How is the 90-day FDA review clock for a 510k actually calculated?

## Understanding the 510(k) Review Clock: A Guide to "FDA Days" vs. Calendar Days The FDA’s 90-day performance goal for reviewing a 510(k) submission is a foundational metric in medical device commercialization planning. However, this number represents 90 "FDA Days," not 90 calendar days. This distinction is critical, as the review clock stops and starts based on interactions between the sponsor and the agency. Understanding how this clock is calculated is essential for sponsors of any Class II device—from an orthopedic implant to a diagnostic Software as a Medical Device (SaMD)—to manage timelines effectively and provide realistic forecasts to internal stakeholders. The total time to clearance is rarely just 90 calendar days. The clock pauses whenever the FDA places the submission on hold to request additional information from the sponsor. These "clock stops" can occur during the initial administrative review or the later substantive scientific review. By anticipating common pitfalls and preparing a robust submission, sponsors can minimize these delays and navigate the process more predictably. ### Key Points * **FDA Days vs. Calendar Days:** The 90-day review goal is an FDA performance metric that counts only the days the submission is actively under review by the agency. It does not include the time a submission is on hold waiting for a sponsor's response. * **The Clock Stops for Holds:** The review clock is paused for two primary reasons: a "Refuse to Accept" (RTA) hold during the initial 15-day administrative review, or an "Additional Information" (AI) request during the substantive review. * **RTA is Largely Preventable:** Most RTA holds result from administrative or formatting errors, such as missing forms, inconsistent information, or a failure to follow FDA's eCopy guidance. A meticulous internal pre-submission check can prevent these initial delays. * **Plan for at Least One AI Request:** It is common for the FDA to issue at least one AI request for additional data or clarification, especially for devices with novel features, complex software, or new materials. Building this cycle into the project timeline is a realistic approach. * **Comprehensive AI Responses are Critical:** When responding to an AI request, providing a thorough and complete package is more effective than a rushed, partial answer. An incomplete response can lead to further questions or a negative final decision. * **Proactive Engagement Reduces Uncertainty:** Using the Q-Submission program to gain FDA feedback on critical aspects like predicate selection or testing strategies *before* filing the 510(k) is one of the most effective ways to de-risk the review process and prevent major clock stops. --- ### ## Understanding the 510(k) Review Clock: A Two-Clock System To accurately forecast a 510(k) timeline, it's best to think of the process as a "two-clock" system: the FDA clock and the sponsor clock. 1. **The FDA Clock (Goal: 90 Days):** This clock starts the day the FDA receives the 510(k) submission. It tracks the time the agency spends on active review. The FDA’s MDUFA performance goals aim for a final decision on 95% of 510(k)s within 90 FDA Days. 2. **The Sponsor Clock (Variable):** This clock starts whenever the FDA places a submission on hold. For an AI request, regulations under 21 CFR give sponsors up to 180 calendar days to respond. This period, which is entirely controlled by the sponsor, does not count against the 90-day FDA clock. The typical 510(k) review journey unfolds in these phases: * **Phase 1: Acceptance Review (First ~15 Days):** The FDA conducts an administrative and completeness check known as the Refuse-to-Accept (RTA) review. If the submission passes, it is accepted for substantive review. If it fails, the FDA clock stops, and the sponsor clock starts. * **Phase 2: Substantive Review (Days ~16-60):** FDA reviewers conduct a detailed scientific and technical evaluation of the submission to determine substantial equivalence. * **Phase 3: Interactive Review & AI Holds (Days ~60-90):** If deficiencies are found, the FDA will typically issue an AI request around day 60-75. At this point, the **FDA clock stops**. The sponsor then has up to 180 calendar days to submit a complete response. Once the response is submitted, the **FDA clock restarts** from where it left off. * **Phase 4: Final Decision:** After reviewing the sponsor's response, the FDA completes its remaining review days and issues a final decision (e.g., Substantially Equilavent or Not Substantially Equivalent). --- ### ## Phase 1: The Acceptance Review (RTA) – Avoiding the First Hurdle The RTA review is a checklist-driven process to ensure the submission is administratively complete and formatted correctly for an efficient substantive review. An RTA hold is a common and entirely preventable cause of delay. #### Common Reasons for an RTA Hold Sponsors can minimize the risk of an RTA by performing a thorough internal audit against the FDA's RTA checklist, which is publicly available. Key areas to scrutinize include: 1. **Administrative Completeness:** * **Missing or Incorrect Forms:** Ensure the Premarket Review Submission Cover Sheet (Form FDA 3514) is complete and accurate. * **User Fee Payment:** Confirmation of the Medical Device User Fee Act (MDUFA) payment must be included. * **eCopy Requirements:** The submission must be formatted precisely according to the FDA’s eCopy Program guidance. Failure to do so is a frequent cause of rejection. 2. **Predicate Justification:** * **Unclear Predicate:** The submission must clearly identify the primary predicate device. * **Missing Comparison Table:** A detailed, side-by-side comparison of the subject device and the predicate is required, addressing Indications for Use, technology, and performance. 3. **Indications for Use (IFU):** * **Inconsistency:** The IFU statement must be identical on the cover sheet, in the dedicated IFU section, in the proposed labeling, and wherever else it appears. Even minor wording differences can trigger an RTA. 4. **Testing and Data Summaries:** * **Missing Data:** The submission must contain summaries of all required performance testing (e.g., biocompatibility, electrical safety, software validation). It is not enough to state that testing will be done. * **Lack of Declarations:** If relying on consensus standards, the submission must include a Declaration of Conformity. --- ### ## Phase 2: Substantive Review and Additional Information (AI) Requests Once a 510(k) is accepted, it moves to substantive review. This is where FDA scientific and engineering staff evaluate the core of the substantial equivalence argument. An AI request during this phase is not a sign of failure; it is a standard part of the interactive review process. #### Common Technical Deficiencies Triggering an AI Request * **For Physical Devices (e.g., Orthopedic Implant):** * **Biocompatibility:** Inadequate rationale for why certain ISO 10993 tests were or were not performed; missing chemical characterization data for novel materials. * **Mechanical Performance:** Test methods that do not adequately simulate the clinical use environment; insufficient sample sizes for bench testing; acceptance criteria not clinically justified. * **Sterilization:** Incomplete validation data for the proposed sterilization method and packaging. * **For SaMD and AI/ML Devices:** * **Software Validation:** Missing documentation for all life cycle phases, as outlined in FDA guidance; inadequate unit, integration, or system-level testing. * **Cybersecurity:** Failure to provide a comprehensive cybersecurity risk assessment and management plan, as detailed in FDA's guidance on the topic. * **AI/ML Transparency:** For AI/ML-enabled devices, the algorithm's description may be too vague. FDA often asks for more detail on the training and testing datasets, the model architecture, and the retraining plan. #### Strategy for Responding to an AI Request When an AI request is received, the sponsor faces a strategic choice: respond quickly or respond completely. * **Quick, Partial Response:** This approach is rarely advisable. Submitting an incomplete answer to get the FDA clock running again often leads to follow-up questions, another hold, or a negative decision if the remaining deficiencies are significant. * **Comprehensive, Complete Response:** The best practice is to take the necessary time (within the 180-day sponsor clock) to fully address every point in the AI letter. This may involve conducting new testing or rewriting entire sections. A comprehensive response demonstrates a commitment to resolving the issues and significantly increases the chances of a favorable outcome in the next review cycle. --- ### ## Communicating Timelines: Modeling Scenarios for Stakeholders Regulatory professionals must translate the fluid concept of "FDA Days" into concrete project plans. Using best-case, average-case, and worst-case scenarios is an effective way to manage expectations. #### ### Scenario 1: Best-Case (No Clock Stops) This scenario is rare and assumes a perfect submission with no RTA or AI holds. * **Total FDA Days:** 90 * **Total Sponsor Days:** 0 * **Estimated Calendar Time:** **~90-100 days.** This is the "ideal" path but should be presented as the most optimistic and least likely outcome. #### ### Scenario 2: Average-Case (One AI Cycle) This is the most realistic model for planning purposes. It assumes the submission passes RTA but receives one AI request. * **Phase 1 (RTA/Substantive Review):** 60 FDA Days (~60 calendar days) * **AI Request Issued:** **FDA Clock Stops.** * **Phase 2 (Sponsor Response):** 60 Sponsor Days (~60 calendar days to gather data and write the response) * **Phase 3 (Final Review):** 30 FDA Days (~30 calendar days) * **Estimated Calendar Time:** **~150 calendar days.** The 60-day sponsor response time is an estimate; this phase can range from 30 to over 100 days depending on the complexity of the request. #### ### Scenario 3: Worst-Case (RTA Hold + Complex AI) This scenario accounts for significant early delays and a challenging substantive review. * **Phase 1 (RTA Hold):** 15 FDA Days -> RTA Hold Issued. **FDA Clock Stops.** * **Phase 2 (Sponsor Response to RTA):** 45 Sponsor Days (~45 calendar days to fix administrative issues) * **Resubmission:** A new 90-day FDA clock starts. * **Phase 3 (Substantive Review):** 70 FDA Days (~70 calendar days) -> AI Request Issued. **FDA Clock Stops.** * **Phase 4 (Sponsor Response to AI):** 120 Sponsor Days (~120 calendar days for new testing and analysis) * **Phase 5 (Final Review):** 20 FDA Days (~20 calendar days) * **Estimated Calendar Time:** **~270+ calendar days.** --- ### ## Strategic Considerations and the Role of Q-Submission The most effective strategy for managing the 510(k) clock is to address potential issues *before* the submission is filed. The FDA's Q-Submission program is the ideal mechanism for this. By requesting a pre-submission meeting, sponsors can get direct, device-specific feedback from their likely review team on critical topics such as: * The choice of predicate device(s). * The proposed testing plan (clinical or non-clinical). * The framework for demonstrating substantial equivalence for a novel technology. Addressing these high-risk areas upfront can prevent a major AI request that would otherwise stop the clock for months. Early engagement and alignment with the FDA are invaluable for increasing the predictability of the 510(k) timeline. ### ## Key FDA References - FDA Guidance: general 510(k) Program guidance on evaluating substantial equivalence. - FDA Guidance: Q-Submission Program – process for requesting feedback and meetings for medical device submissions. - 21 CFR Part 807, Subpart E – Premarket Notification Procedures (overall framework for 510(k) submissions). ## How tools like Cruxi can help Navigating the complexities of the 510(k) process requires meticulous organization and document control. Tools like Cruxi can help sponsors manage their submission content, ensuring that elements like the Indications for Use statement are consistent across all sections. By structuring documentation according to regulatory requirements from the start, teams can streamline the authoring process, reduce the risk of administrative errors that lead to RTA, and maintain a clear audit trail for all supporting evidence. *** *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.* --- *This answer was AI-assisted and reviewed for accuracy by Lo H. Khamis.*