FDA Issues Draft Guidance on Demonstrating Biosimilar Interchangeability | Goodwin
Last month, the FDA issued draft guidance, which, if implemented, would remove a requirement for a switching study for demonstrating biosimilar interchangeability. For a biologic product that is administered more than once to an individual, a switching study refers to a clinical study used to determine the impact of alternating between the reference product and the proposed interchangeable biosimilar compared to using the reference product without any such alternation. In May 2019, the FDA issued a guidance, titled “Considerations in Demonstrating Interchangeability With a Reference Product,” stating that the FDA “anticipates that data and information acquired from a switching study or studies will be useful in assessing the risk, in terms of safety and diminished efficacy, of alternating or switching between the products.” The new draft guidance, issued in June 2024, provides updated recommendations to applicants for proposed interchangeable biosimilar products that would eliminate the need for a switching study.
The draft guidance cites research which, according to the FDA, found effectively no additional safety concerns in patients who were switched between reference biologics and biosimilars. The FDA states that, since publication of the May 2019 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.” The FDA also notes, that “currently available analytical technologies can structurally characterize highly purified therapeutic proteins and model in vivo functional effects with a high degree of specificity and sensitivity using in vitro biological and biochemical assays.”
The new draft guidance allows companies seeking a biologics license application (BLA) for a biosimilar to be reviewed for interchangeability status to submit either switching study data or a an assessment “of why the comparative analytical and clinical data provided in the application or supplement support a showing that the switching standard set forth in section 351(k)(4)(B) of the PHS Act has been met.” The assessment should include “any other information the applicant considers relevant to support a showing that the risk, in terms of safety and diminished efficacy, from alternating or switching between the reference product and the proposed interchangeable product is not greater than the risk of using the reference product without such alternation or switch.” Companies with pending BLAs can amend their applications to include this information.
Sarah Yim, MD, Director of the Office of Therapeutic Biologics and Biosimilars, stated that the 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.” Dr. Yim also noted that over the past 10 years, both biosimilars and interchangeable biosimilars have met “the same high standard of biosimilarity for FDA approval and both are as safe and effective as the reference product.”
To date, the FDA has approved thirteen biosimilar products as interchangeable. The FDA noted in a press release that, for the thirteen approved interchangeable biosimilars to date, nine were approved without switching study data.
Relatedly, in a 2025 Fiscal Year budget proposal, the FDA has also recently stated that it would seek to amend the Public Health Service (PHS) Act to “no longer include a separate statutory standard for a determination of interchangeability and to deem all approved biosimilars to be interchangeable with their respective reference products.” According to the FDA, its proposal “would make the U.S. biosimilar program more consistent with current scientific understanding as well as with the approach adopted by other major regulatory jurisdictions such as the European Union where biosimilars are interchangeable with their respective reference products upon approval.
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