PK Studies in the Crosshairs: FDA Revises Biosimilar Development Guidance

The FDA continues to refine its approach to biosimilar development. On March 9, 2026, the Agency announced the release of the revised draft guidance titled “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4).”

The guidance updates FDA recommendations for biosimilar – and interchangeable – product development and is part of the Agency’s broader effort to streamline development programs while maintaining the scientific standards required to demonstrate biosimilarity.

The latest draft revises three questions and answers—Q&A I.8, I.10, and I.19—from the Agency’s earlier guidance “Questions and Answers on Biosimilar Development and the BPCI Act” issued in September 2021. These Q&As have been withdrawn from the final guidance while FDA seeks public comment on the revised versions.

The most significant changes appear in Q&A I.8, which now addresses the use of clinical data generated from a comparator product approved outside the U.S. (non-U.S. licensed comparator product). The revised Q&A is organized into two parts.

Part (a) explains how clinical studies—including pharmacokinetic (PK) studies—comparing a proposed biosimilar with a non-U.S.-licensed comparator product may, in certain circumstances, help address statutory requirements and support a demonstration of biosimilarity to a U.S.-licensed reference product. It also outlines when clinical data generated using a non-U.S. licensed comparator product may be acceptable.

Overall, this signals the Agency’s flexibility for scientifically justified scenarios in which prospective biosimilar applicants may be able to rely on clinical data generated using a comparator product approved outside the United States without conducting an additional three-way PK study involving the proposed biosimilar, the U.S.-licensed reference product, and the non-U.S. licensed comparator product.

The revised recommendations also remove an earlier expectation that at least one clinical PK study directly compare the proposed biosimilar with the U.S.-licensed reference product. Instead, a PK study using a non-U.S. comparator product may be acceptable if scientifically justified.

Part (b) focuses on the comparative analytical data needed between the non-U.S.-licensed comparator product and the U.S.-licensed reference product. These analytical comparisons can help justify the scientific relevance of clinical data generated using the non-U.S. licensed comparator product.

FDA is specifically requesting comment on the value of these analytical comparisons as part of the scientific justification supporting the relevance of clinical data derived from studies using non-U.S. licensed comparator products.

These changes reflect the Agency’s evolving scientific thinking after more than a decade of experience reviewing biosimilar applications. As part of this shift, FDA also announced it is withdrawing the guidance “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product,” issued in 2015, because it no longer reflects the Agency’s current thinking.

For biosimilar applicants, the draft guidance offers another indication that FDA is continuing to refine the biosimilar development framework—particularly around the role of clinical studies and the use of non-U.S. licensed comparator products. According to FDA, streamlining comparative efficacy studies could save biosimilar manufacturers up to $150 million in development costs and approximately 2 to 4 years of time. Similarly, reducing unnecessary PK testing could lower study costs by as much as 50%, unlocking competition and facilitating market entry of more biosimilar manufacturers.

Stakeholders have an opportunity to weigh in. FDA is accepting comments on the draft guidance through May 11, 2026, before the Agency begins work on a final version.