FDA Finalizes Guidance Documents on Biosimilars

The U.S. Food and Drug Administration (FDA) has finalized three guidance documents outlining its expectations for biosimilars. The first is a question-and-answer document outlining how FDA interprets the Biological Price Competition and Innovation Act, including its provisions on exclusivity, biosimilarity and interchangeability. Some of the high-level expectations for biosimilars include:

• Biosimilars may be formulated differently than the drug they reference in an application, but must be supported by data indicating that such differences are minor and do not result in “meaningful differences” in safety, purity and potency.
• Differences in the delivery device or container system may also be acceptable as long as differences in the delivery do not result in clinically meaningful differences and do not employ a different route of administration.
• A biosimilar product may be approved for some of the strengths for which a reference product has obtained approval. It does not need to obtain licensure for all strengths.
• Sponsors may rely on comparative animal or clinical data using a non-U.S.-licensed product to support an indication of biosimilarity. “However, as a scientific matter, analytical studies and at least one clinical pharmacokinetic (PK) study and, if appropriate, at least one pharmacodynamic (PD) study, intended to support a demonstration of biosimilarity must include an adequate comparison of the proposed biosimilar product directly with the U.S.-licensed reference product unless it can be scientifically justified that such a study is not needed.”

The second document details the quality factors companies need to take into account when characterizing a biosimilar product. Specifically, the document states: “Sponsors should use appropriate analytical methodology that has adequate sensitivity and specificity to detect and characterize differences between the proposed product and the reference product.” In addition, it states that companies are required by law “to include data supporting the analytical similarity of the proposed biosimilar product to the reference product.”

The third document explains FDA’s recommended approach for demonstrating biosimilarity using scientific data. According to the document: “As a scientific matter, analytical studies and at least one clinical PK study, and if appropriate, at least one PD study, intended to support a demonstration of biosimilarity for purposes of section 351(k) of the PHS Act must include an adequate comparison of the proposed biosimilar product directly with the U.S.-licensed reference product unless it can be scientifically justified that such a study is not needed.” And, it states that FDA encourages a “stepwise approach”: “At each step, the sponsor should evaluate the extent to which there is residual uncertainty about the biosimilarity of the proposed product and identify next steps to try to address that uncertainty.”

The documents can be downloaded at www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM444661.pdf, www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291134.pdf and www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf.