Draft Guidance for Industry on Considerations in Demonstrating Interchangeability with a Reference Product

Considerations in Demonstrating Interchangeability with a Reference Product is a draft guidance for industry intended to assist sponsors in demonstrating that a proposed therapeutic protein product (e.g., monoclonal antibody) is interchangeable with a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 Act (PHS Act). Products approved as interchangeable may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.

For a biological product to be deemed interchangeable with a reference product, the data and 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. As described in the draft guidance, the FDA expects that sponsors seeking an interchangeability determination will submit data and information to support a showing that the proposed interchangeable product can be expected to produce the same clinical result as the reference product in all of the reference product’s licensed conditions of use.

In addition, for products that will be administered more than once to an individual, the data and information must show 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. Current FDA thinking is that postmarketing data generally will not be sufficient to support a demonstration of interchangeability; sponsors will need to submit data derived from appropriately designed, prospective, controlled switching studies.

The draft guidance provides an overview of important scientific considerations in demonstrating interchangeability, including:

  • Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability.
  • The 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.
  • Recommendations regarding the use of U.S.-licensed reference products in a switching study or studies.
  • Considerations for developing presentations, container closure systems, and delivery device constituent parts for proposed interchangeable products.

The draft guidance does not detail how multiple biosimilars would be considered interchangeable with each other.

The full document is available on the FDA website.