[Federal Register Volume 79, Number 32 (Tuesday, February 18, 2014)]
[Notices]
[Pages 9226-9229]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-03453]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0530]


Requests for Feedback on Medical Device Submissions: The Pre-
Submission Program and Meetings With Food and Drug Administration 
Staff; Guidance for Industry and Food and Drug Administration Staff; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of the guidance entitled ``Requests for Feedback on 
Medical Device Submissions: The Pre-Submission Program and Meetings 
with

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FDA Staff.'' The purpose of this guidance is to provide an overview of 
the mechanisms available to application sponsors through which to 
obtain FDA feedback regarding potential or planned medical device 
submissions reviewed in the Center for Devices and Radiological Health 
(CDRH) and the Center for Biologics Evaluation and Research (CBER), 
including the Pre-Submission program (formerly the pre-Investigational 
Device Exemption (pre-IDE) program). In addition, the guidance provides 
recommendations regarding information that should be included in a Pre-
Submission Package. This guidance also describes the procedures that 
CDRH and CBER intend to follow when manufacturers, their 
representatives, or application sponsors request a meeting with review 
staff.

DATES: Submit either electronic or written comments on this guidance at 
any time. General comments on Agency guidance documents are welcome at 
any time.

ADDRESSES: Submit written requests for single copies of the guidance 
document entitled ``Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with FDA Staff'' 
to the Division of Small Manufacturers, International and Consumer 
Assistance, Center for Devices and Radiological Health, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 4613, Silver 
Spring, MD 20993-0002. Send one self-addressed adhesive label to assist 
that office in processing your request, or fax your request to 301-847-
8149. See the SUPPLEMENTARY INFORMATION section for information on 
electronic access to the guidance.
    Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852. Identify comments with the docket number 
found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Program Operations Staff (IDE), Center 
for Devices and Radiological Health, Food and Drug Administration, 
10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 301-796-5640; 
or Elizabeth Hillebrenner, Office of In Vitro Diagnostics and 
Radiological Health, Center for Devices and Radiological Health, Food 
and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 5616, 
Silver Spring, MD 20993-0002, 301-796-6346; or Stephen Ripley, Center 
for Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-
1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    Since its establishment in 1995, the pre-IDE program has been a 
successful resource for both medical device applicants and the FDA. 
Originally, this program was designed to provide applicants 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 other device submission program areas, such as Premarket Approval 
(PMA) applications, Humanitarian Device Exemption applications, 
Evaluation of Automatic Class III Designations (de novo petitions), 
Premarket Notification (510(k)) Submissions, and Clinical Laboratory 
Improvement Amendments Waiver by Application, as well as to address 
questions related to whether a clinical study requires submission of an 
IDE.
    The purpose of this guidance is to update the pre-IDE program to 
reflect this broader scope and make important modifications to reflect 
changes in the premarket program areas as a result of the Food and Drug 
Administration Amendments Act of 2007 (Pub. L. 110-85). This guidance 
also further expands the scope of the program to include those devices 
regulated by CBER, including those that are regulated as biologics 
under the Public Health Service Act and require submission of an 
Investigational New Drug Application (IND) and/or a Biologics License 
Application. Accordingly, FDA is changing the name for this program 
from the pre-IDE program to the Pre-Submission (Pre-Sub) program.
    Though successful, the Pre-Sub program has faced challenges, and 
the guidance is intended to address them and improve the Pre-Sub 
program by: (1) Describing the types of information that FDA would 
recommend submitting in order to get the best possible feedback from 
FDA; (2) outlining the process by which FDA meetings should be 
scheduled; and (3) explaining the Agency's expectations regarding 
advice given during the Pre-Sub process. This guidance outlines clear 
recommendations for sponsors and FDA staff.
    In addition to the Pre-Sub program, the guidance addresses other 
types of FDA feedback already available to applicants through other 
mechanisms. The Food and Drug Administration Modernization Act of 1997 
(FDAMA) (Pub. L. 105-115) established two types of formal early 
collaboration meetings (``determination meetings'' as described in 
section 513(a)(3)(D) of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) and ``agreement meetings'' as described in section 520(g)(7) of 
the FD&C Act) to provide clear direction for testing and development of 
devices requiring clinical investigations to support marketing. FDAMA 
also requires that FDA, upon written request, must meet with a PMA 
applicant no later than 100 days after the receipt of a PMA application 
that has been filed to discuss the review status of the application 
(referred to as a ``day-100 meeting'' and described in section 
515(d)(3) of the FD&C Act). For other premarket submissions under 
review, FDA will also grant meetings on an informal basis to discuss 
our requests for additional information to better ensure that the 
formal response to FDA's request will fully address the outstanding 
questions (these meetings are referred to as ``submission issue 
meetings''). FDA will respond to requests for a determination (called 
``study risk determinations'') whether a proposed device study is 
exempt from or subject to the IDE regulation (21 CFR part 812). For 
device studies that are subject to the IDE regulations, FDA will also 
provide its determination whether the study is a significant risk or 
nonsignificant risk study in response to a voluntary request for this 
information. In some cases, sponsors may wish to inform or educate FDA 
about ongoing device development or planned submissions without a 
specific request for feedback. FDA will, as resources allow, grant 
requests for such ``informational meetings.''
    As part of the Medical Device User Fee Amendments of 2012 (MDUFA 
III), FDA committed to instituting a structured process for managing 
Pre-Subs. This final guidance establishes such a structured process for 
submission and management of Pre-Subs as well as other types of 
requests for feedback. In addition, the guidance describes how FDA will 
internally track these requests as ``Q-Submissions,'' or ``Q-Subs,'' 
including what types of submissions will be handled as supplements and 
amendments to an initial Q-Sub. FDA has also revised the optional CDRH 
Cover Sheet (Form FDA 3514) to include submission types that more 
closely track with the types of feedback requests discussed in the 
guidance.
    FDA intends to provide the best possible advice in accordance with 
the information provided by the sponsor, to ensure it is captured 
accurately in the meeting minutes drafted by the sponsor,

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and commit to that advice unless the circumstances sufficiently change 
such that our advice is no longer applicable, such as when a sponsor 
changes the intended use of their device after we provide feedback. It 
is also our intention to hold timely meetings with appropriate staff 
and managers present, as resources permit. However, both our ability to 
provide advice and to hold timely meetings are dependent on our 
receiving the necessary information from the sponsor in advance of the 
meeting.
    Finally, the guidance describes the procedures that CDRH and CBER 
intend to follow when manufacturers, their representatives, or 
application sponsors request a meeting with review staff as the 
preferred method of feedback in response to a Pre-Sub, as an early 
collaboration meeting, or to discuss an existing regulatory submission. 
This guidance also recommends how to prepare for meetings with FDA 
staff.
    In the Federal Register of July 13, 2012 (77 FR 41413), FDA 
announced the availability of the draft guidance document. Interested 
persons were invited to comment by October 11, 2012. Seventeen sets of 
comments were received with multiple recommendations pertaining to the 
administrative processes and policies regarding the Pre-Sub program and 
meetings with FDA staff. The guidance was revised to provide a broader 
overview of available mechanisms for FDA feedback prior to a planned 
submission, with references to other existing guidance documents for 
those mechanisms where available. The guidance was also reorganized to 
discuss the various feedback mechanisms first, with a second section 
including specifics about meeting procedures that apply to all types of 
FDA feedback mechanisms where a meeting or teleconference is requested. 
Finally, an acceptance checklist for these submissions has been added 
as an appendix to clearly outline how FDA intends to determine if a Q-
Sub meets the definition of the identified Q-Sub type, and to determine 
if a qualifying request is administratively complete. It is not 
necessary for each element in the checklist to be present for the 
submission to be accepted. Instead, the acceptance checklist is 
intended to ensure only that the submission includes sufficient 
information for FDA to provide the requested feedback and/or identify 
the appropriate FDA attendees so that the meeting or teleconference can 
be scheduled.
    FDA received comments regarding the proposed timeframes for 
feedback to be provided to the applicant. Specifically, the guidance 
outlines a proposed target of 75 days, but generally no longer than 90 
days, for feedback in response to a Pre-Sub. Comments requested that 
FDA modify the guidance to include a timeframe of 60 days for response 
to a Pre-Sub. As part of the MDUFA III Commitment Letter (Ref. 1), FDA 
agreed to improve the Pre-Sub process ``as resources permit,'' but, 
because there were no additional resources provided for this program as 
part of the overall MDUFA III program, the recommended timeframe for 
FDA feedback in a Pre-Sub represents the time in which FDA believes 
that feedback generally can be provided without the application of 
additional resources to this specific program.
    Some comments expressed concern regarding FDA's recommendation that 
if more than 1 year has passed since our last feedback on key clinical 
trial design elements without a submission to the Agency, the sponsor 
should contact the review branch to confirm that the previous advice is 
still valid. The guidance has clarified that the reason for this 
recommendation is because clinical practice (including available 
alternative therapies or diagnostics) is rapidly evolving. The guidance 
has been further modified to clarify that a new Pre-Sub to the Agency 
is no longer recommended. Instead, confirmation that prior feedback is 
still valid can be accomplished through a phone call to the lead 
reviewer or branch chief.
    In response to other minor substantive and editorial comments, FDA 
revised the guidance document to clarify the processes and policies as 
appropriate.

II. Significance of Guidance

    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
Agency's current thinking on requests for FDA feedback, including the 
Pre-Sub program, and meetings with FDA staff. It does not create or 
confer any rights for or on any person and does not operate to bind FDA 
or the public. An alternative approach may be used if such approach 
satisfies the requirements of the applicable statute and regulations.

III. Electronic Access

    Persons interested in obtaining a copy of the guidance may do so by 
using the Internet. A search capability for all CDRH guidance documents 
is available at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm. Guidance 
documents are also available at http://www.regulations.gov. To receive 
``Requests for Feedback on Medical Device Submissions: The Pre-
Submission Program and Meetings with FDA Staff,'' you may either send 
an email request to [email protected] to receive an electronic copy of 
the document or send a fax request to 301-847-8149 to receive a hard 
copy. Please use the document number 1677 to identify the guidance you 
are requesting.

IV. Paperwork Reduction Act of 1995

    This guidance also refers to previously approved information 
collections found in FDA regulations. These collections of information 
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 
collections of information in 21 CFR part 803 are approved under OMB 
control number 0910-0437; the collections of information in 21 CFR part 
807, subpart E are approved under OMB control number 0910-0120; the 
collections of information in 21 CFR part 812 are approved under OMB 
control number 0910-0078; the collections of information in 21 CFR part 
814 are approved under OMB control number 0910-0231; and the 
collections of information for Request for Feedback on Medical Device 
Submissions are approved under OMB control number 0910-0756.

V. Comments

    Interested persons may submit either electronic comments to http://www.regulations.gov or written comments regarding this document to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

VI. Reference

    The following reference is available electronically at http://www.regulations.gov. (FDA has verified the Web site address in this 
reference section, but we are not responsible for any subsequent 
changes to the Web site after this document publishes in the Federal 
Register.)

    1. MDUFA III Commitment Letter, April 18, 2012, available at 
http://www.fda.gov/downloads/MedicalDevices/NewsEvents/WorkshopsConferences/UCM295454.pdf.



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    Dated: February 12, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-03453 Filed 2-14-14; 8:45 am]
BILLING CODE 4160-01-P