FAQ: What FDA’s New Approach to Biosimilar Interchangeability Means for Developers

FDA is proposing a significantly less burdensome path for biosimilar developers, with changes that could reduce several clinical studies historically used to support biosimilar and interchangeable biosimilar applications. The changes could lower development costs and timelines, but because the recommendations remain in draft form, important questions about how the revised framework will work in practice remain.¹,²

What is FDA actually proposing to change?

Two draft guidance documents, issued five months apart, form the core of the changes. In October 2025, FDA proposed reducing the need for comparative efficacy studies, a clinical testing step that can require one to three years and cost $24 million.¹ In March 2026, the agency followed with a second draft guidance recommending streamlined clinical pharmacokinetic (PK) testing when scientifically justified. The guidance removes the previous recommendation for at least one direct PK comparison between the proposed biosimilar and the US-licensed reference product and describes circumstances in which developers could use a non-US-licensed comparator instead.²

FDA estimates the March changes could reduce PK study costs by up to 50%, or approximately $20 million per program.²

Why did switching studies become such a flashpoint in the first place?

For years, earning an interchangeable designation has meant conducting a switching study, in which patients alternate between the reference product and the biosimilar to evaluate whether switching introduces additional risk, on top of the multi-switch, extended-follow-up PK study FDA historically recommended for interchangeability.³^,⁴ Industry has pushed back on this burden directly. “The additional research burden and costs for a biosimilar drug to be considered interchangeable are substantial and may deter biosimilar manufacturers from seeking interchangeability,” said Hillel P. Cohen, PhD, executive director, scientific affairs, at Sandoz, a Novartis company, arguing that an approved biosimilar should be considered interchangeable with its reference product by default.⁴

FDA's current draft guidance states that the agency now generally does not recommend switching studies.³ FDA had already signaled this shift in its June 2024 draft guidance, which said accumulated experience with approved biosimilars indicated that the risk of safety or diminished efficacy following switching was insignificant. The agency said applicants could instead provide an assessment explaining why comparative analytical and clinical data support a demonstration that the statutory switching standard has been met.³

Does this affect biosimilars that are already on the market?

No. The draft guidance would apply to future applications rather than retroactively changing the status of already-approved products. FDA had approved 82 biosimilars as of March 2026.²

Will pharmacists be able to automatically substitute any biosimilar now?

No. FDA's proposed changes would reduce the evidence generally recommended to support interchangeability, but they would not by themselves change state substitution laws or mean that every FDA-approved biosimilar can automatically be substituted at the pharmacy. FDA says an interchangeable biosimilar may be substituted for its reference product at the pharmacy without intervention from the prescribing health care professional, depending on state law. Not all biosimilars are interchangeable.⁵

The practical importance of interchangeability can also vary by how a biologic is administered. For products administered directly by health care professionals in clinical settings, pharmacy-level substitution is not the mechanism through which the product is selected.⁴

Has any of this actually taken effect?

No. The major changes discussed here remain draft guidance and are not for implementation.¹^,²^,³ FDA's March 2026 action also withdrew its 2015 final guidance, Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, because the agency said it no longer represented its current thinking after years of additional experience reviewing biosimilar applications.²

What does this mean for the looming biosimilar patent cliff?

Only about 10% of the 118 originator biologics expected to lose patent exclusivity over the next decade currently have a biosimilar in development, according to a study cited by FDA.² Lower development costs could make additional programs more economically attractive, but regulatory streamlining addresses only one part of the development equation. Manufacturing complexity and commercial considerations can also affect whether a biosimilar program moves forward.²

References

1. US Food and Drug Administration. FDA moves to accelerate biosimilar development and lower drug costs. Published October 29, 2025. Accessed August 24, 2026. https://www.fda.gov/news-events/press-announcements/fda-moves-accelerate-biosimilar-development-and-lower-drug-costs
2. US Food and Drug Administration. FDA takes further steps to streamline biosimilar development and make medicines more affordable. Published March 9, 2026. Accessed August 24, 2026. https://www.fda.gov/news-events/press-announcements/fda-takes-further-steps-streamline-biosimilar-development-and-make-medicines-more-affordable
3. US Food and Drug Administration. Considerations in demonstrating interchangeability with a reference product: update. Published: June 20, 2024. Accessed August 24, 2026. FDA interchangeability guidance
4. Mirasol F. Biosimilars tackle interchangeability standards. BioPharm International. 2020;33(4):28-32. Accessed August 24, 2026. BioPharm International article
5. US Food and Drug Administration. 9 things to know about biosimilars and interchangeable biosimilars. Published June 20, 2024. Accessed August 24, 2026. FDA biosimilars resource