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Drug Administration Staff" (Guidance).2 This Guidance contains substantive changes from the pre-submission (Pre-Sub) draft guidance released by the Agency on July 13, 2012, and it replaces and supersedes FDA's 1999 guidance "Pre-IDE Program and Meetings with Food and Administration Staff: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.

In association with
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
Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:
  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.
  • Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.
    If you do not want us to provide your name and email address you may opt out by clicking here
    If you do not wish to receive any future announcements of products and services offered by Mondaq you may opt out by clicking here

    Terms & Conditions and Privacy Statement

    Mondaq.com (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

    Use of www.mondaq.com

    You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). 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 & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about Mondaq.com’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


    Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd 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 or performance of information available from this server.

    The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


    Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

    • To allow you to personalize the Mondaq websites you are visiting.
    • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
    • To produce demographic feedback for our information providers who provide information free for your use.

    Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

    Information Collection and Use

    We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

    We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to unsubscribe@mondaq.com with “no disclosure” in the subject heading

    Mondaq News Alerts

    In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


    A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

    Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

    Log Files

    We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


    This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

    Surveys & Contests

    From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


    If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


    From time to time Mondaq may send you emails promoting Mondaq services including new services. You may opt out of receiving such emails by clicking below.

    *** If you do not wish to receive any future announcements of services offered by Mondaq you may opt out by clicking here .


    This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to webmaster@mondaq.com.

    Correcting/Updating Personal Information

    If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to EditorialAdvisor@mondaq.com.

    Notification of Changes

    If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

    How to contact Mondaq

    You can contact us with comments or queries at enquiries@mondaq.com.

    If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at problems@mondaq.com and we will use commercially reasonable efforts to determine and correct the problem promptly.

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