FDA has released an 18-page internal decision memo which for the first time lays out the agency's interpretation of how regulatory exclusivity rights operate for “Interchangeable Biosimilar” products. The memo addresses a specific dispute between Pfizer and Boehringer Ingelheim over First Interchangeable Exclusivity ("FIE") rights for interchangeable biosimilar versions of Abbvie's blockbuster biologic product Humira.  This FDA decision harkens back to the heyday of legal disputes that arose under the Hatch-Waxman Amendments involving NCE exclusivity, 3-year exclusivity, and especially 180-day exclusivity disputes involving first-filer generic applicants. Given the complexity of the biosimilars law, the seemingly infinite variety of potential fact patterns that can arise, and the potentially huge financial stakes involved in FIE eligibility and expiration issues, this could mark the dawn of a new era of contentious administrative advocacy before, and litigation against, the FDA.

The Biologics Price Competition and Innovation Act ("BPCIA") created the biosimilars approval pathway and the FIE mechanism in 2010, after years of negotiation and numerous legislative proposals. In broad strokes, BPCIA allows sponsors to obtain approval of “biosimilar” versions of innovator biologic products in two ways: (1) as a “mere” biosimilar that would be expected to have similar safety and efficacy as the reference biologic such that it generally could be used as an alternative to the reference product; or (2) as an “interchangeable” biosimilar product that, based on additional evidence and data submitted by the applicant, can be directly substituted for the reference product (there are many nuances to potential biosimilar substitutability beyond the scope of this post). 

As an incentive for companies to develop interchangeable biosimilars, the BPCIA provides a potential market exclusivity period to the first interchangeable biosimilar, which delays FDA from approving subsequent interchangeable products for a specified time (the FIE does not, however, prevent FDA approval of non-interchangeable biosimilar versions of the same reference biologic). The date on which such exclusivity period begins depends on multiple factors, including whether patent litigation occurred between the first interchangeable biosimilar applicant and the reference product sponsor; whether and how such litigation was concluded; when the first interchangeable biosimilar applicant received FDA approval; and when the interchangeable product was first marketed. 

Importantly, many biosimilar product applications are first approved only under the “biosimilarity” approval pathway, but may later be supplemented to seek approval as an interchangeable product. If, as in the case here, patent litigation ensued as part of the original biosimilar application process, but no new litigation (and no new “patent dance”) was associated with the supplemental application for interchangeability, the statutory exclusivity “trigger” provisions can become subject to starkly competing interpretations. 

In a non-public dispute resolution process, Pfizer and Boehringer each submitted legal position memos to FDA and to each other, addressing whether (or when) Boehringer's claimed FIE for its interchangeable version of Humira was "triggered' and when it expired. Pfizer argued that Boehringer's exclusivity expired as early as November 2020, but no later than April 2023. Boehringer argued, among other issues, that its FIE does not expire until July 2024, the date that is one year after its product's first commercial marketing. 

FDA “decline[d] to adopt either Pfizer’s or BI’s proposed interpretation.” Rather, the agency determined that Boehringer was entitled to separate FIEs for different strengths of its product, that the FIE for two of those strengths expired in April 2023, and that the FIE for another strength expired in September 2023.  The extensive details of FDA's statutory and factual interpretations and reasoning are complex, and will be analyzed closely by industry for clues as to how other FIE determinations may be made for other biosimilar products under varying fact patterns.  

Regardless of how persuasive FDA's reasoning may (or may not) be, based on analogous history under the Hatch-Waxman exclusivity regimes, it seems highly likely that lawsuits against FDA will arise (whether in this particular case, or in emerging situations involving other products and applicants). In any event, the blossoming of FIE as a concrete set of legal issues, while a long time coming, is a significant development that should quickly focus the minds of legal departments throughout the biotechnology industry. 

An interesting procedural sidenote: FDA's approach of announcing its legal interpretation of certain FIE provisions of the BPCIA in a case-specific decision memo (as opposed to promulgating a regulation or a Guidance document), has generated some criticism from stakeholders. However, this approach is neither new nor particularly unusual; Indeed, it mirrors the agency's long-ago approach of deciding 180-day generic exclusivity disputes under Hatch-Waxman by “regulat[ing] directly from the statute.”  Back then (the late 1990's) FDA was forced into that procedural posture by adverse court decisions that nullified the agency's key regulatory interpretation of 180-day exclusivity eligibility (the “successful defense” rule). With respect to FIE issues, the courts may yet disagree with FDA's interpretation(s), but at least the agency has saved itself time and effort in bypassing the rulemaking process and proceeding straight to the “regulating directly from the statute” phase.