FDA Proposes to Remove Comparative Efficacy Studies to Accelerate Biosimilar Development
With the aim of accelerating approval of biosimilars, the U.S. Food and Drug Administration ("FDA"), in its draft guidance "Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies," proposes relying on comparative analytical assessments in lieu of clinical studies with efficacy endpoints (comparative efficacy studies) to support a demonstration of biosimilarity.
On October 29, 2025, FDA issued draft guidance in which FDA proposes that comparative efficacy studies ("CES") may not be needed to support a demonstration of biosimilarity. With a focus on therapeutic protein products (e.g., antibodies), FDA proposes that CES may not be necessary where a comparative analytical assessment ("CAA") of attributes such as protein structure, physiochemical, and functional attributes supports a demonstration that a proposed biosimilar is highly similar to its reference product. FDA proposes consideration of this approach when: (i) the reference product and biosimilar product "are manufactured from clonal cell lines, are highly purified, and can be well-characterized analytically"; (ii) "[t]he relationship between quality attributes and clinical efficacy" for the reference product is understood, and these attributes are evaluable; and (iii) "[a] human pharmacokinetic similarity study is feasible and clinically relevant." Draft guidance at 4. FDA's recently published final guidance provides information regarding CAA and quality-related considerations for therapeutic protein biosimilar development.
As justification, FDA relies on its accrued experience and the high degree of specificity and sensitivity provided by currently available analytical technologies, such that a CAA is generally more sensitive than a CES in detecting differences between a biosimilar and its reference product. FDA's shift away from CES aligns with FDA's June 2024 draft guidance in which FDA, similarly relying on its experience and the precision of currently available analytical tools, proposed that clinical switching studies will generally not be needed to support a demonstration of interchangeability with a reference product. Moreover, FDA's proposals to remove clinical study recommendations for biosimilar approval are consistent with the growing global trend to remove regulatory hurdles in favor of generics and biosimilars and may spark new interest for biosimilar development.
Removal of the clinical study requirements will likely accelerate biosimilar approval, which may result in more biosimilar competition and, according to FDA Commissioner Makary, "achieve massive cost reductions for advanced treatments for cancer, autoimmune diseases, and rare disorders." To address the array of potential implications, we will be issuing a series of commentaries on this topic.
FDA is accepting comments on the latest draft guidance here.
