On March 9, 2026, the Food and Drug Administration (FDA) issued a revised draft Q&A guidance intended to further streamline biosimilar development by allowing the use of non-U.S.-licensed comparator products in clinical studies. This action represents the FDA's second major step toward reducing biosimilar development burdens. Previously, we published our analysis of the FDA's October 2025 draft guidance, which suggested that comparative efficacy studies (CES) are no longer the default requirement for biosimilar development.
The newly revised draft Q&A guidance builds on that approach by providing additional flexibility for the use of non-U.S.-licensed comparator products in pharmacokinetic (PK) studies. Taken together, these developments signal a shifting landscape for biosimilar development as the FDA contemplates a streamlined biosimilar clinical data package, requiring only a comparative PK study between the proposed biosimilar product and a non-U.S.-licensed comparator product.
Before the issuance of this revised draft Q&A guidance, the FDA's September 2021 final guidance (Section I.8) provided the following recommendation for sponsors using non-U.S.-licensed products in clinical studies:
[A]s a scientific matter, analytical studies and at least one clinical pharmacokinetic (PK) study, which may include pharmacodynamic (PD) endpoint(s) intended to support a demonstration of biosimilarity, must include an adequate comparison of the proposed biosimilar product directly with the U.S.-licensed reference product unless it can be scientifically justified that such a study is not needed.
Although the guidance permitted scientific justification, the FDA's interpretation historically limited this to cases where a PK study was not feasible or clinically relevant (e.g., for locally acting ophthalmic products).
The September 2021 final guidance also specified the need for bridging when sponsors use a non-U.S.-licensed comparator product in a CES. Specifically, it stated:
As a scientific matter, the type of bridging data needed will always include data from analytical studies (e.g., structural and functional data) that directly compare all three products (i.e., the proposed biosimilar product, the U.S.-licensed reference product, and the non-U.S.-licensed comparator product), and is likely to also include bridging clinical PK data or, when appropriate, PD data, for all three products.
This framework effectively required a comparative analysis of all three products—the proposed biosimilar product, the U.S.-licensed reference product, and the non-U.S.-licensed comparator product—for both analytical bridging and PK bridging. Using non-U.S.-licensed comparator products is critical for biosimilar developers because reference products for the U.S. market are often purchased in Europe, where they are more accessible and less expensive. As a result, the FDA's bridging expectations significantly increased development costs and complexity.
This issue was raised in a citizen petition on April 18, 2025, requesting that the FDA revise its policy and guidance to update recommendations on the data necessary to justify use of non-U.S.-licensed comparator products. The FDA acknowledged the complexity of the issue in its interim response on October 15, 2025. The newly revised draft Q&A guidance provides further clarity on this topic.
This change represents a continued shift toward greater reliance on analytical and pharmacokinetic data in biosimilar development. Advances in analytical technologies and manufacturing science allow protein products to be extensively characterized by their physicochemical and biological properties. Consistent with this trend, we recommend a recent article by the FDA's leading experts on controlled vocabulary and structured taxonomical naming approaches for therapeutic protein quality attributes.
This guidance also strengthens global harmonization of biosimilar development programs. The European Medicines Agency (EMA) already permits a flexible approach to using non-European Economic Area reference products and has approved biosimilars based on analytical-only bridging. By issuing this revised draft Q&A guidance, the FDA signals greater alignment with international regulatory practices, acknowledges the use of non-U.S.-licensed products in clinical studies, and helps avoid duplicative and unnecessary efforts. Ultimately, enhanced global harmonization of biosimilar regulatory requirements may enable an applicant to have a single development program capable of satisfying regulatory expectations across multiple regions.
Interested parties can submit comments on the draft guidance to Docket No. FDA-2011-D-0611. Alston & Bird continues to closely monitor the FDA's biosimilar policy developments, and we stand ready to assist clients in evaluating regulatory strategies and engaging with the agency.
If you have any questions, or would like additional information, please contact one of the attorneys on our FDA: Drug & Device team.
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