On April 28, 2015, the federal Food and Drug Administration (FDA) finalized three guidances for industry on developing biosimilar drugs. The guidances, which follow the FDA’s first approval of a biosimilar drug in March, are intended to clarify both scientific and regulatory considerations for a broad range of stakeholders, including drug companies, in manufacturing biosimilars. The guidances include: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; and Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.

Scientific Considerations

The guidance on scientific considerations provides an overview of FDA’s approach to determining biosimilarity. Specifically, this guidance purports to assist sponsors in demonstrating that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submitting a marketing application through an abbreviated licensure pathway under section 351(k) of the Public Health Service Act. Under the guidance, FDA highlights the Agency’s intention to consider the totality of the evidence submitted in a 351(k) application. FDA also notes the importance of particular scientific considerations in demonstrating biosimilarity, including a stepwise approach to demonstrating biosimilarity and general scientific principles in conducting comparative structural analyses, functional assays, animal testing, human pharmacokinetics and pharmacodynamics studies, clinical immunogenicity assessment, and comparative clinical trials, including clinical study design issues.

Quality Considerations

The guidance on quality considerations provides sponsors with an overview of analytical factors that are relevant to assessing whether a proposed biosimilar product (i.e., a therapeutic protein product) and the reference product are highly similar for the purpose of submitting a marketing application through the 351(k) abbreviated licensure pathway. By way of background, biosimilarity is defined to mean that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components and that there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. In making this highly similar determination, FDA deemed the following factors important: expression system, manufacturing process, assessment of physiochemical properties, functional activities, receptor binding and immunochemical properties, impurities, reference product and reference standards, finished drug product, and stability.

Questions and Answers

Lastly, FDA issued answers to common questions from sponsors interested in developing proposed biosimilar products, biologic license application (BLA) holders, and other interested parties regarding FDA’s interpretations of the Biologics Price Competition and Innovation Act of 2009, which created the abbreviated licensure pathway for biosimilar products. The Q&A’s cover biosimilarity vs. interchangeability, provisions related to requirement to submit a BLA for a “biological product,” and exclusivity. FDA also noted that an alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.