SILVER SPRING, Md.—In late June, the U.S. Food and Drug Administration (FDA) issued a proposed rule to amend its regulations on the use of master files for biological products. The proposed rule, if finalized, would allow certain applications for biological products approved under the Federal, Food, Drug, and Cosmetic Act to continue incorporating by reference information on drug substances, drug substance intermediates, or drug products contained in drug master files (DMF) after the approved applications for those products are deemed to be licenses under the Public Health Service Act (PHS Act) on March 23, 2020.
The proposed rule would also codify the FDA’s existing practice that an application for a biological product under the PHS Act may rely on a master file, except for information on drug substances (active pharmaceutical ingredient, or API), drug substance intermediates (a material produced during steps of the processing of an API that undergoes further molecular change or purification before it becomes an API), or drug products (finished dosage forms, such as tablets or capsules).
In addition, the proposed rule would codify the FDA’s existing practice that information from a master file, including drug substance, drug substance intermediate or drug product information, may be relied on at the investigational phase of development for a product subject to licensure under the PHS Act.
Some of the applications (approximately 17, such as reproductive hormones and enzymes) that will be transitioned currently incorporate reference information contained in DMFs to support their application and were approved by the FDA based in part on the drug substance, drug substance intermediate or drug product information contained in those DMFs.
As the FDA says, “Many of these products have been marketed for decades and over this period, none of these products have been withdrawn or removed from the market for reasons of safety or effectiveness. For these products, the FDA has no reason to believe that the March 23, 2020, transition in and of itself introduces new risks to product safety, purity and potency.”
Additionally, after the transition, a proposed biosimilar and/or interchangeable product to one of these transitioned biologics may not reference the DMF for the drug substances, drug substance intermediates or drug products information, consistent with existing practice for biological products submitted in Biologics License Applications and the use of master files.