We support medical device and IVD manufacturers through premarket approval (PMA) under 21 CFR Part 814, from evidence strategy to the conditions of approval. The FDA requires independent proof of safety and effectiveness, with effectiveness resting principally on well-controlled investigations.
Overview
Premarket approval for class III medical devices and IVD · 21 CFR Part 814 Subparts A to E · FD&C Act Sec. 515 · 21 CFR 860.7 · FDA guidance on modular review, acceptance and filing, benefit-risk and post-approval studies
Last updated: October 31, 2026
A PMA is not reviewed against a comparison device. The FDA asks for valid scientific evidence that the device is safe and effective for its intended use (21 CFR 860.7), and for manufacturing, labeling and study conduct that support that evidence. Each of these questions can hold up the application.
Industries
Services
Building the application with summary, device description, manufacturing information, reference to standards, nonclinical studies under Part 58, clinical investigations, bibliography, draft labeling, financial disclosure under Part 54 and information on pediatric patients. Where an item is omitted, the justification under 814.20(d) stands as a separate section of the application.
Drafting the shell with the content and date of each module, agreement with the FDA review team before formal submission, modules for instance on nonclinical studies and engineering, separate modules for manufacturing and bioresearch monitoring, and the final module with clinical data, labeling and SSED. The basis is FD&C Act Sec. 515(c)(4) and the guidance of January 13, 2025.
Pre-check against the acceptance review checklist, request for the day-100 meeting under FD&C Act Sec. 515(d)(3), responses to questions as amendments under 21 CFR 814.37 and to approvable or not approvable letters. Every response cites its location in the application and keeps the 180 days in view after which the FDA treats an unanswered PMA as withdrawn.
Preparation for a public advisory committee meeting under 21 CFR 814.44(b) and Part 14: key messages on benefit and risk, answers to the questions the panel is likely to ask, alignment with the FDA presentation. Whether a PMA goes to a panel is the FDA's decision; on the applicant's request it refers the PMA unless the application substantially duplicates information a panel has already reviewed (814.44(a)).
How we work together
A PMA is the application for approval of a class III device. The FDA reviews it without a comparison device: it asks whether valid scientific evidence provides reasonable assurance that the device is safe and effective for its intended use (21 CFR 860.7). The outcome is an approval order with conditions that bind manufacturing, labeling and advertising (21 CFR 814.80).
Between receipt and decision there are fixed stations. The FDA files the application for review, may refer it to an advisory panel that meets in public (21 CFR 814.44(b)), and answers with approval, an approvable letter, a not approvable letter or denial. If the applicant does not respond in writing to a request for an amendment or to one of these letters within 180 days, the PMA is considered withdrawn (814.44(g)).
How the application reaches the FDA is the applicant's choice.
| Traditional PMA | Modular PMA | |
|---|---|---|
| What is submitted | the complete application under 21 CFR 814.20 at once | modules following a shell agreed in advance, the last one with clinical data, labeling and SSED |
| When the FDA reviews | from receipt of the complete application | each module on its own, FDA goal: a response within 90 days |
| When the 180 days start | on filing | on filing after the final module, typically the date that module is received |
| When it fits | when all data are available at the same time | when the clinical investigation is at an early stage and the design is fixed |
Inspections accompany the PMA in two places: in manufacturing, whose compliance with Part 820 the FDA can make a condition of approval, and in the records pertinent to the PMA (if applicable) it can verify at the same time (21 CFR 814.44(e)(1)(iii)); the modular PMA keeps the bioresearch monitoring information in a separate module. How the preapproval inspection works is described on the page FDA Inspection Readiness & QMSR.
Outside this page lie the choice between 510(k), De Novo and PMA on the page FDA Strategy & Pathways, the other two routes on the pages 510(k) Premarket Notification and De Novo Classification, the requirements of the HDE, the decision on PMA supplements for changes and the inspection itself.
Our approach
Step
Result
Plan the evidence
An evidence plan in which every claimed indication is supported by well-controlled investigations or by other valid scientific evidence with a justification.
Choose the submission format
A decision between a traditional and a modular PMA; for the modular route, a shell with a schedule agreed with the FDA.
Pass acceptance
An application that passes acceptance review and filing; the 180 days start on the filing date.
Support review and panel
Answered questions, a prepared panel and, where the FDA requires it, a passed preapproval inspection.
Implement the approval
An approval order whose conditions are anchored in manufacturing, labeling, studies and reports.
Common pitfalls
A modular PMA is chosen for an application that is nearly complete.
If the final module is six months away or less, the FDA may consider modular review inappropriate under the guidance of January 13, 2025, and it recommends a traditional PMA when modules would arrive in close succession. The same applies while the design is still changing: a major change to the device reopens closed modules.
The clinical data come only from Europe.
A PMA based solely on data from outside the United States may be approved under 21 CFR 814.15(b) if the data apply to the U.S. population and U.S. medical practice, the investigators are of recognized competence and the data can be validated with or without an FDA inspection. Arguing this only during review is arguing it too late; 814.15(c) encourages a meeting before submission.
A major amendment arrives unsolicited.
New study data or new analyses during review can extend the review period by up to 180 days (21 CFR 814.37(c)(1)); the modular review guidance warns that this also delays the FDA response there.
The post-approval study is planned only after approval.
According to its guidance of October 7, 2022, the FDA wants to agree the protocol with the applicant during PMA review and write enrollment and completion targets into the approval order; failing to meet a postapproval requirement is a ground for withdrawal of approval under 21 CFR 814.82(c).
Regulatory Affairs
In a first call we assess your situation and say what needs clarifying first in your case. Without obligation, reply usually within one working day.
FAQ
Image notice: The images on this page were generated using artificial intelligence. They do not depict real people, places, or events.
Projects from this industry
Latest insights
All insights →FDA Strategy & Pathways →
Choosing between 510(k), De Novo and PMA by classification and risk
FDA Inspection Readiness & QMSR →
The PMA preapproval inspection under Compliance Program 7382.850
Regulatory Change Assessment & Notification →
Whether a change to a PMA device requires a supplement
Clinical Compliance →
Clinical investigations whose data support the PMA
510(k) Premarket Notification →
The route via a predicate when no PMA is required
De Novo Classification →
The route for novel low to moderate risk devices without a predicate
Briefly outline your situation. We'll respond with an initial assessment, usually within one business day.
Prefer direct? +39 02 8904 1000
contact@theentourage.it
