
[Federal Register Volume 77, Number 186 (Tuesday, September 25, 2012)]
[Notices]
[Pages 58998-58999]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-23545]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Draft Guidance for 
Industry: Oversight of Clinical Investigations: A Risk-Based Approach 
to Monitoring

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by October 
25, 2012.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All 
comments should be identified with the OMB control number 0910-New and 
title ``Draft Guidance for Industry on Oversight of Clinical 
Investigations: A Risk-Based Approach to Monitoring; Availability.'' 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Food and Drug 
Administration, 1350 Piccard Dr., PI50-400B, Rockville, MD 20850, 301-
796-7726, Ila.Mizrachi@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Draft Guidance for Industry: Oversight of Clinical Investigations: A 
Risk-Based Approach to Monitoring--(OMB Control Number 0910-New)

    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    Burden Estimate: The draft guidance is intended to assist sponsors 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 investigational new drug (IND) or investigational device 
exemption (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 
investigation(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,

[[Page 58999]]

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 Center for Drug 
Evaluation and Research (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).
    In the Federal Register of August 29, 2011 (76 FR 53683), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. The following is a summary of the comments 
and FDA's response to the comments for the two collections of 
information associated with the draft guidance that are not currently 
approved by OMB.
    Development of Comprehensive Monitoring Plan:
    FDA received comments that the guidance lacks specific information 
on development and initialization of risk assessment plans, appropriate 
mitigation plans, and execution of mitigation plans through the 
monitoring plan. Addition of use of risk management tools, along with 
potential applications for using risk-based monitoring strategies would 
help facilitate implementation.
    In response to the comments, FDA included additional detail in the 
final guidance in an effort to enhance the quality, utility, and 
clarity of the information collected. Specifically, FDA included 
additional detail on the development of a monitoring plan, which 
focuses on the important and likely risks, identified by the risk 
assessment, to critical data and processes. In addition, FDA included 
additional guidance on the steps involved in performing a risk 
assessment and references to tools and methodologies that can be used 
to perform a risk assessment. FDA clarified that the guidance does not 
provide comprehensive detail on how to perform a risk assessment.
    FDA received several comments that the guidance should specify that 
it is acceptable for monitoring plans to reference existing standard 
operating procedures (SOPs) or other documents.
    The draft guidance specifies that a monitoring plan may reference 
existing policies and procedures in order to minimize the burden of the 
collection of information.
    Voluntary Submission of Monitoring Plans to FDA:
    FDA received numerous comments that the lack of specific details 
about FDA review of the monitoring plans early enough in the IND 
process could delay startup of clinical trials. In addition, numerous 
comments requested a detailed process or procedure.
    Although the draft guidance stated that CDER was considering 
establishing processes through which sponsors could voluntarily submit 
monitoring plans for CDER feedback, CDER has concluded that CDER does 
not have the resources necessary to commit to such a review at this 
time. CDER is exploring the possibility of a pilot program in this area 
in the future.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                                         Number of
        Draft guidance on monitoring clinical investigations            Number of      responses per     Total annual   Average  burden    Total hours
                                                                       respondents       respondent       responses      per  response
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Development of Comprehensive Monitoring Plan.......................              88              1.5              132                4              528
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: September 17, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-23545 Filed 9-24-12; 8:45 am]
BILLING CODE 4160-01-P


