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.
Official resources
Standard Review: FDA has 180 calendar days from filing acceptance to issue a decision. Priority Review: FDA has 180 calendar days from filing acceptance to complete substantive review (expedited for devices with significant advantages over existing alternatives).
FDA may condition PMA approval on postapproval requirements such as postapproval studies, postapproval surveillance, restrictions on distribution, or annual reporting of new safety or effectiveness information.