
[Federal Register Volume 76, Number 167 (Monday, August 29, 2011)]
[Notices]
[Pages 53683-53685]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-21972]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0597]


Draft Guidance for Industry on Oversight of Clinical 
Investigations: A Risk-Based Approach to Monitoring; 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availability of a draft guidance for industry entitled ``Oversight of 
Clinical Investigations: A Risk-Based Approach to Monitoring.'' This 
guidance is intended to assist sponsors in developing risk-based 
monitoring strategies and plans for clinical investigations of human 
drugs, biologics, medical devices, and combinations thereof. The 
overarching goal of this guidance is to enhance human subject 
protection and the quality of clinical trial data. The guidance is 
intended to make clear that sponsors can use a variety of approaches to 
meet their monitoring responsibilities when conducting investigational 
new drug (IND) or investigational device exemption (IDE) studies.

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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by November 28, 2011.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002; the 
Office of Communication, Outreach and Development (HFM-40), Center for 
Biologics Evaluation and Research, Food and Drug Administration, 1401 
Rockville Pike, suite 200N, Rockville, MD 20852-1448; or the Office of 
Communication, Education and Radiation Programs, 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 requests. See the SUPPLEMENTARY INFORMATION section for 
electronic access to the draft guidance document.
    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.

FOR FURTHER INFORMATION CONTACT: Ann Meeker-O'Connell, Center for Drug 
Evaluation and Research (HFD-45), Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 51, rm. 5339, Silver Spring, MD 20993-0002, 
301-796-3150; 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; or Chrissy Cochran, 
Center for Devices and Radiological Health (HFZ-311), Food and Drug 
Administration, 10993 New Hampshire Ave., Bldg. 66, rm. 3453, Silver 
Spring, MD 20993-0002, 301-796-5490.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Oversight of Clinical Investigations: A Risk-Based Approach 
to Monitoring.'' FDA is publishing this new draft guidance to assist 
sponsors of clinical investigations in developing risk-based monitoring 
strategies and plans for clinical investigations of human drug and 
biological products, medical devices, and combinations thereof. This 
guidance is intended to make clear that sponsors can use a variety of 
approaches to meet their monitoring responsibilities during clinical 
investigations. This guidance describes a modern, risk-based approach 
to monitoring that focuses on critical study parameters and relies on a 
combination of monitoring activities to effectively oversee a study. 
For example, the guidance encourages greater use of centralized 
monitoring methods where appropriate. The guidance also makes 
recommendations about how to develop monitoring plans and document 
monitoring activities.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will

[[Page 53684]]

represent the Agency's current thinking on implementing a risk-based 
approach to the oversight of 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 statutes and 
regulations.

II. The Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal Agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information they 
conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 
60-day notice in the Federal Register for each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is publishing this notice of the 
proposed collection of information set forth in this document.
    With respect to the collection of information associated with this 
draft guidance, FDA invites comments on the following topics: (1) 
Whether the proposed collection of information is necessary for the 
proper performance of FDA's functions, including whether the 
information will have practical utility; (2) the accuracy of FDA's 
estimated burden of the proposed collection of information, including 
the validity of the methodology and assumptions used; (3) ways to 
enhance the quality, utility, and clarity of the information collected; 
and (4) ways to minimize the burden of the collection of information on 
respondents, including through the use of automated collection 
techniques, when appropriate, and other forms of information 
technology.
    Title: Draft Guidance for Industry: Oversight of Clinical 
Investigations: A Risk-Based Approach to Monitoring.
    Description of Respondents: Respondents to this collection of 
information are sponsors that monitor clinical investigations.
    Burden Estimate: The draft guidance is intended to assist sponsors 
of clinical investigations in developing risk-based monitoring 
strategies and plans for investigational studies of medical products, 
including human drug and biological products, medical devices, and 
combinations thereof. The guidance is intended to make clear that 
sponsors can use a variety of approaches to fulfill their 
responsibilities related to monitoring investigator conduct and the 
progress of IND or IDE studies. The guidance describes strategies for 
monitoring activities performed by a sponsor, or contract research 
organizations (CROs), that focus on the conduct, oversight, and 
reporting of findings of an investigation by clinical investigators. 
The guidance recommends strategies that reflect a risk-based approach 
to monitoring that focuses on critical study parameters and relies on a 
combination of monitoring activities to oversee a study effectively. 
The guidance specifically encourages greater reliance on centralized 
monitoring methods, where appropriate.
    Sponsors are required to provide appropriate oversight of their 
clinical investigations to ensure adequate protection of the rights, 
welfare, and safety of human subjects and the quality and integrity of 
the resulting data submitted to FDA.\1\ As part of this oversight, 
sponsors of clinical investigations are required to monitor the conduct 
and progress of their clinical investigations.2 3 The 
regulations are not specific about how sponsors are to conduct 
monitoring of clinical investigations and, therefore, are compatible 
with a range of approaches to monitoring. FDA currently has OMB 
approval for the information collection required under part 812 (OMB 
control number 0910-0078) and part 312, including certain provisions 
under subpart D (OMB control number 0910-0014).
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    \1\ Part 312 (21 CFR part 312), subpart D, generally 
(Responsibilities of Sponsors and Investigators) and part 812 (21 
CFR part 812), subpart C, generally (Responsibilities of Sponsors).
    \2\ Section 312.50 requires a sponsor to, among other things, 
ensure ``proper monitoring of the investigation(s)'' and ``that the 
investigations(s) is conducted in accordance with the general 
investigational plan and protocols contained in the IND.''
    \3\ Also see Sec. Sec.  312.53(d), 312.56(a), 812.40, and 
812.43(d).
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    However, the collections of information associated with this draft 
guidance that are not currently approved under OMB control numbers 
0910-0014 or 0910-0078 are as follows:
    Development of Comprehensive Monitoring Plan: Section IV.D of the 
draft guidance recommends that sponsors develop a prospective, detailed 
monitoring plan that describes the monitoring methods, 
responsibilities, and requirements for each clinical trial. The plan 
should provide those involved in monitoring with adequate information 
to effectively carry out their duties. All sponsor and CRO personnel 
who may be involved with monitoring, including those who review and/or 
determine appropriate action regarding potential issues identified 
through monitoring, should review the monitoring plan. The components 
of a monitoring plan are described in the draft guidance, including 
monitoring plan amendments (i.e., the review and revision of monitoring 
plans and processes for timely updates). FDA understands that sponsors 
currently develop monitoring plans; however, not all monitoring plans 
contain all the elements described in the guidance. Therefore, our 
following burden estimate provides the additional time that a sponsor 
would expend in developing a comprehensive monitoring plan based on the 
recommendations in the guidance. We estimate that approximately 88 
sponsors will develop approximately 132 comprehensive monitoring plans 
in accordance with the draft guidance, and that the added burden for 
each plan will be approximately 4 hours to develop, including the time 
needed for preparing monitoring plan amendments when appropriate (a 
total of 528 hours).
    Voluntary Submission of Monitoring Plans to FDA: Section IV.D of 
the draft guidance permits sponsors to voluntarily and prospectively 
submit their monitoring plans to the appropriate CDER review division 
and request input from the division's clinical trial oversight 
component (sponsors of significant risk device studies are already 
required under Sec.  812.25(e) to submit and maintain written 
procedures for monitoring). We estimate that approximately 22 sponsors 
will submit approximately 33 monitoring plans to CDER for feedback and 
that each submission will take approximately 2 hours to complete (a 
total of 66 hours).
    FDA estimates the burden of this collection of information as 
follows:

[[Page 53685]]



                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                     Number of                        Average
  Draft guidance on monitoring       Number of     responses per   Total annual     burden per      Total hours
     clinical investigations        respondents     respondent       responses       response
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Development of Comprehensive                  88             1.5             132               4             528
 Monitoring Plan................
Voluntary Submission of                       22             1.5              33               2              66
 Monitoring Plans to FDA........
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    Total.......................             N/A             N/A             N/A               6             594
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

III. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed 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.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm, http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm, or http://www.regulations.gov.

    Dated: August 23, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-21972 Filed 8-26-11; 8:45 am]
BILLING CODE 4160-01-P


