Drugs

Draft Biologic Interchangeability Guidance Out

David McFarland

— 2 min read
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FDA has published a draft guidance, Considerations for Demonstrating Interchangeability with a Reference Product, to help sponsors show that a proposed therapeutic protein product is interchangeable with a reference product for the purpose of submitting a marketing application or supplement under the Biologics Price Competition and Innovation Act (BPCIA). The agency says the long-awaited document is one of a series of guidances being developed to implement the act.

FDA says it “intends to consider the totality of the evidence provided by a sponsor when the agency evaluates the sponsor’s demonstration of interchangeability according to the criteria set forth in the BPCIA.” The act says that the terms “interchangeable” and “interchangeability” mean in this context that the biological product may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product, the guidance says.

The data and information to support a showing that the proped interchangeable product can be expected to produce the same clinical result as the reference product in all the reference product’s licensed conditions of use may vary depending on the nature of the proposed interchangeable product and may include, but not be limited to, an evaluation of data and information generated to support a demonstration of biosimilarity such as: 

  •          identification and analysis of the critical quality attributes;
  •          identification of analytical differences between the reference product and the proposed interchangeable product and an analysis of the potential clinical impact of the differences;
  •          analysis of mechanism(s) of action in each condition of use for which the reference product is licensed;
  •          pharmacokinetics and biodistribution of the product in different patient populations;
  •          immunogenicity risk of the product in different patient populations;
  •          differences in expected toxicities in each condition of use and patient population; and
  •          any other factor that may affect the safety or efficacy of the product in each condition of use and patient population for which the reference product is licensed.

“Where applicable,” the guidance says, “the data and information should include a scientific justification as to why any differences that exist between the reference product and the proposed interchangeable product, with respect to the factors described, do not preclude a showing that the proposed interchangeable product can be expected to produce the same clinical result as the reference product in any given patient.”

The guidance includes an introduction, scope, background, general principles, factors impacting the type and amount of data and information needed to support a demonstration of interchangeability, data and information needed to support a demonstration of interchangeability, use of a U.S.-licensed reference product in a switching study or studies, considerations for developing presentations for proposed interchangeable products, and postmarketing safety monitoring considerations.

In a CDER From Our Perspective blog post, Office of New Drugs associate director for therapeutic biologics Leah Christl says that for products that will be administered more than once, the data and information must show that switching a patient back and forth between the reference product and the proposed interchangeable product presents no greater risk to the patients in terms of safety or diminished efficacy when compared to treating them with the reference product continuously.

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