The FDA recently proposed an amendment to its regulations defining the term “biological product.” The proposed amendment incorporates changes made by the Biologics Price Competition and Innovation Act (BPCIA) into the FDA’s regulations, and provides the FDA’s interpretation of the statutory terms “protein” and “chemically synthesized polypeptide.” The proposed definitions of the statutory terms are not too surprising because they are the same definitions that the FDA has provided in previously issued guidance documents.

The FDA’s proposed definition of “protein” is “any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size.” The proposed definition of “chemically synthesized polypeptide” is “any alpha amino acid polymer that is made entirely by chemical synthesis and is greater than 40 amino acids but less than 100 amino acids in size.” The proposed definitions for both terms include the proviso that if two or more chains of an amino acid polymer are associated with one another as they are in nature the size of the amino acid polymer will be based on the total number in the chain and is not limited by the number in a contiguous sequence. The FDA also explains in the rulemaking document that if a product comprises amino acid chains that are associated in a manner not found in nature, then the FDA will conduct a fact-specific, case-by-case analysis to determine whether the size of the amino acid polymer should be determined by adding the total number of amino acids together, or if it should be based on the amino acid chain lengths in isolation.

The purpose of the proposed amendment is to clarify the statutory authority under which protein products are regulated. In particular, the proposed amendment will help determine whether a product comprised of amino acids will be regulated under section 351 of the Public Health Service Act (PHSA), or section 505 of the Food, Drug, and Cosmetic Act (FD&C Act). For example, under the proposed rule, an amino acid polymer with a specific, defined sequence less than 40 amino acids in size will be considered a peptide, and will be regulated under the FD&C Act instead of the PHSA. In contrast, non-chemically synthesized proteins greater than 40 amino acids in length will be regulated by the PHSA.

The FDA also explains that the phrase “made entirely by chemical synthesis” in its proposed definition of “chemically synthesized polypeptide” means that the amino acids in the chain were added by a process that does not involve cell-based or cell-free recombinant DNA directed synthesis or recombinant RNA directed synthesis. If that condition is met, and the product does not otherwise fall under the definition of biological product, such as by being a vaccine, then the chemically synthesized polypeptide product will be regulated under the FD&C Act.

The clarification provided by the proposed rule is important as the end of the BPCIA transition period draws near. More specifically, on March 23, 2020, NDAs for certain biological products will be transitioned to BLAs as mandated by the BPCIA. For this reason, it is not surprising that the FDA also released guidance on how it will interpret certain statutory provisions relating to that transition on the same day as it published its proposed rule. The transition guidance documents will be discussed in a separate post.

Electronic or written comments on the FDA’s proposed amendment may be submitted until February 25, 2019.