USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 1 of 27
[PUBLISH]
IN THE UNITED STATES COURT OF APPEALS
FOR THE ELEVENTH CIRCUIT ________________________
No. 20-13922 ________________________
D.C. Docket No. 1:19-cv-22425-BB
CATALYST PHARMACEUTICALS, INC.,
Plaintiff - Appellant,
versus
XAVIER BECERRA, Secretary of Health and Human Services, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, JANET WOODCOCK, Acting Commissioner of the Food and Drug Administration, U.S. FOOD AND DRUG ADMINISTRATION,
Defendants – Appellees,
JACOBUS PHARMACEUTICAL COMPANY, INC.,
Intervenor-Defendant – Appellee.
________________________
Appeal from the United States District Court for the Southern District of Florida ________________________
(September 30, 2021) USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 2 of 27
Before LAGOA, ANDERSON, and MARCUS, Circuit Judges.
LAGOA, Circuit Judge:
This appeal asks us to determine whether the statutory phrase “same disease
or condition” contained in the Orphan Drug Act, see 21 U.S.C. § 360cc, is
ambiguous. It is not. By finding this statutory phrase ambiguous and then deferring
to the U.S. Food and Drug Administration’s interpretation of it, the district court
erred. We therefore reverse the district court’s grant of summary judgment in favor
of the Defendants 1 and Jacobus, and remand with instructions to grant summary
judgment in favor of Catalyst.
I. FACTUAL AND PROCEDURAL HISTORY
A. The Orphan Drug Act
In 1983, Congress enacted the Orphan Drug Act, thereby amending the
Federal Food, Drug, and Cosmetic Act (“FDCA”). See Pub. L. 97-414, 96 Stat. 2049
(codified as amended at 21 U.S.C. §§ 360aa–360ee). The Orphan Drug Act
1 Catalyst named Alex Azar, Secretary of Health and Human Services; Norman Sharpless, Acting Commissioner of the FDA; the U.S. Department of Health and Human Services; and the U.S. Food and Drug Administration as the Defendants in its Complaint. During the pendency of this case, the administration changed, and Secretary Azar and Acting Commissioner Sharpless resigned their positions. We therefore have substituted as defendants-appellees the proper individuals in their official capacity. See Fed. R. Civ. P. 25(d) (“An action does not abate when a public officer who is a party in an official capacity dies, resigns, or otherwise ceases to hold office while the action is pending. The officer’s successor is automatically substituted as a party. Later proceedings should be in the substituted party’s name, but any misnomer not affecting the parties’ substantial rights must be disregarded. The court may order substitution at any time, but the absence of such an order does not affect the substitution.”).
2 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 3 of 27
incentivizes pharmaceutical companies to develop “orphan drugs”—drugs for rare
diseases that affect such a small portion of the population that there otherwise would
be no financial incentive to research and develop treatments. One such incentive is
to grant market exclusivity to the manufacturer of an FDA-approved orphan drug
for a seven-year period. The framework established by the Orphan Drug Act is fairly
straightforward: designation as an orphan drug followed by FDA approval results in
market exclusivity. Each of these steps is governed by a separate part of the Orphan
Drug Act.
1. Designation
Pursuant to 21 U.S.C. § 360bb(a)(1), a drug manufacturer may request the
FDA to designate a drug as an orphan drug—one that “is being or will be
investigated for a rare disease or condition.” Section 360bb(a)(2) defines a “rare
disease or condition” as one that “(A) affects less than 200,000 persons in the United
States, or (B) affects more than 200,000 in the United States and for which there is
no reasonable expectation that the cost of developing and making available in the
United States a drug for such disease or condition will be recovered from sales in
the United States of such drug.” Designation allows the manufacturer to take
advantage of certain resulting financial benefits—such as tax credits—while testing
for safety and efficacy continues. See, e.g., 26 U.S.C. § 45C.
2. Approval
3 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 4 of 27
Before any new drug—orphan or otherwise—can be brought to market, it
must be approved by the FDA. See 21 U.S.C. § 355(a)–(b). The Orphan Drug Act
expressly requires approval pursuant to § 355 before market exclusivity arises. See
id. § 360bb(a). When the manufacturer files a new drug application (“NDA”), it
must include clinical data demonstrating that the drug is safe for use and effective in
use. See id. § 355(b)(1)(A). The manufacturer must identify the new drug’s
“proposed indications for use,” see 21 C.F.R. § 314.50(a)(1), and, if approved by the
FDA, see § 355(c)(1), the manufacturer may market the drug solely for the specific
indications2 for which the FDA approved it, see Ironworks Local Union 68 v.
AstraZeneca Pharms., LP, 634 F.3d 1352, 1356 n.5 (11th Cir. 2011). “The process
of submitting an NDA is both onerous and lengthy,” Mut. Pharm. Co. v. Bartlett,
570 U.S. 472, 476–77 (2013), and it involves significant “risk and expense,”
Ethypharm S.A. Fr. v. Abbott Labs., 707 F.3d 223, 226 (3d Cir. 2013).
3. Exclusivity
To incentivize the development of orphan drugs, upon designation and FDA
approval of the orphan drug, the manufacturer of the orphan drug is granted market
exclusivity for a defined period of time. Specifically, the Orphan Drug Act provides:
Except as provided in subsection (b), if the Secretary--
2 “Indications” is a term of art that means the drug’s “intended use or uses.” United States ex rel. Polansky v. Pfizer, Inc., 822 F.3d 613, 615 (2d Cir. 2016).
4 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 5 of 27
(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 the same drug for the same 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.
21 U.S.C. § 360cc(a) (emphasis added). The Orphan Drug Act does not define
“same disease or condition,” the statutory phrase that is the subject of this dispute. 3
B. Statutory Exceptions to Market Exclusivity for Orphan Drugs
There are three statutory exceptions to the seven-year period of exclusivity.
The first two are found in 21 U.S.C. § 360cc(b).4 First, the FDA can abrogate the
3 Through regulation, the FDA has defined “same drug” as “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.” 21 C.F.R. § 316.3(b)(14)(i). “Moiety,” in this context, means the same active ingredient. See id. § 316.3(b)(2). 4 Specifically, § 360cc(b) states:
During the 7-year period described in subsection (a) for an approved application under section 355 of this title or license under section 262 of Title 42, the Secretary may approve an application or issue a license for a drug that is otherwise the same, as determined by the Secretary, as the already approved drug for the same rare disease or condition if—
(1) the Secretary finds, after providing the holder of exclusive approval or licensure notice and opportunity for the submission of views, that during such period the holder of the exclusive approval or licensure cannot ensure 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
5 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 6 of 27
manufacturer’s exclusivity and approve another manufacturer’s NDA if the FDA
finds “that during such period the holder of the exclusive approval or licensure
cannot ensure the availability of sufficient quantities of the drug.” Id. § 360cc(b)(1).
Second, a drug manufacturer can waive its exclusivity by written consent. Id.
§ 360cc(b)(2).
Third, as part of the 2017 reauthorization and statutory overhaul of the Orphan
Drug Act,5 Congress codified the concept of “clinical superiority” to § 360cc(c) and
(e). Under these provisions, during the statutory exclusivity period, a different
manufacturer of the same drug can obtain approval of an NDA to use the drug to
treat the same disease or condition—effectively abrogating the original
manufacturer’s exclusivity—if that second manufacturer demonstrates that its drug
“provides a significant therapeutic advantage over and above an already approved
or licensed drug in terms of greater efficacy, greater safety, or by providing a major
contribution to patient care.” § 360cc(c)
(2) the 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. 5 See FDA Reauthorization Act of 2017, Pub. L. No. 115-52, § 607, 131 Stat. 1005, 1049– 50.
6 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 7 of 27
C. LEMS and the Competing Drugs Firdapse and Ruzurgi
Lambert-Eaton Myasthenic Syndrome (“LEMS”) is a rare autoimmune
disease that causes the immune system to attack the body’s own tissues. It is
considered an “orphan disease” with less than 0.001% of the population affected—
diagnosed cases in the United States range from roughly 950 to 1,300. And the
number of pediatric cases is infinitesimal—believed to be a “couple of dozen”
nationwide. From all indications in the record evidence, LEMS affects adults and
children equally—the disease mechanism, the pathophysiology, the clinical
symptoms, the treatment regimens, and even adverse events all point to the same
diagnosis, prognosis, and treatment of LEMS for both adults and children.
LEMS is treatable with the chemical amifampridine. Catalyst developed
Firdapse (generic name: amifampridine phosphate) for the treatment of LEMS. On
November 12, 2009, the FDA designated Firdapse as an orphan drug for the
treatment of LEMS pursuant to § 360bb, and there is nothing in the FDA’s
designation that limits the “rare disease or condition” to subsets of people (e.g.,
adults or children) suffering from LEMS. Catalyst filed its first NDA in December
2015, which the FDA rejected as “not sufficiently complete to permit a substantive
review.” In March 2018, Catalyst re-filed its NDA, and the FDA approved Firdapse
for the treatment of LEMS “in adults” on November 28, 2018. Consistent with the
7 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 8 of 27
Orphan Drug Act, the FDA granted Catalyst exclusivity through November 28,
2025. See § 360cc(a).
Jacobus developed its own drug—Ruzurgi (generic name: amifampridine)—
for the treatment of LEMS. In fact, the FDA had designated Ruzurgi as an orphan
drug to treat LEMS in 1990—nineteen years prior to Catalyst’s designation. Like
the agency’s designation of Firdapse, the FDA’s designation of Ruzurgi is not
limited to specific groups or subsets of individuals suffering from LEMS, i.e., the
“rare disease or condition.” While Jacobus continued its development and testing
for more than two decades, physicians at the Mayo Clinic and Duke University have
used Ruzurgi to treat patients with LEMS for free since at least January 1993 under
the FDA’s “compassionate use” program. Jacobus submitted its first NDA for
Ruzurgi in August 2017, which the FDA rejected. In June 2018, Jacobus re-filed its
NDA. In its NDA, Jacobus included the following label for Ruzurgi:
Safety and effectiveness of RUZURGI have been established in patients 6 to less than 17 years of age. Use of RUZURGI in patients 6 to less than 17 years of age is supported by evidence from adequate and well-controlled studies of RUZURGI in adults with LEMS.
In reviewing Jacobus’s NDA, the FDA recognized that Catalyst, through
Firdapse, had exclusivity “for the treatment of LEMS in adults that could potentially
block approval of amifampridine (Ruzurgi) in that population.” Because of this, the
FDA “administratively divided” Jacobus’s NDA into two parts: one for the treatment
of LEMS in pediatric patients, and the other for the treatment of LEMS in adult
8 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 9 of 27
patients, “to allow for independent action in these populations.” Following its
review, the FDA approved Ruzurgi on May 6, 2019 “in patients 6 to less than 17
years of age.”
By the FDA’s own admission, this was likely the first time it ever “approved
an application for a drug with an indication to treat pediatric patients for a certain
disease while another sponsor has obtained orphan drug exclusivity for a drug
application for the same drug with only an indication to treat adult patients for that
disease.” Nevertheless, the FDA concluded that approving Ruzurgi did not violate
Catalyst’s exclusivity because the approval of Ruzurgi for pediatric patients
constituted a different “indication or use” from Firdapse’s approval for adult
patients.
Catalyst contends this decision by the FDA to “administratively divide”
Jacobus’s NDA was unique for several additional reasons. First, Jacobus never
expressed an interest in—much less submitted or requested an NDA based on—
pediatric-only approval, and Catalyst contends this would have been “plainly
uneconomic,” as there are only a couple of dozen pediatric LEMS patients
nationwide. Second, Jacobus never conducted any clinical trials in children; every
single patient in its clinical trials was an adult. Indeed, Jacobus was able to submit
limited data only on pediatric safety, not efficacy—and Jacobus’s data came from
the expanded access program of compassionate use, not its clinical trials. Pursuant
9 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 10 of 27
to 21 U.S.C. § 355(b)(1), however, both safety and efficacy data are required for
approval of an NDA.
D. Catalyst’s Lawsuit Against the FDA and Jacobus’s Intervention
Catalyst filed a four-count complaint against the FDA alleging multiple
violations of the Administrative Procedure Act (“APA”) relating to its approval of
Ruzurgi. See 5 U.S.C. § 706(2)(A); 21 U.S.C. §§ 355(d), 360cc. Shortly thereafter,
Jacobus intervened. Catalyst sought declaratory and injunctive relief, as well as
“[a]n order vacating Defendants’ approval of Ruzurgi.” Catalyst based its claims on
two premises. First, Catalyst argued that the plain language of the Orphan Drug Act
prohibited the FDA from approving Ruzurgi because it is the “same drug” as
Firdapse and treats the “same disease or condition” as Firdapse. Second, Catalyst
argued that Ruzurgi could not be approved under the FDCA because it contains
“false or misleading” labeling as a matter of law—specifically, because it suggests,
in plain violation of an FDA regulation, that “the drug can be used for adult patients
with LEMS, notwithstanding the fact that Ruzurgi only obtained approval to treat
pediatric patients.”
Each party moved for summary judgment. For purposes of these motions, it
was undisputed that: (1) Firdapase and Ruzurgi are the “same drug” under the
Orphan Drug Act, and (2) LEMS is “a single disease.” The district court referred
the motions to the magistrate judge for a report and recommendation. Based on its
10 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 11 of 27
application of the Chevron-deference doctrine, 6 the magistrate judge determined that
the phrase “same disease or condition” in § 360cc(a) of the Orphan Drug Act is
ambiguous and that the FDA’s interpretation of the phrase was reasonable. The
magistrate judge also determined that the FDA’s approval of Ruzurgi’s labeling did
not violate the FDCA. As a result, the magistrate judge recommended granting the
Defendants’ motions for summary judgment and denying Catalyst’s motion for
summary judgment.
The district court affirmed and adopted the report and recommendation in full.
The district court stated that the crux of the case was “whether the language of
section 360cc is ambiguous.” Like the magistrate judge, the district court first noted
that there was no dispute between the parties that Firdapse and Ruzurgi are the “same
drug.” The district court focused on the statutory phrase “same disease or
condition,” finding it ambiguous and quoting with approval the magistrate judge’s
conclusion that “‘it is unclear whether that phrase refers to the use for which the drug
is approved after it submits its [NDA]’—here, LEMS for adults—‘or the disease or
condition for which it . . . received orphan [drug] designation’—LEMS for all
patients.” The district court also found that because § 360cc was ambiguous it
needed to determine whether the FDA’s interpretation of the statute was reasonable.
As for Catalyst’s count alleging Ruzurgi’s false or misleading labeling, the district
6 See Chevron, U.S.A., Inc. v. Nat. Res. Def. Council, Inc., 467 U.S. 837, 842 (1984).
11 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 12 of 27
court noted that Catalyst “fail[ed] to present any case law in support of its
position . . . [and] present[ed] no authority that would call into question the FDA’s
interpretation of its regulation under Chevron’s highly deferential standard.”
Catalyst timely appealed.
II. STANDARD OF REVIEW
We review de novo the district court’s “interpretation and application of
statutory provisions, as well as any grant of summary judgment based on that
interpretation.” Williams v. Sec’y, U.S. Dep’t of Homeland Sec., 741 F.3d 1228,
1231 (11th Cir. 2014). In reviewing an order granting summary judgment, we are
guided by the well-established rule that summary judgment is appropriate “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). Because this case
involves a challenge to agency action, our de novo review of the district court’s grant
of summary judgment is, in effect, a direct review of the agency’s decision. Purepac
Pharm. Co. v. Thompson, 354 F.3d 877, 883 (D.C. Cir. 2004). Under the APA, we
must “hold unlawful and set aside agency action . . . found to be . . . arbitrary,
capricious, an abuse of discretion, or otherwise not in accordance with law.” 5
U.S.C. § 706(2)(A); accord Miami-Dade County v. EPA, 529 F.3d 1049, 1058 (11th
Cir. 2008).
12 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 13 of 27
III. ANALYSIS
On appeal, Catalyst raises three issues. First, Catalyst argues that the Orphan
Drug Act’s language providing exclusivity for “the same disease and condition” is
unambiguous, and therefore, the district court erred in determining that the Orphan
Drug Act permits the FDA to grant orphan drug exclusivity to the “same drug” based
on the drug’s “use or indication.” Second, Catalyst argues that, even if the Orphan
Drug Act is ambiguous, the district court erred in concluding that the FDA’s “use or
indications” interpretation of the Orphan Drug Act was reasonable. Third, Catalyst
argues that the district court erred in concluding that Jacobus’s NDA for Ruzurgi did
not violate the FDCA’s labeling requirements. Because we agree with Catalyst on
its first argument and reverse on that basis, we do not reach or address the merits of
the remaining issues raised by Catalyst on appeal.
In any question of statutory interpretation, we begin with the language of the
statute itself. CBS Inc. v. PrimeTime 24 Joint Venture, 245 F.3d 1217, 1225 n.6
(11th Cir. 2001); Alfaro-Garcia v. U.S. Atty. Gen., 981 F.3d 978, 981–82 (11th Cir.
2020) (“The fundamental principle governing any exercise in statutory interpretation
is that ‘[courts] “begin[] where all such inquiries must begin: with the language of
the statute itself,” and . . . give effect to the plain terms of the statute.’” (second
alteration in original) (quoting In re Valone, 784 F.3d 1398, 1402 (11th Cir. 2015))).
Section 360cc(a) states, in relevant part:
13 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 14 of 27
[I]f the Secretary--
(1) approves an application filed pursuant to section 355 of this title, or
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 the same drug for the same 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. . . .
(emphasis added). The district court found this section of the Orphan Drug Act
ambiguous because (1) the statute does not define “same disease or condition” and
(2) Congress failed to clarify whether that phrase refers to the use for which the drug
is approved after it submits its NDA or for which it received orphan drug
designation.
We conclude that the district court erred in finding § 360cc of the Orphan
Drug Act ambiguous. First, “a statute is not ambiguous merely because it contains
a term without a statutory definition.” United States v. Sepulveda, 115 F.3d 882,
886 n.9 (11th Cir. 1997). Indeed, “Congress is ‘not required to define each and every
word in a piece of legislation in order to express clearly its will.’” Id. (quoting
Newsom v. Friedman, 76 F.3d 813, 817 (7th Cir. 1996)). As we have recognized,
“[w]e interpret words that are not defined in a statute with their ordinary and plain
meaning because we assume that Congress uses words in a statute as they are
14 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 15 of 27
commonly understood.” Polycarpe v. E&S Landscaping Serv., Inc., 616 F.3d 1217,
1223 (11th Cir. 2010) (alteration in original) (defining various terms in the Fair
Labor Standards Act using everyday dictionaries). Moreover, courts do not read
individual words or terms in isolation, but instead in light of their context within a
particular text. Ruiz v. Wing, 991 F.3d 1130, 1138 (11th Cir. 2021). Indeed, “[w]hile
most words carry more than one dictionary definition, ‘[o]ne should assume the
contextually appropriate ordinary meaning unless there is reason to think
otherwise.’” Id. (quoting Antonin Scalia & Bryan A. Garner, Reading Law 70
(2012)).
Because neither the FDA nor Jacobus disputes that LEMS is a “disease,” the
issue before us is the meaning of the word “same” as used in the phrase “same
disease or condition.” “Same,” when used as an adjective, has more than one
definition (although they are related). Merriam Webster’s Collegiate Dictionary
defines “same” as: (1) “resembling in every relevant respect; conforming in every
respect (used with “as”)”; (2) “being one without addition, change, or
discontinuance: identical; being the one under discussion or already referred to”; (3)
“corresponding so closely as to be indistinguishable”; and (4) “equal in size, shape,
value, or importance (usually used with the or a demonstrative (such as that, those).”
Same, Merriam-Webster’s Collegiate Dictionary, https://unabridged.merriam-
webster.com/collegiate/same.
15 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 16 of 27
As noted earlier, § 360cc(a) provides that if the FDA approves an “application
filed pursuant to section 355 of this title . . . for a drug designated under section
360bb . . . for a rare disease or condition, the Secretary may not approve another
application under section 355 . . . for the same drug for the same disease or
condition” until the expiration of seven years. Here, the word “same” is being used
in the sense of “being the one under discussion or already referred to.” The only
“disease or condition” already referred to in § 360cc(a) is the “rare disease or
condition” for which the drug was “designated under § 360bb.” The ordinary and
plain meaning of “same drug or condition” read in the context of this sentence yields
only one result—the term unambiguously refers to the “rare disease or condition”
designated under § 360bb. Thus, the scope of exclusivity under § 360cc(a) is
determined by what has been designated under § 360bb.
As it relates to the facts here, pursuant to § 360bb, the FDA designated
Catalyst’s Firdapse as an orphan drug for treating the “rare disease or condition” of
LEMS. As discussed earlier, LEMS is the same disease in all people suffering from
it, regardless of their age, and there is nothing in the record to suggest that the FDA
qualified its § 360bb designation with an age-restriction or that the designation of
Firdapse applied to anything other than LEMS for all people suffering from the
disease. The active ingredient in Firdapse is amifampridine. Under § 360cc(a), the
FDA could not approve another manufacturer’s NDA seeking approval of
16 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 17 of 27
amifampridine to treat LEMS, i.e., the “same disease or condition” that was
designated under § 360bb, for a seven-year period. Because the active ingredient in
Jacobus’s Ruzurgi is also amifampridine, § 360cc(a) therefore temporarily barred
the FDA from approving Jacobus’s NDA to use Ruzurgi to treat LEMS.
In determining that the statutory phrase “same disease or condition” as used
in § 360cc(a) was ambiguous, the district court looked to another section of the
FDCA—21 U.S.C. § 355—which governs NDAs for many drugs, including orphan
drugs. The district court noted that § 360cc(a) expressly refers to § 355 and that
§ 355 requires a drug manufacturer, as part of its NDA, to provide evidence that the
drug is safe and effective for its intended use. 7 The district court further noted that
the FDA’s approval of Catalyst’s NDA under § 355 was for the treatment of LEMS
“in adults.” The district court concluded that it was not clear whether “same disease
or condition” refers to the “use” approved by the FDA to treat a disease or condition
pursuant to § 355 or to the “rare disease or condition” designated by the FDA
pursuant to § 360bb of the Orphan Drug Act. Because it concluded that either
interpretation was reasonable, the district court deferred to the FDA’s interpretation
under the Chevron-deference doctrine.
7 See § 355(b)(1)(A) (stating that drug manufacturer must provide the FDA with “full reports of investigations which have been made to show whether or not such drug is safe for use and whether such drug is effective in use.”
17 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 18 of 27
The district court’s determination that the phrase “same disease or condition”
is ambiguous, however, is not supported by the statutory text. First, the provisions
of § 355, which apply generally to all NDAs and not solely those for orphan drugs,
use different, more limited language, e.g., “safe” and “effective” for “use,” rather
than the broader, disease-specific language found in § 360cc(a). We must presume
that Congress acts intentionally when it omits language included elsewhere in the
same statute, see Dep’t of Homeland Sec. v MacLean, 574 U.S. 383, 392 (2015)
(explaining the interpretive canon that Congress acts intentionally when it omits
language included elsewhere); Jian Le Lin v. U.S. Att’y Gen., 681 F.3d 1236, 1240
(11th Cir. 2012) (“[An] inference may be drawn from the exclusion of language from
one statutory provision that is included in other provisions of the same statute.”
(quoting Hamdan v. Rumsfeld, 548 U.S. 557, 578 (2006))), and we must give
meaning to Congress’s choice. Indeed, “[c]ourts have no authority to alter statutory
language.” CBS Inc., 245 F.3d at 1228 (alteration in original). And “we are not
allowed to add or subtract words from a statute; we cannot rewrite it.” Friends of
the Everglades v. S. Fla. Water Mgmt. Dist., 570 F.3d 1210, 1224 (11th Cir. 2009).
If Congress wanted to make the “use or indication” inquiry relevant to a holder’s
market exclusivity for an orphan drug, it could have done so by including such
language in § 360cc(a). The fact that Congress did not include that language
counsels against an interpretation that finds an ambiguity in § 360cc(a)’s language.
18 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 19 of 27
And, as we have already discussed, the “same disease or condition” already referred
to in § 360cc(a) is the “rare disease or condition” for which the drug was “designated
under § 360bb.”
Second, while it is certainly true that § 366cc(a) refers to approval of
applications submitted pursuant to § 355, it also refers to issuance of licenses
pursuant to 42 U.S.C. § 262:
if the Secretary—
(1) approves an application filed pursuant to section 355 of this title, or
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 section or issue another license under section 262 of Title 42 for the same drug for the same disease or condition . . . .
The references to § 355 and § 262 simply identify what must occur to trigger market
exclusivity (approval of an application under § 355 or issuance of a license under
§ 262) and what the FDA is prohibited from doing once both the designation and
approval conditions are met (approve another application under § 355 or issue
another license under § 262.) There is nothing in the express language of § 360cc
that incorporates by reference the substantive provisions, requirements, or
limitations of either § 355 or § 262, nor does the context in which the language
appears or the structure of § 360cc(a) suggest that be done.
19 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 20 of 27
Third, although Congress did not define “same disease or condition,” it did
define “rare disease or condition”—the first phrase used and then referred back to in
§ 360cc—elsewhere in the Orphan Drug Act. As already noted, a manufacturer may
request the FDA designate its drug “as a drug for a rare disease or condition.”
§ 360bb(a)(1). Congress defined “rare disease or condition” as:
any disease or condition which (A) affects less than 200,000 persons in the United States, or (B) affects more than 200,000 in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug.
§ 360bb(a)(2). The statutory definition depends solely upon the modifier “rare.” In
other words, a disease or condition is “rare” under the Orphan Drug Act if it meets
one of the two statutory conditions relating to how many people it affects. And while
Congress could have included an additional use-specific definition for the words
“disease or condition,” it chose not to do so. By defining the term “rare disease or
condition” in this manner—“rare” being defined, but the words “disease” and
“condition” left without a statutory-specific definition—Congress left to the courts
the obligation to interpret those words and apply the ordinary and plain meaning of
those words as they are commonly understood. See Polycarpe, 616 F.3d at 1223.
Moreover, “reasonable statutory interpretation must account for both ‘the specific
context in which . . . language is used’ and ‘the broader context of the statute as a
whole.’” Util. Air Regul. Grp. v. EPA, 573 U.S. 302, 321 (2014) (quoting Robinson
20 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 21 of 27
v. Shell Oil Co., 519 U.S. 337, 341 (1997)). The Orphan Drug Act addresses drugs
developed and designated for rare diseases or conditions. By its express language,
§ 360cc provides exclusivity and protection from others marketing the same drug
for the rare disease or condition for which the orphan drug was designated pursuant
to § 360bb.
Fourth, the district court’s reliance on Spectrum Pharmaceuticals, Inc. v.
Burwell, 824 F.3d 1062 (D.C. Cir. 2016), and Sigma-Tau Pharmaceuticals, Inc. v.
Schwetz, 288 F.3d 141 (4th Cir. 2002), in support of its finding of ambiguity was
misplaced. In Spectrum, the question before the court was whether intended off-
label use mattered for purposes of § 360cc(a)’s exclusivity. See 824 F.3d at 1067.
Spectrum first obtained orphan drug designation and FDA approval for a drug to
treat liver damage, with its market exclusivity expiring in 2015. Id. at 1064.
Spectrum then obtained orphan drug designation and FDA approval for the same
drug to treat a different condition—pain management for patients with advanced
colorectal cancer, with its market exclusivity expiring in 2018. Id. After exclusivity
for the liver damage treatment expired, another manufacturer obtained FDA
approval to sell a generic version of Spectrum’s drug to treat liver damage. Id.
Spectrum filed suit, asserting that the generic manufacturer intended to market the
drug for off-label use for pain management, thereby infringing on Spectrum’s
remaining exclusivity period for that condition. Id. The district court granted
21 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 22 of 27
summary judgment against Spectrum, and the D.C. Circuit affirmed, stating that “the
words ‘for such disease or condition’ suggest that Congress intended to make section
360cc ‘disease-specific, not drug-specific,’ and the rest of the statutory language
focuses on protecting approved indications, not intended off-label uses.” Id. at 1067
(quoting Sigma-Tau, 288 F.3d at 145). 8
Like Spectrum, the issue in Sigma-Tau dealt with the scope of market
exclusivity in the context of off-label use. Sigma-Tau first obtained orphan drug
designation and FDA approval for a drug to treat carnitine deficiency in people with
inborn metabolic disorders, with its market exclusivity expiring in 1999. 288 F.3d
at 143. Sigma-Tau then obtained orphan drug designation and FDA approval for the
same drug to treat a different condition—carnitine deficiency in patients suffering
with end-stage renal disease (“ESRD”), with its market exclusivity expiring in 2006.
Id. After exclusivity for the treatment of inborn metabolic disorders expired, two
manufacturers obtained FDA approval to sell a generic version of Sigma-Tau’s drug
to treat carnitine deficiency in people with inborn metabolic disorders. Id. Like the
manufacturer in Spectrum, Sigma-Tau sued, arguing that the generic manufacturers
intended to market the drug for ESRD-related treatment and that the market
8 Both Spectrum and Sigma-Tau Pharmaceuticals involved claims arising under the prior version of § 360cc, which used the term “such disease or condition.” That language was amended as part of the 2017 overhaul of the Orphan Drug Act to the current term “same disease or condition.” See 131 Stat. at 1049–50.
22 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 23 of 27
exclusivity Sigma-Tau still held for ESRD-related treatment precluded FDA
approval. Id. at 143–44. The Fourth Circuit concluded that the Orphan Drug Act
allowed for the approval of a generic version of a drug “for an indication that was
no longer protected by market exclusivity.” Id. at 143. The court noted that the
Orphan Drug Act is disease-specific and stated, “[i]n other words, the statute as
written protects uses, not drugs for any and all uses.” Id. at 145. While the Fourth
Circuit in Sigma-Tau certainly used the terms “uses” and “indications,” to read that
language as supportive of the FDA’s interpretation, or as supportive of ambiguity in
general, is to take the court’s language out of context, as it is clear that the Fourth
Circuit is comparing use of the same drug to treat different diseases and is using
those terms to refer to that situation. Nothing in either Spectrum or Sigma-Tau
Pharmaceuticals supports the notion that § 360cc incorporates the substantive
provisions, requirements, or limitations of either § 355 or § 262.
Indeed, we agree that § 360cc(a) is “disease-specific, not drug-specific.” But
Spectrum and Sigma-Tau Pharmaceuticals both addressed the application of market
exclusivity in the context of the treatment of different diseases; neither court was
asked to address whether the phrase “same disease or condition” referred to
designation under § 360bb or to the terms and conditions for approving an
application under § 355 or issuing a license under § 262. We hold therefore that the
23 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 24 of 27
disease referred to in the phrase “same disease or condition” is the “rare disease or
condition” for which the drug received designation under § 360bb.
We further hold that the phrase “same disease or condition” in § 360cc of the
Orphan Drug Act is not ambiguous, as it plainly refers back to the term—“rare
disease or condition”—used earlier in the same statutory provision. Additionally,
the references in § 360cc(a) to § 355 and § 262 simply identify what agency actions
satisfy the approval condition and what actions cannot occur once both designation
and approval occurs. In this case, § 360cc prohibits the approval of subsequent
NDAs for amifampridine to treat LEMS—the “rare disease or condition” designated
under § 360bb—while Catalyst holds its seven-year exclusivity. Unless one of the
three statutory exemptions applies—and there is no record evidence to suggest that
any do apply—it is irrelevant if the subsequent NDA is intended to address only a
subset of the population for LEMS. The district court therefore erred in finding that
the statutory phrase “same disease or condition” in § 360cc was ambiguous.
And because the statutory phrase “same disease or condition” in § 360cc is
not ambiguous, we also conclude that the district court erred in treating this as a
Chevron-deference case and deferring to the FDA’s interpretation of the statutory
language. “When a court reviews an agency’s construction of the statute which it
administers, it is confronted with two questions.” Nat’l Ass’n of State Util.
Consumer Advocs. v. FCC, 457 F.3d 1238, 1253 (11th Cir. 2006) (quoting Chevron,
24 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 25 of 27
U.S.A., Inc. v. Nat. Res. Def. Council, Inc., 467 U.S. 837, 842 (1984)), modified on
denial of reh’g, 468 F.3d 1272 (11th Cir. 2006). We first consider whether Congress
has directly spoken to the precise question at issue in the case, and, if Congress’s
intent is clear, we “must give effect to the unambiguously expressed intent of
Congress.” Id. (quoting Chevron, 467 U.S. at 843). Where a statute is silent or
ambiguous with respect to the specific issue, however, we must determine “whether
the agency’s answer is based on a permissible construction of the statute.” Id.
(quoting Chevron, 467 U.S. at 843).
Because the statute here is unambiguous, “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.” Wilderness Watch & Pub. Emps. for Env’t Resp. v. Mainella, 375
F.3d 1085, 1091 (11th Cir. 2004). Courts “do not defer to an agency’s interpretation
of a statute when the text is clear.” Villarreal v. R.J. Reynolds Tobacco Co., 839
F.3d 958, 970 (11th Cir. 2016). And here, the FDA’s interpretation of Orphan Drug
Act is contrary to the clear statutory language enacted by Congress.
We now address the parties’ cross-motions for summary judgement. Our
review is de novo, and the parties agree that no genuine issues of material fact exist.
The undisputed record evidence establishes that: (1) LEMS is a rare disease as
defined in § 360bb(a)(2); (2) Firdapse was designated as an orphan drug to treat
LEMS pursuant to § 360bb; (3) the FDA’s designation of Firdapse to treat LEMS
25 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 26 of 27
was not for a specific category of patients suffering from LEMS; (4) Firdapse was
granted approval by the FDA pursuant to § 355 and was granted market exclusivity
pursuant to § 360cc prior to the FDA’s approval of Jacobus’s NDA for Ruzurgi; (5)
the active ingredient in both Firdapse and Ruzurgi is amifampridine; (6) Ruzurgi is
the “same drug” as Firdapse; (7) Firdapse and Ruzurgi both treat LEMS; and (8)
Firdapse’s exclusivity had not expired at the time the FDA approved Ruzurgi.
Additionally, none of the three statutory exceptions to market exclusivity apply here:
(1) the parties agree that Catalyst can ensure sufficient quantities of Firdapse, see
§ 360cc(b)(1); (2) there is no record evidence that Catalyst waived its exclusivity by
written consent, see § 360cc(b)(2); and (3) there is no record evidence that Jacobus
filed its NDA based on the representation that Ruzurgi is clinically superior to
Firdapse, see § 360cc(c), (e).
Based on these undisputed facts and record evidence, the FDA’s approval of
Ruzurgi was contrary to the unambiguous language of the Orphan Drug Act.
Catalyst Pharmaceuticals, Inc., held the exclusive right to market, Firdapse, an
orphan drug, for a period of seven years in order to treat the rare autoimmune disease,
LEMS. Because it is undisputed that none of the statutory exceptions to Catalyst’s
market exclusivity apply, the FDA was prohibited from approving for sale the same
drug manufactured by Jacobus Pharmaceutical Company, Inc., to treat the same
autoimmune disease during the period of Catalyst’s market exclusivity. As a result,
26 USCA11 Case: 20-13922 Date Filed: 09/30/2021 Page: 27 of 27
the FDA’s agency’s action was arbitrary, capricious, and not in accordance with law,
and its approval of Ruzurgi must be set aside. See 5 U.S.C. § 706(2)(A); Miami-
Dade County, 529 F.3d at 1058.
IV. CONCLUSION
Because it is undisputed that Catalyst held the exclusive right to market
Firdapse, i.e., amifampridine, to treat LEMS and that none of the statutory
exceptions to market exclusivity apply here, we conclude that Catalyst is entitled to
summary judgment in its favor. The district court’s grant of summary judgment in
favor of Defendants and Jacobus is reversed, and on remand, the district court shall
enter summary judgment in favor of Catalyst.
REVERSED and REMANDED.