Overview
Asking the right questions during pre-submission or Q-submission is essential for manufacturers who want to get effective feedback from the U.S. Food and Drug Administration (FDA). Failure to ask the right questions will set companies up for at least two more rounds of back-and-forth, since they won’t even know what they don’t know yet. Thoroughly reviewing the FDA’s documentation of their Q-submission program is essential, as is anticipating the kinds of issues that a specific product will face in getting through the regulatory process. Failure to prepare in this way is going to lead to a much longer and more costly review process.
When used correctly, the Q-submission process allows companies to figure out exactly what type of information they need to submit to the FDA for final approval, as well as any changes that may need to be made to the final product design. This in turn can speed up the whole product development process, allowing companies to get products to market more quickly. This all comes down to asking the right questions.
The FDA’s pre-submission program is especially useful with, for example, medical devices on in-vitro diagnostics. As long as you ask the right questions, the FDA will give you the feedback you need to speed up the approval process.
The FDA offers feedback on proposed bench, pre-clinical, and clinical programs, and this feedback is key to choosing the best regulatory strategy for each product. FDA feedback can also include useful predicate devices to consider, allowing manufacturers to choose the best comparable product to their own.
Common Mistakes to Avoid
It’s important for companies to take the Pre-Sub program seriously. This isn’t just a nice way to get some information in advance, or a trial run. Mistakes in the pre-sub process, most often because of poorly thought-out questions, will lead to lengthy delays and even to rejection of products altogether. It’s important to remember that direct contact with the FDA’s regulators is especially valuable; it can take them a long time to get back around to your product if you have follow-up questions to ask or need to reformulate some questions.
Manufacturers that submit incomplete or incorrect descriptions of their products, vague details about how products function, or data that fails to demonstrate the key features of their products are going to have a hard time getting effective feedback from the FDA.
Sample Pre-Submission Questionnaire
When submitting your device to the FDA, one of the first and most important steps is to provide detailed information about your device, including its history, available data on its use, and any concerns you’re aware of or anticipating. Companies also need to review past development programs and use them as a model for developing their own regulatory strategy. Consider the following examples of bad questions–and better versions of them.
Poorly-formatted question: Are the proposed biocompatibility studies sufficient to support the clinical trials?
Improved question: It is clearly stated that the biocompatibility testing for the device will follow the recommended protocol that is used for devices with limited blood contact. The design team will use industry-standard materials for the device. The team will follow the standard manufacturing process. Therefore, there is no need for carcinogenicity testing. I would appreciate hearing the FDA’s perspective on this issue.
Explanation: The initial question clearly reflects what the design team needs to know, but it doesn’t offer any context or explanation to guide the FDA’s understanding. The improved question clearly references what kind of testing protocol the device will follow, and offers a line of reasoning for why it’s sufficient. The phrasing of the question also suggests confidence. All of this will make it easier for the FDA to correctly answer the question.
Poorly-formatted question: Would the FDA consider this device suitable for the De Novo pathway?
Improved question: We investigated the FDA database extensively but found no current predicates for our device. Nonetheless, our product is made of low-risk ordinary materials like water and salts. As a result, it qualifies for a De Novo request. Our product has been proven to be biocompatible. Furthermore, the earliest Good Laboratory Practices (GLP) reports have demonstrated its safety. Again, scientific trials involving over 2,000 patients have proved that our technology is safe and effective. Given the supporting evidence, we’d like to know if the FDA agrees that a De Novo submission is the best regulatory route.
Explanation: Again, the improved question provides abundant context and persuasively makes an argument for the De Novo pathway. It’s not simply asking the FDA for an answer; it’s making an argument.
Poorly-formatted question: Can this device be used for the De Novo pathway as per FDA guidelines?
Improved question: A primary predicate device shows how the Alpha Graft is substantially equivalent to the predicate. Alpha Graft was chosen as the primary predicate based on its indication for use and technology (absorption over time). We have also proven that this device is the same as other 510(k)-approved devices that use the same technology or have the same usage. The Alpha Graft is compared and contrasted with already cleared graft material in Section 3 of the Pre-Submission form. We think that the material is an appropriate predicate. Are there any other suggestions for a predicate device that the FDA may have?
Explanation: The format of this question includes clear reference to a proposed predicate device. Choosing the correct predicate device is one of the most important steps in getting 510(k) approval, so walking the FDA through your thinking on this particular question is always a good idea. Note that the initial question doesn’t even mention a predicate device. An FDA regulator would have a hard time determining the correct context for answering this question.
Poorly-formatted question: Does the FDA agree with the proposed Modular Pre-Market Approval (PMA) strategy?
Improved question: Section 5 of the Pre-Submission packet states that we plan to submit N (specify the number) of PMA modules. The first module, due in January 2024, will contain pre-clinical testing results, including biocompatibility, sterilization, and bench testing.The second module will include manufacturing information.Section 6 of the Pre-Submission packet states that the third module will contain literature, U.S. data, and OUS data.We will use literature to support the device’s application to individuals over 85 years old. The U.S. and OUS data were collected using the same protocols and criteria as the predicate device. The data will be presented per the IDE Number. We will also provide sales and complaint data, as the device has been commercially available in Canada since 2017. Do you agree with this approach for module three, FDA?
Explanation: This question serves to guide FDA regulators through the documentation being submitted, and clearly demonstrates that the manufacturer has made good progress towards submitting everything they need for full approval. Again, this helps the regulators understand the question more clearly, and also demonstrates that this is a serious, well-researched submission.
Final Thoughts
When manufacturers submit clear, well-thought-out questions that guide FDA regulators though their thinking, they can get clear, accurate, actionable feedback in return. Rushing through the Pre-Q process when important planning and research have yet to be completed will ultimately waste the time of manufacturers and the FDA.
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