Proposed Rule Designed to Open Biosimilar Competition

July 2, 2019

FDA proposes rule to help ensure availability of hormones and enzymes formerly classified as drugs, and to stimulate biosimilars competition.

In an effort designed to ensure adequate supplies and to stimulate biosimilars competition, FDA has proposed a new rule that would clarify the use of information contained in drug master files (DMFs) for certain biologics (i.e., hormones and enzymes previously licensed under the Food, Drug and Cosmetics Act [FD&C Act] that will transition to licensing under the Public Health Service [PHS Act] on March 23, 2020). Currently, FDA does not allow licensed biologics applications to reference DMFs for information on drug substances or intermediates.

Released for comment on June 28, 2019, the new rule would implement aspects of 7002(e) of the Biologics Price Competition and Innovation (BPC) Act of 2009 for the 89 compounds that meet this description. They include hormones such as insulin, which is currently classified as a drug, but would be classified as a biologic, and supplies of which are tightening globally. HYPERLINK https://www.bbc.com/news/world-asia-india-46354989. 

Of the 89 compounds, approximately 17 of these biologics in transition currently incorporate information related to the drug and its compounds in DMFs.

The proposed rule would allow applications for biological products approved under the FD&C to reference information (e.g., data on drug substances and intermediates, or drug products) contained in DMFs and would allow this practice to continue after they have been approved and licensed under the PHS Act. The proposed rule would also formalize current FDA practice, so that, for example:

  • An application for a biological product under the PHS Act may rely on a master file, except for information on APIs, for intermediates that become APIs during processing, or for finished dosage forms

  • Information from the DMF might be relied upon during the early development phase for products that would be licensed under the PHS Act.

By allowing transitioned products to continue to refer to existing DMF, FDA leadership estimates that the proposed rule will generate annual net cost savings of roughly $2.5 million.

Acting FDA commissioner Ned Sharpless expects the new rule to help prevent shortages or other supply disruptions for these drugs and to spur competition via biosimilars. “While [inclusion of drug substance information via a DMF] is a technical detail for a limited number of products, it presents a complication for the transition [to PHS] since under our current practice, licensed biologics are not permitted to reference master files for this type of information,” he said in an FDA statement, noting the agency’s goal to “facilitate the seamless transition of these products.” The proposed rule is also intended to help mitigate any unintended consequences of the transition, including the potential for drug shortages, if manufacturing were to be disrupted, Sharpless said.

Many of these products have been sold for decades, and FDA regulators are certain that the new rule will not introduce any new risks to product safety, purity, or potency. However, after the transition to PHS, any proposed biosimilar or other interchangeable product will not be able to refer to the DMF for drug substance, intermediate or product information, as stipulated by existing FDA requirements for Biologics License Applications.

The agency is actively requesting comment on the new proposed rule via the US Office of the Federal Register.

Source: FDA