FDA Finalizes ‘Biological Product’ Definition Ahead of BPCIA Transition

A month before the long-anticipated transition of applications for certain biological products, including insulin and human growth hormone, to be deemed to be licensed as biologics, the US Food and Drug Administration (FDA) on Thursday issued a final rule amending its definition of “biological product.”
 
The final rule is one of the last steps in the decade-long transition set in motion by the Biologics Price Competition and Innovation Act of 2009 (BPCIA) to deem applications for biologics approved under section 505 the Federal Food, Drug, and Cosmetic Act as being licensed under section 351 of the Public Health Service Act.
 
Effectively, on 23 March 2020, some 100 products approved under new drug applications (NDAs) will transition to biologics license applications (BLAs). “This transition will open new pathways for manufacturers to bring biosimilar and interchangeable versions of insulin and other transitioning products to market, facilitating greater competition in the marketplace,” said FDA Commissioner Stephen Hahn.
 
Under the rule, FDA is amending its definition of “biological product” in line with the statutory definition set by the BPCIA, as amended by the Further Consolidated Appropriations Act, 2020 (FCA). Initially, the BPCIA amended the definition of a “biological product” to include “protein (except any chemically synthesized polypeptide).” In December 2019, the FCA struck the parenthetical excluding chemically synthesized polypeptides from the definition.
 
As such, FDA now interprets the term “protein” to mean “any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size.”
 
FDA says this interpretation is consistent with what it proposed in 2018 and with the term’s use in its 2015 biosimilars questions and answers guidance. Within the final rule, FDA also defended its decision to limit its interpretation of proteins to those greater than 40 amino acids in size.
 
“Given the lack of a clear scientific consensus that FDA could consider for adoption, the agency is applying its scientific expertise to interpret the statutory term ‘protein’ in a manner that establishes a scientifically reasonable, bright-line rule that provides regulatory clarity and facilitates the implementation of the [BPCIA],” FDA writes.
 
FDA also notes that it decided against including structural or functional attributes, such as folding, to its interpretation of the term “protein,” as doing so would raise questions and “result in regulatory uncertainty and inefficiency.”
 
In addition to the final rule, FDA also released two frequently asked questions (FAQ) documents for patients and healthcare providers explaining the transition and how it will affect them.
 
FDA, Final Rule