Jazz Pharmaceuticals, Inc. v. Robert F. Kennedy, Jr., Secretary of the Department of Health and Human Services

United States Court of Appeals
FOR THE DISTRICT OF COLUMBIA CIRCUIT
Argued May 5, 2025 Decided June 27, 2025
No. 24-5262
JAZZ PHARMACEUTICALS, INC.,
APPELLANT
v.
ROBERT F. KENNEDY, JR., SECRETARY OF THE DEPARTMENT
OF HEALTH AND HUMAN SERVICES, ET AL.,
APPELLEES
Appeal from the United States District Court
for the District of Columbia
(No. 1:23-cv-01819)
Kwaku A. Akowuah argued the cause for appellant. With
him on the briefs was Peter A. Bruland. Tobias S. Loss-Eaton
entered an appearance.
Brian J. Springer, Attorney, U.S. Department of Justice,
argued the cause for appellees. With him on the brief was
Melissa N. Patterson, Attorney.
Phillip J. Perry argued the cause for intervenor in support
of appellees. With him on the brief were Nicholas L.
Schlossman, John R. Manthei, Andrew D. Prins, Peter E.
Davis, and Richard Frohlichstein.

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Charles Duan was on the brief for amici curiae 12
Narcolepsy Patients, et al. in support of appellees.
Before: HENDERSON, WILKINS and PAN, Circuit Judges.
Opinion for the Court filed by Circuit Judge HENDERSON.
KAREN LECRAFT HENDERSON, Circuit Judge: This case
involves a dispute about drug marketing exclusivity under the
Orphan Drug Act (ODA or Act). The Food and Drug
Administration (FDA) approved for marketing a drug
containing oxybate produced by Avadel CNS Pharmaceuticals
Inc. (Avadel) to treat narcolepsy during Jazz Pharmaceuticals,
Inc.’s (Jazz) seven-year exclusivity period for a drug
containing the same active ingredient approved for the same
disease or condition.
The question before us is whether Avadel’s and Jazz’s
drugs are the “same drug” within the meaning of the ODA so
that Jazz’s exclusivity period barred the FDA from granting
marketing approval to Avadel’s drug. See 21 U.S.C.
§ 360cc(a). We conclude they are not.
Under the FDA’s longstanding regulatory definition of
“same drug,” a clinically superior drug is not the same as a drug
that is otherwise the same. See 21 C.F.R. § 316.3(b)(14)(i). In
2017, the Congress amended the ODA’s exclusivity provision,
replacing the phrase “such drug” with “same drug.” See 21
U.S.C. § 360cc(a). The statutory history, context and scheme
show that, in doing so, the Congress incorporated the FDA’s
regulatory definition of “same drug.” And it is undisputed on
appeal that Avadel’s drug, Lumryz, is clinically superior to
Jazz’s drug, Xywav.

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Because the FDA did not act beyond its statutory authority
when it approved Lumryz for marketing during the exclusivity
period for Xywav, we affirm the district court’s grant of
summary judgment to the FDA and Avadel.
I. BACKGROUND
A. The 1983 Orphan Drug Act
The Congress enacted the ODA in 1983 as an amendment
to the Federal Food, Drug, and Cosmetic Act of 1938 (FD&C
Act). Orphan Drug Act, Pub. L. No. 97-414, §§ 1, 2, 5, 96 Stat.
2049, 2049–51, 2056–57 (1983) (codified as amended at 21
U.S.C. §§ 360aa–360ee). After having found that
pharmaceutical companies needed financial incentives to make
drug development for rare diseases economically feasible, the
Congress determined it was in the public interest to provide
such incentives.1 Id. § 1(b).
To qualify for these incentives, the manufacturer or
sponsor of a drug first requests that the FDA designate the drug
as an orphan drug.2 21 U.S.C. § 360bb(a)(1). That designation
provides benefits such as assistance with investigations and the
approval process, monetary grants to defray drug development
costs and tax credits. See Eagle Pharms., Inc. v. Azar, 952 F.3d
1 A “rare disease or condition” is one that affects fewer than
200,000 people in the United States or that affects more than 200,000
people but for which there is no reasonable expectation that the cost
of developing the drug and making it available domestically will be
recovered from domestic sales. 21 U.S.C. § 360bb(a)(2).
2 The Secretary of the U.S. Department of Health and Human
Services (HHS) carries out responsibilities under the Act through the
FDA Commissioner. See 21 U.S.C. § 393(d)(2). For brevity, this
opinion refers simply to the FDA.

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323, 325 (D.C. Cir. 2020) (citing 21 U.S.C. §§ 360aa, 360ee;
26 U.S.C. § 45C). Before any drug can be sold or marketed in
interstate commerce, the FDA also must approve a drug
application certifying the drug’s safety and efficacy. 21 U.S.C.
§ 355(a)–(b). Once an orphan drug application is approved, the
drug sponsor receives a seven-year period of marketing
exclusivity. Id. § 360cc(a).
As originally enacted, subsection 360cc(a) provided that
the FDA could not approve another section 355 application for
“such drug for such disease or condition” for a sponsor other
than the holder of the approved application during the seven-
year exclusivity period. Id. (1983). The Congress provided
two exceptions to the exclusivity period: if (1) the Secretary
finds, after providing the exclusivity holder with notice and an
opportunity to submit views, that the holder cannot ensure
sufficient drug quantities; or (2) the holder consents to FDA
approval of another section 355 application. Id. § 360cc(b).
Since 1992, FDA regulations have interpreted “such drug”
to mean “same drug.” See 21 C.F.R. § 316.31(a); Orphan Drug
Regulations, 57 Fed. Reg. 62,076, 62,078 (Dec. 29, 1992)
(1992 Rule). For a small-molecule drug like oxybate, the FDA
has defined “same drug” to mean a drug that “contains the same
active moiety” and is “intended for the same use” as a
previously approved drug unless it is “clinically superior.” 21
C.F.R. § 316.3(b)(14)(i); see also 1992 Rule, 57 Fed. Reg. at
62,077–80.
As relevant here, an “active moiety” roughly equates to an
“active ingredient” or “drug substance,” which forms part of
the “drug product” or “finished dosage form.” Compare 21
C.F.R. § 316.3(b)(2) (defining “active moiety” under the
ODA), with id. § 314.3(b) (defining “active moiety,” “active
ingredient,” “drug substance” and “drug product” under the

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FD&C Act). The dosage form includes “design features that
affect frequency of dosing.” Id. § 314.3(b). For example, a
drug may be formulated for immediate-, extended- or delayed-
release. A drug is considered to be “[c]linically superior” if it
“provide[s] a significant therapeutic advantage over” an
approved drug that is otherwise the same, as shown by
“[g]reater effectiveness,” “[g]reater safety,” or “[i]n unusual
cases . . . a demonstration that the drug otherwise makes a
major contribution to patient care.” 21 C.F.R. § 316.3(b)(3).
“[L]onger periods between doses” or a “change in drug
delivery systems” (such as “innovative time-release delivery
mechanisms”) can constitute a “major contribution to patient
care” on a “case-by-case basis.” 1992 Rule, 57 Fed. Reg. at
62,079.
The FDA applies its clinical superiority scheme differently
at two stages of the orphan-drug process. First, at the
designation stage, the sponsor of a drug that is otherwise the
same as an already-approved drug must present a “plausible
hypothesis” that its drug is clinically superior to obtain orphan-
drug designation. 21 C.F.R. §§ 316.20(a), 316.25(a)(3).
Second, at the approval stage, the FDA will grant orphan-drug
exclusivity after a drug has received marketing approval under
21 U.S.C. § 355 only if the sponsor “demonstrate[s]” that the
drug is clinically superior. 21 C.F.R. § 316.34(c). The “post-
approval clinical-superiority requirement” is intended to
prevent a sponsor from obtaining serial exclusivity periods—
known as “evergreening”—or securing exclusivity without
providing an additional or different benefit to patients over a
previously approved therapy. See Eagle Pharms., 952 F.3d at
327 & n.4 (quoting Orphan Drug Regulations, 78 Fed. Reg.
35,117, 35,127 (June 12, 2013) (2013 Rule)).
In 2014, a district court determined that the plain language
of the Act required the FDA to grant orphan-drug exclusivity

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if the FDA has designated an orphan drug and approved the
drug for marketing, precluding the FDA from applying the
second step of its clinical-superiority requirement. Depomed,
Inc. v. HHS, 66 F. Supp. 3d 217, 229–37 (D.D.C. 2014). We
agreed with that interpretation in Eagle Pharmaceuticals,
although we recognized our holding was superseded for
approvals after 2017, when the Congress codified a clinical-
superiority requirement in subsection 360cc(c) and made the
change to subsection 360cc(a) that is the subject of this appeal.
952 F.3d at 325, 329 n.9.
B. The 2017 Amendments
The 2017 amendments altered the Act to make three
changes relevant here. FDA Reauthorization Act of 2017, Pub.
L. No. 115-52, § 607, 131 Stat. 1005, 1049–50 (2017 Act)
(amending 21 U.S.C. § 360cc). First, in subsection 360cc(a),
the Congress replaced “such drug for such disease or
condition” with “the same drug for the same disease or
condition,” so the FDA “may not approve another application
. . . for the same drug for the same disease or condition” for
seven years from the orphan-designated drug’s approval. Id.
§ 607(a)(1) (amending 21 U.S.C. § 360cc(a)). Second, the
Congress similarly changed the language in the exclusivity
exceptions from “such drug for such disease or condition” to
“a drug that is otherwise the same,” among other alterations not
relevant here. Id. § 607(a)(2)(A) (amending 21 U.S.C.
§ 360cc(b)).
Third, the Congress codified a clinical superiority
requirement for exclusivity. If a sponsor of an orphan-
designated drug that is “otherwise the same” as an already-
approved drug seeks exclusivity for the same rare disease or
condition as the approved drug, the FDA is to require the
sponsor to “demonstrate that such drug is clinically superior”

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to the approved drug “that is the same drug.” Id. § 607(a)(3)
(adding 21 U.S.C. § 360cc(c)). The amended statute defines
clinical superiority in line with FDA regulations to mean that a
drug provides greater efficacy or safety or makes a major
contribution to patient care. Id. It also grants the FDA
authority to issue regulations to implement subsection 360cc(c)
and “apply any definitions set forth in regulations that were
[previously] promulgated” if not inconsistent with the amended
statute. Id. (adding 21 U.S.C. § 360cc(d)). Finally, to assist
in demonstrating clinical superiority, the FDA is to (1) notify
the sponsor of the “basis for the [orphan-drug] designation,”
including the “plausible hypothesis” of clinical superiority
offered by the sponsor and relied on by the FDA, and
(2) publish a summary of the “demonstrate[ed]” “clinical
superiority findings” upon granting exclusive approval under
subsection 360cc(a). Id. (adding 21 U.S.C. § 360cc(e)).
C. Rival Orphan Drugs for Narcolepsy
Narcolepsy is a sleep disorder that, at the time the drugs at
issue here received orphan-drug designation, affected around
180,000 people in the United States, making it a rare disease or
condition.3 The molecule oxybate is effective in treating
narcolepsy symptoms. In 1994, Jazz’s predecessor obtained
orphan-drug designation for the active moiety of oxybate for
treating narcolepsy. Jazz later received approvals and seven-
year exclusivity periods for several different narcolepsy
treatment indications of its first oxybate-based drug, Xyrem.4
3 Narcolepsy now affects over 200,000 people and is no longer
considered a rare disease but that change in status is not a basis on
which to revoke orphan-drug designation. 21 C.F.R. § 316.29(c).
4 Xyrem had exclusivity periods from 2002 to 2009 to treat
cataplexy associated with narcolepsy, from 2005 to 2012 to treat

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In July 2020, the FDA approved Jazz’s Xywav, an oxybate-
based drug that the FDA determined was clinically superior to
Xyrem because of its lower sodium content. Xywav was
covered for orphan-drug designation by Jazz’s designation of
oxybate to treat narcolepsy and was entitled to orphan-drug
exclusivity because it is clinically superior to Xyrem and, under
Jazz’s view, because exclusivity only bars approval of another
sponsor’s drug.
In January 2018, Avadel received orphan-drug designation
for the active moiety oxybate for narcolepsy because it
provided a plausible hypothesis that its proposed drug
product’s once-nightly dosing regimen from an extended-
release formulation would make the drug clinically superior to
Xyrem, which require patients to wake during the night to take
a second dose.5 Avadel then applied for marketing approval of
Lumryz in December 2020, requiring the FDA to determine
whether Xywav’s exclusivity period until July 2027 blocked
approval of Lumryz. Although Lumryz contains more sodium
than Xywav, the FDA determined in May 2023 that the benefits
of Lumryz’s once-nightly dosing made a major contribution to
excessive daytime sleepiness (EDS) associated with narcolepsy and
from 2018 to 2025 to treat cataplexy and EDS in pediatric patients.
Avadel seeks approval to treat cataplexy or EDS in adults and so
Xyrem’s exclusivity for the pediatric indication is not at issue.
5 The Xywav drug product is an immediate-release calcium,
magnesium, potassium and sodium oxybate oral solution whereas the
Lumryz drug product is an extended-release sodium oxybate oral
suspension. See 21 C.F.R. 314.3(b) (defining “drug product” as the
finished dosage form that contains a drug substance—an active
ingredient—along with other ingredients); id. (defining “dosage
form” as the physical manifestation of a drug, including the (1)
physical appearance, (2) physical form, (3) way it is administered
and (4) design features affecting frequency of dosing).

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patient care, rendering it clinically superior and therefore not
the “same drug.” Accordingly, the FDA concluded that
Xywav’s exclusivity did not bar marketing approval for
Lumryz and that Lumryz was entitled to its own seven-year
exclusivity period.6
In June 2023, Jazz sued in district court under the
Administrative Procedure Act (APA) to challenge the FDA’s
approval of Lumryz, arguing that the FDA acted not in
accordance with law and in excess of statutory authority by
approving Lumryz in violation of subsection 360cc(a)’s
exclusivity provision. Jazz Pharms., Inc. v. Becerra, No. 23-
cv-1819, 2024 WL 4625731, at *10 (D.D.C. Oct. 30, 2024).
Avadel intervened as a defendant and the district court granted
summary judgment to the FDA and Avadel, reasoning that
statutory text, history and purpose show that the Congress
meant to ratify and incorporate the FDA’s definition of “same
drug” in subsection 360cc(a). Id. at *13. As a result, the FDA
properly approved Lumryz during Xywav’s exclusivity period
because Lumryz’s clinical superiority means it is not the “same
drug” as Xywav. Id. at *17. In the alternative, the court
determined that even if Lumryz is the “same drug” as Xywav,
subsection (c)(1) nevertheless authorizes the FDA to grant
6 In a letter submitted to the FDA before it approved Lumryz,
Jazz conceded that the FDA could approve Lumryz if it was
clinically superior to Xywav. J.A. 382–85; see also J.A. 145 n.118.
Jazz does not renew on appeal its argument made in district court that
FDA erred in finding that Lumryz is clinically superior to Xywav.
Nevertheless, during this litigation Jazz has consistently maintained
its position that the FDA may not approve Lumryz even if it is
clinically superior. We of course have an “obligation to
independently interpret the statute[]” to “determine the best reading.”
Loper Bright Enters. v. Raimondo, 603 U.S. 369, 373 (2024).

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exclusive approval based on clinical superiority.7 Id. at *17–
18. Jazz timely appealed.
II. ANALYSIS
We review questions of statutory interpretation under the
APA de novo. See Loper Bright Enters. v. Raimondo, 603 U.S.
369, 392 & n.4 (2024). “We start where we always do: with
the text of the statute.” Bartenwerfer v. Buckley, 598 U.S. 69,
74 (2023) (citation modified). It is also a “fundamental canon
of statutory construction that the words of a statute must be
read in their context and with a view to their place in the overall
statutory scheme.” Util. Air Regul. Grp. v. EPA, 573 U.S. 302,
320 (2014) (quotation omitted). “Statutory history is an
important part of this context,” including, in this case,
considerations of incorporation and the old-soil canon. United
States v. Hansen, 599 U.S. 762, 775 (2023); see also id. at 778–
79.
A. The Statutory Text
Pursuant to the text, as amended, the Act prohibits the
FDA from approving another application “for the same drug
for the same disease or condition” as an orphan-designated and
approved drug during the earlier drug’s seven-year exclusivity
period. 21 U.S.C. § 360cc(a). Jazz argues that “same” here
means “the one previously referred to; aforesaid.” See Same,
Collins English Dictionary 1750 (12th ed. 2014).
For support, Jazz relies on the Eleventh Circuit’s
interpretation of “same” in this context to mean “being the one
7 Because we affirm the district court’s interpretation of
subsection 360cc(a), we do not reach its alternative holding that
subsection 360cc(c) created a third exception to exclusivity.

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under discussion or already referred to.” Catalyst Pharms.,
Inc. v. Becerra, 14 F.4th 1299, 1307–08 (11th Cir. 2021) (citing
Same, Merriam-Webster’s Collegiate Dictionary Online). But
the Eleventh Circuit brushes past Merriam-Webster’s first
sense of the adjective “same,” which defines it as “resembling
in every relevant respect,” and instead adopts the second
definition of the term without explanation. Id. (citing Same,
Merriam-Webster’s Collegiate Dictionary Online). Merriam-
Webster’s first sense also fits with Black’s contemporary
definition. Same, Black’s Law Dictionary 1541 (10th ed. 2014)
(“Identical or equal; resembling in every relevant respect.”).
As a matter of ordinary meaning, a drug that is clinically
superior to another drug does not resemble that drug in every
relevant respect. Indeed, narcolepsy patients would most likely
find it “relevant” that they no longer must wake up at night for
a second dose of medication.
Even if the second sense were the better reading, it would
remain to define the earlier referent. In Jazz’s view, that
referent is the “drug designated under section 360bb,” which in
this case is the active moiety of oxybate. For its part, Avadel
points out that subsection 360cc(a) prohibits the FDA from
approving another “application” after it approves an earlier
“application,” arguing as a result that the correct referent is
instead the drug product. Thus, it is far from clear from plain
meaning only what the correct referent would be—the active
moiety (oxybate), the drug product (calcium, magnesium,
potassium and sodium oxybate immediate-release oral
solution) or something in between (including consideration of
clinical superiority).
B. The Statutory History
“When Congress adopts a new law against the backdrop of
a longstanding administrative construction, this Court

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generally presumes the new provision should be understood to
work in harmony with what has come before.” Monsalvo v.
Bondi, 145 S. Ct. 1232, 1242 (2025) (citation modified); see
also Bragdon v. Abbott, 524 U.S. 624, 631 (1998) (“Congress’
repetition of a well-established term carries the implication that
Congress intended the term to be construed in accordance with
pre-existing regulatory interpretations.” (citations omitted));
Wash. All. of Tech. Workers v. DHS, 50 F.4th 164, 180 (D.C.
Cir. 2022) (“If a statute uses words or phrases that have already
received authoritative construction by a responsible
administrative agency, they are to be understood according to
that construction.” (citation modified) (quoting A. Scalia & B.
Garner, Reading Law 322 (2012)).
Jazz contends that changing “such drug” to “same drug”
in subsection 360cc(a) was a “modest” alteration made simply
to “clarify” the phrase and should be ascribed “no meaning.”
Appellant Br. 15–16; see also id. at 44. Jazz’s argument
conflicts with the Supreme Court’s guidance that “when
Congress amends legislation, courts must presume it intends
the change to have real and substantial effect.” Ross v. Blake,
578 U.S. 632, 641–42 (2016) (citation modified). We find
more plausible that the Congress incorporated and ratified the
FDA’s longstanding regulatory definition of “same drug.”
Granted, the Congress did not expressly incorporate that
definition by cross-referencing in the statute the regulatory
provision, as it has done in certain other provisions of the
FD&C Act. E.g., 21 U.S.C. § 355(c)(3)(E)(ii) (“active moiety
(as defined by the Secretary in section 314.3 of title 21, Code
of Federal Regulations (or any successor regulations))”). For
Jazz, “Congress’s failure to use such an express incorporation
of prior regulations . . . cuts against the proposed inference” of
incorporation. New York v. EPA, 413 F.3d 3, 19 (D.C. Cir.
2005), cited by Env’t Def. v. Duke Energy Corp., 549 U.S. 561,

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576 (2007). But that is not the end of the inquiry. New York’s
overall test asks whether there are “indications in the statutory
language or history to infer that Congress intended to
incorporate into a statute a preexisting regulatory definition.”
Id. Such indications abound here.
New York and Environmental Defense interpreted the
Clean Air Act’s (CAA) pollution control schemes regarding
New Source Performance Standards (NSPS) and Prevention of
Significant Deterioration (PSD). The NSPS provisions defined
the term “modification” whereas the later PSD provisions
employed that word “as defined in” the NSPS. Env’t Def., 549
U.S. at 566. Despite this cross-reference, implementing
regulations promulgated by the Environmental Protection
Agency (EPA) differed between the NSPS and PSD because
the EPA interpreted the statutory definition differently in each
context. The High Court was unconcerned by the incongruity.
“Although we presume that the same term has the same
meaning . . . in a single statute,” we “also understand that most
words . . . may be variously construed, not only when they
occur in different statutes, but when used more than once in the
same statute or even in the same section.” Id. at 574 (citation
modified). Because “[n]othing in the text or the legislative
history . . . suggest[ed] that Congress had details of regulatory
implementation in mind” when it added the cross-reference, the
Supreme Court held that the EPA retained discretion to define
the same term differently depending on the context in which it
appeared. Id. at 576.
Of course, the Supreme Court has emphasized that
“legislative history is not the law.” Azar v. Allina Health
Servs., 587 U.S. 566, 579 (2019) (quotation omitted). But in
any event neither the FDA nor Avadel relies on the threadbare
legislative history here for their common reading of the statute.
Instead, both the text and statutory history of the 2017

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amendments demonstrate that the Congress “had details of
regulatory implementation in mind” when it changed the Act.
Env’t Def., 549 U.S. at 576; see also Scalia & Garner, supra, at
256 (explaining that statutory history forms part of the context
of the statute and distinguishing it from legislative history).
The changes the Congress did make also tell us more about the
statute’s meaning than the earlier failed bills Jazz cites. See
Caraco Pharm. Labs., Ltd. v. Novo Nordisk A/S, 566 U.S. 399,
422 (2012) (warning of “the perils of relying on the fate of prior
bills to divine the meaning of enacted legislation”).
The parties agree that the Congress made the 2017
amendments in large part to codify in statute the FDA’s clinical
superiority requirement and supersede Depomed’s holding.
Thus, the Congress had in mind the FDA’s regulations, which
in 2013 had codified in regulation the FDA’s longstanding
practice imposing a clinical-superiority requirement for
orphan-drug exclusivity. 2013 Rule, 78 Fed. Reg. at 35,127,
35,132 (explaining the rationale for adding 21 C.F.R.
§ 316.34(c)). Equally, in subsection 360cc(d) the Congress
granted the FDA authority to promulgate regulations to
implement subsection 360cc(c), likewise making clear that it
was thinking about regulatory implementation when it enacted
the 2017 amendments. 21 U.S.C. § 360cc(d). This statutory
context lends support to the view that the Congress’s change
from “such drug” to “same drug” incorporated the FDA’s
longstanding regulatory definition of that term and not that it
was a mere housekeeping exercise.
This reading also fits with the old-soil canon of
construction, despite Jazz’s arguments to the contrary. “Where
Congress employs a term of art ‘obviously transplanted from
another legal source, it brings the old soil with it.’” George v.
McDonough, 596 U.S. 740, 746 (2022) (quoting Taggart v.
Lorenzen, 587 U.S. 554, 560 (2019)). That other legal source

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may be, for example, statute, regulation, common law, equity
or court practice. See, e.g., Waetzig v. Halliburton Energy
Servs., 145 S. Ct. 690, 697–98 (2025) (statute); George, 596
U.S. at 746 (regulation); Hansen, 599 U.S. at 778 (common
law); Taggart, 587 U.S. at 560 (equity); Kemp v. United States,
596 U.S. 528, 538–39 (2022) (state procedural rules). The
term’s meaning in the first context must also be “‘well-settled’
before the transplantation.” Sackett v. EPA, 598 U.S. 651, 683
(2023) (quoting Kemp, 596 U.S. at 539). Thus, “mere months”
in the context of “rapidly changing . . . regulatory programs” is
not enough, id. (quotation omitted), but “roughly 100 years” of
regulatory history is, George, 596 U.S. at 744; see also id. at
746–47.
In George, where the Congress “used an unusual term that
had a long regulatory history in th[at] very context”—namely
“clear and unmistakable error”—it codified the doctrine as
developed under earlier agency practice. 596 U.S. at 746. By
contrast, in Bruesewitz v. Wyeth LLC, 562 U.S. 223, 233–35
(2011), a statute that spoke about “unavoidable” side effects
did not incorporate a comment from the Second Restatement
of Torts that carved out “unavoidably unsafe products” because
“unavoidable” is “hardly a rarely used word” and there is no
“special significance to the term ‘unavoidable’ standing alone.”
And in Yellen v. Confederated Tribes of Chehalis Rsrv., 594
U.S. 338, 353 (2021), the Court rejected the notion that a 69-
word definition of an Indian tribe was somehow longhand for
the term of art “federally recognized tribe” in part because
“recognized” is “too common and context dependent a word to
bear so loaded a meaning.” Finally, the Eleventh Circuit found
the old-soil canon inapplicable to a statute otherwise similarly
worded to a regulation because a one-word variation between
them was “material” and thereby “suggest[ed] a variation in
meaning.” CSX Corp. v. United States, 18 F.4th 672, 681 (11th
Cir. 2021) (quoting Scalia & Garner, supra, at 170).

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This case is more like George than Bruesewitz, Yellen or
CSX. First, the FDA has used the same definition of “same
drug” in the ODA context since 1992—a quarter century before
the amendments—which is more like George’s 100-year
period of regulatory history than Sackett’s mere months in the
context of rapid change. Second, Jazz’s reliance on
Bruesewitz, Yellen and CSX requires inconsistently defining
the unit of analysis here as either broader or narrower than the
FDA’s reading. To draw support from Bruesewitz and Yellen,
Jazz adopts a narrow reading, arguing that the Congress simply
replaced “such” with “the same,” which is too commonly used
a word to support an inference of incorporation under the old-
soil canon. But later referencing CSX, Jazz offers a broad
reading, arguing for too much linguistic variation between the
amended statute and the regulation. Jazz points out that the
Congress replaced the entire phrase “such drug for such disease
or condition” with “the same drug for the same disease or
condition,” 2017 Act, § 607(a)(1), 131 Stat. at 1049, which in
turn varies from the FDA’s regulations defining the scope of
orphan-drug exclusive approval. See 21 C.F.R. § 316.31(a)
(using the phrase “the same drug for the same use or
indication” (emphasis added)); id. § 316.3(b)(12) (similar).
In Bruesewitz, the Supreme Court contrasted cases
“putting a definitive gloss” on the Restatement comment at
issue—which had used the adverbial “precise phrase
‘unavoidably unsafe product’”—with the statute’s use of the
adjectival form “unavoidable.” 562 U.S. at 234–35 (citing
cases). Here, by replacing “such” with “same,” the Congress
created the precise phrase “same drug” used in the FDA’s
regulatory definition. And this case is far from Yellen’s
implausible argument for retrofitting a 69-word-long definition
into a three-word term of art. Equally, there is no incongruity
with CSX because the term “same drug” does not vary across
the statute or the relevant regulation.

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Jazz also argues that the Congress would have changed
“disease or condition” to “use or indication” if it wanted to
incorporate the FDA’s regulatory definition of “same drug”
because several regulatory provisions employ the phrase “same
drug for the same use or indication” not “same drug for the
same disease or condition.” However, the term “use or
indication” appears in the FDA’s regulatory definition of
“exclusive approval” and its rule on the scope of orphan-drug
exclusivity but not in its definition of “same drug.” Contrast
21 C.F.R. §§ 316.3(b)(12) (“same drug for the same use or
indication”), 316.31(a) (same), with id. § 316.3(b)(14)
(defining “same drug”). And it makes sense that the Congress
would retain the phrase “disease or condition” because the
ODA is replete with that language rather than “use or
indication.”8 See generally 21 U.S.C. §§ 360aa–ee.
Relatedly, Jazz’s argument that a clinical superiority
requirement in subsection 360cc(a) would render the phrase
“same disease or condition” redundant fails because “disease
or condition” has a different meaning from “use or indication.”
Catalyst, 14 F.4th at 1306; see also id. at 1302 n.2, 1310
(explaining that indication typically means intended use,
8 The regulatory definition of “same drug” provides that being
“intended for the same use” is one of the conditions for a drug to be
the same as another drug. 21 C.F.R. § 316.3(b)(14). It follows that
a drug intended for a different use would be different from a drug
that is otherwise the same and therefore not barred by the latter’s
exclusivity period. Catalyst is not to the contrary. There, the parties
agreed the two drugs were the “same drug” so the Eleventh Circuit
interpreted only “same disease or condition,” not “same drug.” See
14 F.4th at 1301, 1306. Because the court determined that “same
disease or condition” was unambiguous, it held that the FDA erred
in interpreting that phrase to allow it to approve a drug for a different
use or indication. Id. at 1306–13.

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although approved indications may differ from intended off-
label uses); Caraco Pharm. Labs., 566 U.S. at 417 n.7
(explaining that an indication “refers generally to what a drug
does” (citing 21 C.F.R. § 201.57(c)(2))).9 In other words, the
amended subsection 360cc(a) exclusivity test includes
concepts of active moiety, intended use, clinical superiority—
which together make up the regulatory definition of “same
drug”—and disease or condition.
Thus, the Congress decided to incorporate fully the FDA’s
“same drug” regulatory definition and then made a second
change from “such” to “the same” to retain the parallel
sentence structure. Accordingly, the relevant unit of analysis
is “same drug,” which is a sufficiently “unusual term” with a
“long regulatory history” to support inferring incorporation
under the old-soil canon. George, 596 U.S. at 746.
C. Other Orphan Drug Act Provisions
The statutory context of the other section 360cc
subsections and the statutory scheme as amended in 2017
further reinforce our interpretation. Taking each of the other
subsections of section 360cc in turn, Jazz argues for the first
time on appeal that the FDA’s reading of the statute fits poorly
with section 360cc(b)—enumerating exceptions to
exclusivity—because it divests Jazz of its property interest in
orphan-drug exclusivity without comparable process. Despite
9 In this context, the disease or condition is narcolepsy and
Lumryz’s approved indication is the treatment of cataplexy or EDS
in adults with narcolepsy. These are not coextensive—narcolepsy
can occur without cataplexy, for example. And an indication can
change over time, as evidenced by the subsequent approvals of
Xyrem to treat cataplexy in adults, then EDS in adults and eventually
cataplexy and EDS in children.

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the FDA’s contention otherwise, Jazz has not forfeited this
argument by not raising it in district court. That is so because
Jazz is not introducing a standalone due process challenge.
Instead, in the context of the parties’ narrow dispute over
statutory interpretation, Jazz is offering another argument that
the FDA’s reading of subsection 360cc(a) is implausible
because of an alleged incongruity with the amount of process
provided in subsection 360cc(b). See Yee v. City of Escondido,
503 U.S. 519, 534 (1992) (“Once a federal claim is properly
presented, a party can make any argument in support of that
claim; parties are not limited to the precise arguments they
made below.” (citations omitted)). And despite the FDA’s
longstanding view that there is “no property right to exclusive
approval under the Orphan Drug Act,” 1992 Rule, 57 Fed. Reg.
at 62,083, that is, at most, only persuasive authority and we
must still independently interpret the statute, Loper Bright, 603
U.S. at 394 (citing Skidmore v. Swift & Co., 323 U.S. 134, 140
(1944)).
Jazz’s due process argument nevertheless fails because,
even assuming that Jazz has a property interest in its exclusivity
entitled to due process protections, it has not shown that the
process available under subsection 360cc(a) or provided to it
here is deficient. Due process requires “notice and opportunity
for hearing appropriate to the nature of the case.” Mullane v.
Ctrl. Hanover Bank & Trust Co., 339 U.S. 306, 313 (1950). To
determine whether a hearing is required before instead of after
the deprivation of a property interest, courts consider (1) the
private interest affected, (2) the risk of erroneous deprivation
of that interest and the probable value of additional procedures
and (3) the government’s interest, including the function
involved and the burden and cost of additional procedures. See
Mathews v. Eldridge, 424 U.S. 319, 333–35 (1976). The
Supreme Court has often found that post-deprivation
procedures are enough. Gilbert v. Homar, 520 U.S. 924, 930–

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31 (1997) (collecting cases). At times, only a very limited pre-
deprivation hearing is required, followed by a more
comprehensive post-deprivation hearing. Id. at 929 (discussing
Cleveland Bd. of Educ. v. Loudermill, 470 U.S. 532, 544–46
(1985)).
In declining to create by regulation a notice and hearing
process for exclusivity holders before approving a drug that the
FDA considers to be different, the FDA reasoned that
exclusivity holders had enough post-approval process because
they could petition the FDA under 21 C.F.R. § 10.30 or obtain
post-decisional review in federal court. 1992 Rule, 57 Fed.
Reg. at 62,083. Moreover, pre-decisional review would be
time-consuming, could be used for delay and would present
challenges due to the need to evaluate non-public information.
Id. The enumerated exceptions in subsection 360cc(b) are
distinguishable. As to the first exception, it makes sense to
require notice and the opportunity to submit views before
finding that an exclusivity holder cannot meet market needs
because the holder best knows its manufacturing capacity and
can assist the FDA’s decisional process. 21 U.S.C.
§ 360cc(b)(1). The second exception in no way deprives an
exclusivity holder of property rights because the holder
consents to the approval of the other drug. Id. § 360cc(b)(2).
In any event, here the FDA provided ample pre-decisional
process by reviewing written submissions and hearing an oral
presentation from Jazz’s counsel before going on to address
Jazz’s arguments for 20 pages in determining that Xywav’s
unexpired exclusivity did not bar its approval of Lumryz.
Turning to other subsections of section 360cc, Jazz
remarks that the phrase “clinical superiority” appears in
subsections 360cc(c) and (e) but not (a) and (b). True enough.
But the requirement to demonstrate clinical superiority in
paragraph 360cc(c)(1) tracks closely the FDA’s longstanding

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regulation on “recognition of exclusive approval” requiring
that a sponsor of a drug that is “otherwise the same”
demonstrate clinical superiority. 21 C.F.R. § 316.34(c). And
paragraph 360cc(c)(2) mirrors the FDA’s regulatory definition
of “clinical superiority.” Compare 21 U.S.C. § 360cc(c)(2),
with 21 C.F.R. § 316.3(b)(3). In turn, clinical superiority is
used in the FDA’s definition of “same drug.” 21 C.F.R.
§ 316.3(b)(14)(i). Thus, the references to clinical superiority
in other subsections only underscore that the Congress “plainly
was aware” that the FDA’s regulatory definition of “same
drug” employed the concept of clinical superiority. Hikvision
USA, Inc. v. FCC, 97 F.4th 938, 946 (D.C. Cir. 2024).
Jazz goes on to point out a redundancy in paragraph
360cc(c)(1) from interpreting the term “same drug” to include
the concept of “clinical superiority.” Under that paragraph, for
exclusive approval a drug sponsor of a drug that is “otherwise
the same” as an already approved drug must “demonstrate that
such drug is clinically superior” to the already approved drug
“that is the same drug.” 21 U.S.C. § 360cc(c)(1). Granted, it
would be redundant for “same drug” as used at the end of
paragraph 360cc(c)(1) to include a concept of clinical
superiority. And our “normal presumption” is that “when
Congress uses a term in multiple places within a single statute,
the term bears a consistent meaning throughout.” Allina
Health, 587 U.S. at 576 (citation omitted).
However, we “also understand that most words . . . may be
variously construed . . . when used more than once in the same
statute or even in the same section.” Env’t Def., 549 U.S. at
574 (citation modified). In context, it is clear that “same drug”
in paragraph 360cc(c)(1) refers back to the condition that a
drug be “otherwise the same.” Put differently, only a drug that
is otherwise the same as another drug and is not clinically
superior to the other drug is the same drug as the other drug.

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Subsection (a) simply uses the term “same drug” without more,
i.e., without breaking down sameness into “otherwise the
same” and “clinical superiority.” Thus, the Congress used a
clinical superiority test in subsection (a) because clinical
superiority vel non is part of what determines overall sameness,
as demonstrated by subsection (c).
Jazz further argues that the requirement in subsection
360cc(d) that any existing regulatory definitions applied in
implementing subsection 360cc(c) be consistent with the
statute cuts against inferring incorporation. But if, as we
conclude, the Congress incorporated the FDA’s regulatory
definition of “same drug” in subsection 360cc(a), it necessarily
would be consistent with the statute. Finally, subsection
360cc(e) also weighs in favor of inferring incorporation. By
adding reference to the FDA’s longstanding requirement at the
designation stage that a sponsor provide a plausible hypothesis
of clinical superiority to an already approved drug, the 2017
amendments evince the Congress’s intent to adopt the FDA’s
orphan-drug designation process set forth in 21 C.F.R.
§§ 316.20, 316.25. Those regulations require a sponsor of a
drug that is “otherwise the same” as an already approved drug
to present a plausible hypothesis of clinical superiority, which
is consistent with the FDA’s and Avadel’s reading of
subsection 360cc(a), further revealing the Congress’s
familiarity with the regulations.
Beyond the context of the other subsections in section
360cc, Jazz’s statutory interpretation fits poorly with the
statutory scheme as amended in 2017. For Jazz, the Congress
wanted to limit serial exclusivity or “evergreening” by
superseding Depomed but also wanted to limit the FDA’s
practice of approving clinically superior drugs notwithstanding
an exclusivity period for a drug that is otherwise the same. But
as the district court pointed out, it makes little sense for the

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Congress to take clear action to undo a district court’s holding
constraining the FDA’s authority while sub silentio repudiating
the FDA’s longstanding regulations on the scope of
exclusivity. Jazz Pharms., 2024 WL 4625731, at *16.
Instead, the Congress acted both to prevent evergreening
and to endorse the FDA’s longstanding regulations allowing
approval of a clinically superior drug during another drug’s
exclusivity period. That understanding of the Congress’s
action more plausibly balances its earlier findings both that
more “promising orphan drugs” are needed and that
“incentives” are needed to develop such drugs. Orphan Drug
Act, § 1(b)(5), (6), 96 Stat. 2049. Under this scheme, sponsors
are incentivized to develop innovative treatments for rare
diseases by the prospect of an exclusivity period while, at the
same time, other drugmakers that demonstrate their drug is
more effective, safer or otherwise provides a major
contribution to patient care are not blocked from entering the
market either. That is the balance that the Congress ratified by
incorporating the FDA’s regulatory definition of “same drug”
in subsection 360cc(a).
In sum, both the statutory context and the regulatory
scheme that the 2017 amendments endorsed support the FDA’s
authorization to approve Lumryz’s marketing despite the
ongoing exclusivity period for Xywav.
* * *
For the foregoing reasons, the judgment of the district
court is affirmed.
So ordered.

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