Modified on November 17, 2021
Issue: The approval, by the U.S. Food and Drug Administration (FDA), of an interchangeable biosimilar product, in July 2021, culminated an 11-year process that began in 2010 with the passage of the Biologics Price Competition and Innovation Act. While there are now two interchangeable products that can be automatically substituted in a retail pharmacy setting (the primary benefit of pursuing an interchangeable designation), there is still uncertainty as to what effect the unique U.S. regulatory construct of interchangeability should have on use and development of biosimilars in the U.S. This issue brief explores the current landscape of scientific evidence on switching between biosimilar and reference products as well as issues affecting the perception of biosimilar and interchangeable products. Consideration is given to studies that came close to following the recommended “three-switch” guidance. There is also a focus on product-class specific switching evidence.
Key Findings: The overwhelming majority of trials conducted during biosimilar development support the fact that there is no evidence of safety and efficacy concerns when switching from or to a reference product. The absence of evidence for safety and efficacy of concerns is mirrored in real-world settings as well. This growing evidence base has implications for regulatory requirements to demonstrate interchangeability while also revealing the continued difficulty of demonstrating interchangeability via a substantial clinical comparative assessment.
Policy Recommendations: To help advance biosimilar development, the FDA should consider opportunities for increased regulatory flexibility in interchangeability determinations for well understood products. Starting with drug classes where the evidence of clinical equivalence supporting interchangeability is strongest, FDA should consider a pathway to market that does not require switching studies on top of requirements to demonstrate biosimilarity. Working with international regulatory bodies, the FDA should explore how to further utilize post-market data from the U.S. and elsewhere in the world, including requiring post-market studies using real-world data on the approved interchangeable product, which would further ensure that the product is safe and effective for switches. Alternatively, outlining a clear process of demonstrating biosimilarity then utilizing post-market real-world data collection to demonstrate interchangeability could be considered. FDA should also consider a clear path to reduce the need for bridging studies for reference products from other countries and work closely with international regulators to harmonize regulatory requirements for biosimilar products. FDA can continue to work with other federal agencies, disease specific professional societies, and patient organizations to develop succinct and easily understandable education material to increase provider and patient comfort with these products. Additionally, educational material should clarify that interchangeability is only relevant for products dispensed in retail pharmacy settings.
Congress has demonstrated bipartisan interest in seeing increased adoption of biosimilars to benefit patients. As they evaluate user fee reauthorization legislation, including BsUFA III, Congress should also re-evaluate whether the unique U.S. interchangeability designation is accomplishing its desired goals. An alternative regulatory model, more in line with the rest of the world and the growing U.S. and global experience with biosimilars, would focus on biosimilarity and have a clear scientific foundation for any restrictions on interchangeability.