Q-Submission-Feedback-Meetings-Guidance

Q-Submission and Early Payor Feedback Request Programs for Medical Devices

Q-Submission-Feedback-Meetings-Guidance

OMB: 0910-0756

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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 January 6, 2021.
Document originally issued on May 7, 2019.

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.
The OMB control number for this information collection is 0910-0756 (expires December 31,
2022).

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Center for Biologics Evaluation and Research

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. 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 e-mail request to CDRHGuidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 1677
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.,
Bldg. 71, Room 3128, Silver Spring, MD 20993-0002, or by calling 1-800-835-4709 or 240-4028010, by email, ocod@fda.hhs.gov or from the Internet at https://www.fda.gov/vaccines-bloodbiologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.

Contains Nonbinding Recommendations

Table of Contents
I.

Introduction ............................................................................................................................................... 1

II.

Background ............................................................................................................................................... 2

III.

Scope ..................................................................................................................................................... 2

Pre-Submissions (Pre-Subs) .................................................................................................................. 2

Submission Issue Requests (SIRs) ........................................................................................................ 3

Study Risk Determinations ................................................................................................................... 4

Informational Meetings ......................................................................................................................... 5

Other Q-Submission Types ................................................................................................................... 5

Other Uses of the Q-Submission Program ............................................................................................ 6

Interactions Not Within the Q-Submission Program ............................................................................ 8

IV.

Q-Submission Program ......................................................................................................................... 9

General Q-Submission Considerations ............................................................................................... 10
1. Relating Q-Submissions to Future IDE, IND, CWs, and Marketing Submission(s) (“Related
Submission(s)”) ....................................................................................................................................... 10
2.

Combination Product Considerations.............................................................................................. 10
Q-Submission Processes ..................................................................................................................... 11

1. Submission Content ........................................................................................................................... 11
2. FDA Submission Tracking ................................................................................................................. 13
3. Meeting Information........................................................................................................................... 15
4. Processes by Q-Submission Types ..................................................................................................... 17
5. Other Q-Sub Types or Uses of the Q-Sub Program ........................................................................... 25
V.

Paperwork Reduction Act of 1995 .......................................................................................................... 25

Appendix 1 – Pre-Submission (Pre-Sub) Acceptance Checklist..................................................................... 26
Appendix 2 – Example Pre-Sub Questions ..................................................................................................... 27
Appendix 3 – Example of Meeting Minutes ................................................................................................... 31

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.

Introduction 1

The purpose of this guidance is to provide an overview of the mechanisms available to
submitters through which they can request feedback from or 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

The Office of Combination Products (OCP) was consulted in the preparation of this guidance.
Some 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.

Contains Nonbinding Recommendations
by teleconference. When there is a distinction between those two types of meetings, it will
be noted in this guidance.
FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s 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 guidance 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 FDA’s 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. 4 This
guidance reflects those changes and clarifies other elements of the Q-Sub program.

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
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)
3

See 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.
4
See 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.

Contains Nonbinding Recommendations
A Pre-Sub includes a formal written request from a submitter 5 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 in which any additional feedback or clarifications are
documented in meeting minutes. Such a Pre-Sub meeting can be in-person or by teleconference
as the submitter prefers.
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 issues relevant to a planned IDE, CW, or marketing submission (e.g., questions
regarding cybersecurity considerations for the device; non-clinical testing protocols; design and
performance of clinical studies and acceptance criteria). A Pre-Sub is appropriate when FDA’s
feedback on specific questions is necessary to guide product development and/or submission
preparation.
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 FDA’s
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 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 principles, 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
approval or clearance of 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.
Note that for an Accessory Classification Request for an existing accessory type, FDA must
provide an opportunity for the submitter to meet with FDA to discuss the appropriate
classification of the accessory prior to submission as described in Section III.A of this
guidance. 6 FDA is also willing to meet with manufacturers who intend to submit an
Accessory Classification Request for a new accessory type. We recommend that requests for
feedback regarding a planned Accessory Classification Request be submitted as a Pre-Sub.
Submission procedures for the Accessory Classification Request itself are further described in
Section III.E.

B. Submission Issue Requests (SIRs)
5

For 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.
6
See section 513(f)(6)(D)(ii) of the FD&C Act.

Contains Nonbinding Recommendations
A SIR is a request for FDA feedback on a proposed approach to address issues conveyed in a
marketing submission (i.e., PMA, HDE, De Novo request, 510(k), Dual, or BLA) 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).

The SIR is intended to facilitate interaction between FDA and the submitter to quickly resolve or
clarify issues identified in these letters so that projects can move forward, and so that submitters
are able to fully address outstanding questions and issues in their formal responses. 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.
Please 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, please see FDA’s
guidance entitled “Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors
Significant Risk and Nonsignificant Risk Medical Device Studies.” 7 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).

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/significant-risk-and-nonsignificantrisk-medical-device-studies

Contains Nonbinding Recommendations

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.
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 FDA’s guidance entitled “Guidance on
PMA Interactive Procedures for Day-100 Meetings and Subsequent Deficiencies.” 8

•

Agreement and Determination Meetings as described in FDA’s guidance entitled
“Early Collaboration Meetings Under the FDA Modernization Act (FDAMA).” 9

•

Submissions associated with the Breakthrough Devices Program as described in
FDA’s guidance entitled, “Breakthrough Devices Program” 10:
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.

Contains Nonbinding Recommendations
•

Submissions associated with the Safer Technologies Program (“STeP”) as
described in FDA’s guidance entitled, “Safer Technologies Program for Medical
Devices” 11:
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.

•

Accessory Classification Requests as described in FDA’s guidance entitled,
“Medical Device Accessories – Describing Accessories and Classification
Pathways” 12:
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
Please note that 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 QSub 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 vehicle is currently used for tracking
include:

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safer-technologies-program-medicaldevices
12
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-device-accessoriesdescribing-accessories-and-classification-pathways

Contains Nonbinding Recommendations
•

Request for FDA feedback on specific questions or cross-cutting policy matters
(e.g., submission strategies unrelated to a specific premarket submission, nonclinical 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 FDA’s substantive review. 13

•

Request for feedback regarding development of a Medical Device
Development Tool (refer to FDA’s guidance entitled “Qualification of Medical
Device Development Tools”). 14

•

Request for recognition of publicly accessible genetic variant databases (refer
to FDA’s guidance entitled “Use of Public Human Genetic Variant Databases
to Support Clinical Validity for Genetic and Genomic-Based In Vitro
Diagnostics”). 15

•

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.

For these types of meetings with CBER staff, please see https://www.fda.gov/about-fda/about-center-biologicsevaluation-and-research-cber/contacts-center-biologics-evaluation-research-cber#indcont.
14
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-medical-devicedevelopment-tools
15
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-public-human-genetic-variantdatabases-support-clinical-validity-genetic-and-genomic-based-vitro

Contains Nonbinding Recommendations

G. Interactions Not Within the Q-Submission Program
There are several other means by which industry may obtain feedback from FDA which are
outside the scope of the Q-Sub Program, including, but not limited to, the following:
•

Teleconferences or emails with FDA staff (e.g., by the lead reviewer or Regulatory
Project Manager (RPM) 16) 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 FDA’s guidance entitled “Types of
Communication During the Review of Medical Device Submissions.” 17

•

Requests for appeal meetings made to CDRH, which are described in FDA’s guidance
entitled “Center for Devices and Radiological Health (CDRH) Appeals Processes”, 18 or
to CBER, which are described in FDA documents entitled “Formal Dispute Resolution:
Sponsor Appeals Above the Division Level” 19 and CBER SOPP 8005: Formal Dispute
Resolution Process. 20

•

Requests for Designation (RFD) or Pre-RFDs 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 product’s Center assignment
(or both), is unclear or in dispute. 21 Procedures for these processes can be found in
FDA’s guidances entitled, “How to Write a Request for Designation (RFD)” 22 and
“How to Prepare a Pre-Request for Designation (Pre-RFD).” 23 Such classification and
assignment information should not be solicited via a 513(g) Request for Information
(see below).

CBER 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.
17
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/types-communication-duringreview-medical-device-submissions
18
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/center-devices-and-radiologicalhealth-appeals-processes
19
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/formal-dispute-resolution-sponsorappeals-above-division-level-guidance-industry-and-review-staff
20
https://www.fda.gov/media/108908/download
21
Additional information on how combination products are assigned a lead Center for their premarket review and
their regulation is available on OCP’s 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-anddevices-and-additional-product-classification-issues).
22
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/how-write-request-designation-rfd
23
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/how-prepare-pre-requestdesignation-pre-rfd

Contains Nonbinding Recommendations
•

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
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.” 24

•

Requests for feedback from FDA outside the Q-Submission process via other resources
including, but not limited to CDRH Device Advice website, 25 CDRH’s Division of
Industry and Consumer Education (DICE), 26 or CBER’s Manufacturers Assistance and
Technical Training Branch. 27

•

Requests for clarification on device-specific guidance documents or voluntary consensus
standards that are not related to a specific device in development.

IV. Q-Submission Program
The term “Q-Submission” or “Q-Sub” refers to the system used to track the collection of
interactions described 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 interactively 28 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 product’s development cycle, a submitter may wish to conduct an
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. The Q-Sub program is not meant to be an iterative process, i.e., one in which FDA
considers the same or similar information more than once. If you intend to submit more than
24

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-procedures-section513g-requests-information-under-federal-food-drug-and-cosmetic
25
CDRH Device Advice, https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance.
26
You may contact DICE by email at DICE@fda.hhs.gov or by telephone: 1-800-638-2041 or 301-796-7100.
27
CBER’s Manufacturers Assistance and Technical Training Branch may be contacted by email at
industry.biologics@fda.gov.
28
See FDA Guidance Document, “Types of Communication During the Review of Medical Device Submissions”,
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/types-communicationduring-review-medical-device-submissions.

Contains Nonbinding Recommendations
one Q-Sub to request discussion and/or feedback on additional 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. The intent is for FDA and the submitter to focus on the
submitter’s current priority. As such, for any given device, only one Q-Sub should 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, FDA’s 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 QSubs are not identified in the cover letter of the subsequent related submission, they will not be
linked in FDA’s records. Therefore, there may be a delay in determining FDA’s previous
feedback, and the subject device may not be incorporated in any future analyses of Q-Sub
program effectiveness.
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 center’s corresponding processes. Accordingly, Qsubmissions 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 OCP, and then submit their
meeting request to the center determined to be the lead center. If CDRH or CBER receives a QSub for a combination product as the lead center for the product, the center’s staff intends to
10

Contains Nonbinding Recommendations
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. Please note that 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 days 29 after receiving such request and intends to provide written
feedback prior to the meeting. Please note that for products that are combination products, the
submitter is responsible for identifying it as such in the submission. 30 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. 31

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.

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 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.

•

If a Q-Sub type includes the option for a meeting (e.g., a Pre-Sub, SIR, and
Informational Meeting requests), please 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 (i.e., in-person or by teleconference; see
Section 3.a. below);

Unless otherwise specified, in this guidance document, days refers to calendar days.
See section 503(g)(8)(c)(v)(I) of the FD&C Act.
31
The following website contains contact information for OCP: https://www.fda.gov/about-fda/office-specialmedical-programs/office-combination-products.
30

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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 your proposed dates do not allow for adequate preparation, FDA may not be
able to accommodate your requested dates and will offer you alternative dates
within an appropriate timeframe. Please 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 4.d.2 below) in considering proposed
dates that are likely to be accepted by FDA.
iv. The planned attendees, including each attendee’s position, or title, and
affiliation.
a)
If you have not yet identified all of your attendees, you should indicate
the type of subject matter experts you plan to invite. (See Section 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).
The following should be easily identified within the Q-Sub:
•

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 FDA’s 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.

•

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.

•

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.

Contains Nonbinding Recommendations
Use of the CDRH Premarket Review Submission Cover Sheet 32 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, please refer to https://www.fda.gov/medicaldevices/how-study-and-market-your-device/ecopy-program-medical-device-submissions,
including the guidance entitled “eCopy Program for Medical Device Submissions.” 33 In addition
to the eCopy guidance, for Q-Subs for products regulated in CBER, additional information
regarding electronic submission can be located at the following website:
https://www.fda.gov/about-fda/about-center-biologics-evaluation-and-research-cber/regulatorysubmissions-electronic-and-paper.
Submission packages should be mailed to the CDRH Document Control Center (DCC) or the
CBER DCC. The current mailing address for CDRH’s DCC and a link to CBER’s DCC mailing
address are provided on the eCopy Program for Medical Device Submissions webpage at
https://www.fda.gov/medical-devices/how-study-and-market-your-device/ecopy-programmedical-device-submissions.
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
FDA assigns 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 QSub cover letter that contains the unique tracking number and date received by the
Document Control Center (DCC). Any future communications regarding your Q-Sub
should include this unique Q-Sub identifier.

See Form 3514, https://www.fda.gov/media/72421/download.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-devicesubmissions
33

Contains Nonbinding Recommendations
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 or similar device and indications for use as an original Q-Sub that already
exists. For example, it may be appropriate to request an Informational Meeting to
familiarize the review team with the new device design, then submit a Pre-Sub to request
feedback on non-clinical testing, then 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
14

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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 FDA’s views on clinical, nonclinical, 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 any written
feedback the Agency has already provided. Please note that we are generally unable to
comment on new information provided by the submitter between receiving FDA written
feedback and holding the meeting or during the meeting. If a submitter would like feedback on
new information, such 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 in-person or via teleconference. Generally,
teleconferences may be more easily scheduled. While in person meetings may take longer to
schedule due to conference room or staff availability, they can also be helpful depending on the
situation (e.g., in providing live demonstrations), and some submitters may prefer them. 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.
Please note that, in our experience, one (1) hour is adequate for most meetings. If you believe
that more than one hour is needed, please 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

Contains Nonbinding Recommendations
FDA will 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
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
Force’s website. 34 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 we have
included an example format of meeting minutes in Appendix 3 for your reference. You should
have a member of your 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 through
the appropriate DCC within 15 days of the meeting. If slides were presented, the actual version
used in the meeting or teleconference 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 DCC, the submitter is encouraged to
submit an identical version of the meeting minutes in a format that facilitates editing and
34

https://www.fda.gov/about-fda/cdrh-innovation/payor-communication-task-force

Contains Nonbinding Recommendations
commenting (e.g., Microsoft Word) under the miscellaneous files section of the eCopy package
(see FDA Guidance Document “eCopy Program for Medical Device Submissions” 35,
Attachment D.2).
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. Additional information or follow-up items that were not part of the meeting
discussion should not be included in the meeting minutes.
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 FDA’s
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, 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 in additional Q-Sub meetings 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.

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ecopy-program-medical-devicesubmissions

Contains Nonbinding Recommendations

Table 1 – Q-Sub types and corresponding feedback mechanisms and timelines

Q-Sub Type

Pre-Submission

Method of Feedback

Meeting (face-to-face or
teleconference) with written
feedback provided in advance

Written Feedback Only

Timeframe for Sending Feedback
or Scheduling Meeting
(from receipt of submission)
Written Feedback:
70 days or 5 days prior to
scheduled meeting, whichever is
sooner
Meeting:
Date based on mutual agreement
(typically at 60-75 days)
70 days
If SIR is received within 60 days of
FDA’s marketing submission letter:
21 days as resources permit

Submission Issue Request
(SIR)

Meeting or Written Feedback

If SIR is received more than 60
days after FDA’s 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.

Contains Nonbinding Recommendations

a) Pre-Submission
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), the following
information should be included in a Pre-Sub:
•

Planned Follow-On Submission. Please 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 FDA’s feedback.

•

Background Information: Please 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 feedback.
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.

•

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 FDA’s 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 indepth 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.
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 focus on.
Additional guidance regarding common types of questions submitted in Pre-Subs is
provided below:

Contains Nonbinding Recommendations

o Study Protocols
Please note that resource constraints do not permit FDA to prepare or design
particular study plans. If a submitter would like FDA’s feedback on a protocol,
they should submit a proposed outline, with a rationale for the chosen
approach.
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 generally 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
Please note that 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. 36 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.
Examples of questions that lead to productive Pre-Sub interactions are provided in
Appendix 2 of this guidance.
2) Review Process
The review process for a Pre-Sub, including timelines outlined in the MDUFA IV 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 – PreSubmission (Pre-Sub) Acceptance Checklist). When completed, the submitter will
receive notification regarding whether or not the submission has been accepted for review

See 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-guidancedocuments/fda-and-industry-procedures-section-513g-requests-information-under-federal-food-drug-and-cosmetic.

Contains Nonbinding Recommendations
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 submitter’s
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
this decision with the reasons for refusal. The submitter may respond to an RTA
notification by submitting additional information to the DCC, 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 (in person or
teleconference) on one of the submitter’s requested meeting dates, if feasible. Meeting
dates between 60-75 days following FDA receipt of your submission are most likely to be
feasible. If FDA cannot accommodate one of the submitter’s 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 or fax and will
include: written responses to the submitter questions; FDA’s suggestions for additional
topics for the meeting or teleconference, 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 days of receipt of the accepted submission and will serve as
the official record of the Agency’s 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 submitter’s questions are addressed to the
submitter’s satisfaction, the submitter may cancel the meeting and the written
response will serve as the official record of the Agency’s feedback. If a meeting is
held, the meeting minutes along with the written feedback will constitute the
official record of the Agency’s feedback. The process of the meeting minutes and
timeline are described in Section IV.B.3.c of this guidance.

Contains Nonbinding Recommendations
FDA will generally be unable 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. Any information that
necessitates additional FDA review should be submitted as a supplement to the PreSub. It is, however, appropriate to narrow your agenda to focus on specific questions
or topics in the feedback.
FDA feedback represents our best advice based on the information provided in the PreSub 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 the data 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 FDA’s 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 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. 37
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 is 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 is not needed.
b) Submission Issue Request (SIR)
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), the following
information should be included in a SIR:
37

The 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-needspremarket-submissions.

Contains Nonbinding Recommendations

•

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
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 generally 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.
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. 38 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 FDA’s 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 FDA’s letter, FDA will aim to provide feedback within 70 days, as
resources permit.

See 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.

Contains Nonbinding Recommendations
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.
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; FDA’s determination is
final.
d) Informational Meeting
1) Additional Recommended Submission Contents

There is no specific additional information requested 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.

Contains Nonbinding Recommendations

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, 39 Agreement and Determination
Meetings, 40 Breakthrough Device submissions, 41 Qualification of Medical Device Development
Tools, 42 Accessory Classification Requests, 43 STeP submissions, 44 requests for recognition of
publicly accessible genetic variant databases, 45 and CPAMs. 46
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.

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.

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-pma-interactiveprocedures-day-100-meetings-and-subsequent-deficiencies-use-cdrh-and
40
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/early-collaboration-meetings-underfda-modernization-act-fdama-final-guidance-industry-and-cdrh
41
See section 515B(c) of the FD&C Act and https://www.fda.gov/regulatory-information/search-fda-guidancedocuments/breakthrough-devices-program.
42
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-medical-devicedevelopment-tools
43
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-device-accessoriesdescribing-accessories-and-classification-pathways
44
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safer-technologies-program-medicaldevices
45
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-public-human-genetic-variantdatabases-support-clinical-validity-genetic-and-genomic-based-vitro
46
Defined under section 503(g)(2)(A) of the FD&C Act.

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:

1 Has the submitter provided a purpose or goal for their Pre-Sub?

Yes No



2 Has the submitter identified device(s) or other product(s) to be discussed in their Pre-Sub?
3 Has the submitter provided questions that request FDA feedback?




4 Does the submission indicate that the submitter intends to submit a future IDE, CLIA
Waiver by Application, IND, or marketing submission related to the feedback being
requested?



No for question 1, 2, 3, or 4  Recommend Refuse to Accept Pre-Submission (RTA1) or consider
conversion to appropriate Q-Sub type
Yes for questions 1, 2, 3, and 4 Continue to questions 5 and 6

5 Do the provided questions pertain to a file under active review?
6 Do the provided questions relate to a marketing submission or CLIA hold letter, 47 an IND
Clinical Hold letter, or an IDE letter?

Yes No






No for questions 5 and 6 Recommend Accept (RTAA)
Yes for question 5  RTA1 and resolve during interactive review of the open file
Yes for question 6  Convert to Submission Issue Request (SIR)

FDA considers the following to be marketing submission hold letters or CLIA hold letters:

- Additional Information Needed for 510(k)s, De Novos 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.

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 FDA’s experience, questions that lead to productive Pre-Sub interactions
share the following characteristics:
o Questions 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)
o Questions have considered and include reference 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)
o Questions 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)
o Questions 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)
o Questions do not request decisions regarding approval or clearance of a future IDE, CW, IND, or
marketing submission; that is, a question should not ask “Will an IDE that includes results from
the proposed testing be approved?”
o Questions do 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 background 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)
o Questions do not ask FDA to design a study or indicate how a submitter should proceed; that is,
a question should not ask “What should my clinical study design be?”
o Questions do not request formal regulatory determination; that is, a question should not ask “Is
my device a Class II medical device to be regulated under CFR 892.2050?”
The following are examples of questions, provided by review topic category, expected to lead to productive
Pre-Sub interactions.
Regulatory Strategy Questions
• Are there concerns with the predicate device proposed?
• Can we obtain FDA's feedback and guidance on pursuing a De Novo request for classification
pathway given that there is not a currently marketed device that we believe could serve as predicate
under the 510(k) pathway?
• Based on the regulatory strategy provided, does FDA agree, based on the discussion provided, that
additional clinical data is 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?
27

Contains Nonbinding Recommendations
•
•

Does FDA agree with the proposed definition of drug-resistant hypertension provided in the draft
indications for use statement?
Does the Agency agree with the proposed size range offered for the new device, based on the
intended use?

Clinical Study Questions
• Does FDA have any comments on the provided OUS study protocol regarding its ability to support a
future HDE?
• Does FDA agree with the revised clinical study designs, statistical analysis and acceptance criteria
included in this Pre-Sub supplement?
• Are the primary and secondary analyses appropriate for the Indications for Use for the monitoring
indication proposed?
Labeling Questions
• Does FDA agree with the proposed test plan in support of MR Conditional labeling for 1.5T
scanners with an exclusion zone between the neck and groin?
• 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 FDA agree with this plan?
Reprocessing, Sterilization & Shelf Life Questions
• Does FDA have any comments about the methods described in the Microbiology protocol "Microbiology Study Protocol" included in Appendix 3?
• Does FDA concur that accelerated testing outlined in Appendix 2 conducted to represent 1 year shelf
life is sufficient for an IDE with real time testing provided in the PMA?
• 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?
• Does FDA agree with our recommendation to low level disinfect the cannula device between uses?
Benchtop Performance Testing Questions
• Does FDA agree with the provided justification for the proposed worst-case comparison testing?
• In the event that the prospective collection does not meet the protocol’s 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?
• 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.
• Does the Agency agree with our approach to use the average of valid measurements of the five
replicate measurements?
• 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.

Contains Nonbinding Recommendations
Animal Study 48 Questions
• Does FDA concur that the revised GLP Study design is sufficient to address potential device risks
and support initiation of a pivotal clinical trial?
• Is our alternative approach to an animal study appropriate?
• Please advise if FDA believes that additional animal studies outside of those already conducted (and
described in this submission) are recommended to support a future marketing application.
• Does the Agency agree that the proposed animal study is designed to 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. Does FDA concur with the testing protocol?
• We propose to conduct chemical characterization (described in Appendix 1) in lieu of chronic
implantation testing. Please provide any comments on the acceptability of this approach.
• Is our justification for not conducting carcinogenicity studies adequate?
• Is our alternative test method to the material-mediated sensitization testing, which does not use a
traditional rabbit model but an in vitro alternative, acceptable?
Software/Firmware Questions
• Does FDA agree that our software/instrument is a moderate level of concern and that the level of
documentation that will be included in an upcoming marketing submission is consistent with FDA’s
recommendations provided in FDA’s guidance entitled “Guidance for the Content of Premarket
Submissions for Software Contained in Medical Devices” 49 as part of the upcoming device
submission?
• Does FDA expect any further data validating functional operation of alerts and alarms in real or
simulated circumstances beyond that recommended in FDA’s guidance entitled "Guidance for the
Content of Premarket Submissions for Software Contained in Medical Devices"? 50 If so, can FDA
give us additional guidance on what additional information is needed?
• Does FDA agree that the software documentation defined in Section 4.2 of this Pre-Sub does not
need to be included in the PMA supplement for the device as it was previously reviewed and
approved in other PMA supplements (i.e., the PMA supplement will reference previously submitted
information)?
Human Factors Questions
• Does the Agency have comments on our proposed human factors engineering process?
• Is the attached use-related risk analysis plan adequate? Does the Agency agree that we have
identified all the critical tasks?
48

FDA supports the principles of the “3Rs,” to reduce, refine, and replace 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.
49
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissionssoftware-contained-medical-devices
50
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-premarket-submissionssoftware-contained-medical-devices

Contains Nonbinding Recommendations
•

Does the Agency agree with our proposed test participant recruitment plan for the human factors
validation testing?

Cybersecurity Questions
• Does the Agency agree with the attack vectors that have been identified for our product as described
in Appendix R?
• Does the Agency have comments on our overall cybersecurity management plan?
• Does FDA agree with the proposed risk model adopted for assessing cybersecurity in this device?
• Is the level of security described appropriate for the risk of the device?

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 committed to 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: Face-to-Face 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.
31

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 FDA’s 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 FDA’s written feedback, and if the company
agreed or stated what its next steps would be. 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.)

File Type	application/pdf
File Title	Q-Submission Guidance - Level 2 Update
Author	Elaine Katrivanos, Erin Cutts, Allen Hill
File Modified	2022-12-06
File Created	2021-01-04