FDA Guidance on Biosimilar Interchangeability Hits the Right Points, Stakeholders Say

Stakeholders seemed satisfied with last week’s release of the FDA’s final guidance on demonstrating interchangeability of a biosimilar with its reference.

The guidance is intended to help biosimilar developers demonstrate that their products are interchangeable with a reference biologic for the purposes of submitting their marketing applications or supplementing them under the Public Health Service Act. A designation of interchangeability will allow a product to be substituted for its reference at the pharmacy level in the United States.

The guidance explains that the data and information needed to meet the legal standard for interchangeability, which shows that the proposed interchangeable product can be expected to produce the same clinical result as the reference product in any given patient, will vary by case.

The American College of Rheumatology (ACR), in a statement attributed to Angus B. Worthing, MD, FACR, FACP, who heads its government affairs committee, said it is “pleased to see that the final guidance expects manufacturers to use robust switching studies. At least 3 switches with each switch crossing over to the alternate product will be needed to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. The ACR believes these studies will provide an understanding of what patients are likely to experience when changing formularies in a multipayer, multistate market.”

The ACR said it is also glad the FDA finalized its approach to safety, immunogenicity, and efficacy for the demonstration of interchangeability.

In addition to the FDA setting up some parameters for postmarketing surveillance, the ACR suggested that “FDA prescribing information for all biosimilars include statements about whether each agent is or is not interchangeable to the reference product.”

The Biosimilars Council, a division of the Association for Accessible Medicines (AAM), said the final guidance is an improvement over the draft version. It said “each of our respective companies are now closely analyzing its potential impact. We look forward to continue its work with the FDA on this update and other policies that support biosimilar use in the [United States].”

In a joint statement attributed to Christine Simmon, executive director of the Biosimilars Council, the Council and AAM highlighted what they called “streamlined data and study design requirements that allow flexibility and the use of global comparator products to support applications. While the interchangeability designation does not confer any additional quality or safety attributes for FDA-approved biosimilars, we look forward to continue working with the agency to bring biosimilar medicines to America’s patients.”

The FDA is requiring data that may include:

• Identification and analysis of critical quality attributes
• Identification of analytical differences and an analysis of the potential clinical impact of such differences
• An analysis of the mechanism of action in each condition of use
• An analysis of differences in expected pharmacokinetics (PK) and biodistribution in different patient populations
• An analysis of differences in expected immunogenicity risk
• An analysis of differences in expected toxicity
• Information on factors that could affect safety or efficacy