Quick Answer
A De Novo submission is an FDA request to classify a novel medical device into Class I or Class II when there is no legally marketed predicate device and general controls, or general plus special controls, can provide reasonable assurance of safety and effectiveness. As of October 1, 2025, De Novo requests must be submitted electronically using eSTAR unless exempted. A complete De Novo request includes device description, regulatory history, classification rationale, benefit-risk analysis, proposed controls, performance data, labeling, and other evidence needed to support FDA's risk-based classification decision.
Key Takeaways
- The De Novo pathway is for novel devices without a legally marketed predicate that are appropriate for Class I or Class II classification.
- A De Novo request can be submitted after a not substantially equivalent 510(k) decision or directly when the requester determines no predicate exists.
- FDA's De Novo content requirements are codified in 21 CFR 860.220.
- Starting October 1, 2025, De Novo submissions must use eSTAR unless exempted.
- A granted De Novo establishes a new device classification and may create a predicate for future 510(k) submissions.
- A De Novo submission is the FDA pathway for novel low-to-moderate-risk devices that do not fit the 510(k) predicate model. It is especially important for new digital health, diagnostic, AI-enabled, and other innovative device types where no legally marketed predicate exists.
- The risk is strategic as much as technical. If a device has a valid predicate, a 510(k) submission may be the better route. If the device is novel but can be controlled through general or special controls, De Novo may be appropriate. If the device is high risk and requires valid scientific evidence of safety and effectiveness, PMA may be required.
- This guide explains when De Novo is appropriate, what FDA expects in a De Novo request, how eSTAR affects filing, and how to prepare a complete submission package.
- In this guide, you will learn:
- What a De Novo submission is
- When to use De Novo instead of 510(k) or PMA
- What content FDA expects under 21 CFR 860.220
- How FDA technical screening and substantive review work
- How to build a De Novo submission checklist
- Related guides:
- From QMSR to eSTAR
- Quality records for regulatory submissions
- 510(k) vs De Novo classification
- Predicate device search
- Medical device regulatory pathway
- eSTAR Validation
What Is a De Novo Submission?
A De Novo submission, formally a De Novo classification request, asks FDA to classify a novel medical device into Class I or Class II when there is no legally marketed predicate and the device can be regulated with general controls or general plus special controls.
FDA describes De Novo as a risk-based classification pathway. It is used when a device would otherwise be automatically classified into Class III because no predicate exists, but the device's risk profile supports Class I or Class II classification.
A De Novo submission asks FDA to answer several linked questions:
- Is the device eligible for De Novo? FDA must confirm that no legally marketed device of the same type exists.
- What is the device's risk profile? The submission must identify probable risks and benefits.
- Are controls adequate? The requester must explain why general controls alone, or general plus special controls, provide reasonable assurance of safety and effectiveness.
- Does the evidence support classification? Nonclinical, clinical, software, biocompatibility, electrical safety, cybersecurity, sterilization, shelf-life, or other testing may be needed depending on the device.
If FDA grants the request, the device may be marketed subject to applicable controls. FDA also establishes a new classification regulation for the device type, and future devices of the same type may be able to use the De Novo device as a predicate for 510(k) submissions.
When to Use De Novo Instead of 510(k) or PMA
De Novo is appropriate only when the device is novel, lacks a legally marketed predicate, and is suitable for Class I or Class II controls.
| Pathway | Use When | Not a Good Fit When |
|---|---|---|
| 510(k) | A legally marketed predicate exists and substantial equivalence can be shown | No predicate exists or technology raises new questions of safety/effectiveness |
| De Novo | No predicate exists, but risk is low-to-moderate and controls can manage risks | Device risk requires PMA-level evidence |
| PMA | Device is high risk or Class III and requires valid scientific evidence | Device can be classified into Class I or II through De Novo |
Two De Novo Submission Options
FDA describes two ways to submit a De Novo request:
| Option | When Used |
|---|---|
| After NSE decision | The submitter receives a not substantially equivalent decision in response to a 510(k), often because no predicate exists or differences raise new safety/effectiveness questions. |
| Direct De Novo | The requester determines that no legally marketed device exists on which to base substantial equivalence and submits De Novo without first filing a 510(k). |
For borderline cases, FDA recommends considering a Pre-Submission to obtain feedback from the appropriate review division before filing. This is especially important when predicate status, classification, testing scope, or clinical evidence needs are uncertain.
De Novo Submission Requirements Under 21 CFR 860.220
FDA's De Novo content requirements are codified in 21 CFR 860.220 and reflected in the eSTAR template. Unless the requester justifies an omission, a De Novo request must include enough information for FDA to make a risk-based classification decision.
| Required Area | What FDA Needs | Practical Preparation Notes |
|---|---|---|
| Table of contents | Organized navigation for the request | eSTAR helps structure the package, but attachments still need clear naming. |
| Administrative information | Requester, U.S. representative if applicable, establishment information | Keep contacts and owner/operator details current. |
| Regulatory history | Prior 510(k), PMA, HDE, IDE, Q-Sub, 513(g), RFD, EUA, prior De Novo, or statement of no prior submissions | FDA uses this to understand device history and prior feedback. |
| Device name | Generic, proprietary, and trade names | Align across labeling, cover letter, and device description. |
| Indications for use | Disease or condition, patient population, user, prescription/OTC designation | Drives classification and benefit-risk analysis. |
| Device description | Technology, conditions of use, accessories, components, and principles of operation | Include diagrams and technical descriptions where helpful. |
| Classification recommendation | Proposed Class I or II and rationale | Explain why general or special controls are adequate. |
| Proposed special controls | Controls that mitigate identified risks for Class II devices | Be specific and connect each control to a risk. |
| Probable benefits and risks | Benefit-risk analysis for intended use | Address uncertainty, evidence strength, and residual risk. |
| Performance data | Bench, animal, clinical, software, biocompatibility, sterilization, shelf-life, electrical safety, EMC, cybersecurity, or literature evidence as applicable | Match the evidence package to the device's risks. |
| Labeling | Proposed labeling, instructions, warnings, limitations, and claims | Labeling is part of risk control. |
Device Description
The device description should explain how the device works and why its technology can be controlled safely. For software or AI-enabled devices, this may include:
- System architecture
- Inputs and outputs
- Data flow
- User workflow
- Algorithm function
- Training and validation approach, when applicable
- Cybersecurity considerations
- Risk controls
- Human factors or usability information, when relevant
Benefit-Risk Analysis
The De Novo pathway depends on whether probable benefits outweigh probable risks under the proposed controls. A strong benefit-risk section should:
- Identify each known or reasonably foreseeable risk
- Explain severity and likelihood where possible
- Connect risks to mitigations
- Explain expected clinical or user benefit
- Address residual uncertainty
- Tie labeling and special controls to risk management
Special Controls
For Class II De Novo requests, proposed special controls are central. Special controls can include performance standards, testing requirements, labeling requirements, clinical study requirements, postmarket surveillance, or other controls that provide reasonable assurance of safety and effectiveness.
When FDA grants a De Novo, those special controls can become the baseline for future devices of the same type.
eSTAR Requirements for De Novo Submissions
As of October 1, 2025, FDA requires De Novo submissions to be submitted electronically using eSTAR unless exempted. FDA also states that eSTAR is the only currently available electronic submission template to facilitate De Novo request electronic submissions.
The eSTAR requirement applies to De Novo requests and subsequent supplements, amendments, and other subsequent submissions to the original submission unless an exemption applies.
What eSTAR Changes for De Novo
| Area | Practical Impact |
|---|---|
| Structure | eSTAR guides the requester through required sections. |
| Completeness | Required fields and embedded prompts reduce formatting omissions. |
| Technical screening | FDA uses technical screening for De Novo eSTAR submissions. |
| Attachments | Evidence still needs to be complete, traceable, and correctly attached. |
| Strategy | eSTAR does not decide classification strategy or evidence sufficiency. |
eSTAR improves the submission container. It does not replace regulatory reasoning. The De Novo request still needs a coherent classification rationale, risk analysis, controls strategy, and evidence package.
De Novo Submission Process and Timeline
The De Novo review process includes receipt, technical screening or acceptance review, substantive review, possible Additional Information requests, and final action.
| Stage | FDA Activity | Timeline Signal |
|---|---|---|
| Submission receipt | FDA receives the De Novo eSTAR and verifies fee/submission validity | FDA assigns a De Novo number after proper receipt. |
| Technical screening / acceptance review | FDA evaluates whether the submission meets the minimum threshold for review | Technical screening should occur within 15 calendar days for De Novo eSTAR submissions. |
| Substantive review | FDA evaluates eligibility, risk, controls, and evidence | FDA's goal is to decide within 150 review days, excluding hold time. |
| Additional Information request | FDA requests information that cannot be resolved through interactive review | Submitter has 180 calendar days to provide a complete response. |
| Final action | FDA grants or declines the request, or considers it withdrawn in defined circumstances | A grant authorizes marketing and establishes a classification regulation. |
Technical Screening
FDA states that eSTAR submissions are not anticipated to undergo a traditional refuse-to-accept process. Instead, FDA uses virus scanning and technical screening as part of acceptance review. If the eSTAR is incomplete, FDA can notify the requester and place the De Novo on hold.
If a replacement eSTAR is not received within 180 days of the technical screening deficiency notification, FDA considers the De Novo withdrawn.
Substantive Review
During substantive review, FDA confirms whether the device is eligible for De Novo classification and evaluates the evidence supporting safety, effectiveness, probable benefits, probable risks, and controls.
If deficiencies can be resolved interactively, FDA may use interactive review. If they cannot, FDA may issue an Additional Information letter. The requester has 180 calendar days from the date of the AI letter to submit a complete response. FDA states that no extensions beyond 180 days will be granted.
FDA Decisions on a De Novo Request
FDA may grant, decline, or consider a De Novo request withdrawn.
| Decision | Meaning |
|---|---|
| Grant | FDA determines that general controls or general plus special controls provide reasonable assurance of safety and effectiveness and probable benefits outweigh probable risks. |
| Decline | FDA determines that controls are insufficient, data are insufficient, or probable benefits do not outweigh probable risks. |
| Withdrawn | Requester withdraws, fails to respond completely within 180 days, or fails to permit required inspection access. |
If FDA grants a De Novo request, the device can be marketed subject to applicable controls, a new classification regulation is established, and the device may serve as a predicate for future 510(k) submissions when applicable.
If FDA declines the request, the device remains Class III. The requester may need to pursue PMA or collect additional information and submit a new De Novo request.
De Novo Submission Checklist
Use this checklist before finalizing a De Novo eSTAR.
| Area | Checklist Item |
|---|---|
| Pathway decision | Confirm no legally marketed predicate supports a 510(k). |
| Risk classification | Confirm the device is appropriate for Class I or Class II, not PMA. |
| Pre-Submission | Consider Q-Sub feedback for novel technology, testing scope, clinical evidence, or special controls. |
| Regulatory history | Include prior 510(k), Q-Sub, 513(g), IDE, EUA, RFD, or previous De Novo history, or state none. |
| Device description | Provide complete technical description, components, accessories, technology, and operation. |
| Indications | Define intended use, population, user, environment, and prescription/OTC status. |
| Risk analysis | Identify probable risks, severity, mitigations, and residual uncertainty. |
| Benefit analysis | Explain probable benefits and how evidence supports them. |
| Proposed classification | Recommend Class I or II and justify the controls. |
| Special controls | Map each proposed special control to specific risks. |
| Performance evidence | Include bench, software, cybersecurity, biocompatibility, sterilization, animal, clinical, or other evidence as applicable. |
| Labeling | Ensure labeling is consistent with intended use, warnings, limitations, and risk mitigations. |
| eSTAR completeness | Resolve required fields, attachments, and technical screening prompts. |
| Internal QC | Check cross-references, version dates, attachment names, and consistency across sections. |
How Assyro Supports De Novo Submission Readiness
De Novo submissions are high-stakes because they create a new classification path. The package must explain the device, justify the classification, identify risks, propose controls, and support the benefit-risk decision with evidence.
Assyro supports De Novo teams through eSTAR Validation, medical device regulatory submission software, and structured submission readiness workflows. The practical value is finding missing content, inconsistent claims, weak cross-references, and eSTAR issues before the submission reaches FDA technical screening.
For novel devices, readiness is not only whether the eSTAR opens. It is whether the classification argument, risk controls, performance evidence, and labeling all support the same regulatory story.
A De Novo submission is a request for FDA to classify a novel medical device into Class I or Class II when there is no legally marketed predicate and controls can provide reasonable assurance of safety and effectiveness.
References
This guide reflects FDA De Novo and eSTAR requirements current as of May 2026. Requirements can change; always confirm the latest FDA guidance, eSTAR requirements, device-specific guidance, and review-division feedback before filing.
About the author
Assyro Team
Expert regulatory operations consultants helping pharmaceutical companies navigate complex compliance challenges.
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