Clarity for biosimilarity, FDA releases three guidance documents

The FDA published notices regarding publication of three guidance documents related to the development of biosimilar products and the demonstration of biosimilarity to a reference product for purposes of FDA marketing application approval under Section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. § 262). The three notices correspond to guidance documents related to quality considerations, scientific considerations, and questions and answers in the biosimilar approval process. The FDA is releasing the documents as part of a series intended to allow the agency to develop its position on the technical development and approval of biosimiliar products.


The guidance documents address abbreviated licensure pathway in Section 351(k) of the PHS Act, known as the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI provisions were created by Sections 7001 through 7003 of the Patient Protection and Affordable Care Act (ACA) (P.L. 111-148).

Quality consideration

The first guidance document is designed to help sponsors understand comparisons of a therapeutic protein product to a biosimilar reference product for purposes of processing marketing applications through the FDA’s abbreviated licensure pathway. Specifically, the guidance provides “recommendations to sponsors on the scientific and technical information for the chemistry, manufacturing, and controls (CMC) section of a marketing application for a proposed product.” The guidance focuses on the use of analytical studies to determine the similarities of products.

Scientific consideration

The guidance document related to scientific considerations is focused primarily on therapeutic protein products and important scientific considerations for demonstrating their biosimilarity to a reference product. Although the guidance is directed towards protein products, the FDA clarifies that the guidance may have applicability to other types of proposed biosimilar products. The guidance is designed to help sponsors consider the particular scientific issues associated with a demonstration of biosimiliarity of protein products. For example, the guidance addresses the reality that proteins, unlike small molecule drugs, are often too complex to allow a showing that they are structural identical to a reference product.

Q and A

The final guidance addresses common questions that the FDA receives from sponsors regarding the development of biosimilars and the provisions of the BPCI Act. The questions and answers are grouped by three areas: (1) biosimilarity and interchangeability; (2) the requirements for submission of a biologics license application (BLA); and (3) exclusivity. The questions address basic issues, like who a sponsor should “contact with questions about its proposed biosimilar development program.” The guidance also addresses more complex issues like whether a biosimilar can have a different formulation or delivery device than a reference product.