In March 2026, the US Food and Drug Administration (FDA) released a revised draft guidance aimed at streamlining biosimilar development and clarifying the agency’s current interpretation of key provisions under the Biologics Price Competition and Innovation Act (BPCI Act).
The document, titled ‘New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4)’ [1] updates earlier guidance issued in 2021 [2] and introduces significant changes related to the use of comparator products approved outside the United States.
Presented in a question-and-answer format, the guidance is intended to assist companies developing biosimilars and interchangeable biosimilars by outlining FDA’s current recommendations and regulatory expectations.
Key revisions regarding comparator products
One of the most notable revisions concerns the use of non-US-licensed comparator products in biosimilar development programmes. Under previous recommendations, developers were generally expected to conduct a three-way clinical pharmacokinetic (PK) study comparing the proposed biosimilar, the US-licensed reference product, and the non-US comparator product.
In the updated draft guidance, the FDA indicates that such studies may no longer be necessary in certain situations. Revised draft Q&A I.8 states that applicants may be able to justify the relevance of comparative clinical data generated using a non-US-licensed comparator through analytical evidence alone, without needing a three-way PK study.
The agency also removed an earlier recommendation that biosimilar developers conduct at least one direct clinical PK comparison between their product and the US-licensed reference product to support a demonstration of biosimilarity.
The FDA said the revisions are intended to provide updated recommendations for developers seeking more efficient pathways for demonstrating biosimilarity while maintaining scientific rigour.
Additional Updates
Additional updates were made to draft Q&As I.10 and I.19, both of which previously referenced three-way PK studies involving non-US comparator products. These sections have been revised to align with the agency’s updated position. Another section, Q&A I.12, remains unchanged from the previous revision.
As part of the update, FDA also reissued the final guidance document ‘Questions and Answers on Biosimilar Development and the BPCI Act’ [3] to formally withdraw the Q&As currently under revision.
The agency noted that it continues to review other sections of the guidance as part of broader efforts to improve efficiency in biosimilar development programmes. The FDA said additional updates may be introduced if existing recommendations no longer reflect current scientific or regulatory thinking.
Withdrawal of 2015 Guidance
Separately, FDA announced the withdrawal of its 2015 final guidance, ‘Scientific Considerations in Demonstrating Biosimilarity to a Reference Product’ [4], stating that the document no longer represents the agency’s current perspective. According to FDA, newer biosimilar guidance documents now address many of the topics covered in the earlier publication and are intended to better support modern biosimilar development approaches.
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References
1. New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4). FDA.
2. GaBI Online - Generics and Biosimilars Initiative. FDA issues new guidance on biosimilar development and the BPCI Act [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2026 Jun 12]. Available from: www.gabionline.net/guidelines/fda-issues-new-guidance-on-biosimilar-development-and-the-bpci-act
3. Questions and Answers on Biosimilar Development and the BPCI Act. FDA.
4. GaBI Online - Generics and Biosimilars Initiative. US guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2026 Jun 12]. Available from: www.gabionline.net/guidelines/US-guidelines-for-biosimilars
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