83 FR 34139 - E17 General Principles for Planning and Design of Multiregional Clinical Trials; International Council for Harmonisation; Guidance for Industry; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 139 (July 19, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 139 (July 19, 2018)
| Page Range | 34139-34140 | |
| FR Document | 2018-15395 |
[Federal Register Volume 83, Number 139 (Thursday, July 19, 2018)] [Notices] [Pages 34139-34140] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-15395] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2016-D-2567] E17 General Principles for Planning and Design of Multiregional Clinical Trials; 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 final guidance entitled ``E17 General Principles for Planning and Design of Multiregional Clinical Trials.'' The guidance was prepared under the auspices of the International Council for Harmonisation (ICH), formerly the International Conference on Harmonisation. The guidance describes general principles for planning and designing multiregional clinical trials (MRCTs). The guidance is intended to increase the acceptability of data from MRCTs as the primary source of evidence supporting marketing approval in global regulatory submissions and thereby facilitate more efficient drug development and earlier access to medicines. DATES: The announcement of the guidance is published in the Federal Register on July 19, 2018. ADDRESSES: You may submit either electronic or written comments on Agency guidances at any time as follows: 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-2016-D-2567 for ``E17 General Principles for Planning and Design of Multiregional Clinical Trials; International Council for Harmonisation.'' 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 office 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 [[Page 34140]] 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.thefederalregister.org/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. You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)). Submit written requests for single copies of this guidance 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 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: Aloka Chakravarty, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Bldg. 21, Rm. 3514, Silver Spring, MD 20993-0002, 301- 796-1655; or R. Douglas Pratt, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. G112, Silver Spring, MD 20993-0002, 301-796-2640. 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, regulatory authorities and industry associations from around the world have participated in many important initiatives to promote international harmonization of regulatory requirements under the ICH. FDA has participated in several ICH meetings designed to enhance harmonization and FDA is committed to seeking scientifically based 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 established 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 FDA; the Japanese Ministry of Health, Labour, and Welfare; the Japanese Pharmaceutical Manufacturers Association; 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. The Assembly is responsible for the endorsement of draft guidelines and adoption of final guidelines. FDA publishes ICH guidelines as FDA guidance. In the Federal Register of September 9, 2016 (81 FR 62506), FDA published a notice announcing the availability of a draft guidance entitled ``E17 General Principles for Planning and Design of Multi- Regional Clinical Trials.'' The notice gave interested persons an opportunity to submit comments by November 8, 2016. After consideration of the comments received and revisions to the guideline, a final draft of the guideline was submitted to the ICH Assembly and endorsed by the regulatory agencies in November 2017. The guidance provides guidance on general principles for planning and designing MRCTs. MRCTs conducted according to the guidance will investigate treatment effects in overall populations with multiple ethnic factors (intrinsic and extrinsic factors as described in Appendix A of the ICH guidance entitled ``E5 Ethnic Factors in the Acceptability of Foreign Clinical Data'') and evaluate the consistency of treatment effects across populations. The guidance explicitly states that MRCTs are planned under the assumption that the treatment effect applies to the entire target population, particularly to the regions included in the trial. The concept of ``consistency of treatment effect'' across regions is defined in the text and in the glossary, and the terms ``pooled populations'' and ``pooled regions'' are also added to the glossary. The guidance further clarifies that prespecified strategies for pooling regions and/or subpopulations provide flexibility in sample-size allocation to regions, and that the strategies facilitate the assessment of consistency in treatment effects across regions. 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 ``E17 General Principles for Planning and Design of Multiregional Clinical Trials.'' 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. Electronic Access Persons with access to the internet may obtain the document 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 13, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-15395 Filed 7-18-18; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 83, No. 139 / Thursday, July 19, 2018 / Notices 34139
DEPARTMENT OF HEALTH AND ‘‘Drugs@FDA’’ website at https:// confidential information that you or a
HUMAN SERVICES www.accessdata.fda.gov/scripts/cder/ third party may not wish to be posted,
daf/. such as medical information, your or
Food and Drug Administration Dated: July 13, 2018. anyone else’s Social Security number, or
Leslie Kux,
confidential business information, such
[Docket No. FDA–2017–N–0809]
as a manufacturing process. Please note
Associate Commissioner for Policy.
Issuance of Priority Review Voucher; that if you include your name, contact
[FR Doc. 2018–15393 Filed 7–18–18; 8:45 am] information, or other information that
Rare Pediatric Disease Product BILLING CODE 4164–01–P identifies you in the body of your
AGENCY: Food and Drug Administration, comments, that information will be
HHS. posted on https://www.regulations.gov.
DEPARTMENT OF HEALTH AND • If you want to submit a comment
ACTION: Notice.
HUMAN SERVICES with confidential information that you
SUMMARY: The Food and Drug do not wish to be made available to the
Food and Drug Administration
Administration (FDA) is announcing the public, submit the comment as a
issuance of a priority review voucher to [Docket No. FDA–2016–D–2567] written/paper submission and in the
the sponsor of a rare pediatric disease manner detailed (see ‘‘Written/Paper
product application. The Federal Food, E17 General Principles for Planning Submissions’’ and ‘‘Instructions’’).
Drug, and Cosmetic Act (the FD&C Act), and Design of Multiregional Clinical
Trials; International Council for Written/Paper Submissions
as amended by the Food and Drug
Administration Safety and Innovation Harmonisation; Guidance for Industry; Submit written/paper submissions as
Act (FDASIA), authorizes FDA to award Availability follows:
priority review vouchers to sponsors of • Mail/Hand delivery/Courier (for
AGENCY: Food and Drug Administration, written/paper submissions): Dockets
approved rare pediatric disease product HHS.
applications that meet certain criteria. Management Staff (HFA–305), Food and
ACTION: Notice of availability. Drug Administration, 5630 Fishers
FDA is required to publish notice of the
award of the priority review voucher. Lane, Rm. 1061, Rockville, MD 20852.
SUMMARY: The Food and Drug • For written/paper comments
FDA has determined that EPIDIOLEX Administration (FDA or Agency) is
(cannabidiol oral solution) submitted to the Dockets Management
announcing the availability of a final Staff, FDA will post your comment, as
manufactured by GW Research Ltd., guidance entitled ‘‘E17 General
meets the criteria for a priority review well as any attachments, except for
Principles for Planning and Design of information submitted, marked and
voucher. Multiregional Clinical Trials.’’ The identified, as confidential, if submitted
FOR FURTHER INFORMATION CONTACT: guidance was prepared under the as detailed in ‘‘Instructions.’’
Althea Cuff, Center for Drug Evaluation auspices of the International Council for Instructions: All submissions received
and Research, Food and Drug Harmonisation (ICH), formerly the must include the Docket No. FDA–
Administration, 10903 New Hampshire International Conference on 2016–D–2567 for ‘‘E17 General
Ave., Silver Spring, MD 20993–0002, Harmonisation. The guidance describes Principles for Planning and Design of
301–796–4061, Fax: 301–796–9856, general principles for planning and Multiregional Clinical Trials;
email: althea.cuff@fda.hhs.gov. designing multiregional clinical trials International Council for
SUPPLEMENTARY INFORMATION: FDA is (MRCTs). The guidance is intended to Harmonisation.’’ Received comments
announcing the issuance of a priority increase the acceptability of data from will be placed in the docket and, except
review voucher to the sponsor of an MRCTs as the primary source of for those submitted as ‘‘Confidential
approved rare pediatric disease product evidence supporting marketing approval Submissions,’’ publicly viewable at
application. Under section 529 of the in global regulatory submissions and https://www.regulations.gov or at the
FD&C Act (21 U.S.C. 360ff), which was thereby facilitate more efficient drug Dockets Management Staff office
added by FDASIA, FDA will award development and earlier access to between 9 a.m. and 4 p.m., Monday
priority review vouchers to sponsors of medicines. through Friday.
approved rare pediatric disease product DATES: The announcement of the • Confidential Submissions—To
applications that meet certain criteria. guidance is published in the Federal submit a comment with confidential
FDA has determined that EPIDIOLEX Register on July 19, 2018. information that you do not wish to be
(cannabidiol oral solution) ADDRESSES: You may submit either made publicly available, submit your
manufactured by GW Research Ltd., electronic or written comments on comments only as a written/paper
meets the criteria for a priority review Agency guidances at any time as submission. You should submit two
voucher. EPIDIOLEX (cannabidiol oral follows: copies total. One copy will include the
solution) is indicated for the treatment information you claim to be confidential
of seizures associated with Dravet Electronic Submissions with a heading or cover note that states
Syndrome or Lennox-Gastaut Syndrome Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS
in patients 2 years of age and older. following way: CONFIDENTIAL INFORMATION.’’ The
For further information about the Rare • Federal eRulemaking Portal: Agency will review this copy, including
Pediatric Disease Priority Review https://www.regulations.gov. Follow the the claimed confidential information, in
Voucher Program and for a link to the instructions for submitting comments. its consideration of comments. The
sradovich on DSK3GMQ082PROD with NOTICES
full text of section 529 of the FD&C Act, Comments submitted electronically, second copy, which will have the
go to https://www.fda.gov/ForIndustry/ including attachments, to https:// claimed confidential information
DevelopingProductsforRareDiseases www.regulations.gov will be posted to redacted/blacked out, will be available
Conditions/RarePediatricDiseasePriority the docket unchanged. Because your for public viewing and posted on
VoucherProgram/default.htm. For comment will be made public, you are https://www.regulations.gov. Submit
further information about EPIDIOLEX solely responsible for ensuring that your both copies to the Dockets Management
(cannabidiol oral solution), go to the comment does not include any Staff. If you do not wish your name and
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![34140 Federal Register / Vol. 83, No. 139 / Thursday, July 19, 2018 / Notices
contact information to be made publicly Ave., Bldg. 51, Rm. 1176, Silver Spring, opportunity to submit comments by
available, you can provide this MD 20993–0002, 301–796–4548. November 8, 2016.
information on the cover sheet and not SUPPLEMENTARY INFORMATION: After consideration of the comments
in the body of your comments and you received and revisions to the guideline,
must identify this information as I. Background a final draft of the guideline was
‘‘confidential.’’ Any information marked In recent years, regulatory authorities submitted to the ICH Assembly and
as ‘‘confidential’’ will not be disclosed and industry associations from around endorsed by the regulatory agencies in
except in accordance with 21 CFR 10.20 the world have participated in many November 2017.
and other applicable disclosure law. For important initiatives to promote The guidance provides guidance on
more information about FDA’s posting international harmonization of general principles for planning and
of comments to public dockets, see 80 regulatory requirements under the ICH. designing MRCTs. MRCTs conducted
FR 56469, September 18, 2015, or access FDA has participated in several ICH according to the guidance will
the information at: https://www.gpo.gov/ meetings designed to enhance investigate treatment effects in overall
fdsys/pkg/FR-2015-09-18/pdf/2015- harmonization and FDA is committed to populations with multiple ethnic factors
23389.pdf. seeking scientifically based harmonized (intrinsic and extrinsic factors as
Docket: For access to the docket to technical procedures for pharmaceutical described in Appendix A of the ICH
read background documents or the development. One of the goals of guidance entitled ‘‘E5 Ethnic Factors in
electronic and written/paper comments harmonization is to identify and reduce the Acceptability of Foreign Clinical
received, go to https:// differences in technical requirements for Data’’) and evaluate the consistency of
www.regulations.gov and insert the drug development among regulatory treatment effects across populations.
docket number, found in brackets in the agencies. The guidance explicitly states that
heading of this document, into the ICH was established to provide an MRCTs are planned under the
‘‘Search’’ box and follow the prompts opportunity for harmonization assumption that the treatment effect
and/or go to the Dockets Management initiatives to be developed with input applies to the entire target population,
Staff, 5630 Fishers Lane, Rm. 1061, from both regulatory and industry particularly to the regions included in
Rockville, MD 20852. representatives. FDA also seeks input the trial. The concept of ‘‘consistency of
You may submit comments on any from consumer representatives and treatment effect’’ across regions is
guidance at any time (see 21 CFR others. ICH is concerned with defined in the text and in the glossary,
10.115(g)(5)). harmonization of technical and the terms ‘‘pooled populations’’ and
Submit written requests for single requirements for the registration of ‘‘pooled regions’’ are also added to the
copies of this guidance to the Division pharmaceutical products for human use glossary. The guidance further clarifies
of Drug Information, Center for Drug among regulators around the world. The that prespecified strategies for pooling
Evaluation and Research, Food and six founding members of the ICH are the regions and/or subpopulations provide
Drug Administration, 10001 New European Commission; the European flexibility in sample-size allocation to
Hampshire Ave., Hillandale Building, Federation of Pharmaceutical Industries regions, and that the strategies facilitate
4th Floor, Silver Spring, MD 20993– Associations; the FDA; the Japanese the assessment of consistency in
0002, or the Office of Communication, Ministry of Health, Labour, and Welfare; treatment effects across regions.
Outreach and Development, Center for the Japanese Pharmaceutical This guidance is being issued
Biologics Evaluation and Research Manufacturers Association; and the consistent with FDA’s good guidance
(CBER), Food and Drug Administration, Pharmaceutical Research and practices regulation (21 CFR 10.115).
10903 New Hampshire Ave., Bldg. 71, Manufacturers of America. The The guidance represents the current
Rm. 3128, Silver Spring, MD 20993– Standing Members of the ICH thinking of FDA on ‘‘E17 General
0002. Send one self-addressed adhesive Association include Health Canada and Principles for Planning and Design of
label to assist that office in processing Swissmedic. Any party eligible as a Multiregional Clinical Trials.’’ It does
your requests. The guidance may also be Member in accordance with the ICH not establish any rights for any person
obtained by mail by calling CBER at 1– Articles of Association can apply for and is not binding on FDA or the public.
800–835–4709 or 240–402–8010. See membership in writing to the ICH You can use an alternative approach if
the SUPPLEMENTARY INFORMATION section Secretariat. The ICH Secretariat, which it satisfies the requirements of the
for electronic access to the guidance coordinates the preparation of applicable statutes and regulations. This
document. documentation, operates as an guidance is not subject to Executive
international nonprofit organization and Order 12866.
FOR FURTHER INFORMATION CONTACT: is funded by the Members of the ICH
Regarding the guidance: Aloka Association. II. Electronic Access
Chakravarty, Center for Drug Evaluation The ICH Assembly is the overarching Persons with access to the internet
and Research, Food and Drug body of the Association and includes may obtain the document at https://
Administration, 10903 New Hampshire representatives from each of the ICH www.regulations.gov, https://
Ave, Bldg. 21, Rm. 3514, Silver Spring, members and observers. The Assembly www.fda.gov/Drugs/Guidance
MD 20993–0002, 301–796–1655; or R. is responsible for the endorsement of ComplianceRegulatoryInformation/
Douglas Pratt, Center for Biologics draft guidelines and adoption of final Guidances/default.htm, or https://
Evaluation and Research, Food and guidelines. FDA publishes ICH www.fda.gov/BiologicsBloodVaccines/
Drug Administration, 10903 New guidelines as FDA guidance.
sradovich on DSK3GMQ082PROD with NOTICES
GuidanceComplianceRegulatory
Hampshire Ave., Bldg. 71, Rm. G112, In the Federal Register of September Information/Guidances/default.htm.
Silver Spring, MD 20993–0002, 301– 9, 2016 (81 FR 62506), FDA published
796–2640. a notice announcing the availability of Dated: July 13, 2018.
Regarding the ICH: Amanda Roache, a draft guidance entitled ‘‘E17 General Leslie Kux,
Center for Drug Evaluation and Principles for Planning and Design of Associate Commissioner for Policy.
Research, Food and Drug Multi-Regional Clinical Trials.’’ The [FR Doc. 2018–15395 Filed 7–18–18; 8:45 am]
Administration, 10903 New Hampshire notice gave interested persons an BILLING CODE 4164–01–P
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Document Created: 2018-07-19 01:35:05
Document Modified: 2018-07-19 01:35:05
| 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 of availability. | |
| Dates | The announcement of the guidance is published in the Federal Register on July 19, 2018. | |
| Contact | Regarding the guidance: Aloka Chakravarty, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave, Bldg. 21, Rm. 3514, Silver Spring, MD 20993-0002, 301- 796-1655; or R. Douglas Pratt, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. G112, Silver Spring, MD 20993-0002, 301-796-2640. | |
| FR Citation | 83 FR 34139 |
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