[Federal Register Volume 88, Number 15 (Tuesday, January 24, 2023)]
[Rules and Regulations]
[Pages 4086-4087]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-01179]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 316

[Docket No. FDA-2011-N-0583]


Clarification of Orphan-Drug Exclusivity Following Catalyst 
Pharms., Inc. v. Becerra; Notification

AGENCY: Food and Drug Administration, Department of Health and Human 
Services (HHS).

ACTION: Notification.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is publishing 
this notification in light of the recent decision by the U.S. Court of 
Appeals for the Eleventh Circuit in Catalyst Pharms., Inc. v. Becerra. 
The Catalyst decision addressed the orphan-drug exclusivity provision 
of the Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by 
the Orphan Drug Act and subsequent amendments, and concluded that FDA's 
approval of Jacobus Pharmaceutical Company's (Jacobus's) drug (the drug 
at issue in the litigation) must be set aside. Consistent with the 
court's decision, FDA has set aside its approval of Jacobus's drug. 
This notification announces that, at this time, while complying with 
the court's order in Catalyst, FDA intends to continue to apply its 
regulations tying the scope of orphan-drug exclusivity to the uses or 
indications for which a drug is approved to matters beyond the scope of 
that order.

DATES: The policy set out in this document is effective January 24, 
2023.

FOR FURTHER INFORMATION CONTACT: Aaron Friedman, Office of Orphan 
Products Development, Food and Drug Administration, 10903 New Hampshire 
Ave., Silver Spring, MD 20993, 301-796-2989.

SUPPLEMENTARY INFORMATION: 

I. Background

    On September 30, 2021, the U.S. Court of Appeals for the Eleventh 
Circuit issued a decision in Catalyst Pharms., Inc. v. Becerra 
(Catalyst), 14 F.4th 1299 (11th Cir. 2021).
    At the time of the litigation, Jacobus and Catalyst Pharmaceuticals 
(Catalyst) each had orphan-drug designation for the drug amifampridine 
for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). In 
November 2018, FDA approved Catalyst's drug for the treatment of LEMS 
in adults. FDA recognized Catalyst's drug as eligible for orphan-drug 
exclusivity for its only approved indication--the treatment of LEMS in 
adults.
    In May 2019, FDA approved Jacobus's drug for the treatment of LEMS 
in children. In approving Jacobus's drug, FDA followed its longstanding 
rule, codified in its regulations, that the orphan-drug exclusivity for 
Catalyst's drug protected only the approved use or indication within 
the designated disease. See 21 CFR 316.3(b)(12), 316.31(a)-(b). The 
regulation in 21 CFR 316.31(b) states, in part, that: ``Orphan-drug 
exclusive approval protects only the approved indication or use of a 
designated drug.'' \1\
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    \1\ Emphasis added. Other regulatory provisions also reflect the 
understanding that orphan-drug exclusivity is tied to the use or 
indication for which the drug was approved. See Sec.  316.3(b)(12) 
(stating that ``no approval will be given to a subsequent sponsor of 
the same drug for the same use or indication for 7 years'' (emphasis 
added)); see also id. Sec.  316.31(a) (explaining that FDA may 
approve an orphan drug for ``select indication(s) or use(s) within 
the rare disease or condition for which the drug was designated'' 
and that ``FDA will not approve another sponsor's marketing 
application for the same drug for the same use or indication before 
the expiration of 7 years from the date of such approval'' (emphases 
added)).
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    In June 2019, Catalyst filed suit against FDA, challenging FDA's 
approval of Jacobus's application under the Administrative Procedure 
Act, 5 U.S.C. 701-706. Among other things, Catalyst argued that the 
phrase ``same disease or condition'' in the Orphan Drug Act, 21 U.S.C. 
360cc(a), unambiguously prohibited FDA from approving Jacobus's drug 
application. Specifically, Catalyst argued that the Orphan Drug Act 
required orphan-drug exclusivity to extend to all uses or indications 
within the orphan-designated disease or condition--even uses or 
indications for which Catalyst had not received approval, such as the 
treatment of LEMS in children.
    The district court rejected Catalyst's argument that the Orphan 
Drug Act required orphan-drug exclusivity to apply to all uses or 
indications within the orphan-designated disease or condition. The 
district court concluded that, given the context and the overall 
statutory scheme, the statute was ambiguous on the disputed issue, and 
that FDA had reasonably interpreted the statute to tie orphan-drug 
exclusivity to the uses or indications for which the drug was approved.
    On appeal, the U.S. Court of Appeals for the Eleventh Circuit 
reversed. The circuit court concluded that the phrase ``same disease or 
condition'' in the Orphan Drug Act, 21 U.S.C. 360cc(a), unambiguously 
foreclosed FDA's interpretation of the provision. Accordingly, the 
circuit court held that orphan-drug exclusivity for Catalyst's

[[Page 4087]]

drug blocked FDA's approval of Jacobus's drug for all uses or 
indications within the orphan-designated disease (LEMS)--even though 
Catalyst's drug was approved at that time only for use in the treatment 
of LEMS in adults. The court concluded that FDA's approval of Jacobus's 
drug for the treatment of LEMS in children must be set aside. 
Consistent with the court's decision, the Agency set aside the approval 
of Jacobus's drug.

II. Orphan-Drug Exclusivity

    The Agency is issuing this statement to address the uncertainty 
created by the circuit court's decision in Catalyst. The court ordered 
FDA to set aside its approval of Jacobus's drug, and FDA has set aside 
that approval. This notification announces that, at this time, in 
matters beyond the scope of that court order, FDA intends to continue 
to apply its existing regulations tying orphan-drug exclusivity to the 
uses or indications for which the orphan drug was approved. The Agency 
believes that this approach is appropriate for several reasons. FDA 
continues to believe that the statutory text does not unambiguously 
require that orphan-drug exclusivity extend to the entire disease or 
condition for which a drug received orphan-drug designation if the drug 
is only approved for some uses within that disease or condition. 
Further, FDA believes that its statutory interpretation embodied in its 
regulations best advances the Orphan Drug Act's purposes, appropriately 
balancing the need to incentivize the development of drugs for rare 
diseases and conditions with the need to provide patient access to 
orphan drugs. The regulations accomplish this by tying the scope of 
orphan-drug exclusivity to only the approved use or indication of the 
drug, which permits other sponsors to obtain approval of the drug for 
uses or indications within the same orphan-designated disease or 
condition that have not yet been approved (i.e., that are ``new''). 
Under the regulations, a drug approved for a new use or indication 
within the same orphan-designated disease or condition may also be 
eligible for orphan-drug exclusivity for such use or indication. These 
regulations incentivize sponsors to continue to develop a drug for use 
in all persons affected by a rare disease or condition. Thus, FDA 
believes that continued adherence to its validly promulgated 
regulations will best serve the public health by facilitating patient 
access to orphan drugs, especially for difficult-to-study patients such 
as young children.

III. Conclusion

    For the above reasons, at this time, the Agency intends to continue 
to apply its longstanding regulations tying the scope of orphan-drug 
exclusivity to the uses or indications for which the orphan drug was 
approved.

    Dated: January 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-01179 Filed 1-23-23; 8:45 am]
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