M4E(R2): The Common Technical Document-Efficacy; International Council for Harmonisation; Guidance for Industry; Availability, 34538-34540 [2017-15534]
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Federal Register / Vol. 82, No. 141 / Tuesday, July 25, 2017 / Notices
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 December
24, 1997 (62 FR 67377), FDA published
a notice announcing the availability of
the ICH guidance for industry entitled
‘‘Q3C Impurities: Residual Solvents.’’
The guidance makes recommendations
as to what amounts of residual solvents
are considered toxicologically
acceptable for some residual solvents.
Upon issuance in 1997, the text and
appendix 1 of the guidance contained
several tables and a list of solvents
categorizing residual solvents by
toxicity, classes 1 through 3, with class
1 being the most toxic. The ICH Quality
Expert Working Group (EWG) agreed
that the PDE could be modified if
reliable and more relevant toxicity data
were brought to the attention of the
group and the modified PDE could
result in a revision of the tables and list.
In 1999, ICH instituted a Q3C
maintenance agreement and formed a
maintenance EWG (Q3C EWG). The
agreement provided for the revisitation
of solvent PDEs and allowed for minor
changes to the tables and list that
include the existing PDEs. The
agreement also provided for new
VerDate Sep<11>2014
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Jkt 241001
solvents and PDEs that could be added
to the tables and list based on adequate
toxicity data. In the Federal Register of
February 12, 2002 (67 FR 6542), FDA
briefly described the process for
proposing future revisions to the PDE.
In the same notice, the Agency
announced its decision to delink the
tables and list from the Q3C guidance
and create a stand-alone document
entitled ‘‘Q3C: Tables and List’’ to
facilitate making changes recommended
by ICH, available at https://
www.fda.gov/downloads/drugs/
guidancecomplianceregulatory
information/guidances/ucm073395.pdf.
The ‘‘Q3C: Tables and List’’ has been
updated as of January 2017 to include
the recommended PDE for triethylamine
and methylisobutylketone.
In the Federal Register of October 16,
2015 (80 FR 62537), FDA published a
notice announcing the availability of
draft recommendations for the PDEs for
two solvents, trimethylamine and
methylisobutylketone, according to the
maintenance procedures for the
guidance entitled ‘‘Q3C Impurities:
Residual Solvents,’’ available at https://
www.fda.gov/ucm/groups/fdagovpublic/@fdagov-drugs-gen/documents/
document/ucm073394.pdf. The notice
gave interested persons an opportunity
to submit comments by December 15,
2015. After consideration of the
comments received and revisions to the
guidance, a final draft of the
recommendations was submitted to the
ICH Assembly and endorsed by the
regulatory agencies in November 2016.
The guidance provides a new PDE for
the solvent trimethylamine and a
revised PDE for the solvent
methylisobutylketone. In addition, the
data used to derive the PDEs are
summarized. Revisions made to the
final guidance as a result of comments
include a modification of the PDE for
methylisobutylketone from 22.6
milligrams (mg)/day to 45 mg/day based
on reconsideration of the severity of
effects identified in rat studies and the
human relevance of effects identified in
mouse carcinogenicity study. The
recommendation to place
methylisobutylketone into class 2
remains. The ‘‘Q3C: Tables and List’’
has been updated as of January 2017 to
include the recommended PDE for
triethylamine and
methylisobutylketone.
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 ‘‘Q3C Impurities:
Residual Solvents.’’ It does not establish
any rights for any person and is not
binding on FDA or the public. You can
PO 00000
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use an alternative approach if it satisfies
the requirements of the applicable
statutes and regulations.
II. Electronic Access
Persons with access to the Internet
may obtain the document at https://
www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm, https://
www.fda.gov/BiologicsBloodVaccines/
GuidanceCompliance
RegulatoryInformation/Guidances/
default.htm, or https://
www.regulations.gov.
Dated: July 18, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning,
Legislation, and Analysis.
[FR Doc. 2017–15537 Filed 7–24–17; 8:45 am]
BILLING CODE 4164–01–P
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.
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.
SUMMARY:
Submit either electronic or
written comments on Agency guidance’s
at any time.
ADDRESSES: You may submit comments
as follows:
DATES:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
E:\FR\FM\25JYN1.SGM
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Federal Register / Vol. 82, No. 141 / Tuesday, July 25, 2017 / Notices
mstockstill on DSK30JT082PROD with NOTICES
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
VerDate Sep<11>2014
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Jkt 241001
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/201523389.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.
PO 00000
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34539
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,
E:\FR\FM\25JYN1.SGM
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34540
Federal Register / Vol. 82, No. 141 / Tuesday, July 25, 2017 / Notices
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 benefitrisk 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
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Jkt 241001
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, https://
www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm, or https://
www.fda.gov/BiologicsBloodVaccines/
GuidanceCompliance
RegulatoryInformation/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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
Office of the Commissioner; Statement
of Organization, Functions, and
Delegations of Authority
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA), Office of the
Commissioner (OC), and Office of
Operations (OO) have modified their
structures. This new organizational
structure was approved by the Secretary
of Health and Human Services on
SUMMARY:
PO 00000
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January 10, 2017 and effective on
February 11, 2017.
FOR FURTHER INFORMATION CONTACT:
Segaran Pillai, Ph.D., Director, Office of
Laboratory Science and Safety, Office of
the Commissioner, Food and Drug
Administration, White Oak Bldg. 1, Rm.
2218, 10903 New Hampshire Ave.,
Silver Spring, MD 20993–0002, 240–
402–2856.
SUPPLEMENTARY INFORMATION: Part D,
Chapter D–B, (Food and Drug
Administration), the Statement of
Organization, Functions, and
Delegations of Authority for the
Department of Health and Human
Services (35 FR 3685, February 25,
1970, 60 FR 56606, November 9, 1995,
64 FR 36361, July 6, 1999, 72 FR 50112,
August 30, 2007, 74 FR 41713, August
18, 2009, and 76 FR 45270, July 28,
2011) is amended to reflect the
reorganization of the Office of the
Commissioner and the Office of
Operations.
This reorganization establishes the
Office of Laboratory Science and Safety,
and will authorize the consolidation of
the laboratory science, safety functions,
and program activities across FDA
under one organizational component
that will report directly to the Office of
the Commissioner. The Employee Safety
and Environmental Management Staff
will be realigned from the Office of
Safety, Security and Crisis Management
to the Office of Laboratory Science and
Safety. As a result of the staff
realignment the Office of Safety,
Security and Crisis Management within
the Office of Operations will be re-titled
to the Office of Security and Emergency
Management. The Office of Crisis
Management within the newly titled
Office of Security and Emergency
Management will change its title to the
Office of Emergency Management.
Additionally, the Office of Security and
Emergency Management has established
the Emergency Planning, Evaluation,
and Exercise Staff, and the Program
Operations and Coordination Staff
within the Office of Emergency
Management.
The Food and Drug Administration,
Office of the Commissioner (OC), has
been restructured as follows:
DA. ORGANIZATION. The Office of
the Commissioner is headed by the
Commissioner of Food and Drugs and
includes the following organizational
units:
Office of the Commissioner (DA)
Office of the Chief Counsel (DAA)
Office of the Executive Secretariat
(DAB)
Executive Secretariat Staff (DAB1)
Freedom of Information Staff (DAB2)
E:\FR\FM\25JYN1.SGM
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]]>Agencies
[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, https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
https://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
