in vitro laboratory data and data from “clinical experience” with the drug (21 C.F.R. § 316.20(b)(2));(5) Clarified that FDA will notify the sponsor in writing whenever FDA considers a designation request voluntarily withdrawn (21 C.F.R. § 316.24(a));(6) Clarified that the reasons for denying a designation request identified in 21 C.F.R. § 316.25 are not exhaustive and that FDA can refuse to grant a designation request if the drug is otherwise ineligible for designation under Part 316; (7) Stated that, if a drug loses designation after the effective date of this final rule (either because the sponsor voluntarily withdrew designation or because FDA revoked designation), FDA’s publicly available posting of designated drugs will include identification of the fact that the drug is no longer designated and the date it lost designation (21 C.F.R. § 316.28);(8) Clarified that the scope of orphan drug exclusivity is limited to the indications or uses for which the designated drug is approved (21 C.F.R. § 316.31(a) and (b)); and(9) Clarified that a designated drug that is otherwise the same as a previously approved drug will receive orphan drug exclusivity upon approval only if the sponsor demonstrates that its drug is clinically superior to the previously approved drug.Below we discuss some of the preamble statements in the final rule that we think merit special attention.Demonstration of an “Orphan Subset” of a Non-Rare Disease or Condition. FDA stated that it carefully considered whether to retain “medically plausible” in the discussion of the “orphan subset” concept.

Director, Frank J. Sasinowski) on the flexibility in FDA’s review of potential treatments for patients with rare diseases.FDA’s proposed rule addresses 13 specific issues (some of which we touched on earlier this week when we reported on an OOPD Standard Operating Procedures and Policies):(1) Demonstration of an appropriate “orphan subset” of persons with a particular disease or condition that otherwise affects 200,000 or more persons in the United States, for the purpose of designating a drug for use in that subset (21 C.F.R. § 316.20(b)(6));(2) Eligibility for orphan-drug designation of a drug that is otherwise the same drug for the same orphan indication as a previously approved drug (21 C.F.R. §§ 316.3(b)(3), 316.20(a), and 316.20(b)(5));(3) Eligibility for multiple orphan-drug exclusive approvals when a designated orphan drug is separately approved for use in different subsets of the rare disease or condition (21 C.F.R. § 316.31);(4) Requirement for demonstrating clinical superiority for the purpose of orphan-drug exclusive approval (21 C.F.R. § 316.3(b)(3)(iii));(5) Requirement for submitting the name of the drug in an orphan-drug designation request (21 C.F.R. § 316.20(b)(2));(6) Required drug description and scientific rationale in a designation request (21 C.F.R. § 316.20(b)(4));(7) Required information in a designation request relating to the sponsor's interest in the drug (21 C.F.R. § 316.20(b)(9));(8) Timing of a request for orphan-drug designation (21 C.F.R. § 316.23(a));(9) Responding to a deficiency letter from FDA on an orphan-drug designation request (21 C.F.R. § 316.24(a));(10) FDA publication of information regarding designated orphan drugs (21 C.F.R. § 316.28);(11) FDA recognition of orphan drug exclusive approval (21 C.F.R. § 316.34(c));(12) Miscellaneous terminology changes (21 C.F.R. Part 316); and(13) OOPD address change (21 C.F.R. § 316.4). Below we note some of the proposed changes and cl

The bottom line is that, while FDA agreed to comply with the 11th Circuit’s decision for the specific case, the agency said that it plans to continue its policy of applying “its regulations tying the scope of orphan-drug exclusivity to the uses or indication for which a drug is approved to matters beyond the scope of the order.”2The Notification went into effect on January 24, 2023.SummaryBoth Jacobus Pharmaceutical Company and Catalyst Pharmaceuticals 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 granted Catalyst’s drug orphan-drug exclusivity for the adult indication.Shortly thereafter, FDA approved Jacobus’s drug for the treatment of LEMS in children.FDA followed its longstanding rule, codified in its regulations (e.g., 21 C.F.R. §316.31), that the orphan-drug exclusivity for Catalyst’s drug protected only the approved use or indication within the designated disease (i.e., adult patients).Catalyst sued FDA, challenging approval of Jacobus’s application, arguing that the statute prohibited FDA from approving Jacobus’s new drug application. 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 found for FDA, holding that the agency reasonably interpreted the statute to tie orphan-drug exclusivity to the uses or indications for which the drug was approved.On appeal, the 11th Circuit reversed, noting that the phrase, “same disease or condition” in the Orphan Drug Act, unambiguously foreclosed FDA’s interpretation. Therefore, orphan-drug exclusivity for Catalyst’s drug blocked FDA’s appr

nnovators, generic and biosimilar applicants, and their investors will need to consider the impact of the IRA’s drug price negotiations on drug discovery and development, sources of investment, patent litigation and settlement, and new opportunities for competitor drug approval and market entry. We can expect significant interest of all of these stakeholders in the regulations from CMS that are likely forthcoming in order to implement the complex framework of the IRA statute.Inflation Reduction Act of 2022, Pub. L. No. 117-169. Medicare Part B drugs will not be eligible for selection until 2028.An authorized generic does not constitute a generic or biosimilar under this provision.Compare Food, Drug and Cosmetic Act (FDCA) § 505(j) (providing a five-year exclusivity period for small-molecule drugs), with Patient Protection and Affordable Care Act, 42 U.S.C. § 262(k) (providing a 12-year exclusivity period for biologics).See Orphan Drug Act, Pub. L. No. 97-414, 96 Stat. 2049 (1983). See 21 C.F.R. § 316.31 (2011); FDCA § 505(j).See, e.g., Impact of NIH Research: Our Society, NIH (May 1, 2018), https://www.nih.gov/about-nih/what-we-do/impact-nih-research/our-society; What We Do:Mission and Goals, NIH (July 27, 2017), https://www.nih.gov/about-nih/what-we-do/mission-goals. See, e.g., Letter from Congresswoman Cathy McMorris Rodgers and Congressman Kevin Brady to Sec’y of U.S. Dep’t of Health and Human Servs. (Aug. 29, 2022), https://republicans-energycommerce.house.gov/wp-content/uploads/2022/08/08.29.22-Letter-to-HHS-re-IRA22-Drug-Pricing-Implementation.pdf.

By regulation, FDA has therefore limited the scope of orphan exclusivity only to the approved “indication or use,” even if the underlying designation is for a broader “disease or condition.” 21 CFR 316.31(a). FDA’s interpretation has now been called into question by the Eleventh Circuit’s decision in favor of Catalyst.On November 12, 2009, Catalyst obtained designation for Firdapse (amifampridine phosphate) as an orphan drug for the treatment of Lambert-Eaton myasthenic syndrome (LEMS).

See id. § 316.3(b)(14).If the new drug later obtains marketing approval for a use or indication within the rare disease or condition for which it received orphan drug designation, the FDA will determine if the drug is eligible for orphan drug exclusivity. See 21 C.F.R. § 316.31(a). In this situation, to receive exclusivity, the sponsor of the new drug must show that its drug is clinically superior to the “same” previously-approved drug for the same rare disease or condition.