United States: Medical Device Update: FDA Releases Final Pre-Submission Guidance

Last Updated: March 12 2014
Article by M. Elizabeth Bierman, Phoebe Mounts and Jonathan A. Havens


As we noted in our recent Medical Device Update,1 on February 18, the U.S. Food and Drug Administration (FDA or the Agency) issued a final guidance titled "Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff" (Guidance).2 This Guidance contains substantive changes from the pre-submission (Pre-Sub) draft guidance released by the Agency on July 13, 2012, and it replaces and supersedes FDA's 1999 guidance "Pre-IDE Program and Meetings with Food and Administration Staff: Issues and Answers." The new guidance includes requirements on the type, timing, format, and content of requests for feedback meetings and telephone conferences with FDA. Therefore, it will be important for the medical device industry to be aware of these requirements in planning their device development activities and timelines.

Q-Sub Organizational Structure

One significant difference between the draft and final guidance documents is that the Agency introduced the concept of the "Q-Submission" (Q-Sub) organizational structure in the final guidance. Q-Subs encompass various types of requests for feedback, including Pre-Submissions, Informational Meetings, Study Risk Determinations, Formal Early Collaboration Meetings (i.e., Agreement and Determination Meetings), Submission Issue Meetings, and Premarket Approval (PMA) Day 100 Meetings. The Agency will refer to these requests for feedback collectively as "Q-Subs," and the goal for the Q-Sub program is to provide a convenient and effective way to track such requests.

When to Submit a Q-Sub

Q-Subs can be invaluable for early feedback on specific questions during submission preparation, such as in the following circumstances:

  • Before conducting clinical, nonclinical, or analytical studies or submitting an investigational device exemption (IDE) or marketing application when:
    • The new device involves novel technology, and it may be helpful to familiarize the FDA review team with the technology in advance of the submission.
    • A company is proposing a "first of a kind" indication or a new indication for an existing device.
    • The new device does not clearly fall within an established regulatory pathway, and the company desires informal input on a proposed regulatory strategy.
    • The new device is a multiplex device capable of simultaneously testing a large number of analytes.
    • The new device is an in vitro diagnostic (IVD) device that contains a new technology, a new intended use, a new analyte, new clinical questions, complex data/statistical questions, and/or where the predicate of or the reference method is unclear or uncertain.
    • FDA guidance is desired on specific issues related to nonclinical study protocols and/or animal study protocols before initiating a study.
    • FDA input is desired on specific issues related to a planned clinical study, especially if it involves complex or novel statistical approaches.
    • FDA input is desired on the extent that existing data may be leveraged in preparing a PMA submission for a device in accordance with section 520(h)(4) of the Federal Food, Drug, and Cosmetic Act.
    • FDA input is desired on a clinical protocol before conducting a clinical study that does not require FDA review of an IDE, such as for a nonsignificant risk device or a study that will be conducted entirely outside the United States (OUS).
  • Before submitting a marketing application in order to:
    • Apprise the FDA review team on the particulars of the device and the clinical study (if there have been changes since the initiation of the IDE).
    • Obtain FDA feedback on the use of data collected from an OUS study to support clearance or approval.
    • Obtain FDA feedback on its preferred data presentation and to ensure clarity with respect to expectations regarding the elements to be included in the marketing application.
    • Gain insight into potential hurdles for approval or clearance (e.g., numerous protocol deviations, missing data, or a failed study endpoint), some of which could require additional data or analyses.

However, Q-Subs are not appropriate for any of the following:

  • General questions on FDA policy or procedure
  • Questions that can be readily answered by an FDA reviewer based on his or her experience and knowledge and that do not require the involvement of a broader number of FDA staff
  • Requests for clarification on technical guidance documents

Manufacturers may request more than one Q-Sub meeting/teleconference for a device submission. However, the Agency will not grant more than one meeting/teleconference covering the same or similar issues. Thus, it would be appropriate to request a meeting on preclinical studies and, subsequently, a meeting on a clinical study, but it would not be appropriate to request multiple meetings on the iterative versions of the same clinical study.

Q-Subs for Combination Products

FDA's guidance acknowledges that manufacturers often seek input on issues relating to the device component of a combination product, for example, on devices such as pumps that deliver a drug. Combination product manufacturers should be aware that the new guidance recommends that the Center for Devices and Radiological Health (CDRH) staff notify the lead center for the combination product whenever it receives a Q-Sub and that review staff from the other center(s) be involved to ensure that the entire review team is aware of the questions raised and the responses provided.

Reliability of Agency Feedback

FDA intends that its feedback in response to a Q-Sub will not change, provided that the information submitted in support of the Q-Sub remains accurate. The Agency intends to limit modifications to its feedback to those situations where the initial feedback does not address important new issues relevant to a determination of safety or effectiveness that emerge after the Q-Sub is submitted. However, FDA recommends that sponsors contact the review branch to confirm the feedback guidance if more than one year has passed since the last feedback on key clinical trial design elements. An additional Q-Sub is not required to obtain such confirmation; the confirmation may be obtained through a phone call with the review branch.

Timeframes for Requested Feedback

FDA has established new procedures and timelines for Q-Subs that could significantly impact a device company's timelines for bringing a device to market. For example, many device stakeholders have found that it is increasingly important to obtain FDA feedback prior to conducting a clinical study on a novel device or a novel modification to an existing device. Because the costs of designing and conducting a clinical study have increased substantially in recent years, companies often seek to avoid the risk of undertaking a study that FDA might later determine is not adequate to support the proposed intended use or marketing claims. Now, for those companies that wish to avoid such risk by obtaining FDA feedback prior to conducting a clinical study, it will be necessary to build into the development plan adequate time to request and obtain such feedback.

In the Guidance, the Agency specifically addresses the timeframes within which FDA intends to provide the requested feedback. Significantly, however, the timeframes provided in the Guidance do not begin until the Q-Sub is deemed "accepted." In a process similar to that adopted for 510(k) and PMA submissions, during the first 14 days after a request is submitted to FDA, Agency staff will review the submission to determine whether it (1) includes a valid eCopy, (2) meets the definition of the identified Q-Sub type, and (3) is administratively complete. If the submission is not complete, FDA will inform the applicant that it is not accepted and will identify the reasons for not accepting it. The following chart, provided by the Agency in the Guidance, sets forth the timeframes for meetings/teleconferences for each Q-Sub type and indicates whether a meeting is available as an avenue of receiving feedback from FDA.

Q-Sub Type

Meeting as Method of Feedback?

Timeframe for Meeting/Teleconference
(from receipt of submission)


Upon request

75–90 days**

Informational Meeting


90 days

Study Risk Determination



Agreement Meeting


30 days or within timeframe agreed to with sponsor

Determination Meeting


Date for meeting agreed upon within 30 days of request

Submission Issue Meeting


21 days

PMA Day 100 Meeting


100 days (from PMA filing date)

*As defined in MDUFA III Commitment Letter
**21 days for urgent public health issues

We recommend that companies use the Acceptance Checklist in Appendix 2 of the Guidance prior to submission to ensure all of the required criteria are explicitly addressed.


1. View our March 2014 Medical Device Update here.

2. View the Guidance here.

This article is provided as a general informational service and it should not be construed as imparting legal advice on any specific matter.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Similar Articles
Relevancy Powered by MondaqAI
In association with
Related Topics
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions