
[Federal Register Volume 78, Number 115 (Friday, June 14, 2013)]
[Notices]
[Pages 35937-35939]
From the Federal Register Online via the Government Printing 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Exemption Clinical Investigations; Draft Guidance for Industry and Food 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availability of the draft guidance entitled ``FDA Decisions for 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

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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draft guidance is not final nor is it in effect at this time.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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by September 12, 2013.

ADDRESSES: Submit written requests for single copies of the draft 
guidance document entitled ``FDA Decisions for Investigational Device 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 dsmica@fda.hhs.gov 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]
BILLING CODE 4160-01-P


