FDA Pre-Subs: Best Practices, FAQs, and Examples

Innolitics partner David Giese, who has helped bring 35+ AI-enabled diagnostic devices to the US market, published a guide on FDA Pre-Submissions, noting that the FDA currently charges no fee for Pre-Subs but may introduce a $2,000 fee under the proposed MDUFA VI agreement. The guide recommends one device per Q-Sub, suggests using the PreSTAR template, and notes that meetings are typically held 70–75 days after submission.

Hi, I’m David Giese, a Partner at Innolitics. I help companies bring AI-enabled diagnostic devices onto the US market 35+ devices to date . I write in-depth articles https://innolitics.com/people/j-david-giese/ on related topics. I’d love to connect on LinkedIn , where I post pragmatic tips about medical-device strategy, pre-subs, and regulations for my 8k followers. A Pre-Sub is a mechanism for requesting formal written feedback from the FDA, and optionally a one-hour meeting. A Pre-Sub is appropriate when FDA’s feedback on specific questions would help guide product development, performance testing, predicate selection, or other aspects of a 510 k , De Novo, PMA, or IDE submission. Currently, FDA does not charge a fee for Pre-Subs, although preparing a good package takes effort. FDA may start charging a $2,000 fee if the proposed MDUFA VI agreement is accepted. You can do as many as you like. Although it is allowed, FDA recommends against having multiple Pre-Subs for the same device at a time, because feedback from one Pre-Sub often affects others. Therefore, unless the Pre-Subs are for widely different topics e.g., cybersecurity and clinical study design , we generally suggest against holding multiple pre-subs at once. See this section https://innolitics.com/articles/2023-q-sub-guidance/ iv-q-submission-program of the guidance for more details. As a rule, we recommend one device per Q-Sub. A single Pre-Sub can cover multiple functions that are part of one integrated system, but separate products should get separate Pre-Subs. Combining products makes the device story harder for FDA to follow and dilutes the limited number of questions you can ask effectively. Formally, no: FDA's Pre-Sub feedback applies to the device and facts presented in that Q-Sub. In practice, reviewers are reasonably consistent when two products share the same technology, intended use, or testing approach. We still would not rely on another product's feedback for a strategy-critical decision; ask FDA directly if getting it wrong could change your pathway or evidence plan. No. They are always optional, but recommended in many cases. If you have a strong predicate, see “Can we skip the Pre-Sub if we have a strong predicate?” https://innolitics.com/articles/fda-pre-subs/ can-we-skip-the-pre-sub-if-we-have-a-strong-predicate below. Here is a diagram showing how pre-subs relate to a typical pre-market submission: We recommend requesting a presubmission meeting with FDA early in the process e.g., before preparing 510 k submission, executing testing, collecting data but once you have a clear regulatory strategy in place. The typical process looks like this: If no meeting is requested, then steps 4 and 5 are skipped. The meeting date is mutually agreed upon with FDA and is typically 70–75 days after submission. The 70-day written-feedback timeline is a MDUFA performance goal measured across a cohort of submissions, not a binding deadline for every individual Pre-Sub. We often hold them over video calls. There is also an in-person option. Here is a summarized list of content that’s included in a Pre-Sub. Note a lot of this is quoted and slightly modified from the FDA guidance: We suggest using the PreSTAR dynamic PDF to compile a Pre-Sub. You can download the PreSTAR template here https://www.fda.gov/medical-devices/how-study-and-market-your-device/estar-program . Once you download it, you can select the options for a Pre-Sub and then fill in the various sections. Once you have filled in this information, you can see the detailed fields related to the Pre-Sub. It is generally too early to do a Pre-Sub if you don’t have a somewhat settled indications for use and device description. Once these are settled, we suggest doing a Pre-Sub about as early as key regulatory risks have become clear. See “How finished does our device need to be before a Pre-Sub?” https://innolitics.com/articles/fda-pre-subs/ how-finished-does-our-device-need-to-be-before-a-pre-sub and “Can we start our 510 k work before FDA answers our Pre-Sub?” https://innolitics.com/articles/fda-pre-subs/ can-we-start-our-510k-work-before-fda-answers-our-pre-sub below. At Innolitics, we focus on Software as a Medical Device SaMD products. We most typically do Pre-Subs for the following topics: In general, we suggest Pre-Subs to de-risk expensive medical-device development activities. Risk is higher when activities are more expensive, take a long time, or there isn’t much FDA guidance on a topic. The term “Q-Submission” or “Q-Sub” refers to the system used to track a few different types of interactions with FDA. Pre-Sub is a particular type of Q-Sub. Informational meetings are another useful type of Q-Sub in some cases. An Informational Meeting is a request to share information with FDA without the expectation of feedback. This information sharing can be helpful in providing an overview of ongoing device development particularly when there are multiple submissions planned within the next 6-12 months and familiarizing the FDA review team about new device s with significant differences in technology from currently available devices. While FDA staff may ask clarifying questions during an informational meeting, they will generally be listening during the meeting and not prepared to provide any feedback. You can read more about other Q-Sub types here https://innolitics.com/articles/2023-q-sub-guidance/ iii-scope . The key FDA guidance is here: 2025 FDA Guidance—Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program https://innolitics.com/articles/2023-q-sub-guidance/ The following podcast episode with Mike Drues includes a lot of great advice for running successful Pre-Subs: June 2021 - Preparing Your Pre-Submission with the Content FDA Wants to See - Greenlight Guru Podcast https://www.greenlight.guru/blog/preparing-pre-submission-with-content-fda-wants-to-see . If you are putting together a pre-sub for an AI-enabled device, I recommend my partner Yujan’s article: How to Document AI/ML Algorithms in FDA Presubmissions Q-Sub https://innolitics.com/articles/how-to-document-ai-ml-algorithms-in-fda-presubmissions-q-sub/ A Pre-Sub is not the starting point of regulatory strategy. We first combine the clinical, business, engineering, and regulatory context to define the product, determine whether FDA regulates it as a device, identify the pathway, and establish the evidence requirements. Only then can we decide whether a Pre-Sub is worth the time and cost—and which questions should go into it. No, it really depends on the situation. Pre-Subs are a means of controlling regulatory risk. Thus the need for a pre-sub depends on: Consider these two examples: | Regulatory Risk | Likelihood | Severity | Possible Mitigations | |---|---|---|---| | The FDA doesn’t accept your clinical study design on a new type of device. | Moderate; it’s a new type of device without much precedent | High; re-running the study could cost $100,000+ | 1. Do a Pre-Sub | | You’re done with development and didn’t realize you needed to do penetration testing. You think your device may not require it. The risk is the FDA requires that you do cybersecurity penetration testing. | High; FDA almost always requires penetration testing | Low; you may lose some time, but either way you’ll pay the cost of the pen testing | 1. Submit now; start pen testing in parallel; be ready with the results when FDA issues an AINN 2. Submit now; wait to see if FDA requires pen testing; if so, do it at that time it should take less than the 180 days . | In the first example, a Pre-Sub may avoid the need to re-run the study. In the second example, a Pre-Sub would be an unnecessary delay. You do not need a regulatory consultant to do a Pre-Sub, although it is highly recommended. Good regulatory consultants who have experience with your type of device will have a better understanding of how FDA regulates that device type. Without them, it is very easy to waste time and money asking unnecessary questions—questions experienced consultants could answer directly. Thus, another possible mitigation to your regulatory risks is to hire consultants with relevant experience e.g., Innolitics is one of the world experts in SaMD and Medical Device AI . We often take over projects from other regulatory consultants after a pre-sub has gone poorly. It is also worth noting that regulatory consultants can sometimes push to do a pre-sub when it isn’t necessary, since they can bill more for it and also it reduces the risk of them looking bad. Regulatory consultants have experience running pre-submission meetings, and thus, can provide expert guidance on the types of questions to ask, how to ask those questions, and what type of information is needed to support them. Submitting them in parallel can save months, but only when the intended use, device description, and evidence story are stable and identical across both packages. The same FDA review group may see both submissions, and some subject-matter experts may overlap, but you should not assume the exact same reviewers will handle them. We usually sequence them when the Breakthrough decision or FDA's reasoning could change the Pre-Sub strategy; we run them in parallel when timing matters more and neither package depends on the other's answer. See our Breakthrough Device and STeP FAQs https://innolitics.com/articles/fdas-breakthrough-device-and-step-programs-faqs/ for more on the designation programs. They certainly can be. Some common ways they are a waste of time include: A well-chosen Pre-Sub often reduces the total cost to clearance by preventing the wrong study, predicate, or claims strategy. We recommend investing in one when the cost of guessing wrong—an Additional Information request, an NSE decision, or repeating validation—materially exceeds the cost and roughly 2–3 months required for the Pre-Sub. If FDA's answer cannot change what you will do, the Pre-Sub probably will not pay for itself. Yes. If the only regulatory risk is your predicate selection, then you can skip the pre-sub if you have a strong predicate. Our clients often have clinical-evidence or human factors risks and submit a pre-sub related to those topics. You only need a stable device definition including the intended use, intended patient population, intended users, and device description and a clear list of the regulatory questions. Go too early and you waste questions on a moving target; go too late and FDA's feedback can no longer change your design without expensive rework. Yes. We often work on the design and development file DDF while waiting for Pre-Sub. We wait to work on deliverables the FDA feedback can invalidate, especially executing validation or clinical protocols and anything downstream of a contested predicate or indication. FDA aims to provide written feedback within 70 calendar days or at least 5 calendar days before the meeting, which is generally scheduled around days 70–75. This is a performance goal, not a binding deadline, so FDA can miss it. We often keep other work moving in parallel, which can make the net schedule impact close to zero. No. FDA can change its position. This is especially common if the reviewer team changes, if your device changes, or the guidance or political landscape moves. Unfortunately, it is not uncommon for FDA feedback to change especially if there’s a large gap in time between when you submit and your pre-sub. FDA’s feedback is often non-committal if you didn’t provide sufficient background material going into the pre-sub. This is a common mistake for inexperienced regulatory consultants. If their feedback is negative, it can be a big problem, as that feedback goes into your record that future FDA reviewers will consult. This is one of the reasons why you need to be careful how you run your FDA pre-subs; there’s a lot of strategy regarding what you ask or don’t ask. Most of the time, FDA is open minded if you have good evidence to back your position, so don’t treat negative feedback as set inn stone. It’s possible, but strongly not recommended. I don’t have time to write out the details right now, but reach out if you’re curious. Almost never. A 513 g request answers a narrow question: how FDA would classify a device under the FD&C Act. I’ve seen these submissions take very long—even over a year. If you’re not sure if your product is a medical device, reach out to us and we can help you explore your options, whether a pre-sub is appropriate, or if taking some business risk is appropriate. Pre-Submissions offer two options: written feedback only or written feedback followed by a meeting. You must specify whether you want a meeting in your initial Pre-Sub submission. If you request written feedback only, you cannot add a meeting later after reviewing FDA's preliminary written feedback. Conversely, if you originally requested a meeting but find that FDA's written feedback adequately addresses your questions, you can cancel the meeting. This saves time for both you and FDA, and allows you to move forward more quickly with your development plans. To cancel a meeting, contact the lead reviewer of the FDA review team managing your Pre-Sub. It's courteous to notify FDA as soon as possible if you wish to cancel a meeting, as this allows them to reallocate their resources. In our experience at Innolitics, we almost always recommend requesting and holding the Pre-Sub meeting, even if FDA's written feedback seems clear. The meeting provides valuable opportunities to ask clarifying questions, discuss nuances that may not be fully captured in writing, and build a rapport with the FDA review team. While there's no guarantee the same reviewers will handle your future submission, establishing a positive relationship can still be beneficial. You should never have a Pre-Sub end early Agree upon a few extra “informal” questions to ask FDA in the case that the meeting goes quicker than expected. If these questions are somewhat related to the existing questions, we’ve had FDA provide useful answers even if they weren’t include in the original pre-sub. FDA will occasionally stay on the call an extra 5-10 minutes, but don’t count on it. Typically, the call will end on the hour and if you didn’t get to some questions, well, too bad 😢. After the one-hour FDA meeting, you must submit minutes that FDA may review and edit. Here are the key requirements for FDA Pre-Sub meeting minutes: The FDA has 30 days to review and edit the minutes. If there are disagreements about the content, a teleconference can be scheduled to resolve the issues. See here https://innolitics.com/articles/2023-q-sub-guidance/ 3-meeting-information for additional information in the FDA guidance on the topic of minutes. Also see this example https://innolitics.com/articles/2023-q-sub-guidance/ appendix-3--example-of-meeting-minutes . Minutes should be attached as an amendment to the pre-sub. Meeting minutes should be written in complete sentences using a clear paragraph format. The FDA guidance states that minutes should "summarize the discussion" rather than being a transcript. Focus on locking in the key decisions made by the FDA in the minutes. Although FDA can still change their mind if it is written plainly and agreed upon in the minutes, it is unlikely FDA will change without a clear reason. Also keep the minutes succinct. Meeting minutes should include a preamble that provides key information about the meeting: Following the preamble and key decisions at the top, organize the minutes by question, with each section including the original question as submitted and a summary of the discussion and any agreements reached. Additionally, any discussion items that came up during the meeting but were not part of the original pre-sub questions should also be documented in the minutes. The minutes are crucial because they become part of your official file and will be referenced by FDA reviewers during future submissions. When FDA agrees to a specific testing approach and confirms it in the minutes, they are less likely to change their position later though this remains possible . For this reason, be sure to document all decisions made and agreements reached in the meeting minutes. We suggest putting the most important ones in a list at the top to be sure the reviewers will read them. Pre-subs require time and money to prepare, and they add a 60-70 day delay to your roadmap. Therefore, they only make sense when they help de-risk a decision whose cost significantly outweighs the cost of the pre-sub itself. Here's an example to illustrate this: Consider an AI-enabled device where product development is complete and you're ready to submit. You know the FDA may request a subgroup analysis of your model's performance across different ethnic groups. However, you have several academic papers suggesting that ethnicity won't affect your device's input variability. Should you: The answer depends on the time and costs of collecting the data. If data collection and analysis is relatively quick say, 2 months , then option 2 makes more sense. If FDA disagrees with your justification for not including ethnic data, you can collect it within the 180-day hold clock. However, if you're early in product development and the pre-sub won't delay your submission timeline, it's worth doing the pre-sub to de-risk the decision and avoid lengthy holds during review. The FDA’s 2021 De Novo Classification /4c5f66bd3f6341fa861a8cd5062b3e95 Guidance includes some sample questions for pre-subs before a De Novo. They also mention special information that should be included if you’re doing a De Novo. Examples of questions to pose to FDA in a De Novo Pre-Sub include: In a past presubmission meeting, we presented a device with multiple AI algorithms, each targeting different anatomical areas and providing distinct outputs. Our aim was to maximize the meeting's value by seeking FDA feedback on as many algorithms as possible. However, upon receiving the written feedback, we realized this approach had backfired. We had overwhelmed the FDA with information, obscuring the device's overall intended purpose. Consequently, the FDA couldn't address many of our original questions. This misstep forced us to spend a significant portion of the meeting clarifying our device description, workflow, and intended use. Even then, the FDA couldn't offer final recommendations during the call due to their initial lack of understanding about the device. Sponsor Question Does the FDA have any concerns about the proposed marketing claims and the methods for supporting them? Official FDA Response We are not able to answer this question before we fully understand the intended use of your device. Please see the FDA’s response to Question 1, which discusses our current thinking of the functionalities and indications of the device, the choice of predicates, and regulatory strategy currently proposed. In one of our recent presubmissions, FDA shared a "CLIIP Questions for Software Review" document with us. CLIIP stands for “clinical, labeling, indications for use, intended use, and performance testing”. This document is a way for the FDA to share informal recommendations to provide some guidance for all the information for a SaMD that may be required for a review of the device. Below is a copy of the CLIIP questions. | Date | Changes | |---|---| | 2024-04-23 | Initial Version | | 2024-08-22 | Added a couple of examples, including the CLIPP questions. Clarified a few of our earlier points. | | 2024-12-17 | Added another example of a situation when you shouldn’t do a pre-sub. Added another section with questions and answers related to running the meetings. Expanded the answers to some existing questions. | | 2025-11-10 | Added more questions about the strategy of doing a pre-sub, when you’d do one vs not do one, and so on. Add example questions from the De Novo guidance. | | 2026-08-29 | Added timing, scope, post-feedback, Breakthrough, and cost-risk questions based on recurring prospect and client calls. Updated fee and timing details based on proposed MDUFA VI changes. |