78_F.Supp.3d_65

TAKEDA PHARMACEUTICALS, U.S.A., INC. v.
BURWELL 65
Cite as 78 F.Supp.3d 65 (D.D.C. 2015)
tion to dismiss under Rule 12(b)(6). A lated Food, Drug, and Cosmetic Act
separate final order accompanies this (FDCA) when it approved a competitor’s
Memorandum Opinion. New Drug Application (NDA) for a drug
that was substantially similar to manufac-
turer’s gout medication. Competitor inter-
, vened as a defendant, and parties cross-

moved for summary judgment.
Holdings: The District Court, Ketanji
Brown Jackson, J., held that:
(1) FDA’s approval of NDA did not violate
TAKEDA PHARMACEUTICALS, FDCA, and
U.S.A., INC., Plaintiff, (2) FDA’s approval of NDA was neither
v. arbitrary nor capricious.
Ordered accordingly.
Sylvia Mathews BURWELL, in her offi-
cial capacity as Secretary, United
States Department of Health and Hu- 1. Administrative Law and Procedure
man Services, et al., Defendants, O811
and In a case involving review of final
administrative action under the Adminis-
Hikma Pharmaceuticals PLC, et trative Procedure Act (APA), summary
al., Intervenor–Defendants. judgment serves as a mechanism for decid-
and ing, as a matter of law, whether the agen-
cy action is supported by the administra-
Elliott Associates, L.P., tive record and is otherwise consistent
et al., Plaintiffs, with the APA standard of review. 5
v. U.S.C.A. § 706.
Sylvia Mathews Burwell, in her official 2. Administrative Law and Procedure
capacity as Secretary, United States O788
Department of Health and Human Under the Administrative Procedure
Services, et al., Defendants, Act (APA), it is the role of the agency to
and resolve factual issues to arrive at a deci-
sion that is supported by the administra-
Hikma Pharmaceuticals PLC, et tive record, whereas the function of the
al., Intervenor–Defendants. district court is to determine whether or
Civil Action No. 14–cv–1668 (KBJ), not as a matter of law the evidence in the
Civil Action No. 14–cv–1850 administrative record permitted the agen-
(KBJ) cy to make the decision it did. 5 U.S.C.A.
§ 706.
United States District Court,
District of Columbia. 3. Administrative Law and Procedure
O760
Signed January 13, 2015 In reviewing final agency action under
Background: Pharmaceutical manufactur- the Administrative Procedure Act (APA),
er brought action against Food and Drug the court cannot substitute its judgment
Administration (FDA), alleging that it vio- for that of the agency, especially when the
66 78 FEDERAL SUPPLEMENT, 3d SERIES
agency’s scientific expertise informs its 7. Health O317

judgment. 5 U.S.C.A. § 706. An applicant submitting a New Drug
Application (NDA) that relies on the stud-
4. Administrative Law and Procedure ies of a Reference Listed Drug (RLD) has
O749 the discretion under the FDCA to select a
Given that the scope of review under reference drug of its choosing and to make
the Administrative Procedure Act’s (APA) that selection in relation to the scope of
arbitrary and capricious standard is nar- the materials the applicant desires to sub-
row, the agency action under review is mit. Federal Food, Drug, and Cosmetic
entitled to a presumption of regularity. 5 Act § 505, 21 U.S.C.A. § 355(b)(2).
U.S.C.A. § 706. 8. Administrative Law and Procedure
O432, 433
5. Health O317
A court reviews an agency’s own in-
Food and Drug Administration’s terpretation of a statute it administers un-
(FDA) approval of a New Drug Applica- der the two-step framework of Chevron,
tion (NDA) for a drug that was substan- which first requires the court to consider
tially similar to pharmaceutical manufac- whether Congress has spoken to the pre-
turer’s gout medication without requiring a cise question at issue, and, if there is no
reference to manufacturer’s drug or a cer- clear answer, second requires the court to
tification to its patents did not violate give deference to the agency’s interpreta-
Food, Drug, and Cosmetics Act (FDCA); tion of the statute so long as the agency’s
FDA did not rely on studies underlying reading of the statute is based on a per-
manufacturer’s previously approved appli- missible construction.
cation in approving NDA, but merely con-
9. Health O317
sidered differences between findings of
those studies and findings of studies cited Under the FDCA, a New Drug Appli-
by applicant, even if FDA had relied on cation (NDA) that relies on the studies of a
manufacturer’s studies, such reliance by Reference Listed Drug (RLD) need only
FDA did not trigger FDCA’s patent certi- certify to the product patents or the meth-
fication requirements, applicant had dis- od-of-use patents that are associated with
cretion to select a reference drug of its the RLD. Federal Food, Drug, and Cos-
choosing for its NDA, and applicant was metic Act § 505, 21 U.S.C.A. § 355(b)(2).
only required to certify to patents associat- 10. Health O317
ed with reference drug it chose. Federal Food and Drug Administration’s
Food, Drug, and Cosmetic Act § 505, 21 (FDA) approval of a New Drug Applica-
U.S.C.A. § 355(b)(2). tion (NDA) for a single-ingredient oral col-
chicine product that was substantially simi-
6. Health O317
lar to pharmaceutical manufacturer’s gout
The Food and Drug Administration’s medication was not an unreasoned change
(FDA) reliance on studies underlying a of FDA’s prior position and was not arbi-
previously approved drug in considering a trary or capricious, even though NDA
New Drug Application (NDA) does not product’s label differed from that of manu-
trigger the FDCA’s patent certification re- facturer’s medication; FDA determined
quirements. Federal Food, Drug, and that recent scientific research about inter-
Cosmetic Act § 505, 21 U.S.C.A. action between colchicine and certain
§ 355(b)(2). classes of inhibitor drugs cast doubt on
TAKEDA PHARMACEUTICALS, U.S.A., INC. v. BURWELL 67
ability to generalize manufacturer’s drug- 1. Mutual Relies On ColBenemid, Pub-

drug interaction studies, FDA rationally lished Literature, And Its Own Clinical
concluded that instructions on manufactur- Studies To Support The Colcrys Applica-
er’s label about additional low-dose tion For Acute Flares Of Gout TTT 74
amounts that a user might take for treat- 2. Mutual Relies on ColBenemid and
ment of gout flares were inappropriate for Published Literature To Support The Col-
NDA product, given that it was being ap- crys Application For Prophylactic Treat-
proved for prophylaxis of gout flares, and ment of Gout TTT 76
deference was owed to FDA’s scientific
3. FDA Takes Enforcement Action
determination that NDA product was safe.
Against Unapproved Oral Colchicine Prod-
ucts Because Their Labels Do Not Reflect
The Most Current Data TTT 76
D. FDA’s Approval Of Mitigare (A
Jessica L. Ellsworth, Susan Margaret Colchicine Capsule) TTT 77
Cook, Catherine E. Stetson, Hogan Lovells
1. Mutual Files A Citizen Petition Pro-
US LLP, Matthew D. McGill, Lucas C.
testing West–Ward’s Application And
Townsend, Mithun Mansinghani, Gibson
FDA Responds TTT 77
Dunn & Crutcher LLP, Washington, DC,
Michael Sitzman, Gibson, Dunn & Crutch- 2. FDA Approves Mitigare Capsule For
er LLP, San Francisco, CA, for Plaintiff. Prophylaxis Of Gout Flares Based On Col–
Probenecid, Published Literature, and
Jessica R. Gunder, U.S. Department of West–Ward’s Own Studies TTT 79
Justice, Washington, DC, for Defendant.
3. West–Ward Launches Mitigare, Alert-
ing Takeda To The Existence Of Mitigare
UNDER SEAL TTT 80
MEMORANDUM OPINION E. Procedural History TTT 80

II. LEGAL STANDARDS TTT 83
KETANJI BROWN JACKSON, United
III. DISCUSSION TTT 84
States District Judge
A. FDA’s Approval Of Mitigare With-
Table Of Contents
out A Colcrys Reference And Related Cer-
I. BACKGROUND TTT 69 tifications To The Colcrys Patents Did Not
Violate The Agency’s Rules Or The FDCA
A. Colchicine: A Drug For The Treat-
TTT 84
ment Of Gout TTT 69
1. FDA’s Procedural Rules Did Not Re-
B. FDA’s Drug Approval Framework:
quire West–Ward To Reference Colcrys
The Hatch–Waxman Amendments TTT 71
Because West–Ward Did Not Rely On Col-
1. NDAs, ANDAs, and 505(b)(2) NDAs crys Data To Support West–Ward’s Appli-
TTT 71 cation For FDA Approval Of Mitigare TTT
85
2. The Patent Certification Requirement
TTT 72 a. No FDA Policy Establishes That
FDA’s Reliance—As Opposed To That Of
3. The Labeling Requirements TTT 73
The Section 505(b)(2) Applicant—Gives
C. FDA’s Approval Of Colcrys (A Col- Rise To Patent Certification Obligations
chicine Tablet) TTT 74 TTT 86
b. Even If Agency Reliance On Third– liott Associates, L.P., Elliott International,

Party Data Is Relevant, FDA Did Not L.P., and Knollwood Investments, L.P.
Approve Mitigare In Reliance On Mutual’s (collectively, ‘‘Elliott’’) allege that the Food
Information TTT 90 and Drug Administration (‘‘FDA’’) upset
Hatch–Waxman’s careful balance when the
2. Under FDA’s Procedural Rules, An
agency approved an application that Hik-
Applicant—Not FDA—Has The Right To
ma Pharmaceuticals PLC (‘‘Hikma’’) sub-
Choose The ‘‘Most Appropriate’’ Or ‘‘Most
mitted through its U.S. agent West–Ward
Similar’’ Reference Drug For Its 505(b)(2)
Pharmaceuticals Corp. (‘‘West–Ward’’) for
Application TTT 92
a gout medication named Mitigare. Miti-
3. The FDCA Unambiguously Requires gare is a single-ingredient 0.6 milligram
A Section 505(b)(2) Applicant To Certify (‘‘mg’’) oral colchicine drug product that is
Only To Patents Associated With The Ref- substantially similar to Plaintiffs’ colchi-
erence Listed Drug TTT 95 cine drug, Colcrys, which FDA approved
B. FDA’s Approval Of Mitigare Was five years prior to Mitigare based in part
Not An Unreasoned Change Of The Agen- on research studies that Takeda’s prede-
cy’s Prior Position Regarding Single–In- cessor Mutual Pharmaceutical Company,
gredient Oral Colchicine Products TTT 103 Inc. (‘‘Mutual’’) conducted. In seeking ap-
proval for Mitigare, West–Ward neither
C. FDA’s Decision To Approve Miti- referenced Colcrys nor certified to the Col-
gare With A Label That Contains Safety crys patents, and Hikma has now author-
Information That Differs From Colcrys ized West–Ward to market a generic ver-
Was Not Arbitrary And Capricious TTT sion of Mitigare that will compete with—
107 and cost less than—Plaintiffs’ Colcrys.
IV. CONCLUSION TTT 108
In the separate but consolidated com-
The Hatch–Waxman Amendments to the plaints that Takeda and Elliott have filed
Food, Drug, and Cosmetic Act (‘‘FDCA’’), in this Court against Defendants Sylvia
Pub. L. No. 98–417, 98 Stat. 1585 (1984), Mathews Burwell (in her official capacity
‘‘balance two competing interests in the as Secretary of the Department of Health
pharmaceutical industry: (1) inducing pio- and Human Services) and Margaret Ham-
neering research and development of new burg (in her official capacity as head of the
drugs and (2) enabling competitors to FDA), Plaintiffs maintain that FDA’s ap-
bring low-cost, generic copies of those proval of Mitigare without a Colcrys refer-
drugs to market.’’ Janssen Pharmaceuti- ence or the related patent certifications
ca, N.V. v. Apotex, Inc., 540 F.3d 1353, violates the Administrative Procedure Act
1355 (Fed.Cir.2008) (internal quotation (‘‘APA’’) because that approval was incon-
marks and citation omitted). Hatch–Wax- sistent with the agency’s procedural rules
man achieves this balance, in part, by al- and the certification provisions of the
lowing new applicants for drug approval to FDCA. Plaintiffs also claim that FDA’s
rely on research and data that an innova- approval of Mitigare was arbitrary and
tor company generates so long as the new capricious because Mitigare’s label lacks
applicant ‘‘references’’ the innovator’s drug certain safety information that is on the
and ‘‘certifies’’ to the innovator’s patents. Colcrys label—information that is related
See infra Part I.B.2; see also 21 U.S.C. to Mutual’s research and that FDA previ-
§ 355(b)(2)(A). Plaintiffs Takeda Pharma- ously suggested should be on the label of
ceuticals U.S.A., Inc. (‘‘Takeda’’) and El- future colchicine drug products. The law-
suits that Takeda and Elliott have filed fendants’ and Defendant–Intervenors’
(and in which Hikma and West–Ward have cross-motions for summary judgment in
now intervened) request a stay or rescis- Elliott Associates, L.P. v. Burwell, No. 14–
sion of FDA’s approval of Mitigare as a 1850–KBJ (D.D.C.), are GRANTED. This
remedy for these alleged violations. Court issued a separate order consistent
Before this Court at present are four with this opinion on January 9, 2015.
cross-motions for summary judgment that
I. BACKGROUND
the Plaintiffs, the Defendants, and the De-
fendant–Intervenors have submitted in the The instant dispute involves two drug
context of the two pending actions.1 This products, both of which have the active
Court has considered these dispositive mo- ingredient colchicine, which is a pharmaco-
tions, the oppositions thereto, the supple- logical substance that has been used his-
mental briefing, and the arguments made torically for the treatment of gout.2 Plain-
orally at the two hearings that this Court tiffs have a financial interest in Colcrys—
has held in relation to this matter. Be- an FDA-approved 0.6 mg single-ingredient
cause this Court agrees with Defendants oral colchicine tablet—and they have
and Defendant–Intervenors that (1) no brought this challenge to Defendant FDA’s
statute, regulation, or policy required FDA recent approval of Intervenors’ Mitigare,
to reject West–Ward’s application for Miti- which is a 0.6 mg single-ingredient oral
gare because the application did not refer- colchicine capsule. In order to understand
ence Colcrys or certify to the Colcrys pat- the Plaintiffs’ challenge fully, some back-
ents; (2) FDA’s scientific judgment that ground information about both colchicine
Mitigare is safe as labeled is well-reasoned itself and FDA’s prior approval of Plain-
and entitled to deference; and (3) FDA did tiff’s Colcrys, is necessary. The underly-
not make an unreasoned change in policy ing facts are not in dispute.
when it approved Mitigare, Takeda’s Mo-
tion for Summary Judgment in Takeda A. Colchicine: A Drug For The
Pharmaceuticals U.S.A., Inc. v. Burwell, Treatment Of Gout
No. 14–1668–KBJ (D.D.C.), is DENIED; Doctors have used colchicine—an agent
Elliott’s Motion for Summary Judgment in derived from the Colchicum Autumnale
Elliott Associates, L.P. v. Burwell, No. 14– plant—to treat gout for centuries. (See
1850–KBJ (D.D.C.), is DENIED; and De- Admin. R. (hereinafter, ‘‘AR’’) at 3 (‘‘The
1. Takeda originally filed a motion for a pre- tion of the merits of Takeda’s complaint and
liminary injunction against Burwell and converted Takeda’s motion for a preliminary
Hamburg on October 6, 2014. (See Mot. for injunction into a motion for summary judg-
TRO or Prelim. Inj., Takeda Pharms. U.S.A., ment. (See Order, Takeda Pharms. U.S.A.,
Inc. v. Burwell, et al., No. 14–1668–KBJ Inc. v. Burwell, et al., No. 14–1668–KBJ
(D.D.C. Oct. 6, 2014), ECF No. 9.) That same (D.D.C. Nov. 5, 2014), ECF No. 40.)
day, Takeda also initiated a patent infringe-
ment action against Hikma and West–Ward in
2. ‘‘Gout is a common metabolic disorder
the United States District Court for the Dis-
characterized by chronically elevated uric
trict of Delaware. (See Compl., Takeda
acid levels (hyperuricemia)TTTT These depos-
Pharms. U.S.A., Inc. v. West–Ward Pharm.
its of uric acid crystals characteristically trig-
Corp. et al., No. 14–1268–SLR (D.Del. Oct. 6,
2014.) In light of subsequent developments ger intense but self-limited bouts of acute
in the parallel patent litigation that prohibited arthritis and over time also may lead to a
Hikma and West–Ward from marketing Miti- chronic inflammatory and erosive arthritis
gare, this Court consolidated Takeda’s motion and, in some patients, kidney stones.’’ (Ad-
for a preliminary injunction with the resolu- min.R. (hereinafter, ‘‘AR’’) at 4.)
first use of colchicine as a selective treat- ber of drugs that were already on the
ment for gout is attributed to the Byzan- market, including ColBenemid, which is a
tine physician Alexander of Tralles in 6 combination tablet that contains both 0.5
A.D.’’).) Colchicine can be used both for mg of colchicine and 500 mg of probenecid.
the targeted treatment of gout flares (See AR at 4, 668.) FDA determined that
(‘‘acute treatment’’) and for longer-term ColBenemid was ‘‘effective for the treat-
maintenance treatment that is aimed at ment of chronic gouty arthritis when com-
preventing flares (‘‘prophylaxis’’). (See id. plicated by frequent, recurrent acute at-
at 4, 116–17, 157, 204.) However, there is tacks of gout,’’ 37 Fed.Reg. 15189–02 (July
a relatively small window of doses in which 28, 1972) (see also AR at 50), and approved
colchicine provides therapeutic benefits that product for, ‘‘essentially, prophylactic
without causing severe complications. treatment of gout flares’’ (AR at 668). It
(See AR at 202.) This ‘‘narrow therapeutic subsequently approved a generic version of
index’’ means that minor dosing changes ColBenemid—known as Col–Probenecid—
can have a grave effect on patient out- that is also a tablet with 0.5 mg of colchi-
comes because toxic levels of colchicine can cine and 500 mg of probenecid and is still
be reached relatively quickly and ‘‘can re-
on the market today. (See id. 4, 349, 353.)
sult in serious life-threatening adverse
Other drug manufacturers have relied
events and death.’’ (Id.; see also id. at
upon FDA’s findings that colchicine and
117 (noting that, although colchicine is
probenecid effectively treat gout in the
therapeutic ‘‘at doses of approximately
context of the agency’s approval of Col-
0.015 mg/kg,’’ the drug is ‘‘toxic in doses
Benemid and Col–Probenecid, including
greater than 0.1 mg/kg, and typically lethal
the two drug companies that have spon-
at doses of approximately 0.8 mg/kg’’).)
sored the colchicine drug products at issue
Even doses of colchicine that are within
in the instant case. (See id. at 4, 8).
the normal therapeutic range can be toxic
if colchicine is used concomitantly with Just as combination colchicine products
certain other drugs called ‘‘CYP3A4 and P- were legally marketed and sold for many
gp inhibitors.’’ (Id. at 202.) years in the pre-approval era, ‘‘[s]ingle-
Consistent with colchicine’s long history, ingredient colchicine tablets’’—tablets that
drug manufacturers in the United States contain only colchicine and are not com-
marketed a variety of forms and dosages bined with another drug—‘‘were available
of colchicine for decades prior to Con- for decades as marketed but unapproved
gress’s 1962 enactment of amendments to products, in 0.6 mg strength.’’ (Id. at 668.)
the FDCA that required FDA to ‘‘ap- The practice of marketing single-ingredi-
prove’’ a drug—i.e., to make findings that ent colchicine products as an unapproved
a drug is safe, effective, and properly la- drug continued even after Congress re-
beled—prior to marketing. (See AR at 50, quired premarket approval of drugs (see
255); see also Peter Barton Hutt, et al., id. at 421), and it persisted until at least
Food and Drug Law 577 (3rd ed.2007).3 2006, when ‘‘FDA announced a new drug
After Congress passed the 1962 amend- safety initiative to remove unapproved
ments that established a premarket ap- marketed drugs from the market’’ (id. at
proval requirement, FDA reviewed a num- 349). FDA undertook this initiative with
3. Early versions of the FDCA did not require 384, 34 Stat. 768 (1906); Federal Food, Drug,
a drug sponsor to seek premarket approval and Cosmetic Act of 1938, Pub.L. No. 75–717,
from the federal government. See, e.g., Pure 52 Stat. 1040 (1938) (codified at 21 U.S.C.
Food and Drugs Act of 1906, Pub. L. No. 59– § 301 et seq.).
the knowledge that ‘‘[f]or historical rea- is effective in use’’ (i.e., clinical trials); all
sons, some drugs are available in the Unit- components of the drug; the methods used
ed States that lack required FDA approval for the drug’s manufacture, processing,
for marketing[,]’’ FDA Ctr. For Drug and packing; examples for proposed label-
Evaluation & Research, Guidance for FDA ing for the drug; and any patents claimed
Staff and Indus.: Marketed Unapproved in relation to the drug. See 21 U.S.C.
Drugs—Compliance Policy Guide Sec. §§ 355(b)(1)(A), (B), (D), (F), (G). This
440.100: Marketed New Drugs Without path is used by drug manufacturers for
Approved NDAs & ANDAs 2 (June 2006, ‘‘new branded drug[s],’’ Ethypharm S.A.
as revised Sept. 2011), and with the intent France, 707 F.3d at 226, which are some-
to bring all prescription drug products into times called ‘‘pioneer’’ or ‘‘innovator’’
compliance with an FDA approval process drugs.
that Congress had adopted in 1984, as part A drug manufacturer may also choose to
of a statute that is formally named the file an Abbreviated New Drug Application
‘‘Drug Price Competition and Patent Term (‘‘ANDA’’) pursuant to 21 U.S.C. § 355(j).
Restoration Act of 1984’’ and is commonly The ANDA process facilitates efficient ap-
referred to as the ‘‘Hatch–Waxman proval of generic versions of pioneer drug
Amendments.’’ Pub. L. No. 98–417, 98 products that have already been deter-
Stat. 1585 (1984), codified at 21 U.S.C. mined to be safe and effective. Rather
§ 355. than requiring generic manufacturers to
conduct expensive and time consuming
B. FDA’s Drug Approval Frame-
clinical trials, the ANDA process allows
work: The Hatch–Waxman
the manufacturer to rely on the clinical
Amendments
trials already performed in connection with
In brief, Hatch–Waxman requires drug the approval of the previously approved
manufacturers seeking to market a new drug, provided that the generic manufac-
drug to first obtain FDA approval via one turer can show that its drug has the same
of three different application pathways: (1) relevant characteristics (including, inter
a full New Drug Application (‘‘NDA’’); (2) alia, the same labeling, active ingredient,
an Abbreviated New Drug Application route of administration, dosage form,
(‘‘ANDA’’); or (3) an intermediate process strength, and bioequivalency). See 21
known as a Section 505(b)(2) NDA. See 21 U.S.C. § 355(j)(2)(A). In other words, an
U.S.C. § 355; see also, e.g., Ethypharm ANDA does not attempt to demonstrate
S.A. France v. Abbott Labs., 707 F.3d 223, safety or effectiveness; instead, the appli-
226–27 (3d Cir.2013) (describing the three cant’s only goal is to establish that the
different approval methods). generic product is equivalent to another
1. NDAs, ANDAs, and 505(b)(2) NDAs drug that is already known to be safe and
The full NDA process, see 21 U.S.C. effective. Thus, this path is used by drug
§ 355(b)(1), requires the manufacturer to manufacturers ‘‘for the introduction of ge-
submit detailed safety and efficacy data for neric versions of previously approved
the drug, including, among other things, branded drugs.’’ Ethypharm S.A. France,
‘‘full reports of investigations which have 707 F.3d at 227.
been made to show whether or not such The Section 505(b)(2) NDA is a sort of
drug is safe for use and whether such drug hybrid of the other two pathways.4 Like
4. The 505(b)(2) NDA is sometimes also called a ‘‘paper NDA.’’ See AstraZeneca LP v. Apo-
the full NDA, a 505(b)(2) NDA must di- has concluded that the statutory scheme
rectly demonstrate that the proposed drug should include effective incentives for inno-
product is safe and effective; however, like vation such as patent protection for the
the ANDA, a 505(b)(2) applicant can rely substantial ‘‘investments necessary to re-
on clinical studies that were previously search and develop new drug products’’
submitted to FDA in support of another that pioneering companies undertake, My-
drug and that were not conducted or li- lan Pharm., Inc. v. FDA, 454 F.3d 270,
censed by the 505(b)(2) applicant. See 21 272 (4th Cir.2006) (internal quotation
U.S.C. § 355(b)(2). The drug for which marks omitted). With property rights
the borrowed studies were conducted is comes the potential for price manipulation,
referred to as the ‘‘Reference Listed however; and Congress is also perpetually
Drug’’ (RLD), and the RLD-related clini- concerned about drug manufacturer mo-
cal studies that a Section 505(b)(2) appli- nopolies and the rising prices of prescrip-
cant relies upon may be proffered to satis- tion drugs. The Hatch–Waxman Amend-
fy the applicant’s entire burden of proving ments to the FDCA are aimed at
safety and effectiveness, or they may only ‘‘strik[ing] a balance between [creating] in-
support some of the necessary findings; in centives TTT for innovation,’’ on the one
the latter case, the applicant can supple- hand, and ‘‘quickly getting lower-cost ge-
ment with studies of its own. This means neric drugs to market[,]’’ on the other.
that a Section 505(b)(2) NDA may include Teva Pharm. Indus. Ltd. v. Crawford, 410
the applicant’s own research supporting F.3d 51, 54 (D.C.Cir.2005). This balance is
the basic safety and efficacy of the drug in reflected in statutory process for the
addition to the research studies related to FDA’s approval of new drugs.
the RLD, or it may rely entirely on the Specifically, the Hatch–Waxman Amend-
RLD, but, in any event, the Section ments mandate that the FDA must record
505(b)(2) applicant must present informa- patent information about approved drug
tion that bears upon the safety and effec- products in a publication entitled ‘‘Ap-
tiveness of its drug product in light of the proved Drug Products with Therapeutic
difference between the pioneer drug prod-
Equivalence Evaluations,’’ which is gener-
uct and the applicant’s modification of that
ally called the ‘‘Orange Book,’’ after the
drug product. The 505(b)(2) NDA path-
color of its cover.5 If a drug product is the
way is often used when the new drug
first-approved innovator of its kind, FDA
differs only slightly from the pioneer drug,
will designate the product as an RLD that
and this pathway is often favored by drug
other products may later rely upon. Addi-
manufactures seeking to market drugs
tionally, any 505(b)(2) NDA that is submit-
that are neither ‘‘entirely new’’ nor ‘‘simply
ted to FDA for approval must identify the
a generic version of a branded drug.’’
previously approved drug that the appli-
Ethypharm S.A. France, 707 F.3d at 227.
cant is relying upon for approval, see 21
2. The Patent Certification Requirement C.F.R. § 314.54, and must contain certain
Because development of a new drug statements (‘‘certifications’’) regarding any
product is notoriously ‘‘expensive and ‘‘product patents’’ (patents covering a drug
time-consuming[,]’’ Pfizer Inc. v. Shalala, product or the drug substance that is a
182 F.3d 975, 976 (D.C.Cir.1999), Congress component of the drug product) and
tex, Inc., 633 F.3d 1042, 1045 (Fed.Cir.2010). 5. See generally FDA Electronic Orange Book,
http://www.accessdata.fda.gov/scripts/cder/ob/
(last visited January 8, 2015).
‘‘method-of-use patents’’ (patents covering in order to permit any potential patent

approved methods of using a drug product) litigation to proceed. See 21 U.S.C.
that are listed in the Orange Book for the § 355(c)(3)(C), (j)(5)(B)(iii).
referenced drug, see 21 U.S.C.
Thus, Congress has permitted new drug
§ 355(b)(2)(A).
applicants to piggyback on the approved
Notably, patent certifications are essen- research of prior drug manufacturers—
tially promises that relate to the status of and thus forgo costly and time-consuming
the drug product’s patents, as known or studies aimed at proving the safety and
understood by the applicant: (I) no such effectiveness of drug substances that have
patents exist, (II) any such patents have already been approved—in exchange for
expired, (III) the proposed drug will not requiring those applicants to notify the
be marketed before the patents expire, or owners of the drug that the new applicant
(IV) any such patents are invalid or will relies upon so that the drug owner has an
not be infringed by the proposed drug. opportunity to take steps to protect its
See id. § 355(b)(2)(A)(i)-(iv). This last re- patent rights. See Abbott Labs. v. Young,
quirement—often referred to as a ‘‘Para- 920 F.2d 984, 985 (D.C.Cir.1990) (‘‘Facing
graph IV certification’’—is particularly the classic question of the appropriate
relevant here because Mutual and its affil-
trade-off between greater incentives for
iates received numerous patents directed
the invention of new products and greater
to colchicine. Seventeen of these patents
affordability of those products, Congress
are listed in FDA’s Orange Book for Col-
struck a balance [in the Hatch–Waxman
crys, and the earliest of the Colcrys pat-
Amendments] between expediting generic
ents expires on October 6, 2028.6
drug applications and protecting the inter-
In addition to the obligation to reference ests of the original drug manufacturers.’’).
the drug upon which the 505(b)(2) applica-
3. The Labeling Requirements
tion relies and certify to its patents, a
505(b)(2) applicant must also provide no- In addition to selecting an approval
tice of any Paragraph IV certification to path, as part of the Hatch–Waxman drug
owner of the RLD and each patent owner, approval process drug sponsors must sub-
explaining the factual and legal basis for mit to FDA for approval the ‘‘proposed
the applicant’s opinion that the patent is text of labeling,’’ 21 C.F.R.
invalid or not infringed. See 21 U.S.C. § 314.50(c)(2)(i); see also 21 U.S.C.
§ 355(b)(3)(C)–(D). This notice enables § 355(b), including ‘‘adequate directions
the owners of the RLD and its related for use,’’ 21 U.S.C. § 352(f)(1). The label-
patents to litigate the patent issue before ing must contain all material facts and
FDA approves the 505(b)(2) NDA appli- adequate warnings, and the product must
cant’s new drug product.7 To this end, be safe for the uses indicated in the label-
upon the filing of a Paragraph IV certifica- ing. Id. §§ 321(n), 352(f), and 352(p).
tion, FDA is required to stay any approval FDA evaluates the information included in
for at least 45 days, and up to 30 months, the text of the proposed labeling and has
6. See Ex. E to Decl. of Matthew D. McGill, within hours of obtaining final FDA approval,
Elliott Associates, L.P. v. Burwell, No. 14– see e.g., In re Buspirone Patent Litig., 185
1850–KBJ (D.D.C. Nov. 17, 2014), ECF No. F.Supp.2d 340, 346 (S.D.N.Y.2002), lessening
14–2 at 55–57. the effect of any successful patent infringe-
ment claim pursued after the FDA approves a
7. The timing of this notice is important. Ge-
new drug.
neric manufacturers can flood the market
the authority to deny a drug application if did not need to submit full NDAs support-
it finds that the labeling information is not ing the safety and effectiveness of Colcrys
adequate or is false or misleading. See 21 for the treatment of gout. (See id. at 5–9.)
U.S.C. § 355(d); 21 C.F.R. Instead, Mutual submitted two successive
§§ 314.125(b)(6) and (b)(8). 505(b)(2) NDAs in order to have its 0.6 mg
single-ingredient oral colchicine tablet Col-
C. FDA’s Approval Of Colcrys (A crys approved for two indications: the
Colchicine Tablet) treatment of acute gout flares and the
When FDA finally undertook vigorous prophylaxis of gout flares. (See id. at
enforcement of Hatch–Waxman’s drug ap- 668.) 9 The contents of Mutual’s abbrevi-
proval protocol in 2006, colchicine drug ated new drug applications provide impor-
products that had previously been market- tant context for understanding Plaintiffs’
ed as prescription drugs but had not gone challenge to FDA’s subsequent approval of
through the new approval process were Mitigare.
among the many types of pharmaceuticals 1. Mutual Relies On ColBenemid, Pub-
that were forced to exit the market. (See lished Literature, And Its Own Clini-
AR at 5, 349.) The two drug companies cal Studies To Support The Colcrys
that are at odds in the instant dispute— Application For Acute Flares Of Gout
Takeda (previously Mutual) and Hikma (in Mutual’s first Section 505(b)(2) applica-
conjunction with its U.S. agent West– tion for Colcrys, which requested approval
Ward)—had both previously marketed col- of a 0.6 mg single-ingredient oral colchi-
chicine products as prescription drugs in cine tablet for treatment of acute gout
the U.S., and both companies sought to flares, identified the combination drug
have those products approved for re-entry product ColBenemid as the reference list-
into the marketplace.8 ed drug. (See id at 7.) In addition, Mutu-
On July 31, 2006, Mutual met with FDA al’s application cited FDA’s earlier finding
to discuss the new regulatory require- that ColBenemid is effective for the chron-
ments and to get information regarding ic treatment of gout, and also relied on
what would be necessary to bring Mutual’s published literature about the use of col-
colchicine drug product into compliance chicine. Mutual also conducted its own
with the statutory and regulatory scheme. research; specifically, it sponsored two
(See id. at 5.) Because of the wealth of sets of studies that contributed to the ex-
pre-existing information concerning the isting body of knowledge about the poten-
use of colchicine for the treatment of gout tial toxicity of colchicine.
and FDA’s prior approval of combination Mutual’s Acute Gout Flare Receiving
colchicine products like ColBenemid and Colchicine Evaluation trial (‘‘the AGREE
Col–Probenecid, Mutual discovered that it trial’’) was a ‘‘randomized, double-blind,
8. Hikma’s generics business apparently oper- 9. Mutual also sought and obtained FDA ap-
ates as West–Ward Pharmaceuticals (see proval for Colcrys for treatment of Familial
http://www.hikma.com/about-hikma/our- Mediterranean Fever (‘‘FMF’’), and received
businesses.aspx (last visited Jan. 8, 2015)), seven years of orphan drug exclusivity for that
although the precise contours of the relation- indication because FMF is a rare disease.
ship between these two companies is not rele- (See AR at 5–6.) FDA’s approval of Colcrys
vant to the instant dispute. In order to avoid for FMF and Mutual’s exclusivity for that
unnecessary confusion, this opinion refers to indication are not relevant to the instant case.
both of these companies hereinafter collec-
tively, as ‘‘West–Ward.’’
placebo-controlled clinical trial’’ that evalu- tual developed a new dosing regimen for
ated ‘‘the efficacy, safety, and tolerability concomitant use of Colcrys with certain
of colchicine in patients with an acute gout CYP3A4 inhibitors and P-gp inhibitors.
flare[.]’’ (Id. at 6.) ‘‘The AGREE trial Thus, although the potential for adverse
was necessary for approval of colchicine reactions from the interaction of certain
for the treatment of acute gout flares be- drugs with colchicine was already well-
cause only a single randomized, controlled known prior to Mutual’s research, Mutual’s
clinical trial of colchicine in this indication DDI studies ‘‘allowed for a more precise
existed in the medical literature.’’ (Id. at quantitative assessment of the interac-
22.) The AGREE trial showed that a low- tions.’’ (Id. at 668; see also id. at 50
dose regimen of colchicine for the treat- (summarizing dose modifications developed
ment of acute gout flares reduced the by Mutual).)
number of adverse events that patients FDA approved Mutual’s 505(b)(2) NDA
experienced but was still as effective at for Colcrys for the treatment of acute gout
treating gout flares as a higher dose regi- flares on July 30, 2009. (See AR at 6.)
men.10 (Id. at 6–7.) This new data ‘‘im- On that same day, based on Mutual’s
prove[d] the safety profile of colchicine AGREE trial and DDI studies, FDA is-
when used to treat acute gout flares’’ and sued a related drug safety communication
permitted Mutual to develop a new, low- for healthcare providers (an ‘‘FDA Alert’’).
dose regimen for the use of colchicine for See FDA, Information for Healthcare Pro-
the treatment of acute gout flares. (Id. at fessionals: New Safety Information for
7.) 11 Colchicine (marketed as Colcrys) (July 30,
Mutual also conducted certain drug-drug 2009).12 This FDA Alert informed health-
interaction studies (‘‘DDI studies’’) com- care professionals of the results of the
paring colchicine administered alone with Mutual colchicine studies, namely that ‘‘a
colchicine administered in conjunction with substantially lower dose of colchicine was
other drugs. (Id.) Such drugs included as effective as the traditional higher dose
cytochrome P4503 (‘‘CYP3A4’’) inhibitors in treatment of acute gout flares’’ and that
and Pglycoprotein (‘‘P-gp’’) inhibitors— colchicine could have dangerous ‘‘drug in-
pharmaceuticals that can affect the mecha- teractions with P-gp inhibitors or strong
nisms that the body uses to metabolize CYP3A4 inhibitors[.]’’ (AR at 7.) FDA
colchicine, and thus were already known to purportedly took this action to combat
have the potential of leading to toxic col- ‘‘outdated assumptions of what is safe and
chicine blood levels. (Id. at 50, 58–60, effective for treatment with oral colchi-
668.) As a result of its DDI studies, Mu- cine’’ and to ensure that patients would not
10. ‘‘The standard (historical) high-dose regi- which expired on July 30, 2012. (Id. at 7) See
men consisted of 1.2 mg followed by six addi- also 21 U.S.C. § 355(c)(3)(E)(iii) (FDA may
tional doses of 0.6 mg at hourly intervals, for grant a drug sponsor a 3–year period of exclu-
a total dose of 4.8 mg colchicine. The lower sivity for conducing new clinical investiga-
dose regimen consisted of 1.2 mg followed by tions essential to the approval of an applica-
0.6 mg in 1 hour, for a total dose of 1.8 mg tion).
colchicine.’’ (See AR at 6 n.21.)
11. Because the AGREE trial was a new clini- 12. Available at http://www.fda.gov/Drugs/
cal investigation essential to the approval of DrugSafety/PostmarketDrugSafety
Colcrys for the treatment of acute gout flares, informationforPatientsandProviders/Drug
FDA granted Mutual a 3–year period of exclu- SafetyinformationforHeathcareProfessionals/
sivity for the treatment of acute gout flares, ucm174315.htm.
‘‘suffer from adverse reactions such as se- against unapproved single-ingredient oral
vere gastro-intestinal complications—and colchicine products and persons who man-
even death—needlessly.’’ (Id. at 8 (inter- ufacture or cause the manufacture of such
nal quotation marks omitted.) The FDA products or their shipment in interstate
Alert also ‘‘referred healthcare profession- commerce.’’ (Id. at 9.) This action was
als to the dosing recommendations and part of the broader initiative that the
additional drug interaction information in agency had launched in 2006 against unap-
Colcrys product labeling.’’ (Id. at 7.) proved marketed drugs generally, and
2. Mutual Relies on ColBenemid and with respect to colchicine products in par-
Published Literature To Support The ticular, FDA remarked that ‘‘the labeling
Colcrys Application For Prophylactic for unapproved single-ingredient oral col-
Treatment of Gout chicine products listed with FDA TTT does
Approximately three months after the not reflect the most current data regard-
FDA Alert was issued, on October 16, ing the safety and effectiveness of single-
2009, FDA approved a second Colcrys ap- ingredient oral colchicine.’’ See Single–
plication, this time for the prophylaxis of Ingredient Oral Colchicine Products; En-
gout flares. (See id. at 8.) Unlike Mutu- forcement Action Dates; Notice, 75 Fed.
al’s application for approval of Colcrys for Reg. 60768 at 60769–70 (effective October
the treatment of acute gout flares, Mutu- 1, 2010); see also FDA News Release,
al’s application for Colcrys for the prophy- ‘‘FDA orders halt to marketing of unap-
laxis of gout flares did not include new proved single-ingredient oral colchicine’’
studies in support of the safety and effica- (Sept. 30, 2010).
cy of the drug product. (Id.) Instead, Notably, the agency expressed a partic-
Mutual’s assertion that Colcrys is a safe ular concern with how the labels of unap-
treatment for the prophylaxis of gout proved colchicine products dealt with the
flares was based on ‘‘an assessment of use of colchicine for the treatment of acute
adverse events from the worldwide litera- gout flares and potential drug-drug inter-
ture and postmarketing adverse event da- actions—the two areas that Mutual had
tabases’’ and ‘‘cross-reference to Mutual’s
studied and had specifically addressed in
earlier colchicine NDAs.’’ (Id.) Mutual’s
the Colcrys label. Unlike Colcrys, the la-
assertion that Colcrys is an effective treat-
bels of unapproved colchicine products
ment for the prophylaxis of gout flares
generally used vague warnings suggesting
‘‘was based entirely on the published liter-
‘‘avoidance when possible and caution
ature, including published reports of two
when necessary, with vigilant monitoring
randomized, controlled trials of colchicine
of clinical signs of toxicity.’’ (AR at 668.)
for this indication and the DESI finding
By contrast, consistent with the findings of
for ColBenemid’’ (id. at 22–23 (footnote
Mutual’s DDI studies and AGREE trial,
omitted)).
the Colcrys label contained both: (1) a
3. FDA Takes Enforcement Action two-page table of dose modifications in-
Against Unapproved Oral Colchicine tended to help mitigate the risk of colchi-
Products Because Their Labels Do cine toxicity for patients taking Colcrys in
Not Reflect The Most Current Data combination with the drug products listed
On September 30, 2010—nearly one in the table (see Compl. Ex. 5 at 5–6), and
year after Colcrys was approved for pro- (2) a low dose regimen of colchicine for
phylaxis of gout flares—‘‘FDA announced treatment of acute gout flares that occur
its intention to take enforcement action while colchicine is already being used to
treat prophylaxis (see id. at 3). FDA sug- West–Ward filed the aforementioned
gested that it was important that similar Section 505(b)(2) application for approval
information appear on the labels of all of a colchicine tablet that referenced Col–
colchicine products, calling Mutual’s find- Probenecid in August 2010. (See AR at
ings about lower dosing for acute gout 50.) Although FDA’s new drug approval
flares ‘‘the standard of care’’ at the time, process is confidential, Mutual learned of
and also noting that ‘‘awareness regarding West–Ward’s application through public
colchicine interactions may not be wide- sources while approval was pending.
spread in the healthcare community.’’ 75 (Compl., Takeda Pharms. U.S.A., Inc. v.
Fed.Reg. 60769. Burwell, No. 14–1668–KBJ (D.D.C. Oct. 6,
2014), ECF No. 1, ¶ 35.)
D. FDA’s Approval Of Mitigare (A 1. Mutual Files A Citizen Petition Pro-
Colchicine Capsule) testing West–Ward’s Application
And FDA Responds
West–Ward removed its unapproved sin-
On November 26, 2010, Mutual filed a
gle-ingredient 0.6 mg colchicine tablet
‘‘citizen petition’’ with FDA regarding the
from the market in response to FDA’s
agency’s requirements for ANDAs and
enforcement announcement, just as Mutual
Section 505(b)(2) NDAs for colchicine tab-
had done. (AR at 50.) West–Ward had
lets.13 Mutual specifically requested that
been marketing its 0.6 mg single-ingredi-
FDA take, or refrain from taking, a num-
ent oral colchicine tablet since the early
ber of actions; as relevant here, Mutual
1970s. (Id.) In an attempt to comply
asked the agency to:
FDA’s new approval scheme and an-
nounced enforcement measures, West– (1) ‘‘[r]efrain from filing or approving
Ward submitted a Section 505(b)(2) appli- any application for a 0.6 mg oral colchicine
tablet with a proposed indication already
cation to FDA for approval of its pre-
approved for Colcrys (i.e., a ‘‘duplicate’’ of
existing colchicine tablet. (Id. at 50–51.)
Colcrys) that is not submitted as an
Before filing its application, however,
ANDA’’;
West–Ward specifically inquired of FDA
whether the agency would entertain a (2) ‘‘[r]efrain from filing or approving
505(b)(2) application for a colchicine tablet any ANDA or 505(b)(2) application for a
that referenced and relied upon Col–Pro- single-ingredient oral colchicine product
benecid, rather than Mutual’s recently-ap- that does not reference Colcrys and in-
proved Colcrys, and the agency answered clude certifications to the patents listed in
in the affirmative. (See id. at 6.) It is FDA’s [Orange Book] for Colcrys;’’ and
undisputed that West–Ward wanted to cite (3) ‘‘[r]equire the labeling for any sin-
Col–Probenecid instead of Colcrys be- gle-ingredient oral colchicine product to
cause, unlike Colcrys, Col–Probenecid is include all information related to drug-
not tied to any patents that would require drug interactions that is in the Colcrys
West–Ward to submit a Paragraph IV cer- labeling, including relevant dose adjust-
tification that would delay the approval ments needed to prevent unnecessary tox-
and re-marketing of West–Ward’s colchi- icity[.]’’ (AR at 1.) In other words, Mu-
cine product. tual asked FDA to mandate that every
13. A citizen petition is a written request that any form of administrative action. See 21
any interested person can file with FDA, ask- C.F.R. §§ 10.25(a), 10.30.
ing the agency to take, or refrain from taking,
single-ingredient oral colchicine product ‘‘must necessarily cite Colcrys as its listed
submitted to the agency for approval both drug, irrespective of whether the proposed
reference Colcrys and have the same safe- product shares the same strength, phar-
ty information and dose adjustments that macokinetic (PK) profile, or other charac-
are on Colcrys’s label; and also that FDA teristics such as dosage form or conditions
reject any application for a drug product of use.’’ (Id. at 3.) FDA denied this
exactly like Colcrys that is submitted request. (See id.) The agency explained
through the 505(b)(2) pathway. that a drug product that differs from Col-
On May 25, 2011, FDA responded to crys in one of the above listed ways is not
Mutual’s Citizen Petition, granting the pe- a ‘‘duplicate’’ of Colcrys and therefore
tition in part and denying it in part. (See presents a different set of circumstances
id. at 2.) For present purposes, FDA than West–Ward’s admittedly incorrect
made three significant decisions. First, 505(b)(2) application for a 0.6 mg single-
the Colchicine Citizen Petition Response ingredient oral colchicine tablet that did
sustained Mutual’s objections to West– not reference Colcrys.14 (See id. at 12–13.)
Ward’s 505(b)(2) application for a 0.6 mg FDA stressed that, although requiring du-
single-ingredient colchicine tablet that was plicate products to be approved through
identical to Colcrys. FDA acknowledged the ANDA pathway ‘‘ensures that dupli-
that it had previously advised West–Ward cate products are marketed with the same
that West–Ward could submit an applica- or similar labeling that FDA has deter-
tion for its 0.6 mg single-ingredient colchi- mined contains the scientific information
cine tablet via the 505(b)(2) pathway and necessary for the safe and effective use’’
without referencing Colcrys, but admitted (id. at 13), a 505(b)(2) NDA must directly
in the Response that the agency had been demonstrate that the proposed drug prod-
‘‘incorrect’’ about that, and added that uct is safe and effective. (See id. at 3
‘‘FDA regrets that [ ] advice to West– (noting that ‘‘any 505(b)(2) application for
Ward.’’ (Id. at 17.) Thus, FDA granted a proposed single-ingredient colchicine
Mutual’s request that the agency require product must meet the statutory approval
any application for a single-ingredient oral standard for safety and effectiveness’’).)
colchicine product that was identical to The agency also remarked that, ‘‘in light of
Colcrys ‘‘be submitted as an ANDA that the significant amount of non-product-spe-
cites Colcrys as the RLD and complies cific published scientific literature on col-
with applicable regulatory requirements.’’ chicine and additional non-product-specific
(Id. at 2–3.) FDA also stated that the scientific literature that may become avail-
West–Ward application needed to be with- able over time, FDA declines to speculate
drawn and resubmitted as an ANDA (see on whether a 505(b)(2) applicant for a non-
id. at 11–16). pharmaceutically equivalent product could
Second, FDA’s Citizen Petition Re- submit adequate safety and effectiveness
sponse addressed Mutual’s broader con- data to support approval without reference
tention that any single-ingredient colchi- to Colcrys.’’ (Id. at 21.) Thus, although
cine product—not just a 0.6 mg tablet such FDA promised that it would reject an
as the one submitted by West–Ward— application for a duplicate of Colcrys that
14. Here, ‘‘duplicate’’ is a term of art that as a listed drug. See Abbreviated New Drug
refers to a drug product that has the same Application Regulations; Proposed Rule, 54
active ingredient(s), dosage form, strength, Fed.Reg. 28872 at 28877 (July 10, 1989).
route of administration, and conditions of use
did not reference Colcrys, FDA also antici- application for a colchicine capsule named
pated that the agency might approve a Mitigare. West–Ward’s application for
single-ingredient oral colchicine product Mitigare relied on published literature
that did not cite Colcrys, so long as the about colchicine, FDA’s findings of safety
new drug product differed from Colcrys in and effectiveness from Col–Probenecid,
some way and the new drug product’s and new clinical pharmacology studies
505(b)(2) application made the requisite West–Ward conducted. (See AR at 108.)
showing of safety and effectiveness. This application differed from West–
Third, FDA’s Citizen Petition Response Ward’s earlier application for a single-in-
gredient colchicine product in at least two
described what type of information FDA
significant ways.
would require for the label of a single-
ingredient oral colchicine product. With First, Mitigare is a capsule, not a tablet.
respect to label information about concomi- Like Colcrys, Mitigare contains 0.6 mg of
tant use of colchicine with other drugs, colchicine administered orally, but the dif-
FDA commented that ‘‘Mutual’s drug-drug ference in dosage form means that Miti-
interaction studies [had] provided new, gare is not a duplicate of Colcrys, and as a
quantitative information about the extent result, FDA permitted West–Ward to file
of changes in exposure that can occur with its application for Mitigare using the
co-administration of certain drugs with col- 505(b)(2) pathway rather than the ANDA
chicine.’’ (Id. at 19.) Thus, the label ‘‘for pathway. (See Ex. 11 to Takeda Compl.,
ECF No. 1–1, at 217–32, FDA Ctr. for
any single-ingredient oral colchicine prod-
Drug Evaluation & Research, Guidance for
uct needs to include adequate information
Indus.: Appls. Covered By Sec. 505(b)(2),
on drug-drug interactions, including rele-
Draft Guidance (Oct. 1999) at 6 (noting
vant dose adjustments needed to prevent
that ‘‘[a]n application that is a duplicate of
unnecessary toxicity.’’ (Id. at 3.) As for
a listed drug and eligible for approval un-
the use of colchicine to treat the acute
der section 505(j)’’ ‘‘can’t be submitted as
flares of patients who were already taking
505(b)(2) application’’).)
colchicine for prophylaxis, FDA stated that
‘‘the labeling for a single-ingredient colchi- Second, West–Ward conducted new DDI
cine product seeking approval for prophy- studies to support its application. In an
laxis of gout flares must inform healthcare effort to produce a single-ingredient oral
providers that the lower dose colchicine colchicine product that did not reference
regimen evaluated in the AGREE trial is Colcrys or rely upon Mutual’s data, West–
Ward commenced a development program
adequate to treat an acute gout flare that
that FDA recommended in which West–
may occur during chronic colchicine use[.]’’
Ward sponsored DDI studies similar to
(Id. at 3.)
Mutual’s but involving a different set of
2. FDA Approves Mitigare Capsule For
CYP3A4 and P-gp inhibitor drugs. (AR at
Prophylaxis Of Gout Flares Based On 118, 669.) Per FDA’s advice, West–Ward
Col–Probenecid, Published Literature, chose to study the same classifications of
and West–Ward’s Own Studies drugs that Mutual studied; however, con-
After FDA determined that it was unac- trary to expectations, the results of West–
ceptable for West–Ward to submit a Sec- Ward’s studies differed substantially from
tion 505(b)(2) application for a colchicine the results of Mutual’s studies. (See id. at
tablet that was a duplicate of Colcrys, as 669–70.) Mutual’s studies had indicated
explained above, West–Ward reformulated that colchicine dosing regimens should be
its product, and submitted a new 505(b)(2) modified when colchicine is co-adminis-
tered with certain types of drugs, but dentially, in accordance with FDA rules
West–Ward’s results indicated that dose and regulations. See 21 C.F.R.
modifications are ‘‘not warranted’’ when § 314.430(b) (‘‘FDA will not publicly dis-
0.6 mg colchicine is administered concomi- close the existence of an application or
tantly with certain CYP3A4 inhibitors and abbreviated application before an approval
P-gp inhibitors. (Id. at 670.) When letter is sent to the applicant under
West–Ward submitted its research as part § 314.105 or tentative approval letter is
of the Mitigare application, FDA wrestled sent to the applicant under § 314.107[.]’’).
with these unexpected results, comparing Moreover, because West–Ward neither cit-
Mutual’s data with West–Ward’s data and
ed Colcrys as the RLD nor certified to any
attempting to understand the differing re-
Colcrys patents in West–Ward’s 505(b)(2)
sults. (See id. at 667–711.)
application for Mitigare, West–Ward did
FDA ultimately reached the conclusion not inform Takeda of West–Ward’s appli-
that Mitigare is safe and effective for the cation for Mitigare. Consequently, Plain-
prophylaxis of gout, and approved West– tiffs did not know about West–Ward’s ap-
Ward’s 505(b)(2) application on September
plication for Mitigare until September 30,
26, 2014. (See id. at 28.) As approved,
2014, when West–Ward issued a press re-
Mitigare not only differs from Colcrys in
lease regarding FDA’s approval of its new
dosage form, it also has a substantially
single-ingredient colchicine product. (See
different label than Colcrys. In contrast
Confidential Decl. Matthew Woods, Take-
to the Colcrys label, the Mitigare label
da Pharms. U.S.A., Inc. v. Burwell, No.
does not include the lower dose colchicine
regime for the treatment of acute gout 14–1668–KBJ, ECF No. 3–6 ¶ 33.) More-
flares that Mutual evaluated in its AGREE over, Takeda only discovered that West–
trial; rather, the Mitigare label states un- Ward intended to market an authorized
der the ‘‘[l]imitations of use’’ section that generic version of Mitigare that will com-
‘‘[t]he safety and effectiveness of Mitigare pete with—and cost less than—Takeda’s
for acute treatment of gout flares during Colcrys, on October 1, 2014. (See id. ¶ 34.)
prophylaxis has not been studied.’’ (id. at
32 (Mitigare label)). Furthermore, instead E. Procedural History
of the detailed dose modifications for pre-
venting drug-drug interaction toxicity that On October 6, 2014, Takeda filed a two-
the Colcrys label contains, the Mitigare count complaint and a Motion for a Prelim-
label warns generally that patients taking inary Injunction against Defendants Bur-
certain drugs in combination with Mitigare well and Hamburg. (See Compl., Takeda
should avoid the combination entirely, or if Pharms. U.S.A., Inc. v. Burwell, No. 14–
avoidance is not possible, adjust the dose 1668–KBJ (D.D.C. Oct. 6, 2014), ECF No.
of Mitigare ‘‘by either reducing the daily 1 (‘‘Takeda Compl.’’); Mot. for TRO or
dose or reducing the dose frequency, and Prelim. Inj., Takeda Pharms. U.S.A., Inc.
the patient should be monitored carefully v. Burwell, No. 14–1668–KBJ (D.D.C. Oct.
for colchicine toxicity.’’ (AR at 141 (cita- 8, 2014), ECF No. 9, see also Mem. Supp.
tion omitted).) Pl.’s Confidential Mot. for TRO or Prelim.
3. West–Ward Launches Mitigare, Inj., Takeda Pharms. U.S.A., Inc. v. Bur-
Alerting Takeda To The Existence well, No. 14–1668–KBJ (D.D.C. Oct. 8,
Of Mitigare 2014), ECF No. 10 (‘‘Takeda PI Mem.’’).)
FDA’s evaluation of West–Ward’s appli- In its complaint, Takeda alleges that FDA
cation for Mitigare was undertaken confi- acted wrongfully in three respects: (1)
‘‘FDA acted arbitrarily and capriciously in 5780611 (D.Del. Nov. 4, 2014), ECF No.
approving [West–Ward’s] Section 505(b)(2) 78, 2014 WL 5088690; see also Order,
application for Mitigare without requiring Takeda Pharms. U.S.A., Inc. v. West–
the label to contain critical safety informa- Ward Pharm. Corp., No. 14–1268–SLR, 72
tion that FDA previously stated was nec- F.Supp.3d 539, 2014 WL 5780611 (D.Del.
essary for single-ingredient oral colchicine Nov. 4, 2014), ECF No. 79.)
products[;]’’ (2) ‘‘FDA’s approval of Meanwhile, in the instant District of Co-
[West–Ward’s] application for Mitigare
lumbia case, West–Ward moved to inter-
was unlawful, arbitrary and capricious be-
vene in Takeda’s suit against FDA, and
cause, as approved, Mitigare is not safe in
this Court granted that request. (See
light of the defects in its label[;]’’ and (3)
Unopposed Mot. to Intervene, Takeda
‘‘FDA’s failure to require [West–Ward] to
Pharms. U.S.A., Inc. v. Burwell, No. 14–
reference Takeda’s own colchicine drug,
1668–KBJ (D.D.C. Oct. 9, 2014), ECF No.
Colcrys, in its application interfered with
11; Minute Entry dated Oct. 9, 2014,
Takeda’s rights to participate in the ad-
Takeda Pharms. U.S.A., Inc. v. Burwell,
ministrative process, including the Para-
No. 14–1668–KBJ.) West–Ward and the
graph IV certification process under Hatch
Government then filed oppositions to
Waxman and the Citizen Petition process.’’
Takeda’s Motion for a Preliminary Injunc-
(Takeda Compl. ¶ 1.)
tion. (See Hikma and West–Ward’s Opp’n
Takeda initiated a patent infringement to Mot. for TRO (‘‘West–Ward Opp.
action against West–Ward in the United
Mem.’’), Takeda Pharms. U.S.A., Inc. v.
States District Court for the District of
Burwell, No. 14–1668–KBJ (D.D.C. Oct.
Delaware shortly before it brought this
17, 2014), ECF No. 16; Burwell and Ham-
action against FDA. (See Compl., Takeda
burg’s Resp. to Mot. for TRO (‘‘FDA Opp.
Pharms. U.S.A., Inc. v. West–Ward
Pharm. Corp., No. 14–1268–SLR, 2014
WL 5241780 (D.Del. Oct. 3, 2014), ECF
17, 2014), ECF No. 15.) Takeda field a
No. 1.) On October 9, 2014, the Delaware
reply on October 20, 2014. (See Reply to
court entered a Temporary Restraining
Opp’n to Mot. for TRO (‘‘Takeda Reply
Order enjoining West–Ward from market-
ing Mitigare pending further proceedings
in the patent litigation. (See Memoran-
20, 2014), ECF No. 21.)
dum Order, Takeda Pharms. U.S.A., Inc.
v. West–Ward Pharm. Corp., No. 141268– On November 4, 2014, this Court heard
SLR, 2014 WL 5088690 (D.Del. Oct. 9, argument from Takeda, FDA, and West–
2014, ECF No. 21.) The Delaware court Ward on Takeda’s Motion for a Prelimi-
eventually denied Takeda’s Motion for a nary Injunction. (See Minute Entry dated
Preliminary Injunction, but ‘‘given the sig- Nov. 4, 2014, Takeda Pharms. U.S.A., Inc.
nificance of this dispute to both parties’’ is- v. Burwell, No. 14–1668–KBJ). However,
sued an order maintaining the status in light of the stay that was issued in the
quo—that is, prohibiting West–Ward from Delaware patent litigation, this Court con-
marketing Mitigare—pending Takeda’s ap- solidated Takeda’s Motion for a Prelimi-
peal of that court’s decision regarding the nary Injunction with the resolution of the
preliminary injunction. (Memorandum merits of Takeda’s complaint and, with
Opinion at 16, Takeda Pharms. U.S.A., Takeda’s consent, construed the merits ar-
Inc. v. West–Ward Pharm. Corp., No. 14– guments in Takeda’s preliminary injunc-
1268–SLR, 72 F.Supp.3d 539, 2014 WL tion motion as a motion for summary judg-
ment. (See Order, Takeda Pharms. capricious manner by approving [West–

U.S.A., Inc. v. Burwell, No. 14–1668–KBJ Ward’s] 505(b)(2) application without re-
(D.D.C. Nov. 5, 2014), ECF No. 40.) The quiring a certification as to the Colcrys
parties subsequently filed supplemental patents.’’ (Id.¶ 9–11.) Elliott filed a mo-
briefs on Takeda’s converted motion. (See tion for summary judgment on November
Burwell and Hamburg’s Supplemental 17, 2014. (See Mot. for Summ. J, Elliott
Mem. (‘‘FDA Suppl. Mem.’’), Takeda Assocs. v. Burwell, No. 14–1850–KBJ
Pharms. U.S.A., Inc. v. Burwell, No. 14– (D.D.C. Nov. 17, 2014), ECF No. 14, see
1668–KBJ (D.D.C. Nov. 14, 2014), ECF also Pl.’s Mem. Supp. Mot. for Summ. J.,
No. 43; Takeda’s Supplemental Mem. Elliott Assocs. v. Burwell, No. 14–1850–
(‘‘Takeda Suppl. Mem.’’), Takeda Pharms. KBJ (D.D.C. Nov. 17, 2014), ECF No. 14–
U.S.A., Inc. v. Burwell, No. 14–1668–KBJ 1 (‘‘Elliott MSJ Mem.’’).) Just as they had
(D.D.C. Nov. 14, 2014), ECF No. 44; Hik- in Takeda v. Burwell, Hikma and West–
ma and West–Ward’s Supplemental Mem., Ward moved to intervene in Elliott v. Bur-
(‘‘West–Ward Suppl. Mem.’’), Takeda well. (See Consent Mot. to Intervene, El-
Pharms. U.S.A., Inc. v. Burwell, No. 14– liott Assocs. v. Burwell, No. 14–1850–KBJ
1668–KBJ (D.D.C. Nov. 14, 2014), ECF (D.D.C. Nov. 18, 2014), ECF No. 47.)
No. 45.) This Court granted the motion. (See Min-
On the same day that this Court heard ute Entry dated Nov. 21, 2014, Elliott
argument on Takeda’s then-pending pre- Assocs. v. Burwell, No. 14–1850–KBJ.)
liminary injunction motion (November 4,
2014), Elliott Associates, L.P., Elliott In- In light of the overlap between the par-
ternational, L.P., and Knollwood Invest- ties, facts, and allegations in Takeda v.
ments, L.P. (collectively, ‘‘Elliott’’) filed a Burwell and Elliott v. Burwell, this Court
two-count complaint against Defendants that the two cases should be considered in
Burwell and Hamburg that is substantially tandem. (See Minute Entry dated Nov.
similar to Takeda’s action. (See Compl. 18, 2014, Elliott Assocs. v. Burwell, No.
Elliott Assocs. v. Burwell, No. 14–1850– 14–1850–KBJ.) On November 19, 2014,
KBJ (D.D.C. Nov. 4, 2014), ECF No. 1 this Court held a second motions hearing
(‘‘Elliott Compl.’’).) Elliott ‘‘owns a legal- in which the parties in both cases partici-
ly-enforceable right tied to the Colcrys pated. (See Minute Entry dated Nov. 19,
patents to receive a percentage of the roy- 2014, Takeda Pharms. U.S.A., Inc. v. Bur-
alties from the sale of Colcrys,’’ and be- well, No. 14–1668–KBJ.) After the hear-
cause Elliott expects that Mitigare will ing, West–Ward and FDA filed cross-mo-
compete directly with Colcrys, these plain- tions for summary judgment in Elliott v.
tiffs allege that FDA’s failure to require Burwell. (See Cross Mot. for Summ. J. by
West–Ward to certify to the Colcrys pat- Hikma and West–Ward, Elliott Assocs. v.
ents has injured them. (Elliott Compl. Burwell, No. 14–1850–KBJ (D.D.C. Dec. 9,
¶ 7.) The Elliott complaint specifically al- 2014), ECF No. 60; Mem. in Opp. by
leges that FDA acted wrongfully in two Hikma and West–Ward, Elliott Assocs. v.
respects: (1) that ‘‘FDA’s decision to ap- Burwell, No. 14–1850–KBJ (D.D.C. Dec. 9,
prove Mitigare without requiring that 2014), ECF No. 61 (‘‘West–Ward XMSJ
[West–Ward] certify to the patents cover- Mem.’’); Cross Mot. for Summ. J. by Bur-
ing the use of colchicine for the prophylax- well and Hamburg (‘‘FDA XMSJ Mem.’’),
is of gout flares violates the plain text of Elliott Assocs. v. Burwell, No. 14–1850–
Section 505(b)(2)(A) of the FDCA[;]’’ and KBJ (D.D.C. Dec. 9, 2014), ECF No. 62;
(2) that ‘‘FDA acted in an arbitrary and Mem. in Opp by Burwell and Hamburg,
Elliott Assocs. v. Burwell, No. 14–1850– [2–4] In reviewing agency action, a

KBJ (D.D.C. Dec. 9, 2014), ECF No. 63 court must be mindful of the division of
(‘‘FDA XMSJ Mem.’’).) Elliott filed a re- labor between the court and the agency.
ply to both Cross–Motions on December ‘‘Under the APA, it is the role of the
13, 2014. (See Reply to Opp’n and Cross agency to resolve factual issues to arrive at
Mot. for Summ. J. (‘‘Elliott MSJ Reply a decision that is supported by the admin-
Mem.’’), Elliott Assocs. v. Burwell, No. 14– istrative record, whereas the function of
1850–KBJ (D.D.C. Dec. 13, 2014), ECF the district court is to determine whether
No. 64.) The motions for summary judg- or not as a matter of law the evidence in
ment in Takeda v. Burwell and Elliott v. the administrative record permitted the
Burwell are now ripe. agency to make the decision it did.’’ Hi–
Tech Pharmacal Co. v. FDA, 587
II. LEGAL STANDARDS F.Supp.2d 13, 18 (D.D.C.2008) (internal
[1] Under Federal Rule of Civil Proce- quotation marks and citation omitted).
dure 56, summary judgment is appropriate Accordingly, a reviewing court cannot
when the moving party demonstrates ‘‘that ‘‘substitute its judgment for that of the
there is no genuine dispute as to any mate- agency,’’ Motor Vehicle Mfrs. Ass’n v.
rial fact and the movant is entitled to State Farm Mut. Auto. Ins. Co., 463 U.S.
judgment as a matter of law.’’ Fed. 29, 43, 103 S.Ct. 2856, 77 L.Ed.2d 443
R.Civ.P. 56. However, in a case involving (1983), especially when the agency’s scien-
review of final administrative action—such tific expertise informs its judgment. See
as FDA’s approval of a new drug—the Balt. Gas & Elec. Co. v. Natural Res. Def.
standard set forth in Rule 56 does not Council, Inc., 462 U.S. 87, 103, 103 S.Ct.
apply. See, e.g., ViroPharma, Inc. v. 2246, 76 L.Ed.2d 437 (1983) (holding that
Hamburg, 916 F.Supp.2d 76, 79 (D.D.C. ‘‘[w]hen examining TTT [a] scientific deter-
2013). Instead, ‘‘FDA’s administrative de- mination TTT a reviewing court must gen-
cisions are subject to review under the erally be at its most deferential’’). More-
Administrative Procedure Act (‘APA’), 5 over, given that ‘‘[t]he scope of review
U.S.C. § 706, which requires the reviewing under the ‘arbitrary and capricious’ stan-
court to set aside an agency action that is dard is narrow[,]’’ State Farm, 463 U.S. at
‘arbitrary, capricious, an abuse of discre- 43, 103 S.Ct. 2856, the agency action under
tion, or otherwise not in accordance with review is ‘‘entitled to a presumption of
law.’ ’’ ISTA Pharm., Inc. v. FDA, 898 regularity[,]’’ Citizens to Preserve Overton
F.Supp.2d 227, 230 (D.D.C.2012). ‘‘Sum- Park, Inc. v. Volpe, 401 U.S. 402, 415, 91
mary judgment thus serves as a mecha- S.Ct. 814, 28 L.Ed.2d 136 (1971), overruled
nism for deciding, as a matter of law, on other grounds by Califano v. Sanders,
whether the agency action is supported by 430 U.S. 99, 97 S.Ct. 980, 51 L.Ed.2d 192
the administrative record and is otherwise (1977). In sum, the court performs ‘‘only
consistent with the APA standard of re- the limited, albeit important, task of re-
view.’’ Hill Dermaceuticals, Inc. v. FDA, viewing agency action to determine wheth-
No. 11–1950, 2012 WL 5914516, at *7 er the agency conformed with controlling
(D.D.C. May 18, 2012) (citing Richards v. statutes[,]’’ Balt. Gas, 462 U.S. at 97, 103
INS, 554 F.2d 1173, 1177 & n. 28 (D.C.Cir. S.Ct. 2246, and/or whether the agency has
1977)); see also Am. Bioscience, Inc. v. committed ‘‘a clear error of judgment[,]’’
Thompson, 269 F.3d 1077, 1083–84 Overton Park, 401 U.S. at 416, 91 S.Ct.
(D.C.Cir.2001) (collecting cases). 814.
III. DISCUSSION products. (See id. at 26–36.) Takeda also

Although the instant cross-motions for argues that ‘‘FDA’s failure to enforce its
summary judgment focus on the alleged own labeling requirements allowed [West–
impropriety of one agency action—FDA’s Ward] to circumvent the statutory di-
approval of Mitigare—Plaintiffs make rective that it file a Paragraph IV certifica-
myriad arguments in an attempt to sup- tion to Takeda’s patents[.]’’ (Id. at 36.)
port their claim that FDA’s approval of For the reasons explained below, this
that drug product was wrongful and Court concludes that Plaintiffs are wrong
should be rescinded. First, both Takeda to characterize FDA’s actions with respect
and Elliott steadfastly maintain that FDA to Mitigare as unauthorized, unsafe, or
should not have approved Mitigare without unreasoned; to the contrary, it is clear on
requiring West–Ward to certify to the Col- the record presented that FDA’s approval
crys patents that cover the use of colchi- of Mitigare was consistent with the FDCA,
cine for the prophylaxis of gout flares, with the regulations the agency has promulgat-
Takeda asserting that the agency relied on ed pursuant to the FDCA, the Citizen
Colcrys’s data to approve Mitigare and Petition Responses FDA has issued, and
thus FDA’s failure to require West–Ward the policies and practices under which the
to reference Colcrys and certify to the agency operates. Furthermore, the rec-
Colcrys patents violated the agency’s own ord clearly reveals the reasonableness of
procedural rules (see Takeda Reply Mem. FDA’s expert determination that Mitigare
at 19–22; Takeda Suppl. Mem. at 6–13), is safe and effective as labeled, and it
and Elliott arguing additionally that the supports the agency’s conclusion that Miti-
agency’s failure to require West–Ward to gare’s labeling best reflects current scien-
certify to the Colcrys patents without re- tific information regarding the risks and
gard to any reliance on Colcrys contra- benefits of Mitigare–a conclusion that, in
vened both the agency’s longstanding poli- any event, is entitled to a high degree of
cies and the FDCA itself (see Elliott MSJ deference. Consequently, Plaintiffs have
Mem. at 23–46).15 In addition, Takeda failed to establish that summary judgment
takes issue with Mitigare’s label, arguing should be entered in their favor on their
that ‘‘[t]he Mitigare label contains neither APA claims, and this Court finds that De-
the FDA-approved low-dose-treatment no- fendants are entitled to summary judg-
tation for acute gout nor the drug-drug ment as a matter of law.
interaction dosing adjustments, both of
which FDA expressly required in light of A. FDA’s Approval Of Mitigare
the severe safety concerns it identified Without A Colcrys Reference And
during the Colcrys review process.’’ Related Certifications To The
(Takeda PI Mem. at 32 (citation omitted).) Colcrys Patents Did Not Violate
Consequently, Takeda contends that Miti- The Agency’s Rules Or The FDCA
gare is unsafe as labeled, and also that Both Plaintiffs contend that, when FDA
FDA’s approval of Mitigare constitutes an approved Mitigare without a Paragraph IV
unreasoned change in the agency’s position certification to the Colcrys patents, FDA
regarding the requirements for the label- permitted West–Ward to ‘‘circumvent’’ the
ing of single-ingredient oral colchicine agency’s own Hatch–Waxman directives
15. Citations to documents that the parties Court’s electronic filing system assigns.
have filed refer to the page numbers that the
regarding the filing of patent certifications, the requirement that a Section 505(b)(2)
in a manner that was arbitrary, capricious, applicant reference another product if the
an abuse of discretion, and otherwise not agency itself relies on studies or data re-
in accordance with law. (See Takeda PI lating to that other product in approving
Mem. at 36; Takeda Compl. ¶¶ 1, 56; El- the applicant’s application, and (2) the re-
liott MSJ Mem. at 29; Elliott Compl. ¶ 14); quirement that a Section 505(b)(2) appli-
see also 5 U.S.C. § 706(2)(A). It bears cant choose the ‘‘most appropriate’’ listed
noting at the outset that the assertion that drug to be its reference drug. (Takeda
FDA should have required West–Ward to Reply Mem. at 17; see also id. at 16–22.)
reference Colcrys and to certify to the Elliott makes the slightly different argu-
Colcrys patents is, from a broad perspec- ment that FDA not only violated the agen-
tive, the same argument that Takeda’s cy’s own policies, its actions also breached
predecessor Mutual made to FDA in its the FDCA itself, which, according to El-
2010 Citizen Petition (see supra Part liott, requires a Section 505(b)(2) applicant
I.D.1), when Mutual specifically asked that to certify to all method-of-use patents that
the agency refrain from approving any claim a use for the drug substance for
future Section 505(b)(2) application for a which the applicant is seeking approval.
single-ingredient oral colchicine product (See Elliott MSJ Mem. at 23–46). As ex-
that does not reference Colcrys and in- plained below, this Court discerns no basis
clude certifications to the Colcrys patents. in law or fact for Plaintiffs’ insistence that
(See AR at 1.) As explained above, FDA FDA was legally required to force West–
specifically rejected that request in its Col- Ward to reference Colcrys and to certify
chicine Citizen Petition Response, stating, to the Colcrys patents under the circum-
inter alia, that a Section 505(b)(2) applica- stances presented here. Consequently,
tion for a single-ingredient oral colchicine this Court cannot accept Plaintiffs’ argu-
product might not need to cite Colcrys as ments that FDA arbitrarily and capricious-
its reference listed drug if the new drug ly violated any such requirements when it
does not share the same dosage form. approved West–Ward’s application for Mi-
(See AR at 3; see also supra Part I.D.1.) tigare.
The agency also emphasized that ‘‘[w]heth-
1. FDA’s Procedural Rules Did Not Re-
er another 505(b)(2) application for a sin-
quire West–Ward To Reference Col-
gle-ingredient colchicine product that does
crys Because West–Ward Did Not
not cite Colcrys as a listed drug could ever
Rely On Colcrys Data To Support
be appropriate will depend on the facts
West–Ward’s Application For FDA
and circumstances of the particular appli-
Approval Of Mitigare
cation[.]’’ (AR at 21.)
Takeda appears to accept that reliance
[5] Plaintiffs argue now that the facts on the studies of another drug product is a
and circumstances of Mitigare’s approval necessary prerequisite to the obligation of
are such that the agency should have re- a Section 505(b)(2) applicant to certify to
quired a Colcrys reference and patent cer- that product’s patents, and it vigorously
tifications, and that FDA arbitrarily and asserts that the obligation to certify to the
capriciously failed to do so. To be specific, Colcrys patents was triggered here under
Takeda asserts that FDA’s refusal to make FDA’s own rules because ‘‘FDA relied re-
West–Ward reference Colcrys and certify peatedly and extensively upon Colcrys’s
to the Colcrys patents violated two of the safety and efficacy data in approving Miti-
agency’s ‘‘procedural requirements’’: (1) gare.’’ (Takeda Suppl. Mem. at 5.) As
Takeda puts it, ‘‘the triggering event for regulation or clearly applicable agency
identifying a reference drug in a 505(b)(2) statement to bolster its assertions in this
application and certifying to patents is not regard; instead, Takeda points to various
based solely the applicant’s actions’’ (id. at sources—e.g., section 505(b)(2) of the
6 (emphasis in original)), and, as Takeda FDCA, a few lines from FDA’s implement-
views the record, FDA’s actions with re- ing regulations, a case that settled, and
spect to the approval of Mitigare clearly selective quotations from Citizen Petition
involved the degree of reliance on the Col- Responses (see Takeda Suppl. Mem. at 8–
crys data that is necessary to require FDA 9)—to cobble together a legal argument
to make West–Ward certify to the Colcrys that, in essence, asks this Court to apply
patents. (See id. at 5 (‘‘Colcrys was refer- its own logic to conclude that FDA’s reli-
enced 246 times in the Mitigare adminis- ance matters, when, as explained below,
trative record, and FDA expressly relied this conclusion is hardly logical.
on Colcrys data to support findings of The key to understanding why Takeda’s
Mitigare’s safety and efficacy.’’ (emphasis agency-reliance argument fails is recogniz-
in original)).) Boiled to bare essence, ing its linchpin: the proposition that, with-
Takeda’s reliance argument has two major out ‘‘a right of reference or use,’’ FDA
corollaries: (1) that, under FDA’s rules, lacks the authority to review or access
‘‘[t]he ultimate reference and certification third-party data from a previously ap-
obligations depend on whether FDA relies proved new drug application when it is
on other drug studies or data’’ regardless evaluating a Section 505(b)(2) new drug
of whether the Section 505(b)(2) applicant application. (See Takeda Suppl. Mem. at 9
does so (id. at 6 (emphasis in original)), (‘‘FDA’s use of third-party data [to consid-
and (2) that the instant administrative rec- er and approve a 505(b)(2) application]
ord shows that ‘‘FDA explicitly referenced without a right of reference would trigger
and relied on the Colcrys data—over and the 505(b)(2) obligations.’’ (emphasis add-
over and over again—in approving Miti- ed)); see also id. (‘‘If there is no right of
gare.’’ (Takeda Reply Mem. at 19.) This reference or use, FDA does not have carte
Court finds that Takeda is wrong on both blanche to consult or rely on third-party
counts. data that might be relevant to an applica-
tion without requiring the applicant to ref-
a. No FDA Policy Establishes That
erence and certify to the relevant patents.’’
FDA’s Reliance—As Opposed To
(emphasis altered)).) As Takeda explains
That Of The Section 505(b)(2) Appli-
it, in the absence of a right of reference or
cant—Gives Rise To Patent Certifica-
use, FDA is not entitled ‘‘to refer to data
tion Obligations
from a previously approved application
[6] First of all, the contention that, during the review of another party’s
under established agency policy, the pat- 505(b)(2) application’’ (id. at 9), and it is
ent certification requirement is triggered precisely because of the agency’s limited
by the agency’s reliance on the investiga- authority to access such data that, if the
tions underlying another drug product is agency does undertake to consult third-
entirely unsupported. (See Takeda Suppl. party data as part of its evaluation of a
Mem. at 7 (maintaining that ‘‘[i]f FDA Section 505(b)(2) application, the agency
relied on Colcrys to support the approval must require the applicant to certify to the
of Mitigare, [West–Ward] was required to data owner’s patents. (See id. at 10 (as-
reference Colcrys and certify to its pat- serting that, ‘‘where the [505(b)(2) ] appli-
ents’’).) Takeda does not cite to any one cant fails in its duty to identify a refer-
enced drug, to the extent FDA relies on approve a Section 505(b)(2) application, the
that drug’s studies or data, FDA must ‘‘right of reference’’ definition that the
require that applicant to reference the agency provides in 21 C.F.R. § 314.3 is
drug and certify to its patents’’ (emphasis similarly silent on the issue of whether the
in original); see also Mot. Hr’g Tr. Nov. agency itself needs such a ‘‘right’’ before it
19, 2014 (hereinafter, ‘‘MSJ Mot. Hr’g can ‘‘refer to data from a previously ap-
Tr.’’) 26:24 (emphasizing that ‘‘[t]he data proved application during the review of
that Takeda and Mutual submitted is pro- another party’s 505(b)(2) application[,]’’ as
priety’’); id. at 28:12–20 (arguing that Takeda maintains. (Takeda Suppl. Mem.
‘‘[w]hen FDA takes it upon itself to do an at 9.)
applicant’s work for it and opens that
locked file drawer and pulls out the Mutual Pfizer Inc. v. FDA, No. 03–2346 (D.D.C.
file and consults the Mutual studies and filed Nov. 13, 2003) also fails to shed any
uses the Mutual data and combines them light on the subject. Takeda cites Pfizer
with [West–Ward]’s data in order to reach as an example of a circumstance in which
certain conclusions about the safety and ‘‘FDA was sued for improperly referencing
effectiveness of [West–Ward’s] drug, then third-party data to approve a 505(b)(2) ap-
TTT there’s an obligation that adheres in plication submitted by Dr. Reddy’s Labs
the Hatch–Waxman Act for FDA to go for the drug amlodipine maleate.’’ (Take-
back to [West–Ward] and say, ‘Before we da Suppl. Mem. at 9.) What Takeda does
go further you need to reference the right not explain in its brief is that the court in
drug’ ’’).) Of course, FDA’s purported ob- Pfizer never reached any legal conclusion
ligation to require certification to a third- regarding whether the agency has a blan-
party data owner’s patents when the agen- ket policy of prohibiting its employees
cy relies on third-party data without a from consulting third-party data without a
right of reference assumes that FDA can- right of reference or use—the case was
not otherwise rely on such data—a conten- ultimately dismissed—and, indeed, it is
tion that Takeda repeatedly makes—but highly likely that FDA requested the stay
this critical limitation simply does not ap- and dismissal based on doubts about the
pear in any of the sources that Takeda particular studies its reviewer relied upon
cites. in that case and not on the basis of some
Specifically, although Congress uses the unstated agency policy prohibiting unau-
phrase ‘‘right of reference or use’’ in 21 thorized reliance on third-party studies en-
U.S.C. § 355(b)(2), that statutory section tirely. See Pfizer Inc. v. FDA, No. 03–
expressly applies only to the Section 2346 (D.D.C. Nov. 13, 2003), ECF No. 1,
505(b)(2) applicant, and pertains only to Compl. ¶ 15–37, see also id. ¶ 36 (alleging
what application materials such sponsor is that ‘‘there could be no reasonable scienti-
required to submit; Takeda fails entirely fic basis to rely on data contained in Pfiz-
to explain its suggestion that this statutory er’s NDA for Norvasc to approve Reddy’s
language can somehow be read to bind drug’’ (emphasis added)). In other words,
FDA in its consideration of data pertinent although FDA may have seen fit, under
to a submitted application. (See Takeda the circumstances presented in Pfizer, to
Suppl. Mem. 8.) And just as the statute ‘‘reevaluate whether the approval of the
says nothing about the circumstances un- NDA TTT was based upon data from ap-
der which FDA can, or cannot, consult propriate sources’’ (Takeda Suppl. Mem. at
third-party data when it makes a scientific 9 (alteration in original) (internal quotation
determination regarding whether or not to marks and citation omitted)), that case by
no means establishes an FDA policy that it sponsor’s proprietary data contributes to

is inappropriate for the agency to rely on the general body of scientific knowledge
any data or information from third-party about what a particular pharmacological
sources without a right of reference, as agent is or does, it is not at all clear that it
Takeda maintains.16 would even be feasible to prevent FDA’s
This Court is also at a loss to ascertain scientists from applying that knowledge
how any supposed ‘‘right of reference or when other new drug applications are con-
use’’ requirement for the agency’s consid- sidered in the future. Moreover, and in
eration of third-party data (the flip side of any event, any agency effort to secure a
Takeda’s assertion that the agency cannot ‘‘right of reference or use’’ from a prior
proceed to rely on third-party data without applicant with respect to proprietary data
such a right) would work, as a practical such applicant previously submitted would
matter. Given the confidential nature of almost certainly alert that prior applicant
the Section 505(b)(2) application process, it to the possibility of a potential new com-
makes little sense to suggest, as Takeda petitor, obviating any need for Hatch–
does, that FDA cannot consider the previ- Waxman’s patent certification and notice
ously-submitted safety and effectiveness process. Thus, Takeda’s contention that
data of third-party drug sponsors as part FDA cannot consult or rely upon third-
of its review of a Section 505(b)(2) applica- party data in the absence of a right of
tion without securing the data owner’s per- reference, or conversely, that it must se-
mission. (Cf. MSJ Mot. Hr’g Tr. at 23:22– cure such right if it desires to access third-
24:17 (arguing that, ‘‘when FDA looks at [a party data, has practical implications that
505(b)(2) ] application and concludes that it render the assertion manifestly inconsis-
is going to need to go to a different file tent with the Hatch–Waxman scheme,
and pull a different file out of the drawer which is perhaps why no such limitation on
and consult those studies and those data in FDA authority is articulated anywhere in
that file in order to make its decision,’’ the the FDCA or the agency’s regulations—
agency must not do so without taking fur- Takeda cites none, and as far as this Court
ther action). Surely the prior applicant’s can tell, the contention that ‘‘FDA had no
voluntary submission of its proprietary right to use [proprietary third-party data]
data to FDA waived any right that appli- to approve a competing product’’ (Takeda
cant may have had to prohibit FDA from Suppl. Mem. at 8; see also id. at 8–10) has
‘‘open[ing] th[e] locked file drawer’’ to ac- been crafted entirely out of whole cloth.
cess the applicant’s data in the future. Nor will it do for Takeda to insist that
(Id. at 28:13.) And to extent that a drug (fear not!) FDA actually can do what the
16. Takeda’s attempt to find an FDA policy 2007) (responding to Citizen Petition Dkt.
regarding its need for a ‘‘right of reference or Nos.2007P–0110/CP1 and 2007P–0111/PSA1);
use’’ in a citizen petition response that the however, FDA made this statement in the
agency issued in in 2007 is likewise unavail- context of a dispute between two private par-
ing. Takeda asserts that ‘‘FDA has previously ties over the continued validity of a right of
acknowledged that the ‘right of reference or reference that one of the parties had previous-
use’ permits FDA to refer to data from a ly secured from the other, and when the state-
previously approved application during the ment is read in context, it is clear that FDA
review of another party’s 505(b)(2) applica- was not in any way addressing whether the
tion,’’ Takeda Suppl. Mem. at 9 (citing Ltr.
agency itself needed a right of reference to
from Randall W. Lutter, Assoc. Comm’r for
access third-party documents, as Takeda sug-
Pol’y and Planning, FDA, to Jeffrey Chasnow
gests.
and Kelly Falconer, Pfizer, Inc., (May 18,
law otherwise would not permit it to do uation and Research, FDA, to Donald O.
when the agency undertakes to consider a Beers, Arnold & Porter LLP and William
Section 505(b)(2) new drug application F. Cavanaugh, Jr., Patterson, Belknap,
(i.e., rely on third-party data without a Webb & Tyler LLP at 10 (Nov. 30, 2004)
right of reference), so long as the agency (hereinafter ‘‘Fenofibrate Citizen Petition
requires the applicant to certify to the Response’’) (responding to Docket No.
patents that are related to the third par- 2004P–0386/CP1 & RC1)).) But FDA
ty’s drug product. (See Takeda Suppl. made this statement in the context of a
Mem. at 10 (‘‘The statute expressly author- letter that rejects Abbott Labs’s broad
izes reliance on third-party data without a proposition that a Section 505(b)(2) appli-
right of reference from the third-party. cant must certify ‘‘not only to the patents
But the quid pro quo Congress established for the listed drug that [the] 505(b)(2) ap-
for using such data is that the 505(b)(2) plication references and on which it relies
application must identify the product for for approval, but also to all patents on all
which the data was generated, as well as other later-approved [products in the same
certify to any patents listed for that prod- product line] that were approved based, in
uct.’’). In suggesting this simple solution part, on some or all of the same underlying
to a problem of its own design, Takeda is investigations[.]’’ (Id. at 1.) Read in con-
merely igniting a straw man. That is, text, FDA’s use of the phrase ‘‘[e]ach ap-
because there is no basis whatsoever for plication will certify only to patents listed
concluding that FDA’s authority to rely on for drugs on whose finding of safety and
third-party data without a right of refer- effectiveness FDA relies for approval ’’
ence is limited, there is likewise no basis merely clarifies the limited scope of the
for Takeda’s assertion that Congress has
applicant’s patent certification obligation
constructed a statutory scheme in which
as far as the universe of drug products
requiring patent certification is the ‘‘quid
that may share the same underlying inves-
pro quo’’ for being relieved of that limita-
tigations are concerned, and it is by no
tion.
means addressed to the question of wheth-
Takeda also plainly struggles to recon- er the agency’s own reliance on data out-
cile its agency-reliance argument with side that which is submitted or referred to
what the agency has said repeatedly about in the 505(b)(2) application triggers the
when the patent certification obligation is patent certification obligation.
triggered. For example, Takeda points to
a Citizen Petition Response to Abbott Furthermore, in the course of pulling
Labs dated November 30, 2004, in which FDA’s quotation out of context, Takeda
the agency stated that ‘‘[e]ach application has deftly sidestepped numerous instances
will certify only to patents listed for drugs in this same petition response in which
on whose finding of safety and effective- FDA clearly explains that its policy re-
ness FDA relies for approval (including garding a Section 505(b)(2) applicant’s pat-
patents for pharmaceutical equivalents or, ent certification obligations relates solely
if there is no pharmaceutical equivalent, to the applicant’s reliance, to wit:
for the most similar alternative), not to [A] [S]ection 505(b)(2) applicant is per-
patents submitted for applications on mitted to rely in whole or in part on the
which FDA could have relied but did not.’’ Agency’s previous findings of safety and
(Takeda Suppl. Mem. at 7 (emphasis in the effectiveness for one or more previously
original) (citing Ltr. from Steven K. Gal- approved drugs (listed drugs). As a
son, Acting Dir., FDA Ctr. for Drug Eval- condition of doing so, however, the [S]ec-
tion 505(b)(2) applicant must identify in regarding the safety and effectiveness of
its application the drug product or prod- marketed drug products—which, in and of
ucts on which it relies and certify to any itself, strongly indicates that Congress in-
relevant patents for those drug prod- tended for the agency to have more data
ucts. Patent certification obligations and information at its disposal, rather than
TTT are linked to identification of the less—and there can be no question that
listed drug or drugs on which the appli- making science-based safety decisions is
cation relies and are limited to the pat- FDA’s core function. Consequently, there
ents submitted and published for the is no reasonable explanation for the view
listed drug or drugs identified. that Congress somehow also intended for
(Id. at 8 (emphasis added) (footnote omit- the privilege that it has given FDA to
ted).) Thus, contrary to Takeda’s argu- access proprietary data and information in
ment, FDA makes clear in this Citizen the fulfillment of its core responsibilities to
Petition Response that the agency’s own be linked to, and potentially hampered by,
reliance on third-party data is not even a duty to protect third-party patent rights.
relevant to a Section 505(b)(2) applicant’s (See MSJ Mot. Hr’g Tr. at 26:7–29:3.) Put
obligation to reference a drug and file a another way, if Takeda is correct that,
related patent certification, much less ‘‘the under the statutory scheme, ‘‘[t]he critical
triggering event’’ for that obligation. [patent certification] issue is whether
(Takeda Suppl. Mem. at 6.) third-party data were used [by FDA] to
In the final analysis then, this Court support the approval of a 505(b)(2) applica-
finds no basis for Takeda’s contention that, tion’’ (Takeda Suppl. Mem. at 10), then
as a matter of FDA policy, ‘‘[t]he ultimate another crucial question remains unan-
reference and certification obligations de- swered: why would Congress require the
pend on whether FDA relies on other federal agency that is tasked with deter-
studies or data.’’ (Takeda Suppl. Mem. at mining the safety and efficacy of new
6 (emphasis in original).) Moreover, when drugs to ‘‘lock’’ an agency file drawer that
Takeda makes the assertion that FDA’s contains scientific data pertinent to the
reliance on third-party data triggers the evaluation of a new drug marketing appli-
Section 505(b)(2) patent certification obli- cation (MSJ Mot. Hr’g Tr. at 28:13), and to
gation under the Hatch–Waxman Act, it access that information for the purpose of
presents a puzzling conundrum: for all of the agency’s own review only if the agency
Takeda’s efforts to convince this Court first forces the applicant to certify to the
that Congress intended for FDA itself to data owner’s patents?
be a party to the Hatch–Waxman ex-
b. Even If Agency Reliance On Third–
change—prohibited from consulting pro-
Party Data Is Relevant, FDA Did
prietary third-party data and information
Not Approve Mitigare In Reliance On
to approve a 505(b)(2) application unless it
Mutual’s Information
forces the applicant to certify to the own-
er’s patents—it not only fails to identify Even if one were to accept Takeda’s
any statutory or regulatory provision that legal argument that the agency’s reliance
says this, it also has failed to articulate any on third-party studies and data gives rise
benefit that would redound to the agency to an obligation on the part of the agency
(or the public) as a result of that supposed to require the applicant to reference the
bargain. It is beyond dispute that Con- relied-upon drug product and certify to its
gress has entrusted FDA with the respon- patents, this Court concludes that the rec-
sibility of making scientific determinations ord here does not demonstrate FDA ‘‘reli-
ance’’ on Colcrys in its approval of Miti- envisioned when it developed the Hatch–
gare in the relevant sense. Takeda tallies Waxman patent-certification scheme.
up the number of times that ‘‘Colcrys’’
As will be discussed fully below in Part
appears in the administrative record—
246—and, largely on this basis, asserts III.A.3, with the Hatch–Waxman Amend-
that FDA’s approval of Mitigare was ments to the FDCA, Congress established
based, at least in part, on the Colcrys data. a drug approval system in which a Section
(See Takeda Suppl. Mem. at 5, 7; see also 505(b)(2) applicant can satisfy the clinical
Takeda Reply Mem. at 18–22.) It is true research requirement by using the results
that there are a substantial number of of research studies that were not conduct-
Colcrys mentions in the Mitigare record, ed by the applicant and ‘‘for which the
and there are also tables and memos that applicant has not obtained a right of refer-
indisputably demonstrate that FDA scien- ence.’’ 21 U.S.C. § 355(b)(1), (2). Here,
tists studied and compared the data that West–Ward conducted its own drug-drug
Mutual submitted with the data that interaction studies, and it also relied on
West–Ward proffered. (See id. at 19–20; published literature about colchicine and
see also, e.g., AR at 688, 692, 701.) But it FDA’s safety and efficacy findings for the
is a big leap to conclude that ‘‘FDA plainly drug Col–Probenecid. The fact that FDA
relied on Colcrys, over and over again’’ considered the differences between what
(Takeda Suppl. Mem. at 7) solely on this West–Ward’s clinical studies found and
basis, nor is it necessarily the case that what Mutual’s clinical studies had conclud-
FDA’s many mentions of the Coclrys stud- ed does not necessarily mean that West–
ies were essential to FDA’s findings that Ward’s own submissions had failed to show
Mitigare is safe and effective as labeled. that Mitigare is safe and effective for the
(See Takeda Reply Mem. at 21–22 (assert- prophylaxis of gout independently of the
ing that FDA ‘‘inherently relied’’ on Col- Colcrys data. In fact, FDA specifically
crys data).) stated that, based on West–Ward’s sub-
Takeda strongly suggests that every missions alone, the agency had come to the
mention of—or reference to—Colcrys that conclusion that Mitigare is safe and should
the agency made during its consideration be approved. (See, e.g., AR at 28–30 (Miti-
of the Mitigare application counts as an gare approval letter); id. at 162 (noting
instance of ‘‘reliance’’ for the purpose of that ‘‘the clinical pharmacology data sub-
the patent certification obligation, and cer- mitted by the applicant are sufficient for
tainly that the combined 246 times that the approval of this application for colchicine,
agency refers to Colcrys in the instant and a product label can be written based
administrative record is sufficient to satis- on case reports described in the published
fy the reliance threshold for the purpose of literature and the specific clinical pharma-
the patent certification requirement. (See, cology studies conducted by the appli-
e.g., Takeda Suppl. Mem. at 3 (‘‘[T]he cant’’); id. at 170 (‘‘No clinical pharmacolo-
agency repeatedly consulted and referred gy/biopharmaceutics deficiencies were
to Colcrys data in considering whether and identified in the original application for
how to approve Mitigare.’’); MSJ Mot. [Mitigare.]’’).) Thus, from the standpoint
Hr’g Tr. at 6 (emphasizing ‘‘the number of the type of reliance that Section
246,’’ as the number of Colcrys references 505(b)(2) requires and that Congress clear-
in the record).) In this regard, however, ly cares about, FDA did not ‘‘rely’’ on
Takeda is employing a ‘‘reliance’’ concept Mutual’s Colcrys studies to fill in an identi-
that is much broader than what Congress fied gap in the safety and effectiveness
studies that West–Ward submitted with mination would be for Congress, not this
its) application for Mitigare, as would ordi- Court, to make. In the meantime, even if
narily be the case when a Section 505(b)(2) this Court agreed with Takeda that a Sec-
applicant exercises its right of reliance on tion 505(b)(2) applicant’s patent certifica-
such studies under the statute. tion obligations are tied to the data that
Nevertheless, Takeda confidently main- FDA consults when reviewing a Section
tains that sufficient reliance was achieved 505(b)(2) application as a matter of law and
for the purpose of the Section 505(b)(2) FDA policy, Takeda has fallen short of
patent certification obligations because making a persuasive argument that FDA’s
FDA made repeated substantive refer- actions here—including its repeated ‘‘sub-
ences to Colcrys data during its review of stantive references to Colcrys data’’ (Take-
the Mitigare application (Takeda Suppl. da Suppl. Mem. at 5)—qualify as the type
Mem. at 5)—in stark contrast to the scant of reliance that Congress intended to give
number of times that Col–Probenecid was rise to the patent certification obligation.17
referenced (MSJ Mot. Hr’g Tr. at 22:3– 2. Under FDA’s Procedural Rules, An
13)—and because ‘‘Mitigare’s labeling TTT Applicant—Not FDA—Has The
would make no sense if they hadn’t looked Right To Choose The ‘‘Most Appropri-
at Colcrys’ studies.’’ (Id. at 62:10–12.)
ate’’ Or ‘‘Most Similar’’ Reference
But, given the nature of the Section
Drug For Its 505(b)(2) Application
505(b)(2) application process, Takeda’s cer-
titude that FDA’s repeated references to The second ‘‘procedural requirement’’
the Colcrys data triggered the patent cer- that Takeda and Elliott argue FDA violat-
tification requirement seems unwarranted. ed when it approved Mitigare without re-
In Takeda’s world view, it might be the quiring a reference to Colcrys and certifi-
case that the type of reliance necessary to cations to the Colcrys patents has to do
give rise to patent certification when an with the drug that a Section 505(b)(2) ap-
agency actively consults third-party stud- plicant selects as its reference listed drug.
ies and data can be different in nature (See Takeda Suppl. Mem. at 13–18.)
from the applicant reliance that the Sec- Takeda cites a Citizen Petition Response
tion 505(b)(2) process requires—i.e., the in which FDA states that a ‘‘505(b)(2) ap-
fill-in-the gap variety—but Takeda has plicant should determine which listed
provided no basis upon which this Court drug(s) is most appropriate for its devel-
can conclude that Congress intended any opment program[,]’’ (id. at 13–14 (citing
such distinction, and of course, that deter- Ltr. from Janet Woodcock, Dir., Ctr. for
17. Even page 701 of the administrative rec- sults that the two different colchicine prod-
ord—which contains ‘‘FDA’s assessment of ucts had generated about the potential inter-
the Colcrys data when combined with the Mi- action of 0.6 mg of colchicine with the same
tigare data’’ (Takeda Suppl. Mem. at 8 (em- two classifications of drugs. Indeed, FDA’s
phasis added)), and which Takeda calls a ‘‘telling’’ statement (Takeda Suppl. Mem. at 8)
‘‘smoking gun’’ example of agency reliance does not appear to be about the safety of
(MSJ Mot. Hr’g Tr. at 12:25)—does not sup- Mitigare or Colcrys at all, but is a statement
port the contention that FDA ‘‘relied’’ on the about the nature of P-gp and CYP3A inhibitors,
Colcrys data when it approved Mitigare in the in light of what, combined, the Colcrys and
sense that it was a basis for FDA’s finding of
Mitigare data showed. (See AR 701 (conclud-
safety and effectiveness. FDA was not ex-
ing that ‘‘West–Ward and Mutual’s DDI data
pressing the agency’s concerns or doubts
combined, suggests that P-gp inhibition may
about West–Ward’s submissions regarding the
play a more dominant role than CYP3A4 inhi-
safety of Mitigare, but instead was merely
comparing the two different sets of data re- bition’’).)
Drug Evaluation & Research, FDA, to also provides a clear explanation as to why
David B. Clissold, Hyman, Phelps & the agency has chosen to cede the refer-
McNamara, P.C., at 8 (Sept. 18, 2013) ence determination to the applicant in this
(hereinafter ‘‘Suboxone Citizen Petition way: because, under the Section 505(b)(2)
Response’’) (responding to Citizen Petition scheme, the applicant uses the reference
Dkt Nos. FDA–2011–P–0869 & FDA– listed drug to supply safety and effective-
2013–P–0995) (emphasis added))), and it ness data in total or partial fulfillment of
argues that, because of the similarities be- the applicant’s obligation to prove that its
tween Colcrys and Mitigare, Colcrys, rath- drug is safe and effective—meaning that
er than Col–Probenecid, was the ‘‘most there is a direct correlation between the
appropriate’’ listed drug for Mitigare to drug the applicant chooses to reference
reference. (See Takeda Suppl. Mem. at and the applicant’s burden of proof. (See
13–18.) Elliott joins in this contention, id. (‘‘An applicant choosing to rely on
putting a slightly different spin on the FDA’s finding of safety and/or effective-
argument (see Elliott MSJ Mem. at 41–42); ness for a listed drug very similar to the
ultimately, though, both Plaintiffs insist proposed product submitted in the
that West–Ward was required to identify 505(b)(2) application would generally need
Colcrys as the reference listed drug for its to submit less additional data to support
proposed new drug Mitigare ‘‘[u]nder the differences between the proposed
FDA’s governing standard,’’ such that product and the listed drug for approval of
FDA acted arbitrarily and capriciously in the 505(b)(2) application.’’).) Thus, it is
failing to insist that West–Ward follow this FDA policy that, ‘‘so long as a sponsor
rule. (Takeda Suppl. Mem. at 13; see provides the necessary data and informa-
Elliott MSJ Mem. at 41 (arguing that FDA tion to support the difference(s) between
has a policy of requiring applicants to ref-
the reference drug and its proposed drug,
erence and certify to ‘‘the most similar
and so long as the proposed drug is not an
drug with the most current safety and
exact duplicate of the reference drug, a
efficacy data’’).)
sponsor is free to choose the listed drug
Both Plaintiffs are mistaken. Put blunt- that it deems ‘most appropriate’ for reli-
ly, their argument hinges on the existence ance in its 505(b)(2) application.’’ (FDA
of an FDA drug reference policy that does Suppl. Mem. at 3; see also Fenofibrate
not exist. First, the Citizen Petition Re- Citizen Petition Response at 9 (‘‘[B]ecause,
sponse that Takeda says shows that an under 21 CFR 314.54(a), a 505(b)(2) appli-
applicant must select the reference drug cant seeking approval for a change to a
that is ‘‘most appropriate’’ contains the listed drug need only supply information
clear disclaimer that ‘‘this suggested ap- sufficient to support the change proposed,
proach does not reflect a statutory or reg- it follows that the more similar a proposed
ulatory requirement.’’ (Suboxone Citizen drug is to the listed drug cited, the smaller
Petition Response at 7). Then, when one the quantity of data that will be needed to
actually reads that document, FDA clearly
support the proposed change.’’).)
states that ‘‘a sponsor interested in sub-
mitting a 505(b)(2) application that relies To be sure, in the Suboxone Citizen
upon FDA’s finding of safety and/or effec- Petition Response, FDA states that ‘‘the
tiveness for one or more listed drugs applicant should identify the pharmaceuti-
should determine which listed drug is cally equivalent product as a listed drug
most appropriate for its development pro- relied upon[,]’’ and ‘‘should determine
gram.’’ (Id. (emphasis added).). FDA which listed drug(s) is most appropriate
for its development program.’’ (Suboxone requirements’’ (id. at 38), and that the re-
Citizen Petition Response at 7; see also quirement that an applicant reference the
Takeda Reply Mem. at 17–19.) But the ‘‘most similar drug’’ in its Section 505(b)(2)
agency also warns that ‘‘the determination application (Fenofibrate Citizen Petition
of which listed drug is ‘most similar’ to a Response at 9) does the work of enforcing
proposed product may be difficult (except this objective insofar as it constrains spon-
in cases in which a pharmaceutical equiva- sors who select the 505(b)(2) pathway as a
lent previously has been approved)[,]’’ and means of ‘‘shirk[ing]’’ their patent certifi-
that this reference determination is ‘‘de- cation obligations. (Elliott MSJ Mem. at
pendent on the sponsor’s approach to its 38.) But Elliott provides no evidence that
development program.’’ (Suboxone Citi- FDA actually monitors or mandates a
zen Petition Response at 7.) When all of ‘‘most similar drug’’ requirement within
the agency’s statements are read in con-
the 505(b)(2) context (see id. at 38–39 (pro-
text, then, it is clear that FDA’s policy is
viding only examples of ANDAs)), much
to view the ‘‘most appropriate’’ drug to be
less that the agency views this alleged
whatever drug fills in the gaps in the data
requirement as a mechanism for keeping
the drug sponsor submits to support the
applicants who approach the agency with a
sponsor’s contention that the drug is safe
questionable Section 505(b)(2) application
and effective, and not whatever listed drug
in line. Nor has Elliott explained how any
is most similar in nature to the one the
applicant proffers, as Takeda and Elliott supposed FDA policy of restraining a Sec-
maintain.18 tion 505(b)(2) applicant’s discretion re-
garding the reference drug jibes with the
Elliott’s attempt to craft a mandatory
agency’s well-established reasons for per-
reference policy out of the agency’s sup-
mitting the applicant itself to make the
posed ‘‘most similar drug’’ requirement
reference determination. (See FDA
fares no better. (Elliott MSJ Mem. at 38–
Suppl. Mem. at 2–3; FDA XMSJ Mem. at
42 (citing Fenofibrate Citizen Petition Re-
1516.) 19
sponse).) In essence, Elliott argues that
FDA has a long-standing policy of ‘‘pro- This Court also notes that, in addition to
hibiting 505(b)(2) applicants from circum- the lack of any policy on the part of FDA
venting the FDCA’s patent certification regarding which drug must be referenced
18. This is not to suggest that FDA relinquish- FDA diverged from its own policies in an
es to the applicant the ultimate determination arbitrary and capricious fashion when it re-
of whether or not the referenced drug studies fused to insist that West–Ward—a Section
successfully fill the research gap in an appli- 505(b)(2) applicant—follow the same refer-
cant’s portfolio. FDA makes that determina- ence and certification procedures as an ANDA
tion, and it may certainly reject a Section applicant must follow. (See Elliott MSJ
505(b)(2) application if, in the agency’s own Memo at 38–42.) FDA’s alleged ‘‘long-stand-
expert judgment, the investigations and stud- ing anti-circumvention policy’’ (id. at 39) is
ies that the applicant refers to do not demon-
not in conflict with its equally long-standing
strate that the applicant’s drug is safe and
view that the ANDA and Section 505(b)(2)
effective. What the agency does not do is
pathways differ substantially. To assert that
what Plaintiffs here suggest: it does not to
FDA somehow violated the former because it
force a Section 505(b)(2) applicant to refer-
evaluated Mitigare as a Section 505(b)(2) ap-
ence the drug product that is most pharmaco-
plication does not establish any APA violation;
logically similar to the applicant’s own prod-
uct. rather, it merely begs the question of whether,
under FDA’s rules, the agency properly per-
19. This is, of course, is precisely why this mitted West–Ward to proceed as a 505(b)(2)
Court cannot accept Elliott’s argument that applicant in the first place.
in a Section 505(b)(2) new drug application, the sponsor would like to do less work and
there is also no record evidence that clear- rely on a very similar drug, or do more
ly demonstrates that the mere existence of work and rely on a dissimilar drug. (See
‘‘similar’’ approved drug products matters id.) Given that policy choice—which is the
to FDA in practice. Takeda seems to opposite of Elliott’s ANDA-related asser-
think it does—one of its briefs takes care tion that ‘‘[u]nder longstanding FDA poli-
to explain Colcrys’s own reliance on Col– cy, applicants do not have unfettered dis-
Probenecid—a dissimilar combination drug cretion to choose any prior drug as the
product—by emphasizing that, ‘‘when Mu- reference listed drug’’ (Elliott MSJ Mem.
tual was seeking approval of Colcrys, no at 41)—neither the agency nor West–Ward
approved single[-]ingredient colchicine needs to provide any explanation as to
product was available, so Col–Probenecid ‘‘why Col–Probenecid was more similar or
was the most similar and most appropriate more appropriate for [West–Ward] to cite
drug for Mutual to have referenced[,]’’ and than Colcrys’’ (Takeda Reply Mem. at 17).
adding: ‘‘[t]hat was no longer true by the Regardless, it is clear that Plaintiffs’ argu-
time [West–Ward] submitted its Mitigare ment that FDA violated its own procedural
application.’’ (Takeda Reply Mem. at 18 rules when it refused to force West–Ward
n.6.) But Takeda does not, and apparently to reference the obviously most similar/ap-
cannot, show that the general state of the propriate drug (Colcrys) fails.
market at the time that a Section 505(b)(2)
3. The FDCA Unambiguously Requires
application is submitted is relevant to
A Section 505(b)(2) Applicant To Cer-
FDA’s assessment of whether a Section
tify Only To Patents Associated With
505(b)(2) applicant has established the
The Reference Listed Drug
safety and effectiveness of its new drug
product. And without such proof, Plain- Whereas Takeda’s patent certification
tiffs are hard-pressed to demonstrate that argument is primarily about whether, and
the agency has a policy of requiring an to what the extent, FDA’s approval pro-
applicant to reference the listed drug prod- cess for Mitigare relied on Colcrys data,
uct that is ‘‘most similar’’ to the applicant’s Elliott maintains that FDA should have
own. required West–Ward to certify to the Col-
crys patents regardless. Elliott’s conten-
[7] The bottom line is this: FDA’s pri- tion is primarily a statutory one: that the
or statements confirm that, other than text of the FDCA required West–Ward to
where duplicate drug products are in- file a certification to the Colcrys method-
volved, a Section 505(b)(2) applicant has of-use patents when it sought FDA ap-
the discretion to select a reference drug, proval for Mitigare, even if West–Ward
and to make that selection in relation to did not rely on the investigations or data
the scope of the materials the applicant underlying Colcrys in its application for
desires to submit. (See Fenofibrate Citi- approval. (See Elliott MSJ Mem. at 2328.)
zen Petition Response at 8–10; Suboxone In this regard, Elliott homes in on lan-
Citizen Petition Response at 8–10; AR at guage in subdivision (A) of 21 U.S.C.
12–14 (Colchicine Citizen Petition Re- § 355(b)(2); specifically, the statement
sponse).) Thus, to the extent that the that a Section 505(b)(2) application must
agency has any ‘‘policy’’ about what drug include ‘‘a certification TTT with respect to
should be referenced in a Section 505(b)(2) each patent which claims the drug for
application, FDA has decided to leave it up which such investigations were conducted
to the drug sponsor to determine whether or which claims a use for such drug for
which the applicant is seeking approval of Mitigare ‘‘was in excess of its statutory
under this subsection [.]’’ 21 U.S.C. authority and must be vacated under the
§ 355(b)(2)(A) (emphasis added).20 As El- APA.’’ (Id. at 23.)
liott reads this statute, Congress intended
Section 505(b)(2) applicants to certify not [8] As a threshold matter, Elliott is
only to the product and method-of-use pat- correct that the APA requires a reviewing
ents that claim the drug product upon court to set aside FDA’s final action in
whose investigations the applicant relied in approving a drug product for marketing if
seeking approval for the new drug—i.e., the court finds that that approval violates
every patent for the reference listed limitations that a federal statute imposes.
drug—but also to certify to all ‘‘controlling See 5 U.S.C. § 706(2)(C); see, e.g., Am.
use patents’’ related to the underlying Bioscience, Inc. v. Thompson, 269 F.3d
drug substance, even if the product associ- 1077 (D.C.Cir.2001) (holding that FDA im-
ated with the use patent is not the drug properly approved an ANDA for a generic
product referenced in the Section 505(b)(2) form of a patented drug because FDA had
application—i.e., all patents ‘‘ ‘claim[ing] a arbitrarily and capriciously removed a new
use for such drug for which the applicant patent from the Orange Book listing and
is seeking approval[.]’ ’’ (Elliott MSJ approved the ANDA without requiring the
Mem. at 25 (quoting 21 U.S.C. competitor to address the de-listed pat-
§ 355(b)(2)(A)); see also id. (explaining ent); Bayer HealthCare, LLC v. FDA, 942
that the second requirement is focused ‘‘on F.Supp.2d 17 (D.D.C.2013) (suspending
the uses for the drug for which the appli- FDA’s approval of an ANDA where FDA
cant is seeking approval, not the investiga- had approved the application for a generic
tions upon which the applicant relies’’).) version of plaintiff patent owner’s drug
Because there are four Colcrys patents without responding to plaintiff’s Citizen
listed in the Orange Book claiming a meth- Petition for years and without providing a
od of using colchicine for the prophylaxis reasoned basis for rejecting the petition).
of gout, Elliott argues that the FDCA Courts review FDA’s own interpretation of
required West–Ward to include in its ap- what the FDCA (the agency’s organic stat-
plication for approval of Mitigare certifica- ute) permits under the two-step frame-
tions to the Colcrys patents, and the fact work of Chevron, U.S.A., Inc. v. Natural
that West–Ward did not make any such Res. Def. Council, Inc., 467 U.S. 837, 104
certifications means that FDA’s approval S.Ct. 2778, 81 L.Ed.2d 694 (1984), see, e.g.,
20. The full text of Section 505(b)(2)(A) states tions were conducted or which claims a
that: use for such drug for which the applicant
(2) An application submitted under para- is seeking approval under this subsection
graph (1) for a drug for which the investiga- and for which information is required to
tions described in clause (A) of such para- be filed under paragraph (1) or subsec-
graph and relied upon by the applicant for tion (c) of this section—
approval of the application were not con- (i) that such patent information has not
ducted by or for the applicant and for been filed,
which the applicant has not obtained a (ii) that such patent has expired,
right of reference or use from the person by (iii) of the date on which such patent
or for whom the investigations were con- will expire, or
ducted shall also include— (iv) that such patent is invalid or will
(A) a certification, in the opinion of the not be infringed by the manufacture, use,
applicant and to the best of his knowl- or sale of the new drug for which the
edge, with respect to each patent which application is submitted[.]
claims the drug for which such investiga- 21 U.S.C. § 355(b)(2)(A).
AstraZeneca Pharm. LP v. FDA, 713 F.3d v. FDA, 869 F.Supp.2d 95, 102 (D.D.C.
1134, 1139 (D.C.Cir.2013); Apotex, Inc. v. 2012); Serono Labs., Inc. v. Shalala, 158
FDA, 226 Fed.Appx. 4, 5 (D.C.Cir.2007); F.3d 1313, 1319 (D.C.Cir.1998)); Eagle
Teva Pharm. Indus. Ltd. v. Crawford, 410 Broad. Grp., Ltd. v. FCC, 563 F.3d 543,
F.3d 51, 53 (D.C.Cir.2005)—a staged anal- 552 (D.C.Cir.2009). Notably, after wield-
ysis that requires the court to consider, ing these standard implements in the con-
first, ‘‘whether Congress has spoken to the text of this case, the parties here not only
precise question at issue. If the intent of have competing interpretations of subsec-
Congress is clear, that is the end of the tion (b)(2)(A)’s plain text, they also differ
matter; for the court, as well as the agen- as to whether this statutory subsection is
cy, must give effect to the unambiguously ambiguous.21 However, this Court finds
expressed intent of Congress.’’ Chevron, that Congress’ intent regarding the scope
467 U.S. at 842–43, 104 S.Ct. 2778. If of a Section 505(b)(2) applicant’s patent
there is no clear answer, however, the certification obligation is clear on the face
court must proceed to the second step, of the statute: such applicant need only
which involves giving deference to FDA’s
certify to the product patents or the meth-
interpretation of the statute so long as
od-of-use patents that are associated with
FDA’s reading of the statute is ‘‘based on
the reference listed drug (i.e., the drug
a permissible construction.’’ Id. at 843,
product on whose investigations the
104 S.Ct. 2778.
505(b)(2) applicant relies).
[9] The statutory question that Elliott
raises here is, in essence, whether 21 Examining the text of the statute, one
U.S.C. § 355(b)(2)(A) requires not only must begin at the beginning, recognizing
certification to those patents that claim the that the language of section 355 of Title
drug product on whose investigations the 21 opens with an unmistakably clear man-
505(b)(2) applicant relied (i.e., the refer- date to sponsors of new drugs: before any
ence listed drug), but also certification to new drug can be marketed, the sponsor
all patents that claim a method of using must seek FDA approval for the drug by
the drug substance (i.e., the active ingredi- filing an application with FDA that in-
ent) in the new drug product that the cludes certain specified components. See
applicant has proffered for approval. To 21 U.S.C. § 355(a) (‘‘No person shall in-
determine whether Congress has spoken troduce or deliver for introduction into in-
directly this issue under the first step of terstate commerce any new drug, unless
the Chevron analysis, this Court must use an approval of an application filed pursu-
the traditional tools of statutory construc- ant to subsection (b) or (j) of this section
tion, which include an examination of the is effective with respect to such drug.’’).
statute’s text, structure, purpose, and leg- Subsection (b)(1), which clarifies that
islative history. See, e.g., Stat–Trade Inc. ‘‘[a]ny person may file with the [agency]
21. Elliott argues that Congress unambiguous- Waxman unambiguously requires a Section
ly intended to protect all method-of-use patent 505(b)(2) applicant to certify only to patents
holders regardless of whether a Section associated with the listed drug on which the
505(b)(2) applicant references that patent applicant relies for approval. (See West–
holder’s drug, and thus that the Court’s evalu- Ward XMSJ Mem. at 7–16.) For its part,
ation of § 355(b)(2)(A) should stop at Chevron FDA argues that the statute could be inter-
Step One. (See Elliott MSJ Mem. at 23.) preted either way—i.e., it is ambiguous—but
West–Ward also argues that the Court’s analy- the agency’s interpretation is reasonable and
sis should stop at Chevron Step One, but un- is therefore entitled to deference at Chevron
like Elliott, West–Ward insists that Hatch– Step Two. (See FDA XMSJ Mem. at 7–13.)
an application with respect to any drug[,]’’ applicant is seeking approval[,]’’ id.

states that, ‘‘as a part of the application[,]’’ § 355(b)(2)(A), and also, if applicable, (B)
the applicant ‘‘shall submit’’ to the agency ‘‘a statement’’ that confirms that an exist-
several pieces of information, including: ing method-of-use patent ‘‘with respect to
(A) full reports of investigations which the drug for which investigations TTT
have been made to show whether or not were conducted’’ ‘‘does not claim a use
such drug is safe for use and whether for which the applicant is seeking approv-
such drug is effective in use; (B) a full al under this subsection,’’ id.
list of the articles used as components of § 355(b)(2)(B). In this Court’s view, the
such drug; (C) a full statement of the plain text of subdivision (b)(2) unambigu-
composition of such drug; (D) a full ously evidences Congress’ intent to re-
description of the methods used in, and quire a patent certification to be filed
the facilities and controls used for, the only with respect to patents that either
manufacture, processing, and packing of claim the drug product that is the basis
such drug; (E) such samples of such for the investigations upon which the ap-
plicant is relying (the reference listed
drug and of the articles used as compo-
drug), or that claim a method of using
nents thereof as the Secretary may re-
the reference listed drug for which the
quire; (F) specimens of the labeling pro-
applicant is seeking approval.
posed to be used for such drug, and (G)
any assessments required under section The textual support for this conclusion is
355c of this title. abundant. First, Congress lists the pat-
ents for which certifications are required
21 U.S.C. § 355(b)(1) (emphasis added).
in a single sentence—without break or
The dispute at issue here involves new numerical delineation—indicating that the
drug applications that seek to satisfy the categories of patents being referred to in
clause (A) ‘‘investigations’’ requirement this single run-on statement are generally
by relying on studies that ‘‘were not con- of the same type and bear some relation-
ducted by or for the applicant and for ship to one another, i.e., both relate to the
which the applicant has not obtained a reference-listed drug, as opposed to being
right of reference or use from the person of an entirely different species. See De-
by or for whom the investigations were Naples v. Office of Comptroller of Curren-
conducted[.]’’ Id. § 355(b)(2). Congress cy, 706 F.3d 481, 490 (D.C.Cir.2013). Sec-
specifically addresses this circumstance in ond, the disputed clause uses the word
subsection (b)(2). Pursuant to that sub- ‘‘drug’’ twice when identifying the patents
section, when an applicant wishes to rely that require certification: every patent
on the safety and efficacy investigations ‘‘which claims the drug for which such
that were conducted with respect to an- investigations were conducted or which
other drug and the applicant has not se- claims a use for such drug for which the
cured the right to reference those stud- applicant is seeking approval under this
ies, additional application materials must subsection[.]’’ 21 U.S.C. § 355(b)(2)(A).
be submitted. Specifically, the statute Although the term ‘‘drug,’’ as used in the
requires the applicant to make certain FDCA, can refer to both the finished drug
patent-related representations: ‘‘(A) a product and also its active ingredient, see
certification TTT with respect to each pat- 21 U.S.C. § 321(g)(1), the fact that Con-
ent which claims the drug for which such gress repeated the word ‘‘drug’’ twice
investigations were conducted or which within such a short span of text strongly
claims a use for such drug for which the suggests that it intended the same defini-
tion to apply to that term. See Brown v. States v. Chi Tong Kuok, 671 F.3d 931, 945
Gardner, 513 U.S. 115, 118, 115 S.Ct. 552, n. 8 (9th Cir.2012) (‘‘ ‘Such’ in this context
130 L.Ed.2d 462 (1994) (explaining that the means ‘of the sort or degree previously
presumption that a given term is used to indicated or implied.’ ’’) (quoting Webster’s
mean the same thing throughout a statute Third New Int’l Dictionary 2283 (2002);
is ‘‘surely at its most vigorous when a term Nieves v. United States, 160 F.2d 11, 12
is repeated within a given sentence’’). (D.C.Cir.1947) (‘‘The word ‘such’ is restric-
Thus, construing ‘‘drug’’ to mean the refer- tive in its effect and obviously relates to an
enced and relied-upon drug product in antecedent.’’).
both places in the disputed clause of sec-
Thus, in accordance with its plain mean-
tion (b)(2)(A) is manifestly superior to El-
ing, the term ‘‘such drug’’ unambiguously
liott’s interpretation of the text, which re-
refers back to the ‘‘the drug for which such
quires that same word to be given two
investigations were conducted’’; much like
different meanings within the same sen-
‘‘such investigations’’ plainly refers back to
tence. (See Elliott MSJ Mem. at 25–27
‘‘the investigations TTT relied upon by the
(arguing that the drug ‘‘for which the ap-
applicant for approval of the application[.]’’
plicant is seeking approval’’ refers to the
21 U.S.C. § 355(b)(2)(A). By contrast, El-
drug substance (colchicine), whereas the
liott’s reading of subsection (b)(2)(A) ig-
‘‘drug for which such investigations were
nores ‘‘such’’ entirely, and essentially re-
conducted’’ refers to the referenced drug
places it with ‘‘the,’’ so that the statute
product (here, Col–Probenecid)).
requires an applicant to submit a certifica-
The fact that Congress uses the phrase tion ‘‘with respect to each patent which
‘‘such drug’’ after the conjunction further
claims the drug for which such investiga-
indicates its intent to reference only one
tions were conducted or which claims a use
drug—the drug for which the relied-upon
for [such the ] drug for which the applicant
investigations were conducted—in section
is seeking approval.’’ As much as Elliott
(b)(2)(A). The term ‘‘such,’’ when used as
may wish that Congress had employed an-
an adjective, is an inclusive term, showing
other article in the method-of-use clause of
that the word it modifies is part of a larger
subsection (b)(2)(A), Congress selected
group. See, e.g., Black’s Law Dictionary
‘‘such,’’ and this Court is required to take
1446 (7th ed. 1999) (defining ‘‘such’’ as ‘‘[o]f
Congress at its word. See Am. Meat Inst.
this or that kind,’’ or ‘‘[t]hat or those;
v. USDA, 968 F.Supp.2d 38, 56 (D.D.C.
having just been mentioned’’); Am. Heri-
2013) (‘‘Plaintiffs TTT cannot escape the
tage Dictionary of the English Language
fact that the North Star of any exercise of
1285 (New College ed. 1976) (defining
statutory interpretation is the intent of
‘‘such’’ as ‘‘[b]eing the same as that which
has been last mentioned or implied’’). Re- Congress, as expressed in the words it
latedly, and even more important, ‘‘such’’ uses.’’).
nearly always operates as a reference back Turning to an examination of the overall
to something previously discussed. See structure of the statute, this Court finds
United States v. Ashurov, 726 F.3d 395, that its view of the plain meaning of
398–99 (3d Cir.2013) (citation, internal quo- § 355(b)(2)(A) is only reinforced. This is
tation marks, and alterations omitted) because the certification subsection is
(noting that it is ‘‘a commonly recognized clearly embedded in a section of the stat-
rule in American jurisprudence that the ute that mandates reliance upon another
word ‘such’ naturally, by grammatical us- drug’s investigations as a non-negotiable
age, refers to the last precedent’’); United prerequisite to any additional action on the
part of the applicant. See 21 U.S.C. listed drug, whether or not the 505(b)(2)
§ 355(b)(2). The fact that the entire Sec- applicant is seeking approval for a patent-
tion 505(b)(2) process concerns applica- ed use.22 Elliott’s alternative reading
tions that rely, at least in part, on the would mean that, in subsection (b)(2)(A),
safety and effectiveness finds of another Congress intended for applicants to certify
drug, lends clear credence to FDA’s argu- to all of the method-of-use patents that
ment that reliance matters under this stat- exist related to uses of the active ingredi-
utory scheme (see FDA XMSJ Mem. at ent in the applicant’s drug, but somehow
1113), and it certainly casts doubt on El- the disclaimer of potentially infringing use
liott’s assertion that the drug the Section (in subsection (b)(2)(B)) is only required
505(b)(2) applicant references and relies with respect to the method-of-use patents
upon is essentially irrelevant to an appli- related to the reference listed drug. El-
cant’s obligation to certify to patents that liott provides no reason for why Congress
may be infringed by the proffered prod- would do such a thing, and this Court sees
uct’s method of use. none.
Adding to the structural difficulty with It is also clear that the fundamental
Elliott’s proposition is the fact that the purpose of the Hatch–Waxman Amend-
subsection (b)(2)(A) certification requirements themselves confirms this Court’s
ment—which, according to Elliott, Con- reading of subsection (b)(2)(A). As has
gress intended to be completely unmoored been stated repeatedly above, Congress
from the essential reliance underpinnings intentionally designed Hatch–Waxman to
of the Section 505(b)(2) process—is fol- balance two important and potentially con-
lowed by a subsection that concerns itself flicting objectives: incentivizing invest-
expressly with the method-of-use patents ment in the innovation of new drugs, and
‘‘with respect to the drug for which investi- encouraging the production of less-costly
gations TTT were conducted.’’ 21 U.S.C. alternative drug products. Janssen Phar-
§ 355(b)(2)(B). This subsection requires maceutica, N.V., 540 F.3d at 1355. To
an applicant to file a ‘‘statement’’ in lieu of ensure that both of these goals are
a certification, when the method-of-use achieved, Congress constructed a system
patents for the referenced and relied-upon in which having to certify to patents and
drug cover uses that are not the same as provide the patent owners with notice
the uses for which the applicant seeks (protecting the innovator’s work product)
approval. (Id.) Thus, as FDA explains, is the price that a new drug applicant pays
this subsection clearly works in conjunc- for being able to rely on work already
tion with subsection (b)(2)(A), to address approved (promoting efficient drug devel-
all method-of-use patents for the reference opment). See 21 U.S.C. § 355(b)(2). (See
22. FDA provides an illuminating example: to file a certification to the patent concerning
‘‘Although neither of the patent certification that use (i.e., the use of Col–Probenecid ‘for
requirements from Section 505(b)(2)(A) apply which the applicant is seeking approval’).’’
here because no patents are listed for Col– (FDA XMSJ Mem. at 12.) ‘‘In that hypotheti-
Probenecid (the listed drug upon which West– cal situation, West–Ward would also have had
Ward relied), if, hypothetically, there were to file a statement pursuant to [S]ection
two method-of-use patents listed for Col–Pro- 505(b)(2)(B) explaining that the use patent
benecid, one concerning prophylaxis of gout listed for Col–Probenecid for treatment of
flares and one concerning treatment of acute acute gout flares does not claim a use for
gout flares, and West–Ward were seeking ap-
which the applicant is seeking approval.’’
proval of Mitigare only for prophylaxis of
(Id. at 12 n.7.)
gout flares, then West–Ward would only have
also Fenofibrate Citizen Petition Re- balanced Hatch–Waxman scales so dra-

sponse, at 11 (‘‘To divorce patent certifica- matically toward the protection of innova-
tion obligations from reliance and require tor’s patent rights, there would be no rea-
[an applicant] to certify to patents on addi- son for the statute to so clearly reflect
tional drug products on which FDA did not Congress’s interest in achieving that bal-
rely for approval would upset the delicate ance at all.23
balance struck by the Hatch–Waxman
Amendments.’’).) This quid pro quo ar- For all these reasons, this Court is con-
rangement is preserved if subsection vinced that subsection (b)(2)(A) must be
(b)(2)(A) is interpreted as it was written— read in accordance with the plain meaning
to require a new drug applicant to certify of its terms, and that those terms unam-
to the product and method-of-use patents biguously describe two related types of
that are related to the drug the applicant patents that require certification when an
references and relies upon for approval— applicant files a Section 505(b)(2) applica-
and is effectively undone if, as Elliott in- tion in reliance on another drug’s safety
sists, the applicant’s certification obligation and efficacy studies: patents that claim
does not depend at all on the applicant’s the reference listed drug and patents that
reliance on another’s work product, and claim a method of using the reference list-
instead applies across-the-board, to any ed drug, so long as the applicant is seeking
and all patented drugs that share the same approval for that patented use. In this
active ingredient and thus have a potential regard, the phrase ‘‘for which the applicant
to be infringed (however remote that po- is seeking approval’’ plainly relates to the
tential may be). As FDA points out, term ‘‘use’’—as in, ‘‘which claims a use for
‘‘there is no quid pro quo in the scenario such drug for which the applicant is seek-
that Elliot proposes; there is only a bene- ing approval ’’—and not, as Elliott argues,
fit for patent owners whose data is not the term ‘‘drug’’—as in ‘‘which claims a use
being relied on by another manufacturer.’’ for such drug for which the applicant is
(FDA XMSJ Mem. at 10.) And from the seeking approval ’’ (see Elliott MSJ Mem.
standpoint of what Congress intended, if at 26–28). As a practical matter, this
Congress really meant to tip the carefully- means that the statute requires certifica-
23. The House Committee on Energy and the applicant must certify to the referenced
Commerce’s statement that ‘‘the applicant drug’s method-of-use patents. Indeed, in the
must certify’’ with respect to ‘‘all product very same paragraph from which Elliott
patents which claim the listed drug and all draws the quotation, the Committee suggests
use patents which claim an indication for the that it intends for the statute to be read in
drug for which the applicant is seeking ap- precisely this fashion. See H.R.Rep. No. 98–
proval,’’ H.R.Rep. No. 98–857, pt. 1 at 32, 857, pt. 1 at 32 (explaining that a 505(b)(2)
does little to bolster Elliott’s contention that NDA ‘‘must include a certification by the ap-
Congress’ primary interest in crafting the plicant regarding the status of certain patents
Hatch–Waxman quid pro quo scheme was the applicable to the listed drug if such informa-
protection of all innovator’s patent rights as tion has been provided to the FDA’’ (emphasis
far as method-of-use patents are concerned, added)); see also id. at 33 (hypothesizing a
without regard to an applicant’s reliance on referenced drug that is ‘‘approved for two
the innovator’s studies. (See Elliott MSJ at indications’’ and explaining that ‘‘[i]f the ap-
2831.) As this Court reads it, this sentence plicant is seeking approval for indication No.
from the House Report says no more than 1, and not indication No. 2 because it is
what the statute states: that, where an appli- protected by a use patent, then the applicant
cant seeks approval for a use of his drug that must make the appropriate certifications and
is the same as one claimed by the listed drug a statement explaining that it is not seeking
the applicant references and relies upon, then approval for indication No. 2’’).
tion for any product patents for the refer- In short, Elliott has cast aside all of the
ence listed drug and/or any patents that very clear textual indications that Con-
claim a use for that same drug, if the gress intended a Section 505(b)(2) appli-
applicant is seeking approval for that use. cant to certify only to the patents that are
This reading does not render the statute associated with the drug that the applicant
redundant, or the method-of-use clause su- referenced and relied upon and, neverthe-
perfluous, because product patents and less, insists that, where method-of-use pat-
method-of-use patents are two different ents are concerned, Congress meant to
things, and one or the other patent type jettison the reference listed drug product
(or both) can apply to the referenced listed entirely and to require certification with
respect to all patents that claim a use for
drug product; for example, when a prod-
the active ingredient that is in the appli-
uct patent for the reference listed drug
cant’s new drug. This Court has little
does not exist or has expired but there is
doubt that Elliott’s reading is a distortion
nevertheless a valid and enforceable patent
of the statutory text, rather than a state-
for a method of using that drug product.
ment of its unambiguous plain meaning.
See Caraco Pharm. Labs., Ltd. v. Novo But even if there were any ambiguity in
Nordisk A/S, ––– U.S. ––––, 132 S.Ct. statute, and it thus became necessary to
1670, 1676, 182 L.Ed.2d 678 (2012) (‘‘[P]at- proceed to the second step of the Chevron
ents come in different varieties. One type analysis, this Court believes that it is en-
protects the drug compound itself. Anoth- tirely reasonable for FDA to interpret the
er kind—the one at issue here—gives the certification provision in subsection
brand manufacturer exclusive rights over a (b)(2)(A) to require a Section 505(b)(2) ap-
particular method of using the drug. In plicant to certify only to the product and
some circumstances, a brand manufacturer use patents that claim the reference listed
may hold such a method-of-use patent drug, which, according to FDA, has been
even after its patent on the drug com- its long-held view of the statute. (See
pound has expired.’’).24 FDA XMSJ Mem. at 11.) 25 The instant
24. One need look no further than Colcrys would need to reference Colcrys and to certify
itself to find a suitable example. Apparently, to any patent that ‘‘claims a use’’ for Colcrys,
Mutual was not able to secure a product pat- notwithstanding the fact that no Colcrys prod-
ent for Colcrys, given that Mutual did not uct patents exist.
create or develop colchicine, which has been
used as a drug for the treatment of gout for 25. This means Elliott is mistaken once again
centuries. (See AR at 3.) What Mutual was when it contends, as a corollary to its statuto-
able to patent, however, is its research and ry argument, that ‘‘longstanding FDA policy
findings related to the dosages of colchicine makes clear that patents claiming the indica-
to be used in certain instances for the prophy- tion for which approval is sought must be
laxis of gout and the treatment of acute gout addressed through the certification process.’’
flares; as noted, according to Elliott, there (Elliott MSJ Mem. at 42.) To support this
are at least four such ‘‘method of use’’ patents assertion, Elliott points to—and miscon-
for Colcrys in FDA’s Orange Book. (See El- strues—21 C.F.R. § 314.50(i)(1)(iii)(B), which
liott MSJ Mem. at 17; see also AR at 8 (listing concerns proper labeling and makes only the
the patents for Colcrys in the Orange Book at unremarkable statement that, if the labeling
the time of FDA’s 2011 Colchicine Citizen of the ‘‘drug product for which the applicant
Petition Response).) Presumably, if a future is seeking approval includes an indication
Section 505(b)(2) applicant relies on Colcrys that TTT is claimed by a use patent, the appli-
to support its application for a new drug for cant shall submit an applicable certification.’’
the prophylaxis of gout or the treatment of Id. (emphasis added). Elliott reads this regu-
gout flares, that Section 505(b)(2) application lation to mean that it is FDA’s policy that all
administrative record establishes that al of Mitigare is the fact that the agency
FDA’s position is that ‘‘[t]he language of previously and specifically addressed the
[S]ection 505(b)(2) of the Act explicitly labeling of single-ingredient oral colchicine
links the drug relied on for approval to the products in a response to a Citizen Petition
drug for which patent certifications must that Mutual filed in 2010. (See AR at 18–
be madeTTTT FDA interprets drug in 20, 24.) As explained above (see supra
[S]ection 505(b)(2) to refer to drug prod- Part I.D.1), when Mutual learned that
uct, not active ingredient [,]’’ Fenofibrate West–Ward had submitted an application
Citizen Petition Response at 6–7 (emphasis for a single-ingredient oral colchicine prod-
in original), and this Court’s view of the uct that was identical to Colcrys, Mutual
reasonableness of this interpretation is in- filed a petition that asked that the agency
herent in its findings regarding Congress’s
to restrict the marketing of such products
intent with respect to that statute, which
in the future, by, among other things: (1)
have been explained at length above. Suf-
‘‘[r]equir[ing] labeling for any single-ingre-
fice it to say here that ‘‘[t]here is nothing
dient oral colchicine product to include all
plainly wrong or impermissible about this
information related to drug-drug interac-
statutory interpretation; indeed, based on
tions that is in the Colcrys labeling includ-
the analysis above, the agency’s view of
ing relevant dose adjustments needed to
the statute TTT is entirely reasonable.’’
Am. Meat Inst., 968 F.Supp.2d at 59. prevent unnecessary toxicity;’’ (AR at 1),
Thus, even if a Chevron Step Two analysis and (2) ‘‘not allow[ing] an applicant to
was warranted, deference to FDA’s rea- carve-out the protected gout flares labeling
sonable interpretation of the statute would information because the information is es-
be warranted as well, and Elliott’s statuto- sential to prophylaxis.’’ (Id. at 22.) Take-
ry argument would fail. da now reads FDA’s written response to
this request, which the agency filed in
B. FDA’s Approval Of Mitigare Was 2011, as establishing ‘‘two specific labeling
Not An Unreasoned Change Of requirements’’ that Takeda says the agen-
The Agency’s Prior Position Re- cy arbitrarily and capriciously ‘‘aban-
garding Single–Ingredient Oral doned’’ three years later with the approval
Colchicine Products of Mitigare: ‘‘one pertaining to the low-
[10] Shifting away from the patent cer- dose regimen for treating gout flares that
tification issue that is at the heart of the occur during prophylaxis, and one pertain-
instant action, Takeda also trains its focus ing to specific safety data showing drug-
on the extent to which FDA has permitted drug interactions.’’ (Takeda Suppl. Mem.
Mitigare’s label to differ from Colcrys. at 18.) As this Court reads the record,
The basis for this attack on FDA’s approv- however, FDA did no such thing.
method-of-use patents claiming the same indi- own policy, Elliott also fails to appreciate that
cation as the applicant’s drug must be certi- the regulation it points to is part of set of
fied to, but that is not what the regulation agency rules that use nearly identical lan-
says; indeed, consistent with the FDCA, FDA guage to that of Section 505(b)(2)(A) of the
has long maintained that the only ‘‘applica- FDCA. Compare 21 C.F.R. § 314.50(i)(1)(i)
ble’’ patent certifications are those that are with 21 U.S.C. § 355(b)(2)(A). Thus, ulti-
made in relation to product or use patents mately, Elliott has made the entirely circular
that claim the reference listed drug. In its argument that language in an FDA regulation
zeal to underscore the argument that the that is nearly identical to the disputed statuto-
FDA’s statement in the regulation contravenes ry provision says what Elliott thinks the stat-
the agency’s present representations of its ute says.
To begin with, it cannot reasonably be FDA engaged in an extensive analysis of

asserted that FDA’s Colchicine Citizen Pe- this very issue. Among other things, the
tition Response established an agency poli- agency looked at the drug-drug interaction
cy that the labels for single-ingredient oral instructions on the Colcrys label and the
colchicine products must contain all of the studies Mutual had conducted regarding
drug-drug interaction information that ap- the interaction of colchicine with certain
pears on the Colcrys label, as Takeda prescription drug products. (See id. at
maintains. To support this position, Take- 681–82.) It also looked at the drug-drug
da interprets a sentence from the 27–page interaction studies that West–Ward sub-
Citizen Petition Response—the statement mitted with its Mitigare approval applica-
that ‘‘product labeling for any single-ingre- tion—studies that, quite surprisingly, had
dient oral colchicine product needs to in- come to the opposite conclusion about
clude adequate information on drug-drug whether health problems were likely to
interactions, including relevant dose ad- arise when a person taking certain inhibi-
justments needed to prevent unnecessary tor medications also takes colchicine for
toxicity’’ (AR at 3)—to mean that the la- the prophylaxis of gout. (See id. at 668,
bels of all future single-ingredient oral col- 692–94). Ultimately, in a memo entitled
chicine products have to contain the specif- ‘‘The Curious Case of Colchicine: What to
ic results of Mutual’s drug-drug interaction Do About Conflicting Drug Interaction
studies, including Colcrys’s dose-modifica- Study Results for the Same Molecular En-
tion tables. (See Takeda Reply Mem. at tity’’ (id. at 667–672), Michelle Garner, who
10–11, 15; see also, supra, Part I.C.3.) was the Senior Regulatory Management
However, FDA’s carefully worded state- Officer, represented the conclusion of a
ment does not go nearly that far; rather, ‘‘regulatory briefing panel’’ of FDA re-
the agency agrees only that the labeling of search scientists about what information
such products must contain ‘‘adequate in- needs to be conveyed regarding drug-drug
formation on drug-drug interactions, in- interactions: the panel determined both
cluding relevant dose adjustments needed that ‘‘in light of the new information pro-
to prevent unnecessary toxicity.’’ (AR at vided by the West–Ward DDI studies, and
19–20) (emphasis added).) the questions about the generalizability of
Accordingly, when it came time for FDA dose modification recommendations, TTT it
to evaluate the proposed label for Miti- was reasonable to forego detailed dose
gare, and, in particular, to make a determi- modification recommendations,’’ and also
nation regarding what dose instructions that ‘‘a general precaution to reduce the
would adequately inform patients taking daily dose and monitor closely for colchi-
Pg-p and CYP3A4 inhibitors how to use cine toxicity is reasonable[.]’’ (Id. at
the product safely for prophylaxis of gout, 672).26 Given that FDA never promised in
26. According to Takeda, FDA’s acceptance of (Compare AR at 19 (describing pre-Colcrys

a more general warning in lieu of Colcrys’s warnings as no more than ‘‘avoidance when
specific drug-drug interaction table marked a possible and caution when necessary, with
capricious return to the ‘‘pre-Colcrys wild, vigilant monitoring of clinical signs of toxici-
wild west world of ‘we have no information ty’’) with AR at 32, 33, 34–35, 38–39 (Mitigare
about this drug.’ ’’ (See PI Mot. Hr’g Tr. at label repeatedly explaining the potential toxic-
40:5–6.) But there is a significant difference ities that can result from the interaction of
between what Mitigare’s label says about colchicine and certain other products and de-
drug-drug interactions and the information scribing the four drug-drug interaction stud-
that colchicine products conveyed on this sub- ies conducted by West–Ward).) Furthermore,
ject back in the days prior to FDA regulation. rather than indicating the agency’s intent to
the Colchicine Citizen Petition Response to proved for the treatment of acute gout
require that Colcrys’s drug-drug interac- flares on the basis of the AGREE Trial
tion table appear on all future products, data. FDA did specifically state in the
and also that the agency did engage in Colchicine Citizen Petition Response that
precisely the kind of individualized assess- ‘‘labeling for a single-ingredient colchicine
ment of Mitigare’s label that the Colchi- product seeking approval for prophylaxis
cine Citizen Petition Response said would of gout flares must inform healthcare pro-
be required regarding single-ingredient viders that the lower dose colchicine regi-
oral colchicine products in the future, men evaluated in the AGREE trial is ade-
FDA’s conclusion that Mitigare did not quate to treat an acute gout flare that may
need to include the same low-dose require- occur during chronic colchicine use’’ (AR
ments as appear on Colcrys’s label was at 3); yet, as Takeda points out, FDA did
hardly a change of FDA’s position, much not require the AGREE trial information
less an ‘‘arbitrary’’ or ‘‘capricious’’ devia- to appear on Mitigare’s label. (Takeda PI
tion from its prior policy. Mem. at 27–28.) To the extent that FDA’s
A closer question is presented when one decision to approve Mitigare without a la-
considers a statement that FDA made in bel that included Colcrys’s AGREE trial
the Colchicine Citizen Petition Response regimen can be viewed as a departure
regarding Mutual’s AGREE Trial results from the agency’s prior position, this
and the extent to which the labels of future Court concludes that it was not an unrea-
single-ingredient oral colchicine products soned change in position in violation of the
approved for the prophylaxis of gout flares APA (see Takeda PI Mem. at 26–29), be-
must provide information about the use of cause the record clearly reflects the agen-
the product for the treatment of acute gout cy’s well-reasoned and well-supported ra-
flares. In the Citizen Petition Response, tionale for reaching this conclusion.
FDA considered whether the labels of sin-
gle-ingredient oral colchicine products Specifically, it is clear that FDA focused
must alert health care providers to the primarily on the undisputed fact that
possibility that a low-dose regimen of oral West–Ward had submitted an application
colchicine could be safely added to treat for approval of its colchicine capsule solely
the acute gout flares of a person who is for prophylaxis of gout. In fact, West–
regularly taking oral colchicine for prophy- Ward expressly disclaimed that Mitigare
laxis of gout. As explained in Part I.C.1, should be indicated for the treatment of
supra, Mutual had studied precisely how acute gout flares. (See AR at 28, 51).
much additional colchicine could be added With this in mind, when the agency consid-
to a regular oral colchicine regimen to ered whether the product’s packaging nev-
treat an acute gout flare in its AGREE ertheless needed to include the specific
Trial, and Colcrys was specifically ap- lower-dose regimen instructing patients
retreat to ‘‘the old, pre-Colcrys regime that tions about the generalizability of detailed
had resulted in unnecessary toxicity and dose modification recommendations to drugs
deaths’’ (Takeda Reply Mem. at 15), the rec- that have not been directly studied and asked
ord clearly demonstrates that the general the team whether safety concerns had arisen
warnings on Mitigare’s label were instead based on the detailed dose modification rec-
largely motivated by doubts that FDA scien- ommendations in the Colcrys labelingTTTT
tists had developed regarding Mutual’s find- There was some discussion of whether the Col-
ings based on West–Ward’s more recent re- crys labeling should be revised.’’ (emphasis
search. (See AR at 672 (‘‘The panel agreed added).)
that the West–Ward DDI studies raise ques-
how to use oral colchicine safely for the during prophylaxis has not been studied’’
treatment of gout acute flares that Mutual (id. at 32), and the Mitigare Medication
developed based on the AGREE Trial and Guides instructs patients that ‘‘[i]f you
that appears on Colcrys’s label, the agency have a gout flare while taking Mitigare,
came to the utterly rational conclusion that tell your healthcare provider’’ (id. at 43).
a label with the lower-dose instructions
In light of the agency’s clear and con-
was not only unwarranted, it might also
confuse users into taking more Mitigare vincing record statements about why it
than the recommended daily dosage, ex- permitted the Mitigare label to differ from
posing them to greater risk of harm. (See that of Colcrys, it is puzzling that Takeda
id. at 113.) What is more, FDA was fully puts so much stock into trying to persuade
aware that the medical community largely the Court that FDA somehow failed to
discourages patients who are taking oral explain its decisions regarding Mitigare’s
colchicine for the ongoing prophylaxis of label adequately. To this end, Takeda
gout to take additional oral colchicine for complains that FDA has not sufficiently
the treatment of a gout flare—other medi- articulated its reasons for approving a Mi-
cations are typically prescribed for this tigare label that omitted specific, known
purpose. (See id. at 4, 817; see also Mot. information about the drugs that Takeda
Hr’g Tr. Nov. 4, 2014 (hereinafter, ‘‘PI had studied (see Takeda Reply Mem. at
Mot. Hr’g Tr.’’) at 57:23–58:5). This 11–12), and it suggests that the agency
meant that requiring West–Ward to in- was not justified in refusing to require
clude on Mitigare’s label instructions for inclusion of Mutual’s findings in addition
adding doses of colchicine to treat an acute to West–Ward’s, along with an explanatory
gout flare would send exactly the wrong statement that the Colcrys research find-
message about how the product should be ings might not be generalizable (see id.).
use and for what purpose. FDA scientist Takeda also presses the argument that
Dr. Sarah Yim explained the agency’s rea- FDA needed to say more than it did re-
soning this way: garding its decision to jettison the
It is well-recognized that recent colchi- AGREE trial’s lower dose regimen for the
cine use (i.e., for prophylaxis of gout treatment of acute gout flares, which, ac-
flares) increases the susceptibility to cording to Takeda, was a must-have item
toxicity related to additional doses of for Mitigare’s label in light of the agency’s
colchicine. Although the applicant is not ‘‘own regulations, which specifically ac-
seeking an indication for the treatment knowledge that risk information related to
of acute gout flares, to the extent that a common ‘off label uses’ may be required in
healthcare provider may be considering labeling.’’ (Takeda Reply Mem. at 9 (cit-
use of additional Mitigare for treatment ing 21 C.F.R. § 201.57(c)(6)). Of course,
of an acute gout flare in a patient receiv- by the plain terms of these same regula-
ing Mitigare for prophylaxis, the review tions (specifically, the ‘‘may’’) the agency
team determined that it would be appro- has discretion regarding whether or not to
priate for the label to note that Mitigare require a product’s label to include infor-
should not be used in this way, as it has mation related to off-label uses. See 21
not been studied. C.F.R. § 201.57(c)(6) (providing that ‘‘[a]
(AR at 113 (emphasis added).) Thus, as specific warning relating to a use not pro-
approved, the Mitigare label proclaims vided for under the ‘Indications and Us-
that ‘‘[t]he safety and effectiveness of Miti- age’ section may be required by FDA in
gare for acute treatment of gout flares accordance with sections 201(n) and 502(a)
of the act if the drug is commonly pre- strates that FDA employed its scientific
scribed for a disease or condition and such expertise to reach these reasoned conclu-
usage is associated with a clinically signifi- sions about Mitigare’s label, and the agen-
cant risk or hazard’’ (emphasis added)). cy showed its work, in the form of various
Moreover, as far as the APA is concerned, memos detailing its considerations and
it is well established that just because the conclusions in this regard. Takeda has not
agency could have chosen to require established that the APA requires any-
West–Ward to adopt the Colcrys label (or thing more.
parts thereof) does not mean that the
agency had to do so. See, e.g., Hospira, C. FDA’s Decision To Approve Miti-
Inc. v. Burwell, 2014 WL 4406901, at *17 gare With A Label That Contains
(D.Md.2014) (‘‘FDA is not obligated to con- Safety Information That Differs
sider how the product might be used by From Colcrys Was Not Arbitrary
physicians beyond the approved labeling.’’ And Capricious
(emphasis in original)). Finally, Takeda attempts to cast the dis-
In any event, under the relevant review similarity between the Mitigare and Col-
standard, this Court has no choice but to crys labels in a slightly different light, by
defer to ‘‘the agency[’s] TTT choice between arguing that FDA’s approval of Mitigare
rational alternatives.’’ Rempfer v. Von Es- was arbitrary and capricious because, ‘‘[a]s
chenbach, 535 F.Supp.2d 99, 107 (D.D.C. approved, Mitigare is not safe in light of
2008) (citing Alliance for Bio–Integrity v. the significant deficiencies in its labeling.’’
Shalala, 116 F.Supp.2d 166, 177 (D.D.C. (PI Takeda Mem. at 30 (citing Food and
2000) aff’d sub nom. Rempfer v. Sharf- Drug Admin. v. Brown & Williamson To-
stein, 583 F.3d 860 (D.C.Cir.2009)). Here, bacco Corp., 529 U.S. 120, 133, 120 S.Ct.
FDA determined that the recent scientific 1291, 146 L.Ed.2d 121 (2000).) On its face,
research about the interaction between col- this contention suggests that Takeda be-
chicine and certain classes of inhibitor lieves FDA was mistaken in its ultimate
drugs cast doubt on the generalizability of determination that Mitigare is safe and
Mutual’s drug-drug interaction studies, so effective (a hard contention to make for a
the agency thought it best not to require drug manufacturer that also maintains
that the detailed Colcrys tables be includ- that its own drug product is substantively
ed on Mitigare’s label. In addition, the identical to the drug it challenges); as it
agency made the entirely rational decision turns out, however, Takeda’s actual argu-
that instructions about the additional low- ment appears to be that, in light of the
dose amounts that a user might take for long history of adverse events related to
the treatment of gout flares were inappro- colchicine toxicity, a 0.6 milligram single-
priate for Mitigare, given that Mitigare ingredient oral colchicine product simply
was being approved solely for the prophy- cannot be safe and effective without a
laxis of gout flares.27 The record demon- label that contains the low-dose regimen
27. West–Ward points out that Colcrys’s lower split the tablet. You can’t do that with [West–
dose regimen for acute gout flares also simply Ward]’s Mitigare, because our product is a
cannot be achieved, as a practical matter, capsule. You can’t split a capsule. Every-
with Mitigare’s capsule product. (See PI Hr’g thing will fall apart.’’).) This fact, too, sup-
Tr. at 51–52 (‘‘[T]he specific dose adjustment ports the rationality of FDA’s conclusion that
in the Colcrys label often are .03 milligrams. the lower dose information need not be in-
Colcrys is a .6–milligram tablet. The only cluded on Mitigare’s label.
way you get to .3 milligrams is you have to
for treating acute gout flares and the F.3d 1313, 1324 (D.C.Cir.1998)); see also
drug-drug interaction information that is Am. Wildlands v. Kempthorne, 530 F.3d
part of the Colcrys package. (Takeda PI 991, 1000 (D.C.Cir.2008) (‘‘The rationale
Mem. at 30–32.) Of course, as explained for deference is particularly strong when
in some detail in the previous section, FDA the [agency] is evaluating scientific data
has specifically determined otherwise. within its technical expertise’’) (citing Int’l
Raised again in this context, Takeda’s safe- Fabricare Inst. v. EPA, 972 F.2d 384, 389
ty concerns essentially invite this Court to (D.C.Cir.1992)); Troy Corp. v. Browner,
disagree with FDA’s underlying scientific 120 F.3d 277, 283 (D.C.Cir.1997) (courts
judgments about whether it is necessary to ‘‘review scientific judgments of the agency
include the Colcrys label information on ‘not as the chemist, biologist, or statistician
Mitigare’s label. that [they] are qualified neither by train-
That request will not be honored. As ing nor experience to be, but as a review-
explained above, on this record, Takeda ing court exercising [its] narrowly defined
cannot reasonably maintain that FDA duty of holding agencies to certain minimal
made a ‘‘clear error’’ of administrative standards of rationality.’ ’’) (quoting Ethyl
judgment when it decided to permit Miti- Corp. v. EPA, 541 F.2d 1, 36 (D.C.Cir.
gare to be marketed with a label that 1976)); Schering Corp. v. FDA, 51 F.3d
differs from Colcrys. Overton Park, 401 390, 399 (3d Cir.1995) (‘‘[FDA’s] judgments
U.S. at 416, 91 S.Ct. 814. Furthermore, as to what is required to ascertain the
the agency’s scientific determination that safety and efficacy of drugs falls squarely
Mitigare is safe and effective as labeled is within the ambit of the FDA’s expertise
entitled to the highest degree of deference, and merit deference from us.’’); Henley v.
meaning that, even if this Court had the FDA, 77 F.3d 616, 621 (2d Cir.1996)
expertise to reevaluate FDA’s safety and (‘‘FDA possesses the requisite know-how
efficacy decision, it could not freely sup- to conduct such [scientific] analyses, by
plant the agency’s scientific judgments sifting through the scientific evidence to
about what a drug product’s label must determine the most accurate and up-to-
include in order to ensure safe use of that date information regarding a particular
product, any more than it could roll up its drugTTTT We therefore defer to its rea-
sleeves and dig into the data or run its sonable findings.’’).
own clinical experiments in order to deter- Applying the necessary deference here,
mine whether FDA was wrong to conclude this Court adopts its own findings about
that such drug product was, in fact, safe. the rationality of FDA’s decisions regard-
FDA is the administrative body that has ing Mitigare’s label that are the discussion
both the expertise and the authority to in the previous section, and the bases for
evaluate the safety and efficacy of drugs, them (i.e., it concludes that Takeda’s chal-
and its conclusion that a drug product lenge fails because FDA fully explained its
submitted to it for approval—including a conclusion that Mitigare meets the applica-
product with a label that differs substan- ble safety standards as labeled, and that
tially from one that is already on the mar- explanation appears to be reasonable).
ket—is safe and effective must be respect-
ed. See Sanofi–Aventis U.S. LLC v. FDA, IV. CONCLUSION
842 F.Supp.2d 195, 209 (D.D.C.2012) When it established the Section
(‘‘[D]eference is particularly appropriate 505(b)(2) new drug approval process as
when FDA approval of drugs is involved’’) part of the Hatch–Waxman Amendments
(citing Serono Labs., Inc. v. Shalala, 158 to the FDCA, Congress placed the burden
G.B. v. DIST. OF COLUMBIA 109
of proving that a new drug product is safe

and effective squarely on the Section G.B. et al., Plaintiffs,
505(b)(2) applicant, and it charged FDA
with the responsibility of determining v.
whether that burden has been carried as a
DISTRICT OF COLUMBIA, Defendant.
scientific matter and, thus, whether a new
drug may be marketed. Although Plain- Civil Action No. 15–27 (CKK)
tiffs here maintain that FDA’s drug-ap-
proval duties carry with them the respon- United States District Court,
sibility of ensuring that third-party patent District of Columbia.
rights are protected, nothing in the FDCA
or the agency’s procedural rules required Signed January 14, 2015
FDA to force West–Ward to reference
Background: Parents and next friends of
Colcrys and to certify to its patents under
the circumstances presented here, because minor student who was eligible for special
(1) West–Ward’s Mitigare is not a dupli- education brought action against District
cate of Colcrys, and (2) West–Ward did not of Columbia under Individuals with Dis-
rely upon Colcrys data or FDA’s findings abilities Education Improvement Act
of safety and effectiveness with respect to (IDEA) to force District to fund student’s
Colcrys in order to support the Mitigare placement in private educational program
Section 505(b)(2) new drug application. while challenge to her Individualized Edu-
Moreover, it is clear from the administra- cation Program (IEP) was under review
tive record that FDA’s decision to approve by an administrative hearing officer. Par-
Mitigare with a label that differs from ents moved for temporary restraining or-
Colcrys was well-supported, and that
der and preliminary injunction.
FDA’s determination was not unreason-
able, unwarranted, or unexplained. Holding: The District Court, Colleen Kol-
Accordingly, as set forth in the separate lar–Kotelly, J., held that District proposed
order that was issued on January 9, 2015, fundamental change in disabled student’s
the Plaintiff Takeda Pharmaceuticals IEP, and thus student was entitled to stay-
U.S.A., Inc.’s Motion for Summary Judg- put injunction under IDEA pending reso-
ment in Takeda Pharms. U.S.A., Inc. v. lution of her parents’ due process com-
Burwell, et al., Civ. No. 14–1668–KBJ plaint against proposed change.
(D.D.C. Oct. 6, 2014) is DENIED; Plain-
tiffs Elliott Associates, L.P., Elliott Inter- Motions granted.
national, L.P., Knollwood Investments,
L.P.’s Motion for Summary Judgment in
Elliott Assocs., et al. v. Burwell, et al., Civ. 1. Education O862
No. 14–1850–KBJ (D.D.C. Nov. 4, 2014), is
Individualized education program
DENIED; and Defendants’ and Defen-
dant–Intervenors’ cross-motions for sum- (IEP) for a disabled student must be for-
mary judgment in Elliott Assocs., et al. v. mulated in accordance with the terms of
Burwell, et al., Civ. No. 14–1850–KBJ the IDEA and should be reasonably calcu-
(D.D.C. Nov. 4, 2014), are GRANTED. lated to enable the child to achieve passing
marks and advance from grade to grade.
, Individuals with Disabilities Education Act

§ 601, 20 U.S.C.A. § 1400(d)(1)(A); 20
U.S.C.A. § 1414.

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TAKEDA PHARMACEUTICALS, U.S.A., INC. v.

, vened as a defendant, and parties cross-

agency’s scientific expertise informs its 7. Health O317

ability to generalize manufacturer’s drug- 1. Mutual Relies On ColBenemid, Pub-

MEMORANDUM OPINION E. Procedural History TTT 80

b. Even If Agency Reliance On Third– liott Associates, L.P., Elliott International,

‘‘method-of-use patents’’ (patents covering in order to permit any potential patent

ment. (See Order, Takeda Pharms. capricious manner by approving [West–

Elliott Assocs. v. Burwell, No. 14–1850– [2–4] In reviewing agency action, a

III. DISCUSSION products. (See id. at 26–36.) Takeda also

no means establishes an FDA policy that it sponsor’s proprietary data contributes to

an application with respect to any drug[,]’’ applicant is seeking approval[,]’’ id.

also Fenofibrate Citizen Petition Re- balanced Hatch–Waxman scales so dra-

To begin with, it cannot reasonably be FDA engaged in an extensive analysis of

26. According to Takeda, FDA’s acceptance of (Compare AR at 19 (describing pre-Colcrys

of proving that a new drug product is safe

, Individuals with Disabilities Education Act

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