How does the FDA calculate the 90-day 510k review clock?

## Understanding the FDA 510(k) Review Clock: A Detailed Breakdown A common point of confusion for medical device sponsors is the FDA's performance goal to review a 510(k) submission within 90 days. While this figure is widely cited, it represents 90 "FDA Days," not 90 calendar days from submission to clearance. The total elapsed time for a 510(k) review is almost always longer due to various administrative and substantive review phases where the clock is not running. Understanding how the FDA calculates this review time is critical for accurate project planning, resource allocation, and stakeholder communication. The 90-day clock does not begin the moment a submission is filed. It only starts after the submission passes an initial administrative review, known as the Refuse to Accept (RTA) policy. Furthermore, if the FDA requires additional information during its scientific review—a common occurrence—it will place the submission on hold, stopping the clock entirely. This "Sponsor Time" to respond to FDA's questions is often the largest variable in the overall timeline. This article provides a detailed, phase-by-phase breakdown of how the 510(k) review clock functions, common pitfalls, and strategic considerations for navigating the process efficiently. ### Key Points * **FDA Days vs. Calendar Days:** The 90-day review goal refers to the cumulative time the submission is actively under review by the FDA. It excludes time spent in administrative processing and periods when the submission is on hold awaiting sponsor response. * **The Clock Starts After RTA:** The 90-day review clock does not begin upon submission. It only starts after the FDA has completed its Refuse to Accept (RTA) review and formally accepted the 510(k) for substantive review, a process that typically takes about 15 calendar days. * **Additional Information (AI) Requests Stop the Clock:** The most significant factor extending total review time is an AI request. When the FDA issues an AI request, the review clock is paused. The sponsor typically has up to 180 calendar days to provide a complete response. This period is known as "Sponsor Time." * **The Clock Resumes, It Doesn't Reset:** Once a sponsor submits a complete response to an AI request, the FDA review clock resumes from where it left off. For example, if a hold was placed on FDA Day 65, the agency has 25 FDA Days remaining to complete its review. * **Total Elapsed Time is Variable:** The total time from submission to a final decision is a combination of RTA review time, FDA review time, and sponsor response time. A single AI hold can easily extend the total timeline to 150–200 days or more. * **Proactive Planning is Essential:** Sponsors must build potential clock-stopping events into their internal project timelines. Assuming a 90-calendar-day path to clearance is a common and costly planning error. ### Deconstructing the 510(k) Review Timeline: A Phase-by-Phase Guide To accurately forecast a 510(k) timeline, it is essential to understand each distinct phase of the process and how it affects the review clock. #### Phase 1: Submission and the Refuse to Accept (RTA) Review (Clock is OFF) When a 510(k) is first submitted to the FDA, the 90-day review clock has **not** started. The submission first enters an administrative screening process governed by the FDA's RTA policy. * **Purpose:** The RTA review is a checklist-based assessment to ensure the submission is administratively complete and formatted correctly for a substantive review. FDA staff are not evaluating the scientific merits of the device; they are confirming that all required elements, as specified in FDA guidance, are present. * **Timeline:** The FDA's goal is to conduct the RTA review within 15 calendar days of receiving the submission. * **What FDA Checks:** The RTA checklist includes items such as: * Presence of a signed cover letter and required forms. * Payment of the correct user fee. * A clear device description and comparison to a valid predicate device. * Inclusion of all required sections (e.g., labeling, performance testing, sterilization). * Compliance with eCopy or eSTAR program requirements. * **Possible Outcomes:** 1. **Accepted:** If the submission passes the RTA review, the FDA issues an Acknowledgment Letter. The 90-day substantive review clock starts on the day the letter is issued. 2. **RTA Hold:** If the submission is found to be incomplete, the FDA will issue an RTA hold letter detailing the deficiencies. The sponsor has up to 180 calendar days to correct the issues and resubmit the file. The 90-day clock does not start until the revised submission is received and accepted. **Best Practice:** Before submitting, manufacturers should perform a thorough internal audit of their 510(k) using the most current FDA RTA guidance checklist. An RTA hold is an avoidable delay that can add weeks or months to the project timeline before the substantive review even begins. #### Phase 2: Substantive Review (Clock is ON) Once a 510(k) is accepted, the 90-day "FDA Day" clock begins, and the submission moves into Substantive Review. This is where FDA reviewers (e.g., lead reviewers, engineers, clinicians) conduct a thorough scientific and regulatory assessment of the device's substantial equivalence claim. * **Purpose:** To determine if the new device is as safe and effective as its identified predicate device. Reviewers scrutinize performance data, labeling, and the technological characteristics of the device. * **Timeline:** The FDA has a total of 90 FDA Days to complete this review. * **Interactive Review:** During this phase, the FDA may have minor questions or requests for clarification. The agency often uses an "Interactive Review" process to communicate these via email or phone. These exchanges are intended for simple issues and **do not stop the review clock**. Responding promptly and clearly is crucial to keeping the review moving. #### Phase 3: The Additional Information (AI) Request (Clock STOPS) If the FDA identifies significant deficiencies or has questions that cannot be resolved through Interactive Review, it will issue a formal AI request. This is the most common clock-stopping event. * **Purpose:** An AI request formally communicates the FDA's questions about the submission. These can range from requests for additional performance testing data to clarifications on the device's indications for use or a reassessment of the chosen predicate. * **Clock Impact:** The moment an AI request is issued, the **FDA review clock stops**. * **Sponsor Time:** A "Sponsor Time" clock begins. The sponsor has a maximum of **180 calendar days** to provide a complete response to all questions raised in the AI letter. * **Strategic Importance:** This is a critical juncture. A well-organized, comprehensive response that directly addresses every FDA question is necessary to resume the review. An incomplete or inadequate response can result in the FDA considering the submission withdrawn or, in some cases, lead directly to a Not Substantially Equivalent (NSE) decision. #### Phase 4: Resuming the Review (Clock is ON Again) After the sponsor submits a complete response to the AI request, the FDA review clock resumes from where it left off. * **Clock Impact:** If the AI request was issued on FDA Day 60, the FDA has 30 FDA Days remaining on its 90-day clock to complete the review and issue a final decision. * **Final Decision:** Upon completing the resumed review, the FDA will issue a final decision letter, which is typically either: * **Substantially Equivalent (SE):** The device is cleared for marketing in the U.S. * **Not Substantially Equivalent (NSE):** The device is not cleared. The sponsor may need to resubmit a new 510(k), pursue a De Novo classification request, or file a Premarket Approval (PMA) application. ### Scenario 1: An Ideal Review Timeline This scenario illustrates a smooth review with only minor clarifications, which is possible for well-prepared submissions for devices with a strong predicate. * **Device:** A Class II clinical electronic thermometer with well-established technology. * **Timeline Visualization:** * `[Day 1-15: RTA Review]` -> `[Submission Accepted]` -> `[Day 16-85: Substantive Review]` -> `[SE Decision]` * **Breakdown:** * **Day 0:** 510(k) submitted. * **Day 14:** FDA completes RTA review and issues an Acknowledgment Letter. The 90-day clock starts. * **Day 60 (FDA Day 46):** FDA sends an email via Interactive Review asking for a minor clarification in the labeling. The sponsor responds within 24 hours. The clock does not stop. * **Day 84 (FDA Day 70):** The FDA completes its review and issues an SE letter. * **Total Elapsed Time:** Approximately 84 calendar days. ### Scenario 2: A Typical Review Timeline with One AI Hold This scenario is more common, especially for devices with novel features, new materials, or complex software. * **Device:** A wearable cardiac monitor (Class II) that uses a novel algorithm for arrhythmia detection. * **Timeline Visualization:** * `[Day 1-15: RTA Review]` -> `[Submission Accepted]` -> `[Day 16-80: FDA Review (65 days)]` -> `[AI HOLD]` -> `[Day 81-170: Sponsor Time (90 days)]` -> `[Day 171-195: FDA Review (25 days)]` -> `[SE Decision]` * **Breakdown:** * **Day 0:** 510(k) submitted. * **Day 15:** Submission is accepted. The 90-day clock starts. * **Day 80 (FDA Day 65):** FDA issues an AI request asking for additional clinical performance data to validate the new algorithm against a recognized standard. **The FDA clock stops at 65 days.** * **Day 81 - Day 170 (90 Calendar Days of Sponsor Time):** The sponsor performs the requested data analysis, prepares a detailed report, and drafts a comprehensive response. * **Day 171:** The sponsor submits the complete AI response. **The FDA clock resumes with 25 days remaining.** * **Day 195 (FDA Day 90):** The FDA completes its review of the new data and issues an SE letter. * **Total Elapsed Time:** Approximately 195 calendar days. ### Strategic Considerations and the Role of Q-Submission The most effective way to manage the 510(k) review clock is to minimize the chances of it stopping. The best strategy is proactive engagement with the FDA before the 510(k) is even submitted. The Q-Submission program provides a formal pathway for sponsors to get feedback from the FDA on key aspects of their planned submission. Engaging in a Q-Submission (or "Pre-Submission") allows a manufacturer to discuss and gain alignment on critical topics such as: * The choice of predicate device(s). * The proposed testing plan (non-clinical and clinical). * Specific data requirements for novel features or materials. * Cybersecurity or software documentation needs. By obtaining FDA feedback early, sponsors can prepare a more complete and robust 510(k) package, significantly reducing the likelihood of a major AI request during the substantive review. Investing time in a Q-Submission can save months of delay and uncertainty later in the process. ### 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 Successfully navigating the 510(k) process and managing the review clock requires meticulous organization and documentation. Regulatory intelligence platforms like Cruxi can help teams structure their submission evidence, track predicate device data, and manage the extensive documentation required for performance testing and labeling. By ensuring all necessary components are systematically organized and cross-referenced, sponsors can build a higher-quality submission from the start, helping to minimize the risk of avoidable delays like RTA holds or AI requests. *** *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.*