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Q-Submission Program: Strategic Framework for FDA Interactions in Medical Device Development

This guidance provides an overview of the Q-Submission (Q-Sub) Program, which offers various mechanisms for medical device submitters to request interactions with FDA. The program covers Pre-Submissions, Submission Issue Requests, Study Risk Determinations, Informational Meetings, PMA Day 100 Meetings, and other specialized submission types. These voluntary interactions can include written feedback and/or meetings related to potential or submitted medical device applications including IDE, PMA, HDE, De Novo requests, 510(k), CLIA Waivers, Accessory Classification Requests, and certain INDs and BLAs.

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By ReguVirta
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What You Need to Know? 👇

What is the Q-Submission Program and how does it benefit medical device companies?

The Q-Submission Program is FDA’s system for tracking voluntary interactions between medical device companies and FDA outside of formal submissions. It includes Pre-Submissions, Submission Issue Requests, Study Risk Determinations, and other meeting types that help streamline device development and improve submission quality.

How long does FDA take to provide feedback on Pre-Submissions?

FDA provides written feedback within 70 calendar days from receipt of an accepted Pre-Submission. If a meeting is requested, written feedback is provided at least 5 days before the scheduled meeting, with meetings typically occurring between days 70-75.

What types of questions should I include in a Pre-Submission for maximum value?

Include 3-4 substantial topics with no more than 7-10 specific questions total. Focus on requesting feedback on proposed approaches rather than asking FDA to design studies. Examples include biocompatibility testing plans, clinical study endpoints, or regulatory pathway confirmation.

When should I submit a Submission Issue Request (SIR) instead of a Pre-Submission?

Submit a SIR when you need feedback on addressing issues in FDA hold letters, Major Deficiency letters, or IDE/IND Clinical Hold letters. SIRs submitted within 60 days of the FDA letter receive prioritized review with 21-day feedback timelines.

What are the key requirements for meeting minutes in Q-Submissions?

Submitters must draft meeting minutes within 15 days of any Q-Sub meeting. Minutes should summarize discussions, document agreements and action items, and avoid assigning statements to individuals. Include actual presentation slides used during the meeting.

How does the Q-Submission Program handle combination products and digital health devices?

Submit Q-Submissions to the lead FDA center for your combination product. For digital health devices, include cybersecurity questions and software documentation level determinations. FDA coordinates with other centers as needed to provide comprehensive feedback on combination products.

What You Need to Do 👇

  1. Establish Q-Sub Strategy: Develop a comprehensive Q-Sub strategy early in device development, considering the sequence and timing of different Q-Sub types based on development priorities.
  2. Prepare Focused Submissions: Limit Pre-Subs to 3-4 substantial topics and 7-10 questions maximum to ensure thorough FDA review and productive feedback.
  3. Implement Early Engagement: Submit Pre-Subs prior to executing planned testing to maximize the value of FDA feedback in guiding development decisions.
  4. Utilize Acceptance Checklist: Use the Pre-Sub Acceptance Checklist (Appendix 1) to ensure submissions meet requirements before submission.
  5. Plan Meeting Logistics: For meetings, provide draft agendas, preferred dates 70-75 days from submission, and identify appropriate attendees and FDA expertise needed.
  6. Document Interactions: Prepare comprehensive meeting minutes within 15 days of meetings and maintain clear records of all FDA interactions.
  7. Link Related Submissions: Always reference relevant Q-Sub numbers in subsequent marketing submissions and explain how previous feedback was addressed.
  8. Consider Combination Products: For combination products, submit RFDs when classification is unclear and ensure proper center assignment before Q-Sub submission.
  9. Monitor Timelines: Track FDA performance goals and timelines for different Q-Sub types to plan development activities accordingly.
  10. Leverage Specialized Programs: Consider utilizing Breakthrough Device Program, Safer Technologies Program, or other specialized pathways when appropriate for your device.

Key Considerations

Clinical testing

  • Pre-Subs are highly recommended for obtaining feedback on clinical study protocols prior to execution
  • Study Risk Determination requests help determine if planned clinical investigations are significant risk (SR), nonsignificant risk (NSR), or exempt from IDE requirements
  • Clinical study endpoints, inclusion criteria, and follow-up duration should be clearly articulated
  • For NSR or IDE exempt studies, submitters should consider submitting entire protocols through Pre-Sub process
  • Clinical practice and testing methods evolve constantly - if more than one year has passed since previous FDA feedback on significant study design topics, submitters should contact the review division to confirm advice is still applicable

Non-clinical testing

  • Pre-Subs should include specific questions about non-clinical testing protocols needed to support submissions
  • Animal studies should include appropriate models, endpoints, and follow-up schedules
  • Bench performance testing should justify worst-case comparison testing approaches
  • FDA supports the “3Rs” principles (replace, reduce, refine) for animal testing when feasible

Human Factors

  • Human factors test protocols should be adequate to collect safety data
  • Use-related risk analysis plans should be comprehensive
  • Test participant recruitment plans for human factors validation testing should be appropriate
  • Critical tasks should be properly identified and considered

Labelling

  • Proposed labeling statements should be clearly articulated in submissions
  • Reprocessing instructions and cleaning protocols should be consistent with FDA guidance
  • MR Conditional labeling requires appropriate test plans
  • Indications for use statements should include clear definitions and appropriate size ranges

Software

  • Software documentation level designation should be consistent with FDA guidance
  • Multiple function device products require assessment of impact of other functions on device safety and effectiveness
  • Cybersecurity management plans must be sufficient for device risk level
  • Attack vectors should be properly identified and assessed

Cybersecurity

  • Cybersecurity management plans should ensure device cybersecurity for submissions
  • Risk models for assessing cybersecurity should be acceptable
  • Security levels should be appropriate for device risk
  • Attack vectors must be comprehensively identified

Labelling

  • Proposed indications for use or intended use must include disease/condition descriptions and patient population
  • Generic and proprietary device names should be included
  • Manufacturing process descriptions should be included if they may affect safety/effectiveness

Biocompatibility

  • Testing should align with recommended contact classification and duration
  • Chemical characterization may be conducted in lieu of chronic toxicity testing with proper justification
  • Carcinogenicity studies may be omitted with adequate justification
  • Alternative test methods to traditional animal models may be acceptable

Safety

  • Device description should include significant physical and performance characteristics
  • Safety data collection should be adequate through appropriate testing protocols
  • Risk assessments should be comprehensive and appropriate for device type

Other considerations

  • Predetermined Change Control Plans (PCCPs) - Pre-Subs are highly recommended for obtaining feedback on PCCP development
  • Computational modeling and simulation requires credibility assessment plans with appropriate context of use
  • Combination products require identification as such and may involve multiple FDA centers
  • Related submissions should reference previous Q-Subs and explain how feedback was addressed
  • Regulatory history should list any relevant previous FDA communications

Relevant Guidances 🔗

Related references and norms 📂

  • ISO 11135-2014: Sterilization of health care products — Ethylene oxide — Requirements for development, validation and routine control of a sterilization process for medical devices
  • 21 CFR part 812: Investigational Device Exemptions
  • 21 CFR 10.65(e): Administrative practices and procedures
  • Section 515C of the FD&C Act: Predetermined Change Control Plans for Devices
  • Section 515B of the FD&C Act: Breakthrough Devices Program
  • Section 513(g) of the FD&C Act: Requests for Information
  • Section 513(f)(6) of the FD&C Act: Accessory Classification
  • Section 515(d)(3) of the FD&C Act: PMA Day 100 Meetings
  • Section 503(g) of the FD&C Act: Combination Product Agreement Meetings

Original guidance

  • Q-Submission Program: Strategic Framework for FDA Interactions in Medical Device Development
  • HTML / PDF
  • Issue date: 2025-05-29
  • Last changed date: 2025-05-28
  • Status: FINAL
  • Official FDA topics: Medical Devices, Investigational Device Exemption (IDE), Biologics, Administrative / Procedural
  • ReguVirta ID: 7d9885ed8dd231f0d097b32c01ece020
FDA guidance, Final
Medical Devices Investigational Device Exemption (IDE) Biologics Administrative / Procedural
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