FDA Issues Biosimilars Draft GuidanceBy
The US Food and Drug Administration (FDA) has issued draft guidance, Statistical Approaches to Evaluate Analytical Similarity Guidance for Industry, to describe the type of information a sponsor of a proposed biosimilar product should obtain about the structural/physicochemical and functional attributes of the reference product, how that information is used in the development of an analytical similarity assessment plan for the proposed biosimilar, and the statistical approaches recommended for evaluating analytical similarity.
The guidance is one in a series of guidance documents that the FDA is developing or has developed to implement the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which created an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product. It serves as a companion document to the guidance, Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product.
“The analytical similarity acceptance criteria should be derived using data from an analysis of the US-licensed reference product, and the similarity assessment should be based on a direct comparison of the proposed biosimilar product to the US-licensed reference product,” the draft says. “To establish meaningful similarity acceptance criteria, sponsors should acquire a sufficient number of reference product lots. We recommend a minimum of 10 reference product lots be sampled. In cases where limited numbers of reference product lots are available (e.g., for certain orphan drugs), alternate analytical similarity assessments should be proposed and discussed with the agency.”
The draft says the final analytical similarity report, which should include the analytical similarity assessment plan, should contain: differences in age of the lots produced at testing; multiple testing results; assay performance; and differences in attributes that will be considered acceptable.
Additionally, the draft listed three tiers that the FDA believes, with appropriate similarity acceptance criteria, should help support a demonstration that the proposed biosimilar is highly similar to the reference product. Equivalence testing (Tier 1) is typically recommended for quality attributes with the highest-risk ranking and should generally include assay(s) that evaluate clinically relevant mechanism(s) of action of the product for each indication for which approval is sought. The use of quality ranges (Tier 2) is recommended for quality attributes with a lower-risk ranking, and an approach that uses visual comparisons (Tier 3) is recommended for quality attributes with the lowest risk ranking.