Navigating FDA's Q-Submission Process: A Strategic Advantage for Medical Device Developers

In the highly regulated medical device industry, navigating FDA’s submission process can be daunting, especially for start-ups. However, FDA’s Q-Submission (Q-Sub) program offers a valuable opportunity for early and meaningful interactions with the Agency. This post will delve into the Q-Submission process and its benefits.

Now more than ever, Pre-Subs and formal submissions must be clear, focused, and accompanied by unequivocal objectives. With recent layoffs, the Agency does not have time to review meandering or unfocused content. Most recently, we have seen Pre-Sub feedback limited to just two or three key issues — it is critical that Sponsors clearly present the key points they need FDA to opine on and make the interaction count.

Understanding FDA’s Q-Submission Program

The Q-Submission program, as outlined by FDA, provides a structured mechanism for medical device manufacturers (Sponsor) to obtain feedback on various regulatory issues before submitting a formal application. This program encompasses several types of submissions, including Pre-Submissions (Pre-Subs), which are the most common and beneficial for guiding early navigation of novel marketing applications. Q-sub interactions are a critical opportunity for Sponsors to de-risk their development programs.

What are the different types of FDA Q-Submissions?

1. Pre-Submissions (Pre-Subs): These are requests for feedback on specific questions related to product development, clinical study protocols, or regulatory pathways. Pre-Subs are particularly useful for clarifying regulatory requirements and identifying potential issues early in the medical device development process, including clinical study design and performance analysis.
2. Informational Meetings: These meetings allow Sponsors to share information with FDA without expecting feedback. They are useful for introducing FDA to new technologies or providing updates on ongoing projects.
3. Study Risk Determinations: These submissions seek FDA’s determination on whether a planned clinical study is considered significant risk (SR) or non-significant risk (NSR).
4. Submission Issue Meetings: These meetings address specific issues identified during the review of a pending submission.

The Pre-Submission Process

The Pre-Submission process is a cornerstone of the Q-Submission program. It allows Sponsors to engage with the FDA early and often, fostering a collaborative relationship that can significantly enhance the likelihood of a successful future premarket application. Steps in the Pre-Submission process are summarized below.

1. Planning: Timing of Pre-Submissions is a crucial factor that should not be underestimated. Although FDA has set timelines for both responding to Pre-Subs and reviewing formal regulatory submissions, the total time from initial Pre-Sub to final approval can be lengthy, particularly if additional information or revisions are required. Device developers must plan accordingly and allocate sufficient time for the entire process in alignment with their product development timelines.
2. Preparation: Before submitting a Pre-Sub, Sponsors must thoroughly prepare by identifying specific questions or issues they need feedback on. This preparation includes gathering relevant data and documentation to support their questions, such as regulatory strategy, bench testing plans, draft clinical study protocols, and proposed equivalence rationales. Questions should be carefully drafted with precision and detail to receive actionable guidance.  
3. Submission: The Pre-Sub is submitted through FDA’s electronic submission gateway. It should include a cover letter, a detailed description of the device, preclinical testing plans and/or proposed V&V activities, specific questions for the FDA, and any supporting documentation. The submission package should be comprehensive and well-organized.
4. FDA Review: Upon receipt, FDA will assign a lead reviewer who coordinates the review process. The FDA aims to provide written feedback within 70 days of receiving the Pre-Sub.
5. FDA Meeting: If requested, a meeting (in-person, teleconference, or video conference) is scheduled to discuss the Agency’s feedback, which is typically provided one week prior to the scheduled meeting date. This meeting provides an opportunity for real-time interaction and clarification of any outstanding issues. Any slides the Sponsor plans to present during this meeting should be provided to the FDA no less than two business days prior to the meeting and should be a tightly-presented slide deck. It is important to note that FDA will not be able to comment on any new information provided during this meeting that was not part of the pre-submission package.
6. Follow-up: Minutes are due to FDA within 15 days of the meeting and must be submitted through the same electronic submission process as the Pre-Sub. If FDA has any edits or corrections, these will be communicated via email. It is important for Sponsors to give serious consideration to all FDA feedback, ensuring it is incorporated into testing plans and future marketing applications accordingly. Failure to do so can lead to non-compliance with regulatory requirements, ultimately resulting in approval delays or denials. Issues and feedback that remain outstanding following the meeting may be resolved through additional Pre-Subs.

What are the benefits of Pre-Submission interactions with FDA?

The Pre-Submission process offers several strategic advantages to medical device developers:

1. Early Feedback: Engaging with FDA early in the development process allows Sponsors to identify and address potential regulatory hurdles and study design challenges before they become critical issues. This proactive approach can save time and resources by preventing costly delays later in the process.
2. Regulatory Clarity: The Pre-Submission process provides clarity on regulatory requirements, helping Sponsors understand what data and documentation will be needed for their formal submission. This clarity can streamline the development process and improve the quality of the final submission.
3. Risk Mitigation: By obtaining feedback on clinical study protocols and other critical aspects of product development, Sponsors can mitigate risks and cost overruns associated with regulatory non-compliance. This risk mitigation is particularly important for start-ups with limited resources.
4. Relationship Building: Regular interactions with FDA through the Pre-Submission process help build a collaborative relationship with the Agency. This relationship can be invaluable for navigating the regulatory landscape and addressing any issues that arise during the review process.
5. Strategic Planning: The insights gained from Pre-Submission interactions can inform strategic planning and decision-making. Start-ups can use this information to prioritize development activities, allocate resources more effectively, and align their regulatory strategy with business objectives.

What is a Successful Pre-Submission Interaction?

Let’s consider a hypothetical start-up developing a novel medical device for remote patient monitoring. By engaging in FDA’s Pre-Submission process, the company can seek feedback on their regulatory strategy and least burdensome pathway to market. The company can also receive valuable Agency insights on their clinical study design, ensuring it meets FDA’s requirements for testing safety and efficacy of the device. FDA’s feedback might highlight the need for proving up substantial equivalence claims, or a modification in strategy which allows moving from a PMA to a less burdensome de novo pathway approach. From a clinical perspective, feedback often includes suggested modifications to the study protocol which will better ensure robust, relevant and valid data collection points allowing the Sponsor to make necessary adjustments before initiating the study. This early interaction not only enhances the likelihood of a successful submission, it also builds a foundation for ongoing collaboration with FDA.

Submission Considerations in the Current and Evolving FDA Landscape: Ensure Your Submissions Are Set Up for Success

Pre-sub conversations are now shorter, more selective, and less exploratory—which will especially impact newer and more complex technologies. In order to be successful, medical device Sponsors will need to adapt the ways in which they engage with FDA, including:

• Streamlined, Strategic Submissions: Now more than ever, Pre-Subs and formal submissions must be clear, focused, and accompanied by unequivocal objectives. The Agency doesn’t have time to review long-winded or unfocused content. We’ve seen Pre-Sub feedback limited to just two or three key issues—so it is critical that Sponsors make them count.
• Stick to the Guidance: In the absence of bandwidth for personalized advice, reviewers will increasingly stick closely to previously published guidance documents. Aligning your approach to existing frameworks will increase your chances of successful navigation.
• Prioritize Experience: Sponsors should seek advice from individuals who have worked at or directly with the FDA. These professionals can help shape submissions that anticipate agency expectations and streamline the path to approval.
• Plan for Parallel Regulatory Strategy: Given the uncertainties at FDA, Sponsors might consider dual pathways—submitting in other markets (e.g., EMA, PMDA) to avoid putting all their eggs in one regulatory basket.

With reduced review bandwidth, FDA simply cannot spend time unraveling disorganized or unfocused applications. In the current environment, our subject matter experts have found the following core tenets help ensure submissions are best positioned for successful meeting outcomes:

• Tightly structured and logically organized
• Clear in intent, with targeted, well-framed questions and defined objectives
• Aligned with applicable guidance documents, unless a strong rationale is provided
• Strategically scoped, especially in Pre-Submissions where the Agency may only address two or three key topics due to time constraints

ProPharma: Your Medical Device Development Partner

FDA’s Q-Submission program and, particularly, the Pre-Submission process, is a powerful tool for medical device developers, especially start-ups. By leveraging this program, Sponsors can gain valuable insights, mitigate risks, and build a collaborative relationship with FDA. These benefits can significantly enhance the likelihood of regulatory success and accelerate the path to market in the US for innovative medical devices.

Our team of experts is comprised of experienced and regulatory consultants; because of this, we are uniquely positioned to help medical device Sponsors identify and correct gaps before submission, prioritize the most critical elements, and anticipate what FDA is likely to question – or flag – as deficient. For start-ups navigating the complex regulatory landscape, the Q-Submission process is not just a procedural step but a strategic advantage. Embracing this process can pave the way for successful FDA interactions and ultimately, the successful commercialization of new medical technologies.

For more than 40 years, we have been helping clients conduct successful meetings with FDA, effectively reaching the next regulatory milestone for their medical device. Our team of regulatory consultants is comprised of more ex-FDA employees than anyone else out there. Coupled with our extensive team of industry experts and executives with decades of experience, we have exactly the people you need to help get your medical device to the next regulatory milestone.