
[Federal Register Volume 79, Number 246 (Tuesday, December 23, 2014)]
[Rules and Regulations]
[Page 76888]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-29920]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 316

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


Policy on Orphan-Drug Exclusivity; Clarification

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification; clarification on policy.

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SUMMARY: The Food and Drug Administration (FDA) is publishing this 
document to clarify its policy regarding certain aspects of orphan-drug 
exclusivity. This document is being published because of a recent court 
decision interpreting provisions of the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act), as amended by the Orphan Drug Act.

DATES: Effective December 23, 2014.

FOR FURTHER INFORMATION CONTACT: Gayatri R. Rao, Office of Orphan 
Products Development, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 32, Rm. 5271, Silver Spring, MD 20993, 301-796-8660.

SUPPLEMENTARY INFORMATION:

I. Background

    After a designated orphan drug is approved, section 527 of the FD&C 
Act (21 U.S.C. 360cc) generally prohibits the Food and Drug 
Administration (FDA or the Agency) from approving another such drug for 
the same disease for 7 years. Regulations interpreting this provision 
were proposed in 1991 (January 29, 1991, 56 FR 3338) and made final in 
1992 (December 29, 1992, 57 FR 62076). In 2011, FDA issued a proposed 
rule (October 19, 2011, 76 FR 64868) to amend these regulations to 
clarify certain regulatory language and propose areas of minor 
improvement regarding orphan-drug designation and orphan-drug 
exclusivity; these were finalized in 2013 (June 12, 2013, 78 FR 35117). 
These regulations are codified under part 316 (21 CFR part 316).
    FDA has interpreted section 527 of the FD&C Act and its regulations 
such that the Agency will not recognize orphan-drug exclusivity for a 
drug when it has previously approved the same drug for the same use or 
indication in a rare disease or condition. Sec. Sec.  316.3(b)(12); 
316.31(a). A drug will not be considered the same as a previously 
approved drug if, at the time of approval, the sponsor has provided 
evidence that its drug is ``clinically superior'' to the previously 
approved drug, that is, the drug is more effective, safer, or makes a 
major contribution to patient care. Sec.  316.3(b)(3). Accordingly, the 
sponsor of an orphan-designated drug that is the same as a previously 
approved drug, as defined in Sec.  316.3(b)(14), is required to 
demonstrate that its drug is clinically superior to the previously 
approved drug in order for its drug to be eligible for orphan-drug 
exclusivity upon approval.
    The Agency's interpretation of section 527 of the FD&C Act has been 
the subject of legal action in Depomed v. HHS et al., Civil Action No. 
12-1592 (KBJ) (D.D.C. September 5, 2014). Depomed has not demonstrated 
that GRALISE (gabapentin) is clinically superior to a previously 
approved drug, Pfizer's NEURONTIN (gabapentin). Accordingly, under the 
relevant regulations, GRALISE is the same drug as NEURONTIN, because it 
contains the same active moiety (gabapentin), was approved for the same 
use (post-herpetic neuralgia), and was not demonstrated to be 
clinically superior to NEURONTIN. Nevertheless, the Depomed court held 
that FDA must recognize orphan-drug exclusivity for GRALISE for the 
treatment of post-herpetic neuralgia. Following the Depomed decision, 
under the court's order, FDA recognized orphan-drug exclusivity for 
GRALISE for the treatment of post-herpetic neuralgia.

II. Orphan-Drug Exclusivity

    In consideration of any uncertainty created by the court's decision 
in Depomed, the Agency is issuing this statement. It is the Agency's 
position that, given the limited terms of the court's decision to 
GRALISE, FDA intends to continue to apply its existing regulations in 
part 316 to orphan-drug exclusivity matters. FDA interprets section 527 
of the FD&C Act and its regulations (both the older regulations that 
still apply to original requests for designation made on or before 
August 12, 2013, as well as the current regulations) to require the 
sponsor of a designated drug that is the ``same'' as a previously 
approved drug to demonstrate that its drug is ``clinically superior'' 
to that drug upon approval in order for the subsequently approved drug 
to be eligible for orphan-drug exclusivity.

    Dated: December 17, 2014.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2014-29920 Filed 12-22-14; 8:45 am]
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