The U.S. Food and Drug Administration (FDA) recently published the draft guidance, Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act, Guidance for Industry. Comments can be submitted to FDA by January 19, 2021.
This draft guidance provides answers to additional questions regarding the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which created an abbreviated licensure pathway in section 351(k) of the Public Health Service Act for an applicant to submit an abbreviated biologics license application (aBLA) for a biological product to be biosimilar to, or interchangeable with, an FDA-licensed biological reference product.
The criteria for qualifying a product as an interchangeable biosimilar are higher than those for qualifying as biosimilar. To meet the standard for "interchangeability" under section 351(k)(4), an applicant must demonstrate both the proposed product's biosimilarity to the reference product, and also demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient.
This draft guidance provides answers to four questions. First, FDA addresses the question how an applicant seeks FDA's review of an application for an interchangeable biosimilar, including those with data for biosimilarity but no data for interchangeability. If an aBLA submitted under section 351(k) is intended to support licensure as an interchangeable biosimilar, the applicant should include an affirmative statement showing such an intention to trigger FDA's corresponding review. If the applicant indicates on the cover letter that the aBLA contains information to demonstrate interchangeability, FDA will evaluate the aBLA as both an application for licensure of a biosimilar product and an application for licensure of an interchangeable biosimilar. To support licensure of an interchangeable biosimilar, an applicant must first show that the proposed product is biosimilar to the reference product. If the data only supports biosimilarity but not interchangeability, FDA will split the application to license the product as a biosimilar product, notify the applicant of deficiencies on interchangeability, and later determine interchangeability for the product upon submission of supplemental data.
However, an applicant can specifically request FDA's review for an interchangeable biosimilar only by clearly noting the request for "INTERCHANGEABLE-ONLY REVIEW" in the cover letter for the application. FDA will only evaluate whether such a product is interchangeable and will not address whether the product is a biosimilar product alone.
The second question addressed in the draft guidance is how a 351(a) BLA holder should proceed if it seeks licensure of its biological product under section 351(k) as biosimilar to or interchangeable with another biological reference product. Section 351(a) is the pathway for approval of a biological product based on full clinical trials showing both safety and efficacy without reference to another approved BLA. When such a 351(a) BLA holder intends to seek licensure under section 351(k) as biosimilar to or interchangeable with another reference product, the holder should do so by submitting an original application for licensure under section 351(k).
Third, FDA also states that it has the recommendations for labeling of interchangeable biosimilars, and certain principles in the guidance on biosimilar labeling are also applicable to interchangeable biosimilars. For example, FDA states that interchangeable biosimilar labeling should incorporate relevant data and information from the reference product labeling, including clinical data supporting safety and effectiveness of the reference product, and should not include a description of or data from clinical studies conducted to support a demonstration of interchangeability.
Fourth, FDA also recommends that the aBLA-holder of an approved interchangeable biosimilar include a labeling statement that such a product is interchangeable with the reference product. FDA includes several examples of the statement on interchangeability, which is placed on the line immediately beneath the Initial U.S. Approval in the Highlights of Prescribing Information.
This draft guidance includes nonbinding recommendations and provides useful information particularly on applications for interchangeable biosimilar products. Supplemental to the prior guidance documents, this guidance, when finalized, will facilitate the development of biosimilar and interchangeable products as FDA intends.
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