Combination products are assigned to a 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 a 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 a combination product that provides the most important therapeutic action of the combination product” (see also definitions at 21 CFR 3.2. In some cases, the most important therapeutic action cannot be determined. For example, a 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 21 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 no such center, based on which center has the most expertise to evaluate the most significant safety and effectiveness questions raised by the combination product.

I would further like to continue this topic by asking 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 certification, or premarket notification (“510(k)”) if it has a device PMOA). A single marketing application is generally sufficient for a 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

Expanding on what Aasutosh said above, the primary mode of action (PMOA) is a significant process because it determines the regulatory and product development framework. A PMOA is determined by asking these 2 questions, “what is the device’s MOA?” and “what is the drug’s MOA?”. So if it is determined from the PMOA that a drug is involved than an abbreviated new drug application (ANDA) is required. This is submitted to the FDA for review and the potential approval of the drug. The biologic license application (BLA) is required to be submitted to the FDA if it involves a biologic product. Requirements of the BLA is application information, product/manufacturing information/preclinical studies, clinical studies and labeling. If a device is involved than premarket notification (“510(k)) is necessary. This is done if a Premarket Approval application (PMA) is not required.

When it comes to a PMOA there are three regulatory sectors that can be exploited: Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation (CBER) and Center for Devices and Radiological Health (CDRH). With these centers or sectors, the medical device can go to any one of these routes. However, if the device goes to the wrong one it can be a waste of time. So depending on the device, several regulatory pathways are available to the applicants including 520(k) premarket notification, reclassification, product development (PDP), de novo review, and premarket approval (PMA) application. Looking at the FDA website they describe how each of these regulatory pathways is done. In essence, if the medical device is completely new in terms of the device and using a bioactive component then the process, regular less of the pathway, will take extensive time and evaluation before even FDA can pass it.

FDA recognize that timely Pre-market reviews also depends on the timely and effective review consultations and collaborations between and among centers. For this reason, the Agency has established a standard operating procedure for the the Inter center consultative/collaborative review process to help ensure the timeliness and consistency of inter center review. for example,consultation time frames are established taking into account the time frame of agency response to the regulatory submission. Furthermore, OCP actively monitors the progress of consultative reviews to ensure their timely and effective completion .

https://www.fda.gov/RegulatoryInformation/Guidances/ucm126006.htm

Combination products are assigned to Centers with primary jurisdiction for premarket reviews and regulation. The determination is based on “primary mode of action” of the combination product. Sponsors can determine their product’s PMOA, If the PMOA is unclear, a sponsor can petition the OCP to assign its product to a review center through a Request for Designation (RFD), also known as letter of request. In its RFD, a sponsor can suggest how a product should be categorized.After submitting a request for designation by the company the Office of Combinations Products will decide the most important aspect of the combination, either the drug or the device, through the Request for Designation (RFD) process. If it’s deemed the drug is the primary mode of action, it will be reviewed by CDER if its deemed the device is the primary mode of action, CDRH (Center for Devices and Radiological Health) will review it. So the regulatory requirements are not standardized for all combination products, but are specific based on whether it’s a drug/device, a biologic/device, or a drug/biologic.A single application can be submitted to lead center for market approval,however in some cases two applications are needed that allow the sponsor to claim some benefit that accrues only from approval under a particular type of application,

As you have mentioned already, combination products are combined drugs, devices, and/or biological products with one another, and are a growing and important category of therapeutic and diagnostic products. Similar to medical devices classification, combination products are also classified into 9 different types. Regarding the review, combination products are assigned to an FDA center which will have primary jurisdiction for its premarket review and post-market regulation. This is based on a determination of the primary mode of action in short (PMOA) of the combination product that provides the most important therapeutic action of the combination product.

Combination products are medical products that combine a drug, device and/or biological product. in order to ensure efficient review, a single application is generally appropriate for combination products. FDA provides a structured framework for evaluating combination products, considering both device and drug component contributions. FDA also notes  that the premarket review of combination product can be significantly streamlined when its sponsor is legally authorized to rely on FDAs 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 sponsors data.