PMA

Premarket Approval

Dr.-Ing. Benedikt JannySenior Usability Engineer | Managing Partner
Last updated: October 2026
Short definition

PMA (premarket approval) is the approval procedure of the US FDA for Class III medical devices. The legal basis is Section 515 of the FD&C Act and 21 CFR Part 814. Unlike the 510(k), the manufacturer uses valid scientific evidence, mostly clinical data, to demonstrate that the device is safe and effective.

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Premarket approval (PMA) is the procedure by which the US agency FDA reviews Class III medical devices scientifically and from a regulatory perspective. The FDA itself describes the PMA as the most stringent type of device marketing application. A device for which a PMA is required may be marketed in the US only after the PMA has been approved.

The statutory basis is Section 515 of the Federal Food, Drug, and Cosmetic Act (FD&C Act, the US federal law on food, drugs and cosmetics), codified in the US Code as 21 U.S.C. 360e. The details of the procedure are governed by the regulation 21 CFR Part 814 (“Premarket Approval of Medical Devices”).

Which devices the PMA applies to

The PMA applies to Class III devices (see FDA device classification). Under 21 CFR 860.3, a device belongs in this class if the information is insufficient to show that general controls and, where applicable, special controls provide reasonable assurance of safety and effectiveness. In addition, the device must be life-supporting or life-sustaining, be of substantial importance in preventing impairment of human health, or present a potential unreasonable risk of illness or injury.

Part 814 covers in particular Class III devices that were not on the market before May 28, 1976 and are not substantially equivalent to a device marketed at that time or later classified into Class I or II. It also applies to device types for which a regulation under Section 515(b) expressly requires a PMA.

Distinction from the 510(k)

The fundamental difference lies in the standard of review. In the 510(k) premarket notification, the manufacturer shows that its device is substantially equivalent to a legally marketed predicate device (see predicate device and substantial equivalence). In the PMA, by contrast, the application itself must demonstrate reasonable assurance that the device is safe and effective. The FDA names the same standard for the De Novo classification request.

Under 21 CFR 860.7, the FDA bases this decision only on valid scientific evidence. Isolated case reports and unsubstantiated opinions do not count as evidence. Evidence of effectiveness is to be based mainly on well-controlled studies, unless the FDA exceptionally permits other evidence. In practice, this generally means clinical data for the PMA.

Content of the application

21 CFR 814.20 specifies what a PMA application must contain, unless the applicant justifies omitting individual items. This includes, among other things:

  • a summary with the Indications for Use, the device description, alternative practices or procedures, the marketing history and a conclusion with a benefit-risk assessment,
  • a complete description of the device, its principles of operation, and the manufacturing methods and controls,
  • information on applicable standards and a justification for any deviation,
  • results of nonclinical laboratory studies and clinical investigations in humans,
  • copies of all proposed labeling, as well as information on use in pediatric patients.

If the applicant is not based in the US, an authorized representative based in the US must countersign the application. Under 21 CFR 814.15, a PMA can also rely solely on clinical data from outside the US if these are applicable to the US population and US medical practice, the investigators are of recognized competence and the FDA can validate the data. For this case, the regulation recommends a prior meeting with the FDA (see Pre-Submission).

The FDA describes three application methods: the traditional PMA, in which the complete application is submitted at once, the modular PMA, in which defined modules are submitted one after another and reviewed separately, and the Product Development Protocol. A Product Development Protocol declared completed by the FDA is considered an approved PMA.

Review process

After receipt of the application, the FDA decides within 45 days whether it is complete enough for a substantive review (filing). It can refuse incomplete applications (Refuse to File). The filing date starts a review period of 180 days. If the applicant submits a major amendment, the period can be extended by up to 180 days (deadlines under 21 CFR Part 814, as of October 2026).

According to the FDA, the substantive review includes a scientific, regulatory and quality-related assessment, an inspection of the quality management system that is planned for all original PMAs, and an audit of the clinical study data (Bioresearch Monitoring). The FDA can refer the application to an external advisory panel. If the manufacturer requests it, the FDA must do so unless the panel has already reviewed the information. The panel deliberates in a public meeting and issues a recommendation.

The outcome is one of four decisions: an approval (approval order), an approvable letter with conditions, a not approvable letter listing the deficiencies, or a denial. If the applicant does not respond to a request for additional information or to such a letter within 180 days, the application is considered withdrawn.

The approval can be linked to conditions, for example distribution restrictions, further evaluation on the market, prominent warnings in the labeling or periodic reports. In addition, there are the reporting obligations under 21 CFR Part 803 (see post-market surveillance).

A special form is the Humanitarian Device Exemption (HDE) under Subpart H of Part 814. It concerns devices for conditions that affect no more than 8,000 people per year in the US, and it exempts from the requirements for demonstrating effectiveness.

Changes after approval: PMA supplements

If the holder of a PMA wants to change the device in a way that affects safety or effectiveness, it must, under 21 CFR 814.39, first submit a PMA supplement and have it approved. As examples, the regulation names new Indications for Use, changes to the labeling, packaging, sterilization, and the design or performance specifications. Changes without an effect on safety and effectiveness are reported in the periodic reports. This also applies to changes within an approved Predetermined Change Control Plan (PCCP, a change plan defined in advance).

The statute and the FDA distinguish several types:

  • Panel-track supplement: for a significant change in design or performance or a new indication for which extensive clinical data are needed,
  • 180-day supplement: for significant changes, for example to components, materials, design, software or labeling,
  • Real-time supplement: for minor changes that are reviewed in a joint meeting with the FDA,
  • Special PMA supplement (Changes Being Effected): for changes that enhance safety, for example additional instructions for safe use in the labeling, and that may be implemented before approval,
  • 30-day notice: for changes to manufacturing procedures, which becomes a 135-day supplement if the notice is inadequate.

Human factors in the PMA

Which human factors information a submission should contain is described by the FDA guidance “Content of Human Factors Information in Medical Device Marketing Submissions”. It has been final since May 29, 2026 and expressly applies to PMAs as well. For submissions before August 1, 2026, the FDA generally does not yet expect the newly recommended content (as of October 2026). The guidance supplements the FDA human factors guidance and clarifies that human factors information is only one component of the overall assessment.

The guidance assigns each submission to one of three HF Submission Categories. The starting point is the use-related risk analysis (URRA). The decisive question is whether there are hazard-related use scenarios in the sense of IEC 62366-1, which the FDA calls critical tasks. In the highest category, the manufacturer submits a complete HFE/UE report with the results of the human factors validation. According to the guidance, such data are likely needed if the user interface is complex or the device type is known for use errors.

For a PMA, the labeling is doubly significant. The statute requires the FDA to base its decision on the conditions of use in the proposed labeling, and false or misleading labeling is a ground for denial. At the same time, the guidance, in line with IEC 62366-1, counts labeling and training as part of the user interface. If the user interface, the group of users, the use, the use environment, the training or the labeling of an approved device changes, it must therefore be checked whether critical tasks are affected. Whether a PMA supplement is needed for this is governed by 21 CFR 814.39, not by the guidance.

The foundation is provided by design controls (see QMSR and design controls). Since February 2, 2026, the Quality Management System Regulation (QMSR) has applied, which incorporates ISO 13485 by reference. Under 21 CFR 820.10(c), manufacturers of Class II and III devices must meet the requirements for design and development (Section 7.3 of ISO 13485). The FDA recommends keeping human factors information on hand regardless of whether it is submitted. For the PMA, there is the additional point that approval can depend on an inspection confirming conformity with Part 820.

In brief

The PMA is the FDA approval procedure for Class III medical devices under Section 515 FD&C Act and 21 CFR Part 814. Unlike the 510(k), the manufacturer does not show equivalence but demonstrates safety and effectiveness with valid scientific evidence, as a rule clinical data.

After filing within 45 days, the regulation provides for a review period of 180 days, often with an advisory panel and inspection. Later changes go through PMA supplements.

For human factors, the FDA guidance on the content of human factors information, finalized in 2026, also applies to PMAs. Labeling, training and design controls are central building blocks.

Frequently asked questions (FAQ)

When does a medical device need a PMA instead of a 510(k)?

A PMA is required for Class III devices, that is, as a rule for devices that are life-supporting or life-sustaining or present a potential unreasonable risk and for which general and special controls alone are not sufficient. If a device is substantially equivalent to a legally marketed device, the FDA refers to the 510(k) instead.

Are clinical data required for a PMA?

The FDA relies only on valid scientific evidence. Evidence of effectiveness is to come mainly from well-controlled studies, unless the FDA exceptionally permits other evidence. A PMA application therefore generally contains clinical investigations in humans. Data from outside the US can also be sufficient if they are applicable to conditions in the US.

How long does the review of a PMA take?

The regulation provides that the FDA decides on filing within 45 days and acts on the application within 180 days of filing. A major amendment to the application can extend this period by up to 180 days. These deadlines describe the regulatory framework, not the total duration of a project.

Must a PMA contain human factors data?

That depends on the risk assessment. Under the FDA guidance on the content of human factors information, the manufacturer assigns its submission to one of three categories. If there are critical tasks and the user interface is complex or known for use errors, the FDA generally expects a complete HFE/UE report with results of the human factors validation.

What is a PMA supplement?

A PMA supplement is a supplemental application to an already approved PMA. The holder must submit it before changes that affect safety or effectiveness, for example new indications or changes to labeling or design. Depending on the type of change, there are different forms, from the panel-track supplement to the 30-day notice.

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