Learn how to frame clear, specific, and focused questions for your FDA Pre-Submission. Well-crafted questions lead to actionable feedback and streamline your regulatory pathway.
The questions you pose in a Pre-Submission define the entire interaction. High-quality questions yield high-quality feedback. Here are some tips for crafting clear, effective questions for your FDA Pre-Sub:
Each question should tackle a single, specific issue. FDA advises that Pre-Subs include clear, specific questions relevant to the planned submission – for example, questions about non-clinical test protocols, clinical study plans, regulatory pathways, etc. Vague questions like “Do you have any feedback on our device?” are not helpful. Instead, ask something like: “Does the FDA agree that the test method outlined in Appendix A will adequately assess the device’s mechanical strength for its intended use?” Specificity helps FDA give you a targeted answer.
While your overall Pre-Sub package has a background section, it’s useful to tie context to each question. FDA reviewers find it helpful if you indicate which background information relates to which question. You can briefly introduce a question with a one-sentence lead-in if needed. For example: “Given that our device uses a novel coating (see Section X of this package), Question 1: Does FDA agree that performing ASTM cytotoxicity and sensitization tests is sufficient to address biocompatibility for the coating?” This way, FDA can easily connect the dots without wading through unrelated info.
Avoid overly broad or open-ended questions that essentially ask FDA “What should we do?” Remember, FDA will not design your study or identify a predicate for you. For instance, asking “What testing do we need for our device?” is too broad. A better approach is to propose a plan and ask for feedback: “We plan to conduct a 100-patient clinical trial with endpoints A, B, C. Does FDA agree this study design is sufficient, or have any suggestions?” By proposing a solution (be it a predicate choice, test method, or regulatory approach), you give FDA something concrete to respond to. This makes it easier for them to say “yes, that’s acceptable” or “no, here’s what you should change,” rather than expecting them to craft a plan from scratch.
It’s tempting to pack everything into one Pre-Sub, but there is a practical limit. FDA has found it difficult to thoroughly address more than 3–4 substantial topics in a single Pre-Submission. A “substantial topic” could be a focused area like biocompatibility, bench performance, clinical study design, etc. If you include too many big questions, you risk getting superficial feedback due to time constraints. Prioritize your most critical questions – the ones that could make or break your submission or that drive major design/test decisions. It’s fine to include a few additional minor questions (like administrative or labeling queries) if they are quick to answer but keep the core topics limited. If you truly have many unrelated issues to discuss (e.g. a combination of complex software questions and a full clinical protocol review and manufacturing questions), consider splitting into separate Pre-Subs rather than one overwhelming request.
Phrase questions in a neutral, answerable way. Yes/No questions can be effective (e.g., “Does FDA agree…?”), but make sure a simple yes or no is actually useful – often you’ll want a bit of explanation. Ensure each question is numbered or bulleted distinctly so FDA can address them one by one in their written response. Multi-part questions should generally be separated into sub-questions for clarity. It’s also helpful to avoid ambiguous terms; for example, instead of “Is our device substantially equivalent?” (too broad), ask “Do the differences identified in our comparison table raise any new questions of safety or effectiveness in FDA’s view?” This way, FDA can pinpoint any specific concerns.
If you need inspiration, FDA’s guidance document includes an Appendix with example questions on various topics. These can illustrate the level of detail and phrasing FDA expects. While you should tailor questions to your device, following the format of these examples can improve clarity.
In summary, formulate your Pre-Submission questions as if you were asking a trusted advisor – be clear about what you need from them. A well-phrased question might confirm something (“Does FDA concur with our proposed test method?”) or it might seek advice (“Does FDA recommend additional testing to address X risk?”). What you want to avoid is either extreme: too broad (leads to vague answers) or too narrow (not focusing on the key decisions). By providing context and proposing your approach in the question, you invite FDA to fine-tune your plan rather than come up with a plan. Following these principles will help ensure the feedback you receive is actionable and directly relevant to your submission preparation.
