On 13 July 2012, the Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) issued a highly anticipated draft guidance document intended to eventually supersede the 25 March 1999, Blue Book Memorandum Pre-IDE Program: Issues and Answers. While the Pre-IDE process was originally developed for sponsors to obtain feedback on future Investigational Device Exemption (IDE) applications, over time, these meetings evolved to allow for feedback on other types of device applications, such as Premarket Approval (PMA) applications, Humanitarian Device Exemption (HDE) applications, and Premarket Notification (510(k)) notices. The new draft guidance, Medical Devices: The Pre-Submission Program and Meetings with FDA Staff, updates the pre-IDE program to officially provide what will be called pre-submission (Pre-Sub) meetings for applicants to receive feedback on future IDE, PMA, HDE, and 510(k) submissions, as well as the design of IDE-exempt, NSR and OUS studies. This guidance largely reflects how FDA has been handling pre-submission meetings over the last several years.

The guidance also provides significant detail on the purposes of such meetings, the contents of pre-meeting packages, and timelines, and attempts to standardize across the various branches within the Office of Device Evaluation (ODE). It notes that the purpose of the Pre-Sub program will be the same as the Pre-IDE program—to provide the applicant with the opportunity to receive feedback before expending the resources on a complete application, and to provide the FDA with the opportunity to become familiar with the technology prior to receipt of the application. The guidance also specifies that the Pre-Sub program is not intended to be used: for general information requests or questions regarding FDA policies or guidance documents, for informational meetings or meetings to discuss issues with a pending application (see below for more detail on these types of meetings), for minor informal discussions with reviewers, or to replace other existing mechanisms (e.g., the Request for Designation (RFD), or 513(g) classification determination procedures).

Types of meetings introduced by the guidance

The guidance describes three types of meetings which may occur with the FDA prior to a final decision on an application:

  1. Informational meetings – Meetings where the applicant shares information with the FDA, such as to inform the FDA of new technology, but where the FDA will not provide feedback. The FDA will seek to schedule such meetings within 90 days of meeting request.
  2. Pre-sub meetings – The FDA will plan to schedule a meeting within 75 days, but not longer than 90 days. These are described in more detail below.
  3. Submission issue meetings – Meetings where the applicant and the FDA discuss deficiencies identified during review of a premarket submission. The FDA will seek to schedule such meetings within 21 days of a meeting request.  

Requests for all meetings described in the guidance must include: (1) the requested format for the meeting (e.g., in-person or teleconference), (2) three or more preferred dates and times, (3) contact information, (4) planned attendees, and (5) requested audiovisual equipment. Informational or Submission Issue meeting requests must contain: (1) a reference to the related application, (2) a brief statement of the purpose of the meeting, (3) a complete description of the device, (4) a proposed agenda, and (5) focused questions for the FDA. The suggested contents of a Pre-Sub package and the associated meeting process are described below.

Pre-submission program

A pre-submission meeting request is a formal written request from the applicant seeking feedback from the FDA, in the form of a written response or in-person meeting, on specific questions necessary to product development or application preparation. The FDA notes that the Pre-Sub program is entirely voluntary, but “strongly encourage{s}” it as a method for improving an application prior to submission.  The guidance states that Pre-Sub applications are most useful:

  1. Prior to conducting clinical, nonclinical, or analytic studies if the device has novel technology, has an indication which would make it a “first of a kind” device, or if the applicant needs specific guidance on planned nonclinical or clinical studies, or
  2. Before submitting a premarket application in order to inform the FDA of details of a novel device or to receive feedback on the ideal method for presenting data in the application.  

The guidance explains that this process is not intended for the FDA to design individualized study plans, and is not intended to be a back-and-forth, iterative series of meetings. It is intended to provide one-time advice on a certain topic. However, multiple Pre-Sub meetings may be allowed if all questions cannot be covered in one meeting. 

The Pre-Sub meeting request should include the following components:

  1. Cover Letter – including the reason for submission and proposed type of application
  2. Table of Contents
  3. Description of the Device – including pictures of the device, physical characteristics, materials, and mechanism of action; device samples and manufacturing details may be included where appropriate
  4. Proposed Intended Use/Indications for Use
  5. Summary of Related Previous Submissions or Discussions
  6. Overview of Product Development 7.Specific Questions for FDA Feedback 8.Desired Form of Feedback  

An Appendix to the Guidance provides specific recommendations for each of the different types of submissions (IDE, PMA, HDE, and 510(k)), as well as for in vitro diagnostic (IVD) Pre-Subs, including when to make such a submission, the contents of the submission, and examples of possible specific questions that an applicant may wish to pose to the FDA.

Further clarification to the process of obtaining the FDA feedback is provided, which has varied from Branch to Branch in recent years. The guidance states that the FDA will attempt to provide feedback within approximately 90 days of receipt of the Pre-Sub meeting request (which is 30 days longer than FDA’s historical practice of trying to respond within 60 days), and will plan to schedule a meeting within 75 days, but no longer than 90 days. The agency explains that for an in-person or teleconference meeting, the FDA will provide written responses to specific questions or suggestions for additional topics for the meeting at least 3 days prior to the meeting date.

The FDA cautions that supplements to the meeting request made prior to the meeting may delay the meeting. In addition, the agency warns that slides should not contain new information from that included in the briefing package. The FDA requests that the company share their slides with the agency at least two days prior to the meeting. The agency advises that the presentation should not be longer than one-third of the meeting time, and that 10 minutes should be left at the end of the meeting for a discussion of action items. The guidance states that at the meeting, the FDA will only provide feedback regarding questions or issues included in the meeting request. In addition, it clarifies that issues raised during the meeting do not have to be addressed in a subsequent Pre-Sub meeting, but can be addressed in the eventual IDE or marketing application. The FDA notes that the number of Pre-Subs should be limited to avoid unneeded expenditure of resources by the FDA and the sponsor.

The guidance explains that the applicant has the burden of drafting the initial meeting minutes, which are due to the FDA for review 15 days after the meeting. It states that FDA will provide edits in a timely manner, and the minutes will be considered final 15 days after edits are provided (unless the sponsor objects). The final meeting minutes are considered the FDA’s official feedback to the meeting request.

Finally, the FDA explains in the guidance that the agency intends to commit to the advice offered in a Pre-Sub meeting unless the circumstances are so materially altered such that the advice is no longer applicable, for example if a sponsor changes the proposed indication in the eventual submission. The agency recommends checking back in to verify that the FDA’s Pre-Sub advice is valid if more than a year has passed before a submission is filed.


The Pre-Sub guidance document provides a much-needed update to the agency’s pre-IDE guidance and procedures. While the guidance document generally codifies existing procedures that are being followed in the agency today, it provides a significant level of detail regarding the purpose of such meetings, the process, contents of submissions, the types of questions that are appropriate to discuss. Several new aspects to the process are proposed, including a detailed procedure for preparation of meeting minutes following the meeting. Importantly, the draft guidance, if implemented, would extend the agency’s response time on a Pre-Sub submission from 60 days, as outlined in existing guidance, to 90 days.

The guidance has lofty goals but, in practice, scheduling pre-IDE meetings and obtaining feedback has not always been easy due to time constraints and backlogs, especially within certain ODE divisions.  While industry will likely appreciate certain of the specific timelines outlined in the guidance document (regarding scheduling meetings, for example), others may be considered restrictive, such as the requirement for the sponsor to send slides to the FDA two or more days in advance of the meeting, and to submit meeting minutes within 15 days.

Finally, given the current variation between Branches in terms of pre-IDE procedures, the Pre-Sub guidance, when implemented, is expected to provide additional predictability to sponsors. For example, the FDA has been inconsistent in providing written feedback prior to meetings, so obtaining such feedback prior to the meeting would be a welcome addition to the procedures, if the agency lives up to the guidance.


The FDA has opened a public docket for comments on this draft guidance and will be accepting comments through 11 October 2012. Electronic comments on Docket No. FDA-2012-D-0530 can be submitted at www.regulations.gov. Written comments can be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.