[Federal Register Volume 84, Number 172 (Thursday, September 5, 2019)]
[Notices]
[Pages 46742-46744]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-19113]


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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; Guidance for Industry on E6(R2) Good Clinical 
Practice; International Council for Harmonisation; Integrated Addendum 
to International Council for Harmonisation E6(R1)

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing an opportunity for public comment on the proposed collection 
of certain information by the Agency. Under the Paperwork Reduction Act 
of 1995 (PRA), Federal Agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on information collection 
recommendations found in Agency guidance pertaining to 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 November 4, 2019.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. Electronic comments 
must be submitted on or before November 4, 2019. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of November 4, 2019. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://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 https://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 Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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 ``Guidance for Industry on E6(R2) Good Clinical 
Practice; International Council for Harmonisation; Integrated Addendum 
to ICH E6(R1).'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff 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 https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
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, including 
each proposed extension of an

[[Page 46743]]

existing 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.

Guidance for Industry on E6(R2) Good Clinical Practice; International 
Council for Harmonisation; Integrated Addendum to ICH E6(R1)

OMB Control Number 0910-0843--Extension

    This information collection request supports recommendations found 
in the Agency guidance entitled ``E6(R2) Good Clinical Practice; 
Integrated Addendum to ICH E6(R1)'' (ICH E6(R2). The guidance was 
originally prepared under the auspices of the International Council for 
Harmonisation (ICH) (formerly the International Conference on 
Harmonisation); it amends the ICH guidance for industry entitled ``E6 
Good Clinical Practice: Consolidated Guidance'' (issued in April 1996). 
The guidance is intended to facilitate implementation of improved and 
more efficient approaches to clinical trial design, including conduct, 
oversight, recording, and reporting. This is intended to increase 
clinical trial quality and efficiency while continuing to ensure human 
subject protection and reliability of trial results. Included in the 
guidance are additions identified as ``ADDENDUM'' and marked with 
vertical lines on both sides of the text.
    Standards regarding electronic records and essential documents 
intended to increase clinical trial quality and efficiency have also 
been updated. The guidance is available from our website at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e6r2-good-clinical-practice-integrated-addendum-ich-e6r1.
    We estimate the burden of the information collection as follows:

                                           Table 1--Estimated Annual Recordkeeping Burden for Human Drugs \1\
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      Guidance for industry on E6(R2) good clinical practice;                            Number of                      Average  burden
  International Council for Harmonisation; integrated  addendum to      Number of       records per      Total annual         per          Total hours
                             ICH E6(R1)                               recordkeepers     recordkeeper       records       recordkeeping
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Section 5. Quality Management (including sections 5.0.1 to 5.0.7)--           1,457                1            1,457               60           87,420
 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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
      Guidance for industry on E6(R2) good clinical practice;                            Number of
  International Council for Harmonisation; integrated  addendum to      Number of      responses per     Total annual   Average  burden    Total hours
                             ICH E6(R1)                                respondents       respondent       responses      per  response
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Section 5.0.7. Risk Reporting--Describing the Quality Management              1,457              4.6            6,702                3           20,106
 Approach Implemented in a Clinical Trial and Summarizing Important
 Deviations From the Predefined Quality Tolerance Limits and
 Remedial Actions Taken in the 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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
      Guidance for industry on E6(R2) good clinical practice;                            Number of                      Average  burden
International Council for Harmonisation; integrated addendum to ICH     Number of       records per      Total annual         per          Total hours
                               E6(R1)                                 recordkeepers     recordkeeper       records       recordkeeping
--------------------------------------------------------------------------------------------------------------------------------------------------------
Section 5. Quality Management (including sections 5.0.1 to 5.0.7)--             423                1              423               60           25,380
 Developing a Quality Management System............................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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\
--------------------------------------------------------------------------------------------------------------------------------------------------------
      Guidance for industry on E6(R2) good clinical practice;                            Number of
International Council for Harmonisation; integrated addendum to ICH     Number of      responses per     Total annual   Average  burden    Total hours
                               E6(R1)                                  respondents       respondent       responses      per  response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Section 5.0.7. Risk Reporting--Describing the Quality Management                423             1.56              660                3            1,980
 Approach Implemented in a Clinical Trial and Summarizing Important
 Deviations From the Predefined Quality Tolerance Limits and
 Remedial Actions Taken in the Clinical Study Report...............
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


[[Page 46744]]

    In table 1, we estimate 1,457 sponsors of clinical trials of human 
drugs will develop approximately 1,457 quality management systems per 
year (as described in ICH E6(R2) in section 5.0, including sections 
5.0.1 to 5.0.7). We assume it will take respondents 60 hours to develop 
and implement each quality management system, totaling 87,420 hours 
annually. The estimated number of sponsors who will develop a quality 
management system as described in ICH E6(R2) is based on the number of 
annual investigational new drug applications (INDs) and new drug 
applications (NDAs) submitted to FDA's Center for Drug Evaluation and 
Research. The estimated number of hours we assume it takes to develop a 
quality management system is based on informal interactions with 
industry about activities that support drug development plans.
    In table 2, we estimate 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 and remedial actions taken in the clinical 
study report (as described in section 5.0.7 of ICH E6(R2)). 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 20,106 reporting hours annually. These 
estimates are based on our past experiences with INDs and NDAs.
    In table 3, we estimate 423 sponsors of clinical trials of 
biological products will develop 423 quality management systems per 
year (as described in ICH E6(R2) in section 5.0, including sections 
5.0.1 to 5.0.7). We assume it will take respondents 60 hours to develop 
and implement each quality management system, totaling 25,380 hours 
annually. The estimated number of sponsors who will develop a quality 
management system as described in ICH E6(R2) is based on the number of 
annual INDs and biologics license applications (BLAs) submitted to 
FDA's Center for Biologics Evaluation and Research. The estimated 
number of hours we assume it takes to develop a quality management 
system is based on informal interactions with industry about activities 
that support drug development plans.
    In table 4, we estimate 423 sponsors of clinical trials of 
biological products will describe the quality management approach 
implemented in a clinical trial and summarize important deviations from 
the predefined quality tolerance limits and remedial actions taken in a 
clinical study report (as described in section 5.0.7 of ICH E6(R2)). We 
further estimate that sponsors will submit approximately 660 responses 
per respondent and that it will take sponsors 3 hours to complete this 
reporting task, totaling 1,980 reporting hours annually. As described 
previously, these estimates are based on past experiences with INDs and 
BLAs submitted to FDA.
    Although our estimated burden for the information collection 
reflects an overall decrease of 433 hours, we have increased the 
estimate by 861 records. We are making this adjustment based on an 
increase in the number of submissions we received over the last few 
years.

    Dated: August 28, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-19113 Filed 9-4-19; 8:45 am]
 BILLING CODE 4164-01-P


