Biologic Products Approved as NDAs Transition to BLA

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) will require biologic products (which include insulin products and human growth hormones) to be regulated under the Public Health Services (PHS) Act as of March 23, 2020. These products are currently regulated under the provisions of the Food Drug & Cosmetics Act (FD&C Act) where new drug applications (NDAs) are used.  Under the PHS Act, a biologics license application (BLA) will be required.

In a 2018 statement, former FDA Commissioner Scott Gottlieb addressed the upcoming change, stating, “There are currently no approved insulin products that can be substituted at the pharmacy level. One reason is that it was hard to bring a substitutable generic insulin to the market under the conventional drug pathway. The biosimilar pathway should make this kind of competition more accessible. Once an interchangeable insulin product is approved and available on the market, it can then be substituted for the reference product at the pharmacy, potentially leading to increased access and significantly lower costs for patients.”

How will FDA transition these responsibilities? The agency developed a document called “The ‘Deemed to be a License’ Provision of the BPCI Act: Questions and Answers” to provide answers regarding its interpretation of the transition guidelines. The document also includes FDA’s compliance policy for labeling biological products that are subjected to BLA approval. The FDA proposes its “nonbinding recommendations” to create a set of standards to follow after the transition date. These preset guidelines will be used to deem approval of biological products under the FD&C Act for a license for biological products under the PHS Act. The FDA will be sending letters to holders of approved NDAs on March 23, 2020 to notify them the approved application will be “deemed to be a license” for the biological product on the transition date. Current NDA holders are still responsible for post-approval requirements.

The FDA released the “Preliminary List of Approved NDAs for Biological Products That Will Be Deemed to be BLAs on March 23, 2020” which has gone through multiple updates since its original release. The current version has been updated through December 31, 2019. Most recently, the update added three NDAs that now fall into the “biological product” category following an updated definition made by the Further Consolidated Appropriations Act, 2020. The current list contains approximately 95 NDAs set to transition to BLAs in March.

One consequence of the transition from NDAs to BLAs will be that drugs will lose their unexpired exclusivities when transitioning to biological products (with an exception of the orphan drug exclusivity).  Any 3 or 5 year exclusivity applied to an NDA- approved biological product will end at midnight on March 20, 2020. Of the nearly 100 products on the list, only 10 have an initial NDA approval date after March 2015. Newer products will likely feel the effects to a greater extent, as they lose out on years of exclusivity. Manufacturers with pipeline products approved via NDA but expected to transition to BLAs should have already evaluated the consequences of an NDA approval prior to March 23, 2020.

The goal of this change is to promote biosimilar entry to create competition and encourage lower cost options. Insulin products, which have been in the spotlight regarding patient affordability, make up over 25% of NDAs on the list. The FDA released draft guidance for industry in November 2019 to encourage development of biosimilar insulin products. Time will tell if biosimilar entry of these biological products deemed to be BLAs has the intended effect on pricing and availability.


Posted February 2020

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