Addressing a question of statutory interpretation regarding the meaning of the applicable exclusivity provisions of the Federal Food, Drug, and Cosmetic Act (FDCA), the US District Court for the District of Columbia determined the US Food and Drug Administration (FDA) reasonably interpreted that the FDCA’s three-year exclusivity bar blocks only subsequent applications for drugs with the same active moiety. Otsuka Pharmaceutical Co., Ltd. V. Burwell, Civil Action No. 15-1688 (D.D.C. July 28, 2016) (Jackson, J.)

In 2002, the FDA approved a new drug application by Otsuka for Abilify® tablets, an orally administered drug for the treatment of several mental disorders, including schizophrenia. The active moiety of Abilify tablets is the molecule aripiprazole, which is also the drug’s active ingredient. Because the FDA had never before approved a drug with aripiprazole as its active moiety or ingredient, Abilify tablets received a five-year marketing exclusivity period that has since expired. In 2013, the FDA approved an application for another drug by Otsuka, Abilify Maintena®, which also has aripiprazole as its active moiety and ingredient. Abilify Maintena’s novelty was that it is administered through extended-release injectable suspension rather than orally. Because Otsuka relied on new clinical investigations when it sought approval for Ability Maintena, it was entitled to an initial three-year marketing exclusivity period under 21 USC § 355(c)(3)(E)(iii). In 2014, the FDA approved a supplemental new drug application for Abilify Maintena that provided new clinical study results granting Abilify Maintena another separate three-year marketing exclusivity period under 21 USC § 355 (c)(3)(E)(iv).

In late 2014, Alkermes submitted a new drug application (NDA) under 21 USC § 355(b)(2) [(505(b)(2) Application)] for Aristada®, an extended-release injectable suspension formula for the treatment of schizophrenia (like Abilify Maintena). Aristada’s active ingredient is aripiprazole lauroxil, a substance that metabolizes in the body into N-hydroxymethyl aripiprazole, which is Aristada’s active moiety. Alkermes’ Section 505(b)(2) Application relied on investigations Otsuka had sponsored with Abilify Tablets, but did not rely on any new clinical investigations Otsuka had undertaken with respect to Abilify Maintena. Rather, Alkermes conducted and submitted its own original studies to support its Section 505(b)(2) NDA for Aristada.

In 2015, Otsuka objected to Alkerme’s Section 505(b)(2) Application for Aristada in a citizen petition that it filed with the FDA, arguing that the FDA was prohibited from approving Aristada prior to the expiration of the three-year exclusivity periods for Abilify Maintena because Aristada’s 505(b)(2) Application was for the same conditions of approval, treated the condition in a similar way and relied on similar clinical trials (even though both the active ingredients and active moieties were different). The FDA disagreed, stating that the FDCA’s exclusivity provisions do not bar a second-in-time drug application if the drug with exclusivity and the drug for which approval is being sought have different active moieties. Otsuka filed the instant action against the FDA challenging the FDA’s decision as “arbitrary and capricious” and in violation of the law. Otsuka also claimed that the FDA violated the notice and comment procedures.

Applying the two-step framework of Chevron, the district court found that the FDA’s interpretation of the statute was reasonable. As to Chevron’s Step One, the court concluded that there were multiple plausible interpretations of the plain text of the bar clauses making these provisions ambiguous. Turning next to Chevron’s Step Two, the court found that the FDA’s interpretation of the bar clauses was reasonable and permitted by the statutory text. In doing so, the court noted that for “approximately two decades now, the FDA has focused on the active moiety of a drug…to identify and distinguish different drugs.” The court also explained that the FDA’s interpretation was consistent with the relevant legislative history and policy considerations, namely that

employing active moiety as a relevant criterion for determining whether a second-in-time application is barred promotes Hatch-Waxman’s goals by protecting ‘against approval of drugs with the same active moiety for the same exclusivity period use[,]’ while simultaneously encouraging competition by ensuring that exclusivity could ‘not block approval of drugs with different active moieties…that may have some advantages over previously approved active moieties.’

The court acknowledged Otsuka’s claims that it may be unfair to allow a second-in-time drug applicant to rely on an innovator’s clinical investigations while avoiding the exclusivity awarded to that same innovator, but stated that Otsuka’s alternative reading would “extend the marketing exclusivity of the initial innovator drug in perpetuity” which the court explained would be “an even more absurd result.” Finally, the court rejected Otsuka’s contention that the FDA transgressed the Administrative Procedure Act by improperly amending or altering an unambiguous regulation in contravention of the requirements of notice and comment.