By Kate Cook, Greenleaf Health
For 10 years, the date March 23, 2020 has been circled in red on the FDA calendar. On that “transition date,” the Biologics Price Competition and Innovation Act (also known as the Biosimilars Act) decrees that certain drugs FDA approved under the drug approval statute will be “deemed” to have a biologics license (BLA) instead of a New Drug Application (NDA) approval. The FDA has identified a preliminary list of products affected by this law and promises to post a final list shortly after the transition date.
Prominent on the preliminary list are numerous insulin products, many of which have experienced large price increases in recent years. Biosimilar and interchangeable insulins are viewed as one way to counter rising prices, and they are the first class of biosimilar products to be addressed in a product specific guidance document, Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products, issued in draft in November 2019. Other products on the preliminary list include human growth hormones and follicle stimulating hormones, as well as several products added to the transition list after the December 2019 change in the protein component of the biological product definition.
The FDA has prepared diligently for the transition date by issuing guidances addressing several sticky issues. These include whether or not transitioned products would receive new periods of exclusivity and whether products originally approved as NDAs filed under section 505(b)(2), relying on the FDA’s previous finding of safety and effectiveness of another drug product, would transition as biological products licensed under 351(a) or as biosimilars under 351(k). Addressing the exclusivity issues, the FDA determined that NDA exclusivities would end on the transition date and no period of biologics reference product exclusivity would begin on the transition date, but orphan drug and pediatric exclusivities would continue, because those two types of exclusivities apply to both NDAs and BLAs. The FDA further determined that NDAs approved under 505(b)(2) would be deemed to have licenses approved under 351(a) and would not be biosimilars under 351(k).
On March 4, 2020, the FDA issued one more guidance, The “Deemed To Be a License” Provision of the BPCI Act Questions and Answers (final Q&A guidance), finalizing a December 2018 draft guidance of the same title. This guidance reflects the broader definition of “biological product” created by Section 605 of the December 2019 Further Consolidated Appropriations Act, which removed the parenthetical “(except any chemically synthesized polypeptide)” from the statutory category of “protein.” This statutory change expanded the number of “protein” biological products and prompted the addition of several products to the FDA’s preliminary list of transition products.
The changes in the Further Consolidated Appropriations Act were significant and are discussed in some detail in a previous article. While the final Q&A guidance addresses the bridge permitting continued review of certain NDAs for biological products beyond the transition date, provided that the application was filed not later than March 23, 2019, it identifies a limitation for efficacy supplements to NDAs approved using the 505(b)(2) pathway. On the transition date, if a transition product has a supplement under review, the supplement will be administratively converted to a BLA supplement on the transition date. However, the statutory provision in 505(b)(2) that supports an applicant’s reliance on the FDA’s previous finding of safety and effectiveness is not included in the statutory or regulatory framework for a 351(a) BLA. Once the NDA is deemed to be a license, the applicant may be unable to rely on the FDA’s previous finding of safety and effectiveness as evidence supporting approval of that efficacy supplement. Under these circumstances, “To obtain approval under section 351(a) … the applicant may need to amend the administratively converted supplement to provide the scientific data necessary to meet the requirements of section 351(a) … or a right of reference to such data, for the change proposed in the supplement.”
In addition, the final Q&A guidance addresses the following issues:
- The FDA reminds the application holder to ensure that the listing information for the transitioned product is updated in the FDA’s electronic Drug Registration and Listing System (eDRLS) to reflect a change in the prefix of the application number from “NDA” to “BLA.”
- The FDA advises that in the absence of other changes to the product, biological products that are “deemed” to have a license will retain their current National Drug Code (NDC) number after the NDA is deemed to be a BLA.
- References to drug labeling as “prescribing information” have been changed to “approved labeling” and the guidance now states that the “prescription or over-the-counter status of a biological product with an approved application under section 505 … will not change when the approved application is deemed to be a license.” These changes reflect the fact that certain insulins are over-the-counter products that do not require a prescription.
- The document includes a new discussion of additional chemistry, manufacturing, and control requirements that are applicable to “non-specified biological products” and are described in 21 CFR 600.10 (Personnel), 600.11 (Physical establishment, equipment, animals, and care), 600.12 (Records), and 600.13 (Retention samples). The FDA states that these provisions “differ in some respects from establishment standards” applicable to NDA products, but “FDA expect the practical implications for transition biological products to be minimal.” The FDA notes that the additional standards are not applicable to many categories of transition products and, when applicable, will be applied only when the sponsor seeks approval of a supplement to the deemed BLA.
On March 23, 2020, the FDA will undertake the administrative work necessary to deem the transition products to have a license. Once that occurs, we will wait to see how the dust settles. The first biosimilar insulins could be approved by the end of March. Legal challenges will likely follow some FDA decisions made for transitioned biological products, particularly decisions not to grant exclusivity and to permit market access by competitors.
About The Author:
Kate Cook is executive VP of drug and biological products at Greenleaf Health, Inc. She joined Greenleaf after a long career at the FDA, including 15 years in the Office of Chief Counsel, five years in the Office of the Center Director at the FDA’s Center for Biologics Evaluation and Research, and one and a half as associate director for regulations and policy at the FDA’s Center for Devices and Radiological Health. You can contact her at firstname.lastname@example.org.