80 FR 59785 - M4E(R2): The Common Technical Document-Efficacy; International Conference on Harmonisation; Draft Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 80, Issue 191 (October 2, 2015)
Food and Drug Administration
Federal Register Volume 80, Issue 191 (October 2, 2015)
| Page Range | 59785-59786 | |
| FR Document | 2015-25122 |
[Federal Register Volume 80, Number 191 (Friday, October 2, 2015)] [Notices] [Pages 59785-59786] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-25122] [[Page 59785]] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2015-D-3235] M4E(R2): The Common Technical Document--Efficacy; International Conference on Harmonisation; Draft Guidance for Industry; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance entitled ``M4E(R2): The CTD-- Efficacy'' (M4E(R2)). The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). In August 2001, FDA made available guidance on preparing the efficacy components of an application file in the common technical document (CTD) format (``M4E: The CTD--Efficacy'' (M4E guidance)). This draft guidance revises the M4E guidance. The revised draft guidance standardizes the presentation of benefit-risk information in regulatory submissions, providing greater specificity on the format and structure of benefit-risk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: Although you can comment on any guidance at any time (see 21 CFR 10.115 (g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by December 1, 2015. ADDRESSES: Submit written requests for single copies of the draft guidance to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research (CDER), Food and Drug Administration, 10001 New Hampshire Ave.,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 the office in processing your requests. The draft guidance may also be obtained by mail by calling CBER at 1-800-835-4709 or 240-402-7800. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document. Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. 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 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: Michelle Limoli, Center for Drug Evaluation and Research, International Programs, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7212, Silver Spring, MD 20993-0002, 301-796-8377. 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 and harmonized technical procedures for pharmaceutical development. One of the goals of harmonization is to identify and reduce differences in technical requirements for drug development among regulatory Agencies. ICH was organized to provide an opportunity for tripartite harmonization initiatives to be developed with input from both regulatory and industry representatives. FDA also seeks input from other interested stakeholders. ICH is concerned with harmonization of technical requirements for the registration of pharmaceutical products among three regions: Europe, Japan, and North America. The eight ICH sponsors 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; the Pharmaceutical Research and Manufacturers of America; Health Canada; and Swissmedic. The ICH Secretariat, which coordinates the preparation of documentation, is provided by the International Federation of Pharmaceutical Manufacturers Associations (IFPMA). The ICH Steering Committee includes representatives from each of the ICH sponsors and the IFPMA, as well as observers such as the World Health Organization. In August 2015, the ICH Steering Committee agreed that a draft guidance entitled ``M4E(R2): The CTD--Efficacy'' should be made available for public comment. The draft guidance is the product of the M4E(R2) Expert Working Group of the ICH. Comments about this draft will be considered by FDA and the Expert Working Group. ICH M4E(R2) revises the M4E guidance (made available in August 2001), which covers the Clinical Overview and Clinical Summary of Module 2 of the CTD and the Clinical Study Reports of Module 5. The revised draft guidance provides more specific guidance regarding the format and structure of the benefit-risk assessment in section 2.5.6; it also revises other sections of the guidance for clarification, given the proposed revisions in section 2.5.6. In addition, the revised draft guidance changes the numbering and the section headings for consistency. 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 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 [[Page 59786]] assessments provided by applicants in their regulatory submissions. 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, consistent with the concept paper that laid the groundwork for the Expert Working Group, the revised draft guidance does not dictate an approach used by a regulator in conducting a benefit-risk assessment. This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent 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. II. Comments Interested persons may submit either electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov. 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: September 28, 2015. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2015-25122 Filed 10-1-15; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 80, No. 191 / Friday, October 2, 2015 / Notices 59785
DEPARTMENT OF HEALTH AND the SUPPLEMENTARY INFORMATION section ICH Secretariat, which coordinates the
HUMAN SERVICES for electronic access to the draft preparation of documentation, is
guidance document. provided by the International
Food and Drug Administration Submit electronic comments on the Federation of Pharmaceutical
[Docket No. FDA–2015–D–3235] draft guidance to http:// Manufacturers Associations (IFPMA).
www.regulations.gov. Submit written The ICH Steering Committee includes
M4E(R2): The Common Technical comments to the Division of Dockets representatives from each of the ICH
Document—Efficacy; International Management (HFA–305), Food and Drug sponsors and the IFPMA, as well as
Conference on Harmonisation; Draft Administration, 5630 Fishers Lane, Rm. observers such as the World Health
Guidance for Industry; Availability 1061, Rockville, MD 20852. Organization. In August 2015, the ICH
FOR FURTHER INFORMATION CONTACT: Steering Committee agreed that a draft
AGENCY: Food and Drug Administration, guidance entitled ‘‘M4E(R2): The CTD—
Regarding the guidance: Pujita Vaidya,
HHS. Efficacy’’ should be made available for
Center for Drug Evaluation and
ACTION: Notice. Research, Food and Drug public comment. The draft guidance is
Administration, 10903 New Hampshire the product of the M4E(R2) Expert
SUMMARY: The Food and Drug
Ave., Bldg. 51, Rm. 1144, Silver Spring, Working Group of the ICH. Comments
Administration (FDA or Agency) is
MD 20993–0002, 301–796–0684; or about this draft will be considered by
announcing the availability of a draft
Stephen Ripley, Center for Biologics FDA and the Expert Working Group.
guidance entitled ‘‘M4E(R2): The CTD—
Efficacy’’ (M4E(R2)). The draft guidance Evaluation and Research, Food and ICH M4E(R2) revises the M4E
was prepared under the auspices of the Drug Administration, 10903 New guidance (made available in August
International Conference on Hampshire Ave., Bldg. 71, Rm. 7301, 2001), which covers the Clinical
Harmonisation of Technical Silver Spring, MD 20993–0002, 240– Overview and Clinical Summary of
Requirements for Registration of 402–7911. Module 2 of the CTD and the Clinical
Pharmaceuticals for Human Use (ICH). Regarding the ICH: Michelle Limoli, Study Reports of Module 5. The revised
In August 2001, FDA made available Center for Drug Evaluation and draft guidance provides more specific
guidance on preparing the efficacy Research, International Programs, Food guidance regarding the format and
components of an application file in the and Drug Administration, 10903 New structure of the benefit-risk assessment
common technical document (CTD) Hampshire Ave., Bldg. 71, Rm. 7212, in section 2.5.6; it also revises other
format (‘‘M4E: The CTD—Efficacy’’ Silver Spring, MD 20993–0002, 301– sections of the guidance for
(M4E guidance)). This draft guidance 796–8377. clarification, given the proposed
revises the M4E guidance. The revised SUPPLEMENTARY INFORMATION: revisions in section 2.5.6. In addition,
draft guidance standardizes the the revised draft guidance changes the
I. Background numbering and the section headings for
presentation of benefit-risk information
in regulatory submissions, providing In recent years, many important consistency.
greater specificity on the format and initiatives have been undertaken by Regulatory authorities approve drugs
structure of benefit-risk information. regulatory authorities and industry that are demonstrated to be safe and
This revision is intended to facilitate associations to promote international effective for human use. The meaning of
communication among regulators and harmonization of regulatory ‘‘safe’’ has historically been interpreted
industry. requirements. FDA has participated in to mean that the benefits of the drug
many meetings designed to enhance outweigh its risks. This benefit-risk
DATES: Although you can comment on harmonization and is committed to assessment of pharmaceuticals is the
any guidance at any time (see 21 CFR seeking scientifically based and fundamental basis of regulatory
10.115 (g)(5)), to ensure that the Agency harmonized technical procedures for decision-making. In the last several
considers your comment on this draft pharmaceutical development. One of years, providing greater structure for the
guidance before it begins work on the the goals of harmonization is to identify benefit-risk assessment has been an
final version of the guidance, submit and reduce differences in technical important topic in drug regulation. The
either electronic or written comments requirements for drug development M4E guidance directs applicants to
on the draft guidance by December 1, among regulatory Agencies. include their conclusions on benefits
2015. ICH was organized to provide an and risks in the Clinical Overview of
ADDRESSES: Submit written requests for opportunity for tripartite harmonization Module 2 of the CTD under section
single copies of the draft guidance to the initiatives to be developed with input 2.5.6. Although general guidance is
Division of Drug Information (HFD– from both regulatory and industry provided in the M4E guidance regarding
240), Center for Drug Evaluation and representatives. FDA also seeks input the expected content of section 2.5.6, no
Research (CDER), Food and Drug from other interested stakeholders. ICH further structure is suggested to aid
Administration, 10001 New Hampshire is concerned with harmonization of industry in developing the benefit-risk
Ave., Hillandale Building, 4th Floor, technical requirements for the assessment. As a result, regulators
Silver Spring, MD 20993–0002, or the registration of pharmaceutical products observe a high degree of variability in
Office of Communication, Outreach, and among three regions: Europe, Japan, and the approaches taken by applicants in
Development, Center for Biologics North America. The eight ICH sponsors presenting this information. This
Evaluation and Research (CBER), Food are the European Commission; the variability may not facilitate efficient
mstockstill on DSK4VPTVN1PROD with NOTICES
and Drug Administration, 10903 New European Federation of Pharmaceutical communication of industry views to
Hampshire Ave., Bldg. 71, Rm. 3128, Industries Associations; the Japanese regulators. Although regulators and
Silver Spring, MD 20993–0002. Send Ministry of Health, Labour, and Welfare; industry have developed approaches for
one self-addressed adhesive label to the Japanese Pharmaceutical structured benefit-risk assessment and
assist the office in processing your Manufacturers Association; CDER and these approaches may take different
requests. The draft guidance may also be CBER, FDA; the Pharmaceutical forms, there is a common thread evident
obtained by mail by calling CBER at 1– Research and Manufacturers of America; that can inform harmonization of the
800–835–4709 or 240–402–7800. See Health Canada; and Swissmedic. The format and structure of benefit-risk
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![59786 Federal Register / Vol. 80, No. 191 / Friday, October 2, 2015 / Notices
assessments provided by applicants in DEPARTMENT OF HEALTH AND comments, that information will be
their regulatory submissions. HUMAN SERVICES posted on http://www.regulations.gov.
• If you want to submit a comment
Recognizing that there are many
Food and Drug Administration with confidential information that you
reasonable approaches for conducting a
[Docket No. FDA–2013–N–0418]
do not wish to be made available to the
benefit-risk assessment, M4E(R2) does public, submit the comment as a
not specify a particular approach to be written/paper submission and in the
used by industry. However, the An Evaluation of the Prescription Drug
User Fee Act Workload Adjuster; manner detailed (see ‘‘Written/Paper
document does offer specific guidance Submissions’’ and ‘‘Instructions’’).
Request for Comments
on the major elements that should be
included in the benefit-risk assessment. AGENCY: Food and Drug Administration, Written/Paper Submissions
Furthermore, consistent with the HHS. Submit written/paper submissions as
concept paper that laid the groundwork ACTION: Notice; request for comments. follows:
for the Expert Working Group, the • Mail/Hand delivery/Courier (for
SUMMARY: The Food and Drug written/paper submissions): Division of
revised draft guidance does not dictate
Administration (FDA) is announcing an Dockets Management (HFA–305), Food
an approach used by a regulator in
opportunity for public comment on an and Drug Administration, 5630 Fishers
conducting a benefit-risk assessment. assessment of the Prescription Drug Lane, Rm. 1061, Rockville, MD 20852.
This draft guidance is being issued User Fee Act (PDUFA) Workload • For written/paper comments
consistent with FDA’s good guidance Adjuster conducted by an independent submitted to the Division of Dockets
practices regulation (21 CFR 10.115). consulting firm. This assessment was Management, FDA will post your
The draft guidance, when finalized, will conducted to fulfill FDA performance comment, as well as any attachments,
represent the current thinking of FDA commitments made as part of the fifth except for information submitted,
on this topic. It does not establish any authorization of PDUFA in section XV, marked and identified, as confidential,
rights for any person and is not binding ‘‘Improving FDA Performance if submitted as detailed in
on FDA or the public. You can use an Management,’’ subsection B, which was ‘‘Instructions.’’
alternative approach if it satisfies the reauthorized by the Food and Drug Instructions: All submissions received
requirements of the applicable statutes Administration Safety and Innovation must include the Docket No. FDA–
and regulations. Act of 2012 (FDASIA). Independent 2013–N–0418 for ‘‘An Evaluation of the
consulting firms conducted two Prescription Drug User Fee Act
II. Comments assessments during PDUFA V. This is Workload Adjuster; Request for
the second assessment to evaluate Comments.’’ Received comments will be
Interested persons may submit either whether the adjustment reasonably placed in the docket and, except for
electronic comments regarding this represents actual changes in workload those submitted as ‘‘Confidential
document to http://www.regulations.gov volume and complexity in the human Submissions,’’ publicly viewable at
or written comments to the Division of drug review program and to present http://www.regulations.gov or at the
Dockets Management (see ADDRESSES). options to discontinue, retain, or modify Division of Dockets Management
It is only necessary to send one set of any elements of the adjustment. After between 9 a.m. and 4 p.m., Monday
comments. Identify comments with the review of the report and receipt of through Friday.
docket number found in brackets in the public comment, FDA can adopt • Confidential Submissions—To
heading of this document. Received appropriate change to the workload submit a comment with confidential
comments may be seen in the Division adjustment methodology, if warranted. information that you do not wish to be
of Dockets Management between 9 a.m. DATES: Submit electronic or written made publicly available, submit your
and 4 p.m., Monday through Friday, and comments by November 2, 2015. comments only as a written/paper
will be posted to the docket at http:// ADDRESSES: You may submit comments submission. You should submit two
www.regulations.gov. as follows: copies total. One copy will include the
information you claim to be confidential
III. Electronic Access Electronic Submissions with a heading or cover note that states
Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS
Persons with access to the Internet
following way: CONFIDENTIAL INFORMATION’’. The
may obtain the document at http:// • Federal eRulemaking Portal: http:// Agency will review this copy, including
www.regulations.gov, http:// www.regulations.gov. Follow the the claimed confidential information, in
www.fda.gov/Drugs/Guidance instructions for submitting comments. its consideration of comments. The
ComplianceRegulatoryInformation/ Comments submitted electronically, second copy, which will have the
Guidances/default.htm, or http:// including attachments, to http:// claimed confidential information
www.fda.gov/BiologicsBloodVaccines/ www.regulations.gov will be posted to redacted/blacked out, will be available
GuidanceComplianceRegulatory the docket unchanged. Because your for public viewing and posted on http://
Information/Guidances/default.htm. comment will be made public, you are www.regulations.gov. Submit both
Dated: September 28, 2015. solely responsible for ensuring that your copies to the Division of Dockets
Leslie Kux,
comment does not include any Management. If you do not wish your
confidential information that you or a name and contact information to be
Associate Commissioner for Policy.
mstockstill on DSK4VPTVN1PROD with NOTICES
third party may not wish to be posted, made publicly available, you can
[FR Doc. 2015–25122 Filed 10–1–15; 8:45 am] such as medical information, your or provide this information on the cover
BILLING CODE 4164–01–P anyone else’s Social Security number, or sheet and not in the body of your
confidential business information, such comments and you must identify this
as a manufacturing process. Please note information as ‘‘confidential.’’ Any
that if you include your name, contact information marked as ‘‘confidential’’
information, or other information that will not be disclosed except in
identifies you in the body of your accordance with 21 CFR 10.20 and other
VerDate Sep<11>2014 20:43 Oct 01, 2015 Jkt 238001 PO 00000 Frm 00067 Fmt 4703 Sfmt 4703 E:\FR\FM\02OCN1.SGM 02OCN1](https://thefederalregister.org/doc/80_FR_59976/page/2.svg)
Document Created: 2015-12-15 08:44:49
Document Modified: 2015-12-15 08:44:49
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice. | |
| Dates | Although you can comment on any guidance at any time (see 21 CFR 10.115 (g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by December 1, 2015. | |
| 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 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. | |
| FR Citation | 80 FR 59785 |
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