The US Food and Drug Administration (FDA) on Tuesday released high-level draft guidance explaining the principles for premarket review of combination products, including how sponsors can determine which type of premarket submission is appropriate.
The 22-page draft, which implements a section of the 21st Century Cures Act
, explains what combination products are, how their various FDA center assignments are determined and considerations for making approval pathway determinations.
FDA’s current thinking is that a single application is generally appropriate for a combination product, the guidance notes, with the primary mode of action (PMOA) determining which type of marketing application should be submitted (e.g., a PMA, De Novo, or 510(k) for a device-led combination product, an NDA or ANDA for a drug-led combination product or a BLA for a biologic-led combination product).
FDA also notes that the premarket review of a combination product can be “significantly streamlined” when its sponsor is legally authorized to rely on FDA’s prior findings of safety or effectiveness or substantial equivalence with respect to an approved or cleared constituent part, or where the sponsor has a right of reference for another sponsor’s data.
“Among other steps, we’re clarifying what pathways to approval are available depending on whether a combination product is drug-led, biologic-led or device-led. We’re seeking feedback on this proposed approach and we’ll also be publishing additional guidance on specific premarket considerations for combination products to ensure efficient product development,” FDA Commissioner Scott Gottlieb said.
The draft discusses the various pathways available for combination products based on their PMOA, and considerations for making such pathway determinations.
The draft guidance’s annex also features five illustrative examples of device-led combination products, including one for an antimicrobial coating added for the first time to a previously classified device.
“We're focused on implementing an efficient framework to ensure the timely and effective review of combination products to create the most robust pathway to advance these kinds of innovations. We’re seeing innovations that hold out great promise, but they’re increasingly blurring the lines across our medical product centers. We believe cross-center collaboration is key to successfully advancing safe and effective combination products,” said Gottlieb.
Principles of Premarket Pathways for Combination Products: Draft Guidance for Industry and FDA Staff