FDA De Novo Process: A Clear Guide for Novel Medical Devices

The FDA De Novo pathway provides a structured route for novel medical devices that have no valid predicate but whose risk can be appropriately controlled through general controls or a combination of general and special controls. It is a classification mechanism designed for devices that do not fit within any existing Class I or Class II regulation and which therefore receive an automatic Class III designation until they are reviewed through the De Novo process. Once granted, a De Novo request establishes a new device type and classification regulation and creates a predicate for future 510(k) submissions. Understanding how the De Novo pathway works is essential for companies developing innovative technologies because the process influences regulatory strategy, timelines, evidence requirements and long-term commercial positioning.

What the De Novo Request Is

The De Novo request is a formal submission asking the FDA to reclassify a novel device from its automatic Class III designation to Class I or Class II. This is only possible when evidence demonstrates that general controls alone, or general and special controls together, can provide reasonable assurance of safety and effectiveness. Devices classified through De Novo can then be legally marketed and used as predicates for follow-on 510(k) submissions. The core philosophy of the pathway is risk-based analysis. Instead of fitting a device into an existing classification structure, the FDA evaluates whether risks can be sufficiently mitigated and whether a new classification regulation should be created.

When to Prepare a De Novo Request

There are two routes into the De Novo pathway. The first route applies when a manufacturer submits a 510(k) and receives a high-level not substantially equivalent determination because no legally marketed predicate exists, the intended use is new or the technological characteristics raise different safety and effectiveness questions. The second route applies when the manufacturer recognises from the outset that no predicate exists and chooses to prepare a De Novo request without first submitting a 510(k). This option avoids unnecessary 510(k) review cycles and delays. In both cases, the FDA recommends using the Q Submission Program when there is uncertainty about data requirements, classification rationale or safety controls. Early FDA engagement helps manufacturers refine the structure and content of their De Novo request and avoid preventable deficiencies.

Required Contents of a De Novo Request

A De Novo request must comply with 21 CFR 860.220 and, from 1 October 2025 onward, must be submitted through eSTAR. Understanding the required content is essential because the FDA conducts an acceptance review that assesses whether the request meets administrative completeness requirements. Before listing the mandatory components, it is helpful to understand that FDA reviewers rely on clear evidence, structured reasoning and well-supported arguments for classification.

A complete De Novo submission includes a coversheet that identifies the request as a Request for Evaluation of Automatic Class III Designation under section 513(f)(2), administrative details regarding intended use and whether the device is prescription or over the counter, a comprehensive device description including technology, proposed conditions of use, components and accessories, and classification information that explains the recommended class and provides justification. Supporting data must include a full explanation of how general controls, or general and special controls, achieve reasonable assurance of safety and effectiveness, all relevant clinical evidence, non-clinical studies, bench performance testing, sterilisation, reprocessing, shelf life, biocompatibility, electrical safety, EMC results, software documentation, animal studies and literature evidence where appropriate. The requester must also describe the probable benefits relative to the probable risks when the device is used as intended. These data form the basis of the FDA’s evaluation, so completeness and coherence are critical.

FDA Review Process and Timeline

The review process consists of an acceptance review followed by a substantive review. Acceptance review, described in 21 CFR 860.230, is an administrative assessment designed to confirm whether the request meets the minimum required elements. If any section is missing, the requester must justify its omission. Acceptance review is largely automated within eSTAR and is typically completed within 15 calendar days of FDA receipt, provided the appropriate user fee has been paid. If information is incomplete, the FDA places the request on hold and issues an email identifying deficiencies. The requester then has 180 days to submit a replacement eSTAR. If the FDA does not complete the acceptance review within 15 days, the De Novo request automatically proceeds to substantive review.

During substantive review the FDA evaluates whether any legally marketed device of the same type exists, confirms De Novo eligibility and analyses whether the evidence demonstrates that risk can be controlled by general or general and special controls. If deficiencies arise, the FDA may resolve them through interactive review or, if not feasible, issue an Additional Information letter. When an Additional Information letter is issued, the De Novo is placed on hold and the requester has 180 days to submit a complete response. No extensions are allowed, and failure to respond within the 180-day period results in withdrawal of the request. The FDA aims to make a final decision within 150 review days, excluding time on hold. The number of review days is calculated based on the days between receipt and decision, minus any hold time awaiting additional information. These timelines mean manufacturers must plan carefully and maintain readiness to respond promptly to FDA requests.

FDA Final Actions on a De Novo Request

After completing the review, the FDA can grant, decline or withdraw the request. A grant is issued when evidence shows that general controls, or general and special controls, provide reasonable assurance of safety and effectiveness and that the probable benefits outweigh the probable risks. When granted, the device may be legally marketed, a new classification regulation is established, and the device can serve as a predicate for future 510(k) submissions. The FDA publishes a notice in the Federal Register announcing the new regulation, posts the granting order on its website and discloses a decision summary that outlines the scientific evidence supporting the decision.

A decline is issued when the FDA determines that general and special controls are insufficient to assure safety and effectiveness or that the data do not allow a reasonable conclusion regarding benefit and risk. In this case, the device remains in Class III and cannot be legally marketed. Manufacturers may either submit a PMA or generate additional evidence and resubmit a new De Novo request.

The FDA may also consider a De Novo withdrawn if the requester voluntarily withdraws in writing, if deficiencies are not addressed within 180 days, or if the requester does not permit necessary inspections. Withdrawn requests are not publicly posted.

FAQs – FDA De Novo Process