Biosimilars: FDA finalizes supplement classification guidance

The US Food and Drug Administration (FDA) on Monday published final guidance to assist sponsors in identifying the appropriate supplement category for biosimilar prior approval supplements – both original and resubmitted – as well as the agency's goals for reviewing them.

The guidance specifies six types of prior approval supplement (PAS) categories under Biosimilar User Fee Amendments of 2022 (BsUFA III) to create consistent reviews of the supplement and articulate the review goals. Publishing this guidance fulfills a commitment outlined in the BsUFA III commitment letter.

The guidance spells out six categories of supplements:

Category A supplements are for “straightforward changes incorporating safety labeling updates” for biosimilars or interchangeable biosimilar products;
Category B is for those supplements seeking additional indications and involve the submission of analytical in vitro data collected through physical, chemical or biological assays;
Category C supplements are for those that remove indications; in this category, applicants must provide information necessary to support the labeling change;
Category D is for supplements seeking to add an indication to a licensed biosimilar or interchangeable biosimilar product;
Category E is for BLA supplements for a licensed biosimilar or interchangeable biosimilar product seeking licensure for an additional indication that has been previously approved for the reference product and where the submission contains efficacy data; and
Category F supplements are for interchangeable products.

The final guidance replaces a draft version that was issued in August 2023 and includes some minor revisions. (RELATED: FDA drafts guidance on classification category for biosimilar supplements, Regulatory Focus 10 August 2023)

FDA noted in a Federal Register announcement that “changes from the draft to the final guidance include clarification that the guidance does not include recommendations for manufacturing-only supplements or for all supplements for safety-related updates to the labeling, clarification that applicants can request reconsideration of classification category with appropriate justification, and clarification that a pediatric assessment or amended initial pediatric study plan may be included in a Category D supplement. In addition, editorial changes were made to improve clarity.”

The final version clarifies the steps an applicant should take if they disagree with the FDA’s classification category assignment. This revision was requested by the Association for Accessible Medicines (AAM).

The updated text reads that “if an applicant does not agree with FDA’s classification category assignment, it may submit a response with updated justifications for its proposal for FDA’s consideration.”

The final version also accedes to a request from AAM to list the guidelines that address supplements that do not fit into Categories A-F.

The list includes the International Council on Harmonization’s (ICH) guidance for industry Q5E “Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process” issued in June 2005; the guidance “Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products” issued in July 1997; the guidance “Comparability Protocols for Postapproval Changes to the Chemistry, Manufacturing, and Controls Information in an NDA, ANDA, or BLA” issued in October 2022; and “CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports” issued in December 2021.

FDA rejected a request from the Biosimilars Forum for an acknowledgment letter prior to 60 days for Category A-D supplements.

“We are concerned by the timelines given here and in the BsUFA III Commitment letter for the following reasons: Receiving an acknowledgement letter for Category A-D supplements within 60 days is outside the standard timeframes set forth by FDA for other supplement and application acknowledgement letters,” said the Biosimilars Forum. “We urge FDA to commit to sending acknowledgement letters sooner, because not receiving confirmation of the supplement classification and timeline for 60 days could have impacts on other changes planned by the applicant.”

Final guidance

Biosimilars: FDA finalizes supplement classification guidance

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