What is the FDA De Novo review timeline in 2024?

For companies developing a novel, low-to-moderate risk medical device without a clear predicate, such as an AI-based diagnostic software, the De Novo pathway offers a route to market. In 2024, a critical part of commercialization planning involves forecasting the regulatory review timeline. While the FDA has established performance goals for reviewing De Novo requests under the Medical Device User Fee Amendments (MDUFA), the total time from submission to a final decision is often longer than this target. The primary factor extending the overall timeline is the issuance of an Additional Information (AI) request from the FDA, which places the submission on hold and "stops the clock" on the official review period. This pause allows the sponsor to gather necessary data and provide a comprehensive response, but it can significantly lengthen the project timeline beyond the initial MDUFA goal. Therefore, sponsors should forecast the total time to a De Novo grant by considering both the FDA's performance goals and the high likelihood of at least one "stop-the-clock" period. The most effective strategy to ensure a more predictable review process is to prepare a thorough, complete submission and engage with the FDA proactively through the Q-Submission program. ### Key Points * **MDUFA Goal vs. Reality:** The FDA has a MDUFA performance goal to make a decision on De Novo requests within a set number of review days. However, this is a target for the agency and not a guaranteed timeline for sponsors. * **The "Stop-the-Clock" Mechanism:** The total calendar time to a decision is almost always longer than the MDUFA goal due to AI requests. When the FDA asks for more information, the review clock pauses until the sponsor provides a complete response. * **Submission Quality is Paramount:** A well-organized, complete De Novo request with robust performance data and a clear risk-benefit profile is the most critical factor in minimizing the number and duration of AI requests. * **Proactive FDA Engagement:** Using the Q-Submission program to gain alignment with the FDA on testing plans and proposed special controls *before* filing the De Novo request is a key strategy for reducing review cycle times. * **Special Controls are Central:** A De Novo submission must include a proposal for general and special controls that can provide a reasonable assurance of safety and effectiveness. An incomplete or inadequate proposal is a common reason for an AI request. ### Understanding the Official De Novo Review Clock The FDA's review of a De Novo request is measured in "FDA days." Under the MDUFA program, the agency has a performance goal to reach a decision within a specific number of these days. However, this clock only runs when the submission is actively under review at the agency. The most significant variable in the De Novo timeline is the "stop-the-clock" period initiated by an Additional Information (AI) request. If the FDA review team finds that information is missing or unclear, they will issue an AI letter to the sponsor. At this point, the MDUFA clock stops. It does not restart until the sponsor submits a complete formal response to all of the FDA's questions. This process can add several months to the total timeline, depending on the complexity of the questions and the time required to generate the necessary data. Because of this dynamic, sponsors should plan for a total timeline that extends well beyond the MDUFA performance goal. ### Common Reasons for Additional Information (AI) Requests To minimize delays, sponsors should anticipate common pitfalls that lead to AI requests. A robust submission addresses these areas comprehensively from the outset. #### 1. Incomplete or Unclear Device Description The FDA must have a crystal-clear understanding of the device, its principles of operation, its intended use, and the technology it employs. For a novel device like an AI-based diagnostic software, this includes a detailed explanation of the algorithm, the datasets used for training and testing, and the user interface. Ambiguity in the device description is a frequent cause for early AI requests. #### 2. Insufficient Performance Data The De Novo request must be supported by sufficient performance data to establish a reasonable assurance of safety and effectiveness. This often includes a combination of non-clinical (bench) testing and clinical data. Common deficiencies include: * **Inadequate sample sizes** in performance studies. * **Lack of a clear, pre-specified study protocol** with well-defined endpoints. * **Failure to test the device** under all relevant conditions of use. * **For SaMD**, insufficient data on algorithm validation, cybersecurity, and human factors. #### 3. Inadequate Risk Analysis A cornerstone of any medical device submission is a thorough risk analysis, conducted in accordance with general principles outlined in FDA guidance. The sponsor must identify all potential risks associated with the device and demonstrate that these risks have been mitigated to an acceptable level. An AI request may be issued if the risk analysis is incomplete, fails to address certain risks, or proposes insufficient mitigation measures. #### 4. Unclear Proposal for Special Controls A successful De Novo request results in the creation of a new device classification regulation under 21 CFR. This regulation includes both general controls and device-specific "special controls." The sponsor must propose a set of special controls that can be used to regulate future devices of the same type. If this proposal is not well-defined, scientifically justified, or sufficient to mitigate known risks, the FDA will require clarification. ### Strategic Considerations and the Role of Q-Submission The most effective strategy to manage the De Novo timeline is to reduce the likelihood of significant AI requests. This is best achieved by submitting a high-quality, complete application and engaging with the FDA early. The Q-Submission program is an invaluable tool for De Novo sponsors. By requesting a Pre-Submission (Pre-Sub) meeting, a company can present its device, risk analysis, and validation plans to the FDA review team before formally submitting the De Novo request. This dialogue provides an opportunity to get direct feedback on the proposed testing strategy, clinical data requirements, and the adequacy of the proposed special controls. Gaining this alignment upfront can prevent major deficiencies in the final submission, leading to a more efficient and predictable review process. ### Key FDA References For sponsors preparing a De Novo request, it is essential to consult the latest official FDA resources. Key documents include: * FDA's guidance on the De Novo Classification Process. * FDA's Q-Submission Program guidance. * Relevant sections of 21 CFR, such as those pertaining to device classification and controls. ### How tools like Cruxi can help Navigating the De Novo pathway requires meticulous organization and management of extensive documentation, from performance data to risk analyses and proposed labeling. Tools designed for regulatory affairs can help teams structure their submission, track requirements against FDA guidance documents, and collaborate on building a comprehensive and well-supported De Novo request, which is foundational to a more streamlined review. This article is for general educational purposes only and is not legal, medical, or regulatory advice. For device-specific questions, sponsors should consult qualified experts and consider engaging FDA via the Q-Submission program.