Premarket Approval of Medical Devices
Implements sections 515 and 515A of the FD&C Act: the premarket approval (PMA) application for class III devices, FDA’s 180-day review and its possible outcomes, PMA supplements for changes affecting safety or effectiveness, postapproval reporting, and the humanitarian device exemption.
What this does not cover
stated in the document's own scope- It does not apply to devices that can be cleared by 510(k) under Part 807 or classified through De Novo under Part 860.
- It does not govern clinical investigations of the device; investigational device exemptions are in Part 812.
- It does not set manufacturing requirements; Part 820 does, and the PMA must describe the methods, facilities and controls used.
- Medical device reporting is required of PMA holders through 814.84, but the reporting rules themselves are in Part 803.
Always verify against the current published text before relying on it for a submission or inspection.
Overview
Part 814 is the premarket approval regulation. A PMA is the most demanding route to the US device market: the applicant must show reasonable assurance that a class III device is safe and effective, usually with clinical data, and FDA approves the device rather than clearing it by comparison. The Part covers what a PMA must contain, how FDA files and reviews it and what decisions it may reach, administrative review of those decisions, what must happen after approval, and the separate humanitarian device exemption for devices intended for small patient populations.
Scope & applicability
Class III devices that are not substantially equivalent to a pre-1976 device or to one later reclassified into class I or II, and devices a classification regulation requires to have a PMA (814.1(c)). Investigational devices exempt under section 520(g) are outside it.
Legal basis & how it acquires force
A regulation in Title 21 of the Code of Federal Regulations implementing sections 515 and 515A of the FD&C Act, which require premarket approval for class III devices and set special rules for pediatric uses. It applies to class III devices not substantially equivalent to a pre-1976 device or one later reclassified into class I or II, and to devices a regulation requires to have a PMA (814.1(c)). It was last amended on 15 March 2024.
Document structure
| Part | Covers |
|---|---|
| Subpart A — General | Scope, definitions, confidentiality of data and research conducted outside the United States |
| Subpart B — Premarket Approval Application | Application content (814.20), including the summary, device description, manufacturing methods, facilities and controls, nonclinical and clinical sections, and proposed labelling; amendments, resubmissions and supplements (814.37–814.39) |
| Subpart C — FDA Action on a PMA | Filing, the 180-day review time frame (814.40), advisory panel referral (814.44), and approval orders, approvable and not-approvable letters and denials |
| Subpart D — Administrative Review | Procedures for review of FDA’s decisions |
| Subpart E — Postapproval Requirements | Conditions of approval, and reports, including Part 803 reporting and periodic reports (814.84) |
| Subpart H — Humanitarian Use Devices | Designation of humanitarian use device status and the humanitarian device exemption application |
Key requirements
- §814.20 — PMA content, including the device description, manufacturing methods and controls, nonclinical and clinical data, and proposed labelling
- §814.40 — FDA review within 180 days of an application accepted for filing, absent a major amendment
- §814.39 — a PMA supplement approved before any change affecting safety or effectiveness, such as new indications, labelling, a different facility, sterilisation, packaging or design specifications
- §814.84 — compliance with Part 803 and periodic reports as the approval order specifies
Implementation tips
- Treat the approval order’s conditions as requirements in the quality system — they are enforceable in the same way as the regulation
- Route every design, supplier and process change through a documented PMA-supplement assessment; the burden of deciding whether a supplement is needed is primarily on the holder
International alignment
Part 814 sits beside Part 807 (510(k)) and Part 860 (classification, including De Novo) as the third premarket route. FDA may inspect manufacturing facilities in reviewing a PMA, and the approved device is made under the Quality Management System Regulation in Part 820. FDA lists eSTAR as voluntary for original PMAs and PMA supplements, and its Q-Submission Program offers Pre-Submissions and PMA Day 100 meetings.
21 CFR Part 814: frequently asked questions
Quick answers to common questions about 21 CFR Part 814.
How long does FDA take to review a PMA?
Section 814.40 says that within 180 days of receiving an application accepted for filing, and to which the applicant does not submit a major amendment, FDA will send an approval order, an approvable letter, a not-approvable letter or an order denying approval, after receiving any advisory panel’s report and recommendation.
Which changes need a PMA supplement?
Any change affecting the safety or effectiveness of the device, unless FDA has said an alternate submission is allowed. Section 814.39(a) lists examples: new indications, labelling changes, a different manufacturing facility, changes in sterilisation or packaging, and changes in performance or design specifications, components or principle of operation.
Does an applicant have to go before an advisory panel?
FDA may refer a PMA to a panel on its own initiative and will do so at the applicant’s request, unless the application substantially duplicates information a panel has already reviewed (814.44(a)).
What is a humanitarian device exemption?
A route in Subpart H for a device designated as a humanitarian use device. It is approved on the basis of probable benefit rather than full effectiveness data, and the Subpart sets the designation and application procedures.