Contains Nonbinding Recommendations
Requests for Feedback and Meetings 
for Medical Device Submissions:
The Q-Submission Program
Guidance for Industry and 
Food and Drug Administration Staff
Document issued on June 2, 2023.
Document originally issued on May 7, 2019.
This document supersedes Requests for Feedback and Meetings for Medical 
Device Submissions: The Q-Submission Program issued January 6, 2021.
For questions about this document regarding CDRH-regulated devices, contact ORP: Office of 
Regulatory Programs/DRP1: Division of Submission Support at 301-796-5640. For questions 
about this document regarding CBER-regulated devices, contact the Office of Communication, 
Outreach, and Development (OCOD) at 1-800-835-4709 or 240-402-8010, or by email at 
ocod@fda.hhs.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Center for Biologics Evaluation and Research 
OMB Control No. 0910-0756
Current expiration date available at https://www.reginfo.gov.
See additional PRA statement in Section V of this guidance. Contains Nonbinding Recommendations
Preface
Public Comment 
You may submit electronic comments and suggestions at any time for Agency consideration to 
https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food 
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852-
1740. Identify all comments with the docket number FDA-2018-D-1774. Comments may not be 
acted upon by the Agency until the document is next revised or updated. 
Additional Copies
CDRH
Additional copies are available from the Internet. You may also send an email request to CDRH-
Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 
GUI00001677 and complete title of the guidance in the request.
CBER
Additional copies are available from the Center for Biologics Evaluation and Research (CBER), 
Office of Communication, Outreach, and Development (OCOD), 10903 New Hampshire Ave., 
WO71, Room 3128, Silver Spring, MD 20993-0002, or by calling 1-800-835-4709 or 240-402-
8010, by email, ocod@fda.hhs.gov, or from the Internet at https://www.fda.gov/vaccines-blood-
biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances. Contains Nonbinding Recommendations
Table of Contents
I. Introduction ........................................................................................................................................... 1
II. Background ........................................................................................................................................... 2
III. Scope ................................................................................................................................................. 2
A. Pre-Submissions (Pre-Subs) .............................................................................................................. 3
B. Submission Issue Requests (SIRs) .................................................................................................... 4
C. Study Risk Determinations ............................................................................................................... 5
D. Informational Meetings ..................................................................................................................... 5
E. Other Q-Submission Types ............................................................................................................... 6
F. Other Uses of the Q-Submission Program ........................................................................................ 7
G. Interactions Not Within the Q-Submission Program ........................................................................ 8
IV. Q-Submission Program ................................................................................................................... 10
A. General Q-Submission Considerations ........................................................................................... 11
(1) Relating Q-Submissions to Future IDE, IND, CWs, and Marketing Submission(s) (Related
Submission(s)) ................................................................................................................................... 11
(2) Combination Product Considerations ......................................................................................... 12
B. Q-Submission Processes ................................................................................................................. 12
(1) Submission Content .................................................................................................................... 13
(2) FDA Submission Tracking.......................................................................................................... 15
(3) Meeting Information ................................................................................................................... 16
(4) Processes by Q-Submission Types ............................................................................................. 19
(5) Other Q-Sub Types or Uses of the Q-Sub Program .................................................................... 26
V. Paperwork Reduction Act of 1995 ...................................................................................................... 27
Appendix 1  Pre-Submission (Pre-Sub) Acceptance Checklist ................................................................ 28
Appendix 2  Example Pre-Sub Questions ................................................................................................. 29
Appendix 3  Example of Meeting Minutes ............................................................................................... 33 Contains Nonbinding Recommendations
Requests for Feedback and Meetings 
for Medical Device Submissions:
The Q-Submission Program
Guidance for Industry and 
Food and Drug Administration Staff
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic. It does not establish any rights for any person and is not binding on 
FDA or the public. You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff 
or Office responsible for this guidance as listed on the title page. 
I. Introduction1 
The purpose of this guidance document is to provide an overview of the mechanisms available to 
 
submitters through which they can request feedback in writing or during a meeting with the 
Food and Drug Administration (FDA) regarding potential or planned medical device 
Investigational Device Exemption (IDE) applications, Premarket Approval (PMA) applications, 
Humanitarian Device Exemption (HDE) applications, Evaluation of Automatic Class III 
Designations (De Novo requests), Premarket Notification (510(k)) Submissions, Clinical 
Laboratory Improvement Amendments (CLIA) Waiver by Applications (CW), Dual 510(k) and 
CLIA Waiver by Application Submissions (Duals), Accessory Classification Requests, and 
certain Investigational New Drug Applications (INDs) and Biologics License Applications 
(BLAs) submitted to the Center for Biologics Evaluation and Research (CBER)) (specifically, 
INDs and BLAs for devices that are regulated as biological products under section 351 of the 
Public Health Service (PHS) Act).2
Throughout this guidance document, the terms we, us and our refer to FDA staff from the 
Center for Devices and Radiological Health (CDRH) or CBER. You and your refers to the 
submitter. A meeting may be conducted in-person (face-to-face) or virtually (by 
1The Office of Combination Products (OCP) was consulted in the preparation of this guidance.
2Some such devices, generally those that are for use in screening donated blood for transfusion transmissible 
diseases, require an IND prior to submission of a BLA. Other such devices do not require an IND prior to the 
submission of the BLA; these devices generally include those reagents used in determining donor/recipient 
compatibility in transfusion medicine.
1 Contains Nonbinding Recommendations
videoconference or teleconference). When there is a distinction between those two types of 
meetings, it will be noted in this guidance.
In general, FDA's guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
II. Background 
The pre-IDE program was established in 1995, to provide sponsors a mechanism to obtain FDA 
feedback on future IDE applications prior to their submission. Over time, the pre-IDE program 
evolved to include feedback on PMAs, HDEs, De Novo requests, and 510(k) submissions, as 
well as to address whether a clinical study requires submission of an IDE. 
To capture this evolution, the Secretary of Health and Human Services (HHS) 2012 
Commitment Letter to Congress regarding the Medical Device User Fee Amendments of 2012 
(MDUFA III) included FDAs commitment to institute a structured process for managing these 
interactions, referring to them as Pre-Submissions.3 The Pre-Submission Guidance, published 
in February 18, 2014, implemented the broader Q-Submission (Q-Sub) Program, which includes 
Pre-Submissions (Pre-Subs), as well as additional opportunities to engage with FDA.
As part of the Medical Device User Fee Amendments of 2017 (MDUFA IV), industry and the 
Agency agreed to refine the Q-Sub Program with changes related to the scheduling of Pre-Sub 
meetings and a new performance goal on the timing of FDA feedback for Pre-Subs.4As part of 
the Medical Device User Fee Amendments of 2022 (MDUFA V), these goals were further 
refined.5 The Agency also committed to issuing a draft guidance update to include additional 
information to assist applicants and review staff in identifying the circumstances in which an 
applicants question is most appropriate for informal communication instead of a Pre-
Submission. The purpose of the current update is to provide minor procedural updates and 
clarifications while the draft guidance for public comment is being developed.
III. Scope 
The types of Q-Subs covered by this guidance in detail are listed in Sections III.A-D of this 
guidance. Some other submission types are noted solely to indicate that they are tracked with a 
Q number and should be submitted following the processes for Q-Subs, while their details and 
3See 158 CONG. REC. S8277-S8281 (daily ed. Corrected December 20, 2012) (Letters from the Secretary of 
Health and Human Services Re: Medical Device User Fee Program), also available at 
https://www.fda.gov/media/83244/download
4See 163 CONG. REC. S4729-S4736 (daily ed. August 2, 2017) (Food and Drug Administration User Fee 
Reauthorization), also available at https://www.fda.gov/media/102699/download
5See 168 CONG. REC. S5194-S5203 (daily ed. September 28, 2022) (Food and Drug Administration User Fee 
Reauthorization), also available at https://www.fda.gov/media/158308/download
2 Contains Nonbinding Recommendations
processes are covered in separate guidance documents (see Sections III.E and F of this 
guidance). Finally, there are other interactions with FDA that are outside the scope of the Q-Sub 
program (Section III.G of this guidance). 
A. Pre-Submissions (Pre-Subs) 
A Pre-Sub includes a formal written request from a submitter6 for feedback from FDA that is 
provided in the form of a formal written response or, if the submitter chooses, formal written 
feedback followed by a meeting. All discussion that occurs during the meeting is documented in 
meeting minutes that are drafted by the submitter and submitted for FDA review. 
A Pre-Sub provides the opportunity for a submitter to obtain FDA feedback prior to an intended 
premarket submission (i.e., IDE, PMA, HDE, De Novo request, 510(k), Dual, BLA, IND), 
Accessory Classification Request, or CW. The request should include specific questions 
regarding review topics relevant to a planned IDE, CW, or marketing submission. Some 
examples of common review topics are biocompatibility, bench testing, cybersecurity, etc. See 
Appendix 2 for examples of specific questions within review topics. A Pre-Sub is appropriate 
when FDAs 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.
The program is entirely voluntary on the part of the submitter. However, early interaction with 
FDA on planned non-clinical and clinical studies and careful consideration of FDAs feedback 
may improve the quality of subsequent submissions, shorten total review times, and facilitate the 
development process for new devices. FDA believes that interactions provided within Pre-Subs 
are likely to contribute to a more efficient and transparent review process for FDA and the 
submitter. Our staff develops feedback for Pre-Subs by considering multiple scientific and 
regulatory approaches consistent with least burdensome requirements and principles7, to 
streamline regulatory processes. FDA has found that feedback is most effective when requested 
prior to execution of planned testing. Issues raised by FDA in a Pre-Sub do not obligate 
submitters to addressing or resolving those in a subsequent submission, though any future 
submission related to that topic should discuss why a different approach was chosen or an issue 
left unresolved. Further, review of information in a Pre-Sub does not guarantee a favorable 
decision in future submissions. Additional questions may be raised during the review of the 
future submission when all information is considered as a whole, or if new information has 
become available since the Pre-Sub.
Pre-Subs can be useful to obtain FDA feedback on a wide variety of future submission types, 
including other Q-Submission types that you intend to submit requesting an FDA decision. One 
6For the purposes of this guidance document, manufacturers or other parties who submit an IDE, IND, CW, Dual, 
or marketing submission to the Agency are referred to as submitters.
7See FDAs guidance, The Least Burdensome Provisions: Concept and Principles, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-concept-
and-principlesand sections 513(i)(1)(D)(i), 513(a)(3)(D)(ii), 515(c)(5)(A), 515(c)(5)(C), 513(a)(3)(D)(iii), 
513(i)(1)(D)(ii), and 515(c)(5)(B) of the FD&C Act.
3 Contains Nonbinding Recommendations
example is an Accessory Classification Request,8 which is another type of Q-Submission 
discussed in Section III.E. Accessory Classification Requests are not Pre-Subs, however, a Pre-
Sub can be submitted prior to a formal Accessory Classification Request to help guide product 
development or request feedback about application preparation. When requested, FDA will 
provide the opportunity for a submitter to meet and discuss the appropriate classification prior to 
submitting an Accessory Classification Request for an existing accessory type.9 This meeting 
would fall within the scope of a Pre-Sub. Submission procedures for the Accessory Classification 
Request itself are further described in Section III.E.
Pre-Subs are also highly recommended for obtaining feedback on Predetermined Change Control 
Plans (PCCPs) prior to inclusion in a premarket submission. PCCPs were added under section 
515C of the FD&C act and allow the manufacturer to make modifications that are within the 
bounds of the PCCP following FDA authorization of the PCCP.10 Under section 515C, FDA can 
approve or clear a PCCP for a device that describes planned changes that may be made to the 
device and that would otherwise require a supplemental premarket approval application or 
premarket notification. For example, section 515C provides that a supplemental premarket 
approval application (section 515C(a)) or a premarket notification (section 515C(b)) is not 
required for a change to a device if the change is consistent with a PCCP that is approved or 
cleared by FDA. Section 515C also provides that FDA may require that a PCCP include labeling 
for safe and effective use of a device as such device changes pursuant to such plan, notification 
requirements if the device does not function as intended pursuant to such plan, and performance 
requirements for changes made under the plan. FDA encourages the use of a Pre-Sub as it 
provides an opportunity to work proactively with the FDA in the development of the PCCP, 
which helps to streamline the premarket review. 
B. Submission Issue Requests (SIRs) 
A SIR is a request for FDA feedback via written feedback or a meeting on a proposed approach 
to address issues conveyed in a marketing submission hold letter, a CW hold letter, an IDE 
Letter, or an IND Clinical Hold letter. To further clarify the scope of SIRs, the following are 
considered appropriate marketing submission hold letters for the purposes of this guidance: 
 
 Additional Information Needed for 510(k)s, De Novo requests, CWs, and Duals;
 Major Deficiencies, Not Approvable, Approvable with Deficiencies, Approvable 
Pending GMP, and Approval with PAS conditions for PMAs and HDEs; 
 Complete Response Letter for Biologics License Applications (BLAs).
A SIR is intended to facilitate interaction between FDA and the submitter to quickly address 
questions about issues identified in these letters so that projects can move forward, and so that
8See section 513(f)(6) of the FD&C Act.
9See section 513(f)(6)(D)(ii) of the FD&C Act.
10Section 3308 of the Food and Drug Omnibus Reform Act of 2022 (FDORA), enacted as part of the Consolidated 
Appropriations Act, 2023, Pub. L. No. 117-328 (2022), added section 515C Predetermined Change Control Plans 
for Devices to the FD&C Act.
4 Contains Nonbinding Recommendations
submitters are able to fully address outstanding questions and issues in their formal responses. A 
SIR may be used to discuss a planned approach or strategy for addressing issues identified in an 
FDA letter. However, a SIR should not be used to request that FDA pre-review an intended 
formal response to assess adequacy.
Submitters are expected to provide a formal response to any letters received from FDA within 
the requested timeline regardless of whether a SIR is submitted. 
Please note, a SIR is not appropriate for discussing letters conveying final decisions, such as Not 
Substantially Equivalent, Withdrawals, and Deletions.
A SIR is not necessary for simple requests for clarification of issues in a letter where the 
involvement of management is not needed (e.g., minor clarification questions or administrative 
issues that can be addressed by the lead reviewer). A SIR is also not necessary to discuss issues 
while a file is under active review. 
Refer to Section IV.B(4)b of this guidance for additional information on Submission Issue 
Requests. 
C. Study Risk Determinations 
A Study Risk Determination is a request for FDA determination for whether a planned medical 
device clinical study is significant risk (SR), non-significant risk (NSR), or exempt from IDE 
regulations as defined by the IDE regulations (21 CFR part 812). For studies that are not exempt, 
sponsors are responsible for making the initial risk determination (SR or NSR) and presenting it 
to the Institutional Review Board (IRB). For more information, see FDAs guidance entitled 
Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors Significant Risk 
and Nonsignificant Risk Medical Device Studies.11 FDA is available to help the sponsor, 
clinical investigator, and IRB in making the risk determination. FDA is the final arbiter as to 
whether a device study is SR or NSR and makes the determination when an IDE is submitted to 
FDA or if asked by the sponsor, clinical investigator, or IRB. See 21 CFR 812.2(b)(1).
D. Informational Meetings 
An Informational Meeting is a request to share information with FDA without the expectation of 
feedback. This information sharing can be helpful in providing an overview of ongoing device 
development (particularly when there are multiple submissions planned within the next 6-12 
months) and familiarizing the FDA review team about new device(s) with significant differences 
in technology from currently available devices. While FDA staff may ask clarifying questions 
during an informational meeting, they will generally be listening during the meeting and not 
prepared to provide any feedback.
11https://www.fda.gov/regulatory-information/search-fda-guidance-documents/significant-risk-and-nonsignificant-
risk-medical-device-studies
5 Contains Nonbinding Recommendations
Informational Meetings can also be used to document FDA and submitter interactions that do not 
fall within the definition of the other types of Q-Submissions. Additional information on these 
can be found in Section III.F of this document. 
E. 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. Currently, in addition to the 
Q-Sub types above, the interactions that are tracked in the Q-Submission program include the 
following:
 PMA Day 100 Meetings as described in FDAs guidance entitled Guidance on 
PMA Interactive Procedures for Day-100 Meetings and Subsequent 
Deficiencies.12
 Agreement and Determination Meetings as described in FDAs guidance entitled 
Early Collaboration Meetings Under the FDA Modernization Act (FDAMA).13
 Submissions associated with the Breakthrough Devices Program as described in 
FDAs guidance entitled, Breakthrough Devices Program14: 
o Breakthrough Device Designation Request: to request inclusion in the 
Breakthrough Devices Program according to the criteria specified in 
section 515B(b) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act).
o Interaction for Designated Breakthrough Device: to request feedback on 
device development and clinical protocols for devices previously 
designated as breakthrough.
 Submissions associated with the Safer Technologies Program (STeP) as 
described in FDAs guidance entitled, Safer Technologies Program for Medical 
Devices15: 
o STeP Entrance Request: to request inclusion in the Safer Technologies 
Program. 
o STeP Interaction Submission: to request feedback on device development 
and clinical protocols for devices previously included in STeP.
12https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-pma-interactive-
procedures-day-100-meetings-and-subsequent-deficiencies-use-cdrh-and
13https://www.fda.gov/regulatory-information/search-fda-guidance-documents/early-collaboration-meetings-under-
fda-modernization-act-fdama-final-guidance-industry-and-cdrh
14https://www.fda.gov/regulatory-information/search-fda-guidance-documents/breakthrough-devices-program
15https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safer-technologies-program-medical-
devices
6 Contains Nonbinding Recommendations
 Accessory Classification Requests as described in FDAs guidance entitled, 
Medical Device Accessories  Describing Accessories and Classification 
Pathways16:
o For an Existing Accessory Type: to request appropriate classification of an 
accessory that has been granted marketing authorization as part of a 
premarket submission for another device with which the accessory is 
intended to be used.
o For a New Accessory Type: to request appropriate classification of an 
accessory that has not been previously classified under the FD&C Act, 
cleared for marketing under a 510(k) submission, or approved in a PMA. 
New Accessory Type classification requests should be submitted together 
with the premarket submission for the parent device. Accessory 
Classification Request will be tracked as a Q-Sub with review and 
decisions being conducted concurrently with the parent premarket 
submission.
Policies and procedures for these other Q-Sub types can be found in their respective guidance 
documents. Further, as FDA works to create additional mechanisms to streamline the device 
development and review process, FDA may create additional Q-Sub types that follow the same 
principles and processes outlined in this guidance document.
F. Other Uses of the Q-Submission Program 
There are interactions that do not meet the definitions of the Q-Sub types described above and 
for which a new formal Q-Sub type has not been created. When a new Q-Sub type does not exist 
to track a particular type of interaction, FDA may use the Informational Meeting Q-Sub type as a 
vehicle to track those interactions. Examples of the types of interactions for which the 
Informational Meeting Q-Sub mechanism is currently used for tracking include: 
 
 Request for FDA feedback on specific questions or cross-cutting policy matters 
(e.g., submission strategies unrelated to a specific premarket submission, non-
clinical testing strategies from third party testing labs) from other government 
agencies, non-profits, trade organizations and professional societies. Note that a 
submission is not necessary for FDA to meet with these groups, but is open to 
accepting them, should organizations voluntarily submit information in advance of 
the meeting for FDAs substantive review.17
16https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-device-accessories-
describing-accessories-and-classification-pathways
17For these types of meetings with CBER staff, see https://www.fda.gov/about-fda/about-center-biologics-
evaluation-and-research-cber/contacts-center-biologics-evaluation-research-cber#indcont
7 Contains Nonbinding Recommendations
 Request for recognition of publicly accessible genetic variant databases (refer to 
FDAs guidance entitled Use of Public Human Genetic Variant Databases to 
Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics).18
 Request for FDA feedback on design elements of a clinical study that do not fall 
within the scope of a Pre-Submission, and therefore would not be eligible for 
discussion under a Pre-Sub. These requests could include requests regarding study 
design for an NSR or IDE exempt study for which the results are not intended to 
support a future IDE or marketing submission.
 Combination product agreement meetings (CPAM) as defined under section 
503(g)(2)(A) of the FD&C Act.
 Requests for FDA feedback related to compliance actions. For example, an 
Informational Meeting Q-Sub could be used to request FDA feedback regarding 
inspectional observations listed in FDA Form 483 to aid in the preparation of a 
response.
Generally, Informational Meetings, as described in Section III.D of this guidance, are intended 
for a submitter to provide information to FDA without the expectation of feedback from FDA. 
However, when Informational Meeting Q-Subs are used for tracking purposes in situations when 
a formal Q-Sub type for that interaction has not been created, feedback may be provided as 
prescribed by the program for which the Informational Meeting Q-Sub type is being used.
G. Interactions Not Within the Q-Submission Program 
There are several other mechanisms, outside the scope of the Q-Sub Program, through which 
industry may obtain feedback from FDA. Some require or necessitate another type of formal 
submission, while some can be addressed using informal interactions.
Some examples of interactions outside the scope of the Q-Sub Program include, but are not 
limited to, the following:
 Requests for feedback regarding development of a Medical Device Development Tool 
(MDDT), previously tracked as Informational Meeting Q-Submissions, are now tracked 
with a universal tracking number (UTN). Submissions for these requests should be 
identified as an MDDT in the cover letter. Additional information about the MDDT 
program can be found in the FDAs guidance entitled Qualification of Medical Device 
Development Tools).19
18https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-public-human-genetic-variant-
databases-support-clinical-validity-genetic-and-genomic-based-vitro
19https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-medical-device-
development-tools
8 Contains Nonbinding Recommendations
 Administrative questions, or questions about the submission process. These do not need a 
formal submission and may be handled via email or telephone call.
 Teleconferences or emails with FDA staff (e.g., by the lead reviewer or Regulatory 
Project Manager (RPM)20) 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, as described in FDAs guidance entitled Types of 
Communication During the Review of Medical Device Submissions.21
 Requests for appeal meetings made to CDRH, which are described in FDAs guidance 
entitled Center for Devices and Radiological Health (CDRH) Appeals Processes,22 or 
to CBER, which are described in FDA documents entitled Formal Dispute Resolution: 
Sponsor Appeals Above the Division Level23 and CBER SOPP 8005: Formal Dispute 
Resolution Process.24
 Requests for Designation (RFD) or Pre-RFDs, which are submitted to the Office of 
Combination Products (OCP) when the classification of a medical product as a drug, 
device, biological product, or combination product, or the products Center assignment 
(or both), is unclear or in dispute.25 Procedures for these processes can be found in FDAs 
guidances entitled, How to Write a Request for Designation (RFD)26 and How to 
Prepare a Pre-Request for Designation (Pre-RFD).27Such classification and assignment 
information should not be solicited via a 513(g) Request for Information (see below).
 Section 513(g) Requests for Information, which provide a means to obtain information 
regarding the class in which a device has been classified or the requirements applicable to a 
device under the FD&C Act. While the potential regulatory pathway for a device may be 
a topic of discussion in a Pre-Sub interaction, device classification is accomplished in 
20CBER submissions: Whenever the term lead reviewer is used in this guidance, the CBER equivalent, with 
respect to interactions with the submitter, is usually the Regulatory Project Manager (RPM); with respect to internal 
activities, the lead reviewer is usually equivalent to the Chairperson or Scientific Lead.
21https://www.fda.gov/regulatory-information/search-fda-guidance-documents/types-communication-during-
review-medical-device-submissions
22https://www.fda.gov/regulatory-information/search-fda-guidance-documents/center-devices-and-radiological-
health-appeals-processes
23https://www.fda.gov/regulatory-information/search-fda-guidance-documents/formal-dispute-resolution-sponsor-
appeals-above-division-level-guidance-industry-and-review-staff
24https://www.fda.gov/media/108908/download
25Additional information on how combination products are assigned a lead Center for their premarket review and 
their regulation is available on OCPs webpage (https://www.fda.gov/combination-products). See also FDA 
Guidance, Classification of Products as Drugs and Devices and Additional Product Classification Issues 
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/classification-products-drugs-and-
devices-and-additional-product-classification-issues). 
26https://www.fda.gov/regulatory-information/search-fda-guidance-documents/how-write-request-designation-rfd
27https://www.fda.gov/regulatory-information/search-fda-guidance-documents/how-prepare-pre-request-
designation-pre-rfd
9 Contains Nonbinding Recommendations
accordance with section 513 of the FD&C Act. Additional information regarding 513(g) 
Requests for Information, can be found in the guidance entitled, FDA and Industry 
Procedures for Section 513(g) Requests for Information under the Federal Food, Drug, 
and Cosmetic Act.28
 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 (EUAs) or requests for feedback about EUA 
submissions and the EUA process.29 There is a separate pre-EUA process that should be 
utilized for discussions about EUAs, which is distinct from the Pre-Submission process. 
Additional information regarding EUAs and Pre-EUAs can be found in the guidance 
entitled Emergency Use Authorization of Medical Products and Related Authorities.30
 Requests for feedback from FDA outside the Q-Submission process via other resources 
including, but not limited to CDRH Device Advice website,31 CDRHs Division of 
Industry and Consumer Education (DICE),32 or CBERs Manufacturers Assistance and 
Technical Training Branch.33
If submitters are unsure if a request should be submitted under the Q-Sub Program, we 
recommend contacting the review division or OPEQ Submission Support 
(OPEQSubmissionSupport@fda.hhs.gov) to discuss the best pathway for your request.
IV. Q-Submission Program 
Theterm Q-Submission or Q-Sub refers to the system used to track the collection of 
interactions described in Section III.A-F above. These are important opportunities for submitters 
to share information with FDA and receive input outside of the submission of an IDE, IND, 
marketing submission, or CW. Q-Subs can serve as helpful tools in the premarket submission 
process and FDA reviewers are encouraged to work interactively34 with submitters while the Q-
Sub is under review to fully utilize this process. The interactions tracked in the Q-Sub program 
may be used at different points along the total product life cycle for a device and are voluntary. 
For example, in a given products development cycle, a submitter may wish to conduct an 
28https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-procedures-section-
513g-requests-information-under-federal-food-drug-and-cosmetic
29EUAs are submitted when requesting emergency use of certain medical products under sections 564, 564A, and 
564B of the FD&C Act as amended or added by the Pandemic and All-Hazards Preparedness Reauthorization Act of 
2013 (PAHPRA; Public Law 113-5).
30https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-
medical-products-and-related-authorities
31CDRH Device Advice, https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance
32You may contact DICE by email at DICE@fda.hhs.govor by telephone: 1-800-638-2041 or 301-796-7100.
33CBERs Manufacturers Assistance and Technical Training Branch may be contacted by email at 
industry.biologics@fda.gov
34See FDA Guidance Document, Types of Communication During the Review of Medical Device Submissions, 
available athttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/types-communication-
during-review-medical-device-submissions
10 Contains Nonbinding Recommendations
Informational Meeting, followed by a request for Breakthrough Device Designation, with later 
discussions to refine specific aspects of non-clinical and clinical testing through Pre-subs. 
Tracking these interactions as Q-Subs facilitates review and serves to document interactions for 
the record.
However, the number of Q-Subs and Q-Sub supplements submitted should be carefully 
considered to avoid confusion and unnecessary expenditure of both FDA and industry time and 
resources. If you intend to submit more than one Q-Sub to request discussion and/or feedback on 
various topics for the same device, we suggest that your initial Q-Sub contain an overview of 
your expected submissions, including general time frames, if known. When submitting more than 
one Q-Sub for the same product, you should consider the order of the submissions carefully. 
There may be dependencies in the review of the Q-Subs that make it beneficial to submit and 
receive feedback on one Q-Sub before initiating another. The intent is for FDA and the submitter 
to focus on the submitters current priority. Limiting the content and number of topics in a single 
Q-Sub allows FDA to focus on the submitters current priority. Once existing priorities are 
addressed, Q-Sub supplements can be used to discuss additional topics related to the same 
device. Further, significant challenges exist regarding the review of multiple Q-subs on the same 
device simultaneously. For example, during the review of related Q-Subs submitted at the same 
time, it may be evident that feedback provided in one Q-Sub might influence the feedback that 
should be provided in the other Q-Sub, which could make it difficult to provide a thorough 
response. As such, for any given device, we recommend only one Q-Sub be submitted at a time.
A Q-Sub cannot be withdrawn after feedback is provided and the file is closed; however, there is 
no requirement for a follow-on premarket submission (i.e., IDE, PMA, HDE, De Novo request, 
510(k), CW, Dual, Request for Accessory Classification, IND, or BLA).
 
FDA will keep the existence of Q-Subs confidential, subject to the confidentiality provisions of 
the FD&C Act, FDAs Part 20 regulations covering information disclosure, and the Freedom of 
Information Act (FOIA) (5 U.S.C.  552). Additional information about confidentiality of 
meeting information can be found below in Section IV.B(3).
A. General Q-Submission Considerations 
(1) Relating Q-Submissions to Future IDE, IND, CWs, and 
Marketing Submission(s) (Related Submission(s)) 
Many Q-Subs are followed by marketing submissions, IDEs, INDs, CWs, and/or supplementary 
Q-Sub interactions. These follow-on submissions are considered related submissions if they 
are for the same device and indications for use as the original Q-Sub. To help link Q-Subs to 
their subsequent related submissions, the submitter should identify the relevant Q-Subs in the 
cover letter of the subsequent related submission. If the relevant Q-Subs are not identified in the 
cover letter of the subsequent related submission, they will not be linked in FDAs records. 
Therefore, there may be a delay in determining FDAs previous feedback, and the subject device 
may not be incorporated in any future analyses of Q-Sub program effectiveness.  
 
11 Contains Nonbinding Recommendations
In addition, the related submission should include a section that clearly references the previous 
communication(s) with FDA about the subject device (or similar device) and explains how any 
previous feedback has been addressed within the current submission. This discussion of previous 
feedback will streamline FDA review even if the submitter elects to address FDA feedback with 
alternative methods to those discussed during the previous interactions. 
(2) Combination Product Considerations  
Requests for meetings regarding a combination product should be submitted to the lead center 
for the product, in accordance with that centers corresponding processes.Accordingly, Q-
 
Submissions should only be submitted for device-led combination products assigned to CDRH or 
CBER. If the classification or center assignment for a medical product is unclear or in dispute, 
the submitter should submit an RFD or Pre-RFD to OCP35, and then submit their meeting request 
to the center determined to be the lead center. Proactively submitting an RFD often saves the 
submitter time by ensuring that the Q-Sub is sent to the correct FDA Center. If CDRH or CBER 
receives a Q-Sub for a combination product as the lead center for the product, the centers staff 
intends to notify the other center(s) involved in the review of the combination product of its 
receipt and include the appropriate review staff from these other center(s) to ensure that the 
entire combination product review team is aware of the questions from the submitter and 
engaged, as needed, in providing comprehensive and aligned feedback. When Q-Subs for 
combination products are submitted, FDA intends to initiate the same review process for the Q-
Sub as for single-entity devices. Meetings and/or requests for written feedback may take longer 
to schedule and/or to address in writing due to factors such as the increased number of Agency 
staff involved and other regulatory complexities that can be associated with combination 
products. However, FDA intends to meet with the submitter of a combination product within 75 
calendar days36 after receiving such request and intends to provide written feedback by day 70, 
prior to the meeting.37 For products that are combination products, the submitter is responsible 
for identifying it as such in the submission.38 FDA recommends this information be provided in 
the cover letter. Where submitters have determined they would like input from the OCP, they 
may also submit a copy of the cover letter to OCP.39
B. Q-Submission Processes  
The general processes for the Q-Sub program are outlined below, including submission tracking 
and meeting logistics as well as recommended content and timelines for each Q-Sub type. 
35Additional information on how to submit an RFD or Pre-RFD to OCP is available at:
https://www.fda.gov/combination-products/rfd-process
36Unless otherwise specified, in this guidance document, days refers to calendar days.
37See 168 CONG. REC. S5194-S5203 (daily ed. September 28, 2022) (Food and Drug Administration User Fee 
Reauthorization), also available at https://www.fda.gov/media/158308/downloadfor Pre-Sub review performance 
goals.
38See section 503(g)(8)(c)(v)(I) of the FD&C Act.
39The following website contains contact information for OCP: https://www.fda.gov/about-fda/office-special-
medical-programs/office-combination-products
12 Contains Nonbinding Recommendations
(1) Submission Content  
To ensure appropriate log in and to facilitate review of a Q-Sub, the following should be 
included in a Q-Sub Cover Letter. Please be advised that your Q-Sub should be written in the 
English language. 
 Contact Information. Company name, address, and contact person(s) including title(s), 
phone number(s), fax number(s), and email address(es). Note that full contact 
information should be provided for the submitter as well as the correspondent (e.g., 
consultant), if different from the submitter. 
 Q-Sub Type. Indication of which Q-Sub type is being requested. Note that only one Q-
Sub type should be included in each submission.
 Method of Feedback. If a Q-Sub includes an option for the method of feedback, you 
should clearly indicate what type of feedback you are requesting. Pre-Submissions offer 
written feedback only or written feedback followed by a meeting, and SIRs offer either 
written feedback or a meeting. To ensure feedback is provided and meetings are 
scheduled in a timely manner, it is important that this is clearly specified in the 
submission. 
 Meeting Information. If a Q-Sub type includes the option for a meeting (e.g., a Pre-Sub or 
a SIR, and Informational Meeting requests), and a meeting is being requested, you should 
indicate the following to facilitate scheduling:
i. A draft agenda proposing the topics to be presented and the estimated time for 
each agenda item, to the extent possible pending FDA feedback; 
ii. The meeting format you are requesting (see Section IV.B(3)a below);
iii. Three (3) or more preferred dates and times when you are available to meet.
a) While you should propose dates that suit your schedule, please keep in mind 
that FDA needs sufficient time to review the material submitted, hold internal 
discussions if needed, and identify a meeting time when the necessary team 
members are available.
b) If FDA is not able to accommodate your requested dates, you will be offered 
alternative dates within an appropriate timeframe. Refer to the timelines for 
Pre-Subs (see Section IV.B(4)a.2 below), SIRs (see Section IV.B(4)b.2 
below), and Informational Meetings (see Section IV.B(4)d.2 below) when 
considering proposed dates that are likely to be accepted by FDA.
iv. The planned attendees, including each attendees position, or title, and affiliation.  
a)  Ifyou have not yet identified all of your attendees, you should indicate the 
type of subject matter experts you plan to invite (see Section IV.B(3)b below). 
b) FDA recommends that submitters identify in their cover letter any appropriate 
FDA staff that are requested to attend the meeting if specific expertise may be 
needed (e.g., staff from other Centers).
To obtain meaningful feedback from FDA, the following should be easily identified within the 
body of the Q-Sub:
13 Contains Nonbinding Recommendations
 Purpose. The overall purpose of the Q-Sub including goals for the outcome of the 
interaction with FDA.
 Device or Product Description. An explanation of how the device functions, the basic 
scientific concepts that form the basis for the device, and the significant physical and 
performance characteristics of the device. A brief description of the manufacturing 
process should be included if the manufacturing process may affect safety and/or 
effectiveness, and may therefore impact FDAs recommendations regarding device 
testing. The generic name of the device as well as any proprietary name or trade name 
should be included. Images, videos, and more detailed information may be included as 
appropriate in the submission itself. In addition to a description of the general device, it is 
important for FDA to have a clear understanding of the specific parts of the device being 
discussed in the Q-Sub and any device technology relevant to the topic of the Q-Sub.
 Proposed Indications for Use or Intended Use. Including a description of the disease(s) 
or condition(s) the device will diagnose, treat, prevent, cure or mitigate, and a description 
of the patient population for which the device is intended. Depending on the topic being 
discussed in the Q-Sub, this information can impact the feedback provided. Therefore, 
this information is important to include so that FDA can provide accurate feedback.
 Regulatory History. Listing of any relevant previous communications with FDA about 
the subject device including but not limited to any marketing submission, IDE, 513(g), 
and/or Q-Sub application numbers relevant to the subject Q-Sub. The submission should 
also include a brief summary of these previous FDA interactions and submissions (and 
submission number(s)), including feedback received and resolution of that feedback (or 
justification of alternative paths) as applicable.
Use of the CDRH Premarket Review Submission Cover Sheet40 for submissions made to CDRH 
or CBER is highly recommended to facilitate correct login and prompt routing to the appropriate 
review group.
You must submit an eCopy of your Q-Sub under section 745(A)(b) of the FD&C Act. For more 
information on eCopy and the submission process, refer tohttps://www.fda.gov/medical-
devices/how-study-and-market-your-device/ecopy-program-medical-device-submissions, 
including the guidance entitled eCopy Program for Medical Device Submissions.41
If you are submitting to CDRH, we recommend eCopy submission packages be submitted 
electronically via the CDRH Customer Collaboration Portal (CDRH Portal) as discussed in the 
following website: 
https://www.fda.gov/medical-devices/industry-medical-devices/send-and-track-medical-device-
premarket-submissions-online-cdrh-portal. Once submitted via the CDRH Portal, the Q-Sub will 
40See Form 3514,https://www.fda.gov/media/72421/download
41https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-device-
submissions
14 Contains Nonbinding Recommendations
be received by the CDRH Document Control Center (DCC). Alternatively, submission packages 
may be mailed to the CDRH DCC. The current mailing address for CDRHs DCC is provided on 
the eCopy Program for Medical Device Submissions webpage at https://www.fda.gov/medical-
devices/how-study-and-market-your-device/ecopy-program-medical-device-submissions.
For products regulated by CBER, we recommend that submission packages be submitted 
electronically through the FDA Electronic Submission Gateway. Alternatively, they can be 
submitted through the CBER submission email inbox (150MB max) at 
CBERDCC_eMailSub@fda.hhs.gov, or via mail to the CBER DCC. Additional information on 
the FDA Electronic Submission Gateway and the current mailing address for the CBER DCC 
can be found at the following website: https://www.fda.gov/about-fda/about-center-biologics-
evaluation-and-research-cber/regulatory-submissions-electronic-and-paper.
The FDA review clock starts when a valid eCopy is received; however, for Q-Subs that utilize an 
acceptance review, if a file is placed on hold, the review clock will begin upon receipt of the 
amendment that is accepted for review. 
(2) FDA Submission Tracking 
FDAassigns a unique identification number to all Q-Subs as described below.  
 
  Original. An original Q-Sub is the first Q-Sub submitted to FDA to discuss a given 
device and its indications for use, a set of one or more devices/products intended to be 
used or marketed together, or a device platform upon which multiple devices will be 
built.  
 
Original Q-subs submitted to CDRH will be 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 calendar year. For example, the first original 
Q-Sub received by CDRH in January of 2018 will be identified as Q180001. FDA will 
send an acknowledgement letter via e-mail to the contact identified in the Q-Sub cover 
letter that contains the unique tracking number and date received by the DCC. Any future 
communications regarding your Q-Sub should include this unique Q-Sub identifier.
Because of organizational differences between CBER and CDRH, the process described 
in the preceding paragraph is not applicable to submissions sent to CBER. Q-Subs 
submitted to CBER will instead be assigned a number starting with BQ. After the 
CBER DCC processes your Device Q-Sub, it will be forwarded to the appropriate 
Product Office for additional processing and review. You will be contacted by the RPM 
who will provide you with a BQ number and who will be your contact for all additional 
communications.
 Supplement. A Q-Sub supplement is any new request for feedback and/or a meeting about 
the same device with the same or similar indications for use as an original Q-Sub that 
already exists. For example, it may be appropriate to initially request an Informational 
Meeting to familiarize the review team with the new device design, then submit a Pre-
15 Contains Nonbinding Recommendations
Sub to request feedback on non-clinical testing, then later submit a Study Risk 
Determination Q-Sub for the pivotal clinical study, all for the same device with the same 
indications for use. The first Informational Meeting in this example would be the original 
Q-Sub, while the Pre-Sub and Study Risk Determination Q-Sub would be tracked as 
supplements to that original Q-Sub. 
At CDRH, each supplement is tracked by appending /S after the original followed by a 
three-digit sequential number, e.g., the first supplement to Q180001 will be identified as 
Q180001/S001. At CBER, S is not used, only the slash (/) is added.
 Amendment. A Q-Sub amendment is any additional information relevant to the original 
Q-Sub or Q-Sub supplement that does not represent a new request for feedback and/or 
meeting. This additional information could include presentation slides, meeting minutes, 
minor clarifications, or requests to change contact information.  
 
If you need to change contact information, such as submitter organization or 
correspondent (e.g., consultant) organization, you should submit a Q-Sub amendment to 
your original clearly stating the change. Note that if you need to change the submitter, the 
Q-Sub submitter of record (the submitter recorded in our system) should provide a letter 
authorizing the change in submitter. If you do not need to change the submitter, but want 
to change the correspondent, there are two possible scenarios: 1) changing the 
correspondent organization and 2) changing just the correspondent contact person. If the 
submitter wants to change the correspondent organization, such as adding or removing 
the use of a consultant, then the submitter should submit the change stating the new 
correspondent organization and providing the name, email address, and phone number of 
the new primary contact in that organization. If you would like to use a different 
correspondent contact person for a given supplement, you do not have to submit an 
amendment; you can indicate the appropriate correspondent contact person when you 
submit that supplement.
At CDRH, each amendment is tracked by appending /A after the original or 
supplement to which it applies. For example, the first amendment to Q180001 will be 
identified as Q180001/A001, while the first amendment to Q180001/S001 will be 
identified as Q180001/S001/A001. At CBER, A is not used, only the slash (/) is 
added.
(3) Meeting Information  
Meetings allow for an open discussion and exchange of technical, scientific, and regulatory 
information that can help build a common understanding of FDAs views on clinical, non-
clinical, or analytical studies related to an IDE, or marketing submission. During a Q-Sub 
meeting, FDA will be prepared to discuss the contents of the Q-Sub as well as the written 
feedback the Agency provided for that Q-Sub (if applicable). Submitters should not expect FDA 
to comment on new information provided by the submitter between receiving FDA written 
feedback and holding the meeting or during the meeting, as there is insufficient time for FDA to 
thoroughly review the information. If a submitter would like feedback on new information, such 
16 Contains Nonbinding Recommendations
a request should be submitted as a supplement to the Q-Sub to allow adequate time for review, 
written feedback, and discussion of the new material, as appropriate. Submitters should provide 
draft slides to FDA electronically (e.g., in Microsoft PowerPoint or PDF) at least two (2) days before 
the meeting. This will allow adequate time to distribute the presentation to all participating FDA 
staff.
Submitters that request a meeting should be aware that all meetings are subject to disclosure 
review pursuant to the Freedom of Information Act (FOIA). Meeting minutes and materials, like 
all Agency records, may be the subject of a FOIA request and unless the information being 
requested is classified as commercially confidential or trade secret, it will be released to 
requesters.
a. Meeting Format  
If desired, FDA is available to meet to discuss our feedback. It is typically most efficient to meet 
virtually (i.e., videoconference or teleconference), as these meetings are easier to schedule in a 
timely fashion. Upon request, in-person meetings may be available, and we recommend that the 
submitter contact the lead reviewer if there is interest in having such a meeting. For an in-person 
meeting, you should inform the lead reviewer or meeting coordinator of any audiovisual 
equipment you will need, such as conference phone or LCD projector or similar. The meeting 
coordinator or lead reviewer will reserve the room and arrange for any audiovisual equipment 
you may have requested. Please note visitors are not allowed access to any FDA/HHS 
information technology systems. This includes attaching USB cables, flash drives and any 
network-connected FDA/HHS equipment. If internet access is needed for the meeting, visitors 
must make this request at least five (5) days prior to the meeting.
Meetings will normally be limited to one (1) hour. In our experience, this is the optimal amount 
of time for discussing selected Q-Sub topics. If more than an hour is needed, the scope of the Q-
Sub may be too large, and we recommend you consider limiting the scope of the submission to 
allow a more focused discussion that may yield more useful feedback. In rare cases, if you 
believe that more than an hour may be needed, you should provide a rationale for the duration 
you propose. You should also refer to that rationale and confirm the duration requested when the 
meeting coordinator or lead reviewer schedules your meeting.
b. Meeting Attendees 
FDAwill always attempt to ensure the appropriate FDA staff is present at your meeting. 
Generally, our attendees will include members of the FDA review team (including consultants 
from other Offices or other Centers), and the first line manager. As appropriate, other members 
of management and program staff may also attend. You can help to ensure that appropriate FDA 
staff is present by suggesting that certain types of experts attend, depending upon the specific 
questions or issues that you wish to address. For example, if statistical issues are included in your 
focused questions, it is appropriate to suggest that our statistician attend. 
 
All non-U.S. citizens attending a meeting in an FDA facility are subject to additional security 
screening. You should inform the meeting coordinator or lead reviewer prior to the meeting date 
17 Contains Nonbinding Recommendations
and work with them to ensure the appropriate information is available and provided. It generally 
takes about two weeks to process requests for foreign visitors.
You are invited and encouraged to include any additional outside individuals (e.g., Centers for 
Medicare & Medicaid Services (CMS), private payers, NIH grant reviewers) in your Q-Sub 
meetings, as appropriate. Including additional representatives may be helpful in maintaining 
transparency, efficiencies, and consistency among the various stakeholders for your device. You 
are responsible for any additional attendees that you wish to invite and defining their roles and/or 
participation during the meeting. For submissions to CDRH, the Payor Communications Task 
Force may be able to assist with engaging payers. Additional information is on the Task Forces 
website.42 However, you are responsible for coordinating the appropriate invitations and 
scheduling for other external stakeholders or for interactions with payers on Q-Subs reviewed in 
CBER.
c.  Meeting Minutes
The submitter is responsible for drafting meeting minutes for all Q-Sub meetings and submitting 
them to FDA as an amendment to the Q-Sub within 15 days of the meeting.43 The meeting 
minutes should be an accurate reflection of the meeting discussion. Rather than being a transcript 
of the meeting, the minutes should summarize the meeting discussion, document how substantial 
or complex issues were resolved, and include agreements and any action items. It should not 
assign statements to individuals, but to the submitter or FDA generally. Additional information 
or follow-up items that were not part of the meeting discussion should not be included in the 
meeting minutes. We have included an example format of meeting minutes in Appendix 3
for your reference.
The submitter should have a member of their team assigned to take meeting minutes, to be 
provided for FDA review following the meeting. At the beginning and end of the meeting, the 
submitter will affirmatively state that they will draft minutes and provide them to FDA within 15 
days. Industry attendees are not permitted to record the meeting by audio or video means. CDRH 
and CBER policy is not to allow outside parties to record (by audio or video) meetings with staff 
in order to prevent interference with the free exchange of information. In accordance with 21 
CFR Sec. 10.65(e), which addresses the issue of recording general meetings with outside parties, 
the authority to record meetings resides with the agency staff, not the outside party.
The draft meeting minutes should be submitted to FDA as an amendment to the Q-Sub within 15 
days of the meeting. Just as with the original Q-Submission package, meeting minutes can be 
submitted through the appropriate DCC (via mail or electronically, as specified in Section 
IV.B(1) above). If slides were presented, the actual version used in the meeting should be 
included with the draft minutes in the amendment. Submission of the meeting minutes as a 
formal amendment is intended to ensure appropriate tracking of the meeting minutes and 
documentation in the official record. In addition to the official meeting minutes submitted to the
42https://www.fda.gov/about-fda/cdrh-innovation/payor-communication-task-force
43See 168 CONG. REC. S5194-S5203 (daily ed. September 28, 2022) (Food and Drug Administration User Fee 
Reauthorization), also available at https://www.fda.gov/media/158308/download
18 Contains Nonbinding Recommendations
DCC, the submitter is encouraged to submit an identical version of the meeting minutes in a 
format that facilitates editing and commenting (e.g., Microsoft Word) under the miscellaneous 
files section of the eCopy package (see FDA Guidance Document eCopy Program for Medical 
Device Submissions,44 Attachment D.2).
If FDA does not have any edits to the draft minutes, the minutes will be considered final and 
FDA will communicate our acceptance of the minutes via email. If FDA does edit your draft 
minutes, FDA intends to email the revised version of the minutes to you within 30 days. These 
edits may include post meeting notes to follow up on action items identified and agreed upon 
during the meeting. Minutes edited by FDA will become final 15 days after you receive FDAs 
edits, unless you indicate to FDA that there is a disagreement with how a significant issue or 
action item has been documented. If such a disagreement exists, you should submit an 
amendment to the Q-Sub through the appropriate DCC (via mail or electronically, as specified in 
Section IV.B(1) above), labeled as a meeting minutes disagreement. In the case of a 
disagreement, we will set up a mutually agreeable time for a teleconference to discuss that issue, 
in a timely manner. At the conclusion of that teleconference, within 15 days, FDA will finalize 
the minutes either to reflect the resolution of the issue or note that this issue remains a point of 
disagreement. This version will be considered the official meeting minutes. The teleconference is 
intended to address disagreements about the content of the minutes; it is not intended to address 
differences of opinion with respect to the regulatory or scientific advice provided to the 
submitter. Any differences of opinion regarding regulatory or scientific advice can be addressed 
by submitting an additional Q-Sub supplement if both the submitter and FDA believe that further 
discourse on such an issue would be productive.
(4) Processes by Q-Submission Types 
Each Q-Sub type has a different review process including timeline and recommended content, 
which are detailed below. The Q-Sub types and corresponding feedback mechanisms and 
timelines are summarized in Table 1. For Q-Sub types outside the scope of this guidance, please 
find this information in their corresponding guidance documents.
44https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-device-
submissions
19 Contains Nonbinding Recommendations
Table 1  Q-Sub types and corresponding feedback mechanisms and timelines
Timeframe for Sending Feedback 
Q-Sub Type Method of Feedback or Scheduling Meeting 
(from receipt of submission)
Written Feedback: 
70 days or 5 days prior to 
scheduled meeting, whichever is 
Meeting with written 
sooner
feedback provided in advance 
Pre-Submission
Meeting: 
Date based on mutual agreement 
(typically day 70-75)
Written Feedback Only  70 days
If SIR is received within 60 days of 
FDAs marketing submission letter: 
21 days as resources permit 
Submission Issue Request 
Meeting or Written Feedback
If SIR is received more than 60 
(SIR)
days after FDAs 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. 
a. Pre-Submission  
1) Additional Recommended Submission Contents
In addition to the general information that should be included in any Q-Sub type to ensure 
appropriate login and submission tracking (see Section IV.B(1)), the following information 
should be included in a Pre-Sub:
 Planned Follow-On Submission. We recommend that you clearly indicate what type of 
future submission (IDE, IND, CW, Accessory Classification Request, or marketing 
submission) is the focus of your Pre-Sub questions to help direct FDAs feedback.
 Background Information. We recommend that you include sufficient background 
information and supporting documents to allow FDA to develop feedback for the Pre-Sub 
questions you pose. This information might include literature articles, full device 
description with engineering drawings, proposed labeling, videos, and/or red-lined 
protocol revisions depending on the specific questions for which you are requesting 
20 Contains Nonbinding Recommendations
feedback. It may also be helpful to include how you addressed, or plan to address, 
relevant guidance documents, regulations, special controls, or other applicable sources 
for your device or submission type.
While the importance of a complete background package cannot be overstated, it should 
also be noted that submission of extraneous information can be counterproductive. We 
recommend that you keep your submission targeted and focused. If significant 
background information is needed to provide appropriate context, it is helpful if you 
clearly indicate which background information is relevant to the specific questions or 
topics you want to discuss. 
 Specific Questions. A Pre-Sub should include clear, specific questions regarding review 
issues relevant to a planned IDE, IND, CW, Accessory Classification Request, or 
marketing submission (e.g., questions regarding non-clinical and clinical testing protocols 
or data needed to support the submission) to allow FDA and the submitter to focus their 
efforts on issues most relevant to moving a project forward. You may wish to describe 
your perspective on the questions you provide FDA to inform FDAs review.  
 
We recommend carefully considering the number of topics and the extent of feedback 
requested in a single Pre-Sub to ensure that FDA has sufficient time to provide an in-
depth response to each question, and to enable focused meetings. In general, FDA has 
found it difficult to address more than 3-4 substantial topics in a single Pre-Sub. A 
substantial topic involves a focused area of expertise. Examples of substantial topics 
include, but are not limited to, pre-clinical/bench testing, biocompatibility, an animal 
study, a PCCP, software, sterilization, clinical study endpoints, and statistical analysis 
plan. Therefore, we recommend that you identify 3-4 substantial topics as this facilitates 
more productive meetings and results in more effective conversations and feedback. 
Additional straightforward questions (e.g., administrative topics) may be appropriate if 
they can be addressed without in-depth review and do not introduce new significant 
topics. If an excessive number of topics are included in your submission, FDA may 
contact you to discuss which topics you would like to prioritize. In some cases, FDA may 
suggest discussing the lower priority topics in subsequent Pre-Subs. 
Additional guidance regarding common types of questions submitted in Pre-Subs is 
provided below:
o Study Protocols 
Resource constraints do not permit FDA to prepare or design particular study 
plans. If a submitter would like FDAs feedback on a protocol, they should submit 
a proposed outline, with a rationale for the chosen approach.  
 
For more productive feedback, we recommend that the submitter include specific 
questions about their protocol. Without directed questions, FDAs feedback may 
be more general in nature and not provide adequate specifics on the area of 
interest.
21 Contains Nonbinding Recommendations
If the Pre-Sub is for a nonsignificant risk device study, IDE exempt device, CW, 
Dual, or a study you plan to conduct outside the US (OUS) to support a marketing 
submission, the submitter should consider submitting the entire protocol through 
the Pre-Sub process prior to initiating the study, particularly if it raises unique 
scientific or regulatory considerations.
o Review of Data 
Requests for a pre-review of data are not appropriate for the Pre-Sub program. 
However, if the data and conclusions are difficult to interpret, it may be 
appropriate to ask a specific question regarding the interpretation of preliminary 
results or the planned approach for addressing the results within the upcoming 
submission. 
 
o Regulatory Approach 
Under the Pre-Sub program, FDA is able to provide feedback regarding 
regulatory strategy and approach. For example, whether a cleared 510(k) device 
or granted De Novo has the potential to serve as a predicate for a proposed device 
and indications for use. A formal written request for classification of a device and 
indications for use requires a 513(g) Request for Information.45 See Section III.G 
of this guidance for information on how to clarify whether a medical product is 
considered a device, drug, biologic, or combination product and/or Center 
assignment for medical products. 
 
Additional examples of questions that lead to productive Pre-Sub interactions are 
provided in Appendix 2of this guidance.
2) Review Process
The review process for a Pre-Sub, including timelines outlined in the MDUFA V Commitment 
Letter, are described below. 
 Acceptance Review. Within 15 days of the review clock starting, FDA staff will conduct 
an acceptance review using the Acceptance Checklist (see Appendix 1  Pre-
Submission (Pre-Sub) Acceptance Checklist). When completed, the submitter will 
receive notification regarding whether or not the submission has been accepted for review 
as well as the contact information for the lead reviewer or the RPM. If a Pre-Sub 
requesting a meeting is accepted, this notification will also either confirm the submitters 
requested meeting date or provide two alternative meeting dates that are scheduled prior 
to day 75.  
If the acceptance review determines that the request does not qualify as a Pre-Submission 
or the submission is not complete, FDA staff will obtain concurrence from management 
of the decision to Refuse to Accept (RTA), and the submitter will receive notification of 
45See FDA guidance document FDA and Industry Procedures for Section 513(g) Requests for Information under 
the Federal Food, Drug, and Cosmetic Act at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/fda-and-industry-procedures-section-513g-requests-information-under-federal-food-drug-and-cosmetic
22 Contains Nonbinding Recommendations
this decision with the reasons for refusal. The submitter may respond to an RTA 
notification by submitting additional information to the DCC (via mail or electronically, 
as specified in Section IV.B(1) above), which will be logged in as an amendment to the 
Q-Sub. Upon receipt of the newly submitted information, the review clock will restart at 
day 0, and FDA staff will conduct the acceptance review again, following the same 
procedure, within the first 15 days of the restarted review clock. The subsequent 
acceptance review will assess whether the new information makes the submission 
complete according to the Acceptance Checklist. 
 Scheduling of Meeting. FDA will attempt to schedule a meeting on one of the submitters 
requested meeting dates, if feasible. Meeting dates between 70-75 days following FDA 
receipt of your submission are most likely to be feasible. If FDA cannot accommodate 
one of the submitters requested dates, FDA will offer at least two alternative dates that 
are prior to 75 days from the receipt date of an accepted submission. FDA intends to 
reach agreement with the submitter regarding a meeting date within 30 days from receipt 
of an accepted submission. For all requests for meetings that do not have an agreed upon 
meeting date scheduled by 30 days from receipt of an accepted submission, an FDA 
manager will contact the submitter to resolve scheduling issues by the 40th day. 
 Feedback. Written feedback will be provided to the submitter by email and will include: 
written responses to the submitter questions; FDAs suggestions for additional topics for 
the meeting, if applicable; or, a combination of both. FDA intends to follow the timeline 
below for providing feedback to a Pre-Sub.
o Pre-Sub Written Feedback: If no meeting is requested, written feedback will be 
provided within 70 calendar days of receipt of the accepted submission and will serve 
as the official record of the Agencys feedback.
o Pre-Sub Meeting: If a meeting is requested, written feedback will be provided at least 
5 days prior to the scheduled meeting, and no later than 70 days from receipt of the 
accepted Pre-Sub. If all the submitters questions are addressed to the submitters 
satisfaction, the submitter may cancel the meeting and the written response will serve 
as the official record of the Agencys feedback. If a meeting is held, the meeting 
minutes Meeting Minutesalong with the written feedback will constitute the official 
record of the Agencys feedback. The process of the meeting minutes and timeline are 
described in Section IV.B(3)c of this guidance.
FDA should not be expected to review and respond to additional information prepared by 
the submitter and provided to FDA between receiving FDA written feedback and holding 
the meeting or during the meeting, as FDA does not have sufficient time to conduct a 
thorough review of this information. Any information that necessitates additional FDA 
review should be submitted as a supplement to the Pre-Sub or in the eventual premarket 
submission. It is, however, appropriate to narrow your agenda to focus on specific 
questions or topics in the feedback.
23 Contains Nonbinding Recommendations
FDA feedback represents our best advice based on the information provided in the Pre-
Sub and other information known at that point in time. FDA intends that feedback the 
Agency provides in response to a Pre-Sub will not change, provided that the information 
submitted in a future IDE, IND, or marketing submission is consistent with that provided 
in the Pre-Sub, and that new information in the future submission, changes in the science, 
or changes in the standards of care do not raise any important new issues materially 
affecting safety or effectiveness. Modifications to FDAs feedback will be limited to 
situations in which FDA concludes that the feedback given previously does not 
adequately address important new issues that have emerged since the time of the Pre-Sub, 
and that are materially relevant to a determination of a reasonable assurance of safety 
and/or effectiveness, substantial equivalence, or other relevant regulatory decision. For 
example, FDA may modify our previous feedback if new scientific findings emerge that 
indicate there is a new risk or an increased frequency of a known risk that affects our 
prior advice; or if there is a new public health concern that affects our prior advice. In 
addition, FDA may modify feedback if the submitter makes significant changes to the 
intended use of the device, device technology, or labeling, or provides new information 
about the device that alters the safety and/or effectiveness. In such cases, FDA will 
acknowledge a change in our advice, will document clearly the rationale for the change, 
and the determination will be supported by the appropriate management concurrence, 
consistent with applicable SOPs.46 Further, FDA intends to work with the submitter to 
address any new issues raised by the change, taking into consideration the stage of device 
development, where possible.
Because clinical practice, testing methods, and medical device technology are constantly 
evolving, we recommend that if more than one (1) year has passed since previous FDA 
feedback was received (via Q-Sub or other formal feedback methods) on significant study 
design topics, and the study has not been initiated, submitters should contact the review 
division to confirm that our previous advice is still valid. This can be accomplished 
through a phone call or email to the lead reviewer or RPM; a new Pre-Sub may not be 
needed for this discussion.
b. Submission Issue Request (SIR) 
1) Additional Recommended Submission Contents
In addition to the general information that should be included in any Q-Sub type to ensure 
appropriate login and submission tracking (see Section IV.B(1)), the following information 
should be included in a SIR:
 Specific Questions. A SIR should include clear, specific questions regarding review 
issues relevant to the planned response to the pending marketing submission hold letter 
(e.g., questions regarding non-clinical and clinical testing protocols or data needed to 
support the submission), IND Clinical Hold, or IDE letter, including identification of the 
46The CDRH SOP: Decision Authority for Additional or Changed Data Needs for Premarket Submissions should be 
followed: https://www.fda.gov/about-fda/cdrh-reports/sop-decision-authority-additional-or-changed-data-needs-
premarket-submissions
24 Contains Nonbinding Recommendations
deficiencies to be discussed, in order to focus FDA and submitter efforts on issues most 
relevant to moving a project forward.
If a submitter would like feedback on plans for collection of new data to address a review 
issue, the submitter should propose a protocol with a rationale for the chosen approach. 
Please note that resource constraints do not permit FDA to prepare or design studies. In 
addition, requests for a pre-review of data are not appropriate for a SIR. However, if data 
and conclusions are difficult to interpret, it may be appropriate to ask a specific question 
regarding the interpretation of preliminary results or the planned approach for addressing 
the results within the upcoming submission.
 Preferred Feedback Format. In the cover letter, the submitter should specify their 
preferred mechanism for obtaining FDA feedback: either written feedback or a meeting 
(not both). If a submitter chooses a SIR meeting, written feedback will not be provided. 
The meeting minutes will serve as the record of the discussion and are the responsibility 
of the submitter (see Section IV.B(3)c). 
 
2) Review Process 
 
 Acceptance Review. There is no Acceptance review for a SIR. 
 Feedback. Feedback will be provided either in the form of a written response, or a 
meeting. In the spirit of the MDUFA Shared Outcome goals for Total Time to Decision 
on most marketing submissions, FDA is committed to resolving review issues promptly 
and will place added emphasis when Industry similarly works expeditiously to address 
such issues.47 Accordingly, FDA intends to prioritize review of SIRs submitted within 60 
days of the marketing submission hold, IND Clinical Hold, or IDE letter. This allows 
FDA to leverage the familiarity with a recent review without the need to re-review the 
issues. This also incentivizes prompt resolution of issues by both FDA and Industry in 
order to achieve the MDUFA Shared Outcome goals for Total Time to Decision. FDA 
intends to provide feedback (either via written feedback or through a meeting, at the 
request of the submitter) according to the timelines below, to the extent resources permit. 
o Submission Issue Request A: If a Submission Issue Request is received within 60 
days of FDAs marketing submission hold, IND Clinical Hold letter, or IDE letter, the 
FDA team will aim to provide feedback within 21 days, as resources permit.
o Submission Issue Request B: If a Submission Issue Request is submitted more than 
60 days after FDAs letter, FDA will aim to provide feedback within 70 days, as 
resources permit. 
If a meeting is held to provide feedback, the submitter is responsible for providing 
meeting minutes as described in Section IV.B(3)c of this guidance. 
47See 168 CONG. REC. S5194-S5203 (daily ed. September 28, 2022) (Food and Drug Administration User Fee 
Reauthorization), also available at https://www.fda.gov/media/158308/download
25 Contains Nonbinding Recommendations
c. Study Risk Determination Requests 
1) Additional Recommended Submission Contents 
In addition to the general information that should be included in a cover letter for any Q-Sub 
type to ensure appropriate login and submission tracking (see Section IV.B(1)), a Study Risk 
Determination Request should include the protocol for the proposed clinical study.
2) Review Process
 Acceptance Review. There is no Acceptance review for a Study Risk Determination 
request. 
 Determination. Once a determination is made, FDA will issue a letter to the submitter 
indicating whether the study is exempt, or, if not exempt, is considered Significant Risk 
(SR) or Not Significant Risk (NSR). You may copy the letter to submit it to IRB(s) with 
the protocol. Once FDA has made a determination, the IRB does not need to conduct an 
independent assessment of risk; FDAs determination is final.
d. Informational Meeting 
1) Additional Recommended Submission Contents
There is no specific additional information recommended for Informational Meeting requests 
beyond the general information that should be included in a cover letter for any Q-Sub type to 
ensure appropriate login and submission tracking (see Section IV.B(1)). As Informational Meeting 
requests may be used for multiple purposes (see Section III), submitters should consider any 
additional information relevant to the goals of their submission.
2) Review Process
 Acceptance Review. There is no Acceptance review for an Informational Meeting. 
 Meeting. FDA aims to hold an Informational Meeting within 90 days of receiving the 
submission, as resources permit. 
(5)  Other Q-Sub Types or Uses of the Q-Sub Program
Please refer to the respective program resources for any additional submission contents and 
timeline information relevant to PMA Day 100 Meetings,48 Agreement and Determination 
Meetings,49 Breakthrough Device submissions,50 Accessory Classification Requests,51 STeP 
48https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-pma-interactive-
procedures-day-100-meetings-and-subsequent-deficiencies-use-cdrh-and
49https://www.fda.gov/regulatory-information/search-fda-guidance-documents/early-collaboration-meetings-under-
fda-modernization-act-fdama-final-guidance-industry-and-cdrh
50See section 515B(c) of the FD&C Act and https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/breakthrough-devices-program
51https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-device-accessories-
describing-accessories-and-classification-pathways
26 Contains Nonbinding Recommendations
submissions,52 requests for recognition of publicly accessible genetic variant databases,53 and 
CPAMs.54
FDA intends to describe policy and procedural information regarding any Q-Sub types that may 
be created in the future through appropriate mechanisms so that timelines and submission 
expectations are known.
V. Paperwork Reduction Act of 1995 
This guidance contains information collection provisions that are subject to review by the Office 
of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 
3501-3520).
The time required to complete this information collection is estimated that an average of 137 
hours is required to prepare a Pre-Submission. Send comments regarding this burden estimate or 
suggestions for reducing this burden to:
FDA PRA Staff,
Office of Operations,
Food and Drug Administration,
PRAStaff@fda.hhs.gov
An agency may not conduct or sponsor, and a person is not required to respond to, a 
collection of information unless it displays a currently valid OMB control number. 
The OMB control number for this information collection is 0910-0756 (To find the 
current expiration date, search for this OMB control number available at 
https://www.reginfo.gov).
52https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safer-technologies-program-medical-
devices
53https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-public-human-genetic-variant-
databases-support-clinical-validity-genetic-and-genomic-based-vitro
54Defined under section 503(g)(2)(A) of the FD&C Act.
27 Contains Nonbinding Recommendations
Appendix 1  Pre-Submission (Pre-Sub) Acceptance Checklist
Reviewer or RPM: 
Office/Division/Branch: 
Q-Number:
Device Name: 
Submitter Name:
RTA Recommendation:
Date of RTA Recommendation:
Yes No
1 Has the submitter provided a specific purpose or goal for their Pre-Sub? o o
2 Has the submitter described the device(s) or other product(s) to be discussed in their Pre- o o
Sub?
3 Has the submitter provided specific questions that request FDA feedback? o o
4 Does the submission indicate that the submitter intends to submit a future IDE, CLIA  o o
Waiver by Application, IND, or marketing submission related to the feedback being 
requested? 
No for question 1, 2, 3, or 4 a Recommend Refuse to Accept Pre-Submission (RTA1) or consider 
conversion to appropriate Q-Sub type
Yes for questions 1, 2, 3, and 4a Continue to questions 5 and 6 
Yes No
5 Do the provided questions pertain to a file under active review? o o
6 Do the provided questions relate to a marketing submission or CLIA hold letter,55 an IND  o o
Clinical Hold letter, or an IDE letter? 
No for questions 5 and 6a Recommend Accept (RTAA) 
Yes for question 5 a RTA1 and resolve during interactive review of the open file
Yes for question 6 a Convert to Submission Issue Request (SIR)
55FDA considers the following to be marketing submission hold letters or CLIA hold letters:
- Additional Information Needed for 510(k)s, De Novo requests, CLIA Waivers by Application, and Dual 510(k) and CLIA 
Waiver by Application Submissions 
- Major Deficiencies, Not Approvable, Approvable with Deficiencies, Approvable Pending GMP, and Approval with PAS 
conditions for PMAs and HDEs 
- Complete Response Letter for BLAs 
 
- Note that final decisions, such as Not Substantially Equivalent, Withdrawals, and Deletions are not considered marketing 
submission hold letters. 
28 Contains Nonbinding Recommendations
Appendix 2  Example Pre-Sub Questions
A Pre-Sub should contain clear, specific questions regarding review issues relevant to a planned IDE, CW, 
IND, or marketing submission in order to focus FDA and submitter efforts on issues most relevant to 
moving a project forward.
In FDAs experience, questions that lead to productive Pre-Sub interactions request specific feedback on a 
limited number of focused topics.
For example, questions leading to the most valuable feedback generally:
 Request specific feedback on a provided proposal (e.g., an animal model is proposed, including 
rationale, and FDA feedback is requested on the acceptability of the animal model)
 Have considered and include references to applicable guidance documents, standards and previous 
discussions with FDA (e.g., chemical characterization testing is proposed with citations to relevant 
biocompatibility guidance document and standards as well as feedback FDA provided in previous 
Pre-Sub interactions)
 Clearly articulate a desired outcome including indications for use or labeled uses (e.g., FDA 
feedback is requested on clinical study endpoints, inclusion criteria, and follow up duration, given 
that the study is intended to expand the currently approved indications for use from prescription use 
only to over-the-counter use, or to support statements in labeling related to device performance)
 Are in submissions that are timed to inform future device development and submission preparation 
(e.g., prior to conducting fatigue testing, a submitter requests feedback regarding proposed pre-
conditioning procedures) 
Questions that ask the review division about the final outcome of an IDE, IND, CW or marketing 
submission, or ask open-ended questions about a study design of a study are, in general, not recommended 
in a Q-Sub. For example, 
 Questions about final outcome such as, Will an IDE that includes results from the proposed testing 
be approved? or Will this proposal support a determination of substantial equivalence?
 Questions requesting FDA to design a study or indicate how a submitter should proceed with their 
clinical study; that is, a question should not ask What should my clinical study design be? or open-
ended questions such as, Does FDA have any other feedback on my clinical study?
 A question should not request a formal regulatory determination such as, Is my device a Class II 
medical device to be regulated under CFR 892.2050? or Can FDA confirm my device is eligible 
for a 510(k) or De Novo?
 In general, a question should not provide data unless necessary as supportive context for a specific 
proposal; that is, a question might provide limited bench, animal or clinical study data, but only to 
provide FDA with the needed information to develop feedback in response to a specific proposal 
(e.g., one page of preliminary feasibility clinical study results are provided when FDA feedback is 
requested for proposed pivotal study endpoints)
The following are examples of questions, provided by review topic category, expected to lead to productive 
Pre-Sub interactions. 
29 Contains Nonbinding Recommendations
Regulatory Strategy Questions
 Is the proposed predicate device appropriate if we demonstrate substantial equivalence?
 We would like to obtain FDA's feedback and guidance on pursuing a De Novo request. We are not 
aware of any predicate devices with this indication with similar technology, but we think our product 
is moderate to low risk and therefore a De Novo would be appropriate. Is FDA aware of any 
additional predicate devices that we should consider? Is FDA aware of any technological concerns 
that we should consider in our risk assessment?
 Based on the regulatory strategy and discussion of pre-clinical testing provided, does FDA concur 
that clinical data is likely not needed to support a future 510(k)?
Indications for Use/Intended Use Questions
 Does FDA have any concerns with our proposal to label the described device as over-the-counter?
 Is the proposed definition of drug-resistant hypertension provided in the draft indications for use 
statement acceptable?
 Is the proposed size range offered for the new device, based on the intended use, appropriate?
Clinical Study Questions
 Is the proposed OUS study adequate to support a future HDE for our device?
 Are the revised clinical study designs, statistical analysis and acceptance criteria included in this 
Pre-Sub supplement adequate to address FDAs concerns?
 Are the primary and secondary endpoint analyses appropriate for the proposed Indications for Use? 
Labeling Questions
 Is the proposed test plan in support of MR Conditional labeling for 1.5T scanners with an exclusion 
zone between the neck and groin acceptable (i.e., does the test plan meet the recommendations of 
FDA guidance)?
 We intend to label our device for re-use if the attached cleaning instructions are followed. The test 
plan to support this label is provided in Attachment B. Does this plan meet the current 
recommendations per FDA guidance for the reprocessing of medical devices?
Reprocessing, Sterilization & Shelf Life Questions
 Are the methods described in the Microbiology protocol "Micro-biology Study Protocol" included in 
Appendix 3 sufficient to ensure the sterility of our device?
 Appendix 2 includes an outline of our proposed approach to provide accelerated aging tests 
conducted to represent 1 year shelf life. Is this approach sufficient for initiation of our planned IDE?
 To address FDA's deficiency regarding our sterilization validation, we propose using Small Lot 
Release in accordance with Annex E of ISO 11135-2014. Does FDA have objections?
 Is our recommendation to low level disinfect the cannula device between uses acceptable per the 
recommendations of FDA guidance on the reprocessing of medical devices?
Non-clinical Bench Performance Testing Questions
 Is our provided justification for the proposed worst-case comparison testing acceptable? 
 In the event that the prospective collection does not meet the protocols intended number of 
specimens of a given type, we propose to use retrospective, characterized (banked) specimens to 
ensure these numbers are achieved. Is this approach acceptable to FDA?
30 Contains Nonbinding Recommendations
 We have provided a justification of the worst-case testing volume that will be used, and provided an 
analysis of the sensitivity of the test, as requested. Does FDA find this justification and analysis 
adequate to support using the methodology described in our testing protocol? If not, please provide 
further guidance.
 Is the approach to use the average of valid measurements of the five replicate measurements 
acceptable/appropriate?
 We have provided a response to FDA's question about sample sizes used in the in vitro test, along 
with a justification based on a power analysis. Is this plan acceptable? If not, please provide further 
guidance.
Animal Study56, 57 Questions 
 Is the revised GLP Study design sufficient to address potential device risks and support initiation of 
a pivotal clinical trial?
 Is our alternative approach to an animal study appropriate to support initiation of a pivotal clinical 
trial?
 Is our proposal to leverage the animal studies already conducted (and described in this submission) 
adequate to support a future marketing application?
 Does the proposed animal study design provide a sufficient assessment of the local tissue and 
systemic response?
 Is the animal model proposed appropriate based on the proposed intended use?
 Are the proposed animal study endpoints and follow-up schedule appropriate?
Biocompatibility Questions
 We propose to conduct the biocompatibility testing identified in Tables 7-9 on only the largest 
model dialyzer. Is the largest model dialyzer adequate to be considered the worst-case test article? Is 
the proposed testing in line with the recommended contact classification and duration [insert 
classification and duration here] to support our future marketing submission? 
 We propose to conduct chemical characterization (described in Appendix 1) in lieu of chronic 
toxicity testing to support the biocompatibility of our device in a future PMA. Is this approach 
adequate to allow for collection of sufficient safety data?
 Is our justification for not conducting carcinogenicity studies adequate?
 Is our alternative test method to the material-mediated pyrogenicity testing, which does not use a 
traditional rabbit model but an in vitro alternative, acceptable?
Software/Firmware Questions
 Is the designation of our software/instrument at a moderate level of concern consistent with the 
recommendations provided in FDAs guidance entitled Guidance for the Content of Premarket 
56FDA supports the principles of the 3Rs, to replace, reduce, and/or refine animal use in testing when feasible. We encourage 
sponsors to consult with us if they wish to use a non-animal testing method they believe is suitable, adequate, validated, and 
feasible. We will consider if such an alternative method could be assessed for equivalency to an animal test method.
57For information on the FDAs recommendations for animal studies intended to evaluate medical devices, see FDAs guidance 
titled General Considerations for Animal Studies Intended to Evaluate Medical Devices, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-considerations-animal-studies-intended-
evaluate-medical-devices
31 Contains Nonbinding Recommendations
Submissions for Software Contained in Medical Devices58 as part of the upcoming device 
submission? 
  Does FDA expect any further data validating functional operation of [the emerging technology] 
beyond that recommended in FDAs guidance entitled "Guidance for the Content of Premarket 
Submissions for Software Contained in Medical Devices"?59 If so, can FDA give us additional 
guidance on what additional information is needed?
 The software documentation defined in Section 4.2 of this Pre-Sub for the device was previously 
reviewed and approved in other PMA supplements (i.e., the PMA supplement will reference 
previously submitted information). Is it acceptable to omit this information from the planned PMA 
supplement?
Human Factors Questions
 Is the human factors test protocol, submitted in Attachment 1, adequate to collect safety data to 
support our future marketing submission?
 Is the attached use-related risk analysis plan adequate? Does the Agency have any additional critical 
tasks that we should consider? 
 Is the proposed test participant recruitment plan for the human factors validation testing appropriate?
Cybersecurity Questions
 Are the attack vectors that have been identified for our product as described in Appendix R 
acceptable?
 Is the cybersecurity management plan, described in Section 2, sufficient to ensure cybersecurity of 
our device for our future 510(k) submission? If not, can FDA provide feedback on what additional 
cybersecurity information is needed?
 Is the proposed risk model adopted for assessing cybersecurity in this device acceptable?
 Is the level of security described appropriate for the risk of the device?
58https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissions-
software-contained-medical-devices
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM089593
59https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissions-
software-contained-medical-devices
32 Contains Nonbinding Recommendations
Appendix 3  Example of Meeting Minutes
To improve understanding of what FDA expects to see in meeting minutes for Q-Subs, the following 
example is provided. While submitters are responsible for taking and submitting meeting minutes, use of 
this format is optional.
As noted above, when you submit your meeting minutes, you should also include a copy of the slides you 
presented at the meeting.
Meeting Minutes
Submission Number: e.g., QYYNNNN or QYYNNNN/SNNN
Submission Type: e.g., Pre-Sub Meeting, Submission Issue Request
Product Name: Test ABC Device/Dx
Submitter: Company name
Meeting Date/Time: e.g., January 1, 2014; 2:00 pm
Meeting Format: In-person or Virtual (videoconference or teleconference)
Date FDA Feedback was Sent: e.g., December 25, 2013
FDA Attendees:
(If you do not have this information, please contact your CDRH lead reviewer or CBER regulatory project 
manager via interactive review)
Full Name  Title; Organization
Full Name  Title; Organization
et cetera
Company Attendees:
(Please include titles and company affiliation if more than one)
Discussion:
(Note: Please include a summary of key questions and decisions; this is not intended to be a transcript of 
the meeting, but should include any agreements reached and any items that necessitate further 
consideration, as applicable. It is suitable to indicate, for example, after some discussion, it was decided 
that the non-clinical testing should address ...)
(Please refer to FDA or Company name, as appropriate, rather than specific individuals.)
(If your presentation included any demonstrations, samples, models, et cetera, please do include a note to 
that effect.)
Company X affirmed that it would be taking meeting minutes for this meeting. 
Company X presented its agenda for the meeting, including anticipated time allotted for each item.
Company X briefly reviewed its purpose in submitting this Q-Sub and the current state of its device 
development.
33 Contains Nonbinding Recommendations
Company X indicated that, of the 5 questions it had posed in submitting this Q-Sub, it wanted to focus the 
meeting on questions 1, 3, and 5, since FDAs responses to questions 2 and 4 appeared to be sufficient. 
Company X also wanted to clarify some of the additional feedback FDA had provided.
Question 1: (Your original question as submitted to FDA)
FDA Response to Question 1: (Optional) (Include the written response FDA provided prior to the meeting)
Meeting Discussion for Question 1:
(Minutes should capture if the company provided clarification or justification to anything in the original 
submission, if there was any clarification or justification to FDAs written feedback, and if the company 
agreed or stated what its next steps would be. We recommend that you do not capture the discussion 
verbatim. Clearly identify agreements and/or disagreements that were reached by FDA and the submitter 
during the discussion related to this specific question.)
Question 3: 
...
Question 5: 
...
Additional Feedback Item 1: 
... 
Decisions made and/or agreements reached:
KEY decisions or agreements should be listed succinctly here for easy reference later. 
Reference the question # relevant to the decision or agreement that was reached during discussion of a 
specific question.
Action Items and Meeting Closure:
Company X indicated that it had taken meeting minutes and would provide those to FDA within 15 days as 
an amendment to this Q-Sub.
(If Company X indicated its next priority for a future FDA premarket submission, that would be useful to 
note)
(If either FDA or the company agreed to any action items post-meeting, beyond submitting the meeting 
minutes, those should be noted with a brief description, owner (FDA or company), and projected date for 
completion.) 
34