US Device Premarket Pathways: 510(k), De Novo and PMA
Most US medical devices reach the market by one of three routes. A 510(k) shows the device is substantially equivalent to a legally marketed predicate. A De Novo request classifies a novel low- or moderate-risk device that has no predicate into class I or II. A PMA demonstrates safety and effectiveness for a class III device. The route follows from the device’s classification and whether a predicate exists, and FDA’s Q-Submission Program lets a sponsor test the plan before committing to it.
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Premarket Notification — 510(k)
A registered establishment must submit a premarket notification at least 90 days before introducing a device into commercial distribution for the first time, or before a change to a device already marketed that could significantly affect its safety or effectiveness, or a major change in intended use (21 CFR 807.81). Many class I and some class II devices are exempt by regulation.
FDA finds a device substantially equivalent if it has the same intended use as the predicate and either the same technological characteristics or, where they differ, data showing it is as safe and effective without raising different questions of safety and effectiveness (807.100(b)). Until the applicant receives an order declaring the device substantially equivalent, it may not market it. Clearance is not approval: 807.97 says a substantial-equivalence determination does not denote official approval, and representing it as approval is misbranding.
De Novo Classification
De Novo is the route for a device that would meet class I or II controls but has no legally marketed device on which to base substantial equivalence. A request may follow a not-substantially-equivalent decision on a 510(k), or be filed directly when the sponsor determines there is no predicate (21 CFR 860.200(b)).
FDA reviews an accepted request and issues an order granting or declining it within 120 days (860.240(a)), and may inspect facilities first to check the integrity of the data or that the QMSR, general controls and any special controls give adequate assurance for critical or novel manufacturing (860.240(c)). A request is treated as withdrawn if the sponsor does not fully answer a request for additional information within 180 days (860.250(a)(1)). A granted De Novo creates a new classification regulation, published within 30 days with its special controls (860.260(a)(2)), and the device can then serve as a predicate for later 510(k)s.
Premarket Approval — PMA
A PMA is required for a class III device that is not substantially equivalent to a pre-1976 device or one later reclassified, or that a regulation requires to have one (21 CFR 814.1(c)). It must demonstrate reasonable assurance of safety and effectiveness, usually with clinical data.
Within 180 days of an application accepted for filing, absent a major amendment, FDA sends an approval order, an approvable or not-approvable letter, or an order denying approval, after any advisory panel’s recommendation (814.40); FDA refers an application to a panel on request unless it substantially duplicates information a panel has already reviewed (814.44(a)). After approval, a PMA supplement is required before any change affecting safety or effectiveness — new indications, labelling, a different manufacturing facility, sterilisation, packaging or design specifications among them (814.39(a)) — and the holder must report under Part 803 (814.84(a)).
Choosing the Route
The decision starts with classification: find the classification regulation and product code that fit the intended use. If the device type is class III and requires a PMA, that is the route. If it is class I or II and not exempt, look for a predicate with the same intended use and comparable technology; a credible predicate means a 510(k). No predicate, but risks that general and special controls can manage, means De Novo.
Where the classification itself is unclear, a 513(g) request for information asks FDA for its view. Intended use drives everything, so the indications statement is a strategic document: a broader claim can move a device into a different classification or remove the predicate.
eSTAR and the Q-Submission Program
FDA’s eSTAR is an interactive PDF that structures a device submission. FDA lists its use as mandatory for 510(k) and De Novo submissions to CDRH and CBER, unless exempted, including those for combination products and dual 510(k)/CLIA waiver submissions. It is voluntary for PMAs and their supplements, Q-Submissions, IDEs and 513(g) requests, the last three through the PreSTAR template.
A Pre-Submission asks FDA for written feedback, with or without a meeting, on a planned submission. FDA’s May 2025 Q-Submission guidance targets written feedback within 70 days, or 5 days before a meeting scheduled typically around day 70–75, and recommends no more than 7–10 questions across no more than four substantial topics. The submitter drafts the minutes and submits them within 15 days of the meeting.
Feedback is FDA’s best advice on the information it was given. FDA intends it not to change if the later submission is consistent with the Pre-Sub and nothing new raises important issues, and will document the rationale if it does change. Issues FDA raises do not bind the sponsor, but the later submission should explain why a different approach was taken.
FREQUENTLY ASKED
Is a 510(k) clearance an FDA approval?
No. Under 21 CFR 807.97, a determination of substantial equivalence does not denote official approval of the device, and any representation that creates an impression of official approval because of a 510(k) is misbranding. Approval is the outcome of a PMA.
How long does FDA have to decide a De Novo request?
The regulation says FDA will issue an order granting or declining the request within 120 days of receiving an accepted request, or the additional information that resulted in its acceptance (21 CFR 860.240(a)).
Does a change to a cleared device need a new 510(k)?
A new premarket notification is required for a change that could significantly affect safety or effectiveness — in design, material, chemical composition, energy source or manufacturing process — or a major change in intended use (21 CFR 807.81(a)(3)). The decision and its rationale should be documented either way.
Is eSTAR required?
FDA lists eSTAR as mandatory for 510(k) and De Novo submissions to CDRH and CBER, unless exempted, and voluntary for PMAs, Q-Submissions, IDEs and 513(g) requests.
Is Pre-Submission feedback binding?
Not in the sense of an approval. FDA intends its feedback not to change if the later submission is consistent with the Pre-Sub and no important new issues arise, and will document the reason if it does. Review in a Pre-Sub does not guarantee a favourable decision later.
The inspection-readiness playbook for this topic
PUT THIS PLAYBOOK TO WORK
- HOW-TO GUIDEHow to Choose a US Device Premarket Pathway →Decide between 510(k), De Novo and PMA, and test the decision with FDA before committing to the testing.
- TEMPLATEQ-Submission (Pre-Sub) Request →
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