United States District Court, District of Columbia
MEMORANDUM OPINION AND ORDER
RANDOLPH D. MOSS UNITED STATES DISTRICT JUDGE.
encourage pharmaceutical companies to study the safety and
effectiveness of pediatric uses of drugs approved for adults,
the Federal Food, Drug, and Cosmetic Act
(“FFDCA”) grants six months of “pediatric
exclusivity” to the sponsor of a brand-name drug if the
sponsor conducts studies that “fairly respond” to
a “written request” from the Food and Drug
Administration (“FDA”). 21 U.S.C. §
355a(d)(4). At the urging of Plaintiff Amgen Inc., the FDA
issued a written request asking that Amgen conduct pediatric
studies of its drug Sensipar (cinacalcet hydrochloride), and
Amgen endeavored to fulfill the request. Ultimately, however,
the FDA found that Amgen had failed to complete a study on
the safety of cinacalcet hydrochloride in children ages 28
days to < 6 years and concluded that Amgen's studies
did not “fairly respond” to the written request.
The FDA, accordingly, denied Amgen's request for
pediatric exclusivity. Subsequently, the FDA denied both
Amgen's request for reconsideration and its appeal of
challenges the FDA's decision as well as the agency's
underlying interpretation of the “fairly respond”
requirement. The matter is now before the Court on
Amgen's motion for summary judgment, Dkt. 60, and
cross-motions for summary judgment filed by the FDA, Dkt. 65,
and four intervenor-defendants, Dkt. 63. For the reasons that
follow, the Court will DENY in part and
GRANT in part Amgen's motion and will
DENY in part and GRANT in
part the FDA's and the intervenor-defendants'
cross-motions for summary judgment.
manufacturer seeking to market a new drug in the United
States must first obtain approval from the FDA. The approval
process is both time-consuming and expensive. Among other
things, the applicant-or “sponsor”-must submit a
new drug application (“NDA”) containing the
extensive data and information necessary to demonstrate that
the new-or “pioneer”-drug is “safe”
and “effective, ” 21 U.S.C. § 355(b)(1), as
well as a “certification” relating to each patent
that claims the drug or a use of the drug, 21 U.S.C. §
Drug Price Competition and Patent Term Restoration Act of
1984, Pub. L. No. 98- 417, 98 Stat. 1585-popularly known as
the Hatch-Waxman Act-created an alternative path for
manufacturers of generic drugs. Instead of submitting its own
clinical data on safety and efficacy, a generic manufacturer
may submit an abbreviated new drug application
(“ANDA”) showing that the generic version of the
drug contains the same active ingredient as the pioneer drug
and is “bioequivalent” to that drug. 21 U.S.C.
§ 355(j); see AstraZeneca Pharm. LP v. FDA, 713
F.3d 1134, 1136 (D.C. Cir. 2013) (“ANDAs need not
include new clinical studies demonstrating . . . safety or
efficacy, but must propose the same basic labeling as
approved for the pioneer drug.”). In creating this
shortcut, Congress sought to encourage “the development
of generic drugs to increase competition and lower
prices.” Amarin Pharm. Ireland Ltd. v. FDA,
106 F.Supp.3d 196, 198 (D.D.C. 2015). But, at the same time,
Congress recognized that it needed to maintain
“incentives for pharmaceutical companies to invest in
innovation and the creation of new drugs.” Id.
Accordingly, Congress “provided increased intellectual
property rights and periods of market exclusivity for those
pioneer manufacturers that invent new drugs.”
Id.; see also 21 U.S.C. §
355(j)(5)(F); AstraZeneca, 713 F.3d at 1136. After
the period of marketing exclusivity ends, however, the FDA
may ordinarily approve ANDAs, thus authorizing the marketing
of competing, generic versions of the pioneer drug.
AstraZeneca, 713 F.3d at 1136; see 21
U.S.C. § 355(j).
this statutory scheme proved successful in encouraging
generic competition while maintaining the impetus to
innovate, it failed to provide sufficient incentives for drug
companies to conduct research on the effects of new drugs on
children. In 1997, Congress found that the pharmaceutical
industry had “studied and labeled for use in
children” only a small portion of the drugs on the
market, even though “children suffer from many of the
same diseases as adults and are often treated with the same
medicines.” S. Rep. No. 107-79, at 3-4 (2001). After
looking for the cause of this lack of pediatric research,
Congress concluded that “there [was] little incentive
for drug sponsors to perform studies for medications which
they intend to market primarily for adults and [the] use [of
which] in children is expected to generate little additional
revenue.” Id. at 4 (quoting S. Rep. No.
104-284 (1996)). The absence of information on pediatric drug
safety and efficacy, moreover, exposed children to a number
of unique risks:
Dosing children based merely on their lower weight is often
imprecise, since their bodies can metabolize medicines
differently than adults. Some drugs may have different
adverse side effects or toxicities in children than in
adults, so estimating dosages for children from dosages found
to be safe and effective in adults may not be appropriate.
The lack of pediatric studies and labeling information may
lead to unintended medical errors and place children at risk
of being under-dosed or overdosed with medication. The lack
of age-appropriate formulations (e.g., liquid form) can also
make it difficult to give children and infants prescribed
amounts of a needed medication.
Id. at 3.
address this problem, Congress enacted a “pediatric
exclusivity” statute. See Food and Drug
Administration Modernization Act of 1997, Pub. L. No.
105-115, § 111, 111 Stat. 2296, 2305-09; Best
Pharmaceuticals for Children Act, Pub. L. No. 107-109, 115
Stat. 1408 (2002); see also Mylan Labs., Inc. v.
Thompson, 389 F.3d 1272, 1276 (D.C. Cir. 2004). Under
that law, a drug sponsor that receives “pediatric
exclusivity” is entitled to an additional six months of
market exclusivity. AR 1390. This protection, moreover, is
sweeping; it applies to all “products containing the
active moiety that has existing patent protection or
exclusivity, ” and it applies both to patent rights and
to the FDA's authority to approve ANDAs for competing
events must occur for a sponsor to qualify for pediatric
exclusivity: (1) the FDA must determine “that
information relating to the use of [the] drug in the
pediatric population may produce health benefits in that
population;” (2) the FDA must make a “written
request for pediatric studies;” (3) the applicant must
agree to that request; (4) the studies must be
“completed using appropriate formulations for each age
group for which the study is requested within [the specified]
timeframe;” and-most importantly for present
purposes-(5) the reports from those studies must be
“submitted [to] and accepted” by the
FDA. 21 U.S.C. § 355a(b)(1) (emphasis added). A sponsor
may ask the FDA to issue a written request by filing “a
proposed pediatric study request” (“PPSR”).
21 U.S.C. § 355a(d)(3). Before issuing the written
request, the FDA must consult with the sponsor, 21 U.S.C.
§ 355a(d)(1)(A), and submit the request for review by
the Pediatric Review Committee, 21 U.S.C. § 355a(f)(1),
(2). That committee includes experts in, among other fields,
pediatrics, biopharmacology, chemistry, and “the
appropriate expertise pertaining to the pediatric product
under review.” 21 U.S.C. § 355d. When issued, the
written request asks the sponsor to “conduct pediatric
studies” within a certain timeframe and to
“propose pediatric labeling resulting from such
studies.” 21 U.S.C. § 355a(d)(1)(A).
written request “serves as a yardstick against which
the sponsor's eligibility for pediatric exclusivity is
later measured.” Dkt. 65-1 at 16. As the FDA explains,
“[g]iven the breadth of the benefit available to
sponsors who qualify for pediatric exclusivity, the agency
generally asks for a full range of studies designed to
provide meaningful information regarding use of the drug in
all of the pediatric populations in which the drug is likely
to be used.” Id. at 15-16. The written request
also includes “specific details regarding study design
and endpoints, [the] number of patients to be studied, and
study duration.” Id. at 16.
the sponsor completes the studies and submits its reports,
the FDA is required to decide within 180 days whether to
“accept or reject such reports.” 21 U.S.C. §
355a(d)(4). The FDA must accept the reports if the
sponsor's studies satisfy the three exclusive conditions
set forth in the statute. In the words of the statute:
The Secretary's only responsibility in accepting
or rejecting the reports shall be to determine, within the
180-day period, whether the studies  fairly respond to the
written request,  have been conducted in accordance with
commonly accepted scientific principles and protocols, and
 have been reported in accordance with the requirements of
the Secretary for filing.
Id. (emphasis added). The Pediatric Review Committee
may review the studies for purposes of making a
recommendation on whether the FDA should accept or reject the
reports, but it is not required to do so. 21 U.S.C. §
case turns on the meaning of the “fairly respond”
requirement, and, it is fair to say, the FDA's approach
to this statutory language has “[e]volv[ed]” over
the years. Dkt. 60-1 at 13. Prior to 2001, the FDA apparently
required that the sponsor satisfy each and every term of the
written request. In Merck & Co. v. FDA, 148
F.Supp.2d 27 (D.D.C. 2001), a drug sponsor challenged that
interpretation after the FDA denied its request for pediatric
exclusivity. Id. at 30. Judge Robertson concluded
that denying pediatric exclusivity “for failure to meet
a single term of a written request would not be in
accordance” with the statute. Id. The statute,
he explained, “plainly does not require compliance with
every single provision of a written request, but requires
only that a pediatric study ‘fairly respond' to a
written request.” Id. The Court, accordingly,
extended its earlier temporary restraining order, which had
“stayed the effectiveness . . . of the FDA's
refusal” of pediatric exclusivity. Id. at 31.
FDA's most recent interpretation of the statute is set
forth in a letter decision issued by the Deputy Director for
Clinical Science, Center for Drug Evaluation and Research on
August 2, 2017, resolving Amgen's administrative appeal.
See AR 1632-50. Under the interpretation set forth
in that letter, the “fairly respond” requirement
can be satisfied in two ways. First, “[w]hen a sponsor
meets the terms” of the written request, “the
resulting studies” will “fairly respond” to
the request because “studies that are carried out in
accordance with the trial's plans and objectives, as
expressed in the [written request], will generally satisfy
the statutory goal of obtaining pediatric use
information.” AR 1637. Neither party disputes this
aspect of the FDA's interpretation. The parties'
disagreement, instead, centers on the second prong of the
test. Under that prong, even where “specific
terms” of the written request are not met, the FDA will
nonetheless “generally consider the sponsor's
studies to have ‘fairly responded'” to the
written request if the agency, “apply[ing] its
scientific expertise, ” determines that the underlying
“objectives of the [written request] have . . . been
met.” Id. That is, the studies will be
accepted if the FDA determines that the studies yielded
information that is “clinically meaningful across all
age groups and uses cited in the” written request.
March 2004, the FDA approved Amgen's drug Sensipar, or
cinacalcet hydrochloride, for secondary hyperparathyroidism
(“HPT”) in adult patients with chronic kidney
disease on dialysis, hypercalcemia in adult patients with
parathyroid carcinoma, and hypercalcemia in adult patients
with primary HPT who are unable to undergo parathyroidectomy.
AR 1403. Several of Amgen's patents claim Sensipar, one
of which expires on March 8, 2018. Dkt. 65-1 at 17.
believing that there was “an unmet medical need for the
treatment of secondary HPT” in children, submitted a
Proposed Pediatric Study Request to the FDA in May 2007. AR
18, 38-42. At that time, cinacalcet's “safety [and]
effectiveness in pediatric patients had not been
established.” Dkt. 65-1 at 17 (citing AR 14). Amgen,
then, submitted a new Proposed Pediatric Study Request in
December 2009, stressing that there was a need for pediatric
studies because cinacalcet was “already being used
off-label in a significant portion of the pediatric dialysis
patient population.” AR 1633-34. In May 2010, after
“several years of discussions and a pre-clinical study,
” Dkt. 60-1 at 14, the FDA issued a written request to
Amgen, see AR 647. As the agency explained,
pediatric studies on cinacalcet were necessary because its
efficacy in adults “cannot be extrapolated to the
pediatric population”: secondary HPT progresses
differently in children, and cinacalcet poses unique risks to
pediatric patients, whose “skeletal and vascular
system[s]” are still developing. AR 648. The written
request, accordingly, proposed that Amgen conduct two
pediatric studies on “the potential use of cinacalcet
hydrochloride in the treatment of secondary
hyperparathyroidism” in children “with chronic
kidney disease . . . receiving dialysis.” AR 647. The
objective of the written request was to obtain information on
cinacalcet's efficacy, safety, and tolerability in
pediatric patients, including “pediatric patients ages
28 days to < 6 years.” AR 647-48.
the next several years, the written request was amended five
times to relax the study parameters, reduce the scope of the
studies, or expand the ways in which the requested
information could be obtained. See AR 730-48,
755-68, 990-1007, 1035-51, 1076-90; see also Dkt.
60-1 at 14-15; Dkt. 65-1 at 18-19. The final-and
operative-version of the written request asked Amgen to
complete four clinical studies:
Study 1: A single dose
(“PK/PD”)] study in pediatric patients
ages 28 days to < 6 years with chronic kidney
disease and secondary hyperparathyroidism receiving dialysis.
Study 2: A 30-week, randomized, double-blind,
placebo-controlled, safety and efficacy study with a
30-week, open-label, safety extension in pediatric patients
ages 6 years to < 18 years with chronic kidney
disease and secondary hyperparathyroidism receiving dialysis.
This study will include an assessment of pharmacokinetic (PK)
parameters using a sparse sampling design. Study 2 has been
terminated early and will be analyzed with available data.
Study 3: A 26-week or time-until-transplantation
(whichever comes first), open-label, safety study in
pediatric patients ages 28 days to < 6 years. . .
Study 4: A 20-week, randomized, open-label,
controlled study in pediatric subjects between the ages
of 6 and < 18 years, with secondary
hyperparathyroidism and chronic kidney disease who are
receiving either hemodialysis or peritoneal dialysis.
AR 1080 (emphasis added). Although Study 1 and Study 3 both
involved pediatric patients ages 28 days to < 6 years,
they focused on different questions. Study 1 examined
cinacalcet's pharmacokinetics (the drug's
“movement . . . within the body” such as
“absorption, distribution, [and] metabolism”) and
pharmacodynamics (“the characteristics of the action
of” the drug). Dkt. 60-1 at 15 n.4 (internal quotation
marks and citation omitted). Study 3, in contrast, focused on
the drug's safety in the youngest pediatric patients.
Compared to Study 2, which also examined safety but in older
pediatric patients, Study 3 was “shorter, smaller[, ]
[and] of limited scope” with a minimum of only 15
completers. Dkt. 65-1 at 19-20; see AR 1063. For a
variety of reasons, Amgen struggled to locate an adequate
number of patients for Study 3, AR 664-66, but eventually
enrolled 18, AR 1159.
December 2012, a patient enrolled in Study 2 died. AR 840.
Following standard protocol, the FDA issued a partial
clinical hold, or a temporary suspension, on further testing
on pediatric patients with secondary HPT. Id. While
the hold was in effect, Amgen and the agency discussed
potential next steps. See AR 858-64. Amgen opted to
continue the studies, AR 862, and the FDA replaced Study 2
with Study 4, AR 991-92. The hold, however, affected
Amgen's ability to complete Study 3. As Amgen explains,
“enrolled patients were not receiving treatment, and
five of the eight patients then[-]enrolled in Study 3
discontinued their participation.” Dkt. 60-1 at 17.
Amgen and the FDA continued to correspond regarding
Amgen's efforts to complete Study 3. See AR
2015, the FDA rejected Amgen's request for a sixth
amendment, which would have lowered the minimum number of
completers in Study 3 from fifteen patients to four
patients-“the number of completers in the study
available at the time.” AR 1338. The agency “did
not agree that [four] completers . . . would allow for an
adequate characterization of safety for the intended
use” and “was not willing to further amend”
the written request to lower the study parameters to fit
“the amount of data collected.” AR 1138-39. Amgen
also sought a meeting with the FDA to discuss Study 3 and the
submission of Amgen's supplemental NDA. AR 1099. The FDA
denied Amgen's request, asserting that it would
“not have any more discussion on” Study 3 and
indicating that Amgen's request to meet regarding
Amgen's supplemental NDA was premature. AR 1102. The
agency eventually met with Amgen on September 21, 2016,
“to discuss the overall cinacalcet pediatric
development program.” AR 1116.
November 23, 2016, Amgen submitted its study reports to the
FDA, requested pediatric exclusivity, and sought approval for
a pediatric indication for Sensipar. AR 1152. The “only
discrepancy” between Amgen's studies and the
written request was “the number of completers”
for Study 3. AR 1159. The written request required a minimum
of 15 patients; Amgen enrolled 18. Id. But only 11
patients exceeded 12 weeks of treatment, and even fewer- just
4 patients-completed the full 26-week study. Id.
Nevertheless, Amgen reported, it had collected
“sufficient data” to “satisfy the primary
objectives” of Study 3, which were to “evaluate
the safety and tolerability” of cinacalcet in pediatric
patients ages 28 days to < 6 years. AR 1160. In
Amgen's opinion, its data was “sufficient . . . to
support an indication” in that pediatric population.
22, 2017, the FDA denied Amgen's request for pediatric
exclusivity in a letter decision. AR 1389-98. The agency
explained that, in issuing the written request, it sought to
“characterize the risks” of using cinacalcet to
treat secondary HPT in children with chronic kidney disease
on dialysis. AR 1391. But the FDA found that it could not
draw “any conclusions about the safety” of the
drug in a key age group-patients ages 28 days to < 6
years-because of “Amgen's failure to provide
sufficient safety data.” AR 1398. This conclusion was
based on the “totality of safety information”
Amgen provided, not merely the data generated in Study 3.
Id. As the FDA explained, Amgen's reports
“could [have] be[en] considered a fair response to the
[written request] as a whole” if the company's
findings in the aggregate “provided an appropriate
safety assessment in younger children.” Id.
Instead, the “lack of sufficient safety data” on
pediatric patients ages 28 days to < 6 years “led to
the inability to clearly establish the safety profile of the
drug . . . in accordance with [the] objectives of the amended
[written request].” Id.
days after the FDA issued its decision, Amgen filed this
action “to compel the FDA” to accept Amgen's
reports and to grant pediatric exclusivity for Sensipar. Dkt.
1 at 2 (Compl. ¶ 1). Amgen claimed that the FDA's
interpretation of “fairly respond” was contrary
to the pediatric exclusivity statute under the Administrative
Procedure Act (“APA”), 5 U.S.C. § 701 et
seq., Dkt. 1 at 21-23 (Compl. ¶¶ 50-56); that
its denial of pediatric exclusivity for Sensipar was
arbitrary and capricious, id. at 29-31 (Compl.
¶¶ 76-88); and that its application of its standard
violated Amgen's due process rights, id. at 31
(Compl. ¶¶ 89-90). On the same day, Amgen moved for
a temporary restraining order or preliminary injunction,
arguing that it might “lose the full benefit of its
pediatric exclusivity” absent injunctive relief. Dkt. 3
at 10. The Court held a hearing on Amgen's motion on June
2, 2017. Minute Entry (June 2, 2017). After the hearing,
however, the parties agreed that Amgen would seek
reconsideration and administrative dispute resolution before
the FDA and that the proceedings before the Court would be
stayed. Dkt. 14. Based on the parties' stipulation, the
Court denied Amgen's motion for preliminary relief as
moot and stayed the case pending completion of the renewed
administrative process. Dkt. 15.
remand, the FDA denied both Amgen's request for
reconsideration, AR 1484, as well as its appeal of that
decision in the FDA's administrative dispute resolution
process, AR 1632. During those proceedings, Amgen
“pressed the same arguments it makes here”-that
the FDA's interpretation of “fairly respond”
is foreclosed by the statute and that FDA's application
of that standard to Amgen “violated foundational
principles of administrative law and due process.” Dkt.
60-1 at 22. In a final letter decision denying Amgen's
administrative appeal, the agency set forth the
interpretation of “fairly respond” described
above. See supra Part I.B. Applying that standard,
the FDA affirmed its earlier conclusions that Amgen's
studies did not “fairly respond” to the written
request because (1) Amgen “fail[ed] to carry out Study
3 in accordance with the [written request]” and (2)
Amgen failed to provide “meaningful pediatric use
information in children 28 days to < 6 years of
age.” AR 1648.
dispute then returned to this Court, where the parties
jointly proposed an expedited briefing schedule. Dkt. 24.
Before either side moved for summary judgment, four generic
drug companies-Teva Pharmaceuticals USA, Inc., Barr
Laboratories, Inc., Watson Laboratories, Inc., and Amneal
Pharmaceuticals LLC-moved to intervene as defendants, Dkt.
26; Dkt. 33, and the Court granted their motions,
see Minute Order (Aug. 15, 2017); Dkt. 61. In
addition, Amgen moved to complete or supplement the
administrative record with several sets of documents that
Amgen asserted were considered by the FDA in denying Amgen
pediatric exclusivity. Dkt. 38. The Court denied Amgen's
motion in part from the bench at a hearing held on September
20, 2017, and directed that the parties meet and confer
regarding the remaining portion of Amgen's motion.
See Minute Entry (Sept. 20, 2017). After the parties
were unable to reach an agreement, they set forth their
respective positions in a further filing, Dkt. 53, and the
Court denied the remainder of Amgen's request,
see Minute Order (Oct. 11, 2017); Dkt. 61.
motions are now before the Court: Amgen's motion for
summary judgment, Dkt. 60, the FDA's cross-motion, Dkt.
65, and the intervenor-defendants' joint cross-motion,
Dkt. 63. The Court held a hearing on those motions on January
11, 2018. See Minute Entry (Jan. 11, 2018). Because
Amgen has represented that a “key patent covering
Sensipar” is due to expire on March 8, 2018, Dkt. 1 at
4-5 (Compl. ¶ 9), the Court has expedited its resolution
of the pending motions.
Federal Rule of Civil Procedure 56, summary judgment is
ordinarily available if the movant demonstrates “that
there is no genuine dispute as to any material fact”
and that, based on the uncontested facts, “the movant
is entitled to judgment as a matter of law.”
Fed.R.Civ.P. 56(a). In the unique context of a case brought
under the APA, however, the district court “sit[s] as
an appellate tribunal, ” Marshall Cty. Health Care
Auth. v. Shalala, 988 F.2d 1221, 1222-23 (D.C. Cir.
1993), to decide “as a matter of law [whether] the
agency action is supported by the administrative record and
is otherwise consistent with the APA standard of review,
” Coal. for Common Sense in Gov't Procurement
v. United States, 821 F.Supp.2d 275, 280 (D.D.C. 2011);
see also Citizens to Preserve Overton Park, Inc. v.
Volpe, 401 U.S. 402, 415 (1971); Sw. Merch. Corp. v.
NLRB, 53 F.3d 1334, 1341 (D.C. Cir. 1995). In short, it
is the role of the administrative agency to “resolve
factual issues” and to “arrive at a decision that
is supported by the ...