Updated: Sep 6
By Beth Loring & Hannah Cutright
On June 2, 2023, the FDA’s Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) released a new guidance document titled “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.” The Q-Submission (Q-Sub) Program provides medical device manufacturers the opportunity to engage in discussions with FDA review teams during the product development process.
This guidance came from CDRH and CBER, but not from CDER. This is surprising because we are used to seeing guidance documents come either from CDRH or CDER/CBER combined. Regardless, there was a great deal of important and interesting information published. Check out below for some of our take-aways and a submission details.
History of the Q-Sub Program
When it was established in 1995, the Pre-Submission Program was intended for Investigational Device Exemptions (IDEs) only, but it was modified in 2012 to include all types of premarket submissions.
In 2014, the Pre-Submission Program was renamed the Q-Submission Program, establishing a method for the FDA to manage all types of interactions with medical device manufacturers.
It's called the "Q-Sub" Program because submissions to CDRH are assigned a number starting with “Q” followed by two digits representing the year, and four digits representing the order in which the request was received during that year.
Similarly, submissions to CBER are assigned a “BQ” number.
Types of Q-Sub Requests
There are four types of Q-Subs:
Submission Issue Requests (SIRs)
Study Risk Determinations
Using the Q-Sub Program
Generally speaking, the Q-Sub Program provides methods for medical device manufacturers to interact with the FDA.
Other uses of the Q-Sub Program include:
Requests for FDA feedback on specific questions or cross-cutting policy matters.
Requests for recognition of publicly accessible genetic variant databases.
Requests for FDA feedback on design elements of a clinical study that do not fall within the scope of a Pre-Submission.
Combination product agreement meetings.
Requests for FDA feedback related to compliance actions.
Examples of interactions outside the scope of the Q-Sub program include:
Requests for feedback regarding development of a Medical Device Development Tool.
Administrative questions, or questions about the submission process.
Interactions with FDA staff discussing general FDA policy, procedures, or simple review clarification questions.
Interactive review of issues identified while an IDE, IND, or marketing submission is under active FDA review.
Requests for appeal meetings made to CDRH.
Requests for Designation or Pre-RFDs, when the classification of a medical product as a drug, device, biological product, or combination product, or the product’s Center assignment (or both), is unclear or in dispute.
Requests for clarification on device-specific guidance documents or voluntary consensus standards that are not related to a specific device in development.
Requests for Emergency Use Authorizations related submissions.
More about Pre-Subs
Pre-Subs are the original and most common type of Q-Sub. The other three are Submission Issue Requests (SIRs), Study Risk Determinations, and Informational Meetings. (The FDA does not usually provide feedback during Informational Meetings, however.)
A Pre-Sub is appropriate when FDA’s feedback on specific questions would help guide product development and/or submission preparation, but is not intended to be a pre-review of an intended submission or a pre-review of data to be provided in a submission.
Manufacturers can request a Pre-Sub meeting in the form of a face-to-face meeting or a video- or teleconference with the FDA, or they can request feedback via email. (Loring Human Factors has participated in all three types of interactions.) Although going to Silver Spring, MD to meet in person is exciting, the guidance document says that it’s most efficient to schedule a virtual meeting.
The guidance recommends that you craft your Pre-Sub in the form of questions to the agency. Often this means stating your intended course of action, then asking, “Does the Agency agree with this approach?” The manufacturer is responsible for drafting meeting minutes for all Q-Sub meetings and submitting them to the FDA as an amendment to the Q-Sub within 15 days of the meeting.
More detailed requirements of what your pre-sub contents should contain can be found in the summary section below this one.
What to Expect
The guidance describes the various types of Q-Submissions with helpful links to their specific FDA guidance documents. The Agency also says that as they work to create additional mechanisms to streamline the device development and review process, they may add additional Q-Subtypes in the future, so stay tuned for updates!
When the FDA raises issues during the Pre-Sub process, manufacturers aren’t obligated to address or resolve all the issues. But if they don’t, then they should explain why they didn’t in future submissions.
Conversely, even if manufacturers take the Agency’s recommended approach following the Pre-Sub, it is not a guarantee that the FDA will approve the final submission because new information may have surfaced in the meantime.
Below, you'll find specific details on how to submit a request for feedback or a meeting through the Q-Submission program.
What should a cover letter include?
Method of Feedback
Purpose of Q-Sub
Device or Product Description
Proposed Indications for Use or Intended Use
What info should be included in each type of submission?
The guidance recommends the following submission contents for each submission type:
Planned Follow-On Submission
Review of Data
Submission Issue Request (SIR):
Preferred Feedback Format
Study Risk Determination:
Protocol for proposed clinical study
How long does it take to hear back from the FDA?
The guidance provides a table describing the type of feedback and timeline you can expect for each type of Q-sub. See Table 1 below this section for more details
Checklist and document examples
The document closes with three appendices:
Appendix 1 – Pre-Submission Acceptance Checklist
Appendix 2 – Example Pre-Sub Questions
Appendix 3 – Example of Meeting Minutes
Table 1: Feedback Methods and Timeframes for Each Q-Sub Type
Q-Submissions are voluntary but important opportunities to share information and receive input from the FDA before a final marketing submission, IDE, or IND. The Pre-Sub Program can be especially valuable for devices that involve novel technologies or pose significant risks. Although some manufacturers prefer to keep a “low profile” regarding the FDA, our most successful clients are those who take full advantage of the Q-Sub Program and communicate with the Agency proactively to de-risk their final submissions, ultimately shortening time to market.
Update - September 6, 2023
Starting October 1, 2023, all 510(k) submissions, unless exempted, must be submitted as electronic submissions using eSTAR, as noted in the:
eSTAR is the only available electronic submission template to facilitate the preparation of 510(k) electronic submissions. You can learn more here on the FDA website.