FDA 510(k), De Novo and PMA: US medical devices

Author Hugues Orgitello Last updated 27 May 2026 ~16 min read

Guide · FDA medical device pathways

Marketing authorisation of a medical device in the United States follows, depending on risk class and the nature of the product, one of three main pathways before the Food and Drug Administration (FDA), a federal agency of the Department of Health and Human Services. The 510(k) carries the bulk of class II devices, based on demonstrating substantial equivalence to a previously marketed product. The PMA (Premarket Approval) governs class III, that is, devices that support or sustain life, with a full requirement of safety and effectiveness evidence. The De Novo pathway covers the specific case of novel low-to-moderate risk devices for which no predicate exists. Alongside these three main pathways, several complementary mechanisms structure the dialogue with the agency, including the 513(g), the IDE for clinical investigations, the HDE for rare diseases, and the Q-Submission programme for preparatory meetings. This page sets out the framework as it applies in 2026, on the eve of the Quality Management System Regulation coming into force.

The legal framework: Federal Food, Drug, and Cosmetic Act

US medical device regulation originates in the Federal Food, Drug, and Cosmetic Act (FD&C Act), as amended by the Medical Device Amendments of 1976 and by later statutes (Safe Medical Devices Act 1990, FDA Modernization Act 1997, FDASIA 2012, 21st Century Cures Act 2016). Its regulatory expression is codified in Title 21 of the Code of Federal Regulations (21 CFR), chapter I, subchapter H, parts 800 to 898.

Within the FDA, the Center for Devices and Radiological Health (CDRH) is the operational body for most medical devices. The Center for Biologics Evaluation and Research (CBER) handles devices linked to blood products and certain cellular therapies. The Center for Drug Evaluation and Research (CDER) handles the drug component of combination products, addressed further below.

The three risk classes (21 CFR 860)

21 CFR Part 860 organises medical devices into three risk classes of increasing severity, on a patient-and-user risk model. The logic differs from the EU MDR (which distinguishes I, IIa, IIb and III), but the risk scale is comparable.

Class	Risk level	Applicable controls	Typical pathway
I	Low risk	General controls	510(k)-exempt for most, otherwise 510(k)
II	Moderate risk	General controls + special controls	510(k) Premarket Notification
III	High risk, supports or sustains life, or presents an unreasonable risk of illness or injury	General controls + Premarket Approval	PMA

General controls (sections 501, 502, 510, 516, 518, 519 and 520 of the FD&C Act) apply to every device without distinction, and cover establishment registration, device listing, general labelling requirements (21 CFR Part 801), Medical Device Reporting (MDR in the FDA sense, 21 CFR Part 803, not to be confused with the EU MDR), records, and good manufacturing practice (Quality System Regulation, 21 CFR Part 820, becoming Quality Management System Regulation in February 2026).

Special controls are additional requirements specific to a product category, set out in the relevant 21 CFR regulation or in guidance. They may cover performance standards, biological tests, specific labelling requirements or stability data.

Operational classification works through a product code, a three-letter identifier the FDA assigns to each regulatory citation. The FDA Product Classification database, openly accessible, lets you identify the applicable product code, its class, its special controls and any exemption status.

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The 510(k) pathway, Premarket Notification

The 510(k) takes its name from section 510(k) of the FD&C Act. By volume, it is the majority pathway for new devices placed on the US market, and the default route for class II.

The principle: substantial equivalence

The 510(k) does not ask the manufacturer to demonstrate safety and effectiveness from scratch. It asks the manufacturer to demonstrate that the device is substantially equivalent (SE) to a device legally marketed in the United States before 28 May 1976 (preamendments device), cleared by 510(k), or authorised via the De Novo pathway and thus usable as a predicate.

Substantial equivalence, within the meaning of 21 CFR 807.92 and the guidance The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications, requires two cumulative conditions:

• same intended use, that is, the same medical purpose claimed in labelling and promotional material,
• same technological characteristics, or different technological characteristics that raise no new question of safety or effectiveness, with performance shown to be equivalent through technical (and where applicable clinical) data.

The predicate must be cited by name, with its 510(k) number (K-number) or its De Novo reference (DEN-number). The manufacturer may rely on one primary predicate complemented by one or more reference devices to support specific technical aspects.

The three flavours: Traditional, Abbreviated, Special

The 510(k) programme has three operational flavours, described in the FDA guidance The New 510(k) Paradigm.

• Traditional 510(k), the full-format submission, applicable by default. The file contains the complete technical data, performance testing, risk analysis and substantial equivalence argument.
• Abbreviated 510(k), a lighter variant relying on conformity with FDA Recognized Consensus Standards or with a specific FDA guidance. The file refers to declarations of conformity rather than re-presenting each raw data set.
• Special 510(k), reserved for manufacturer-driven modifications to its own previously cleared device. The file addresses the change, its risk analysis and verification that the intended use remains unchanged. Review time is generally shorter.

Contents of the 510(k) file

21 CFR 807.87 sets out the headings of a 510(k) file: submitter and device identification, Indications for Use Statement, description and principles of operation, detailed comparison with the predicate, performance testing results (bench, biocompatibility, sterilisation, stability, EMC, software validation as applicable), clinical data where necessary (rare in 510(k)), proposed labelling, truthful and accurate statement.

Since 2023, the FDA has gradually moved to eSTAR, a structured electronic format that guides the manufacturer heading by heading. eSTAR is now the mandatory format for 510(k) submissions, subject to limited exceptions.

The process

The review process unfolds in several stages, documented in the Refuse to Accept Policy for 510(k)s guidance.

1. Submission via the FDA electronic portal, with payment of applicable user fees (FY2026 amounts are published annually on the FDA Medical Device User Fee Amendments page).
2. Acceptance Review, administrative check in the first days (Refuse to Accept checklist).
3. Substantive Review, technical evaluation on the merits by the CDRH review team.
4. Interactive Review and any Additional Information request (AI request), which stops the clock.
5. Final decision, Substantially Equivalent (SE, clearance letter), Not Substantially Equivalent (NSE), or opening of an alternative pathway.

Review timelines run in the order of months, with variations depending on complexity and on any AI request. The FDA publishes performance metrics (MDUFA performance reports). Citing a specific day count without context would be misleading, as timing varies materially by device type.

After clearance

The device is then cleared (not approved, the terminology matters). The 510(k) is public and indexed in the 510(k) Clearances database, searchable by K-number. The manufacturer must then meet general controls (annual establishment registration, device listing, Medical Device Reporting for incidents) and maintain a quality system compliant with 21 CFR 820 (QMSR from February 2026).

The De Novo pathway

The De Novo Classification Request pathway, created by the FDA Modernization Act of 1997 and reshaped by the 21st Century Cures Act of 2016 and the 2021 Final Rule codified at 21 CFR Part 860 Subpart D, answers a specific situation: a novel device, of low or moderate risk, for which no predicate exists, which without a predicate would default into class III. The manufacturer files a classification request together with the technical file and performance data. If the FDA agrees, two acts are issued simultaneously: a marketing authorisation for the device, and the creation of a new classification (new product code, class I or II, optional special controls) that becomes usable as a predicate for future 510(k)s.

By its nature, the De Novo pathway concerns innovative devices. It has been used in particular for the first generations of digital devices, for the first devices integrating AI in a given clinical indication, and for the first diagnostic tests of a new method. A request may be filed directly (Direct De Novo) or after a Not Substantially Equivalent decision on a 510(k) (post-NSE De Novo). Review timing is generally longer than a 510(k), since the FDA commits itself beyond the individual device when creating a classification.

The PMA pathway, Premarket Approval

PMA is the most demanding authorisation pathway in the FDA regime. Codified at 21 CFR Part 814, it applies to class III devices, that is, devices that support or sustain life, that are implanted, or that present an unreasonable risk of illness or injury.

The principle: safety and effectiveness evidence

Unlike the 510(k), PMA is not an equivalence demonstration. It is a demonstration of reasonable assurance of safety and effectiveness based on:

• device-specific clinical data, typically from a clinical investigation conducted under IDE,
• complete non-clinical data (microbiology, biocompatibility, bench performance, engineering, software validation, sterilisation, stability),
• a full description of manufacturing methods, facilities and controls,
• proposed labelling,
• a summary of available data (Summary of Safety and Effectiveness Data, SSED) that will be made public.

The review is conducted by a multidisciplinary CDRH team and, in most cases, referred for an opinion to an Advisory Committee convened publicly, whose recommendations are advisory.

Variants

21 CFR 814 sets out several PMA sub-types: Original PMA, initial submission; Modular PMA, file submitted in successive modules (preclinical, clinical, manufacturing) under prior FDA agreement; PMA Supplement, for any post-approval modification, graded by the magnitude of the change (Panel-Track, 180-Day, Real-Time, Special PMA Supplement); Annual Report, mandatory for every approved PMA device, summarising the year's modifications and post-market data.

The process

The PMA process is longer and more iterative than the 510(k): Pre-Submission (Q-Sub) recommended to scope the data volume expected; IDE approved if a clinical investigation is required; conduct of the clinical study; submission of the PMA with payment of user fees; filing review (administrative); substantive review on the merits; possible Advisory Committee meeting; pre-approval inspection of the manufacturing site (BIMO, Bioresearch Monitoring) and quality system inspection; final decision (approval, approvable letter with conditions, or not approvable); post-approval studies and annual reports in routine.

PMA review time runs over several quarters to years depending on complexity and on the need for supplementary data.

510(k) vs De Novo vs PMA comparison

Criterion	510(k)	De Novo	PMA
Target class	II mainly, some I	I or II (new)	III
Principle	Substantial equivalence to a predicate	Classification of a novel low-to-moderate risk device	Safety and effectiveness evidence
Clinical data	Rare, usually not required	Variable, often required	Mandatory, device-specific study
Predicate required	Yes (510(k), preamendments or De Novo)	No	Not applicable
Outcome	Clearance	Classification + authorisation	Approval
Creates a predicate?	Yes (future 510(k) can cite it)	Yes (creates a product code)	No in the 510(k) sense
Review time (order of magnitude)	Months	Several quarters	Several quarters to years
User fees (order of magnitude, FY2026)	Low, see current FDA schedule	Higher than 510(k)	Highest, see current FDA schedule
Pre-approval QMS inspection	No (post-market control)	Generally no	Yes (pre-approval inspection)
Advisory Committee	Very rare	Possible	Frequent
Public data	510(k) Summary public	DEN decision summary	SSED public

User fee amounts evolve every fiscal year. The FDA publishes the applicable amounts (standard and small business) on its Medical Device User Fee Amendments page. The schedule in force for the relevant fiscal year must be consulted.

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The 513(g): Request for Information

The 513(g) takes its name from section 513(g) of the FD&C Act. It is a written request to the FDA, which returns an opinion letter on:

• the classification of a product (I, II, III),
• its status as a medical device or not,
• the applicable regulatory requirements.

The 513(g) letter is not an authorisation and does not commit the FDA to a review process. It is nonetheless useful to clarify the applicable pathway upstream, especially for borderline products (wellness/medical, software/cleared device, combination product). The request is invoiced according to the annual user fee schedule. Response time runs in the order of a few months.

The IDE, Investigational Device Exemption

The IDE (Investigational Device Exemption, 21 CFR Part 812) allows clinical use of an unapproved device in a clinical investigation conducted in the United States. Without an IDE, using an unapproved device outside a specific exception is unlawful marketing.

21 CFR Part 812 distinguishes significant risk (SR) device study, for invasive, implantable, life-supporting or substantial-risk devices (IDE approved by the FDA plus approval by the local Institutional Review Board), and non-significant risk (NSR) device study, which follows an abbreviated IDE procedure, approved by the local IRB without prior FDA filing, subject to protocol, informed consent and reporting requirements. The IDE frames sponsor and investigator obligations, Adverse Event follow-up and recordkeeping. Generated data subsequently feed, where applicable, the 510(k), De Novo or PMA file.

The HDE, Humanitarian Device Exemption

The HDE (Humanitarian Device Exemption, 21 CFR Part 814 Subpart H) is a mechanism reserved for Humanitarian Use Devices (HUD), devices intended for the treatment or diagnosis of a disease or condition affecting fewer than a certain annual threshold of patients in the United States (in the order of a few thousand, with the exact threshold fixed by regulation and updated periodically, to be verified at the time of filing).

The HDE rationale relaxes the effectiveness requirement, hard to establish on populations too small for a clinical study of sufficient power, while maintaining the safety requirement. The manufacturer must show that the device does not present an unreasonable risk, that the probable benefit outweighs the risk, and that no comparable alternative is available. The device is marketed under control of the IRB at user sites, and is subject to specific reporting.

The Q-Submission programme

The Q-Submission (Q-Sub) programme, described in the FDA guidance Requests for Feedback and Meetings for Medical Device Submissions, structures the exchanges upstream of a submission. It groups several formal interaction categories: Pre-Submission (Pre-Sub) to scope an upcoming 510(k), De Novo, PMA or IDE, with written questions to the FDA followed by a written response and a teleconference; Submission Issue Request (SIR) for specific questions during ongoing review; Study Risk Determination, to have the FDA decide whether a study is SR or NSR; Informational Meeting; PMA Day-100 meeting; Sprint Discussion, an accelerated programme on a bounded topic within a defined time window.

The Q-Sub is non-binding on the FDA, but the positions expressed are generally followed so long as the underlying assumptions remain unchanged. It has become a standard planning tool for significant files.

The Quality System Regulation becomes QMSR in 2026

21 CFR Part 820 establishes the mandatory quality system for every manufacturer of a medical device marketed in the United States. Its historical version, the Quality System Regulation (QSR), rested on an FDA-specific text, close in logic to ISO 13485 but distinct in wording.

The Final Rule published in February 2024 (Federal Register, 89 FR 7496) amends 21 CFR Part 820 to incorporate ISO 13485:2016 by reference. The text renames the regulation Quality Management System Regulation (QMSR) and adds a few clarifications specific to the FDA framework (terminology, articulation with other parts of 21 CFR, reporting, surveillance). The application date is set at 2 February 2026.

The objective is twofold: international alignment, by adopting the grammar of a standard already used globally and easing the reuse of a single quality system across multiple markets; and preservation of the indispensable US specificities, notably reporting obligations (Medical Device Reporting under 21 CFR Part 803) and articulation with establishment requirements.

For a manufacturer already certified to ISO 13485, the transition is mostly documentary: verify terminological consistency, integrate the QMSR-specific additions, update cross-references in the quality documentation. For a manufacturer running on the legacy QSR without ISO certification, the transition requires a deeper review project.

SaMD, software and PCCP

For Software as a Medical Device (SaMD), the FDA has issued several structuring guidances (General Principles of Software Validation, Content of Premarket Submissions for Device Software Functions, Cybersecurity in Medical Devices, and the Predetermined Change Control Plan (PCCP) guidance).

The PCCP is a mechanism introduced for software, including software embedding AI or machine learning, which lets the manufacturer declare in advance, within its 510(k), De Novo or PMA submission, an envelope of planned modifications that may be deployed without a new submission so long as they remain within the approved scope. The PCCP comprises a Description of Modifications, a Modification Protocol describing how each modification will be evaluated and validated, and an Impact Assessment analysing the effects on safety and effectiveness. For AI and machine learning models, the PCCP fits within the broader AI/ML-Based Software as a Medical Device Action Plan, which includes a Good Machine Learning Practice (GMLP) framework currently being co-developed with MHRA and Health Canada.

Combination products: drug, device, biologic

A combination product combines two or more regulatory categories, most often drug + device (an insulin auto-injector, a transdermal patch with controlled release) or device + biologic. The lead-center determination (which FDA center pilots the review) follows the primary mode of action (PMOA) rule defined at 21 CFR Part 3. Where the PMOA is ambiguous, the manufacturer files a Request for Designation (RFD) to the Office of Combination Products (OCP), which rules within 60 days. According to the lead center: CDRH (device primary) follows the 510(k), De Novo or PMA pathway depending on the class; CDER (drug primary) follows the NDA or ANDA pathway; CBER (biologic primary) follows the BLA pathway. The non-lead center is consulted on its component.

When a change requires a new 510(k)

The FDA guidance Deciding When to Submit a 510(k) for a Change to an Existing Device (October 2017, revised since) structures the decision as a series of question trees. The baseline rule: a new 510(k) is required when the change:

• modifies or extends the intended use,
• significantly affects safety or effectiveness,
• introduces a new question of safety or effectiveness, or
• touches the device's principles of operation.

A change controlled by the quality system, with no impact on safety or effectiveness, is documented internally without submission. The manufacturer must keep the rationale for not submitting (commonly known in industry practice as a letter-to-file or memo-to-file, not to be confused with the 513(g)) for traceability during inspection.

For PMA devices, the equivalent mechanism is the PMA Supplement, graded by magnitude (Panel-Track, 180-Day, Real-Time, Special).

Relationship with the EU MDR

The FDA and MDR regimes are independent. A device cleared or approved by the FDA (510(k), De Novo or PMA) is not automatically CE marked, and vice versa.

Aspect	FDA (US)	MDR (EU)
Legal framework	FD&C Act, 21 CFR	Regulation (EU) 2017/745
Authority	FDA (CDRH, CDER, CBER)	Member states + designated notified bodies
Classification	I, II, III (21 CFR 860)	I, IIa, IIb, III (Annex VIII, 22 rules)
Main route, class II / IIa	510(k)	Annex IX (notified body)
High-class route	PMA	Annex IX with full design dossier review
Route for novel device without predicate	De Novo	No direct equivalent
Third-party evaluation	FDA in-house	Third-party notified body
Unique identification	FDA UDI (GUDID database)	MDR UDI (EUDAMED)
Surveillance	MDR (Medical Device Reporting, 21 CFR 803)	Vigilance + PSUR + EUDAMED
Quality system	21 CFR Part 820 (ISO 13485 via QMSR from 2026)	ISO 13485 + MDR requirements

Bridges do exist, however, and some technical data (biocompatibility, sterilisation, bench performance, software validation) can be reused identically from one file to another, subject to adaptation to the applicable regulatory grammar. See our MDR guide, our EU-US dual certification guide and the certification timeline for project planning. The CE page details the general CE marking framework, and the FCC page covers US radio and EMC compliance for the telecommunication component of a connected device.

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Common pitfalls observed in the field

Several pitfalls recur in FDA review statistics and in professional literature.

• Poorly chosen predicate, too old or drawn from a chain of predicates of doubtful quality (split predicate, multiple predicate, reference device confused with predicate). The file ends up fragile, with a higher likelihood of Refuse to Accept or NSE.
• Intended use too broad or too creative. The FDA carefully assesses consistency between Indications for Use, instructions for use, labelling and supplied data. A marketing-driven wording unsupported by data is a frequent reason for return.
• Q-Sub neglected. Going into a 510(k) or PMA without a prior Pre-Sub exposes the file to avoidable AI requests.
• Software validation insufficiently documented. The FDA expectation rests as much on process as on artefacts.
• PCCP undersized for evolving software: a minimal PCCP forces a re-submission for every modification not covered.
• Confusion between clearance and approval. A 510(k) device is cleared, not approved. The nuance matters legally and in communication.

Where this overview leads

This page is a Wave 1 overview. Dedicated pages to follow will cover operational classification by product code and the FDA Product Classification database, the step-by-step mechanics of an eSTAR 510(k) submission, the PCCP for devices integrating AI, the QSR-to-QMSR transition (2 February 2026), and cybersecurity (Cybersecurity in Medical Devices, section 524B of the FD&C Act introduced by the PATCH Act).

The glossary lists key terms (510(k), De Novo, PMA, IDE, HDE, PCCP, QMSR) with their definitions and cross-references.

See also

• QMS: ISO 9001, AS 9100, ISO 13485, TL 9000 compared
• IATF 16949: automotive quality management
• Risk management: ISO 14971, IEC 31010, FMEA, FTA, HAZOP
• MDR: the EU Medical Device Regulation (2017/745)

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Sources & references

1. 21 CFR Part 807, Premarket Notification 510(k) , eCFR www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-807
2. 21 CFR Part 814, Premarket Approval (PMA) , eCFR www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-814
3. 21 CFR Part 820, Quality System Regulation (becoming QMSR in February 2026) , eCFR www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-820
4. FDA, Medical Devices home , U.S. Food and Drug Administration www.fda.gov/medical-devices
5. FDA 510(k) Clearances database , U.S. Food and Drug Administration www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm
6. FDA, De Novo Classification Request , U.S. Food and Drug Administration www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/de-novo-classification-request