FDA Issues Final Guidance on Biosimilar Prior Approval Supplements
The US Food and Drug Administration (FDA) has finalized guidance designed to streamline how sponsors classify and submit prior approval supplements (PAS) for biosimilars and interchangeable biosimilars. Published Monday, September 8, the document clarifies 6 PAS categories under the Biosimilar User Fee Amendments of 2022 (BsUFA III) and establishes review goals intended to ensure greater consistency across submissions.
The release of this guidance fulfills a key commitment under the BsUFA III agreement and provides sponsors with a clearer framework for determining the appropriate supplement category for both original and resubmitted applications.
The final guidance outlines 6 categories:
- Category A – Straightforward safety labeling updates.
- Category B – New indications supported by analytical in vitro data from assays.
- Category C – Removal of indications, requiring information to support the labeling change.
- Category D – Addition of a new indication to a licensed biosimilar or interchangeable biosimilar product.
- Category E – Supplements seeking licensure for an additional indication already approved for the reference product, supported by efficacy data.
- Category F – Supplements for interchangeable products.
The final version replaces an August 2023 draft, with several clarifications added in response to stakeholder feedback. The FDA emphasized that the guidance does not apply to manufacturing-only supplements or all supplements involving safety-related labeling updates. Importantly, applicants now have a mechanism to dispute classification decisions. The guidelines state:
“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.”
This clarification reflects input from the Association for Accessible Medicines (AAM), which had urged the agency to provide a formal path for reconsideration.
Other changes include acknowledging that a pediatric assessment or amended initial pediatric study plan may be submitted with Category D supplements. Editorial revisions were also made for clarity.
The FDA incorporated another AAM request by listing applicable guidance documents for supplements that fall outside the 6 defined categories. These include long-standing resources such as the International Council on Harmonization’s Q5E comparability guidance and more recent FDA guidance on chemistry, manufacturing, and controls (CMC) protocols and annual reporting of certain biological product changes.
This addition may help sponsors navigate more complex or atypical supplement scenarios while maintaining regulatory compliance.
Not all stakeholder requests were met, however. The Biosimilars Forum had asked FDA to issue acknowledgement letters for Category A through D supplements sooner than the 60-day timeframe currently outlined. FDA declined, citing alignment with established acknowledgement practices.
The Forum expressed concern that waiting 60 days to receive confirmation of supplement classification could create bottlenecks for sponsors planning multiple product changes in parallel.
For payers and managed care stakeholders, the new guidance signals more predictable timelines and clearer regulatory pathways for biosimilar indication changes. The categorization may affect when new indications are formally recognized for coverage decisions and formulary updates. Likewise, sponsors’ ability to contest classification could influence how quickly certain supplements move through review, which in turn could shape availability and market access.
References
- Eglovitch JS. Biosimilars: FDA finalizes supplement classification guidance. Regulatory Focus. September 9, 2025. Accessed September 10, 2025. https://www.raps.org/news-and-articles/news-articles/2025/9/biosimilars-fda-finalizes-supplement-classificatio
- US Food and Drug Administration. Classification categories for certain supplements under BsUFA III; guidance for industry - final guidance. Regulations.gov. September 9, 2025. Accessed September 10, 2025. https://www.regulations.gov/document/FDA-2023-D-1954-0007
