FDA releases final guidance documents on biosimilars

The FDA issued three final guidance documents on biosimilars for pharmaceutical manufacturers and others in late April.

The documents, which have been in draft form since 2012, include: “Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009”, “Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product” and “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product”.

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The FDA said it will consider the "totality of the evidence" when assessing a sponsor's evidence of biosimilarity. “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," FDA wrote in the Scientific Considerations guidance.

To demonstrate biosimilarity, 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.

Biosimilars manufacturers are required to include data supporting the analytical similarity of the proposed biosimilar product to the reference product, according to the Quality Considerations guidance, and the rationale for the assessment should be "clearly described" in the submission.

"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,” the FDA wrote.

Although biosimilars may be formulated differently than the drug they reference in an application, the drugs must be supported by data indicating that such differences are minor and do not result in "meaningful differences" in safety, purity, and potency.

The FDA may also accept differences in the delivery device or container system for the biosimilar drugs as long as differences do not result in clinically meaningful differences and do not employ a different route of administration.