Written By: Jorge Sugranes, Regional Director of Latin America, PSC Biotech

Here are some Q&A regarding combination products (CP) that you might like. I found this information, published by the FDA*, very helpful, educational, and clarifies common questions about CP.

*Reference: fda.gov

How are combination products assigned for review?

Combination products are assigned to FDA center that will have primary jurisdiction for its premarket review and regulation. Consistent with section 503(g)(1) of the Act, assignment to a center with primary jurisdiction for premarket review and post-market regulation, or a lead center, is based on a determination of the “primary mode of action” (PMOA) of the combination product. For example, if the PMOA of device-biological combination product is attributable to the biological product, the Agency component responsible for premarket review of that biological product would have primary jurisdiction for the combination product.

Section 503(g) defines primary mode of action as “the single mode of action of combination product that provides the most important therapeutic action of the combination product” (see also definitions at

2 CFR 3.2. In some cases, the most important therapeutic action cannot be determined. For example, combination product may have two independent modes of action, neither of which is subordinate to

the other. To resolve these types of questions, FDA’s regulations at 2 CFR Part 3 include an algorithm for determining center assignment. The algorithm directs center assignment based on which center regulates combination products raising similar types of safety and effectiveness questions, or, if there is n such center, based o which center has the most expertise to evaluate the most significant safety and effectiveness questions raised by the combination product.

What is the process for obtaining an Agency decision regarding the classification or center assignment for my medical product?

Sponsors may request formal assignment through the Request for Designation (RFD) process or alternatively obtain informal non-binding feedback regarding their combination product or product through submission of a Pre-Request for Designation (Pre-RFD).

 

How do I submit a Pre-Request for Designation (Pre-RFD)?

The Pre-RFD process is available to provide informal, non-binding feedback o whether a medical product is a drug, device, biological product, or combination product and/or the Center to which it would be assigned. Sponsors may contact OCP (i.e. at combination@fda.gov for information about how to submit a Pre-RFD. Additionally, OCP recently published a draft guidance about Pre-RFDs that may be helpful.

What types of marketing applications are required for a combination product?

Combination products are typically marketed under a marketing authorization type associated with the constituent part that provides the primary mode of action (PMOA) for the combination product (i.e., a new drug application (NDA) or abbreviated new drug application (ANDA) if it has a drug PMOA, a biologic license application (BLA) if it has a biologic PMOA, or a premarket approval application (PMA), de novo classification, or premarket notification (“510(k)”) if it has a device PMOA). A single marketing application is generally sufficient for combination product. In some cases, however, a sponsor may wish to submit separate marketing applications for different constituent parts of a combination product, and FDA may consider this permissible.

FDA