FDA Rule Shifting Drugs to New Approval Pathway May Cause Continued Generics Delays

The U.S. Food and Drug Administration (FDA) issued a final rule last week that broadened the scope of the Biologics Price Competition and Innovation Act (BPCIA) to include large proteins, even those that could have been previously governed by the Hatch-Waxman Act. The change, which goes into effect on March 23, 2020, increases the number of drugs that are subject to approval as a biosimilar and/or interchangeable drug, but it appears to make offering lower-cost generic versions of some drugs, like insulin, even more difficult.

The “biological products” that were subject to BPCIA (as originally passed) included those drugs that contain “a protein (except any chemically synthesized polypeptide).” The Further Consolidated Appropriations Act, 2020, signed into law in December, removed the exception of chemically synthesized polypeptides from the statutory definition of “biological products.” Last Thursday, the FDA issued a final rule cementing the FDA’s broadened interpretation of the scope of the Act to include all proteins with “any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size.” The FDA confirmed that this rule would apply to proteins that contain multiple amino acid chains if the combined number of amino acids is greater than 40. The FDA declined to consider other aspects of drug structure (such as protein folding), instead opting for a “bright-line rule” that would avoid “regulatory uncertainty and inefficiency.” The FDA announced that this change will now bring more than 100 drugs (including insulin and human growth hormone) under the purview of the BPCIA, and any applications for generic versions of these drugs would require filing an abbreviated Biologics License Application.

The FDA also published two “Frequently Asked Questions” documents, one for patients and another for health care providers. The FDA clarified that the final rule “should not affect existing prescribing or dispensing practices and that patients should not notice any difference in their medications, or how they receive their medications, among other topics.” Thus, according to the FDA, the final rule would only affect the “behind the scenes” of drug manufacturing and approval.

One of the FDA’s stated goals for the final rule is to bring more generic versions of complex protein drugs to market. However, this benefit may not be realized. Previously, generic versions of at least some protein-based drugs—such as insulin—were subject to the lower standard of “therapeutically equivalent” to the reference listed drug. Even under that previous standard, it was still difficult to obtain approval due to the complexity of these drugs. Now, these drugs must meet the higher standard in the BPCIA that requires a showing of “no clinically meaningful difference” to the reference biologic. To date, the FDA has approved only 26 biosimilars under that standard, and no biosimilar has met the even higher standard for interchangeability. Thus, until the FDA provides practical options to navigate the BPCIA more effectively, competition between generic and brand versions of “biological products” will likely remain unchanged.