When thinking about FDA’s 510(k) review clock, there are several nuances that device developers should be aware of, which may impact time to clearance. Congress has given FDA 90 calendar days to review a 510(k), however, the average time to decision in 2016 was 141 days, which is a significantly longer timeline and indicates that 510(k) reviews are often not as simple as you’d hope. Waiting for FDA’s decision will be much easier if you have informed and accurate expectations, and know that you did everything in your power to gain clearance as quickly as possible. A simplified timeline of communication during the 510(k) review is provided below. (Note: Days are in Calendar Days.)
Timeline of Communication During 510(k) Review
Step 1: FDA 510(k) Submission Receipt
The first hurdle is having the FDA acknowledge receipt of your 510(k) submission. FDA will send a formal Acknowledgement Letter or a Hold Letter if you haven’t properly paid the User Fee or submitted in an appropriate format. While technically a complete paper copy is still required according to the regulations, we recommend submitting a paper copy of just the Cover Sheet and the Cover Letter. You will save yourself some time and headache (and some trees) and won’t run the risk of forgetting a section or submitting pages out of order. Once the Acknowledgement Letter is sent to the applicant, FDA starts the Refuse to Accept (RTA) process.
Step 2: Refuse to Accept (RTA)
FDA staff will assess your submission using their Refuse to Accept checklist, which you can find here, to ensure that it contains all of the necessary information to conduct a full review for substantial equivalence. FDA will notify you within 15 calendar days of receipt of the submission whether it has been accepted. This communication will identify the reviewer assigned to your submission and will provide a decision regarding the acceptance/rejection of the submission based on the objective review criteria outlined in the RTA checklist.
Step 3: Substantive Review
Once your submission has been accepted for review, it enters the Substantive Review period, when the FDA review team evaluates the information provided in your submission for demonstration of substantial equivalence. Within 60 calendar days of receipt of the submission, FDA will provide you with a Substantive Interaction. FDA will either let you know that the submission review will continue interactively, signaling that FDA believes the issues in the submission are minor and can be resolved within the remaining 30 days, or FDA will send you a list of deficiencies putting the submission clock on hold with an Additional Information letter.
Step 3(a): Interactive Review
A Substantive Interaction could be a notification that the remainder of the review period can be conducted interactively, with minimal questions and clarifications. The review clock will continue to run, and you should be given your MDUFA decision within the 90 days from when your submission was received.
Step 3(b): Additional Information
Alternatively, if an Additional Information letter is issued, FDA’s 90-day review clock is put on hold, and the applicant then has 180 days to respond to the deficiencies in the letter. In 2018, 63% of 510(k)s received an Additional Information request. It is the large number of submissions that add time from the 180-day applicant review clock which pushes average review times out. Once the applicant submits their response to the Additional Information Letter deficiencies, FDA’s 90-day clock begins again, which would typically have another 30 days left on it.
Step 4: MDUFA Decision
At the end of the review clock, FDA will issue their MDUFA decision (Substantially Equivalent [SE] or Not Substantially Equivalent [NSE]). In 2016, 83% of submissions were determined to be Substantially Equivalent, with an average time to decision of 141 days.
Each year, FDA releases performance goals that they set, and their recently released MDUFA Performance Goals and Procedures for Fiscal Years 2018 through 2020 includes the following goals for 510(k) review times:
Total Time to Decision for 510(k) Submissions Received
FDA has also identified process improvements that they intend to implement in order to reach these goals. Some of these improvements include increased staff training, development of additional guidance documents, and enhanced use of consensus standards, but perhaps the most important is a commitment to increase applicants’ awareness and utilization of the Refuse to Accept process.
According to an independent assessment of FDA’s Device Review Process Management conducted by Booz Allen, submissions that did not pass the Refuse to Accept review were associated with longer review times. Additionally, the most common reasons for rejection were Administrative in nature, easily avoidable mistakes that can be fixed by increasing applicants’ knowledge of the required administrative elements of a 510(k) and their use of the RTA checklist.
As FDA is taking steps internally to reduce the time to decision (SE or NSE), there are steps you as the device manufacturer or developer can take to shorten the review period that can be impactful and ensure swift clearance for your device.
This goes without saying but familiarize yourself with the RTA checklist now (linked above). Refer to it throughout your submission assembly process, and identify any potential missing elements and course correct as soon as possible. You should also complete the RTA checklist yourself and include it with your final submission to ensure that it will be accepted for review. In the RTA checklist, cite the specific page that contains the requirement and help the FDA reviewer find the information.
Utilize the pre-submission process. Pre-submission meetings are free, and while they take some time to schedule (60-75 days from when you submit the request), they can be extremely valuable. They give you the opportunity to have early and open dialogue with FDA about your product and your development, and get feedback on your intended use and predicate device. For example, you can discuss the testing required for your submission, so that you conduct the testing in full to include in the submission, rather than missing something that will end up resulting in an Additional Information deficiency.
Explore alternative pathways that may apply to you. Familiarize yourself with the breakthrough device program, and the Abbreviated 510(k) and Special 510(k) pathways. Notably, FDA has recently proposed expanding the Abbreviated 510(k) program, which would allow applicants to demonstrate safety and effectiveness to predetermined objective criteria. We will be sure to keep you updated with any news regarding this program. Additionally, the Third Party Review program was enacted by FDA to improve efficiency and timeliness in the review process. FDA has accredited third parties that are authorized to conduct the primary review of a 510(k) for certain eligible devices and then forward their review and decision recommendation to FDA. FDA then has 30 days to issue a final determination.
Keep an eye out for news regarding FDA’s Software Precertification Pilot program. This pilot was implemented to inform the development of a future regulatory model for streamlined and efficient regulatory oversight of software-based medical devices. Manufacturers who have demonstrated robust quality and organizational excellence and who are committed to monitoring real-world performance of their products will be able to streamline their medical device submissions. We will certainly also keep you updated of any news regarding this program.
Use software tools to streamline and automate the regulatory submission process. FDA has launched a Quality in 510(k) Review Program using their eSubmitter software template to format and submit 510(k)s for a small set of eligible applicants. However, while this limited pilot runs, other opportunities exist to streamline your assembling and submitting your 510(k). Right Submission’s software products automate, streamline, and promote collaboration for the regulatory submission process, exporting a formatted and hyperlinked eCopy-ready PDF pursuant to FDA’s style and technical standards. Right Submission ensures consistency and completeness, allowing you to assemble your 510(k) in a more timely and compliant way. Every 510(k) built in our software has passed the RTA review on the first try.
At times, the pathway to clearance can seem long and full of roadblocks, but knowledge and preparedness can get you a long way. FDA is doing their part to streamline the review process and to ensure the rapid clearance safe and effective medical devices, and there are important steps industry can do as well. Both parties need to work together to get lifesaving technologies on the market and to patients. And as always, Right Submission is here to help.
About the Author: Elizabeth FitzGerald, the Director of Regulatory Intelligence at Right Submission, is an experienced medical device consultant who has spent her career helping to bring lifesaving technologies to market faster. She has experience with the full life cycle of device development, through clinical operations, data management and analysis, and regulatory affairs.