Central Service Suppl.

2012 recommendations | 5

Guideline for Validation of Packaging

Processes according to ISO 11607-2

|| 1 Scope –– ISO 11607-1:2009 (worst-case scenario, while providing doc-

The standard series ISO 11607 stipulates –– ISO 11607-2:2006 umentary proof to justify this).
validation of the packaging processes –– EN 868:2009, Part 2-104 Worst-case examples:
used for industry, health care facilities –– ISO 11140-1:2009 –– Gusseted pouches and reels are more
and wherever medical devices are pack- critical than flat pouches and reels.
–– ISO 9001:2008
aged and sterilized (examples of health –– Steam sterilization at 134 °C/18 min is
care facilities include hospitals, doctors' –– ISO 13485:2010
more critical than at 134 °C/5 min and
and dentists' surgeries). –– DIN 58953:2010, Part 1, 6, 7, 8, 95 121 °C/20 min.
The ISO 11607, Part 2 standard (Article (German Standard)
A further reduction can be achieved by
5.1.1) explicitly calls for validation of all The standards stated in table 1 are of rel- a deliberate choice of packaging materi-
packaging processes. The present Guide- evance for validation and should be made als (e. g. see through pouch instead of pa-
line deals with the following packaging accessible to the user. per bag).
processes: Annex A.5, B.5 and C.5 show practical
–– pouch, reel or bag sealing2
–– sterilization sheets folding and wrap-
|| 3 Prerequisites examples.
The packaging materials used must be
ping
–– filling and closing of reusable steriliza-
suited to and defined for the intended || 4 Validation of packaging proc-
tion containers
packaging and sterilization processes. esses
Suitability shall be determined on the ba- In principle, a documented process must
Likewise, packaging processes not dealt sis of the information provided by the man- be available for validation. This process
with here must also be validated as per ufacturer. This includes confirmation of comprises:
ISO 11607-2. Non-validable packaging
conformity with the ISO 11607-1 stand- 4.1 Drafting of a validation plan
processes are not acceptable in practice
ard and pertinent sections of the EN 868, 4.2 Validation of packaging processes
anymore (Self Seal pouches or taped pa-
Parts 2–10 standard series, in respect of: 4.2.1 Installation qualification (IQ)
per bags).
–– microbial impermeability 4.2.2 Operational qualification (OQ)
–– compatibility with the sterilization proc- 4.2.3 Performance qualification (PQ)
|| 2 Normative bases ess. 4.3 Drafting of a validation report
The bases for drafting this Guideline in- The number of process validations to be 4.4 Formal approval of validation
clude, inter alia, the following standards3:
conducted can be elucidated and defined 4.5 Process control and monitoring
on the basis of Table 2 (see example An-
4.6 Process changes and revalidation
nex A.5, B.5 and C.5).
The number of combinations outlined in 4.1 Drafting of a validation plan
2 If the sealing processes were already va- the table can be reduced by taking ac- The validation plan should contain, at
lidated in accordance with the «Guideline for count of only the maximum material stress least, the following details:
validation of the sealing process as per ISO
11607-2 (Revision 1, status: July 2008)», there
is no need to repeat initial validation.
3 The publication years of the pertinent stan-
dards are only given here.
Table 1: Standards of relevance for the validation
4 EN 868, Part 1 has been replaced by the Requirements for materials, sterile bar-
ISO 11607-1
ISO 11607-1 standard. rier systems and packaging systems
5 German Standard DIN 58953, Parts 2–5
ISO 11607-2 Validation requirements
have been replaced by EN 868, Parts 2–5.
6 | recommEndations Central Service Suppl. 2012

Then the sealing temperature must be

Table 2: Number of process validations to be conducted
The terms used for sterilization processes are based on the standard ISO 11140-1. specified for routine operations. In gen-
eral this is calculated from the mean value
VH2O2 of the limit values (e. g. mean value from
Sterile bar- STEAM FORM EO (vaporized 170 °C and 200 °C is 185 °C).
rier system (Form- (Ethylene hydrogen-
(SBS) 134 °C/ 134 °C/ 121 °C/ aldehyde) oxide) peroxyde; Manual processes
5 min 18 min 20 min «Plasma»)
Here: sterilization sheets' folding and
Material A wrapping; filling and closing of reusable
sterilization containers9.
Material B First, the most critical packaging config-
uration must be determined (worst case).
Material C Examples include:
–– the heaviest and largest tray (container)
Material D
–– large, unwieldy single instruments
Then these configurations must be packed
according to the standard operating pro-
cedures.
When checking the sterile barrier systems
–– Competences The «Operational qualification (OQ)» produced all defined quality properties as
–– Description of the packaging process checklists in Annex A.3, B.3 and C.3 can well as the correct packing method set out
–– Description of the materials /equipment be used for documentary purposes. in the standard operating procedure (see
–– Description of the sterilization proc- In principle, a distinction must be made Annex B.6 and C.6) must be assured.
esses here between automated and manual proc- Pursuant to the ISO 11607-2, § 5.3.2 c
–– Qualification steps (IQ, OQ and PQ) esses. standard the quality properties required
for sterilization sheets and reusable steri-
The «Validation plan» checklists in Annex Automated processes lization containers are as follows:
A.1, B.1 and C.1 can be used. Here: pouch, reel or bag sealing. –– continuous closeness/integrity
The heat sealing process is defined on the
4.2 Conduct of validation –– no punctures or tears (not applicable to
basis of the following parameters:
4.2.1 Installation qualification (IQ) reusable sterilization containers)
–– Sealing temperature,
Definition: «Process of obtaining and docu- –– no other visible damage or material ir-
–– Contact pressure and
menting evidence that equipment has been regularities10.
–– Sealing time/speed (dwell).
provided and installed in accordance with The quality properties must be verified
the specification.» The contact pressure and sealing speed or
and documented by means of suitable
That means that technical equipment (e. g. time (dwell) are generally set by the manu-
processes or tests. For the combinations
heat sealers) must have been properly in- facturer of the heat sealer.
specified in the validation plan, 10 ster-
stalled and users trained. The optimum sealing temperature for the
ile barrier systems of the same material
In general, the packing processes involv- respective packaging material must be
must be packed and their quality prop-
ing sterilization sheets as well as reus- determined by the user. To that effect, the
erties checked. To document the quality
able sterilization containers are purely technical data sheet supplied by the manu-
properties it is recommended that at least
manual processes, which is why proof of facturer of the packaging material is need-
one photo is taken of each sample.
IQ is based on documentation of train- ed. This must specify the sealing tempera-
ing of staff. ture (e. g.170 – 200 °C). 4.2.3 Performance qualification (PQ)
It is recommended that the corresponding Sealing samples must be produced for the Definition: «Process of obtaining and doc-
checklists be used to conduct installation respective lower and upper limits.
umenting evidence that the equipment, as
qualification (IQ). The «Installation qual- The quality properties listed in ISO 11607-
installed and operated in accordance with
ification (IQ)» checklists in Annex A.2, 2, § 5.3.2 b must be assured:
operational procedures, consistently per-
B.2 and C.2 can be used for documentary –– intact seal for a specified seal width
forms in accordance with predetermined
purposes. –– no channels or open seals criteria and thereby yields product meet-
–– no punctures or tears ing its specification.»
4.2.2 Operational qualification (OQ)
Definition: «Process of obtaining and docu- –– no material delamination or separation During performance qualification proof
menting evidence that installed equipment These quality properties must be veri- must be provided after sterilization that
operates within predetermined limits when fied and documented by means of suit- the process is under control and produc-
used in accordance with its operational pro- able processes. The test methods in Ta- es optimally sealed or closed sterile bar-
cedures.» ble 3, for example, can be used as a guide. rier systems.
Central Service Suppl. 2012 recommEndations | 7

–– no channels or open seals

Table 3: Test methods for verification of quality properties –– no punctures or tears
Suitable for verification of the following –– no material delamination or separation
Test method
quality properties These quality properties must be veri-
Seal integrity test (e. g. «dye penetration fied and documented by means of suit-
– channels or open seals
test/InkTest» according to ISO 11607-1, able processes. The test methods in Table
– punctures or tears
Annex B6) 3, for example, can be used as a guide.

– intact seal for a specified seal width Manual processes

Seal integrity indicator7 (e. g. Seal
– channels or open seals For the test, sterilized packaging systems
Check)
– punctures or tears
must be taken from the running process-
es. From three different cycles (batches)
Peel test according to EN 868, Annex E – material delamination or separation
one sample must be taken in each case.
The batch documentation (protocols) of
– intact seal for a specified seal width
Visual inspection8 the respective sterilization processes is
– punctures or tears
part of validation.

The «Performance qualification (PQ)» –– Recording of the seal seam strength13

checklists in Annex A.4, B.4 and C.4 can –– Evaluation and documentation of the re-
be used for documentation purposes. sults
6 The basis for this test method is ASTM
Here, too, a distinction must be made be- The results of the seal strength test are F1929 2 «Standard test method for detecting
tween automated and manual processes. seal leaks in porous medical packaging by dye
confirmed in a report, containing at least
penetration»
Automated processes the following information:
7 The seal integrity indicator must not under
Verification is done by means of the seal –– Manufacturer and type of heat sealer any circumstances be cut since it must always
strength test as per EN 868-5, Annex D11. –– Serial number of heat sealer be guaranteed that the entire pinch roller of
the sealing device is printed off. Furthermore,
The packaging must be sterilized before –– Specification of the sealing parameters the seal indicator shall always be made of the
verification. The protocols/logs (batch –– Identification of the verified product same type of material as the porous part of
documentation) related to the steriliza- –– Maximum strength of seal of each sam- the packaging (medical grade paper as per EN
868-3 or HDPE as per EN 868-9/10)
tion processes are part of validation. ple measured in N/15 mm width
8 For visual inspection standardized test
For the defined combinations (see also An- –– Whether verification was done with the methods can be used (e. g. ISO 11607-1, Annex
nex A.5) three empty pouches or reels of free end supported or not B [ASTM F1886])
the same material must be sealed, clearly –– The frequency used (data per second of 9 The partial step «Filling of pouches and
labelled (sealing device, serial number, reels» is also a manual process and must be
measurement)
set out in a standard operating procedure. The
sealing parameters) and then sterilized –– Test device (manufacturer, designation)/ heat sealing process itself is normally fully au-
with the specified sterilization program last calibration tomated.
(reels must be sealed at both ends). Each –– Graphic display of resistance 10 The ISO 11607-2 standard uses «No mate-
pouch must be added to a different steri- rial delamination or separation» here.
–– Date of test 11 Alternatively, the test method as per ASTM
lization load to take account of all the fac-
Testing of the sealed and sterilized pouch- F88 can be used (validated and round robin
tors exerting an influence on the sterili- approved test method).
es can, for example, be carried out by an
zation loads. 12 EN 868-5:1999 specified five samples per
accredited test laboratory or by the device/
The test (as per EN 868-5, Annex D) is car- seal seam. EN 868-5:2009 stipulates only one
material manufacturer. sample per seal seam. Additional samples may
ried out as follows:
The maximum strength must be entered be needed if the length of a seal is more than
–– Cuts measuring 15 mm in width are tak- into the table in Annex A.4. The maximum 500 mm.
en of the dried samples and at an an- strength is the relevant value for assess- 13 For further evaluation and documentation it
gle of 90 ° to the seal seam. At least one ment and, as per EN 868-5, must be great- is advisable to specify as a value the maximum
sample of a produced seal seam must (required as per EN 868-5 Annex D.3) and ad-
er than or equal to 1.5 N/15 mm width14. If ditionally the average tensile strength.
be taken from each packaging12. If only the maximum tensile strength of one of the 14 EN 868-5, § 4.5.1 «The minimum seal
one sample of a seal seam is taken, the three tests is less than 1.5 N/15 mm width, strength value for steam sterilization processes
sample must be taken from around the PQ is deemed to have failed. must be 1.5 N per 15 mm in health care facili-
centre. In addition the quality properties listed in ties and 1.2 N per 15 mm in other sterilization
processes in health care facilities». However,
–– Simulation of the peeling process at a ISO 11607-2, § 5.3.2 b must be assured: stipulation of a minimum value of 1.5 N/15 mm
speed of 200 mm/min –– intact seal for a specified seal width is recommended for all sterilization processes.
8 | recommEndations Central Service Suppl. 2012

Assurance of the quality properties must 4.5 Process control and monitoring tial validation (IQ, OQ and PQ). That
be verified for each packaging system The routine tests that are established dur- no changes were made to materials,
(sample). ing the validation as being necessary must processes or sterilization compared to
Pursuant to standard ISO 11607-2, § 5.3.2 c be documented (e. g.in the standard op- the previous validation must be con-
the quality properties for sterilization erating procedure). This is intended as firmed in the revalidation report. If
sheets and reusable sterilization contain- a means of ensuring that changes in the changes are made to materials, proc-
ers are as follows: packaging process are detected on time esses or sterilization how such chang-
before they compromise the sterile bar- es will affect the packaging process
–– continuous closeness/integrity
rier systems and the requirements are no results must be elucidated. The re-
–– no punctures or tears (not applicable to
longer met. These include, e. g.: sults must be documented. Based on
reusable sterilization containers)
–– Visual inspection16 these, an individual revalidation plan
–– no other visible damage or material ir- must be drafted. Accordingly, in the
–– Peelability (e. g. peel test as per EN 868-
regularities15. event of material changes, for exam-
5, Annex E «Method for determination of
These quality properties must be veri- the peel characteristics of paper/plastic ple, operational qualification (OQ) and
fied and documented by means of suita- laminate products») performance qualification (PQ) must
ble processes or tests. The sterile barrier be partially or fully repeated, and if
–– Seal integrity test (e. g. dye penetration
systems or packaging systems are opened changes are made to the packaging
test/ink test as per ISO 11607-1, Annex
one step after the other, verified and docu- process or to the equipment used in-
B17)
mented (for photographic documentation stallation qualification (IQ) must also
see Annex B.8/C.7). –– Seal integrity indicator18 (e.  g. Seal
be repeated. For revalidation it must
Check)
be ensured that the documents used
4.3 Drafting of a validation report –– Tensile strength of seal seam (e. g. de- meet the current requirements. The
The validation procedures and results termination of seal seam strength as per checklists must be updated if neces-
must be documented in a summary re- EN 868-5, Annex D «Method for deter- sary. An individual validation plan is
port. The checklists, protocols and any mination of the seal seam strength of required for each revalidation or per-
photographic documentation used serve pouches and reels» formance requalification. The «Vali-
as evidence and must be enclosed in an –– Stepwise opening of packaging (in the dation plan» checklists in Annex A.1,
annex to the report. case of sterilization sheets or reusable B.1 and C.1 can be used. ■
The report must contain, at least, the fol- sterilization containers).
lowing information:
Intervals (e. g. daily, weekly, monthly,
Validation plan yearly) and acceptance values must be
–– Evidence of implementation of the vali- defined for the routine tests needed, in-
dation plan (IQ, OQ and PQ checklists cluding the action to be taken if a test re-
completed as per Annex) sult is not satisfactory. The routine test
–– Evaluation of the results results must be documented. This proce-
–– Photographic documentation for manual dure must be set out in the quality man-
packing processes agement system.
–– Details and explanation of any devia- 15 The ISO 11607-2 standard uses «No mate-
4.6 Process changes and revalidation rial delamination or separation» here.
tions from validation plan
Processes must be revalidated: 16 For visual inspection standardized test
–– Formal approval of validation methods can be used (e. g. ISO 11607-1,
–– Unscheduled revalidation,
–– Process control and monitoring Annex B [ASTM F1886] for seal seams or EN
• for example in the event of changes 868-8 for reusable sterilization containers.
–– Process changes and revalidation to materials, processes, including 17 The basis for this test method is ASTM
4.4 Formal approval of validation changes to equipment or occurring F1929 «Standard test method for detecting
during sterilization (revalidation) seal leaks in porous medical packaging by dye
Validation, as documented and evaluated
penetration».
in the report, must be formally approved, –– Scheduled revalidation,
18 The seal integrity indicator must not un-
and duly documented, by the competent • at regular intervals, i. e. in general af- der any circumstances be cut since it must
person appointed by the operator. This can ter one year if no changes were made always be guaranteed that the entire pinch
be recorded, for example, in a field pro- to materials, sealing process or steri- roller of the sealing device is printed off.
vided to that effect in the validation plan. lization (performance requalification). Furthermore, the seal integrity indicator shall
always be made of the same type of material
If all validation results are not accepted, • provides evidence that the packag- as the porous part of the packaging (medical
this must be clearly documented, includ- ing process continues to be within grade paper as per EN 868-3 or HDPE as per
ing assessment of any remaining risks. the limits defined at the time of ini- EN 868-9/10)