The FDA issued a long-awaited draft guidance for the biopharmaceutical industry that outlines the agency’s criteria for demonstrating that a biosimilar is interchangeable with a reference product—that it can be substituted for a reference product by a pharmacist without requiring intervention of a prescribing healthcare provider if state regulations allow pharmacy-level substitution. Interchangeability isn’t required for FDA approval of a biosimilar or for commercial adoption of a product, but it is an important advantage in the US marketplace. Prior to the release of this guidance it was not known how the agency wished drug sponsors to prove interchangeability.
Comments on the guidance must be received within 60 days of January 17, 2017, before the FDA makes its interchangeability rules final.
The guidance explains the type and amount of data and information needed to support a demonstration of interchangeability with the reference drug. It specifies that pharmaceutical sponsors of proposed biosimilars should submit data from switching studies or other studies, and how they should be designed to demonstrate that the biosimilar is interchangeable with a reference drug.
The FDA states that the main purpose of a switching study or studies is to demonstrate that the risk in terms of safety or diminished efficacy of alternating or switching between use of the proposed interchangeable product and the reference product is not greater than the risk of using the reference product without such alternation or switch. The switching study should evaluate changes in treatment that result in two or more alternating exposures to the proposed interchangeable product and to the reference drug. In addition, the guidance states that a switching study is to determine a biosimilar product’s interchangeability with a reference product that is licensed for use in US clinical settings; thus, establishing interchangeability with a product that patients will not receive in the United States would generally not be appropriate.
Analysts have suggested that the new guidance will make it harder to achieve an interchangeable designation than the industry had hoped. Switching studies are more complicated than many of the studies already in process, and will be required to include two exposure periods per product. In addition, the guidance suggests that the process of gaining a designation of interchangeability will be a long one.
It is likely that sponsors of biosimilars have been receiving informal guidance from the FDA as they work to bring their products through the approval process, but it is not clear whether drug developers are using study designs that would potentially meet the new standards expressed in the interchangeability draft guidelines.
The guidance notes that because of the complexity of biosimilars, the agency will consider interchangeability on a case-by-case basis. While the FDA will generally not consider postmarketing data, in certain specific circumstances such data from a licensed biosimilar may be a factor to consider concerning what data are needed to support a demonstration of interchangeability.
A perspective piece by Leah Christl, PhD, Associate Director for Therapeutic Biologics and Lead of the Therapeutic Biologics and Biosimilars Staff in the Office of New Drugs provides a detailed explanation of how the FDA approaches the issue of interchangeability to ensure there are rigorous approval standards, as for products administered more than once. “There is no single data package that will work for all proposed interchangeable products,” she writes. “With this in mind, we recommend that applicants developing a proposed interchangeable product meet with FDA early in their development process to discuss their plans.”