Combination Products — 21 CFR Part 3
The US has a formal combination product regulatory framework administered by FDA's Office of Combination Products (OCP). This is a US-specific structure — other jurisdictions handle drug-device combinations differently.
What is a combination product?
Under 21 CFR § 3.2(e), a combination product is a product comprised of two or more regulated components — i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic — that are physically, chemically, or otherwise combined or mixed and produced as a single entity.
Examples:
- Drug-eluting stent (device + drug)
- Prefilled syringe (device + drug)
- Insulin pump with integrated CGM (device + device, may involve software)
- Gene therapy delivered via a medical device
- Inhaler with a drug formulation (drug + device)
Types of combination products
| Type | Description |
|---|---|
| Single-entity | Two components combined in a single product (e.g., drug-eluting stent) |
| Co-packaged | Two or more separate products packaged together (e.g., syringe + drug vial) |
| Cross-labeled | Separate products with labelling indicating intended use together |
Primary Mode of Action (PMOA)
FDA assigns jurisdiction based on the primary mode of action (PMOA) — the single mode of action that provides the most important therapeutic action:
- PMOA is device → CDRH leads (may consult CDER/CBER)
- PMOA is drug → CDER leads (may consult CDRH)
- PMOA is biologic → CBER leads (may consult CDRH)
If PMOA cannot be determined, FDA designates the centre with the most relevant expertise and resources.
Request for Designation (RFD)
When the appropriate FDA centre is unclear, submit a Request for Designation (RFD) to OCP:
- OCP issues a designation within 60 calendar days
- The designation is binding on FDA
- RFD is submitted before any premarket submission
Intercenter agreements
FDA has published intercenter agreements between CDRH, CDER, and CBER specifying which centre leads for common combination product types. These are publicly available on the FDA website.
Regulatory requirements for combination products
Once jurisdiction is established, the lead centre applies its own regulations but may impose requirements from the non-lead centre. For example, a drug-eluting stent (CDRH lead) must comply with:
- Device regulations (21 CFR Part 820 / QMSR)
- Drug manufacturing controls (21 CFR Part 211) as applicable to the drug component