On October 29, 2025, the FDA released a new draft guidance “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies” designed to accelerate the development of biosimilars and reduce drug costs by simplifying the testing process and removing unnecessary clinical study requirements. This action marks one of the most significant updates to the biosimilar approval framework since it was established under the Biologics Price Competition and Innovation Act (BPCIA) in 2010.

Traditionally, biosimilar developers have been required to conduct comparative efficacy studies to support a demonstration of biosimilarity, that can take up to three years. The new draft guidance considers such studies to have low sensitivity compared with modern in vitro analytical technologies for comparing structural and functional similarity and suggests a streamlined approach. Foregoing comparative clinical studies should be considered when “[t]he reference product and proposed biosimilar product are manufactured from clonal cell lines, are highly purified, and can be well-characterized analytically; [t]he relationship between quality attributes and clinical efficacy is generally understood for the reference product, and these attribute can be evaluated by assays included in the comparative analytical assessment; and [a] human pharmacokinetic similarity study is feasible and clinically relevant.”

The draft guidance recognizes that there still may be circumstances where a comparative clinical study may be useful to support a demonstration of biosimilarity, but those should be limited to studies with a clinically relevant endpoint other than efficacy.

The FDA is also revising its guidance for biosimilars seeking an interchangeable designation. In the past, biosimilar developers were generally required to perform “switching studies” to show that alternating between a biosimilar and its reference product posed no additional risk. The new draft guidance generally does not recommend these studies, recognizing that they slow development and can create confusion about biosimilar safety.

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The authors would like to thank April Breyer Menon for her contributions to this article.