FDA Releases Final Guidance on Interchangeability

May 14, 2019

Biosimilars Team

The Food and Drug Administration (FDA) has released a final version of its guidance for industry titled “Considerations in Demonstrating Interchangeability with a Reference Product.” In an accompanying statement, Acting FDA Commissioner Norman E. “Ned” Sharpless, MD, characterized the release as “a significant action that will help promote competition in the biologic market.”

The guidance is intended to assist sponsors in demonstrating that a proposed therapeutic protein product (e.g., a monoclonal antibody) is interchangeable with a reference product for the purposes of submitting a marketing application or supplement under section 351(k) of the Public Health Service (PHS) Act. Products approved as interchangeable may be substituted for the reference product without the involvement of the prescriber, similar to how generic drugs are routinely substituted for brand name drugs.

As stated in section 351(k)(4)(A) of the PHS Act, for a biological product to be deemed interchangeable with a reference product, the information submitted in the application or supplement must be sufficient to show that the proposed interchangeable product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. Further, for products that will be administered more than once to an individual, data (generally from a switching study or studies) must demonstrate that alternating or switching between use of the reference product and the proposed interchangeable product presents no greater risk to the patient in terms of safety or diminished efficacy than using the reference product continuously.

The final guidance provides an overview of important scientific considerations in demonstrating interchangeability, including:

  • Data and information needed to support a demonstration of interchangeability.
  • Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability.
  • Considerations regarding the comparator product in a switching study or studies.
  • Abbreviated considerations for developing presentations, container closure systems, and delivery device constituent parts for proposed interchangeable products.

The guidance incorporates comments received in response to the draft interchangeability guidance released in January 2017.

In the accompanying statement, Acting FDA Commissioner Sharpless noted that the final interchangeability guidance will help enable biosimilar or interchangeable insulin products to come to market in the future. As of March 23, 2020, insulin and other biological products that were approved as drugs under the Federal Food, Drug, and Cosmetic Act will be deemed biological products licensed and regulated under the PHS Act. After this transition, the FDA will be able to license biosimilar and interchangeable insulin products that meet the requirements of the PHS Act.