FDA finalizes 2025 Q-Submission Guidance, streamlining interactions for device sponsors and proposes electronic submission mandate for Q-Submissions using eStar

Background

The Q-Submission (Q-Sub) Program is a voluntary process that allows device sponsors to engage with FDA outside of formal marketing submissions. The program covers a range of communications that can occur throughout the device development lifecycle, from early design discussions aimed at discussing the device verification and validation plan to interaction with FDA while a premarket filing is under review.

Generally, the guidance provides an overview of the Q-Submission process, detailing how sponsors can request written feedback or schedule meetings with FDA regarding various premarket submissions, including Investigational Device Exemption (IDE) applications, Premarket Approval (PMA) applications, Humanitarian Device Exemption (HDE) applications, De Novo requests, and 510(k) submissions.

Notable revisions and clarifications

The guidance largely tracks the 2024 draft guidance, offering greater detail regarding how sponsors can obtain FDA feedback both through the Q-Sub Program, as well as mechanisms outside the Q-Sub Program. For example, the Q-Sub Program has significantly expanded over time to increase the types of meetings for sponsors to engage with FDA, well beyond the initial goal of the Pre-Submission Program, which was rooted in communications in advance of investigational device exemption (IDE) submissions. The guidance also clarifies what falls outside of the Q-Sub Program, noting that informal feedback may be obtained via email or phone without the need for a formal meeting request—provided the questions can be addressed based on the reviewer’s existing knowledge and experience, and do not require additional context, in-depth review, or other FDA staff involvement (for example, whether additional testing may be needed outside the scope of performance criteria provided in guidance documents). Sponsors may also receive informal feedback on topics such as device-specific guidance documents or voluntary consensus standards not tied to a specific device in development. Similarly, processes like Pre-RFDs, 513(g) Requests, Emergency Use Authorizations, and appeals are governed by separate guidance and should not be routed through Q-Subs. FDA encourages sponsors who are unsure about the appropriate submission pathway to contact the relevant review division or the Office of Product Evaluation and Quality (OPEQ) for guidance.

The final guidance also clarifies which submission types are eligible for a submission issue meeting, allowing for a shorter FDA review timeline. In additional to marketing submission hold letters, the guidance makes clear that Clinical Laboratory Improvement Amendments (CLIA) Waiver by Applications (CW) hold letters, Investigational Device Exemption (IDE) Letters, and IND Clinical Hold letters are also eligible for a submission issue meeting.

Since the guidance supersedes the June 2023 version and a 1998 guidance on PMA Day 100 meetings, the final guidance now includes a dedicated section on PMA Day 100 meetings, though there are no significant changes to the process. The guidance notes that FDA aims to hold a PMA Day 100 Meeting no later than 100 days after the receipt of a PMA application that has been filed. In addition, a PMA Day 100 Meeting can be requested as part of the cover letter of a PMA application or by submitting a separate Q-Sub.

Encouraging early and strategic use

The guidance emphasizes that early use of the Q-Sub process—particularly Pre-Subs—can significantly improve the quality of submissions and reduce review times. The guidance further encourages sponsors to utilize the Q-Sub Program for new devices, as well as for Predetermined Change Control Plans (PCCPs), which are used to propose future modifications for devices subsequent to authorization of the device and the PCCP under Section 515C of the FD&C Act.

The guidance also stresses the importance of focused topic and question-selection to ensure productive Pre-Sub discussions. FDA recommends limiting individual submissions to 7-10 questions on no more than 4 substantive topics. The agency also noted that interdependence of questions mars its ability to provide clear and efficient feedback. The guidance recommends thinking strategically about discussion topics to follow the flow of regulatory strategy and development (e.g., as testing requirements are dependent on regulatory pathway, questions regarding intended use and classification should be discussed prior to specific test plans or clinical trial protocols).

However, the feedback provided by FDA may have an expiration. The final guidance, consistent with the draft guidance, states that if more than one (1) year has passed since FDA feedback was received on significant topics, and the study has not been initiated, sponsors should contact the review division to confirm that the feedback remains applicable. This presents challenges for devices with long verification and validation pathways, and for companies that are seeking funding and may have their development on hold. Companies should endeavor to closely follow developments in their device areas to track evolution of FDA expectations with respect to documentation, testing, standards both in terms of FDA guidance, as well as well as other devices in the same area. We also encourage companies to engage with FDA multiple times through the Q-Submission process, particularly for more complex and novel technologies and indications. Early interactions during protracted development and evaluation periods can help reduce questions and shorten review timelines for the marketing application.

FDA proposes electronic submission nandate for Q-Submissions using eSTAR

Furthermore, on May 29, 2025, FDA issued a draft guidance titled “Electronic Submission Template for Medical Device Q-Submissions,” marking a key step toward modernizing the submission process. The draft guidance outlines the framework for requiring Q-Subs, specifically Pre-Subs, to be submitted in electronic-only format via FDA’s eSTAR (electronic Submission Template And Resource) system.

The agency began piloting eSTAR in 2020 and has since expanded its use. Currently, eSTAR filings are mandatory for 510(k) submissions and are set to become mandatory for De Novo requests in October 2025. While electronic Q-Submissions via eSTAR are currently voluntary, the guidance proposes to make them mandatory after a one-year transition period following finalization of the Q-Sub eSTAR guidance.

Once finalized, the guidance will require all Pre-Subs—originals, supplements, and amendments—to be submitted using the eSTAR format. However, certain categories of associated submissions will be exempt from the electronic-only requirement, including meeting minutes, presentation slides, appeals for supervisory review, amendments after decision, and withdrawal requests.

As with the 510(k) eSTAR, there will not be a “Refuse to Accept” (RTA) process, though FDA will conduct a technical screening within 15 days of submission to check for virus scans and completeness. If the submission fails this technical screening, sponsors will be notified and have 180 days to provide corrections. Upon resubmission, the review clock resets.

The draft guidance provides an overview of the structure of the “pre-STAR template,” which features integrated databases for populating the form with FDA product codes and agency-recognized consensus standards, and targeted questions designed to collect specific data and information from sponsors. With the transition to pre-STAR, the format for Pre-Submissions will become more rigid, with the current version of the form requiring identification of a maximum of four topic areas. Sponsors with complex regulatory histories will need to carefully organize their submissions to provide sufficient context for their questions to obtain meaningful feedback from FDA and consider multiple Pre-Submission filings to ensure that all topic areas for FDA feedback are addressed.

The pre-STAR template available on FDA’s website now only has the capability to host Pre-Submissions and 513(g) classification requests, with other Q-Sub types forthcoming. FDA will continue to update the document as other types of Q-Subs are implemented within the eSTAR Program.

FDA is seeking comments on the draft guidance by July 28, 2025.

Next steps

Both guidance documents clarify FDA’s expectations and formalizes procedures under the Q-Sub Program, including the shift to mandating use of the eSTAR system for filing such feedback requests. The final guidance on Q-Submissions largely tracks FDA’s current expectations with minimal changes to the 2024 draft guidance, and reaffirming that FDA believes early engagement from sponsors is beneficial. The shift to the pre-STAR form within the next 2 years will be a more disruptive change to the industry, as sponsors will need to provide comprehensive submissions in the new format.

Authored by Kelliann Payne, Lina Kontos, and Evelyn Tsisin.