Q-Submission (Q-Sub) & Pre-Submission (Pre-Sub)

What is FDA Q-sub?

The Q-Submission (Q-Sub) Program is a mechanism established by the FDA (Food and Drug Administration) that allows sponsors to obtain feedback on various types of medical device applications before their formal submission. Originally known as the Pre-IDE program starting in 1995, it provided a way for sponsors to seek FDA feedback prior to submitting an Investigational Device Exemption (IDE) application. Over time, the program expanded to include feedback on other types of submissions, such as Premarket Approval applications (PMAs), Humanitarian Device Exemption applications (HDEs), De Novo requests, and 510(k) submissions, as well as determining whether a clinical study requires an IDE submission.

In 2012, as part of the Medical Device User Fee Amendments (MDUFA III), the FDA committed to formalizing and structuring this feedback process, referring to it as “Pre-Submissions.” The Pre-Submission Guidance, issued in 2014, established the broader Q-Submission (Q-Sub) Program, which encompasses Pre-Submissions and additional opportunities for interaction with the FDA.

Subsequent amendments to the Medical Device User Fee Amendments, such as MDUFA IV in 2017 and MDUFA V in 2022, further refined the Q-Sub Program. These refinements included changes in scheduling Pre-Sub meetings and setting performance goals for the timing of FDA feedback on Pre-Submissions.

Types of Q-Submissions

The four most common types of Q-Subs include Pre-Submissions (Pre-Subs), Submission Issue Requests (SIRs), Study Risk Determinations and Informational Meetings.

Pre-Submissions (Pre-Subs)

A Pre-Submission (Pre-Sub) is a voluntary formal written request from a medical device submitter to the FDA, seeking feedback on specific questions related to review topics pertinent to their intended premarket submission. This feedback can be provided in the form of a formal written response or a combination of formal written feedback followed by a meeting. The meeting discussions are documented in meeting minutes submitted to the FDA for review.

The purpose of a Pre-Sub is to allow submitters to obtain FDA guidance to guide product development and submission preparation. It is not meant to pre-review an actual submission or the data to be included. Common review topics include biocompatibility, bench testing, cybersecurity, etc.

Engaging in Pre-Subs can lead to improved subsequent submissions by enhancing the quality of submissions, shortening review times, and facilitating the development process for new devices. FDA staff considers various scientific and regulatory approaches to provide feedback consistent with least burdensome requirements.

It’s important to note that feedback provided in a Pre-Sub does not obligate submitters to address the issues raised or guarantee a favorable decision in future submissions. However, addressing FDA feedback early can contribute to a more efficient and transparent review process.

Pre-Subs are recommended for obtaining FDA feedback on various submission types, including Predetermined Change Control Plans (PCCPs), which allow manufacturers to make certain modifications to devices without requiring a supplemental premarket approval application or notification. Engaging in Pre-Subs for PCCPs can streamline the premarket review process by working proactively with the FDA.

Submission Issue Requests (SIRs)

A Submission Issue Request (SIR) is a formal request made by a medical device or drug submitter to the FDA for feedback, either through written responses or meetings. The purpose of an SIR is to address issues raised in specific FDA hold letters, such as marketing submission hold letters, IDE Letters, or IND Clinical Hold letters. These hold letters could include requests for additional information for 510(k)s, De Novo requests, Combination Product submissions, or major deficiencies for PMAs and HDEs, among others.

An SIR aims to facilitate swift interaction between the FDA and the submitter to resolve questions and issues highlighted in these hold letters. It allows submitters to discuss proposed approaches or strategies for addressing these issues, enabling projects to progress smoothly and ensuring that all outstanding questions are adequately addressed in formal responses.

Study Risk Determinations

A Study Risk Determination involves requesting the FDA’s determination regarding whether a planned clinical study for a medical device falls under the categories of significant risk (SR), non-significant risk (NSR), or is exempt from Investigational Device Exemption (IDE) regulations as outlined in 21 CFR part 812. If a study is not exempt, sponsors are responsible for initially assessing and indicating whether it poses significant risk or not, presenting this determination to the Institutional Review Board (IRB). The FDA is available to assist the sponsor, clinical investigator, and IRB in making this risk determination. Ultimately, the FDA has the final authority to decide whether a device study is significant risk or non-significant risk, and this determination is made either when an IDE is submitted to the FDA or upon request by the sponsor, clinical investigator, or IRB.

Informational Meetings

An Informational Meeting is a request made to the FDA with the purpose of sharing information, typically without expecting feedback from the FDA. These meetings are beneficial for providing an overview of ongoing device development, especially when there are multiple submissions planned within the next 6-12 months. They help familiarize the FDA review team with new devices that exhibit significant differences in technology compared to currently available devices.

During an Informational Meeting, FDA staff may ask clarifying questions, but they are primarily there to listen and gather information rather than provide feedback. These meetings can also serve to document interactions between the FDA and the submitter that do not fit into the categories of other types of Q-Submissions.

Other Q-Submission Types

In addition to the Q-Sub types listed above, the Q-Sub program provides a mechanism to track interactions described in other FDA program guidance documents. These include the PMA Day 100 Conference, Agreement and Decision meetings under the United States Food and Drug Administration Modernization Act (FDAMA), submissions for the breakthrough device program, Safer Technologies Program (SteP) submissions, and requests for accessory classification.

What are the benefits of applying Q-sub?

When utilized effectively, participating in the Q-Sub program can yield benefits for both the FDA and device developers. The FDA actively encourages Q-Subs, as they provide valuable insights into emerging developments within the healthcare industry, enhancing the agency’s understanding of novel technologies. Engaging in conversations and exchanges with device manufacturers enables developers to glean crucial information that can streamline both their submission process and overall product development. Additionally, the appointment of a project manager by the FDA under the Q-Sub program proves invaluable to device sponsors, facilitating communication and coordination. Moreover, a significant advantage of the program lies in its lack of fees and absence of restrictions on the number of meetings developers can request.

Who needs a Q-sub?

A Q-Sub meeting with the FDA is not obligatory, but it’s often advised, particularly for medical device developers who seek early engagement with the FDA during the development phase of new devices. This engagement provides an avenue to address specific queries to the agency. By formally requesting a Q-Sub meeting, developers can receive guidance and constructive feedback on various aspects, including expensive bench and animal testing, clinical trials, and overall regulatory strategy.

Here are some example situations where medical device developers may want to consider submitting a Q-Submission to the FDA:

• Before embarking on studies that lack defined guidance: If a device necessitates studies not outlined in existing guidance documents, a Q-Sub is advisable to ensure the appropriateness of proposed testing methods.
• Determining the risk level of device studies: Whether a device study is deemed significant risk (SR), non-significant risk (NSR), or exempt from an Investigational Device Exemption (IDE) requires clarification, which a Q-Sub can provide.
• Devices featuring novel technology or design: Devices with unique technology or design may not neatly fit into existing regulatory categories, necessitating a Q-Sub to ascertain the appropriate regulatory pathway.
• Devices with markedly distinct indications for use: If a device’s indications for use significantly differ from existing 510(k)-cleared devices, seeking FDA feedback through a Q-Sub ensures alignment with the most suitable regulatory pathway.
• Studies conducted outside the United States: For studies conducted abroad, engaging in the Q-Sub program ensures compliance with FDA requirements and streamlines the regulatory review process.

When should we apply for Q-sub?

Planning for a Q-Sub meeting with the FDA requires careful consideration of timelines, as the process can be extensive. While a Q-Sub can be beneficial at any stage of development, it is particularly advantageous before undertaking costly and resource-intensive phases such as bench, animal, and clinical testing. Even if a product has already undergone testing, submitting a Pre-Sub can still be advantageous, as it allows for presenting complex data or conclusions to the FDA before a full submission review.

Following FDA guidelines, the timeline for the meeting starts after preparing Q-Sub materials. The process involves:

1. Understanding regulatory submission requirements and assembling necessary data and documentation.
2. Reviewing application documents and formulating questions for the FDA.
3. Submitting the Pre-Submission meeting application. Within 15 days, the FDA conducts an acceptance review using the Acceptance Checklist. If rejected, the agency provides an explanation, and a Q-Sub Amendment can be submitted.
4. Scheduling the meeting. If accepted, the FDA confirms the requested meeting date or provides alternative dates scheduled before day 75 of submission receipt.
5. Drafting and submitting meeting minutes within 15 days of the meeting. If no revisions are needed, the minutes are considered final. However, if the FDA suggests changes, an updated version is sent within 30 days, and the minutes are finalized 15 days after receiving the edited version.

What are the document requirements for Q-Sub?

First and foremost, all the Q-Sub documents must be in the English language. The content for Q-Sub as per the Q-Sub guidance includes:

• Contact Information
• Q-Sub Type
• Methods of Feedback
• Meeting Information
• Purpose
• Device or Product Description
• Proposed Indications for Use or Intended Use
• Regulatory History

If you need any help towards Q-Sub document preparation and submission, please contact us at info@accelgroups.com.

About Accel

Accel Groups is a dedicated team of seasoned professionals in regulatory, clinical and market access. We help medical device and IVD manufacturers with complete product life cycle solutions from preclinical, strategy, clinical evaluation and trial, regulatory submission, to post market surveillance. Our regional principals have a minimum of 10+ years’ experience in their specialty to enable us to provide the regional in-depth expertise but with global one-stop shop solutions. Ask us about our Start-up kits for start-up companies with key countries regulatory pathway.