Key Takeaways:
- Interchangeable biosimilar products would not be allowed to disclose or explain their interchangeability designations in their products’ labels under FDA’s new draft guidance.
- FDA justified its reversal on including the interchangeability disclosure in labeling by inferring that prescribers pay little heed to interchangeability information in labeling when considering biosimilars for patients.
- This labeling policy eliminates an important advantage of interchangeability designations and hints at a broader agency trend to minimize the designation’s significance.
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Last week, the Food and Drug Administration (FDA) released a new Draft Guidance document, Labeling for Biosimilar and Interchangeable Biosimilar Products, Guidance for Industry. The guidance does not provide biosimilar manufacturers with any instruction regarding how to communicate biosimilar interchangeability for products that qualify for such designation. FDA’s notice announcing the availability of the draft guidance reveals that this omission was deliberate, and that the agency has reversed its previous stance on disclosing interchangeability in a product’s labeling.[1]
The new draft guidance, when finalized, will replace FDA’s 2018 biosimilar labeling guidance, and FDA states that its new labeling instructions supersede certain recommendations expressed in its 2020 Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act guidance document. Specifically, the new draft guidance recommends that interchangeable products should contain the same biosimilarity statement in the Highlights of the Prescribing Information section of the product’s labeling that is contained in the labeling for biosimilars without the designation.
FDA cited its experience approving over 40 biosimilar products in the last eight years and input from prescribers as reasons for its new stance on interchangeable biosimilar labeling. The agency claims that including statements about interchangeability and explaining the interchangeability standard in labeling “is not likely to be useful to prescribers” since prescribers are already able to prescribe biosimilar products lacking an interchangeable designation in place of reference products “with equal confidence that they are safe and effective as their reference products.” The true utility of the interchangeability designation, the agency reasons, lies with pharmacy-level substitution of an interchangeable product without prescriber intervention. FDA believes that its Purple Book Database of Licensed Biological Products (Purple Book), which displays a biosimilar’s interchangeability designation, is a more appropriate resource to convey information regarding interchangeability than the prescribing information or other labeling.
While FDA cites clinical experience in support of its new interpretation and implementation of the Biologics Price Competition and Innovation Act (BPCI Act), it remains unclear if its new guidance adequately achieves the separation between standard biosimilars and interchangeable biosimilars contemplated in the statute. The agency’s rationale for omitting interchangeability language in product labeling suggests that physicians may already be prescribing non-interchangeable biosimilars in an interchangeable fashion, and that the distinction between the two is irrelevant and potentially confusing due to recent prescriber feedback.
Providing interchangeability designation information in the Purple Book alone, however, may not adequately provide manufacturers with the advantages the statute provides and redistributes the balance of benefits and obligations associated with obtaining an interchangeable designation.
To receive an interchangeable designation, a sponsor must demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient. For a product that is administered more than once to an individual, a sponsor must also demonstrate that the risk in terms of safety or diminished efficacy of alternating or switching between use of the biosimilar product and the reference product is not greater than the risk of using the reference product without alternating or switching. FDA has, to date, only made four interchangeable designations thus far.
Biosimilar developers may be wondering whether FDA’s stance on this issue will lead to a further erosion of the interchangeability designation and its advantages. In last year’s year-end omnibus bill, Congress amended the BPCI Act to clarify that the one-year exclusivity period awarded to the first biosimilar to be approved as an interchangeable would be shared among multiple interchangeable products if the products are approved as interchangeable on the same day.[2] Some more recent legislative proposals have surfaced to preserve the distinction but remove barriers for demonstrating interchangeability while other proposals aim to remove the distinction between interchangeable biologics and other biosimilars altogether.
FDA has opened a public docket for interested stakeholders to comment on the draft guidance.
[1] FOOD & DRUG ADMIN., Notice of Availability, Labeling for Biosimilar and Interchangeable Biosimilar Products; Draft Guidance for Industry; 88 Fed. Reg. 63.957 (Sep. 18, 2023).
[2] Consolidated Appropriations Act of 2023, H.R.2617, 117th Congress, § 3206 (Now 42 U.S.C. § 262(k)(6)).
