New guidance from the Food and Drug Administration directs companies on how to demonstrate a biosimilar’s interchangeability with its reference product. The draft outlines the data that companies should submit and explains how switching studies should be designed and analyzed – among other issues. It also confirms the FDA’s intention to make case-by-case approvals based upon a “totality of evidence.”
Achieving interchangeability status represents a significant benchmark for biosimilars, as it will allow pharmacists to substitute biosimilars for their reference biologic.
The draft guidance’s topline points include:
- Product similarity. The agency will analyze a product’s data to determine where it falls on a continuum of similarity to its reference product. “Fingerprint-like characterization” is the strongest level of similarity. The FDA considers issues such as structural complexity and potential impact on patients’ immune systems.
- Approved uses. Follow-on products may pursue approval for fewer, but not for more, indications than its reference product. FDA will also consider indication extrapolation. Extrapolation allows the agency to approve a medication to treat conditions based on the product’s similarity to the reference drug – without requiring thorough clinical trials for that condition.
- Switching data. Some biological products will be administered to patients more than once. For these drugs, the agency requires clinical data from a switching study. The FDA’s guidance outlines the process, scope and endpoints for such studies.
Though directed at industry, the guidance has elicited feedback from some patient and professional groups. The American College of Rheumatology reiterated the importance of data on switching, saying “We also applaud the FDA for suggesting clinical studies which switch back and forth, not just one-way from the reference drug to the biosimilar.”
On the topic of indication extrapolation, however, Patients for Biologics Safety and Access expressed concerns. “How will FDA adequately assure patient safety,” the group questioned in a public statement, “if…a product can be approved as interchangeable for a condition without clinical studies of the safety and efficacy for that condition…?”
Extrapolation has worried patient advocates for some time, but the question of safe switching may now exacerbate those concerns. Little data exists thus far on the safety of switching between reference biologics and biosimilars. Moreover, a single biologic may treat a range of different disease states; data proving the safety of a biosimilar switch for one condition may not indicate equal safety and efficacy for patients with a different disease.
The agency will accept comments and questions on the draft guidance until March 20, 2017.