[6/20/2024] Today, FDA issued a draft guidance for industry “Considerations for Demonstrating Interchangeability with a Reference Product: Update.”

This draft guidance describes considerations regarding a switching study or studies intended to support a demonstration that a biological product is interchangeable with a reference product.

“The recommendations in today’s draft guidance, when finalized, will provide clarity and transparency about the FDA’s thinking and align the review and approval process with existing and emerging science,” said Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars. “We have gained valuable experience reviewing both biosimilar and interchangeable biosimilar medications over the last 10 years. Both biosimilars and interchangeable biosimilars meet the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.” 

This draft guidance is based on updated scientific thinking and experience related to both biosimilars and interchangeable biosimilars. FDA issued the interchangeability guidance for industry in 2019 (Considerations in Demonstrating Interchangeability With a Reference Product) before receiving and reviewing any applications for an interchangeable biosimilar.

Since publication of the interchangeability guidance, experience has shown that for the products approved as biosimilars to date, the risk in terms of safety or diminished efficacy is insignificant following single or multiple switches between a reference product and a biosimilar product.

Accordingly, FDA’s scientific approach to when a switching study, or studies, may be needed to support a demonstration of interchangeability has evolved. FDA researchers found no differences in the risk of death, serious adverse events, and treatment discontinuations between participants who switched between biosimilars and reference products and participants who did not switch in a recently conducted systematic review and meta-analysis. Additionally, today’s analytical tools can accurately evaluate the structure and effects biologic products, both in the lab (in vitro) and in living organisms (in vivo) with more precision and sensitivity than switching studies.

FDA has generally recommended switching studies in the past as part of the data package needed to demonstrate interchangeability of a biosimilar; however, of the 13 approved interchangeable biosimilars, 9 were approved without additional clinical (switching study) data. With the publishing of today’s draft guidance, FDA is seeking comment on a revised approach where such studies will generally not be needed. 

Health care professionals and patients can be confident in the safety and effectiveness of a biosimilar product, whether or not it has also been approved as an interchangeable biosimilar, just as they would be for an originator biologic (reference product).

Interested parties should read the draft guidance and submit comments to the docket using the instructions found in the Federal Register notice.

FDA also has developed “9 Things to Know About Biosimilars and Interchangeable Biosimilars,” which provides an overview and general information related to this topic for health care professionals and patients.