21 CFR Part 814 — Premarket Approval (PMA)
21 CFR Part 814 implements FD&C Act § 515 and governs the premarket approval process for Class III medical devices.
Structure of Part 814
| Subpart | Content |
|---|---|
| Subpart A (§§ 814.1–814.21) | General provisions; PMA application contents |
| Subpart B (§§ 814.37–814.47) | FDA review of PMA applications — filing, review, approval/denial |
| Subpart C (§§ 814.60–814.84) | Postapproval requirements — annual reports, conditions of approval |
| Subpart D | Transitional provisions |
| Subpart H (§§ 814.100–814.126) | Humanitarian Device Exemption (HDE) |
PMA application contents (§ 814.20)
A PMA application must contain:
- Table of contents
- Summary of safety and effectiveness data (SSED) — becomes public upon approval
- Complete device description
- Reference to performance standards
- Technical sections: non-clinical laboratory studies, clinical investigations, manufacturing information
- Proposed labelling
- Environmental assessment or exclusion claim
- Financial certification/disclosure (21 CFR Part 54)
- Truthful and accurate statement
FDA review process
Filing review (§ 814.42)
FDA has 45 days to accept or refuse to file a PMA. A "refuse to file" decision means the application is incomplete — the applicant can resubmit.
Substantive review
FDA conducts a complete review of the PMA, which may include:
- Requests for additional information
- Advisory panel review (for novel or complex devices)
- Pre-approval inspection of manufacturing facilities
Decision (§ 814.45)
FDA issues one of:
- Order approving the PMA — device may be marketed
- Approvable letter — FDA will approve after minor modifications
- Not approvable letter — significant deficiencies; major revision required
- Order denying the PMA
PMA supplements (§ 814.39)
Changes to an approved PMA that could affect safety or effectiveness require a supplement:
| Supplement type | Review time goal |
|---|---|
| 180-day PMA supplement | 180 days |
| Real-time supplement | 30–90 days |
| 30-day notice | 30 days (notification only for qualifying changes) |
Humanitarian Device Exemption (Subpart H)
Subpart H governs the HDE — an approval pathway for Class III devices intended to benefit patients with diseases or conditions affecting ≤ 8,000 individuals per year in the USA.