FDA has reviewed and approved the majority of therapeutic biological products (i.e. Biotechnology Products) under the Public Health Service (PHS) Act. Most are submitted as BLAs and most aspects of the product quality have been reviewed by CDER’s Office of Biotechnology Product (there are some BLA product exceptions which are CBER regulated and a separate group in CDER reviews the process microbiology of BLA products).
However, some very notable exceptions existed to this scheme, including insulin and insulin analogs, human growth hormone, pancreatic enzymes, reproductive hormones. For historical reasons, these have been approved in new drug applications (NDAs) under the Food Drug and Cosmetic Act (FD&C Act). In general, the product quality of most of these have been reviewed by other quality offices in CDER (again with exceptions, the pancreatic enzymes were reviewed in the past few years by OBP).
The Biologics Price Competition and Innovation Act (BPCI Act, signed March 2010) is most known to have created a pathway for biosimilars. However, the BPCI Act also changed the statutory authority under which the NDA protein products will be regulated (and consequently the CMC review groups). Specifically, the BPCI Act amended the statutory definition of a “biological product” in the PHS Act to include a “protein (except any chemically synthesized polypeptide)”. Thus, at the stroke of a pen, all of the above NDA protein products, denoted as “transition products” will now be biologicals (i.e. biotechnology products) effective March 23, 2020, overseen by OBP.
The latest turn in this saga is a very recent small change in the PHS Act. The genesis is the “Further Consolidated Appropriations Act, 2020”, enacted by Congress on December 20, 2019. This new law changed the PHS Act to redefine a “biological product” to include a “protein”, removing the parenthetical “(except any chemically synthesized polypeptide)”.
At the surface, this legislative change seems tiny- unless your firm is producing a chemically synthesized polypeptide product. If you are such a firm, this change is not tiny to you as your product will now be part of the March 2020 transition from NDAs to BLAs, potentially with all of the associated consequences. These changes are not trivial- they include a new CMC review office, a greater emphasis on process microbiology, a new team of pre-approval inspectors and the need for upfront process validation in the BLA.
FDA has helpfully provided the public a January 2020 updated list of transition products, which now apparently includes four new entrants: Acthrel, Elase-chloromycetin, Adlyxin, and Egrifta SV. Note that this change only impacts products more than 40 amino acids in length, FDA still distinguishes “peptides” (i.e., polymers composed of 40 or fewer amino acids) from protein biologics. The full list of transition products can be found in the CDER document: “Preliminary List of Approved NDAs for Biological Products That Will Be Deemed to be BLAs on March 23, 2020 (current as of December 31, 2019)”
Parexel can help you navigate through the complexity of such, often abrupt, changes and provide you with key strategies to assist with conversations with FDA as the conversion process from NDA to BLA becomes final in a couple months. We have experience in providing expertise and solutions to clients in the transition product space. Please contact us to discuss your options and to assist in smoothing this, as can be seen above, unpredictable transition process.