
[Federal Register Volume 81, Number 138 (Tuesday, July 19, 2016)]
[Notices]
[Pages 46938-46940]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-17009]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0315]


E2C(R2) Periodic Benefit-Risk Evaluation Report and E2C(R2) 
Periodic Benefit-Risk Evaluation Report--Questions and Answers; 
International Council for Harmonisation; Guidances for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of guidances for industry entitled ``E2C(R2) Periodic 
Benefit-Risk Evaluation'' (E2C(R2) guidance) and ``E2C(R2) Periodic 
Benefit-Risk Evaluation Report--Questions and Answers'' (E2C(R2) Q&A 
guidance). These guidances were prepared under the auspices of the 
International Council for Harmonisation (ICH), formerly the 
International Conference on Harmonisation. The E2C(R2) draft guidance, 
issued April 11, 2012, updated and combined two ICH guidances, ``E2C 
Clinical Safety Data Management: Periodic Safety Update Reports for 
Marketed Drugs'' (E2C guidance) and ``Addendum to E2C Clinical Safety 
Data Management: Periodic Safety Update Reports for Marketed Drugs'' 
(addendum to the E2C guidance). The E2C(R2) guidance is intended to 
describe the format, content, and timing of a Periodic Benefit-Risk 
Evaluation Report (PBRER) for an approved drug or biologic, and it 
finalizes the draft guidance. The E2C(R2) Q&A guidance is a 
supplementary guidance that is intended to clarify key issues in the 
E2C(R2) guidance.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

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 Submissions'' and ``Instructions'').

[[Page 46939]]

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-2012-D-0315 for ``E2C(R2) Periodic Benefit-Risk Evaluation Report 
and E2C(R2) Periodic Benefit-Risk Evaluation Report--Questions and 
Answers; International Council for Harmonisation; Guidances for 
Industry; Availability.'' 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.
    Submit written requests for single copies of these guidances to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002, or the Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. The guidances may also be obtained by mail by calling 
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance documents.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Maureen 
Melvin, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4480, Silver 
Spring, MD 20993-0002, 301-796-5366; or Stephen Ripley, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911.
    Regarding the ICH: Amanda Roache, Center for Biologics Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 1128, Silver Spring, MD 20993-0002, 301-796-4548.

SUPPLEMENTARY INFORMATION: 

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for harmonization 
initiatives to be developed with input from both regulatory and 
industry representatives. FDA also seeks input from consumer 
representatives and others. ICH is concerned with harmonization of 
technical requirements for the registration of pharmaceutical products 
for human use among regulators around the world. The six founding 
members of the ICH are the European Commission; the European Federation 
of Pharmaceutical Industries Associations; the Japanese Ministry of 
Health, Labour, and Welfare; the Japanese Pharmaceutical Manufacturers 
Association; CDER and CBER, FDA; and the Pharmaceutical Research and 
Manufacturers of America. The Standing Members of the ICH Association 
include Health Canada and Swissmedic. Any party eligible as a Member in 
accordance with the ICH Articles of Association can apply for 
membership in writing to the ICH Secretariat. The ICH Secretariat, 
which coordinates the preparation of documentation, operates as an 
international nonprofit organization and is funded by the Members of 
the ICH Association.
    The ICH Assembly is the overarching body of the Association and 
includes representatives from each of the ICH members and observers.
    In the Federal Register of April 11, 2012 (77 FR 21782), FDA 
published a notice announcing the availability of a draft guidance 
entitled ``E2C(R2) Periodic Benefit-Risk Evaluation Report.'' The draft 
E2C(R2) guidance updated and combined the E2C guidance and the addendum 
to the E2C guidance. The notice gave interested persons an opportunity 
to submit comments by May 11, 2012.
    After consideration of the comments received and revisions to the 
guidance, a final draft of the guidance was submitted to the ICH 
Steering Committee and endorsed by the regulatory agencies in November 
2012.
    The E2C(R2) guidance provides guidance on the format, content, and 
timing of a PBRER for an approved drug or biologic, and it finalizes 
the draft guidance. The PBRER will serve as a common standard for 
periodic reporting on approved drugs or biologics among the ICH 
regions. The harmonized PBRER is intended to promote a consistent 
approach to periodic postmarket safety reporting among the ICH regions 
and to enhance efficiency by reducing the number of reports

[[Page 46940]]

generated for submission to the regulatory authorities.
    Since the E2C(R2) draft guidance was made available in 2012, ICH 
has identified questions linked to the interpretation and application 
of the E2C(R2) guidance. The E2C(R2) Q&A guidance is intended to 
clarify questions relating to implementation of the E2C(R2) guidance.
    These guidances are being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The guidances represent 
the current thinking of FDA on the E2C(R2) PBRER. They do not establish 
any rights for any person and are not binding on FDA or the public. You 
can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.

II. The Paperwork Reduction Act of 1995

    These guidances refer 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 (PRA) (44 U.S.C. 3501-3520). 
The collection of information in the ``Guidance on Reporting in 
Accordance with International Council for Harmonisation--Periodic 
Benefit-Risk Evaluation Report (E2C(R2)) and Providing Waiver-Related 
Materials'' has been approved under OMB control number 0910-0771. The 
guidances also reference other collections of information. The 
collection of information in 21 CFR 314.80 has been approved under OMB 
control number 0910-0230, and the collection of information in 21 CFR 
600.80 has been approved under OMB control number 0910-0308.

III. Electronic Access

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

    Dated: July 13, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-17009 Filed 7-18-16; 8:45 am]
 BILLING CODE 4164-01-P


