Combination products, i.e., those containing any combination of a drug, device, or biological, constitute a growing category of innovative medical products. Examples include a drug with an implantable delivery device, drug-eluting cardiovascular stents, and autologous cells with scaffolds for orthopedic use.
While these products contribute to advancing medical care, they also pose a challenge for the FDA since, by definition, they straddle existing statutory classifications of regulated products, thereby complicating the selection of the appropriate review and approval pathway.
Congress recognized the existence of such combination products (CPs) when it enacted The Safe Medical Devices Act of 1990 and established that the FDA shall classify a CP according to its primary mode of action [see Section 503(g) of the Federal Food, Drug, and Cosmetics Act (21 USC 353(g)].
To implement this new regulatory authority, the FDA defined a CP in 21 CFR 3.2(e), as:
a product comprised of two or more regulated components that are physically, chemically, or otherwise combined or mixed as a single entity; or
two or more separate products packaged together; or
a product packaged separately but intended for use only with an approved, individually specified product where both are required to achieve the intended use, indication, or effect and where, upon approval of the proposed product, the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or where both products are investigational.
From its determination of the primary mode of action (PMOA) of the CP, the Agency could then assign jurisdiction over the product to one of its established Centers.
For example, if the PMOA is that of a drug, the product is assigned to CDER, with similar assignments of devices to CDRH, and biological products to CBER. In 1991, FDA issued a final rule establishing the process (known as a Request for Designation; RFD) by which a product sponsor could petition the Agency to make such an assignment.
The Medical Device User Fee and Modernization Act of 2002 (MDUFMA) modified Section 503(g) of the Act to require the FDA to establish an office with the primary responsibility for providing regulatory oversight of CPs.
The Office of Combination Products (OCP), located within the Office of Commissioner, assigns a CP to the appropriate FDA Center, ensures timely and effective premarket review as well as appropriate and consistent postmarket regulation, resolves any disputes, reviews/updates guidances, agreements, and practices, and is a valuable resource for industry and the FDA Center(s) review staff.
OCP reports to Congress on an annual basis. Although OCP does not actually perform the review process for market clearance or approval, there has been much progress since this Office was established in making this often complex regulatory area more efficient, transparent, and better understood.