The US Food and Drug Administration (FDA) has issued a draft strategy document titled ‘BsUFA III Future Needs in the Development of Interchangeable Products Post-Workshop Strategy Document’, following its 19 September 2025 public workshop on the future needs for developing interchangeable biosimilar products. The document fulfils a Biosimilar User Fee Act (BsUFA III) commitment for FY2023–2027 and summarises workshop and docket comments, as well as future directions
As of August 2026, the FDA has licensed 99 biosimilars, 46 of which carry the interchangeable designation. The agency reported a notable increase in interchangeable approvals in 2025, with 23 products authorised, compared to just 2 in 2022.
A central theme is the growing role of analytical methods over clinical switching studies. FDA stated that comparative clinical studies do not offer the same sensitivity for detecting quality attribute differences as modern analytical technologies, and that clinical data may not always be necessary to demonstrate interchangeability. The June 2024 draft guidance, ‘Considerations in Demonstrating Interchangeability with a Reference Product: Update’ [1], signalled that switching studies would generally not be expected.
Industry stakeholders identified a gap between evolving science and regulatory communication. They sought greater clarity on how FDA makes case-by-case determinations, particularly regarding differences between delivery devices for a proposed interchangeable biosimilar and its reference product, and what information FDA expects to justify those differences. Stakeholders noted that more detailed communication earlier in development would help industry decision-making. FDA presenters outlined human factors complexities, including use-related risk analysis, user-error assessment and side-by-side device comparisons. Industry proposed validation studies with experienced users rather than comparative use human factors studies, while FDA acknowledged limited research in this area.
On analytical methods, FDA and industry agreed that growing confidence in advanced analytics supports greater reliance on analytical data. However, one docket commenter strongly supported maintaining clinical evidence and switching studies, highlighting limitations of analytical assessments, such as device differences or potential immunogenicity risks, and noting that clinical data can increase physician confidence.
Public comments submitted to the docket revealed divergent views: some supported eliminating the separate interchangeable designation entirely, while others advocated for case-by-case determinations or maintained that clinical evidence and switching studies remain essential for physician confidence.
Docket comments revealed divergent views: some supported eliminating the separate interchangeable designation entirely, others advocated for case-by-case determinations, and some maintained that clinical evidence and switching studies remain essential for physician confidence. Another stakeholder, ASBM, argued that FDA or HHS is pursuing a deliberate ‘genericisation’ of biosimilars, collapsing the long-established scientific distinction between biologicals and small-molecule drugs and converting the biosimilar framework into a generic-style mass-substitution model [3].
Pharmacy-level substitution remains a key concern. A primary issue is potential user error when patients face differences in delivery device design. Comparative use human factors studies have been proposed but are costly and challenging. One comment favoured flexibility in device designs; others called for clear substitution procedures and information on accessories such as autoinjectors, pumps or diluents. FDA also published draft guidance on container closure systems and device constituent parts in July 2026 to help applicants navigate these complexities [2]. One encouraged global harmonisation with EMA, Health Canada, WHO and ICH.
FDA plans to publish a revised version of the interchangeability guidance by the end of FY 2028. Comments on the draft strategy document are open for a comment period of 60 days, i.e. until 17 November 2026.
Comments can be submitted online at https://www.regulations.gov, or in written form and mailed to Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, USA, referencing the docket no. FDA-2025-N-2787.
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References
1. GaBI Online - Generics and Biosimilars Initiative. FDA interchangeable biosimilars guidance update on revised approach to switching studies [www.gabionline.net].Mol, Belgium: Pro Pharma Communications International; [cited 2026 Oct 22]. Available from: www.gabionline.net/guidelines/fda-interchangeable-biosimilars-guidance-update-on-revised-approach-to-switching-studies
2. FDA. Biosimilar and Interchangeable Biosimilar Products: Considerations for Container Closure Systems and Device Constituent Parts. Draft Guidance. July 2026.
3. Reilly MS, Schneider PJ, Spiegel A. Biosimilars: still safe, still effective, still not generics. Why is FDA suddenly pretending they are? Generics and Biosimilars Initiative Journal (GaBI Journal). 2026;15(1).22-6. doi:10.5639/gabij.2026.1501.004
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