Depomed, Inc. v. United States Department of Health & Human Services

UNITED STATES DISTRICT COURT

FOR THE DISTRICT OF COLUMBIA

)

DEPOMED, INC., )

)

Plaintiff, )

)

v. ) Civil Action No. 12-cv-1592 (KBJ)

)

UNITED STATES DEPARTMENT OF )

HEALTH AND HUMAN SERVICES, )

et al., )

)

Defendants. )

)

MEMORANDUM OPINION

Plaintiff Depomed, Inc. (“Depomed”) is a pharmaceutical company that, as

relevant here, has developed a drug to treat a rare condition known as post-herpetic

neuralgia (“PHN”). 1 Depomed contends that its drug, which is called Gralise, was

automatically entitled to a seven-year period of marketing exclusivity under the Orphan

Drug Act (the “Act”), 21 U.S.C. §§ 360aa–360ee, once the drug satisfied two statutory

requirements: (1) designation by the Food and Drug Administration (“FDA”) as a so-

called “orphan drug” for use in treating a rare disease or condition, and (2) receipt of

FDA approval to be marketed to the public. Depomed brought the instant action against

the FDA, the United States Department of Health and Human Services, and both

agencies’ respective directors (collectively “Defendants”) after the FDA refused to

recognize the exclusivity period for Gralise despite its having met the statutory criteria;

the one-count complaint alleges that such refusal violated the Administrative Procedure

Act (“APA”), 5 U.S.C. §§ 701–706. Defendants do not dispute that the FDA has

1

PHN is nerve pain that sometimes arises as a complication of the shingles virus.

1

designated Gralise an orphan drug and has approved it to be marketed for treatment of

PHN. Nevertheless, Defendants maintain that the FDA was not required to grant

Gralise orphan drug exclusivity in the instant case because the FDA has already granted

marketing approval to a drug called Neurontin for treatment of PHN, and according to

the FDA, Depomed has not proven that Gralise is “clinically superior” to Neurontin—a

requirement that the FDA has imposed because Gralise and Neurontin have the same

active ingredient (gabapentin). 2 Through the instant action, Depomed requests

declaratory and injunctive relief that, in essence, would force the FDA to recognize that

Gralise is entitled to the statutory exclusivity period.

Before this Court at present are two dispositive motions: Plaintiff’s motion for

summary judgment, and Defendants’ motion to dismiss or, in the alternative, for

summary judgment regarding the complaint’s allegation of a violation of the APA.

Because this Court finds that the plain language of the Orphan Drug Act unambiguously

requires the FDA to recognize that any drug that has been both designated as an orphan

drug for treatment of a qualifying disease or condition and also approved for marketing

is entitled to an exclusivity period, the Court will GRANT Plaintiff Depomed’s motion

for summary judgment and will DENY Defendants’ motion to dismiss or, in the

alternative, for summary judgment. Accordingly, judgment will be entered in

Depomed’s favor in this action, and the Court will order the FDA to recognize orphan-

drug marketing exclusivity for Gralise for a period of seven years from the date the

FDA approved Gralise for marketing. A separate order consistent with this opinion will

follow.

2

As explained in more detail below, Neurontin was never designated as an orphan drug, nor has the

FDA recognized orphan-drug exclusivity for Neurontin.

2

I. BACKGROUND

A. Statutory And Regulatory Framework

1. The Orphan Drug Act

This case turns on the parties’ competing interpretations of the statutory text and

implementing regulations of the Orphan Drug Act. Congress enacted the Orphan Drug

Act in 1983 as an amendment to the Food, Drug, and Cosmetic Act (“FDCA”). See

Orphan Drug Act, Pub. L. No. 97-414, 96 Stat. 2049 (1983) (codified at 21 U.S.C.

§§ 360aa–360ee (2012)). The Act’s fundamental purpose is to provide drug

manufacturers with incentives to research and develop so-called “orphan drugs[,]” see

id. §§ 1(b)(1)–(3), which are drugs that treat certain “rare disease[s] or condition[s][,]”

21 U.S.C. § 360bb(a)(1). 3 As explained in the relevant congressional findings, prior to

the Act’s passage, it was considered generally financially impractical for

pharmaceutical companies to develop such drugs. See § 1(b)(4), 96 Stat. at 2049

(noting that “so few individuals are affected by any one rare disease or condition” that

“a pharmaceutical company which develops an orphan drug may reasonably expect the

drug to generate relatively small sales in comparison to the cost of developing the drug

and consequently to incur a financial loss”). Because Congress believed that it was “in

the public interest” that orphan drugs be developed, it enacted the Act “to reduce the

costs of developing such drugs and to provide financial incentives to develop such

drugs[.]” Id. at §§ 1(b)(5)–(6).

By all accounts, the Act’s chief “financial incentive[ ][,]” id., is a seven-year

period of marketing exclusivity granted to certain drugs pursuant to section 360cc of

3

Under the Act, a “rare disease or condition” is one that either “affects less than 200,000 persons in the

United States” or “for which there is no reasonable expectation” that drug developers will recoup the

considerable costs associated with developing a new drug based on sales of that drug in the United

States. 21 U.S.C. § 360bb(a)(2).

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the Act. See 21 U.S.C. § 360cc(a). 4 The central issue in this case is the parties’

disagreement over what conditions a drug must satisfy to qualify for this exclusivity.

The statute’s exclusivity provision provides in relevant part that

if the [FDA] approves an application filed pursuant to section 355 of this

title . . . for a drug designated under section 360bb of this title for a rare

disease or condition, the [FDA] may not approve another application

under section 355 . . . for such drug for such disease or condition for a

person who is not the holder of such approved application . . . until the

expiration of seven years from the date of the approval of the approved

application[.]

Id. In other words, the plain language of the statute sets forth two procedural

prerequisites for marketing exclusivity: first, the FDA must have “designated” the drug

as an orphan drug, upon request from the drug’s sponsor, pursuant to 21 U.S.C. § 360bb

and its accompanying regulations 5; and second, the FDA must have “approved” the

designated orphan drug for marketing to the public pursuant to 21 U.S.C. § 355, which

is the section of the FDCA that provides the general procedure for marketing approval

of all the pharmaceutical products that the FDA regulates. If both conditions are met,

then the Act provides that the FDA “may not approve another” such drug for marketing

to the public for “seven years from the date” of the designated drug’s approval. 21

U.S.C. § 360cc(a).

Congress also provided two exceptions to the statutorily-mandated exclusivity

period. Under the statute, the FDA may approve the marketing of subsequent drugs

without regard to an existing exclusivity period if:

4

Section 360cc also applies to “biological products” that are licensed pursuant to 42 U.S.C. § 262. No

such products are at issue in this case.

5

The implementing regulations for 21 U.S.C. § 360bb are codified in Subpart C of Part 316 of Title 21

of the Code of Federal Regulations. See 21 C.F.R. §§ 316.20–316.30 (entitled “Designation of an

Orphan Drug”). It is undisputed in the instant case that the FDA has designated Gralise as an orphan

drug within the meaning of Section 360bb and the applicable regulatory framework.

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(1) the [FDA] finds, after providing the [exclusivity] holder notice and

opportunity for the submission of views, that in such period the holder

of the approved application . . . cannot assure the availability of

sufficient quantities of the drug to meet the needs of persons with the

disease or condition for which the drug was designated; or

(2) such holder provides the [FDA] in writing the consent of such holder

for the approval of other applications . . . before the expiration of such

seven-year period.

See id. § 360cc(b).

2. Exclusivity Under The FDA’s Implementing Regulations

While Congress did not direct the FDA to promulgate implementing regulations

for the Act’s exclusivity provision, see 21 U.S.C. § 360cc, the FDA did so nonetheless.

The resulting regulations, which are entitled “Orphan-drug Exclusive Approval” and

codified in Subpart D of Part 316 of Title 21 of the Code of Federal Regulations

(“C.F.R.”), largely parallel the statutory design of section 360cc, with at least one

notable exception. The regulation entitled “Scope of orphan-drug exclusive approval”

provides that

[a]fter approval of a sponsor’s marketing application for a designated

orphan-drug product for treatment of the rare disease or condition

concerning which orphan-drug designation was granted, FDA will not

approve another sponsor’s marketing application for the same drug before

the expiration of 7 years from the date of such approval as stated in the

approval letter from FDA[.]

21 C.F.R. § 316.31(a) (2012) (emphasis added). Elsewhere, the regulations define the

term “same drug”—a term that the regulations use in place of the statutory term “such

drug” that appears in 21 U.S.C. § 360cc—to mean, in relevant part, “a drug that

contains the same active moiety as a previously approved drug and is intended for the

same use as the previously approved drug,” with the exception “that if the subsequent

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drug can be shown to be clinically superior to the first drug, it will not be considered to

be the same drug.” 21 C.F.R. § 316.3(b)(13)(i).

The insertion of the “same drug” concept into the exclusivity regulations

effectively limits the scope of exclusivity protection because under the regulations, only

if a new drug uses the same active ingredient (“active moiety”) to treat the same disease

or condition as a drug that already has orphan-drug exclusivity and the new drug is also

not found to be “clinically superior” to the existing orphan drug will the FDA consider

the new drug to be the “same” as the drug with exclusivity and thereby forbid its

marketing within the exclusivity period. Id.; id. § 316.31(a). Put another way, if the

new drug is “clinically superior” to the drug with orphan-drug exclusivity—i.e., the

new drug has a “significant therapeutic advantage over and above” an “approved orphan

drug[,]” 21 C.F.R. § 316.3(b)(3)—then the drugs are not considered to be the “same,”

and the FDA may approve the new drug notwithstanding the exclusivity period.

In short, the FDA’s regulations permit the FDA to ignore a previously-approved

drug’s orphan-drug exclusivity in order to approve a new, clinically superior drug with

the same active ingredient that will be marketed for treatment of the same disease or

condition. 6

3. Clinical Superiority Under The FDA’s Implementing Regulations

Under the Act’s implementing regulations, a finding of clinical superiority is

also relevant at the designation stage of the orphan-drug exclusivity process. As

explained above, in order to receive the seven-year period of orphan-drug exclusivity

6

The FDA has amended several of the relevant implementing regulations recently, presumably in

response to the filing of the complaint in the instant case. The new regulations went into effect on

August 12, 2013, and while the amended language does shed light on the parties’ arguments in this

case, the FDA concedes that the new regulations do not apply to Depomed’s claims. (See Notice of

Promulgation of Final Rule, ECF No. 30; see also infra n.12.)

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under the Act, the drug must first be “designated under section 360bb of this title for a

rare disease or condition.” 21 U.S.C. § 360cc(a). Congress authorized the FDA to

promulgate regulations governing the section 360bb designation process, which the

agency has done, see 21 C.F.R. §§ 316.20-316.30, and those regulations require, among

other things, an analysis of the potential clinical superiority of a drug that is being

considered for orphan-drug designation under certain specified circumstances.

For example, at all times relevant to the resolution of this case, section 316.20 of

Title 21 of the C.F.R., which governs the “[c]ontent and format of a request for orphan-

drug designation[,]” provided in relevant part that a sponsor may seek designation “of a

drug that is otherwise the same drug as an already approved orphan drug . . . for the

same rare disease or condition if [the sponsor] can present a plausible hypothesis that

its drug may be clinically superior to the first drug.” Id. § 316.20(a). Under that

iteration of this regulatory requirement, when a sponsor seeks orphan-drug designation

for the “same drug as an already-approved orphan drug . . . for the same rare disease or

condition,” the sponsor must include in its designation request “an explanation of why

the proposed variation may be clinically superior to the first drug.” Id. § 316.20(b)(5).

Indeed, the regulation specifically states that the “FDA will refuse to grant a request for

orphan-drug designation if” a sponsor seeking designation of a “same drug as one that

already has orphan-drug exclusive approval for the same rare disease or condition . . .

has not submitted a medically plausible hypothesis for the possible clinical superiority

of the subsequent drug.” Id. § 316.25(a)(3).

B. Factual And Procedural History

There are no material disputes regarding the facts of the instant case, which

begin with the FDA’s approval of Neurontin for treatment of seizures in 1993 and for

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treatment of PHN in 2002, and continue through the procedural history of the instant

case to the motions at issue in this Opinion.

1. The FDA’s Approval Of Neurontin

The FDA first approved a drug with the active ingredient gabapentin in 1993,

under the brand name Neurontin, for use in treating seizures. (Sealed Admin. R.

(“SAR”), ECF No. 18-1, at 19.) 7 Neurontin was subsequently approved for the

treatment of PHN on May 24, 2002. (Admin. R. (“AR”), ECF No. 17-6, at 27.)

Although PHN qualifies as a “rare disease or condition” under the Act, 21 U.S.C.

§ 360bb(a)(2), Pfizer, the manufacturer of Neurontin, never sought or obtained orphan-

drug designation for Neurontin for use in treating PHN and never received the benefit

of the Act’s exclusivity provision. (Defs.’ Mem. in Supp. of Mot. to Dismiss or Mot.

for Summ. J. & in Opp’n to Pl.’s Mot. for Summ. J. (“Defs.’ Br.”), ECF No. 21, at 19.)

Since 2002, nearly 30 gabapentin products—that is, generic versions of Neurontin—

have been approved and marketed for the treatment of PHN. (Id. (citation omitted).)

2. The FDA’s Designation Of Gralise

a. Depomed’s Initial Gralise Designation Request In 2006

On December 21, 2006, Depomed submitted a request to the FDA that the FDA

designate Depomed’s own gabapentin product, Gralise, as an orphan drug for the

treatment of PHN pursuant to 21 U.S.C. § 360bb and 21 C.F.R. § 316.20. (SAR, ECF

No. 18, at 4.) In its request, Depomed acknowledged that Neurontin (and other generic

gabapentin products) had previously been approved for the treatment of PHN, but

argued that no other gabapentin product had ever been designated as an orphan drug for

7

Citations to the administrative record and to other documents the parties have filed refer to the page

numbers assigned by the Court’s electronic filing system.

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treatment of PHN, and therefore Depomed did not need to provide a plausible

hypothesis of clinical superiority in order to satisfy the submission criteria for orphan-

drug designation applications under 21 C.F.R. § 316.20. (Id. at 19-21.) Depomed

additionally argued that, if the FDA nevertheless required a demonstration of clinical

superiority, Gralise satisfied that requirement based on studies showing that the

extended-release formulation of Gralise—which required patients to take the drug only

once per day, as opposed to Neurontin’s three times per day—would result in increased

patient compliance, and also that the extended-release formulation would lessen the side

effects patients taking Neurontin and its generics typically experienced. (Id. at 20-21.)

On May 8, 2007, the FDA denied Depomed’s designation request, on the grounds

that Neurontin had already received marketing approval and thus

there is no rationale for supporting, with taxpayer monies, the clinical

development of an identical product for an identical indication as one

which has been approved after the most thorough evaluation possible.

This point remains valid even when the rare disease product initially

approved to market was never designated as an Orphan product.

(AR, ECF No. 23-2, at 58.) The FDA further rejected Depomed’s contentions regarding

clinical superiority because “there is no data presented in th[e] current application to

bolster the contention” that Gralise would have the potential beneficial effects

Depomed had hypothesized. (Id.) The FDA gave Depomed 60 days to cure the

purported defects in its request for designation, but Depomed declined to do so.

b. Abbott Labs’s Renewed Designation Request For Gralise In

2010

On March 26, 2010, Abbott Labs (“Abbott”), a drug manufacturer that had

acquired the rights to Gralise, renewed Depomed’s previous request for orphan-drug

designation of Gralise for the treatment of PHN. (SAR, ECF No. 18, at 76.) In its

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request, Abbott argued that the FDA’s reasons for denying designation to Gralise the

first time around were incorrect under the Act and also under the FDA’s own

implementing regulations. (Id. at 79.) Abbott asserted that sections 316.23 and 316.25

of Title 21 of the C.F.R. “identify with specificity the circumstances under which a

request for orphan drug designation must, or may, be denied[,]” and that none of the

reasons identified therein applied to Gralise. (SAR, ECF No. 18, at 79-84.) In

particular, Abbott contended that section 316.25(a)(3)—which provided at that time that

an application for designation will be denied where the drug in question is “otherwise

the same drug as one that already has orphan-drug exclusive approval . . . and the

sponsor has not submitted a medically plausible hypothesis for the possible clinical

superiority of the subsequent drug”—was inapplicable to Gralise because there was no

other drug that “already has orphan-drug exclusive approval” for PHN. (SAR, ECF

No. 18, at 83.) In support of its position, Abbott pointed not only to the language of

section 316.25(a)(3), but also to the definition of “orphan drug exclusive approval” in

section 316.2(b)(12), which, in Abbott’s words, “means approval that carries with it the

seven-year orphan drug exclusivity that bars approval of the ‘same drug.’” (SAR, ECF

No. 18, at 83.) Abbott conceded that Neurontin “arguably is the ‘same drug’” as

Gralise, but maintained that even if it was, Neurontin had never received exclusivity

and accordingly could not be considered a drug that “already has orphan-drug exclusive

approval.” (Id.) For the same reasons, Abbott argued that it was not required to

provide a plausible hypothesis of clinical superiority in its renewed designation request

for Gralise. (Id. at 84.) 8

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Abbott also noted in its designation request that it did not believe designating Gralise as an orphan

drug would have any effect on the gabapentin products already on the market for treatment of PHN, nor

10

On June 17, 2010, the FDA sent Abbott a two-page letter rejecting its

designation request. (AR, ECF No. 23-2, at 61-62.) The FDA’s stated reason for the

denial was the “lack of evidence for clinical superiority.” (Id. at 61.) In responding to

Abbott’s arguments regarding section 316.25(a)(3), the FDA focused on the notion that

Gralise was the “same drug” as Neurontin, and therefore, in the FDA’s view, was

subject to the clinical superiority hypothesis. To back up its position, the FDA pointed

to the definition of “orphan drug” found in section 316.3(b)(10), arguing that under that

definition “there is no regulatory requirement that a drug obtain orphan drug

designation in order to be defined as an orphan drug[.]” (Id. at 61.) The FDA also

invoked the regulatory definition of “same drug” to maintain that Abbott “must show

clinical superiority in order for” the FDA to consider Gralise to be a different drug than

Neurontin. (Id. at 61-62.) Finally, the FDA pointed to the language of section

316.20(b)(5), which it claimed requires “an explanation of why” Gralise “may be

clinically superior to” Neurontin before Gralise could be designated as an orphan drug.

(Id. at 62)

c. Abbott Labs’s Amended Designation Request, Which

Included A Hypothesis Of Clinical Superiority

On September 1, 2010, Abbott submitted an amended designation request. (AR,

ECF No. 23-2, at 64-71.) In its amended request, Abbott reiterated its objections to the

FDA’s interpretation of the relevant regulations, but it also presented a clinical

superiority hypothesis based on the same potential effects that Depomed had cited in its

original request for designation (i.e., that because Gralise required only one dose per

day as opposed to Neurontin’s three, it might help patients adhere to their medication

would it have any effect on the approval of gabapentin products for treatment of conditions other than

PHN. (SAR, ECF No. 18, at 84.)

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regime, and would also lessen potential side effects). (Id. at 70-72.) Abbott supported

this hypothesis with data from two studies—one showing that, as a general matter,

patients were more compliant with once-daily medication regimes, and the second

indicating that extended release gabapentin (such as Gralise) may have a lower

incidence of side effects than Neurontin. (Id.)

On November 8, 2010, the FDA granted Abbott’s request and designated Gralise

as an orphan drug for the treatment of PHN, noting that “the comparison of the

incidence of [side effects] of [Gralise] to the reported incidence of [side effects] of

Neurontin . . . is adequate for supporting a plausible hypothesis that [Gralise] is

clinically superior[.]” (AR, ECF No. 23-2, at 116.) Significantly for present purposes,

the FDA also explicitly noted that “should [Abbott] obtain marketing approval for

[Gralise], [Abbott] will have to prove clinical superiority based on improved safety, to

the FDA, in order to obtain seven years of marketing exclusivity[.]” (Id. (emphasis

added).)

3. FDA Approval Of Gralise And Refusal Of Exclusivity

On January 28, 2011, the FDA granted Abbott marketing approval for Gralise

pursuant to 21 U.S.C. § 355(b)(2). 9 (AR, ECF No. 17-2, at 43.) The FDA maintained,

however, that despite securing designation and approval, Gralise was not entitled to the

seven-year period of orphan-drug exclusivity under the Act because Abbott had not

proven that Gralise was clinically superior to Neurontin. (AR, ECF No. 19-1, at 4.) In

a phone call with Abbott on February 9, 2011, the FDA explained, essentially, that it

had considered Gralise’s orphan-drug designation to be conditional because it was

9

Marketing approval pursuant to 21 U.S.C. § 355 comes with a statutory three-year exclusivity period

that is completely separate from the orphan-drug exclusivity period at issue in this case. See 21 U.S.C.

§ 355(c)(3)(E)(iii).

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based on a “hypothesis of clinical superiority over” Neurontin and that “[i]n order for

Abbott to receive exclusivity they would have to prove this hypothesis[,]” which, the

FDA asserted, Abbott had failed to do in its application for approval. (Id.)

4. Subsequent Proceedings

Depomed reacquired the rights to Gralise in March of 2011, and subsequently

pressed the FDA on the agency’s position regarding orphan-drug exclusivity for

Gralise. On September 9, 2011, Depomed sent a letter to the FDA requesting a meeting

and arguing (1) that the plain language of the exclusivity provision of the Act required

the FDA to recognize exclusivity for any designated orphan drug that had been granted

marketing approval; (2) that the FDA had erred in requiring proof of clinical superiority

for orphan-drug designation in the first place; and (3) that the FDA had sufficient

evidence of clinical superiority in any event. (AR, ECF No. 23-2, at 28-56.)

On September 25, 2012—more than one year after Depomed sent the letter to the

FDA, but before the FDA had provided any formal response—Depomed filed its

complaint in the instant lawsuit, alleging that the FDA’s refusal to recognize exclusivity

for Gralise violated the APA. (Complaint (“Compl.”), ECF No. 1.) The FDA finally

responded to Depomed’s September 9, 2011, letter on November 13, 2012. (AR, ECF

No. 17-2, at 1-26.) The FDA’s response largely reiterated its prior positions regarding

the regulations and also alluded to—but declined to detail because of “confidentiality

constraints”—a number of instances in which the FDA had required a hypothesis of

clinical superiority prior to granting designation. (Id. at 16 & n.38.)

Depomed filed its motion for summary judgment on January 1, 2013, essentially

reiterating the arguments from its September 9, 2011 letter. (Pl.’s Mot. for Summ. J.,

ECF No. 20.) The FDA cross-moved for dismissal or, in the alternative, for summary

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judgment on February 8, 2013. (Defs.’ Mot. to Dismiss or Mot. for Summ. J., ECF

No. 22.) This Court held a motions hearing on the parties’ cross motions, and

subsequently took the motions under advisement. (See Minute Entry of August 23,

2013.)

II. LEGAL STANDARDS

A. Standard For Dismissal Or Summary Judgment in Administrative

Review Cases

“[W]hen a district court is reviewing agency action . . . the legal questions

raised by a 12(b)(6) motion and a motion for summary judgment are the same.”

Marshall Cnty. Health Care Auth. v. Shalala, 988 F.2d 1221, 1222-1223 (D.C. Cir.

1993); see also Nat’l Auto Dealers Ass’n v. FTC, 864 F. Supp. 2d 65, 72 (D.D.C. 2012)

(noting that motions to dismiss and motions for summary judgment “are normally

judged under different legal standards,” but “the inquiry in [APA] case[s] is the same”

(citation omitted)). In most civil cases, summary judgment will be granted only “if the

movant shows that there is no genuine dispute as to any material fact and the movant is

entitled to judgment as a matter of law.” Fed. R. Civ. P. 56(a); Anderson v. Liberty

Lobby, Inc., 477 U.S. 242, 247 (1986); Moore v. Hartman, 571 F.3d 62, 66 (D.C. Cir.

2009). “Summary judgment is [also] the proper mechanism for deciding, as a matter of

law, whether an agency action is supported by the administrative record and consistent

with the APA standard of review.” Loma Linda Univ. Med. Ctr. v. Sebelius, 684 F.

Supp. 2d 42, 52 (D.D.C. 2010) (citing Stuttering Found. of Am. v. Springer, 498 F.

Supp. 2d 203, 207 (D.D.C. 2007)); see also Richards v. INS, 554 F.2d 1173, 1177 n.28

(D.C. Cir. 1977). However, due to the limited role a court plays in reviewing the

administrative record to evaluate whether an agency has complied with the APA, the

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typical summary judgment standards are not applicable. Stuttering, 498 F. Supp. 2d at

207. “Under the APA, it is the role of the agency to resolve factual issues to arrive at a

decision that is supported by the administrative record,” while “the function of the

district court is to determine whether or not as a matter of law the evidence in the

administrative record permitted the agency to make the decision it did.” Id. (quoting

Occidental Eng’g Co. v. INS, 753 F.2d 766, 769-770 (9th Cir. 1985)). In other words,

“when a party seeks review of agency action under the APA, the district judge sits as an

appellate tribunal,” and “[t]he ‘entire case’ on review is a question of law.” Am.

Bioscience, Inc. v. Thompson, 269 F.3d 1077, 1083 (D.C. Cir. 2001) (footnote and

citations omitted).

Notably, the APA provides a “default standard” of judicial review of agency

actions on summary judgment when the governing statute does not otherwise provide

one: “[a] court must set aside agency action it finds to be ‘arbitrary, capricious, an

abuse of discretion, or otherwise not in accordance with law.’” Tourus Records, Inc. v.

DEA, 259 F.3d 731, 736 (D.C. Cir. 2001) (quoting 5 U.S.C. § 706(2)(A)). “The

‘arbitrary and capricious’ standard of review as set forth in the APA is highly

deferential,” and the Court must therefore “presume the validity of agency action.” Am.

Horse Prot. Ass’n v. Yeutter, 917 F.2d 594, 596 (D.C. Cir. 1990) (citation omitted).

Although the “court is not to substitute its judgment for that of the agency[,] . . . the

agency nevertheless must examine the relevant data and articulate a satisfactory

explanation for its action[,] including a rational connection between the facts found and

the choice made.” Motor Vehicle Mfrs. Ass’n v. State Farm Mut. Auto. Ins. Co., 463

U.S. 29, 43 (1983) (citations and quotation marks omitted).

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B. Chevron Framework

When assessing the validity of an agency’s interpretation of a statute, the Court

must apply the two-step framework under Chevron, USA., Inc. v. NRDC, 467 U.S. 837

(1984), to determine whether the agency has acted outside its authority. See Ass’n of

Private Sector Colls. & Univs. v. Duncan, 681 F.3d 427, 441 (D.C. Cir. 2012).

The Chevron analysis first requires the reviewing court to determine “whether

Congress has directly spoken to the precise question at issue.” Chevron, 467 U.S. at

842. To resolve whether “the intent of Congress is clear” under this first step of

Chevron, the court must exhaust the “traditional tools of statutory construction,”

including textual analysis, structural analysis, and (when appropriate) legislative

history. Id. at 843 n.9; see also Bell Atl. Tel. Cos. v. FCC, 131 F.3d 1044, 1047 (D.C.

Cir. 1997). “If the intent of Congress is clear, that is the end of the matter; for the

court, as well as the agency, must give effect to the unambiguously expressed intent of

Congress.” Chevron, 467 U.S. at 842-843.

However, if the Court concludes that the statute is silent or ambiguous on the

specific issue after employing these tools, the Court moves on to step two and defers to

any agency interpretation that is based on a permissible construction of the statute. Id.

at 843. An agency’s construction is permissible “unless it is arbitrary or capricious in

substance, or manifestly contrary to the statute.” Mayo Found. For Med. Educ. &

Research v. United States, 131 S. Ct. 704, 711 (2011) (citations and internal quotation

marks omitted). In sum, “the whole point of Chevron is to leave the discretion provided

by the ambiguities of a statute with the implementing agency.” Ass’n of Private Sector

Colls., 681 F.3d at 441 (citations and internal quotation marks omitted).

16

III. ANALYSIS

In its motion for summary judgment, Depomed contends that the FDA’s refusal

to recognize that Gralise is entitled to orphan-drug exclusivity violates the

unambiguous language of the Orphan Drug Act and thus that Depomed is entitled to

judgment as a matter of law under Chevron’s step one. (Pl.’s Combined Mot. for

Summ. J. & Mem. in Support (“Pl.’s Br.”), ECF No. 20, at 24-34.) If the Court should

find it necessary to proceed to step two of the Chevron analysis, Depomed argues that

the FDA’s construction of the Act as permitting the agency to insist on a showing of

clinical superiority as a condition of granting exclusivity is unreasonable and therefore

impermissible. (Id. 34-37.) Depomed also maintains that the FDA’s decision to deny

Gralise orphan-drug exclusivity unless and until Depomed proved that the drug was

clinically superior to Neurontin was arbitrary and capricious in light of the agency’s

own regulations regarding the exclusivity issue. (Id. 38-45.)

In its own defense and in support of the agency’s belief that Depomed’s

complaint must be dismissed, the FDA asserts that this Court must proceed to

Chevron’s step two because nothing in the statute speaks to the precise question at issue

here—which, in the agency’s view, is whether exclusivity must be recognized when a

drug is designated as an orphan drug and approved for marketing but is the same drug

as one that has already been approved for the same disease or condition. (See Defs.’

Br. at 37 (“Congress did not address the possibility that there may already be an

approved same drug (with or without exclusivity) even before the newly approved drug

at issue.”).) The FDA maintains that, as a result of Congress’s alleged silence on this

issue, the Act is ambiguous, and thus the Court is required to defer to the agency’s

decision to deny exclusivity under these circumstances unless the new, approved orphan

17

drug can meet certain regulatory requirements (i.e., the establishment of clinical

superiority). (Id.) Furthermore, Defendants contend that accepting Depomed’s

interpretation of the statute could lead to outcomes that would be absurd insofar as they

would clearly contravene the purpose of the Act.

As explained further below, this Court concludes that the plain language of the

Orphan Drug Act requires the FDA to recognize exclusivity for Gralise. Consequently,

the Court finds no need to proceed beyond Chevron’s step one, meaning that the Court’s

analysis need not, and does not, address Depomed’s argument that the FDA’s

interpretation of the Act to permit regulations that require clinical superiority was

unreasonable. The Court also finds it unnecessary to consider Depomed’s alternative

argument that the agency’s decision to deny Gralise exclusivity was arbitrary and

capricious within the meaning of the APA because that determination violated the

agency’s own exclusivity regulations. 10

A. The Orphan Drug Act Unambiguously Requires Marketing

Exclusivity When The FDA Has Designated An Orphan Drug And Has

Approved That Drug For Marketing

An examination of any statute for indicia of ambiguity under Chevron must

begin (and may end) with an analysis of the statutory text. See, e.g., Chevron, 467 U.S.

at 842-843; Bell Atl. Tel. Cos., 131 F.3d at 1047. Section 360cc of Title 21 of the U.S.

Code is entitled “Protection for drugs for rare diseases and conditions” and includes

two subsections. Subsection (a), which is labeled “Exclusive approval, certification, or

10

This Court also declines to address Depomed’s related argument decrying the alleged arbitrariness of

the FDA’s initial requirement that Gralise present a plausible hypothesis of clinical superiority before it

was designated as an orphan drug. (Pl.’s Br. at 38-45.) The question of whether the FDA violated its

own designation regulations when it inserted a clinical superiority requirement into the designation

process for Gralise need not be answered here because it is undisputed that Gralise was (belatedly)

designated as an “orphan drug” and was subsequently approved for marketing. Therefore, the only

pertinent legal question at issue on the instant facts is whether the FDA was authorized to refuse to

recognize Gralise’s marketing exclusivity under the Orphan Drug Act and its implementing regulations.

18

license[,]” establishes the statutory circumstances under which exclusivity attaches,

while subsection (b), labeled “Exceptions” sets forth the two specific instances in which

marketing exclusivity may nevertheless be denied. In its entirety, section 360cc reads

as follows:

(a) Exclusive approval, certification, or license

Except as provided in subsection (b) of this section, if the Secretary—

(1) approves an application filed pursuant to section 355 of this

title, or

(2) issues a license under section 262 of title 42

for a drug designated under section 360bb of this title for a rare disease or

condition, the Secretary may not approve another application under

section 355 of this title or issue another license under section 262 of title

42 for such drug for such disease or condition for a person who is not the

holder of such approved application or of such license until the expiration

of seven years from the date of the approval of the approved application

or the issuance of the license. Section 355 (c)(2) of this title does not

apply to the refusal to approve an application under the preceding

sentence.

(b) Exceptions

If an application filed pursuant to section 355 of this title is approved

for a drug designated under section 360bb of this title for a rare disease or

condition or if a license is issued under section 262 of title 42 for such a

drug, the Secretary may, during the seven-year period beginning on the

date of the application approval or of the issuance of the license, approve

another application under section 355 of this title or issue a license under

section 262 of title 42, for such drug for such disease or condition for a

person who is not the holder of such approved application or of such

license if—

(1) the Secretary finds, after providing the holder notice and

opportunity for the submission of views, that in such period the

holder of the approved application or of the license cannot assure

the availability of sufficient quantities of the drug to meet the

19

needs of persons with the disease or condition for which the drug

was designated; or

(2) such holder provides the Secretary in writing the consent of

such holder for the approval of other applications or the issuance of

other licenses before the expiration of such seven-year period.

21 U.S.C § 360cc.

Examined closely, the text of the Act’s exclusivity provision (§ 360cc(a))

employs the familiar and readily diagrammable formula, “if x and y, then z.” Congress

has crafted its command to the Secretary of the FDA in a manner that sets forth two

circumstances—a drug that has been designated for a rare disease or condition, and the

FDA’s approval of a marketing application for that drug—that, if present, result in a

particular consequence: a seven-year period of abstinence regarding marketing

approval for other such drugs. When considered against the background fact that

Congress has ordinarily authorized the FDA to approve an application for the marketing

of any new drug, see id. § 355 et seq., section 360cc(a)’s language can only be

interpreted as a limitation on the agency’s authority in that regard. In other words,

although it is convenient to characterize orphan-drug marketing exclusivity as

something in the nature of a benefit that the FDA confers or withholds, (see, e.g., Defs.’

Br. at 10 (“The Orphan Drug Act confers a seven-year exclusivity period to certain

drugs[.]”); Pl.’s Br. at 4 (discussing FDA’s “decision to withhold exclusivity”)), the

text of section 360cc makes clear that the incentive Congress intended to create in the

orphan drug context is not a thing to be “conveyed” to drug manufacturers at all; rather,

it is a restriction of the FDA’s ability to approve the marketing of other such drugs for

the same rare disease or condition (referred to herein as “new such drugs”) when a drug

that has been designated as an orphan drug is approved for marketing.

20

Contrary to Defendants’ Chevron step-one argument, there is nothing ambiguous

about Congress’s statutory statement that if the FDA designates a drug as an orphan

drug and approves that drug for marketing, the agency cannot approve another

application for the marketing of a new such drug for a period of seven years. As luck

would have it for the FDA, the agency has the ability and the opportunity to control the

circumstances under which marketing exclusivity attaches because the FDA is

responsible for determining when to designate a drug as an orphan drug under section

360bb, and it is also the agency that has the duty of deciding when and under what

circumstances a drug will be approved for marketing. But the language of the Act’s

exclusivity provision does not permit or invite any discretion on the part of the FDA

regarding whether or not to continue authorizing new such drug marketing applications

once an orphan drug has been so designated and approved. Indeed, Congress has

specifically established the only two situations in which the FDA can carry on

regardless. See 21 U.S.C. § 360cc(b) (permitting approval of new such drug

applications if the agency “finds” within the seven-year exclusivity period that the

manufacturer of a drug with marketing exclusivity “cannot assure the availability of

sufficient quantities of the drug to meet the needs of persons with the disease or

condition for which the drug was designated” or if the manufacturer of the drug with

marketing exclusivity provides its written consent to the approval of marketing

applications for new such drugs within the exclusivity period).

As applicable here, it is undisputed that Gralise satisfies the exclusivity

provision’s unambiguously-worded circumstances (i.e., designation and approval).

Nevertheless, Defendants have offered several arguments to support their contention

21

that the Act’s exclusivity provision is ambiguous under the circumstances presented and

thus permits the FDA to impose additional criteria for exclusivity even after a drug has

been designated an orphan drug and approved for marketing. First, Defendants point to

the fact that Chevron requires the Court to determine “whether Congress has directly

spoken to the precise question at issue[,]” 467 U.S. at 842, and they argue that the

question at issue here is not what circumstances must exist for orphan-drug marketing

exclusivity to attach but “which drugs are eligible for exclusivity in the first instance.”

(Defs.’ Br. at 37.) Specifically, Defendants maintain that, where a drug for the same

disease or condition has already been approved for marketing (e.g., Neurontin), the

statute fails to speak to whether a subsequent drug that has the same active ingredient

and is for the same rare disease or condition should be entitled to marketing exclusivity,

and it is this alleged “gap” in the statute that the FDA is entitled to fill with its clinical

superiority criteria. (See Defs.’ Br. at 37 (“Congress did not address the possibility that

there may already be an approved same drug[.]”).)

This Court is not persuaded. As an initial matter, “‘the fact that a statute can be

applied in situations not expressly anticipated by Congress does not demonstrate

ambiguity. It demonstrates breadth.’” PGA Tour, Inc. v. Martin, 532 U.S. 661, 689

(2001) (quoting Penn. Dep’t of Corr. v. Yeskey, 524 U.S. 206, 212 (1998)). Moreover,

as the D.C. Circuit has noted repeatedly, the fact that Congress has “not mentioned” a

particular agency concern in a governing statute does not mean that “Congress is ‘silent

or ambiguous’ as to that issue[]” and thus the agency can do what it wishes. Ethyl

Corp. v. EPA, 51 F.3d 1053, 1060 (D.C. Cir. 1995); see also Grocery Mfrs. Ass’n v.

EPA, 693 F.3d 169, 191 (D.C. Cir. 2012) (the proposition that “Chevron step two is

22

implicated any time a statute does not expressly negate the existence of a claimed

administrative power (i.e., when the statute is not written in ‘thou shalt not’ terms), is

both flatly unfaithful to the principles of administrative law, and refuted by precedent”

(citing API v. EPA, 52 F.3d 1113, 1120 (D.C. Cir. 1995))). Rather, “‘it is only

legislative intent to delegate such authority that entitles an agency to advance its own

statutory construction for review under the deferential second prong of Chevron.’”

NRDC v. Reilly, 983 F.2d 259, 266 (D.C. Cir. 1993) (emphasis added) (quoting Kansas

City v. Dep’t of Hous. & Urban Dev., 923 F.2d 188, 191-192 (D.C. Cir. 1991)). Indeed,

“[w]ere courts to presume a delegation of power absent an express withholding of such

power, agencies would enjoy virtually limitless hegemony, a result plainly out of

keeping with Chevron and quite likely with the Constitution as well.” Ethyl Corp., 51

F.3d at 1060 (emphasis omitted).

In Chevron, the Supreme Court explained that Congress’s “intent to delegate”

rulemaking authority to the agency is manifest when the statute leaves the agency room

“to fill any gap left, implicitly or explicitly, by Congress.” 467 U.S. at 843. The D.C.

Circuit has further clarified that “Congress leaves gaps in [a] program, either explicitly

by authorizing the agency to adopt implementing regulations, or implicitly by enacting

an ambiguously worded provision that the agency must interpret[.]” Nat’l Fuel Gas

Supply Corp. v. FERC, 811 F.2d 1563, 1569 (D.C. Cir. 1987). Accordingly, in order to

proceed to Chevron step two, an agency must affirmatively identify either an explicit or

implicit gap in the statutory scheme that is indicative of congressional intent to provide

that agency with the power to interpret the statute.

23

Here, Defendants rely on an alleged implicit grant of authority; specifically, the

word “drug” as used in the Act’s exclusivity provision, which, Defendants’ argue, has

been found to be ambiguous in one of the few cases to consider directly the provisions

of the Orphan Drug Act. (See Defs.’ Br. at 39 (citing Baker Norton Pharms. v. FDA,

132 F. Supp. 2d 30 (D.D.C. 2001) (holding that the FDA’s promulgation of a regulation

that defines “same drug” for the purpose of exclusivity was permissible because the

term such “drug” as used in the Act was ambiguous).) Defendants are correct that the

court in Baker Norton found “the word ‘drug’ in 21 U.S.C. § 360cc(a)” to be

ambiguous; however, Defendants are wrong to suggest that the holding in that case has

any bearing on the Chevron step-one analysis here. Properly understood, the term

“such drug” in the exclusivity provision operates only to define the scope of the limit

on the FDA’s approval authority once a “designated drug” has been “approved” as

required for exclusivity to attach. The court in Baker Norton was concerned only with

the permissibility of the FDA’s interpretation of what counted as “such drug” (and thus

must not be approved within the seven-year preclusion period) under the FDA’s

regulatory framework. See Baker Norton, 132 F. Supp. 2d. at 34-38. But that question

necessarily presumes the existence of a drug that has previously been designated and

approved. See 21 U.S.C. § 360cc(a). Here, there has been no previously designated

gabapentin product for treatment of PHN, so whether Gralise qualifies as a new “such

drug” that is not entitled to marketing approval under the terms of the exclusivity

period is not at issue. Thus, Defendants cannot rely on the “such drug” ambiguity

identified in Baker Norton to justify the FDA’s requirement of a showing of clinical

superiority in the circumstances here.

24

Defendants’ general suggestion that the statute is not clear with respect to

Congress’s intentions regarding exclusivity when there is a prior, non-designated drug

that treats the same rare disease or condition, or that Congress otherwise meant to

delegate the exclusivity determination to the agency under those circumstances, is

similarly baseless. Try as they might, Defendants cannot square their insistence that the

FDA has the discretion to address this situation with the fact that, under the statute,

Congress did not give the FDA any discretionary authority to grant or deny exclusivity

at all—rather, as mentioned previously, Congress forbade the FDA from granting any

further approvals when the statutory conditions were met. 21 U.S.C. § 360cc(a) (the

FDA “may not approve another application” for seven years after a designated drug is

granted approval). This structure suggests that the intent of Congress was to provide

the FDA with a merely ministerial role in the exclusivity process, and certainly not to

give it the authority to interpose additional requirements with respect to a drug that has

received designation and approval. Indeed, based on the fact that the Act’s exclusivity

provision operates by removing FDA discretion to approve the marketing of certain

other drugs, it is at least arguable that the Orphan Drug Act is exactly the kind of “thou

shalt not” statute that the D.C. Circuit has found “expressly negate[s] the existence of a

claimed administrative power” to interpret the circumstances in which the provision

applies. Ry. Labor Execs.’ Ass’n v. Nat’l Mediation Bd., 29 F.3d 655, 671, amended by

38 F.3d 1224 (D.C. Cir. 1994).

Moreover, as noted, Congress not only unambiguously described the conditions

necessary for exclusivity to attach, it also specifically enumerated the circumstances in

which exclusivity would not result despite the fact that a drug had been designated and

25

approved. 21 U.S.C. § 360cc(b). The express statutory exceptions are significant

because it is well-established that “[w]here Congress explicitly enumerates certain

exceptions to a general prohibition, additional exceptions are not to be implied, in the

absence of evidence of a contrary legislative intent.” Andrus v. Glover Const. Co., 446

U.S. 608, 616-617 (1980). Here, the statute generally prohibits the FDA from

approving orphan drugs for the same indication as one that has previously been

approved and designated, and also provides two specifically enumerated exceptions,

neither of which includes the fact that a prior (non-designated) drug for the same

disease or condition and with the same active ingredients might already be on the

market. This Court will not impute to Congress an intention to authorize an exception

that Congress itself did not think worth enacting. See, e.g., NRDC v. EPA, 489 F.3d

1250, 1259-1260 (D.C. Cir. 2007) (holding that where Congress provides certain

enumerated exceptions in a statute, an agency “may not, consistent with Chevron, create

an additional exception on its own”).

Thus, the Court concludes that the plain language of the exclusivity provision

means precisely what it says, to wit, when a drug, like Gralise, has obtained both

orphan-drug designation and marketing approval, the FDA is precluded from approving

any other such drug for seven years from the date of approval.

B. Giving Effect To The Plain Language Of The Act Will Not Lead To

An Absurd Result

Trying a different tack, Defendants offer two additional policy-oriented

arguments regarding why this Court should not resolve this case in Depomed’s favor at

Chevron step one. (See Hr’g Tr., ECF No. 31, at 19:18-21 (“Your Honor, Depomed is

accusing [the] FDA of mounting what they call a policy . . . defense . . . and in some

26

sense that’s true because fundamentally this case really is about a policy choice[.]”).)

Generally speaking, Defendants maintain, first, that affirming exclusivity for Gralise

could allow Depomed to cut off any new gabapentin entrants into the marketplace,

which has been wide open for over a decade, without providing any benefit in the

treatment of PHN; and second, that similarly-situated drug manufacturers could

conceivably obtain successive periods of exclusivity for the same drug, provided that

they obtained seriatim designations and approvals. (See Defs.’ Br. at 47, 38.)

Defendants contend that the FDA’s requirement that Gralise prove its clinical

superiority to Neurontin is reasonable precisely because it avoids such absurd results.

As a threshold matter, with respect to the propriety of addressing policy

arguments in the context of a step-one Chevron analysis, this Court acknowledges that

such arguments may be relevant to the first Chevron inquiry based on “the long-

standing rule that a statute should not be construed to produce an absurd result.” Mova

Pharm. Corp. v. Shalala, 140 F.3d 1060, 1068 (D.C. Cir. 1998). It is clear beyond cavil

that in any exercise of statutory interpretation, whether under Chevron or otherwise,

“[t]he plain meaning of legislation should be conclusive, except in the rare cases [in

which] the literal application of a statute will produce a result demonstrably at odds

with the intentions of its drafters.” United States v. Ron Pair Enters., Inc., 489 U.S.

235, 242 (1989) (emphasis added) (internal quotation marks and citation omitted).

Thus, in the Chevron step-one context, “the rule that statutes are to be read to avoid

absurd results allows an agency to establish that seemingly clear statutory language

does not reflect the unambiguously expressed intent of Congress.” Mova, 140 F.3d at

1068 (internal quotation marks and citations omitted).

27

Here, Defendants struggle valiantly to establish that the instant matter is one of

those rare instances in which interpreting the Act literally would so defeat its purpose

that Congress could not have meant the statute to be read in accordance with its plain

language. As noted, Defendants’ first policy-related argument is essentially that,

because the purpose of the legislative scheme is to incentivize new and better drugs for

the treatment of rare diseases, granting exclusivity to a drug like Gralise under the

circumstances of this case—that is, where numerous functionally identical drugs for

treatment of the same orphan indication are already on the market—is patently

unnecessary and would also have the unfortunate result of essentially truncating the

development of improved pharmaceuticals rather than encouraging them, as the

legislature clearly intended. (See Defs.’ Br. at 42 (“[R]eading the statute to require

exclusivity . . . would undermine the very raison d’etre of the legislative scheme” by

allowing “sponsors who have not shown their drugs to be any better than a previously

approved drug” to get the benefits of exclusivity); Defs.’ Reply in Supp. of Mot. to

Dismiss or Mot. for Summ. J., ECF No. 27, at 26 (noting that, if Gralise receives

exclusivity, “other products could no longer be approved by FDA to treat the orphan

indication, post-herpetic neuralgia”).) 11

This policy argument misses the mark by a mile. To the extent that Defendants’

contention is that Congress never would have intended for a “me too” drug like Gralise

to get a benefit that the legislature devised to entice new entrants into the rare-disease

11

In essence, Defendants’ current position with regard to this scenario is no different than what the

FDA stated in its original rejection of designation for Gralise in 2006: “[T]here is no rationale for

supporting, with taxpayer monies, the clinical development of an identical product for an identical

indication as one which has been approved after the most thorough evaluation possible.” (AR, ECF

No. 23-2, at 58.)

28

treatment market, Defendants’ point is unfounded—nothing in the statute even remotely

suggests that Congress intended to incentivize only one sponsor to produce a particular

drug (although Congress certainly could have specified as much), and general market

forces provide a plausible reason for a legislative scheme that deliberately incentivizes

multiple manufacturers of the same pharmaceutical product. Nor can it be said that

permitting Depomed to grasp the brass ring of exclusivity for Gralise is unfair to the

manufacturers of the prior iterations of the drug, since each had every opportunity to

seek exclusivity and failed to do so. If, on the other hand, Defendants are pointing to

Gralise and are making the conceptually different argument that it would be “absurd”

for the same drug as others already on the market to be permitted to cut off the

development of new and improved versions, that result appears to be a function of

granting a drug marketing exclusivity in any event—i.e., the statute plainly incentivizes

investment in drugs for rare diseases and conditions precisely because it prevents new

(and potentially better) drugs from being adopted and marketed for that same

condition—and thus is inherent in the exclusivity statute. Defendants may find it

“absurd” that the legislature wished to encourage the production and marketing of

certain drugs for rare diseases by prohibiting the marketing of others, but that is the

incentive structure that Congress clearly intended and adopted.

The second potentially absurd result that Defendants identify is a variation on

this same theme—and fails for the opposite reason. Defendants assert that, if the

exclusivity statute is read in the manner that Depomed suggests, it could lead to orphan

drug sponsors obtaining serial exclusivity or evergreen status for their drugs. (See, e.g.,

Defs.’ Br. at 38.) As far as this Court can tell, Defendants are worried that interpreting

29

the statute to mandate exclusivity whenever a drug has obtained designation and

approval could lead to a situation in which sponsors that have exclusivity for a

particular drug could simply tweak their formulation for that drug and resubmit

applications for designation and approval after the initial exclusivity period has

expired, thereby gaining successive exclusivity periods—a result that, according to

Defendants, would contravene the most basic purpose of the statute. (See id.; see also

AR, ECF No. 17-2, at 10.) However, under the statutory scheme as it currently exists,

this result would only occur if the FDA permitted it to happen. While the prior policy

concern (i.e., that new and better drugs will be prevented from coming to market) would

happen under the statute merely by virtue of the exclusivity requirement, the “serial

exclusivity” problem would not arise at all if the FDA fashioned regulations to prevent

such abuse in the context of the designation phase of the exclusivity process. See 21

U.S.C. § 360bb(d) (directing that the FDA “shall by regulation promulgate procedures

for the implementation of” the designation requirement). For example, the FDA could

require designation applicants to show clinical superiority before granting their product

orphan-drug designation, a change in the regulations that would allow the FDA to

maintain the benefits of its clinical superiority requirement and also forestall the

hypothetical “serial exclusivity” problem while at the same time avoiding any conflict

with the plain language of the statute’s exclusivity provision. And, indeed, the FDA

has already shown that it is willing to alter its designation regulations in response to

unforeseen factual circumstances. 12 The Court sees no reason why a change to the

12

As noted supra, n.6, after the complaint in this case was filed, the FDA amended the language of its

regulations to comport more easily with the FDA’s litigation position in this case. See 78 Fed. Reg.

35,117 (Jun. 12, 2013). Specifically, the FDA changed 21 C.F.R. § 316.25 to provide that a clinical

superiority hypothesis is required for designation where “the drug is the same drug as an already

30

designation regulations, if implemented properly, could not remedy the supposedly

“absurd” results that Defendants say may result from the plain language of the

exclusivity provision, which casts doubt on Defendants’ argument that the statute was

not intended to be read in accordance with its plain meaning.

Finally, it is worth noting that, on the record before this Court, Defendants’

policy concerns appear to be somewhat overblown. First of all, because the Orphan

Drug Act simply directs the FDA to refrain from approving any other new such drug for

a seven-year period, it is clear that the fate of Gralise will have no effect on the

marketability of Neurontin or the many generics that were already on the market at the

time Gralise was designated and approved. 13 Moreover, the record reflects that the

particular circumstances of this litigation—that is, where the FDA has declined to

recognize exclusivity for a drug that has been both designated and approved on the

grounds that a prior un-designated same drug is already on the market—appear to be sui

generis. Although the FDA has purported to identify fourteen prior instances that it

claims provide precedent for its decision regarding Gralise (see Defs.’ Br. at 51-53),

none of the cited examples are in fact on all fours with the instant case. In five of those

examples, the FDA denied designation to an applicant on the grounds that it had failed

to provide an adequate hypothesis of clinical superiority, (see AR, ECF No. 17-8, at 41-

44), and in the other nine examples, the FDA denied marketing approval for a drug

approved drug,” where before that regulation read “a drug that is otherwise the same drug as one that

already has orphan-drug exclusive approval.” The FDA also changed 21 C.F.R. § 316.24 by removing

the language indicating that the FDA “will grant” a request for orphan-drug designation absent one of

the problems identified in section 316.25. The new section 316.24 also explicitly ties designation to

receipt of the materials that 21 C.F.R. § 316.20 requires. Finally, the rulemaking changes the term

“already approved orphan drug” to “already approved drug” in section 316.20(b)(5).

13

At the motions hearing in this case, counsel for Depomed acknowledged as much. (See Hr’g Tr. at

8:23-25 (Depomed’s Counsel acknowledging that exclusivity for Gralise “would have no effect on any

of” the gabapentin products already on the market).)

31

where another drug already had exclusivity and the applicant sponsor had not proven

clinical superiority, (see id. at 44-46). In fact, in the only example reflected in the

record that is substantially similar to the instant case, the FDA recognized exclusivity

for a drug, Kogenate, even though another drug with the same active ingredient had

previously been approved for marketing for the same rare disease or condition but had

never been designated an orphan drug (just like Neurontin). (See Pl.’s Br. at 41-44; see

also AR, ECF No. 17-8, at 51.) 14 It appears, then, that the purportedly “absurd” result

that Defendants fear may arise out of the facts of this case rarely, if ever, actually

occurs.

Lastly, it is clear on this record that the circumstances of this case do not raise

the specter of the “serial exclusivity” scenario. No gabapentin product has ever enjoyed

exclusivity for the treatment of PHN, and thus there is nothing “serial” about the relief

Depomed seeks. What is more, the serial exclusivity issue is not unique to the Orphan

Drug Act. In Mova Pharmaceutical Corp. v. Shalala, the D.C. Circuit recognized that a

similar problem could potentially arise in the context of the exclusivity period provided

for generic drugs under 21 U.S.C. § 355(j)(5)(B)(iv), yet that court still rejected an

FDA rationale that would have addressed this potential issue. See 140 F.3d at 1065 n.4

(“[T]he statute might conceivably be read to confer this 180-day [exclusivity] period on

a second or third applicant in some situations.”). This Court, too, is not moved to alter

its reading of the plain language of the Orphan Drug Act based on the potential that,

14

The FDA has attempted to distance itself from its decision regarding Kogenate by characterizing the

decision as an “outlier decision” that is “inconsistent” with the FDA’s other precedents. (See Defs.’

Br. at 51; AR, ECF No. 17-8 at 51.) But Defendants fail to provide any support for this assertion,

particularly because, as explained above, the ordinary course examples it cites are not, in fact, on all

fours with the instant case.

32

under other unspecified circumstances that the agency might easily remedy, the

exclusivity provision could be subject to abuse.

IV. CONCLUSION

The plain language of the exclusivity provision of the Orphan Drug Act requires

the FDA to recognize exclusivity for any drug that the FDA has designated and granted

marketing approval, and there is no dispute that Gralise has satisfied both of those

criteria. Consequently, the Court concludes that Gralise is entitled to exclusivity and

that the FDA must recognize as much without requiring proof of clinical superiority or

imposing any additional conditions on Depomed. As set forth in the separate order

accompanying this opinion, summary judgment will be entered in favor of Depomed.

DATE: September 5, 2014 Ketanji Brown Jackson

KETANJI BROWN JACKSON

United States District Judge

33