[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
[[Page 9227]]
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]
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