A draft guidance by the US Food and Drug Administration signals the agency’s admission that the data on biosimilar switching is now comprehensive and persuasive. If these draft recommendations are unchanged in the final guidance document, expensive biosimilar switching studies will no longer be needed for a manufacturer seeking the interchangeability designation.
The draft guidance, which calls for public comments by September 20, 2024, updates the original FDA guidance on interchangeability, which was published May 2019.
In its press release, the FDA stated, “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.”
As we’ve reported many times, the interchangeability designation has been fraught with confusion, much of which was based on industry misinformation or decisions from the FDA itself. First, the FDA has never required switching studies from all manufacturers seeking the interchangeability designation; the agency has had the authority to waive switching study requirements on a case-by-case basis. In fact, only 7 of the 13 drugs earning the designation were required by the FDA to be subject to switching studies for that purpose. The ones that were not required were VEG-F inhibitors for intravitreal administration and insulin glargine.
Second, granting interchangeability designation, which was only created to allow for automatic substitution at the pharmacy, to ranibizumab and aflibercept products is strange (to say the least). These two products are medical benefit–covered buy-and-bill agents predominantly, and thus are not dispensed by pharmacies. Perhaps the interchangeability designation was granted by the FDA to help convince ophthalmologists and retinal specialists of the quality of the product. This, however, is a direct affront to the campaign against disinformation that the FDA has fought for several years: Interchangeable biosimilars are of no better efficacy or safety than conventional biosimilars.
Third, the exclusivity provision of the interchangeability designation is clear as mud, and has been the subject of biosimilar maker confusion since its initial guidance on the topic was released. Even today, manufacturers are unsure when exclusivity for a product begins and when it ends. The FDA itself just granted the designation to two aflibercept products on the same day, which seems to defy the concept of exclusivity itself!
Finally, the FDA has signaled its own desire that the interchangeability designation be removed by Congress. Its seems to be coming around to thinking, as Europe does, that any approved biosimilar is interchangeable with the reference product, without significant risk of negative outcomes.
In March, the Biden Administration’s 2025 fiscal year budget proposal included the removal of the designation. If the budget is approved, the final updated guidance on interchangeability will be a moot point.
Seemingly, the agency has leaned toward requiring switching studies on products in new biosimilar drug categories, like denosumab and ustekinumab. The strategic issue for manufacturers is that these studies must be designed, approved, and initiated years in advance of biosimilar approval. If you were in a drug maker’s shoes today, and were semi-interested in obtaining the designation for a Keytruda® biosimilar candidate, what would you do?
