United States District Court, District of Columbia
MEMORANDUM OPINION DENYING PLAINTIFF'S MOTION TO
RUDOLPH CONTRERAS UNITED STATES DISTRICT JUDGE.
case returns to this Court one year after the grant of
summary judgment to Plaintiff Ferring Pharmaceuticals, Inc.
(“Ferring”) due to Defendant U.S. Food and Drug
Administration's (“the FDA”) surprise change
of position regarding the chemical classification of a
molecule within Plaintiff's colon cleansing drug,
Prepopik. For years, Ferring and the FDA have agreed that
picosulfate is the active moiety within the molecule sodium
picosulfate, one of the three active ingredients in Prepopik,
and that this active moiety does not exist in any drugs
previously approved by the FDA. Based on this understanding,
Ferring challenged the FDA's interpretation of a rule
that it believed was the only obstacle to obtaining five
years of exclusivity for the drug. After the grant of summary
judgment to Ferring removing this obstacle, and remand to the
FDA for a determination of whether Ferring was entitled to
five years of exclusivity for Prepopik, the FDA returned to
Ferring with a new conclusion: that the active moiety in
sodium picosulfate is actually
an active moiety found in several drugs that have already
been approved. As such, the FDA concluded that Ferring was
not entitled to five-year exclusivity for Prepopik.
now challenges this determination as a violation of the
Court's grant of summary judgment and remand to the
agency, and requests that this Court order the “FDA to
recognize NCE exclusivity of Prepopik, in keeping with the
positions the agency has taken repeatedly throughout the
regulatory process and ensuing litigation.” Mem. P.
& A. Supp. Pl.'s Mot. Enforce J. (“Pl.'s
Mem.”) at 17, ECF No. 64-1. For the reasons set forth
below, the Court denies Ferring's motion to enforce the
FACTUAL AND PROCEDURAL BACKGROUND
a fixed-combination drug product used to cleanse the colon
prior to colonoscopies, contains three active ingredients:
sodium picosulfate, magnesium oxide, and anhydrous citric
acid. A.R. 4, ECF No. 20-3.
“Fixed-combinations are drug products that generally
include two or more drug substances (active ingredients) in a
fixed ratio, synthetically combined into a single dosage
form.” A.R. 200, ECF No. 20-4. While magnesium oxide
and anhydrous citric acid had already been approved in
previous New Drug Applications (“NDA”) when
Ferring submitted its NDA for Prepopik, sodium picosulfate
had not been. Therefore, when it submitted its NDA for
Prepopik, Ferring also sought five years of exclusivity for
the drug as a New Chemical Entity (“NCE”), which
if approved would have prevented other drug manufacturers
from submitting Abbreviated New Drug Applications
(“ANDA”) and § 505(b)(2) NDAs of generic
versions for Prepopik for five years after the approval of
Prepopik's NDA. 21 U.S.C. § 355(j)(5)(F)(ii).
approved Ferring's NDA for Prepopik in 2012. A.R. 201.
However, the agency refused to grant Ferring five years of
exclusivity for Prepopik because two of the active
ingredients in the drug (magnesium oxide and anhydrous citric
acid) existed in drugs previously approved by the FDA.
Id. Instead, it granted Ferring three years of
exclusivity on the ground that its application
“contain[ed] reports of new clinical investigations
(other than bioavailability studies) essential to the
approval of the application and conducted or sponsored by the
applicant.” 21 U.S.C. § 355(j)(5)(F)(iii);
see Ex. D, Pl.'s Mot. Enforce J.
(“Pl.'s Mot.”) at 2, ECF No. 64-5; A.R. 201.
The regulation governing the Food, Drug, and Cosmetic
Act's five-year exclusivity provision instructs that
[i]f a drug product that contains a new chemical entity was
approved after September 24, 1984, in an NDA submitted under
section 505(b) of the [A]ct, no person may submit a 505(b)(2)
application or ANDA under section 505(j) of the [A]ct for a
drug product that contains the same active moiety as in the
new chemical entity for a period of 5 years from the date of
approval of the first approved NDA . . . .
21 C.F.R. § 314.108(b)(2). In contrast, the three-year
exclusivity provision only precludes the FDA from
approving new ANDAs and § 505(b)(2)
applications before the end of the three-year period, rather
than altogether prohibiting the submission of those
applications. Compare 21 U.S.C. §
355(j)(5)(F)(ii), with Id. § 355(j)(5)(F)(iii).
submitted a Citizen Petition requesting that the FDA change
its exclusivity determination for Prepopik. A.R. 64. A year
later, the FDA issued a response to this Citizen Petition and
Citizen Petitions filed by two other pharmaceutical companies
whose respective fixed-combination drug products had also
been denied five-year exclusivity. A.R. 199. The FDA's
response stated that it believed that its then-current
interpretation of the relevant statute and regulations-that
fixed-combination drugs that contain at least one previously
approved active moiety cannot be granted exclusivity, even if
the drug also contains at least one new active moiety-was
“permissible.” A.R. 212. However, it acknowledged
that its existing interpretation “may result in drug
development strategies that are suboptimal from a public
health perspective” because, when sponsors submit two
NDAs-one for a drug with a single active-ingredient
containing the new active moiety and another for a
fixed-combination product-“undue importance” may
be placed on “the order in which these two NDAs are
approved.” A.R. 213-14. Therefore, the FDA agreed to
consider altering its interpretation of the law, issuing a
draft guidance and seeking public comment on a new
interpretation of existing law and regulation that would
“recognize 5-year NCE exclusivity for a drug substance
that does not contain a previously approved active moiety,
even where such a drug substance is approved in a
fixed-combination with another drug substance that contains
at least one previously approved active moiety.” A.R.
the fact that Prepopik met this new standard, the FDA refused
to grant it five years of exclusivity because
“[e]xclusivity runs from the date of approval of the
product” and the agency's old interpretation had
been in effect on the date Prepopik's NDA had been
approved. A.R. 215. After filing a Petition for
Reconsideration and Petition for Stay, which the FDA denied,
Ferring filed this action in federal court, alleging that the
FDA's denial of its application was contrary to the Food,
Drug, and Cosmetic Act, 21 U.S.C. §§ 301-399b, and
the agency's own regulations, and that its refusal to
apply the new interpretation was arbitrary and capricious in
violation of the Administrative Procedure Act, 5 U.S.C.
§ 706(2)(A). See Compl. ¶¶ 58-71, ECF
No. 2. As a remedy, Ferring sought “a declaratory
judgment declaring that the FDA's determination of the
exclusivity period for Prepopik violates the [APA]” and
“injunctive relief ordering the FDA to grant the full
five years of exclusivity for Prepopik.” Compl. ¶
first review, the Court denied Ferring all of the relief it
requested. See generally Ferring Pharm. Inc. v.
Burwell (“Ferring I”), 169
F.Supp.3d 199 (D.D.C. 2016). Performing a Chevron
analysis, at Step One the Court found that it was ambiguous
whether the term “drug” in the relevant sentence
of the statute referred to drug substances or drug products.
Ferring I, 169 F.Supp.3d at 211-12 (citing
Chevron, U.S.A., Inc. v. Nat. Res. Def. Council,
Inc., 467 U.S. 837 (1984)). At Chevron Step
Two, it found that the agency's original construction of
the statute was reasonable, even though that construction
assigned different meanings to the term “drug”
within the same sentence of statutory text. Id. at
212-17. It similarly found that the original interpretation
was not arbitrary and capricious. Id. at 217-19.
This holding was in part predicated on the fact that Ferring
had not produced any examples of the original interpretation
creating circumstances in which a drug substance's
eligibility for five-year exclusivity turned on the order in
which NDAs were approved. Id. at 218 (“If
there were, in fact, situations in which a drug was eligible
for five-year exclusivity under FDA's prevailing
interpretation but failed to receive it because of the order
in which it was approved, those circumstances might render
FDA's policy arbitrary and capricious.”).
the Court's grant of summary judgment to the FDA, Ferring
moved for reconsideration on the grounds that it could
identify several examples of a single-entity drug substance
being denied five-year exclusivity due to the order in which
the NDAs for drugs that include that substance were approved.
See Mem. P. & A. Supp. Pl.'s Mot. Recons.
(“Pl.'s Mot. Recons. Mem.”) at 1-3, ECF No.
39-1. The Court granted the motion for reconsideration,
entered summary judgment for Ferring, and “remand[ed]
th[e] action to FDA for further proceedings not inconsistent
with [its] opinion.” Ferring Pharm., Inc. v.
Burwell (“Ferring II”), No. 15-802,
2016 WL 4734333, at *11 (D.D.C. Sept. 9, 2016).
the result of this remand that Ferring now challenges.
Throughout the NDA process, the NCE exclusivity Citizen
Petition process, and this litigation, the FDA has
consistently agreed with Ferring that the active moiety in
sodium picosulfate is picosulfate. For example, when Ferring
submitted its NDA for Prepopik, the FDA classified the NDA as
a “Type 1 - New Molecular Entity” submission.
See FDA, Drugs@FDA: FDA Approved Drug Products,
Prepopik (NDA 202535),
The term “new molecular entity” is not defined by
statute or regulation, but the FDA defines the term as
“an active ingredient that contains no active moiety
that has been previously approved by [the FDA] in an [NDA] or
has been previously marketed as a drug in the United
States.” See FDA, Drugs@FDA Glossary,
Implied in that classification is the determination that
sodium picosulfate contains an active moiety that had not
previously been approved because magnesium oxide and
anhydrous citric acid contain active moieties that had
already been approved. Throughout the course of this
litigation, the FDA never altered its determination that
sodium picosulfate contains a not previously approved active
months after the Court remanded this matter back to the FDA
for further proceedings consistent with its arbitrary and
capriciousness finding, the FDA changed its mind regarding
the identity of the active moiety in sodium picosulfate. It
now believes, upon “further review, ” that the
active moiety in sodium picosulfate is not picosulfate, but
rather BPHM, an active moiety that is also found in other
previously approved drug products. Ex. B at 2, Pl.'s
Mot., ECF No. 64-3. As such, it concluded that Prepopik was
not entitled to five-year NCE exclusivity. Ex. D at 8-9,
agency's change in position is based in its new chemical
analysis of picosulfate. Following its review of
Ferring's application for five-year NCE exclusivity, it
explained that “[a]t the time the Prepopik application
was submitted, the Agency determined that sodium picosulfate
was [an NME]. It was believed that picosulfate was the active
moiety of the drug substance sodium picosulfate, and that
this active moiety had not been previously approved by
FDA.” Id. at 7.
agency has given no indication of why this determination was
made. It admits that “[i]t is not clear from the
administrative record how the Agency determined that sodium
picosulfate was considered to be an NME, as no documentation
of a structural analysis of this active ingredient has been
found.” Id. The agency continues that at the time
of its approval of Prepopik's NDA and its initial denial
of the application of five-year NCE exclusivity, “there
was no need to closely examine the structure of picosulfate
to more thoroughly assess the assumption that it did not
contain a previously approved active moiety, ” because,
using the agency's interpretation of ...