
[Federal Register Volume 81, Number 104 (Tuesday, May 31, 2016)]
[Notices]
[Pages 34345-34347]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-12651]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-3327]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; E6(R2) Good Clinical Practice; International Council 
for Harmonisation

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA, we, or the Agency) is 
announcing an opportunity for public comment on the proposed collection 
of certain information by the Agency. Under the Paperwork Reduction Act 
of 1995 (the PRA), Federal Agencies are required to publish notice in 
the Federal Register concerning each proposed collection of information 
and to allow 60 days for public comment in response to the notice. This 
notice solicits comments on the collections of information marked as 
``ADDENDUM'' in the draft guidance entitled ``E6(R2) Good Clinical 
Practice'' (E6(R2) draft guidance). The E6(R2) draft guidance was 
prepared under the auspices of the International Council for 
Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH). The E6(R2) draft guidance amends 
the guidance entitled ``E6 Good Clinical Practice: Consolidated 
Guidance'' (E6(R1) consolidated guidance), issued in April 1996, to 
encourage implementation of improved and more efficient approaches to 
clinical trial design, conduct, oversight, recording, and reporting 
while continuing to ensure human subject protection and data integrity. 
Standards regarding electronic records and essential documents intended 
to increase clinical trial quality and efficiency have also been 
updated. The E6(R2) draft guidance was intended to improve clinical 
trial quality and efficiency while maintaining human subject 
protection. This notice solicits comments on the collection of 
information in the draft guidance concerning the development of a 
system to manage quality, as well as information to include in a 
clinical study report about the quality management approach.

DATES: Submit either electronic or written comments on the collection 
of information by August 1, 2016 on the ``ADDENDUM'' sections of the 
E6(R2) draft guidance.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submission'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2015-D-3327 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; E6(R2) Good Clinical Practice; 
International Council for Harmonisation.'' Received comments will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at http://www.regulations.gov or at 
the Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food

[[Page 34346]]

and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: Under 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 concerning each proposed collection of information before 
submitting the collection to OMB for approval. To comply with this 
requirement, FDA is publishing notice of the proposed collection of 
information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these 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 estimate of the 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 to be 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.

E6(R2) Good Clinical Practice Draft Guidance; International Council for 
Harmonisation OMB Control Number 0910-NEW

I. Background

    In the Federal Register of September 29, 2015 (80 FR 58492), we 
announced the availability of and requested public comments on the 
E6(R2) draft guidance. The draft guidance is the product of the ICH E6 
Expert Working Group of the ICH. The E6(R2) draft guidance provides 
additions to the E6(R1) consolidated guidance that are identified as 
``ADDENDUM'' and marked with vertical lines on both sides of the text. 
The additions are intended to encourage implementation of the described 
approaches and processes to improve the quality and efficiency of 
clinical trials while maintaining the protection of human subjects. The 
E6(R2)draft guidance includes information collection provisions that 
are subject to review by OMB under the PRA. This Federal Register 
notice begins the process of requesting public comment and obtaining 
OMB approval for those information collections that are new and are not 
already covered by previously approved collections of information.

II. Burden Estimates for the E6(R2) Draft Guidance

    The E6(R2) draft guidance recommends that sponsors develop and 
maintain a system to manage quality when designing, conducting, 
recording, evaluating, reporting, and archiving clinical trials. The 
draft guidance also recommends that the sponsor describe the quality 
management approach implemented in the trial and summarize important 
deviations from the predefined quality tolerance limits in the clinical 
study report. We are requesting OMB approval for the following 
collections of information identified in the ``ADDENDUM'' sections of 
the E6(R2) draft guidance and are inviting public comments on these 
sections.
    In table 1 of this document, we estimate that approximately 1,457 
sponsors of clinical trials of human drugs will develop approximately 
1,457 quality management systems per year (as described in section 5.0 
of the E6(R2) draft guidance). We further estimate that it will take 
sponsors approximately 60 hours to develop and implement each quality 
management system, totaling 87,420 hours annually. These estimates are 
based on the number of annual investigational new drug applications 
(IND) and new drug applications (NDA) submitted to the Center for Drug 
Evaluation and Research in previously approved collections of 
information. The estimated number of sponsors that will develop a 
quality management system as described in the guidance, as well as the 
estimated number of hours it will take, is based on FDA interactions 
with sponsors about activities that support drug development plans.
    In table 2 of this document, we estimate that approximately 1,457 
sponsors of clinical trials of human drugs will describe the quality 
management approach implemented in a clinical trial and summarize 
important deviations from the predefined quality tolerance limits in a 
clinical study report (as described in section 5.0.7 of the E6(R2) 
draft guidance). We further estimate that sponsors will submit 
approximately 4.6 responses per respondent and that it will take 
sponsors 3 hours to complete this reporting task, totaling 20,107 
reporting hours annually. These estimates are based on past experiences 
with IND, NDA, and previously approved collections of information.
    In table 3 of this document, we estimate that approximately 218 
sponsors of clinical trials of biological products will develop 
approximately 218 quality management systems per year (as described in 
section 5.0.7 of the E6(R2) draft guidance). We further estimate that 
it will take sponsors approximately 60 hours to develop and implement 
each quality management system, totaling 13,080 hours annually. These 
estimates are based on past experiences with INDs, biologics license 
applications (BLA), and previously approved collections of information.
    In table 4 of this document, we estimate that 218 sponsors of 
biological products will describe the quality management approach 
implemented in a clinical trial and summarize important deviations from 
the predefined quality tolerance limits in a clinical study report (as 
described in section 5.0.7 of the E6(R2) draft guidance). We further 
estimate that sponsors will submit approximately 3.69 responses per 
respondent and that it will take sponsors 3 hours to complete this 
reporting task, totaling 2,413 reporting hours annually. As described 
previously, these estimates are also based on past experiences with 
IND, BLA, and previously approved collections of information.
    FDA estimates the burden of this collection of information as 
follows:

                                           Table 1--Estimated Annual Recordkeeping Burden for Human Drugs \1\
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                                                                                         Number of                       Average burden
      E6(R2) Good Clinical Practice; International Council for          Number of       records per      Total annual         per          Total hours
             Harmonisation; Draft Guidance for Industry               recordkeepers     recordkeeper       records       recordkeeping
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Section 5.0--Quality Management (including sections 5.0.1 to 5.0.7)           1,457                1            1,457               60           87,420

[[Page 34347]]

 
Developing a Quality Management System.............................
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


                                             Table 2--Estimated Annual Reporting Burden for Human Drugs \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of
      E6(R2) Good Clinical Practice; International Council for          Number of      responses per     Total annual    Average burden    Total hours
             Harmonisation; Draft Guidance for Industry                respondents       respondent       responses       per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Section 5.0.7--Risk Reporting......................................           1,457              4.6            6,702                3           20,107
Describing the Quality Management Approach Implemented in a
 Clinical Trial and Summarizing Important Deviations From the
 Predefined Quality Tolerance Limits in a Clinical Study Report....
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


                                            Table 3--Estimated Annual Recordkeeping Burden for Biologics \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of
      E6(R2) Good Clinical Practice; International Council for          Number of       records per     Total records    Average burden    Total hours
             Harmonisation; Draft Guidance for Industry               recordkeepers     recordkeeper                       per record
--------------------------------------------------------------------------------------------------------------------------------------------------------
Section 5.0--Quality Management (including 5.0.1 to 5.0.7).........             218                1              218               60           13,080
Developing a Quality Management System.............................
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


                                              Table 4--Estimated Annual Reporting Burden for Biologics \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                         Number of
      E6(R2) Good Clinical Practice; International Council for          Number of      responses per     Total annual    Average burden    Total hours
             Harmonisation; Draft Guidance for Industry                 responses        respondent       responses       per response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Section 5.0.7--Risk Reporting......................................             218             3.69              804                3            2,413
Describing the Quality Management Approach Implemented in a
 Clinical Trial and Summarizing Important Deviations From the
 Predefined Quality Tolerance Limits in a Clinical Study Report....
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    The collections of information included in the sections marked as 
``ADDENDUM'' in the E6(R2) draft guidance also refers to previously 
approved collections of information found in FDA regulations. These 
collections of information are subject to review by OMB under the PRA. 
The collections of information found in 21 CFR part 11 have been 
approved under OMB control number 0910-0303; the collections of 
information found in 21 CFR part 312 have been approved under OMB 
control number 0910-0014; and collections of information found in 21 
CFR part 314 have been approved under OMB control number 0910-0001. The 
collections of information found in 21 CFR part 601 have been approved 
under OMB control number 0910-0338.

    Dated: May 24, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-12651 Filed 5-27-16; 8:45 am]
BILLING CODE 4164-01-P


