FDAOn Tuesday, April 28, FDA finalized three “guidances to the industry” that describe FDA’s standards for approving biosimilar products (biosimilars).

A biosimilar is a biological product approved by the FDA based on a showing that (1) it is highly similar to an FDA-approved biological product (reference product), and (2) has no clinically meaningful differences in terms of safety, purity and potency from the reference product.

(1) “Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009

In a Q&A format, FDA includes most of the nonbinding recommendations from the draft guidance regarding three categories of questions:  (i) biosimilarity or interchangeability; (ii) provisions related to requirement to submit a biologics license application for a “biological product”; and (iii) exclusivity.

For example, while FDA reiterated its policy that studies must compare a biosimilar to its US-licensed brand-name version to support a determination of interchangeability with a US-licensed reference product, FDA provided that otherwise it will evaluate whether a comparison to a non-US comparator product can be scientifically justified as adequate on a case-by-case basis.

Nonetheless, FDA explains that, as a scientific matter, establishing an acceptable “bridge” of a non-U.S. version of a product to a U.S. version of the comparator product will include data from analytical studies that compare all three products: proposed biosimilar, the U.S.-licensed reference product, and the non U.S. licensed comparator product. FDA further provided that “[f]or certain complex biological products, a modified approach may be needed.”

It is expected that any questions and answers included in the draft guidance previously, such as inquiries about drug interactions, retention of samples, and whether interchangeability can be obtained via an original application, will be added at a later date to a revised version of this final guidance.

(2) “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein to a Reference Product”

FDA provides recommendations to sponsors of a proposed therapeutic protein biosimilar on the scientific and technical information required for the chemistry, manufacturing, and controls (CMC) section of a marketing application under section 351(k) of the Public Health Service Act.

This final guidance added a recognition that biosimilars sometimes can have distinct impurities. In addition, the document incorporated a section on manufacturing changes proposed in response to certain assessments or studies. Given that drug makers must explain changes in production, the guidance made clear that “the nature and extent of the changes may determine the extent [to which] additional similarity studies [are required].”

(3) “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product”

FDA provides an overview of (1) its stepwise approach to determining biosimilarity, (2) its totality-of-the evidence approach to review applications for biosimilars, and (3) the general scientific principles in demonstrating biosimilarity. The final version reflects various changes from earlier versions, although none appear to be substantive in nature.

Additional guidance on interchangeability, naming and labeling of biosimilars, and statistical approaches to proving biosimilarity are expected later this year.