June 27, 2019
“The FDA has been working hard to implement Congress’ direction to transition biological products approved under the Federal Food, Drug, and Cosmetic Act as drug products to be deemed licensed as biologics under the Public Health Service Act on March 23, 2020 – a shift that ultimately means opening these specific products up to competition through the biosimilars pathway. This includes insulin, which has been historically regulated as a drug and not a biologic. As we move closer to the upcoming transition date, our work is focused on a variety of coordinated steps that will help ensure there is a seamless transition with minimal impacts to the makers of these products and, most importantly, to the patients who rely on them,” said Acting FDA Commissioner Ned Sharpless, M.D. “We have identified approximately 89 approved new drug applications that will transition on March 23, 2020; approximately 17 of them incorporate certain information related to the drug and its components in documents known as drug master files. While this is a technical detail for a limited number of products, this presents a complication for the transition since under our current practice, licensed biologics are not permitted to reference master files for this type of information. To help facilitate the seamless transition of these products, we’re focused on advancing policies, like today’s proposed rule, to provide clarity and predictability, and minimize burden for transitioning products – without compromising the quality, safety or efficacy of the products. The proposed rule is intended to help mitigate any unintended consequences of the transition, including the potential for drug shortages, if manufacturing were to be disrupted.”
Today the U.S. Food and Drug Administration 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. 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.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.