FDA proposes to cut comparative efficacy study requirements for most biosimilars

The US Food and Drug Administration (FDA) announced a streamlined approach to developing biosimilars that could eliminate the need for drugmakers to conduct comparative efficacy studies (CES) to demonstrate biosimilarity to a reference product. Instead, manufacturers would be able to perform comparative analytical assessments (CAAs) to establish the comparability, except in certain cases when a CES is still necessary.

The agency laid out its new approach in a draft guidance issued on Wednesday. At a press conference announcing the guidance, Health and Human Services Secretary Robert Kennedy Jr. said the framework “reflects modern science and common sense. Under this new framework, companies may not always need to conduct large, expensive human trials, when advanced testing can already prove that biosimilars work just as effectively and just as safely as the original drug.”

He pointed out that there are currently only 76 approved biosimilars, which he said should ideally be several times greater.

Makary highlighted the significant delay in brining biosimilars to market, noting that including FDA review, it can take five to eight years to develop a biosimilar.

The draft guidance discusses scientific considerations for determining when a CES may be used to demonstrate biosimilarity. FDA said that as the agency’s experience with biosimilars has grown, so too is the “increasing recognition that CES are not as sensitive as modern analytical technologies for detecting differences between products.” During the press conference, Makary said he expects the guidance to be finalized in three to six months.

In the guidance, FDA said a CES may not be necessary under the following circumstances:

“The reference product and proposed biosimilar product are manufactured from clonal cell lines, are highly purified, and can be well-characterized analytically;
The relationship between quality attributes and clinical efficacy is generally understood for the reference product, and these attributes can be evaluated by assays included in the CAA; and
A human pharmacokinetic similarity study is feasible and clinically relevant.”

However, the agency stated that a CES may be necessary in some circumstances, for example, for a locally acting product where comparative pharmacokinetics is not feasible or clinically relevant. The agency also notes that there may be cases when a comparative clinical study with an endpoint other than an efficacy endpoint may be appropriate and encouraged sponsors to discuss their proposed approaches early on in product development.

Speaking at the press conference, FDA Commissioner Marty Makary said FDA would take steps to make it easier to bring interchangeable biosimilars to market. “Today, the FDA is also announcing its plans to issue final guidance on interchangeability … eliminating the bureaucratic switching studies that have been required,” Makary said. “We are taking a strong stand to advance and promote interchangeability.”

Last year, FDA issued draft guidance explaining when a switching study is needed to demonstrate interchangeability and it has since approved some biosimilars without conducting a switching study. “There have been waivers of those switching studies that have been granted by the FDA; now we’re going to issue clear, final guidance that those are not required. The uncertainty makes it difficult for drug developers,” Makary said.

Makary’s comments on this subject closely echoed those made by Sarah Yim, the director of the FDA’s Office of Therapeutic Biologics and Biosimilars (OTBB) within the Center for Drug Evaluation and Research (CDER), who spoke at recent meeting sponsored by the Association of Accessible Medicines (AAM) GRx+Biosim. Yim issued a similar warning regarding an impending void in biosimilars, and referenced a recent report that highlighted the insufficient development of biosimilars for many biological products that will soon lose patent protection, indicating this could threaten the future affordability of drugs in the US. (RELATED: FDA official issues warning about looming biosimilar void, Regulatory Focus 28 October 2025)

Draft guidance

FDA proposes to cut comparative efficacy study requirements for most biosimilars

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