.
872.1745 Laser fluorescence caries detection 872.3580 Preformed gold denture tooth.
device. 872.3590 Preformed plastic denture tooth.
872.1800 Extraoral source x-ray system. 872.3600 Partially fabricated denture kit.
872.1810 Intraoral source x-ray system. 872.3630 Endosseous dental implant abut-
872.1820 Dental x-ray exposure alignment ment.
device. 872.3640 Endosseous dental implant.
872.1830 Cephalometer. 872.3645 Subperiosteal implant material.
872.1840 Dental x-ray position indicating de- 872.3660 Impression material.
vice. 872.3661 Optical Impression Systems for
872.1850 Lead-lined position indicator. CAD/CAM.
872.1870 Sulfide detection device. 872.3670 Resin impression tray material.
872.1905 Dental x-ray film holder. 872.3680 Polytetrafluoroethylene (PTFE)
872.2050 Dental sonography device. vitreous carbon materials.
872.2060 Jaw tracking device. 872.3690 Tooth shade resin material.
872.3710 Base metal alloy.
Subpart C [Reserved] 872.3730 Pantograph.
872.3740 Retentive and splinting pin.
Subpart D—Prosthetic Devices 872.3750 Bracket adhesive resin and tooth
conditioner.
872.3060 Noble metal alloy. 872.3760 Denture relining, repairing, or re-
872.3070 Dental amalgam, mercury, and basing resin.
amalgam alloy. 872.3765 Pit and fissure sealant and condi-
872.3080 Mercury and alloy dispenser. tioner.
872.3100 Dental amalgamator. 872.3770 Temporary crown and bridge resin.
872.3110 Dental amalgam capsule. 872.3810 Root canal post.
872.3130 Preformed anchor. 872.3820 Root canal filling resin.
872.3140 Resin applicator. 872.3830 Endodontic paper point.

872.3150 Articulator. 872.3840 Endodontic silver point.
872.3165 Precision attachment. 872.3850 Gutta percha.
493
§ 872.1 21 CFR Ch. I (4–1–23 Edition)
872.3890 Endodontic stabilizing splint. 872.6200 Base plate shellac.
872.3900 Posterior artificial tooth with a 872.6250 Dental chair and accessories.
metal insert. 872.6290 Prophylaxis cup.
872.3910 Backing and facing for an artificial 872.6300 Rubber dam and accessories.
tooth. 872.6350 Ultraviolet detector.
872.3920 Porcelain tooth. 872.6390 Dental floss.
872.3930 Bone grafting material. 872.6475 Heat source for bleaching teeth.
872.3940 Total temporomandibular joint 872.6510 Oral irrigation unit.
prosthesis. 872.6570 Impression tube.
872.3950 Glenoid fossa prosthesis. 872.6640 Dental operative unit and acces-
872.3960 Mandibular condyle prosthesis. sories.
872.3970 Interarticular disc prosthesis 872.6650 Massaging pick or tip for oral hy-
(interpositional implant). giene.
872.3980 Endosseous dental implant acces- 872.6660 Porcelain powder for clinical use.
sories. 872.6670 Silicate protector.
872.6710 Boiling water sterilizer.
Subpart E—Surgical Devices 872.6730 Endodontic dry heat sterilizer.
872.6770 Cartridge syringe.
872.4120 Bone cutting instrument and acces- 872.6855 Manual toothbrush.
sories. 872.6865 Powered toothbrush.
872.4130 Intraoral dental drill. 872.6870 Disposable fluoride tray.
872.4200 Dental handpiece and accessories. 872.6880 Preformed impression tray.
872.4465 Gas-powered jet injector. 872.6890 Intraoral dental wax.
872.4475 Spring-powered jet injector.
872.4535 Dental diamond instrument. AUTHORITY: 21 U.S.C. 351, 360, 360c, 360e,
872.4565 Dental hand instrument. 360j, 360l, 371.
872.4600 Intraoral ligature and wire lock. SOURCE: 52 FR 30097, Aug. 12, 1987, unless
872.4620 Fiber optic dental light. otherwise noted.
872.4630 Dental operating light.
872.4730 Dental injecting needle. EDITORIAL NOTE: Nomenclature changes to
872.4760 Bone plate. part 872 appear at 73 FR 35341, June 23, 2008.
872.4770 Temporary mandibular condyle re-
construction plate. Subpart A—General Provisions
872.4840 Rotary scaler.
872.4850 Ultrasonic scaler. § 872.1 Scope.
872.4880 Intraosseous fixation screw or wire.
872.4920 Dental electrosurgical unit and ac- (a) This part sets forth the classifica-
cessories. tion of dental devices intended for
human use that are in commercial dis-
Subpart F—Therapeutic Devices tribution.
872.5410 Orthodontic appliance and acces- (b) The identification of a device in a
sories. regulation in this part is not a precise
872.5470 Orthodontic plastic bracket. description of every device that is, or
872.5500 Extraoral orthodontic headgear. will be, subject to the regulation. A
872.5525 Preformed tooth positioner. manufacturer who submits a pre-
872.5550 Teething ring. market notification submission for a
872.5560 Electrical salivary stimulatory sys-
tem.
device under part 807 cannot show
872.5570 Intraoral devices for snoring and merely that the device is accurately
intraoral devices for snoring and obstruc- described by the section title and iden-
tive sleep apnea. tification provisions of a regulation in
872.5571 Auto titration device for oral appli- this part, but shall state why the de-
ances. vice is substantially equivalent to
872.5580 Oral rinse to reduce the adhesion of other devices, as required by § 807.87.
dental plaque. (c) To avoid duplicative listings, a
Subpart G—Miscellaneous Devices dental device that has two or more
types of uses (e.g., used both as a diag-
872.6010 Abrasive device and accessories. nostic device and as a therapeutic de-
872.6030 Oral cavity abrasive polishing vice) is listed in one subpart only.
agent. (d) References in this part to regu-
872.6050 Saliva absorber.
latory sections of the Code of Federal
872.6070 Ultraviolet activator for polym-
erization. Regulations are to chapter I of title 21
872.6080 Airbrush. unless otherwise noted.

872.6100 Anesthetic warmer. (e) Guidance documents referenced in
872.6140 Articulation paper. this part are available on the Internet
494
at http://www.fda.gov/MedicalDevices/ keted that has been substantially al-

DeviceRegulationandGuidance/ tered, is classified by statute (section
GuidanceDocuments/default.htm. 513(f) of the act) into class III without
FR 19737, Apr. 22, 2003; 79 FR 50552, Aug. 25, issued an order approving a PMA or de-
2014] claring completed a PDP for the device
§ 872.3 Effective dates of requirement tributed unless it is reclassified. If
for premarket approval. FDA knows that a device being com-
A device included in this part that is mercially distributed may be a ‘‘new’’
classified into class III (premarket ap- device as defined in this section be-
proval) shall not be commercially dis- cause of any new intended use or other
tributed after the date shown in the reasons, FDA may codify the statutory
regulation classifying the device unless classification of the device into class
the manufacturer has an approval III for such new use. Accordingly, the
under section 515 of the act (unless an regulation for such a class III device
exemption has been granted under sec- states that as of the enactment date of
tion 520(g)(2) of the act). An approval the amendments, May 28, 1976, the de-
under section 515 of the act consists of vice must have an approval under sec-
(PMA) for the device or declaring com- (c) A device identified in a regulation
pleted a product development protocol in this part that is classified into class
(PDP) for the device. III and that is subject to the transi-
(a) Before FDA requires that a device tional provisions of section 520(1) of the
commercially distributed before the act is automatically classified by stat-
enactment date of the amendments, or ute into class III and must have an ap-
a device that has been found substan- proval under section 515 of the act be-
tially equivalent to such a device, has fore being commercially distributed.
an approval under section 515 of the Accordingly, the regulation for such a
act, FDA must promulgate a regula- class III transitional device states that
tion under section 515(b) of the act re- as of the enactment date of the amend-
quiring such approval, except as pro- ments, May 28, 1976, the device must
vided in paragraphs (b) and (c) of this have an approval under section 515 of
section. Such a regulation under sec- the act before commercial distribution.
tion 515(b) of the act shall not be effec-
tive during the grace period ending on § 872.9 Limitations of exemptions from
the 90th day after its promulgation or section 510(k) of the Federal Food,
on the last day of the 30th full calendar Drug, and Cosmetic Act (the act).
month after the regulation that classi- The exemption from the requirement
fies the device into class III is effec- of premarket notification (section
tive, whichever is later. See section 510(k) of the act) for a generic type of
501(f)(2)(B) of the act. Accordingly, un- class I or II device is only to the extent
less an effective date of the require- that the device has existing or reason-
ment for premarket approval is shown ably foreseeable characteristics of
in the regulation for a device classified commercially distributed devices with-
into class III in this part, the device in that generic type or, in the case of
may be commercially distributed within vitro diagnostic devices, only to the
out FDA’s issuance of an order approv- extent that misdiagnosis as a result of
ing a PMA or declaring completed a using the device would not be associ-
PDP for the device. If FDA promul- ated with high morbidity or mortality.
gates a regulation under section 515(b) Accordingly, manufacturers of any
of the act requiring premarket ap- commercially distributed class I or II
proval for a device, section 501(f)(1)(A) device for which FDA has granted an
of the act applies to the device. exemption from the requirement of
(b) Any new, not substantially equiv- premarket notification must still sub-
alent, device introduced into commer- mit a premarket notification to FDA

cial distribution on or after May 28, before introducing or delivering for in-
1976, including a device formerly mar- troduction into interstate commerce
495
§ 872.1500 21 CFR Ch. I (4–1–23 Edition)
for commercial distribution the device Subpart B—Diagnostic Devices

when:
(a) The device is intended for a use § 872.1500 Gingival fluid measurer.
gally marketed device in that generic (a) Identification. A gingival fluid
type of device; e.g., the device is in- measurer is a gauge device intended to
tended for a different medical purpose, measure the amount of fluid in the gin-
or the device is intended for lay use gival sulcus (depression between the
where the former intended use was by tooth and gums) to determine if there
health care professionals only; is a gingivitis condition.
(b) The modified device operates (b) Classification. Class I (general con-
using a different fundamental sci- trols). The device is exempt from the
entific technology than a legally mar- premarket notification procedures in
keted device in that generic type of de- subpart E of part 807 of this chapter
vice; e.g., a surgical instrument cuts subject to the limitations in § 872.9.
tissue with a laser beam rather than
with a sharpened metal blade, or an in [52 FR 30097, Aug. 12, 1987, as amended at 59
vitro diagnostic device detects or iden- FR 63007, Dec. 7, 1994; 66 FR 38797, July 25,
2001]
tifies infectious agents by using
deoxyribonucleic acid (DNA) probe or
§ 872.1720 Pulp tester.
rather than culture or immunoassay (a) Identification. A pulp tester is an
technology; or AC or battery powered device intended
(c) The device is an in vitro device to evaluate the pulpal vitality of teeth
that is intended: by employing high frequency current
(1) For use in the diagnosis, moni- transmitted by an electrode to stimu-
toring, or screening of neoplastic dis- late the nerve tissue in the dental pulp.
eases with the exception of (b) Classification. Class II (special
immunohistochemical devices; controls). The device is exempt from
(2) For use in screening or diagnosis the premarket notification procedures
of familial or acquired genetic dis- in subpart E of part 807 of this chapter
orders, including inborn errors of me- subject to the limitations in § 872.9.
tabolism;
(3) For measuring an analyte that [52 FR 30097, Aug. 12, 1987, as amended at 84
serves as a surrogate marker for FR 71812, Dec. 30, 2019]
life-threatening diseases such as ac- § 872.1730 Electrode gel for pulp test-
quired immune deficiency syndrome ers.
(AIDS), chronic or active hepatitis, tu- (a) Identification. An electrode gel for
berculosis, or myocardial infarction or pulp testers is a device intended to be
to monitor therapy; applied to the surface of a tooth before
(4) For assessing the risk of cardio- use of a pulp tester to aid conduction
vascular diseases; of electrical current.
(5) For use in diabetes management; (b) Classification. Class I (general con-
(6) For identifying or inferring the trols). The device is exempt from the
identity of a microorganism directly premarket notification procedures in
from clinical material;
(7) For detection of antibodies to
microorganisms other than
immunoglobulin G (IgG) or IgG assays [52 FR 30097, Aug. 12, 1987, as amended at 54
when the results are not qualitative, or FR 13830, Apr. 5, 1989; 66 FR 38797, July 25,
are used to determine immunity, or the 2001]
assay is intended for use in matrices
other than serum or plasma; § 872.1740 Caries detection device.
(8) For noninvasive testing as defined (a) Identification. The caries detection
in § 812.3(k) of this chapter; and device is a device intended to show the
existence of decay in a patient’s tooth

care). by use of electrical current.
[65 FR 2314, Jan. 14, 2000] (b) Classification. Class II.
496
§ 872.1745 Laser fluorescence caries teeth, jaw, and oral structures. The x-
detection device. ray source (a tube) is located inside the
(a) Identification. A laser fluorescence mouth. This generic type of device may
caries detection device is a laser, a flu- include patient and equipment sup-
orescence detector housed in a dental ports and component parts.
handpiece, and a control console that (b) Classification. Class II.
performs device calibration, as well as § 872.1820 Dental x-ray exposure align-
variable tone emitting and fluores- ment device.
cence measurement functions. The in-
tended use of the device is to aid in the (a) Identification. A dental x-ray expo-
detection of tooth decay by measuring sure alignment device is a device in-
increased laser induced fluorescence. tended to position x-ray film and to
(b) Classification. Class II, subject to align the examination site with the x-
the following special controls: ray beam.
(1) Sale, distribution, and use of this (b) Classification. Class I (general con-
device are restricted to prescription trols). The device is exempt from the
use in accordance with § 801.109 of this premarket notification procedures in
chapter; subpart E of part 807 of this chapter
(2) Premarket notifications must in- subject to the limitations in § 872.9.
clude clinical studies, or other relevant [52 FR 30097, Aug. 12, 1987, as amended at 59
information, that demonstrates that FR 63008, Dec. 7, 1994; 66 FR 38797, July 25,
the device aids in the detection of 2001]
tooth decay by measuring increased
laser induced fluorescence; and § 872.1830 Cephalometer.
(3) The labeling must include de- (a) Identification. A cephalometer is a
tailed use instructions with pre- device used in dentistry during x-ray
cautions that urge users to: procedures. The device is intended to
(i) Read and understand all directions place and to hold a patient’s head in a
before using the device, standard position during dental x-rays.
(ii) Store probe tips under proper (b) Classification. Class II.
conditions,
(iii) Properly sterilize the emitter-de- § 872.1840 Dental x-ray position indi-
tector handpick before each use, and cating device.
(iv) Properly maintain and handle (a) Identification. A dental x-ray posi-
the instrument in the specified manner tion indicating device is a device, such
and condition. as a collimator, cone, or aperture, that
[65 FR 18235, Apr. 7, 2000]
is used in dental radiographic examina-
tion. The device is intended to align
§ 872.1800 Extraoral source x-ray sys- the examination site with the x-ray
tem. beam and to restrict the dimensions of
(a) Identification. An extraoral source the dental x-ray field by limiting the
x-ray system is an AC-powered device size of the primary x-ray beam.
that produces x-rays and is intended (b) Classification. Class I (general con-
for dental radiographic examination trols). The device is exempt from the
and diagnosis of diseases of the teeth, premarket notification procedures in
jaw, and oral structures. The x-ray subpart E of part 807 of this chapter
source (a tube) is located outside the subject to the limitations in § 872.9.
mouth. This generic type of device may [52 FR 30097, Aug. 12, 1987, as amended at 61
include patient and equipment sup- FR 1121, Jan. 16, 1996; 66 FR 38797, July 25,
ports and component parts. 2001]
§ 872.1850 Lead-lined position indi-
§ 872.1810 Intraoral source x-ray sys- cator.
tem. (a) Identification. A lead-lined posi-
(a) Identification. An intraoral source tion indicator is a cone-shaped device
x-ray system is an electrically powered lined with lead that is attached to a
device that produces x-rays and is in- dental x-ray tube and intended to aid
tended for dental radiographic exam- in positioning the tube, to prevent the
ination and diagnosis of diseases of the misfocusing of the x-rays by absorbing
497
§ 872.1870 21 CFR Ch. I (4–1–23 Edition)
divergent radiation, and to prevent § 872.2050 Dental sonography device.

leakage of radiation. (a) Dental sonography device for moni-
(b) Classification. Class I (general con- toring—(1) Identification. A dental
trols). The device is exempt from the sonography device for monitoring is an
premarket notification procedures in electrically powered device, intended
subpart E of part 807 of this chapter to be used to monitor
subject to the limitations in § 872.9. temporomandibular joint sounds. The
[52 FR 30097, Aug. 12, 1987, as amended at 61 device detects and records sounds made
FR 1121, Jan. 16, 1996; 66 FR 38797, July 25, by the temporomandibular joint.
2001] (2) Classification. Class I. The device
is exempt from the premarket notifica-
§ 872.1870 Sulfide detection device. tion provisions of subpart E of part 807
of this chapter subject to § 872.9.
(a) Identification. A sulfide detection
(b) Dental sonography device for inter-
device is a device consisting of an AC-
pretation and diagnosis—(1) Identifica-
powered control unit, probe handle,
tion. A dental sonography device for in-
probe tips, cables, and accessories. This
terpretation and diagnosis is an elec-
device is intended to be used in vivo, to
trically powered device, intended to in-
manually measure periodontal pocket terpret temporomandibular joint
probing depths, detect the presence or sounds for the diagnosis of
absence of bleeding on probing, and de- temporomandibular joint disorders and
tect the presence of sulfides in peri- associated orofacial pain. The device
odontal pockets, as an adjunct in the detects, records, displays, and stores
diagnosis of periodontal diseases in sounds made by the
adult patients. temporomandibular joint during jaw
(b) Classification. Class II (special movement. The device interprets these
controls) prescription use in accord- sounds to generate meaningful output,
ance with § 801.109 of this chapter; con- either directly or by connection to a
formance with recognized standards of personal computer. The device may be
biocompatibility, electrical safety, and part of a system of devices, contrib-
sterility; clinical and analytical per- uting joint sound information to be
formance testing, and proper labeling. considered with data from other diag-
[63 FR 59717, Nov. 5, 1998]
nostic components.
(2) Classification. Class II (special con-
§ 872.1905 Dental x-ray film holder. trols). The special control for this de-
vice is FDA’s guidance document enti-
(a) Identification. A dental x-ray film tled ‘‘Class II Special Controls Guid-
holder is a device intended to position ance Document: Dental Sonography
and to hold x-ray film inside the and Jaw Tracking Devices.’’
mouth.
[68 FR 67367, Dec. 2, 2003]
trols). The device is exempt from the § 872.2060 Jaw tracking device.
subpart E of part 807 of this chapter (a) Jaw tracking device for monitoring
subject to the limitations in § 872.9. If mandibular jaw positions relative to the
the device is not labeled or otherwise maxilla—(1) Identification. A jaw track-
ing device for monitoring mandibular
represented as sterile, it is also exempt
jaw positions relative to the maxilla is
a nonpowered or electrically powered
device that measures and records ana-
tomical distances and angles in three
chapter, with the exceptions of
dimensional space, to determine the
§ 820.180, with respect to general re- relative position of the mandible with
quirements concerning records, and respect to the location and position of
§ 820.198, with respect to complaint the maxilla, while at rest and during
files. jaw movement.
[52 FR 30097, Aug. 12, 1987, as amended at 54 (2) Classification. Class I (general con-
FR 13830, Apr. 5, 1989; 66 FR 38797, July 25, trols). The device is exempt from the
2001] premarket notification provisions of
498
subpart E of part 807 of this chapter § 872.3070 Dental amalgam, mercury,

subject to § 872.9. and amalgam alloy.
(b) Jaw tracking device for interpreta-
(a) Identification. Dental amalgam is
tion of mandibular jaw positions for the
diagnosis—(1) Identification. A jaw a device that consists of a combination
tracking device for interpretation of of elemental mercury, supplied as a liq-
mandibular jaw positions relative to uid in bulk, sachet, or predosed capsule
the maxilla for the diagnosis of form, and amalgam alloy composed pri-
temporomandibular joint disorders and marily of silver, tin, and copper, sup-
associated orofacial pain is a nonpow- plied as a powder in bulk, tablet, or
ered or electrically powered device predosed capsule form, for the direct
that measures and records anatomical filling of carious lesions or structural
distances and angles to determine the defects in teeth. This device also in-
relative position of the mandible in cludes the individual component de-
three dimensional space, with respect vices, mercury and amalgam alloy,
to the location and position of the when intended to be combined with
maxilla, while at rest and during jaw each other to form dental amalgam.
movement. The device records, dis- (b) Classification. Class II (special
plays, and stores information about controls). The special control for this
jaw position. The device interprets jaw device is FDA’s ‘‘Class II Special Con-
position to generate meaningful out-
trols Guidance Document: Dental
put, either directly or by connection to
a personal computer. The device may Amalgam, Mercury, and Amalgam
be a part of a system of devices, con- Alloy.’’ See § 872.1(e) for the availability
tributing jaw position information to of this guidance document.
be considered with data from other di- [74 FR 38714, Aug. 4, 2009]
agnostic components.
(2) Classification. Class II (special con- § 872.3080 Mercury and alloy dis-
trols). The special control for this de- penser.
vice is FDA’s guidance document enti- (a) Identification. A mercury and
tled ‘‘Class II Special Controls Guid-
alloy dispenser is a device with a
ance Document: Dental Sonography
spring-activated valve intended to
and Jaw Tracking Devices.’’
measure and dispense into a mixing
[68 FR 67367, Dec. 2, 2003] capsule a predetermined amount of
dental mercury in droplet form and a
Subpart C [Reserved] premeasured amount of alloy pellets.
Subpart D—Prosthetic Devices trols). The device is exempt from the
§ 872.3060 Noble metal alloy. subpart E of part 807 of this chapter
(a) Identification. A noble metal alloy subject to the limitations in § 872.9.
is a device composed primarily of noble
metals, such as gold, palladium, plat- [52 FR 30097, Aug. 12, 1987, as amended at 54
FR 13830, Apr. 5, 1989; 66 FR 38797, July 25,
inum, or silver, that is intended for use
2001]
in the fabrication of cast or porcelain-
fused-to-metal crown and bridge res- § 872.3100 Dental amalgamator.
torations.
(b) Classification. Class II (special (a) Identification. A dental amalga-
controls). The special control for these mator is a device, usually AC-powered,
devices is FDA’s ‘‘Class II Special Con- intended to mix, by shaking, amalgam
trols Guidance Document: Dental capsules containing mercury and den-
Noble Metal Alloys.’’ The devices are tal alloy particles, such as silver, tin,
exempt from the premarket notifica- zinc, and copper. The mixed dental
tion procedures in subpart E of part 807 amalgam material is intended for fill-
of this chapter subject to the limita- ing dental caries.
tions in § 872.9. See § 872.1(e) for avail- (b) Classification. Class I (general con-
ability of guidance information. trols). The device is exempt from the

[69 FR 51766, Aug. 23, 2004] premarket notification procedures in
499
§ 872.3110 21 CFR Ch. I (4–1–23 Edition)
subpart E of part 807 of this chapter § 820.198, with respect to complaint

subject to the limitations in § 872.9. files.
[55 FR 48439, Nov. 20, 1990, as amended at 59 [52 FR 30097, Aug. 12, 1987, as amended at 54
FR 63008, Dec. 7, 1994; 66 FR 38797, July 25, FR 13830, Apr. 5, 1989; 66 FR 38797, July 25,
2001] 2001]
§ 872.3110 Dental amalgam capsule. § 872.3150 Articulator.

(a) Identification. A dental amalgam (a) Identification. An articulator is a
capsule is a container device in which mechanical device intended to simu-
silver alloy is intended to be mixed late movements of a patient’s upper
with mercury to form dental amalgam. and lower jaws. Plaster casts of the pa-
(b) Classification. Class I (general con- tient’s teeth and gums are placed in
trols). The device is exempt from the the device to reproduce the occlusion
premarket notification procedures in (bite) and articulation of the patient’s
subpart E of part 807 of this chapter jaws. An articulator is intended to fit
subject to the limitations in § 872.9. dentures or provide orthodontic treat-
[52 FR 30097, Aug. 12, 1987, as amended at 54 ment.
FR 13830, Apr. 5, 1989; 66 FR 38797, July 25, (b) Classification. Class I (general con-
2001] trols). The device is exempt from the
§ 872.3130 Preformed anchor. subpart E of part 807 of this chapter
(a) Identification. A preformed anchor subject to the limitations in § 872.9. If
is a device made of austenitic alloys or the device is not labeled or otherwise
alloys containing 75 percent or greater represented as sterile, the device is ex-
gold or metals of the platinum group empt from the current good manufac-
intended to be incorporated into a den- turing practice requirements of the
tal appliance, such as a denture, to quality system regulation in part 820 of
help stabilize the appliance in the pa- this chapter, with the exceptions of
tient’s mouth. § 820.180, with respect to general re-
(b) Classification. Class I (general con- quirements concerning records, and
trols). The device is exempt from the § 820.198, with respect to complaint
premarket notification procedures in files.
subject to the limitations in § 872.9. [52 FR 30097, Aug. 12, 1987, as amended at 54
FR 13830, Apr. 5, 1989; 66 FR 38797, July 25,
[52 FR 30097, Aug. 12, 1987, as amended at 59 2001]
FR 63008, Dec. 7, 1994; 66 FR 38797, July 25,
2001] § 872.3165 Precision attachment.
§ 872.3140 Resin applicator. (a) Identification. A precision attach-
ment or preformed bar is a device made
(a) Identification. A resin applicator is
of austenitic alloys or alloys con-
a brushlike device intended for use in
taining 75 percent or greater gold and
spreading dental resin on a tooth dur-
ing application of tooth shade mate- metals of the platinum group intended
rial. for use in prosthetic dentistry in con-
junction with removable partial den-
trols). The device is exempt from the tures. Various forms of the device are
premarket notification procedures in intended to connect a lower partial
subpart E of part 807 of this chapter denture with another lower partial
subject to the limitations in § 872.9. If denture, to connect an upper partial
the device is not labeled or otherwise denture with another upper partial
represented as sterile, the device is ex- denture, to connect either an upper or
empt from the current good manufac- lower partial denture to a tooth or a
turing practice requirements of the crown, or to connect a fixed bridge to a
quality system regulation in part 820 of partial denture.
this chapter, with the exceptions of (b) Classification. Class I (general con-
§ 820.180, with respect to general re- trols). The device is exempt from the
quirements concerning records, and premarket notification procedures in
500
[52 FR 30097, Aug. 12, 1987, as amended at 59 [52 FR 30097, Aug. 12, 1987, as amended at 59
FR 63008, Dec. 7, 1994; 66 FR 38797, July 25, FR 63008, Dec. 7, 1994; 66 FR 38798, July 25,
2001] 2001]
§ 872.3200 Resin tooth bonding agent. § 872.3250 Calcium hydroxide cavity

liner.
(a) Identification. A resin tooth bond-
(a) Identification. A calcium hydrox-
ing agent is a device material, such as
ide cavity liner is a device material in-
methylmethacrylate, intended to be
tended to be applied to the interior of
painted on the interior of a prepared
a prepared cavity before insertion of
cavity of a tooth to improve retention
restorative material, such as amalgam,
of a restoration, such as a filling. to protect the pulp of a tooth.
(b) Classification. Class II. (b) Classification. Class II.
§ 872.3220 Facebow. § 872.3260 Cavity varnish.
(a) Identification. A facebow is a de- (a) Identification. Cavity varnish is a
vice intended for use in denture fab- device that consists of a compound in-
rication to determine the spatial rela- tended to coat a prepared cavity of a
tionship between the upper and lower tooth before insertion of restorative
jaws. This determination is intended materials. The device is intended to
for use in placing denture casts accu- prevent penetration of restorative ma-
rately into an articulator (§ 872.3150) terials, such as amalgam, into the
and thereby aiding correct placement dentinal tissue.
of artificial teeth into a denture base. (b) Classification. Class II (special
(b) Classification. Class I (general con- controls). The device, when it is an ex-
trols). The device is exempt from the ternal cleaning solution, is exempt
premarket notification procedures in from the premarket notification proce-
subpart E of part 807 of this chapter dures in subpart E of part 807 of this
subject to the limitations in § 872.9. If chapter subject to the limitations in
the device is not labeled or otherwise § 872.9.
represented as sterile, the device is ex- [52 FR 30097, Aug. 12, 1987, as amended at 84
empt from the current good manufac- FR 71812, Dec. 30, 2019]
turing practice requirements of the
quality system regulation in part 820 of § 872.3275 Dental cement.
this chapter, with the exceptions of (a) Zinc oxide-eugenol—(1) Identifica-
§ 820.180, with respect to general re- tion. Zinc oxide-eugenol is a device
quirements concerning records, and composed of zinc oxide-eugenol in-
§ 820.198, with respect to complaint tended to serve as a temporary tooth
files. filling or as a base cement to affix a
temporary tooth filling, to affix dental
[52 FR 30097, Aug. 12, 1987, as amended at 54 devices such as crowns or bridges, or to
FR 13830, Apr. 5, 1989; 66 FR 38797, July 25,
2001]
be applied to a tooth to protect the
tooth pulp.
§ 872.3240 Dental bur. (2) Classification. Class I (general con-
(a) Identification. A dental bur is a ro- premarket notification procedures in
tary cutting device made from carbon subpart E of part 807 of this chapter
steel or tungsten carbide intended to subject to § 872.9.
cut hard structures in the mouth, such (b) Dental cement other than zinc
as teeth or bone. It is also intended to oxide-eugenol—(1) Identification. Dental
cut hard metals, plastics, porcelains, cement other than zinc oxide-eugenol
and similar materials intended for use is a device composed of various mate-
in the fabrication of dental devices. rials other than zinc oxide-eugenol in-
(b) Classification. Class I (general con- tended to serve as a temporary tooth

trols). The device is exempt from the filling or as a base cement to affix a
premarket notification procedures in temporary tooth filling, to affix dental
501
§ 872.3285 21 CFR Ch. I (4–1–23 Edition)
devices such as crowns or bridges, or to § 872.3330 Preformed crown.

be applied to a tooth to protect the
(a) Identification. A preformed crown
tooth pulp.
is a prefabricated device made of plas-
(2) Classification. Class II. tic or austenitic alloys or alloys con-
[52 FR 30097, Aug. 12, 1987, as amended at 65 taining 75 percent or greater gold and
FR 2314, Jan. 14, 2000] metals of the platinum group intended
to be affixed temporarily to a tooth
§ 872.3285 Preformed clasp. after removal of, or breakage of, the
(a) Identification. A preformed clasp natural crown (that portion of the
or a preformed wire clasp is a prefab- tooth that normally protrudes above
ricated device made of austenitic al- the gums). It is intended for use as a
functional restoration until a perma-
loys or alloys containing 75 percent or
nent crown is constructed. The device
greater gold and metals of the plat-
also may be intended for use as a func-
inum group intended to be incor-
tional restoration for a badly decayed
porated into a dental appliance, such deciduous (baby) tooth until the adult
as a partial denture, to help stabilize tooth erupts.
the appliance in the patient’s mouth by (b) Classification. Class I (general con-
fastening the appliance to an adjacent trols). The device is exempt from the
tooth. premarket notification procedures in
subpart E of part 807 of this chapter [52 FR 30097, Aug. 12, 1987, as amended at 59
FR 63008, Dec. 7, 1994; 66 FR 38798, July 25,
subject to the limitations in § 872.9. 2001]
FR 63008, Dec. 7, 1994; 66 FR 38798, July 25, § 872.3350 Gold or stainless steel cusp.
2001] (a) Identification. A gold or stainless
steel cusp is a prefabricated device
§ 872.3300 Hydrophilic resin coating made of austenitic alloys or alloys con-
for dentures.
(a) Identification. A hydrophilic resin metals of the platinum group or stain-
coating for dentures is a device that less steel intended to provide a perma-
consists of a water-retaining polymer nent cusp (a projection on the chewing
that is intended to be applied to the surface of a tooth) to achieve occlusal
base of a denture before the denture is harmony (a proper bite) between the
inserted into the patient’s mouth to teeth and a removable denture.
improve denture retention and com- (b) Classification. Class I (general con-
fort. trols). The device is exempt from the
(b) Classification. Class II (special premarket notification procedures in
controls). The device is exempt from subpart E of part 807 of this chapter
the premarket notification procedures subject to the limitations in § 872.9.
in subpart E of part 807 of this chapter [52 FR 30097, Aug. 12, 1987, as amended at 59
subject to the limitations in § 872.9. FR 63008, Dec. 7, 1994; 66 FR 38798, July 25,
2001]
FR 71812, Dec. 30, 2019] § 872.3360 Preformed cusp.
§ 872.3310 Coating material for resin (a) Identification. A performed cusp is
fillings. a prefabricated device made of plastic
or austenitic alloys or alloys con-
(a) Identification. A coating material
for resin fillings is a device intended to metals of the platinum group intended
be applied to the surface of a restora- to be used as a temporary cusp (a pro-
tive resin dental filling to attain a jection on the chewing surface of a
smooth, glaze-like finish on the surface
tooth) to achieve occlusal harmony (a

of the filling. proper bite) before permanent restora-
(b) Classification. Class II. tion of a tooth.
502
(b) Classification. Class I (general con- § 872.3410 Ethylene oxide

trols). The device is exempt from the homopolymer and/or
premarket notification procedures in carboxymethylcellulose sodium
subpart E of part 807 of this chapter denture adhesive.
subject to the limitations in § 872.9. (a) Identification. An ethylene oxide
[52 FR 30097, Aug. 12, 1987, as amended at 59 homopolymer and/or
FR 63008, Dec. 7, 1994; 66 FR 38798, July 25, carboxymethylcellulose sodium den-
2001] ture adhesive is a device containing
ethylene oxide homopolymer and/or
§ 872.3400 Karaya and sodium borate carboxymethylcellulose sodium in-
with or without acacia denture ad- tended to be applied to the base of a
hesive. denture before the denture is inserted
(a) Identification. A karaya and so- in a patient’s mouth to improve den-
dium borate with or without acacia ture retention and comfort.
denture adhesive is a device composed (b) Classification. Class I (general con-
of karaya and sodium borate with or trols). The device is exempt from the
without acacia intended to be applied premarket notification procedures in
to the base of a denture before the den- subpart E of part 807 of this chapter
ture is inserted into patient’s mouth to subject to the limitations in § 872.9.
improve denture retention and com-
fort. FR 63008, Dec. 7, 1994; 66 FR 38798, July 25,
(b) Classification. (1) Class I (general 2001]
controls) if the device contains less
than 12 percent by weight of sodium § 872.3420 Carboxymethylcellulose so-
borate. The class I device is exempt dium and cationic polyacrylamide
from the premarket notification proce- polymer denture adhesive.
dures in subpart E of part 807 of this (a) Identification. A
chapter subject to § 872.9. carboxymethylcellulose sodium and
(2) Class III if the device contains 12 cationic polyacrylamide polymer den-
percent or more by weight of sodium ture adhesive is a device composed of
borate. carboxymethylcellulose sodium and
(c) Date PMA or notice of completion of cationic polyacrylamide polymer in-
a PDP is required. A PMA or a notice of tended to be applied to the base of a
completion of a PDP is required to be denture before the denture is inserted
filed with the Food and Drug Adminis- in a patient’s mouth to improve den-
tration on or before December 26, 1996 ture retention and comfort.
for any karaya and sodium borate with (b) Classification. Class III.
or without acacia denture adhesive (c) Date PMA or notice of completion of
that was in commercial distribution a PDP is required. A PMA or a notice of
before May 28, 1976, or that has, on or completion of a PDP is required to be
before December 26, 1996 been found to filed with the Food and Drug Adminis-
be substantially equivalent to a karaya tration on or before December 26, 1996
and sodium borate with or without aca- for any carboxymethylcellulose sodium
cia denture adhesive that was in com- and cationic polyacrylamide polymer
mercial distribution before May 28, denture adhesive that was in commer-
1976. Any other karaya and sodium bo- cial distribution before May 28, 1976, or
rate with or without acacia denture ad- that has, on or before December 26, 1996
hesive shall have an approved PMA or been found to be substantially equiva-
a declared completed PDP in effect be- lent to a carboxymethylcellulose so-
fore being placed in commercial dis- dium and cationic polyacrylamide
tribution. polymer denture adhesive that was in
[52 FR 30097, Aug. 12, 1987, as amended at 61 commercial distribution before May 28,
FR 50706, Sept. 27, 1996; 65 FR 2315, Jan. 14, 1976. Any other carboxymethylcellulose
2000] sodium and cationic polyacrylamide

polymer denture adhesive shall have an
approved PMA or a declared completed
503
§ 872.3450 21 CFR Ch. I (4–1–23 Edition)
PDP in effect before being placed in sive shall have an approved PMA or a
commercial distribution. declared completed PDP in effect be-
fore being place in commercial dis-
FR 50707, Sept. 27, 1996] tribution.
§ 872.3450 Ethylene oxide FR 50707, Sept. 27, 1996]
homopolymer and/or karaya den-
ture adhesive. § 872.3490 Carboxymethylcellulose so-
(a) Identification. Ethylene oxide dium and/or polyvinylmethylether
homopolymer and/or karaya denture maleic acid calcium-sodium double
adhesive is a device composed of ethyl- salt denture adhesive.
ene oxide homopolymer and/or karaya (a) Identification. A
intended to be applied to the base of a carboxymethylcellulose sodium and/or
denture before the denture is inserted polyvinylmethylether maleic acid cal-
in a patient’s mouth to improve den- cium-sodium double salt denture adhe-
ture retention and comfort. sive is a device composed of
(b) Classification. (1) Class I if the de- carboxymethylcellulose sodium and/or
vice is made of wax-impregnated cot- polyvinylmethylether maleic acid cal-
ton cloth that the patient applies to cium-sodium double salt intended to be
the base or inner surface of a denture applied to the base of a denture before
before inserting the denture into the the denture is inserted in a patient’s
mouth. The device is intended to be mouth to improve denture retention
discarded following 1 day’s use. The and comfort.
class I device is exempt from the pre- (b) Classification. Class I (general con-
market notification procedures in sub- trols). The device is exempt from the
part E of part 807 of this chapter sub- premarket notification procedures in
ject to § 872.9. subpart E of part 807 of this chapter
[52 FR 30097, Aug. 12, 1987, as amended at 59 subject to the limitations in § 872.9.
FR 63008, Dec. 7, 1994; 65 FR 2315, Jan. 14, [52 FR 30097, Aug. 12, 1987, as amended at 59
2000] FR 63008, Dec. 7, 1994; 66 FR 38798, July 25,
2001]
§ 872.3480 Polyacrylamide polymer
(modified cationic) denture adhe- § 872.3500 Polyvinylmethylether ma-
sive. leic anhydride (PVM-MA), acid co-
(a) Identification. A polyacrylamide polymer, and
polymer (modified cationic) denture carboxymethylcellulose sodium
adhesive is a device composed of (NACMC) denture adhesive.
polyacrylamide polymer (modified cat- (a) Identification.
ionic) intended to be applied to the Polyvinylmethylether maleic anhy-
base of a denture before the denture is dride (PVM-MA), acid copolymer, and
inserted in a patient’s mouth to im- carboxymethylcellulose sodium
prove denture retention and comfort. (NACMC) denture adhesive is a device
(b) Classification. Class III. composed of polyvinylmethylether ma-
(c) Date PMA or notice of completion of leic anhydride, acid copolymer, and
a PDP is required. A PMA or a notice of carboxymethylcellulose sodium in-
completion of a PDP is required to be tended to be applied to the base of a
filed with the Food and Drug Adminis- denture before the denture is inserted
tration on or before December 26, 1996 in a patient’s mouth to improve den-
for any polyacrylamide polymer (modi- ture retention and comfort.
fied cationic) denture adhesive that (b) Classification. Class III.
was in commercial distribution before (c) Date PMA or notice of completion of
May 28, 1976, or that has, on or before a PDP is required. A PMA or a notice of
December 26, 1996 been found to be sub- completion of a PDP is required to be
stantially equivalent to a filed with the Food and Drug Adminis-
polyacrylamide polymer (modified cat- tration on or before December 26, 1996
ionic) denture adhesive that was in for any polyvinylmethylether maleic
commercial distribution before May 28, anhydride (PVM-MA), acid copolymer,

1976. Any other polyacrylamide poly- and carboxymethylcellulose sodium
mer (modified cationic) denture adhe- (NACMC) denture adhesive that was in
504
commercial distribution before May 28, § 872.3540 OTC denture cushion or

1976, or that has, on or before Decem- pad.
ber 26, 1996 been found to be substan- (a) Identification. An OTC denture
tially equivalent to a cushion or pad is a prefabricated or
polyvinylmethylether maleic anhy- noncustom made disposable device that
dride (PVM-MA), acid copolymer, and is intended to improve the fit of a loose
carboxymethylcellulose sodium or uncomfortable denture, and may be
(NACMC) denture adhesive that was in available for purchase over-the-
commercial distribution before May 28, counter.
1976. Any other polyvinylmethylether (b) Classification. (1) Class I if the de-
maleic anhydride (PVM-MA), acid co- vice is made of wax-impregnated cot-
polymer, and carboxymethylcellulose ton cloth that the patient applies to
sodium (NACMC) denture adhesive the base or inner surface of a denture
shall have an approved PMA or a de- before inserting the denture into the
clared completed PDP in effect before mouth. The device is intended to be
being placed in commercial distribu- discarded following 1 day’s use. The
tion. class I device is exempt from the pre-
[52 FR 30097, Aug. 12, 1987, as amended at 61 part E of part 807 of this chapter sub-
FR 50707, Sept. 27, 1996] ject to § 872.9.
(2) Class II (special controls) if the
§ 872.3520 OTC denture cleanser. OTC denture cushion or pad is made of
(a) Identification. An OTC denture a material other than wax-impregnated
cleanser is a device that consists of cotton cloth or if the intended use of
material in the form of a powder, tab- the device differs from that described
let, or paste that is intended to remove in paragraph (b)(1) of this section. The
debris from removable prosthetic den- device is exempt from the premarket
tal appliances, such as bridges or den- notification procedures in subpart E of
part 807 of this chapter subject to the
tures. The dental appliance is removed
limitations in § 872.9. The special con-
from the patient’s mouth when the ap-
trols for this device are FDA’s:
pliance is cleaned.
(i) ‘‘Use of International Standard
(b) Classification. Class I (general con- ISO 10993 ‘Biological Evaluation of
trols). The device is exempt from the Medical—Devices Part I: Evaluation
premarket notification procedures in and Testing,’ ’’ and
subpart E of part 807 of this chapter (ii) ‘‘OTC Denture Reliners, Repair
subject to the limitations in § 872.9. Kits, and Partially Fabricated Denture
[52 FR 30097, Aug. 12, 1987, as amended at 59 Kits.’’
FR 63008, Dec. 7, 1994; 66 FR 38798, July 25, [52 FR 30097, Aug. 12, 1987, as amended at 65
2001] FR 2315, 2000; 65 FR 17144, Mar. 31, 2000; 84 FR
71812, Dec. 30, 2019]
§ 872.3530 Mechanical denture cleaner.
§ 872.3560 OTC denture reliner.
(a) Identification. A mechanical den-
ture cleaner is a device, usually AC- (a) Identification. An OTC denture
powered, that consists of a container reliner is a device consisting of a mate-
for mechanically agitating a denture rial such as plastic resin that is in-
cleansing solution. The device is intended to be applied as a permanent
tended to clean a denture by submer- coating or lining on the base or tissue-
sion in the agitating cleansing solution contacting surface of a denture. The
in the container. device is intended to replace a worn
denture lining and may be available for
purchase over the counter.
premarket notification procedures in controls). The device is exempt from
subpart E of part 807 of this chapter the premarket notification procedures
[55 FR 48439, Nov. 20, 1990, as amended at 59 subject to the limitations in § 872.9. The
FR 63008, Dec. 7, 1994; 66 FR 38798, July 25, special controls for this device are
2001] FDA’s:
505
§ 872.3570 21 CFR Ch. I (4–1–23 Edition)
(1) ‘‘Use of International Standard § 872.3590 Preformed plastic denture

ISO 10993 ‘Biological Evaluation of tooth.
Medical Devices—Part I: Evaluation (a) Identification. A preformed plastic
and Testing,’ ’’ and denture tooth is a prefabricated device,
(2) ‘‘OTC Denture Reliners, Repair composed of materials such as methyl
Kits, and Partially Fabricated Denture methacrylate, that is intended for use
Kits.’’ as a tooth in a denture.
[52 FR 30097, Aug. 12, 1987, as amended at 61 (b) Classification. Class II (special
FR 50707, Sept. 27, 1996; 65 FR 17144, Mar. 31, controls). The device is exempt from
2000; 84 FR 71812, Dec. 30, 2019] the premarket notification procedures
§ 872.3570 OTC denture repair kit. subject to the limitations in § 872.9.
(a) Identification. An OTC denture re- [52 FR 30097, Aug. 12, 1987, as amended at 84

CFR 2023 Title21 Vol8 ChapI

Uploaded by

Copyright:

Available Formats

CFR 2023 Title21 Vol8 ChapI

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

CFR 2023 Title21 Vol8 ChapI

Uploaded by

Copyright:

Available Formats

Title 21—Food and

CHAPTER I—Food and Drug Administration, Department of

SUBCHAPTER H—MEDICAL DEVICES

876 Gastroenterology-urology devices .......................... 539

900 Mammography ........................................................ 820

1000 General .................................................................... 860

1100 General .................................................................... 946

ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION

PART 800—GENERAL in the meaning of section 502(j) of the

other dosage forms to be used to make processes. A tamper-resistant package

composition of the closure component barrier to entry be distinctive by de-

ity); diately, keep the glove/filling tube as-

91 to 280 Single sample 32 1 2

281 to 500 Single sample 50 2 3

501 to 1,200 Single sample 80 3 4

1,201 to 3,200 First 32 32 — 4

3,201 to 10,000 First 50 50 0 4

10,001 to 35,000 First 80 80 0 5

35,000 First 125 125 1 7

ACCEPT/REJECT CRITERIA AT 1.5 AQL FOR SURGEONS’ GLOVES—Continued

Third 125 375 8 13

ACCEPT/REJECT CRITERIA AT 2.5 AQL FOR PATIENT EXAMINATION GLOVES

51 to 150 Single sample 20 1 2

151 to 280 Single sample 32 2 3

281 to 500 Single sample 50 3 4

501 to 1,200 Single sample 80 5 6

1,201 to 3,200 First 32 32 0 4

3,201 to 10,000 First 50 50 0 5

10,001 to 35,000 First 80 80 1 7

35,000 and above First 125 125 2 9

(d) Compliance. Lots of gloves that as detention of imported products and

91 to 500 Single sample 50 1 2

501 to 1,200 Single sample 80 2 3

1,201 to 3,200 Single sample 125 3 4

3,201 to 10,000 Single sample 200 5 6

10,001 to 35,000 Single sample 315 8 9

35,000 and above Single sample 500 12 13

ACCEPT/REJECT CRITERIA AT 2.5 AQL FOR RECONDITIONED PATIENT EXAMINATION GLOVES

51 to 280 Single sample 32 1 2

281 to 500 Single sample 50 2 3

501 to 1,200 Single sample 80 3 4

1,201 to 3,200 Single sample 125 5 6

3,201 to 10,000 Single sample 200 8 9

10,001 to 35,000 Single sample 315 12 13

35,000 and above Single sample 500 18 19

(a) Scope. This section specifies the

(B) Symptoms suggesting perceived mild

(C) Advice of availability of professional

(D) ‘‘Red flag’’ conditions. ER17AU22.002</GPH>

(E) Notice of contact information.

(F) Notice of manufacturer’s return pol-

such fact. The outside package shall indicate the

(B) ‘‘Red flag’’ conditions.

(C) Warning about pain from device

(B) Caution about excessive sound out-

(C) Caution about components lodging

(D) Advice to seek professional services.

(E) Note about user expectations.

(E) Note about reporting adverse events

(iv) An illustration(s) of the OTC (vii) Specific instructions for all of