First interchangeable biosimilar exclusivity (FIE) is a market exclusivity period designated for the first biosimilar approved as interchangeable with a reference product. Created by the Biologics Price Competition and Innovation Act (BPCIA), the length of the FIE period has been a subject of debate.
A recent FDA decision regarding Boehringer's Cyltezo (adalimumab-adbm) sought to clarify the FIE exclusivity period and expiration date. According to FDA's interpretation, only interchangeable product approval and litigation count towards FIE expiration calculations—not initial biosimilar litigation (pre-interchangeable supplemental approval).
How Long Is the First Interchangeable Biosimilar Exclusivity Period?
The Biologics Price Competition and Innovation Act (BPCIA), signed into law in 2010, was designed to create a regulatory pathway for the approval of biosimilars.
The BPCIA created two exclusivity periods for biosimilars. The first period, known as the "reference product exclusivity," grants the manufacturer of the original biologic drug a period of 12 years of market exclusivity. This means that during this period, no biosimilar versions of the drug can be approved by the U.S. Food and Drug Administration (FDA). This exclusivity period is similar to the “new chemical entity exclusivity” period for small molecule drugs.
The second exclusivity period created by the BPCIA is known as "first interchangeable biosimilar exclusivity" (FIE). This exclusivity period is specifically for the first biosimilar approved as interchangeable with the reference product.
Under §351(k)(6) of the PHS Act, 42 U.S.C. 262(k)(6), the first approved interchangeable biosimilar to a reference product is granted a period of market exclusivity. FIE exclusivity blocks the approval of other interchangeable biosimilars for—whichever is earliest:
- 1 year after the interchangeable product is marketed, or
- 18 months after approval (even if not marketed), or
- 18 months after litigation final court decision or settlement, or
- 42 months after approval if litigation is ongoing.
Multiple first interchangeable biosimilars will qualify for exclusivity if approved on the same day.
However, the length of the FIE period is still a matter of contention.
AbbVie v. Boehringer Humira Patent Infringement Lawsuit
In August 2017, Cyltezo, an interchangeable biosimilar of AbbVie's Humira (adalimumab), was the first product to be granted FIE status. Filed by Boehringer Ingelheim Pharmaceuticals, Inc., the approval of Cyltezo marked a significant milestone in the biosimilar market.
Just months prior to the Cyltezo FIE approval, AbbVie sued Boehringer for patent infringement, claiming Boehringer's Cyltezo would infringe on over 70 patents covering adalimumab. In May 2019, AbbVie announced it had settled the patent litigation. Under the settlement terms, Boehringer's Cyltezo would not enter the market until July 1, 2023.
The question then became, would the FIE expiration dates for the newly approved Cyltezo subcutaneous injectables be impacted by the prior litigation? If the court determined that the lawsuit significantly impacted the biosimilar's launch, Boehringer could have faced a shorter period of exclusivity for Cyltezo.
This case shed light on some statutory ambiguity surrounding the inclusion of pre-interchangeable supplemental approval litigation. In creating the statute, FDA explained that Congress had not accounted for the overlapping licensure of biosimilars seeking interchangeable status as a supplement and the resulting infringement litigation that could arise between initial and supplemental approvals.
Ultimately, FDA held that Congress' intent in establishing a first interchangeable biosimilar exclusivity period was to:
- create incentives for competition, and
- prevent an applicant's unilateral control over the exclusivity period for a product.
FDA decided that FIE expiration dates should be affected only by patent litigation over submitted interchangeable products, not original biosimilars. Therefore, FDA calculated FIE expiration dates using the date of approval. FDA approved interchangeable Cyltezo 40 mg/0.8 mL and 20 mg/0.4 mL for subcutaneous injection on October 15, 2021 and the interchangeable Cyltezo 10 mg/0.2 mL for subcutaneous injection on March 18, 2022. FDA set the FIE expiration dates at April 15, 2023, and September 18, 2023 respectively—18 months from approval.
Under the biosimilar patent settlement, there would be only one FIE expiration date set at July 1, 2024, since the first commercial marketing of the various interchangeable Cyltezo subcutaneous injectables was on July 1, 2023. However, under the statute, FIE expirations for the Cyltezo injectables are still set at April 15, 2023 and September 28, 2023, respectively, because FIE expiration date determinations are based only on interchangeable approval and related litigation—not biosimilar patent litigation.
Impact of FDA's FIE Expiration Interpretation
Moving forward, drug sponsors concerned about including prior litigation in the FIE expiration date calculation should note that prior litigation will not likely impact the FIE period unless the litigation involved the initial application for determination of interchangeability.
Likewise, drug sponsors wishing to pursue a patent infringement action involving an FIE expiration date must have a case involving the same reference product used in the initial interchangeable application.
Biosimilar companies concerned about competition with other companies potentially pursuing first interchangeable exclusivity referencing the same biologic product should expedite application submission. Similarly, if FDA grants FIE approval to another biosimilar company on a product in progress, the sponsor should consider (1) submitting an application for biosimilarity only and not interchangeability or (2) delaying the application and gathering data to support an interchangeable license for the product.