[Federal Register Volume 78, Number 115 (Friday, June 14, 2013)]
[Notices]
[Pages 35937-35939]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-14137]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-D-0790]
Food and Drug Administration Decisions for Investigational Device
Exemption Clinical Investigations; Draft Guidance for Industry and Food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availability of the draft guidance entitled ``FDA Decisions for
Investigational Device Exemption (IDE) Clinical Investigations.'' This
guidance document was initially issued in draft on November 10, 2011,
and was developed to promote the initiation of clinical investigations
to evaluate medical devices under FDA's IDE regulations. The guidance
was also intended to provide clarification
[[Page 35938]]
regarding the regulatory implications of the decisions that FDA may
render based on review of an IDE and to provide a general explanation
of the reasons for those decisions. This guidance has been revised and
is being reissued for comment because the Food and Drug Administration
Safety and Innovation Act (FDASIA), which became law on July 9, 2012,
amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act) to
specify certain situations in which FDA cannot disapprove an IDE. This
draft guidance is not final nor is it in effect at this time.
DATES: Although you can comment on any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency considers your comment on this
draft guidance before it begins work on the final version of the
guidance, submit either electronic or written comments on the draft
guidance by September 12, 2013.
ADDRESSES: Submit written requests for single copies of the draft
guidance document entitled ``FDA Decisions for Investigational Device
Exemption (IDE) Clinical Investigations'' 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 or
Office of Communication, Outreach and Development (HFM-40), Center for
Biologics Evaluation and Research (CBER), Food and Drug Administration,
1401 Rockville Pike, suite 200N, Rockville, MD 20852-1448. 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 draft 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: Owen Faris, Center for Devices and
Radiological Health, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 66, Rm. 1108, Silver Spring, MD 20993-0002, 301-796-6356;
or Stephen Ripley, Center for Biologics Evaluation and Research, Food
and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD
20852, 301-827-6210.
SUPPLEMENTARY INFORMATION:
I. Background
FDA approval of an IDE submission allows the initiation of a
clinical investigation of a significant risk device. This guidance is
intended to provide clarification regarding the regulatory implications
of the decisions that FDA may render based on review of an IDE and to
provide a general explanation of the reasons for those decisions. In an
effort to promote timely initiation of enrollment in clinical
investigations in a manner that protects study subjects, FDA has
developed methods to allow a clinical investigation of a device to
begin under certain circumstances, even when there are outstanding
issues regarding the IDE submission. These mechanisms, including
approval with conditions, staged approval, and communication of
outstanding issues related to the IDE through study design
considerations and future considerations, are described in this
guidance.
FDA has traditionally referred to IDE approvals that have
conditions as ``conditional approvals.'' FDA believes that the term
``approval with conditions'' is more appropriate because the term
conveys that the IDE has been approved and the study may begin without
awaiting further FDA review. An IDE may be approved with conditions if
FDA has determined that, despite outstanding issues, the information
provided is sufficient to justify human clinical evaluation of the
device and the proposed study design is acceptable with regard to
protection of study subjects.
FDA may now also communicate ``future considerations'', which are
issues and recommendations that FDA believes the sponsor should
consider in preparation for a marketing application or a future
clinical investigation. Future considerations are intended to provide
helpful, non-binding advice to sponsors regarding important elements of
the future application that the IDE may not specifically address. FDA
is considering whether future considerations should be communicated in
our IDE decision letters or whether they should be sent to the sponsor
in a separate communication. The Agency is specifically seeking comment
on this issue.
Consistent with the November 2011 draft guidance, this guidance
also proposes two other mechanisms for approving studies or approving
studies with conditions: ``Staged approval'' and ``staged approval with
conditions,'' by which FDA may grant IDE approval or approval with
conditions, while certain outstanding questions are answered concurrent
with enrollment of a limited number of subjects in the clinical
investigation. Staged approval and staged approval with conditions
permit the clinical investigation to begin in a timely manner while
maintaining appropriate subject protections. Staged approval or staged
approval with conditions is most common for pivotal studies in which
many subjects will be enrolled over an extended period of time, but may
be applicable to other clinical investigations as well.
Section 601 of FDASIA amended section 520(g) of the FD&C Act (21
U.S.C. 360j(g)) to specify certain situations in which FDA cannot
disapprove an IDE. Section 520(g)(4)(C) of the FD&C Act states that,
consistent with section 520(g)(1), FDA shall not disapprove an IDE
because: (1) The investigation may not support a substantial
equivalence or de novo classification determination or approval of the
device; (2) the investigation may not meet a requirement, including a
data requirement, relating to the approval or clearance of a device; or
(3) an additional or different investigation may be necessary to
support clearance or approval of the device. The draft guidance has
been revised in light of this new provision and to introduce the
communication to the sponsor of study design-related issues. If FDA
believes that additional modifications to the study design are needed,
which are unrelated to subject safety, for the study design to be
adequate and ultimately support a marketing application, if that is the
intent of the sponsor, these suggested modifications will be noted in
the ``study design considerations'' section of FDA's letter. Sponsors
are not required to modify the investigational plan to address study
design considerations. However, if these considerations are not
addressed, the study design may not support the study goals (e.g., a
future marketing application). FDA is considering whether study design
considerations should be communicated in our IDE decision letters or
whether they should be sent to the sponsor in a separate communication.
The Agency is specifically seeking comment on this issue.
Section 601 of FDASIA specifies certain situations in which FDA
cannot disapprove an IDE. However, the Agency recognizes that some IDE
sponsors may wish to determine whether the pivotal study design may
support a marketing application if it is successfully executed and
meets its stated endpoints without raising unforeseen safety concerns.
To meet this
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interest, FDA is proposing a new, voluntary program intended to
encourage device manufacturers to engage with the Agency in the
development of trial designs that may support a marketing approval or
clearance. The Agency recognizes that this type of voluntary program
will not likely be suitable for all IDE sponsors and does not intend
that this program become a routine step prior to submission of an IDE.
This program is not intended to replace or be a substitute for the Pre-
Submission process (Refer to the draft guidance entitled ``Medical
Devices: The Pre-Submission Program and Meetings with FDA Staff''
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm310375.htm, which, when finalized, will represent
FDA's current thinking on this topic).
This program, referred to as the ``Pre-Decisional IDE Process,'' is
a voluntary approach to enable sponsors to obtain timely feedback from
review staff on a near-final IDE application, with the opportunity for
a midcycle interaction with the review team to promote clearer
understanding and quicker resolution of major issues with device or
subject safety as well as study design. The Pre-Decisional IDE process
is different from the Pre-Submission process, which is appropriate for
focused discussions with FDA early in device development or when
nonclinical testing is underway. Pre-Submission discussions are
generally limited in nature, as they focus on the proposed protocol and
the specific questions for which the sponsor is requesting FDA
feedback. Additionally, FDA does not typically review data from
nonclinical bench, animal, or other studies when providing feedback on
a clinical study protocol as part of a Pre-Submission. In contrast,
Pre-Decisional IDEs will include data and full study protocols and
reports where appropriate, and will be reviewed in a similar manner as
an IDE, allowing for more complete and meaningful feedback from review
staff. FDA intends to adhere to the feedback and decisions reached
during the Pre-Decisional IDE review. FDA intends that modifications to
our feedback will be limited to situations in which FDA concludes that
the feedback given previously does not adequately address important
issues materially relevant to a determination of safety or
effectiveness that have been identified since the time of the Pre-
Decisional IDE. In such cases, FDA should acknowledge a change in our
advice, document the rationale for the change, and support the
determination with appropriate management concurrence.
Although this process, as proposed, would occur over a 65-day
timeframe (from submission of the Pre-Decisional IDE to complete FDA
feedback, inclusive of the midcycle interaction), FDA believes that
this process could result in faster approval without conditions of IDE
submissions with study designs that are sufficiently robust to support
market approval or clearance. Currently, many IDE submissions are
approved with conditions only after an initial disapproval and
submission of one or more responses, and may remain approved with
conditions over many months while the outstanding issues are addressed.
The Pre-Decisional IDE process is intended to reach an unconditional
approval more quickly, and will help to address several commonly
reported challenges in the initiation of clinical trials, such as
delays in institutional review board approvals and reimbursement from
third-party payers. In addition to seeking comments on the revised
draft guidance as a whole, the Agency is specifically seeking comment
on this new proposed program, as outlined in section 10 of the
guidance.
As a result of this draft guidance, FDA, where appropriate, seeks
to offer flexibility in how outstanding issues can be addressed to
allow clinical investigations to commence without unnecessary delay,
while ensuring that human subjects are adequately protected.
FDA issued this guidance document as draft on November 10, 2011.
The Agency has considered the comments received during the comment
period and incorporated modifications, as appropriate. This guidance
has also been revised to reflect the changes to the FD&C Act described
in this document and is being reissued in draft in order to solicit
comment on these significant revisions.
II. Significance of Guidance
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the Agency's current thinking on FDA
decisions for IDE clinical investigations. 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 draft guidance may do
so by using the Internet. A search capability for all Center for
Devices and Radiological Health 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 ``FDA Decisions for
Investigational Device Exemption (IDE) Clinical Investigations,'' 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 1783 to identify
the guidance you are requesting.
IV. Paperwork Reduction Act of 1995
This draft guidance refers to previously approved collections of
information 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 812 have been approved under
OMB control number 0910-0078.
V. Comments
Interested persons may submit either electronic comments regarding
this document to http://www.regulations.gov or written comments 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.
Dated: June 10, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-14137 Filed 6-13-13; 8:45 am]
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