[xii][i] See 42 U.S.C. ยง 262(m) (Section 351 of the Public Health Service Act). Notice that under ยง 262(m)(1), the rules for submitting pediatric studies are the same for both drugs and biologics under ยง 505A of the Federal Food, Drug, and Cosmetic Act (FDCA) (codified as 21 U.S.C. ยง 355a). More precisely, ยง 262(m)(1) carves out the exclusivity benefits in ยงยง 505A (b)-(c) for drugs, which are then re-inserted as ยงยง 262(m)(2)-(3) as applicable to biologics given the different exclusivity periods.
search Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act, U.S. Food & Drug Administration (May 17, 2023).Guidance โ Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations, U.S. Food & Drug Administration (May 17, 2023).See Guidance โ How to Comply with the Pediatric Research Equity Act, U.S. Food & Drug Administration (September 2005).88 Fed. Reg. 31766.See 21 CFR 201.23, 201.57(c)(7)(ii)(a). FDA defines โpediatric populationโ as the age group from birth to younger than seventeen years of age. See21 CFR 201.57(c)(9)(iv)(A); Regulatory Considerations Guidance at FN 1.See Unofficial Guidance โ Understanding Unapproved Use of Approved Drugs โOff Labelโ, U.S. Food & Drug Administration (Feb. 5, 2018).See Status Report โ The Pediatric Exclusivity Provision, U.S. Food & Drug Administration (Jan. 2001); FDAMA Public Law 105-115, 111 Stat. 2296 (Nov. 21, 1997).21 U.S.C. 355a(b),(c).See Status Report โ The Pediatric Exclusivity Provision at FN 8.See Status Report โ BPCA and PREA, U.S. Food & Drug Administration (July 2016).See 21 U.S.C. 355a(b),(c). Regulatory Considerations Guidance at p. 24.21 U.S.C. 355c(a)(1).21 U.S.C. 355c(a)(2)(A).21 U.S.C. 355c(a)(3)-(4), (k). 21 U.S.C. 355c(a)(3)(A).See Guidance โ Rare Pediatric Priority Review Vouchers, U.S. Food & Drug Administration at p. 18 (July 2019).See id. At p. 19;Pediatric Drug Development: Challenges and Opportunities, National Library of Medicine (December 28, 2018).See Regulatory Considerations Guidance at p. 4.See id. at p. 21.See id. at p. 2.See id.See Scientific Considerations Guidance. Despite the fact that the PREA requirements typically do not apply to orphan drugs, a sponsor that submits an application to market a drug for an orphan indication may still be eligible to qualify for pediatric exclusivity. Additionally, if orphan designation is granted after approval of a drug, and post-marketing studi
Case Name:Otsuka Pharmaceutical Co., Ltd. v. Burwell, Civ. No. GJH-15-852, 2015 U.S. Dist. LEXIS 68230 (D. Md., May 27, 2015) (Hazel, J.)Drug Product and Patent(s)-in-Suit:Abilifyยฎ (aripiprazole); N/ANature of the Case and Issue(s) Presented:The issue here concerns whether the FDA was precluded from approving generic versions of Abilifyยฎ until its orphan drug exclusivity expires in December 2021 because 21 U.S.C. ยง 355a(o) does not permit such pediatric information to be omitted from a generic drugโs label. Otsuka first obtained approval from the FDA to manufacture and market Abilify on November 15, 2002.
On May 27, 2015, the U.S. District Court for the District of Maryland granted FDA and the Defendant-Intervenors summary judgment against Otsuka Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Development and Commercialization, Inc., and Otsuka America Pharmaceutical, Inc. (collectively โOtsukaโ), holding that FDA appropriately interprets the Food, Drug, and Cosmetic Act (โFD&C Actโ) when it grants abbreviated new drug applications (โANDAsโ) by carving out information that is protected by orphan drug exclusivity from the ANDA labeling, so long as the drug โremains safe and effective for the remaining non-protected conditions of useโ without the carved-out language.As previous discussed (see the most recent blog here), Otsuka sought to stop the approval of generic versions of Abilifyยฎ (aripiprazole) by arguing that 21 U.S.C. ยง355a(o) permits FDA to allow generic drugs to omit pediatric labeling in only two scenarios: a) when the branded drug is protected by a patent and b) when the drug has non-orphan drug exclusivity. Abilifyยฎโs blocking Patent No. 5,006,528 (โthe โ528 patentโ) expired on April 20, 2015, and Otsuka had already attempted to enjoin generic entry based on some of its other patents, but had so far been unsuccessful.
With this in mind, Judge Urbina addressed each of FDA's decisions: FDA's Decision that the Effective Date of the Federal Circuit's Ruling is the Date it Issues its MandateJudge Urbina agreed with FDA's decision that Pfizer is entitled to pediatric exclusivity, though he used different reasoning to get there. He reasoned that because 21 USC 355a(c)(2)(B) is silent "as to the particular court which may determine the patent dispute," the January 24, 2006 Northern District of Illinois Order in Pfizer v. Apotex triggered Pfizer's pediatric exclusivity. And, moreover, that decision "is effective and remains so during the pendency of the appeal unless the district court's judgment is stayed or until the Federal Circuit issues its mandate."
Mylanโs ANDA product infringes the โ229 patent. Pursuant to 35 U.S.C. ยง 271(e)(4)(A), the effective date of any final approval of Mylanโs ANDA product shall be a date not earlier than Aug. 18, 2019, the date of expiration of the โ229 patent together with a period of pediatric exclusivity awarded to Novartis under 21 U.S.C. ยง 355a. Pursuant to 35 U.S.C. ยง 271(e)(4)(B), Mylan is enjoined from engaging in the commercial manufacture, use, offer for sale, sale, in the US and/or importation into the US of its ANDA product until Feb. 18, 2019.
If FDA once again denies Amgen pediatric exclusivity, then weโll probably see the parties back in court. Regardless of whether FDA decides to grant pediatric exclusivity, or if the exclusivity is ordered granted by a court, the Order states that โany future decision requiring FDA to accept Amgenโs study reports for Sensipar (cinacalcet) under 21 U.S.C. ยง 355a(d)(3) . . . shall be deemed to relate back, nunc pro tunc, to May 22, 2017, the date of FDAโs initial determination.โ As we previously explained, a โrelate backโ decision is important here, because pediatric exclusivity extends all other types of Orange Book-listed patent and non-patent marketing exclusivity an application holder may have under the FDC Act, provided that at the time pediatric exclusivity is granted there is not less than nine months of term remaining.
This five-year period of exclusivity was extended until December 24, 2005, due to Cephalonโs status as an orphan drug. 3 In March 2006, Cephalon obtainedpediatric exclusivity, which added an additional six months of exclusivity. 21 U.S.C. ยง 355a(c). Thus, in the absence of the โ516 patent, Cephalonโs exclusivity period for modafinil would have ended on June 24, 2006.
These rulings have been seen as a success for the FDA as the court held that the federal agency was correct in its interpretation of the Federal Food, Drug, and Cosmetic Act (FDCA) in a manner to allow the sale of generic versions of Abilify with labeling that omits Otsukaโs exclusivity protected indication for Touretteโs syndrome. The suit revolves around FDCA provision 21 U.S.C. ยง355a(o), which states that proposed generics โshall not be considered ineligible for approvalโฆ on the basis that the labeling of the drug omits a pediatric indication or any other aspect of labeling pertaining to pediatric use when the omitted indication or other aspect is protected by patent or by exclusivityโฆโ While Otsuka argued that this provision only allows the FDA to omit pediatric information from generic drug labels in these two instances, the FDA contended that this provision prevents them from denying approvals based on these omissions, but does not prevent them from allowing omissions in other instances. The court responded to this argument by holding that โOtsuka cannotโฆ turn a provision limiting FDAโs disapproval authority into a provision limiting its approval authority.โ
In order to make any generic Abilify approval decisions, however, the agency may also need to consider other potentially important parts of the regulatory scheme, which Otsukaโs letter does not take into account. These may include the scope of the permissible difference to the same labeling requirement in the statute (see 21 U.S.C. ยง 355(j)(2)(A)(v)), regulations (see 21 C.F.R. ยง 314.94(a)(8)(iv)), and applicable case law, as well as the effect of 21 U.S.C. ยง 355A(o) on labeling that is protected by both Hatch-Waxman and orphan exclusivity. FDA may also deem it important to consider arguments potentially raised by generic drug sponsors.