How long does an FDA 510(k) submission for SaMD and AI actually take?
Many Software as a Medical Device and AI developers are looking to the US for a cheaper and speedier regulatory approval via an FDA 510(k) pre-market clearance. Advertised as a 90 day process, we analysed the data to find out how long it really takes for manufacturers to receive their clearance.
What is a 510(k)?
The American Food and Drug Administration (FDA) is the government body responsible for ensuring that medical devices are safe and effective prior to their use in healthcare settings. There are currently three main routes by which devices can be āapprovedā or āclearedā by the FDA - 510(k), De Novo and PMA - with the 510(k) Pre-Market Notification Program being the most popular route by far, since it allows manufacturers to apply for a clearance based on an argument of substantial equivalence to on-market approved/cleared devices or standards.
There are three types of 510(k). Products using the Traditional 510(k) route must demonstrate substantial equivalence (SE) to another predicate device with the same intended use and product code. If a predicate is not available and the device has FDA standards available, compliance to FDA guidance documents, demonstration of compliance with special controls for the device type, or voluntary consensus standards are required. This is known as an Abbreviated 510(k). Alternatively, if the submission relates simply to an update to a cleared device, manufacturers can submit a Special 510(k).
Once a device receives a 510(k) clearance it may be placed on the US market, and can itself be used as a predicate for others to apply for a 510(k) via the substantially equivalent route. This process has its benefits and disadvantages, and can lead to complex family trees of devices which increasingly deviate from the original predicate, as we have discussed in a previous article.
What is the process?
Letās focus on the most commonly used route - the Traditional 510(k) (demonstration of substantial equivalence to a predicate device). The FDA state that their target for a decision is 90 days, with a maximum total elapsed time of 270 days. The process can be broken down as follows:
1 - Submission
Once you have created all the relevant documentation (which takes a significant amount of time in itself), you first submit your application and pay a fee. The FDA from 1st Oct 2023 is mandating manufacturers to submit digitally via their eSTAR platform (rather than sending in piles of paper) as it is more interactive and, we find, better laid out, making a submission easier to understand. You can find guidance here.
Once submitted, the FDA will then send you an acknowledgement of receipt within 7 days, and assign a 510(k) number (āKā number) to your application. This is a number beginning with the letter "K" followed by 6 digits. The first two digits designate the calendar year the submission was received; the last four digits represent the submission number for the year, starting with 0001 and increasing with each new submission. So, the first submission for 2024 will have the K number of 240001, and so on.
Once the FDA have received your submission, the FDA will officially start the clock on your decision timeline. At the time of writing the FDA states that a traditional 510(k) decision should be provided within 90 days.
2 - Acceptance Review
Your application will then go through processing internally at the FDA. Firstly, they will assign it to the relevant department based on the device type and clinical indication you have given in your application. Once the relevant division receives the application, they assign a lead reviewer.
The second step is an acceptance review, where the lead reviewer checks the documentation in the application to ensure it meets the minimum criteria for acceptance for a substantive 510(k) review. You should receive a letter from the lead reviewer within 15 days of submission letting you know if it has been accepted for review. If you fail at this point, and your application is deemed unacceptable, it will be put on hold and you will have 180 days to address any deficiencies.
3 - Substantive Review
Now comes the proper review. The lead reviewer, and their team of domain experts if applicable, will read everything you have submitted. In our experience, the FDA and their divisions of reviewers are getting increasingly good at picking holes in clinical evidence reports, so this is the stage where they will pick apart your data and arguments!
The FDA, within 60 days of the acknowledgement date, will then interact with you (known as the āSubstantive Interactionā) in one of two ways:
Interactive Review - when they feel that any comments and questions can be answered within the remaining time via email or telephone/video calls. This means your review should likely not incur any further delays or costs.
Additional Information Request - known as an AI request (not to be confused with Artificial Intelligence!). This is used when the reviewers have identified significant deficiencies requiring further information. Essentially, they cannot make a decision on whether the device is in fact substantially equivalent or not based on your application. Your application is then put on hold, and you have 180 days to respond, or you drop out of the process. Once you respond, the countdown clock starts ticking down to 90 days again from where it left off.
Occasionally the FDA will issue an exemption notice or a Not-A-Device decision at this point, but this is rare since most manufacturers are correct in their assumption that a 510(k) was required. You can always check this via the 513(g) and/or Q-Sub pre-submission processes, where the FDA will let you know your device risk classification and the proper submission route in advance of any submission.
4 - Decision Letter
By 90 days (allowing for any holding periods at acceptance review or for an AI request), you should receive a final 510(k) decision letter. This can have two possible outcomes:
1. Substantially Equivalent (SE) - the FDA are satisfied that your device is substantially equivalent to a predicate device, and you are given market clearance. Woo!
2. Not Substantially Equivalent (NSE) - the FDA are not satisfied that your device is substantially equivalent to a predicate device, and you donāt receive market clearance. Boo!
If the FDA take longer than the 90 days, then you will receive a letter 10 days after the missed deadline called a āMissed MDUFA Communicationā. This is written feedback to the submitter to be discussed in a meeting or teleconference, including the major outstanding review topic areas or other reasons that are preventing the FDA from reaching a final decision, with an estimated date of completion.
Soā¦ 90 days?
Not quiteā¦would that it were so simple.
The 90 day timeline is the total calendar days that the FDA takes in reviewing your SaMD or AIaMD device application, NOT including any days while on hold waiting for you to respond. You will note above that you can be put on hold up to 180 days at various points in the process, mainly due to the FDA having further queries that you will need to put in work in order to satisfy. In fact, having a hold period is extremely common. So common that the FDA has a set limit on how long the total time to decision should take - and thatās 270 days - three times as long!
Total time to decision
To highlight how often the ā90 dayā timeline is not achieved in practice due to extra holding periods, we analysed publicly available data from the FDA 510(k) database for the most recent submissions for the two SaMD product codes we deal with the most.
We can see that the vast majority of 510(k) decisions are not made within 90 days. In fact, thatās the exception, not the rule. Only two SaMD products actually achieved that, and only for one product code. Most applications are bunched between 140-200 total days before a final SE decision is made.
Itās important to point out that there is no publicly available information on those products that never made it to a substantially equivalent decision - the NSEās - where either there is no predicate, or the intended use is too different, or performance data showed poorer performance than the predicate device. The FDA does have some info on the small percentage of applications that reached this decision, but the total time is unknown. We always recommend doing a formal pre-submission to gain clarity, and so an NSE situation can be completely avoided.
QFM product code
The QFM product code is assigned to Radiological Computer-assisted Prioritization Software For Lesions - meaning devices that use software, including machine learning and artificial intelligence, to triage and prioritise images in a radiologistās workflow based on high sensitivity and specificity >95% AUC. This is different from the QAS code which only does the triage, not the prioritisation. It is important to note that QAS and QFM products do not direct a radiologistās attention to a specific part of the image.
For QFM coded products the median time to decision was 144 days, and the average was 154 days. Thatās roughly 2 months over the 90 day target, making the whole process from submission to final decision around 5 months. The fastest was Annalise, who managed it in 70 days with a pneumothorax triage tool, which has plenty of predicates and a clear evidence threshold to achieve. The slowest was MedCognetics at 262 days for their mammography triage solution.
QIH product code
The QIH product code is assigned to AI software products that perform image processing for "disease detection, diagnosis or patient managementā by a clinician for all pathologies not including cancer. It is different from the LLZ code which does not cover AI products, and from other codes that do cover cancer.
For QIH coded products the median time to decision was 196 days, and the average was 201 days. Thatās roughly 3 months over the 90 day target, making the whole process from submission to final decision around 6.5 months. The fastest was Andi, who managed it in 116 days for their DW-MRI processing tool. The slowest was BrainLab at 287 days for their BOLD MRI Mapping tool.
Conclusion
So there we have it - it takes on average between 154 (for QFM) to 201 (for QIH) total days to receive a 510(k) decision for SaMD products, if you are deemed substantially equivalent to a predicate device by the FDA. This is due to several points in the process where the FDA can ask for further information, effectively pausing your 90 day countdown while you gather and process more performance data.
Can you do it in 90 days? Yes, of course - but youād need to have everything prepared in advance, with all your documentation up to scratch, and performance data clearly demonstrating equivalence to your chosen predicate. This is more easily done for predicate devices with well established performance thresholds, support from experienced consultancies like Hardian, and for manufacturers who have a solid track record of successful 510(k) submissions.
AI SaMD manufacturers should note these extended practical timelines in their regulatory strategy and planning of internal timelines - allowing at least 200 days, and not 90, for any 510(k) submissions they plan on making. This can be especially crucial if investment milestones or commercial deals are being tied to regulatory proof points - something that we see quite often, but advise against. And remember - if you do a pre-submission first (which we recommend, especially if itās your first time) thatās an additional 60-75 days.
Hardian Health is a clinical digital consultancy focused on leveraging technology into healthcare markets through clinical evidence, market strategy, scientific validation, regulation, health economics and intellectual property.
