21 CFR Part 3 — Combination Product Jurisdiction
21 CFR Part 3 governs the process by which FDA assigns regulatory jurisdiction (i.e., the lead FDA centre) for combination products — articles that combine drug, device, and/or biologic components.
Key provisions
§ 3.2 — Definitions
Defines key terms including "combination product," "primary mode of action (PMOA)," and "sponsor."
A combination product under § 3.2(e) includes:
- Single-entity products (two regulated components combined as one product)
- Co-packaged products (two separately regulated products packaged together)
- Cross-labeled products (two products labeled for use together)
§ 3.4 — Determination of primary mode of action (PMOA)
The PMOA is the single mode of action of a combination product that provides the most important therapeutic action. The centre with the most expertise in the PMOA is designated as the lead centre.
If PMOA cannot be determined, FDA designates the centre with the most relevant expertise (§ 3.4(b)).
§ 3.7 — Request for Designation (RFD)
The RFD process allows sponsors to obtain a binding FDA designation of the lead centre before submitting a premarket application:
- Submit RFD to the Office of Combination Products (OCP)
- OCP issues a designation within 60 calendar days
- The designation is binding on FDA
§ 3.9 — Reconsideration and appeals
A sponsor who disagrees with an OCP designation may request reconsideration within 15 days.
Intercenter agreements
FDA has published intercenter agreements between CDRH, CDER, and CBER specifying lead centre assignments for common combination product types. These are publicly available and are the first place to look before submitting an RFD.