On Jan 23, 2018, U.S. District Judge Randolph D. Moss upheld the FDA’s decision that Amneal Pharmaceuticals LLC forfeited 180-day exclusivity by failing to win approval within 30 months of seeking approval.
The plaintiff in this case, Amneal Pharmaceuticals LLC (“Amneal”), was the first manufacturer to file an ANDA to market a generic version of Namenda XR(memantine hydrochloride extended release capsules), with P-IV certification. Amneal did not, however, obtain tentative approval for its ANDA within the 30-month window. As a result, Amneal’s eligibility for the 180 days of generic market exclusivity turns on whether its failure to obtain timely approval was “caused by a change in or a review of the requirements for approval of the” ANDA. In proceedings before the Food and Drug Administration (“FDA”), Amneal argued (1) that the delay was caused by the FDA’s demand for data from a commercial-scale batch of the drug and (2) that this demand constituted a change in a requirement for approval of the ANDA.
On June 10, 2013, Amneal submitted an ANDA seeking approval to market a generic version of Namenda XR-a medication intended to treat moderate to severe dementia of the Alzheimer’s type. In its ANDA, for purposes of commercial sales, Amneal proposed to produce much larger batches of 1,000,000 capsules and, in doing so, to blend up to six different lots of ER beads with two different lots of iR beads which are different than that of pilot batches. On September 10, 2014, the FDA sent Amneal a letter identifying a number of substantive deficiencies with Amneal’s ANDA. Specifically FD Asked to submit all the required [chemistry, manufacturing, and controls] information for the production of a 7 mg and 28 mg Memantine HCl lot of the size intended for commercial distribution. Overall, the FDA reviewers concluded that, “[d]ue to the complexity of the proposed process, combined with the deficiencies noted in the review,” and because “mixing multiple lots of ER and IR beads could induce additional deviations not observed during the manufacture of the [pilot] lots that may require additional control,” Amneal “should submit a scale up batch before approval.”
The said process took eight months to complete. But, upon review of the additional data, the FDA noted several issues. Most problematically, Amneal’s proposed IR-to-ER bead ratio “was not followed in the newly submitted batches” and, while “some latitude in this ratio [was] required [,] … the deviation … was not justified.” Acknowledging that combining multiple lots of IR and ER beads introduced additional “complexity” into the production process, which “may result in calculation errors,” Amneal proposed an “additional control … to ensure [that the] accurate dose of the drug product is administered to the patients.” The FDA, however, concluded that the additional control was “not acceptable,” and it, accordingly, “recommend [ed]” that Amneal “scale down the proposed commercial batch size to a size with a constant, reproducible capsule filling weight as well as a constant bead type composition.” Amneal accepted the FDA’s recommendation to scale down the proposed commercial-scale batches-from 1,000,000 capsules to 150,000 capsules-thus resolving the issue and clearing the way for approval of its ANDA.
In the meantime, however, Amneal experienced a further delay: an “Import Alert” was issued on October 15, 2015, to the supplier of Amneal’s active pharmaceutical ingredient (“API”). Amneal sought approval to use a different API supplier, and sought to amend its ANDA to substitute the new supplier in place of the one that was previously identified. Amneal’s troubles continued, however, and, on December 7, 2015, the FDA notified Amneal that its proposal to change its source of API was “not acceptable” because Amneal had yet to demonstrate bioequivalence. Amneal provided the missing data demonstrating bioequivalence using the new source of API on February 25, 2016, but FDA chemistry reviewers raised additional deficiencies in Amneal’s product, which were not addressed until August 11, 2016 and September 15, 2016. Finally, on September 28, 2016, the FDA tentatively approved Amneal’s ANDA. By that time, however, the 30-month period for approval had expired on December 10, 2015.
On same day Sep 28, 2016 the FDA tentatively approved Amneal’s ANDA, the agency issued a 17-page letter decision concluding that Amneal had forfeited the 180-day period of exclusivity. In its appeal, most significantly, Amneal disagreed with the FDA’s conclusion that the agency’s “demand for commercial-scale data” did not constitute a “change in a requirement for approval of the application.” Court under Chevronframework held that the FDA did not violate the plain terms of the statute or act unreasonably in deciding that neither of the regulatory steps identified by Amneal constituted “a change in or review of[a] requirement for approval of’ Amneal’s ANDA.
Court said that Amneal presumes that the requirements for the FDA to receive an ANDA mirror the requirements for approval. But the FDA has explained and Amneal has not identified any evidence to the contrary-that the two requirements, even if closely related; are distinct. Understood in this light, nothing in the statutory text supports Amneal’s reading, much less unambiguously forecloses the FDA’s approach. Court further sided with FDA & said that to the contrary, the forfeiture decision makes clear that the FDA’s prior requests for data from commercial-scale batches were “application specific” requests“made during the substantive review of the ANDA by the chemistry reviewers,” based on the applicant’s failure to “demonstrate a good understanding of its product and manufacturing process” and failure to “have appropriate in-process controls.” Thus the FDA’s prior requests merely represented case-by-case evaluations of whether data from a commercial-scale batch was needed to address a case-specific deficiency. Accordingly, the FDA’s conclusion that its request for commercial-scale data did not constitute a “change in … requirements for approval” such that Amneal was exempt from the 30-month forfeiture date was both reasoned and consistent with agency precedent.
As on today, there are 07 ANDAs have been approved by USFDA including Amneal. With respect to litigation, on December 11, 2017, Federal Circuit affirmed district court’s decision of indefiniteness. [Forest Labs, Inc. v. Teva Pharm. USA, Inc., Nos. 2016-2550, 2016-2553, 2017 WL 6311688 (Fed. Cir. Dec. 11, 2017)]. Although the Federal Circuit’s mandate has yet to issue, and a petition for rehearing is pending, a final affirmance in the Teva case would open the door for generic manufacturers with approved ANDAs to market their products.