FDA proposes major change to biosimilar PK study requirements

The US Food and Drug Administration (FDA) has updated its guidance to cut regulatory burdens on biosimilar manufacturers by reducing the need for conducting pharmacokinetic (PK) studies. The agency said that sponsors may meet their regulatory requirements by submitting analytical data rather than PK studies.

On 9 March, FDA published two guidances on biosimilars and the 2009 Biologics Price Competition and Innovation Act (BPCIA), including a draft guidance that the agency says will streamline the need to conduct clinical pharmacokinetic (PK) testing. More specifically, the agency said it reduces the need for such testing that could save biosimilar sponsors half of their PK study costs or about $20M that ultimately could lead to lower drug costs.

In 2021, FDA issued the third version of a draft guidance on biosimilars and the BPCIA. The agency has now issued a final guidance that formalizes most of its previous guidance but also withdraws several questions and inserts them separately in the new draft guidance. Specifically, it has withdrawn Q&As I.8, I.10, and I.19 and updated them in the revised draft guidance.

"The recommendations describe scenarios in which a biosimilar applicant may use clinical data from outside the U.S. without additional data from a three-way PK study (using the proposed biosimilar, the U.S.-licensed reference product, and the non-U.S.-licensed comparator product)," said FDA in a statement about the new revisions. "The revisions also remove the earlier recommendation for at least one clinical PK study that directly compares the proposed biosimilar with the U.S.-licensed reference product to support a demonstration of biosimilarity; instead, a PK study can use a comparator product approved outside the U.S. if scientifically justified."

FDA Commissioner Marty Makary co-authored an article in the Journal of the American Medical Association (JAMA) stating that burdensome regulations have prevented new biosimilars from entering the US market, and that his agency is taking steps to reduce those burdens by updating its guidance. He also noted that as of January 2026, 86 biosimilars were approved by FDA, and 41% of those were approved in just the past two years.

Makary said that the BPCIA has failed to significantly encourage more biosimilars to market, as biosimilars account for only 23% of the overall biologics market. He added that only about 10% of branded biologics scheduled to lose patent protection over the next decade have biosimilars in development to replace them. The commissioner also argued that the costs and duration of patent litigation have made it unattractive for sponsors to develop biosimilars.

"FDA is taking action to remove burdensome and expensive criteria for biosimilar approvals and promote interchangeability to encourage use of biosimilars in place of branded biologics," said Makary. "FDA will eliminate recommendations for unnecessary clinical trials when analytical and pharmacokinetic data can sufficiently demonstrate biosimilarity, help encourage pharmacy-level substitution as appropriate to mirror the successful generic drug model, and provide clearer guidance to expedite development and accelerate market entry.

"These reforms will encourage more biosimilar development and increase competition, expanding access for patients facing unsustainable treatment costs while maintaining rigorous safety standards," he added.

Makary said that pharmacokinetic and pharmacodynamic similarity studies cost on average $40M, approximately 30% of the total cost of developing a biosimilar. He added that FDA does not want to require a 3-group clinical pharmacokinetic study for sponsors who use clinical data with a non-US-licensed comparator product to support a demonstration of biosimilarity to a US-licensed reference product. Instead, he said sponsors should be able to use analytical data to support their premarket application.

"Additionally, FDA will no longer recommend sponsors conduct at least 1 clinical pharmacokinetic study that directly compares the proposed biosimilar with the US-licensed reference product to support a demonstration of biosimilarity," said Makary. "By streamlining these criteria, FDA’s proposed guidance could reduce pharmacokinetic study costs by up to 50%, lowering barriers to market entry and encouraging more manufacturers to develop competing products."

Makary also noted that in October 2025, FDA published a draft guidance on scientific considerations when demonstrating biosimilarity to a reference product that limits the conditions for requiring comparative efficacy studies (CES). He said the move could help shorten the time and costs in the hundreds of millions for biosimilar developers and noted that, in certain cases, a comparative analytical assessment, pharmacokinetic similarity data, and an assessment of immunogenicity may be sufficient to demonstrate biosimilarity without a CES.

FDA also announced that it has withdrawn the 2015 final version of the scientific considerations guidance because regulators have evolved their scientific understanding through their review of biosimilars, and the guidance is no longer representative of the agency's thinking.

Revised guidance, new guidance, JAMA article

FDA proposes major change to biosimilar PK study requirements

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