[Federal Register Volume 82, Number 141 (Tuesday, July 25, 2017)]
[Notices]
[Pages 34538-34540]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-15534]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2015-D-3235]
M4E(R2): The Common Technical Document--Efficacy; International
Council for Harmonisation; Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a guidance entitled ``M4E(R2): The CTD--Efficacy.''
The guidance was prepared under the auspices of the International
Council for Harmonisation (ICH), formerly the International Conference
on Harmonisation. The guidance revises the ICH guidance ``M4E: The
CTD--Efficacy'' (M4E guidance). The revised guidance standardizes the
presentation of benefit-risk information in regulatory submissions,
providing greater specificity on the format and structure of benefit-
risk information. This revision is intended to facilitate communication
among regulators and industry.
DATES: Submit either electronic or written comments on Agency
guidance's at any time.
ADDRESSES: You may submit comments as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the
[[Page 34539]]
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-3235 for ``M4E(R2): The Common Technical Document--Efficacy;
International Council for Harmonisation; Guidance for Industry;
Availability.'' Received comments 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.
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research
(CDER), 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 guidance 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 document.
FOR FURTHER INFORMATION CONTACT:
Regarding the guidance: Pujita Vaidya, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, Rm. 1144, Silver Spring, MD 20993-0002, 301-796-0684; or
Steve 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 Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 1176, 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 October 2, 2015 (80 FR 59785), FDA
published a notice announcing the availability of a draft guidance
entitled ``M4E(R2): The CTD--Efficacy.'' The notice gave interested
persons an opportunity to submit comments by December 1, 2015.
After consideration of the comments received and revisions to the
guidance,
[[Page 34540]]
a final draft of the guidance was submitted to the ICH Assembly and
endorsed by the regulatory agencies on June 16, 2016.
Regulatory authorities approve drugs that are demonstrated to be
safe and effective for human use. The meaning of ``safe'' has
historically been interpreted to mean that the benefits of the drug
outweigh its risks. This benefit-risk assessment of pharmaceuticals is
the fundamental basis of regulatory decision-making. In the last
several years, providing greater structure for the benefit-risk
assessment has been an important topic in drug regulation. The M4E
guidance directs applicants to include their conclusions on benefits
and risks in the Clinical Overview of Module 2 of the Common Technical
Document (CTD) under section 2.5.6. Although general guidance is
provided in the M4E guidance regarding the expected content of section
2.5.6, no further structure is suggested to aid industry in developing
the benefit-risk assessment. As a result, regulators observe a high
degree of variability in the approaches taken by applicants in
presenting this information. This variability may not facilitate
efficient communication of industry views to regulators. Although
regulators and industry have developed approaches for structured
benefit-risk assessment and these approaches may take different forms,
there is a common thread evident that can inform harmonization of the
format and structure of benefit-risk assessments provided by applicants
in their regulatory submissions.
The revised M4E(R2) guidance provides more specific guidance
regarding the format and structure of the benefit-risk assessment in
section 2.5.6. Section 2.5.6 is divided into four subsections: (1)
Therapeutic context, (2) Benefit, (3) Risk, and (4) Benefit-Risk
Assessment. Each subsection describes the aspects that are most
pertinent to the benefit-risk assessment. This guidance also lists
characteristics that should be considered when identifying and
describing key benefits and key risks of the medicinal product.
Recognizing that there are many reasonable approaches for conducting a
benefit-risk assessment, M4E(R2) does not specify a particular approach
to be used by industry. However, the document does offer specific
guidance on the major elements that should be included in the benefit-
risk assessment. Furthermore, the revised guidance does not dictate an
approach used by a regulator in conducting a benefit-risk assessment.
This guidance also revises other sections of the guidance for
clarification, given the proposed revisions in section 2.5.6. In
addition, the revised guidance changes the numbering and the section
headings for consistency.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on this topic. It does not establish any rights
for any person and is not binding on FDA or the public. You can use an
alternative approach if it satisfies the requirements of the applicable
statutes and regulations. This guidance is not subject to Executive
Order 12866.
II. Paperwork Reduction Act of 1995
This guidance refers to previously approved collections of
information that are subject to review by the Office of Management and
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR parts 312 and 314 have
been approved under OMB control numbers 0910-0014 and 0910-0001,
respectively.
III. Electronic Access
Persons with access to the Internet may obtain the guidance at
https://www.regulations.gov, http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
Dated: July 18, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-15534 Filed 7-24-17; 8:45 am]
BILLING CODE 4164-01-P