By Caitlin Bancroft, JD, RAC, senior regulatory affairs specialist, Pharmatech Associates
For any medical device submission, the most powerful source of information will always be communication with the FDA. A mechanism is available to request feedback: the Q-Submission1 program is the pathway for a device sponsor to reach out to request a meeting or written responses. Q-Submissions are designed to address specific questions about a product’s regulatory strategy or testing plan, including bench, animal, and clinical testing.
Gaining agreement with the agency before conducting costly and time-consuming tests avoids the delays and costs of rewriting a submission. Many sponsors have moved forward with regulatory strategies assuming the FDA will agree to their plan, only to receive a not substantially equivalent (NSE) determination or a denial of approval. This article outlines the reasons that a Q-Submission is almost always worth it and describes how to optimize the opportunity. We make the case that the time and money for a Q-Submission pales in comparison with what is needed to correct testing and regulatory strategies resulting from unexpected feedback at the time of a marketing authorization submission.
Medical Device Submissions: Request For Feedback And Meetings
Understanding the FDA’s opinion is vital in preparing to file a medical device submission as a means of seeking guidance that pertains to planned Premarket Notification (510(k)) submissions, Premarket Approval (PMA) applications, or Investigational Device Exemptions (IDE) applications, among many others. Through a Q-Submission, a device sponsor may directly pose questions to the FDA concerning your product, testing, or regulatory strategy and receive guidance in response. Some common types of Q-Submissions include Pre-Submissions, Submission Issue Requests, Study Risk Determinations, and Informational Meetings.
The Q-Submission allows you to share information with the FDA and receive input outside of the formal submission process. This is also the point when the project manager (PM) is identified, assigned, and a relationship begins, which is invaluable for sponsors. Through a Q-Submission, you may receive guidance on many topics, including expensive bench and animal testing, clinical trials, and regulatory strategy.
When To Request A Q-Submission
A Q-Submission is valuable during any point in development, but it is most helpful prior to conducting the most cost- and labor-intensive parts of product development — bench, animal, and clinical testing — a Pre-Submission type. For class II devices, this testing goes hand-in-hand with predicate selection, given that testing plans are generally developed based on the testing conducted on the chosen predicate. If you reach out to the agency prior to beginning testing and choosing a predicate, you can gain clarity on what type of expectations exist regarding collecting data for approval/clearance. However, even if a product has already gone through testing, there is value in submitting a Pre-Submission. It gives you the opportunity to present data or conclusions that are difficult to interpret to the FDA prior to full submission review.
Often, the FDA gives a sponsor a hold letter due to a lack of data. Q-Submissions taking place after receiving a hold letter in response to a pending marketing application, Submission Issue Requests (SIR), can be helpful to address specific questions regarding review issues. An SIR is a way to gain feedback on the sponsor’s plans for additional data collection and confirmation that a bridging protocol addresses the agency’s concerns.
An Argument For Time Savings And Risk Tolerance
From a practical perspective, a Q-Submission will almost always save you time and money by ensuring cost- and labor-intensive development activities are undertaken with the FDA’s blessing. Unless a submission is for an identical device that a sponsor already has on the market, there will be questions surrounding what the testing plan should look like. When questions are raised with the FDA, clarity can be gained before the wrong path is taken. Often the planned testing will be too little or incorrect from the agency’s perspective. Learning that your proposed biocompatibility implantation study is too short before initiation saves you from conducting a second one. Gaining agreement on your predicate prior saves time and money and increases the likelihood of a successful submission avoiding the need to re-submit after receiving a hold letter. Lastly, open communication with the agency gives them a preview into your product and what they can expect from your submission. This may lead to a quicker submission review time.
You may be concerned that going through the Q-Submission process is an extra step that slows time to market. It is an understandable concern, but one that is rooted in the presumption that the planned regulatory and testing strategy is completely correct — a level of confidence that is frequently misplaced. Different products always raise different issues and different reviewers may see distinct problems that had not previously been considered. The time needed for a Q-Submission is generally less than the time required to repeat testing or address issues arising during the review.
Occasionally, companies are concerned about a Q-Submission because they don’t want to “tip their hand” to FDA and receive labor/time-intensive feedback that may not have arisen during the submission review process. In practice, this does not happen. Agency reviewers are as adept at spotting potential issues in a submission as the sponsor. The questions not asked during a Q-Submission will most likely come up during submission review. A sponsor is walking on a high wire if they are operating based on the hope the FDA will not notice the concerns they have about their submission.
Ultimately, it is a question of risk tolerance. Companies should compare the cost/time of a Q-Submission with the potential cost/time of proceeding with a strategy that may be unsuccessful with FDA. A Q-Submission is the more cautious approach and will likely result in a faster time to market due to a targeted product development process and a quicker submission review time. However, if the shortest time to market is paramount, a sponsor may decide that the typical 60 to 90 days needed for a Q-Submission is too high a cost.
How to Increase The Value of A Q-Submission Meeting
Once you have decided to submit a Q-Submission, there are several ways to maximize the opportunity:
- Ask about the areas of greatest concern. The FDA recommends that a limited number of questions and subjects be addressed in each Q-Submission to ensure comprehensive answers. By looking at the program in its entirety, you will be able to accurately identify the areas where you need FDA guidance.
- Carefully craft questions to advocate for your position. Questions that begin “please confirm” or “do you agree” propose a prospective answer and put the agency in a place to agree with your proposal. In spite of the “least burdensome”2 provisions, FDA will take a reasonably expansive view of testing and regulatory requirements. Leading them to the answer you want is beneficial.
- Be aware of what the agency will and will not review. You should review what the Q-Submission guidance says about the type of meeting requested to confirm the questions included are appropriate.
- Consider whether to do a meeting or receive written responses only. There are benefits to a meeting: on-the-spot and unfiltered guidance, a chance to respond to questions in real time and understand the FDA’s thought process. However, there can be drawbacks. Not all personalities are suited for a conversation with the FDA. It is essential that people who tend to be defensive or aggressively argumentative not be included. FDA will disagree with some of a sponsor’s proposals. While meeting attendees can and should advocate for the organization’s position, it is important that guidance and denials be received well during the meeting. Written responses allow for FDA to craft their answers intentionally and avoid any unproductive confrontations.
Is A Q-Submission Worth It?
From a practical perspective, a Q-Submission is almost always worth it. The goal of any sponsor is to get to market as quickly and cost-efficiently as possible. Going through the Q-Submission process allows you to gain FDA insight and provides a preview of a coming submission that will lead to quicker review times and fewer post-submission requests for information. By thoughtfully considering topics to discuss and crafting questions carefully, you will find a Q-Submission to be a valuable and powerfully informative endeavor.
- U.S. Food and Drug Administration. Center for Devices and Radiological Health. (2021). Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program. https://www.fda.gov/media/114034/download
- U.S. Food and Drug Administration. Center for Devices and Radiological Health, Center for Biologics Evaluation and Research. (2019). The Least Burdensome Provisions: Concept and Principles. https://www.fda.gov/media/73188/download
About The Author:
Caitlin Bancroft, JD, is a senior regulatory affairs specialist with Pharmatech Associates – a USP company. Her expertise is in regulatory compliance of medical devices, spanning 510(k), PMA, De Novo, Modification, Reclassification, IDE, and the EU Medical Device Regulation. Her work includes the review and application of FDA and EU regulations concerning quality management systems, current good manufacturing practices, clinical evidence/trials, complaint handling, risk management, and marketing authorization requirements.