Record: Primary Mode of Action (PMOA) Determination

This is a ready-to-use record for documenting a primary mode of action (PMOA) determination. The PMOA sets the lead FDA center and the base cGMP operating system, so it is the first decision a combination-product program writes down. Replace every <<FILL: ...>> placeholder, set your document numbers and dates, and route it through document control. A worked filled specimen follows. Verify each cited regulation against the current source before you rely on it.

Control header

Field	Entry
Document number	`<<FILL: REC-ID>>`
Product	`<<FILL>>`
Version / date	`<<FILL>>`
Prepared by (Regulatory)	`<<FILL>>`
Approved by (Quality / Regulatory head)	`<<FILL>>`

1. Product and constituents

Item	Entry
Product name	`<<FILL>>`
Configuration (21 CFR 3.2(e))	`<<FILL: single-entity / co-packaged / cross-labeled>>`
Constituent 1	`<<FILL: drug / biologic / device, description>>`
Constituent 2	`<<FILL>>`
Intended use / indication	`<<FILL>>`

2. Mode of action of each constituent

The mode of action is how a constituent achieves its intended therapeutic effect.

Constituent	Mode of action	Contribution to the therapeutic effect
`<<FILL>>`	`<<FILL>>`	`<<FILL: primary / supporting>>`
`<<FILL>>`	`<<FILL>>`	`<<FILL>>`

3. PMOA determination (21 CFR 3.2(m))

Item	Entry
Most important therapeutic action	`<<FILL: which mode provides it>>`
PMOA	`<<FILL: drug / biologic / device>>`
Rationale	`<<FILL: why this is the most important action; reasoning, not assertion>>`
Was PMOA unclear?	`<<FILL: yes/no>>`
If unclear, basis used	`<<FILL: which constituent poses the most significant safety/effectiveness questions, per 3.4>>`

4. Consequences of the determination

Item	Entry
Lead FDA center	`<<FILL: CDER / CBER / CDRH>>`
Application type	`<<FILL: NDA / BLA / PMA / 510(k) etc.>>`
Base cGMP operating system	`<<FILL: 210/211 (+600-680) OR 820 / QMSR>>`
Added provisions to apply	`<<FILL: 4.4(b)(1) six device provisions OR 4.4(b)(2) eight drug provisions>>`

5. RFD / Pre-RFD interaction (if any)

Item	Entry
Pre-RFD or RFD filed?	`<<FILL: yes/no>>`
Reference / date	`<<FILL>>`
FDA assignment outcome	`<<FILL: center assigned, any conditions>>`
Correspondence on file	`<<FILL: location>>`

6. Acceptance criteria

Each constituent’s mode of action is described.
The PMOA is stated with a reasoned rationale, not a bare assertion.
The lead center, application type, base system, and added provisions follow from the PMOA and are recorded.
Any RFD or Pre-RFD interaction is referenced and filed.
The record is approved and placed under change control; it is revisited if the product or intended use changes.

7. References

21 CFR 3.2(e) and 3.2(m) (definitions); 21 CFR 3.4 (assignment when PMOA is unclear). 21 CFR Part 4 (cGMP for combination products); 21 CFR Parts 210/211; 21 CFR Part 820 / QMSR.

Confirm the current version and clause numbers before issue.

8. Approvals

Role	Name	Signature	Date
Author (Regulatory)	`<<FILL>>`
Approver (Quality / Regulatory head)	`<<FILL>>`

Filled specimen

The following shows the record completed for an example drug-eluting stent. Illustrative.

Item	Entry
Product	Drug-eluting coronary stent, single-entity
Constituent 1 (device)	Metal stent scaffold; mode of action: mechanical, holds the vessel open. Primary action.
Constituent 2 (drug)	Antiproliferative coating; mode of action: pharmacological, suppresses restenosis. Supporting action.
Most important therapeutic action	Keeping the vessel patent (the stent)
PMOA	Device
Lead center	CDRH
Application type	PMA
Base system	21 CFR Part 820 / QMSR
Added provisions	The eight drug provisions of 4.4(b)(2); stability and expiration dating for the drug coating are the key new builds
RFD	Not required; PMOA clear. Determination rationale on file.

In this example the device provides the primary action, so the product is device-led, runs a Part 820 / QMSR base, and adds the drug provisions, with the drug coating forcing a stability program and a justified expiration date that a pure device would not need.

Common inspection findings this record prevents

A base operating system chosen by habit with no documented PMOA behind it.
A PMOA asserted with no rationale, so the center and base look arbitrary.
RFD correspondence not retained, so the assignment basis cannot be reconstructed.

How to adapt this record

Set your document number and product.
Describe each constituent’s mode of action and which provides the most important therapeutic action.
State the PMOA with reasoning, then record the center, application type, base, and added provisions that follow.
Reference any RFD interaction and approve under change control.