FDA Issues Final Guidance on Interchangeability for Biologics

By Patricia Van Arnum - DCAT Editorial Director

May 16, 2019

The US Food and Drug Administration (FDA) has issued final guidance, Considerations in Demonstrating Interchangeability With a Reference Product, on the pathway for “interchangeable” biologics. The final guidance on interchangeability will provide clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act (PHS Act).

In the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), Congress created an approval pathway for biological products that are demonstrated to be “biosimilar” to or “interchangeable” with an FDA approved biological brand (or reference) product. The final guidance gives an overview of scientific considerations in demonstrating interchangeability with a reference product and explains the scientific recommendations for an application or a supplement for a proposed interchangeable product.

Once an application or supplement seeking licensure as an interchangeable product is submitted, the FDA will approve the biological product as interchangeable with the reference product if the information submitted in the application or the supplement is sufficient to meet the applicable statutory standard: among other things, that the biological 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. The guidance also explains potential ways to address the BPCI Act requirement for interchangeability that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without such alternation or switch.

The final interchangeability guidance will also enable biosimilar or interchangeable insulin products to come to market in the future. There are currently no approved insulin products that can be substituted at the pharmacy level, but under the BPCI Act, on 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, and the guidance will, among other things, help developers seek licensure for such products.

The FDA said that later this month it will hear from patients, advocates and industry about what factors the agency should consider when evaluating data and other information submitted by an applicant, including from analytical and clinical studies, to determine whether an insulin product is biosimilar to or interchangeable with a reference product. It said that it expects to hear stakeholder feedback on whether certain insulin products, such as those that use insulin pumps for continuous subcutaneous infusion among the approved uses, raise unique scientific considerations that the FDA should consider when evaluating biosimilar or interchangeable insulin products.

The FDA said that in advancing its broader policy efforts for biosimilar and interchangeable products, it will also be issuing additional guidance on the agency’s recommendations on the design and evaluation of comparative analytical studies and other scientific considerations needed to support a demonstration that a biological product is biosimilar to a reference product. This data will help build the foundation for a development program for a proposed biosimilar or interchangeable product.

To date, the FDA has licensed 19 biosimilar products.

Source: US Food and Drug Administration