How long does the FDA De Novo review process typically take?

## How Long Does the FDA De Novo Review Process Take? For sponsors of novel low-to-moderate risk medical devices without a clear predicate, such as an innovative AI-powered diagnostic software or a unique wearable biosensor, the De Novo pathway provides a route to market authorization and establishes a new device classification. While the FDA has a Medical Device User Fee Amendments (MDUFA) performance goal to issue a decision on De Novo requests within 150 review days, the total calendar time from submission to a final decision is often longer. This discrepancy arises because the 150-day "review clock" only counts the days the submission is actively under review by the FDA. The clock pauses when the agency issues a Request for Additional Information (AI) and does not restart until the sponsor provides a complete response. Understanding the factors that lead to these AI requests is key for sponsors to forecast timelines more accurately and develop a strategy for a more efficient review cycle. ### Key Points * **MDUFA Goal vs. Calendar Time:** The FDA's performance goal is to make a decision within 150 "FDA review days," not 150 calendar days. The total time is typically longer. * **The Review Clock Stops:** When the FDA issues a request for additional information (AI), the review clock pauses. The time a sponsor takes to prepare and submit a response does not count toward the 150-day goal. * **Common Causes for Delay:** AI requests often stem from an unclear intended use, insufficient performance data (bench, analytical, or clinical), or an incomplete risk-benefit analysis. * **Proactive Planning is Crucial:** A well-prepared submission that anticipates FDA's questions is the most effective strategy to minimize the chance of significant review delays. * **Q-Submissions Reduce Uncertainty:** Engaging the FDA early through the Q-Submission program can help align expectations on data requirements before filing, leading to a more predictable review. ### Understanding the 150-Day Goal vs. Total Calendar Time The De Novo process is designed for novel devices for which general controls alone, or general and special controls, provide a reasonable assurance of safety and effectiveness. The 150-day MDUFA goal represents the time FDA reviewers have to assess the submission. However, this is not an uninterrupted period. The process typically follows these steps: 1. **Submission and Acceptance Review:** After a sponsor submits a De Novo request, the FDA conducts an acceptance review to ensure it is administratively complete. 2. **Substantive Review:** If accepted, the formal "substantive review" begins, and the 150-day clock starts. 3. **Additional Information (AI) Request:** If reviewers identify deficiencies or need more data to complete their assessment, they will issue an AI letter. At this point, **the review clock stops.** 4. **Sponsor Response:** The sponsor has a set period (typically 180 days) to respond to the AI request. This response period can take several months, depending on the complexity of the questions. 5. **Review Resumes:** Once the FDA receives a complete response, the review clock restarts from where it left off. Because a submission can receive one or more AI requests, the total calendar time can easily extend to many months or even over a year, far exceeding the 150-day review goal. ### Common Deficiencies That Lead to Review Delays To minimize clock stoppages, sponsors should focus on preventing the common data gaps that trigger AI requests. These often fall into three main categories: #### 1. Ambiguous Intended Use or Indications for Use The intended use statement defines the device's purpose and the patient population it serves. If this statement is vague or overly broad, the FDA cannot adequately assess the device's risks and benefits. Reviewers may request clarification on the specific disease or condition, the clinical setting, or the user profile. #### 2. Insufficient Performance Data A De Novo request must contain sufficient data to demonstrate a reasonable assurance of safety and effectiveness. A lack of robust data is one of the most common reasons for an AI request. * **Non-Clinical (Bench) Testing:** Data must be provided to characterize the device's technical performance. For an AI-powered diagnostic software, this could include data on algorithm performance, cybersecurity, and validation across different datasets. * **Clinical Data:** While not always required, clinical evidence is often necessary to support the device's performance claims and risk-benefit profile. An AI request may ask for more data, a different analysis of existing data, or justification for why a clinical study was not performed. #### 3. Incomplete Risk-Benefit Analysis The core of a De Novo request is the argument that the device's risks can be mitigated through general and proposed special controls. A submission must include a comprehensive risk analysis (as outlined in ISO 14971) and a compelling benefit-risk assessment. If the analysis is superficial or fails to address key risks, the FDA will request a more thorough evaluation and justification for the proposed controls. ### Strategic Considerations and the Role of Q-Submission The most effective strategy for achieving a predictable De Novo timeline is proactive engagement with the FDA. The Q-Submission program allows sponsors to obtain feedback from the agency on their regulatory strategy and data generation plans *before* submitting the final De Novo request. A Pre-Submission (Pre-Sub) meeting is particularly valuable for novel devices. During this process, sponsors can present their planned intended use, testing protocols (both clinical and non-clinical), and proposed special controls. The FDA's written feedback can help: * Clarify expectations for performance data. * Identify potential deficiencies in the regulatory strategy early. * Gain alignment on the scope and design of a clinical study, if needed. * Confirm that the De Novo pathway is appropriate for the device. Addressing these critical questions before filing the De Novo request can significantly reduce the likelihood of a major AI request, thereby helping the sponsor stay closer to the 150-day review goal and avoid costly delays. ### Key FDA References * FDA's De Novo Classification Program guidance * FDA's Q-Submission Program guidance * 21 CFR Part 860 – Medical Device Classification Procedures ### How tools like Cruxi can help Navigating the De Novo pathway requires meticulous organization of evidence, data, and regulatory arguments. Tools like Cruxi can help sponsors structure their submission narrative, manage supporting documentation, and build a clear, compelling case for classification, ensuring all required elements are addressed before filing. 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.