Written by Michelle Rubin-Onur, PhD, Director of Regulatory at Enzyme
FDA’s approach to regulating medical devices can sometimes be confusing and overwhelming. Thankfully, there is a voluntary program, The Q-Submission Program, that device manufacturers (also called sponsors) can use to obtain FDA feedback—either during a meeting or in writing—during device development, submission review, or even prior to clinical study commencement.
On June 2, 2023, FDA published an updated guidance document as part of the Medical Device User Fee Amendments of 2022 to refine the timing associated with scheduling meetings and obtaining feedback. This provides us with an excellent opportunity to dig into the program, what FDA has added/updated, and really get a sense of when a sponsor can and should use this program.
Program History
The Q-Submission Program is available to any sponsor to obtain feedback regarding a potential or planned medical device submission, including:
- Investigational device exemptions (IDEs)
- Premarket approval (PMA) applications
- Humanitarian device exemption (HDE) applications
- De Novo applications
- Premarket notification (510(k)) applications
- Plus many more
There is even a mechanism to discuss policy or request feedback from FDA if you are another government agency, non-profit, trade organization, and/or professional society. The program itself was established in 1995 as a mechanism to initially obtain feedback prior to an IDE submission. Over time, the program evolved to include feedback on a variety of submissions, as well as a study risk determination (e.g., if a study is significant or nonsignificant risk). Each submission should follow the format recommended by FDA in the guidance document to facilitate a fruitful review from FDA.
As the program expanded, the types of Q-Submissions expanded. As outlined in the recent guidance, there are nine (9) types of submissions:
- Pre-Submissions (Pre-Subs)
- Submission Issue Requests (SIRs)
- Breakthrough Device Designation requests
- Informational Meetings
- Other Q-Submission types, including:
- PMA Day 100 Meetings
- Agreement and Determination Meetings
- Study Risk Determinations
- Submissions associated with the Safety Technologies Program (STeP)
- Accessory Classification Requests
Each submission has its own corresponding feedback mechanisms and timelines (see Table 1). For this blog, we will focus on the submissions we see the most at Enzyme.
Table 1. Q-Submission types, corresponding feedback mechanisms, and timelines. Table taken from FDA guidance. Please note, all days are calendar days.
| Q-Sub Type | Method of Feedback | Timeframe for Sending Feedback or Scheduling Meeting (from receipt of submission) |
| Pre-Submission | Meeting with written feedback provided in advance | Written feedback:
70 days or 5 days prior to scheduled meeting, whichever is sooner Meeting: Date based on mutual agreement (typically day 70-75) |
| Written Feedback Only | 70 days | |
| Submission Issue Request (SIR) | Meeting or Written Feedback | If SIR is received within 60 days of FDA’s marketing submission letter:
21 days as resources permit |
| If SIR is received more than 60 days after FDA’s marketing submission letter:
70 days as resources permit |
||
| Study Risk Determination | Formal Letter | 90 days |
| Informational Meeting* | Meeting | 90 days |
*When used to track requests that do not meet the definition of a Q-Sub type, Informational Meeting timeframe and feedback mechanism can vary. Typically, Informational Meetings do not include FDA feedback.
Pre-Submissions
Purpose: The most commonly used Q-Submission is a Pre-Submission (Pre-Sub). A Pre-Sub is a formal written request from sponsors for feedback from FDA.
When to submit: When a sponsor would like to discuss any topics associated with a future premarket submission or when FDA’s feedback could help guide product development and/or future premarket submission preparation. The revised guidance provides some example questions that a sponsor can ask within different review topics, such as regulatory strategy/approach, biocompatibility, bench testing, and cybersecurity. Please note, requests for review of study results are not appropriate for Pre-Subs.
Method for feedback: This can include written feedback as well as an in-person/teleconference meeting to discuss any follow-up questions or just written feedback alone. The timeline for receiving the feedback will depend on the method of feedback requested; 70 days or 5 days prior to the scheduled meeting or 70 days for written feedback alone. At Enzyme, we recommend having an in-person or teleconference meeting along with getting the written feedback, as the meeting provides a unique chance for sponsors to chat with FDA, ask any clarification questions, and meet the FDA review team that may review any future premarket submissions.
Revised guidance updates: The first change is an updated timeline for Pre-Subs. The new timeline is for the meeting to take place 70-75 days after receipt of the submission instead of 60-75 days. The second change is the addition of a reference to Predetermined Change Control Plans (PCCPs). FDA recommends that a sponsor obtain feedback regarding any future PCCPs prior to including any plans in a future premarket submission. For more information about PCCPs, please refer to our previous blog post.
Submission Issue Request (SIR)
Purpose: A SIR is a request for feedback to discuss a proposed approach to address issues or questions that are conveyed in a hold letter during submission review.
When to submit: When a sponsor has specific questions regarding issues that were included in a hold letter (e.g., additional information hold letter for 510(k)s, De Novo requests, IND clinical hold letter, IDE letter, Major Deficiencies, Not Approvable, Approvable with Deficiencies, Approvable Pending GMP, Approval with PAS conditions for PMAs and HDEs, and complete response letter for biologics license applications).
Method for feedback: Similar to Pre-Subs, sponsors can request written feedback only or written feedback and a teleconference/in-person meeting. The timeline for a SIR is different from a Pre-Sub, as it is tied to the review of premarket submissions. As highlighted in Table 1, it is extremely beneficial to submit a SIR within 60 days of receiving the hold letter rather than after, as it results in a faster response from FDA (21 days vs 70 days).
Revised guidance updates: None.
Informational Meetings
Purpose: Informational Meetings are a bit different from other Q-Submissions. Typically, the goal is to have an in-person or teleconference meeting where a sponsor shares information with FDA without an expectation of feedback and active interaction from FDA. Interestingly, when other government agencies, non-profits, trade organizations, and professional societies request FDA feedback on specific questions or cross-cutting policy matters, it is also classified as an Informational Meeting. So, you don’t need to be a device manufacturer to chat with FDA!
When to submit: Informational Meetings can be particularly useful if a sponsor would like to provide FDA with an update on ongoing device development or informing FDA of any device changes that a sponsor has made.
Method for feedback: There is no written feedback provided. The meeting is conducted either in-person or via teleconference within 90 days of receiving the submission.
Revised guidance updates: None
Breakthrough Device Designation Requests
Purpose: A Breakthrough Device Designation request (BDR) is a mechanism to request inclusion in the Breakthrough Devices Program according to the criteria listed in the FDA guidance.
When to submit: BDRs can be submitted any time before a sponsor submits their premarket submission (e.g., 510(k), De Novo, or PMA). One benefit of being granted Breakthrough status is sprint discussions, where a sponsor can receive feedback from FDA in a shorter timeframe than a Pre-Sub (45 days vs 70-75 days) as well as binding clinical protocol agreement. We recommend submitting a BDR early in device development to be able to take advantage of this feature of the program.
Method for feedback: During BDR review, FDA will request any additional information via a formal letter. A formal decision is conveyed to the sponsor through a written letter.
Revised guidance updates: None.
Other types of Q-Submissions
As mentioned above, there are multiple other types of Q-Submissions. If you’d like to learn more about these submissions, don’t hesitate to reach out to us or refer to the applicable guidance documents listed below.
Overall, there are many mechanisms through which a sponsor can interact with FDA, including obtaining feedback regarding device design and development (Pre-Subs), during premarket review (SIRs and PMA Day 100 Meetings), inclusion into different programs (Breakthrough Device Designation requests and STeP Entrance requests), and even prior to clinical study design (Study Risk Determinations and Pre-Subs). The exact submission type is dependent on where a sponsor is in the total product lifecycle and the goal of the submission. The regulatory team at Enzyme has extensive experience with all types of Q-Submissions and is happy to help with any of the Q-Submissions listed above. The Q-Submission Program is a wonderful mechanism to talk to FDA early and often.
Applicable guidance documents:
| Submission | FDA Guidance Document |
| Breakthrough Device Designation requests | Breakthrough Devices Program |
| PMA Day 100 Meetings | Guidance on PMA Interactive Procedures for Day-100 Meetings and Subsequent Deficiencies for Use by CDRH and Industry |
| Agreement and Determination Meetings | Early Collaboration Meetings Under the FDA Modernization Act (FDAMA) |
| Study Risk Determination | Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors |
| Submissions associated with STeP | Safer Technologies Program for Medical Devices |
| Accessory Classification | Medical Device Accessories Describing Accessories and Classification Pathways |
