FDA Outlines New Plans for Biosimilars in 4 Guidance Documents and Proposed Rule

On Tuesday, the FDA took significant steps toward a long-awaited transition of insulins and other products that have historically been regulated as drugs and follow-ons to regulation as biologics and biosimilars.
Kelly Davio
December 12, 2018
On Tuesday, the FDA took significant steps toward a long-awaited transition of insulins and other products that have historically been regulated as drugs and follow-ons to regulation as biologics and biosimilars.

In a statement, FDA Commissioner Scott Gottlieb, MD, said that, “Until recently, biologics lacked effective competition because there was no abbreviated pathway for bringing generic versions of biologics to market under the Public Health Service Act, similar to the pathway we have for small-molecule drugs under created under the 1984 Hatch Waxman amendments to the Federal Food, Drug, and Cosmetics Act.” In concert with its plans to treat all biologics equally under the law, he said, the FDA has released multiple guidance documents and a proposed rule that explain how the agency will approach a “seamless transition” of these products.

First, the FDA announced its proposed rule that would amend its definition of “biological product” to include proteins and chemically synthesized polypeptides. This definition would encompass any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size, as well as any alpha amino acid polymer that is made entirely by chemical synthesis and is greater than 40 amino acids and less than 100 amino acids in size.  

Concurrently, the FDA released final guidance for industry on the interpretation of the “Deemed to be a License” provision in in section 7002(e) of the Biologics Price Competition and Innovation Act (BPCIA). The BPCIA stipulated that a marketing application for a biologic that could have been submitted under section 505 of the Food, Drug and Cosmetic (FD&C) Act must be submitted under section 351 of the Public Health Service (PHS) Act, but some products were allowed a 10-year transition period, which will expire on March 23, 2020. Starting on that date, approved applications for biologics approved under the FD&C Act will be deemed to be licensed under the PHS Act.

In the new guidance, the FDA explains its interpretation of this provision to mean that, on the transition date, only approved New Drug Applications (NDAs) will be deemed to be Biologics License Applications (BLAs). Any NDA pending a decision (on March 20, 2020) for a biologic that relies on safety or effectiveness findings for a listed biologic will receive a complete response. Additionally, any stand-alone NDA for a biologic that is pending a decision on March 23, 2020, will receive a complete response. These applications can be resubmitted under the BPCIA, and the FDA says it will assist applicants with this process.

The guidance also explains that the FDA will remove biologic products approved through NDAs from the Orange Book and into the Purple Book on March 23, 2020. Furthermore, any unexpired period of exclusivity (with the exception of pediatric or orphan drug exclusivities) associated with approved NDAs for biologics will cease to have effect on the transition date. A biologic first approved via an NDA will not be eligible for exclusivity under the PHS Act, as, according to the FDA, the BPCIA does not suggest that Congress intended for existing products to gain new 12-year exclusivities that would impede biosimilar competition.

The FDA also provided a question-and-answer draft guidance on the “Deemed to be a License” provision, in which it provides a link to a new FDA website that provides a preliminary list of products that will be affected by the transition. These products include insulins, somatropin, follitropin, hyaluronidase, and chorionic gonadotropin, among others.

Additionally, the FDA released 2 new guidances on biosimilar development under the BPCIA. First, a revised question-and-answer document addresses such questions as what type of marketing application a developer should submit for products like antibody–drug conjugates, and how biosimilar developers can determine whether there exist unexpired orphan exclusivities for indications of particular reference products.

Finally, the agency published a new and revised draft question-and-answer guidance on biosimilar development that addresses such questions as how a developer can fulfil the requirement for pediatric assessments and investigations under the Pediatric Research Equity Act, and what kinds of information a sponsor should provide to support post-approval manufacturing changes for licensed biosimilars.

The document also clarifies that sponsors cannot seek approval for routes of administration, dosage forms, strengths, or conditions of use that differ from those of the reference product. Finally, the document explains that a BLA applicant can request a letter from the FDA saying that a developer’s safety protections are comparable to the reference product sponsors’ Risk Evaluation and Mitigation Strategy—or REMS—program.

The FDA will take comments on its draft guidances until February 11, 2019.

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