E14 and S7B Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential-Questions and Answers; International Council for Harmonisation; Guidance for Industry; Availability, 52786-52788 [2022-18515]
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Federal Register / Vol. 87, No. 166 / Monday, August 29, 2022 / Notices
procedures, including those used for
process control and that apply to
multivariate methods. The draft Q14
guideline harmonizes scientific
approaches for analytical procedure
development and describes principles to
facilitate more efficient and sciencebased and risk-based postapproval
change management. The two
guidelines are intended to facilitate
regulatory evaluations and facilitate
potential flexibility in postapproval
change management of analytical
procedures where scientifically
justified.
These draft guidances have been left
in the original ICH format. The final
guidances will be reformatted and
edited to conform with FDA’s good
guidance practices regulation (21 CFR
10.115) and style before publication.
The draft guidances, when finalized,
will represent the current thinking of
FDA on the topics they address. They
do not establish any rights for any
person and are not binding on FDA or
the public. You can use an alternative
approach if it satisfies the requirements
of the applicable statutes and
regulations.
II. Paperwork Reduction Act of 1995
While this guidance contains no
collection of information, it does refer to
previously approved FDA collections of
information. Therefore, clearance by the
Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501–
3521) is not required for this guidance.
The previously approved collections of
information are subject to review by
OMB under the PRA. The collections of
information for investigational new drug
applications have been approved under
OMB control number 0910–0014; the
collections of information for review of
new drug applications have been
approved under OMB control number
0910–0001; and the collections of
information for review of biologics
license applications have been approved
under OMB control number 0910–0338.
khammond on DSKJM1Z7X2PROD with NOTICES
III. Electronic Access
Persons with access to the internet
may obtain the draft guidances at
https://www.regulations.gov, https://
www.fda.gov/regulatory-information/
search-fda-guidance-documents,
https://www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, or https://
www.fda.gov/vaccines-blood-biologics/
guidance-compliance-regulatoryinformation-biologics/biologicsguidances.
VerDate Sep<11>2014
17:01 Aug 26, 2022
Jkt 256001
Dated: August 22, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022–18516 Filed 8–26–22; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2020–D–1791]
E14 and S7B Clinical and Nonclinical
Evaluation of QT/QTc Interval
Prolongation and Proarrhythmic
Potential—Questions and Answers;
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 final
guidance for industry entitled ‘‘E14 and
S7B Clinical and Nonclinical Evaluation
of QT/QTc Interval Prolongation and
Proarrhythmic Potential—Questions and
Answers.’’ The guidance was prepared
under the auspices of the International
Council for Harmonisation of Technical
Requirements for Pharmaceuticals for
Human Use (ICH), formerly the
International Conference on
Harmonisation. The guidance contains
revised questions and answers (Q&As)
for the ICH guidance for industry ‘‘E14
Clinical Evaluation of the QT/QTc
Interval Prolongation and Proarrhythmic
Potential for Non-Antiarrhythmic
Drugs’’ and new Q&As for the ICH
guidance for industry ‘‘S7B Nonclinical
Evaluation of the Potential for Delayed
Ventricular Repolarization (QT Interval
Prolongation) by Human
Pharmaceuticals’’ that provide
recommendations on considerations for
an integrated risk assessment combining
nonclinical and clinical data—in
particular, at later stages of drug
development when clinical data are
available. The guidance is intended to
provide a harmonized approach to
integrate nonclinical and clinical
information for proarrhythmia risk
assessment to streamline drug
development and provide clarity on
regulatory decision making. This
guidance finalizes the draft guidance of
the same title issued in September 2020.
DATES: The announcement of the
guidance is published in the Federal
Register on August 29, 2022.
ADDRESSES: You may submit either
electronic or written comments on
SUMMARY:
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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–
2020–D–1791 for ‘‘E14 and S7B Clinical
and Nonclinical Evaluation of QT/QTc
Interval Prolongation and Proarrhythmic
Potential—Questions and Answers.’’
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, 240–402–7500.
• 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
E:\FR\FM\29AUN1.SGM
29AUN1
khammond on DSKJM1Z7X2PROD with NOTICES
Federal Register / Vol. 87, No. 166 / Monday, August 29, 2022 / Notices
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.govinfo.gov/content/pkg/FR-201509-18/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, 240–402–7500.
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:
VerDate Sep<11>2014
17:01 Aug 26, 2022
Jkt 256001
Regarding the guidance: Devi Kozeli,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 22, Rm. 4183, Silver Spring,
MD 20993–0002, 301–796–1128; 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: Jill Adleberg,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 6364, Silver Spring,
MD 20993–0002, 301–796–5259.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled ‘‘E14
and S7B Clinical and Nonclinical
Evaluation of QT/QTc Interval
Prolongation and Proarrhythmic
Potential—Questions and Answers.’’
The guidance was prepared under the
auspices of ICH. ICH has the mission of
achieving greater regulatory
harmonization worldwide to ensure that
safe, effective, high-quality medicines
are developed, registered, and
maintained in the most resourceefficient manner.
By harmonizing the regulatory
requirements in regions around the
world, ICH guidelines have
substantially reduced duplicative
clinical studies, prevented unnecessary
animal studies, standardized the
reporting of important safety
information, standardized marketing
application submissions, and made
many other improvements in the quality
of global drug development and
manufacturing and the products
available to patients.
The six Founding Members of the ICH
are FDA; the Pharmaceutical Research
and Manufacturers of America; the
European Commission; the European
Federation of Pharmaceutical Industries
Associations; the Japanese Ministry of
Health, Labour, and Welfare; and the
Japanese Pharmaceutical Manufacturers
Association. The Standing Members of
the ICH Association include Health
Canada and Swissmedic. Additionally,
the Membership of ICH has expanded to
include other regulatory authorities and
industry associations from around the
world (https://www.ich.org/).
ICH works by involving technical
experts from both regulators and
industry parties in detailed technical
harmonization work and the application
of a science-based approach to
harmonization through a consensus-
PO 00000
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52787
driven process that results in the
development of ICH guidelines. The
regulators around the world are
committed to consistently adopting
these consensus-based guidelines,
realizing the benefits for patients and for
industry.
As a Founding Regulatory Member of
ICH, FDA plays a major role in the
development of each of the ICH
guidelines, which FDA then adopts and
issues as guidance for industry. FDA’s
guidance documents do not establish
legally enforceable responsibilities.
Instead, they describe the Agency’s
current thinking on a topic and should
be viewed only as recommendations,
unless specific regulatory or statutory
requirements are cited.
In the Federal Register of September
30, 2020 (85 FR 61753), FDA published
a notice announcing the availability of
a draft guidance entitled ‘‘E14 and S7B
Clinical and Nonclinical Evaluation of
QT/QTc Interval Prolongation and
Proarrhythmic Potential—Questions and
Answers.’’ The notice gave interested
persons an opportunity to submit
comments by November 30, 2020.
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
February 2022.
This guidance finalizes the draft
guidance issued on September 30, 2020.
The guidance contains revised Q&As
about the ICH guidance for industry
‘‘E14 Clinical Evaluation of the QT/QTc
Interval Prolongation and Proarrhythmic
Potential for Non-Antiarrhythmic
Drugs’’ and new Q&As about the ICH
guidance for industry ‘‘S7B Nonclinical
Evaluation of the Potential for Delayed
Ventricular Repolarization (QT Interval
Prolongation) by Human
Pharmaceuticals’’ that provide
recommendations on considerations for
an integrated risk assessment combining
nonclinical and clinical data—in
particular, at later stages of drug
development when clinical data are
available. For ICH E14, revised Q&As
provide recommendations for how an
integrated nonclinical and clinical risk
assessment can be particularly valuable
under scenarios when a sufficiently
high multiple of maximum therapeutic
exposure cannot be achieved (ICH E14
Q&A Q12 (5.1)); and under scenarios
where a placebo-controlled comparison
is not possible, safety considerations
preclude administering
supratherapeutic doses to obtain high
clinical exposures and/or safety or
tolerability prohibit the use of the
product in healthy participants (ICH
E14 Q&A Q13 (6.1)). For ICH S7B, new
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Federal Register / Vol. 87, No. 166 / Monday, August 29, 2022 / Notices
Q&As provide recommendations on an
integrated risk assessment and how it
can inform the design of clinical
investigations and the interpretation of
their results (ICH S7B Q&As Q17 (1.1)
and Q18 (1.2)); best-practice
considerations for in vitro (ICH S7B
Q&As Q 19 (2.1) to Q23 (2.5)) and in
vivo (ICH S7B Q&As Q24 (3.1) to Q28
(3.5)) studies; and principles for
proarrhythmia models, including in
silico (ICH S7B Q&As Q30 (4.1) and
4.2). The guidance is intended to
provide a harmonized approach to
integrate nonclinical and clinical
information for proarrhythmia risk
assessment to streamline drug
development and provide clarity on
regulatory decision making.
This guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
This guidance represents the current
thinking of FDA on ‘‘E14 and S7B
Clinical and Nonclinical Evaluation of
QT/QTc Interval Prolongation and
Proarrhythmic Potential—Questions and
Answers.’’ 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.
khammond on DSKJM1Z7X2PROD with NOTICES
II. Paperwork Reduction Act of 1995
While this guidance contains no
collection of information, it does refer to
previously approved FDA collections of
information. Therefore, clearance by the
Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501–
3521) is not required for this guidance.
The previously approved collections of
information are subject to review by
OMB under the PRA. The collections of
information for submitting
investigational new drug applications
are approved under OMB control
number 0910–0014. The collections of
information for submitting new drug
applications are approved under OMB
control number 0910–0001. The
collections of information for submitting
biologics license applications are
approved under OMB control number
0910–0338.
II. Electronic Access
Persons with access to the internet
may obtain the draft guidance at https://
www.regulations.gov, https://
www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, https://www.fda.gov/
regulatory-information/search-fdaguidance-documents, or https://
www.fda.gov/vaccines-blood-biologics/
guidance-compliance-regulatory-
VerDate Sep<11>2014
17:01 Aug 26, 2022
Jkt 256001
information-biologics/biologicsguidances.
Dated: August 22, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022–18515 Filed 8–26–22; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2022–D–1562]
E11A Pediatric Extrapolation;
International Council for
Harmonisation; Draft 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 draft
guidance for industry entitled ‘‘E11A
Pediatric Extrapolation.’’ The draft
guidance was prepared under the
auspices of the International Council for
Harmonisation of Technical
Requirements for Pharmaceuticals for
Human Use (ICH). The draft guidance
provides a comprehensive and
systematic approach to the use of
pediatric extrapolation during drug
development. The draft guidance also
discusses study designs and statistical
methodologies, including modeling and
simulation, that can be utilized to
develop and implement a pediatric
extrapolation approach. The draft
guidance is intended to provide
recommendations for the use of
pediatric extrapolation during drug
development, which, when used
appropriately, can increase the
efficiency of pediatric drug
development and accelerate the
availability of safe and effective drugs
approved for use in children.
DATES: Submit either electronic or
written comments on the draft guidance
by October 28, 2022 to ensure that the
Agency considers your comment on this
draft guidance before it begins work on
the final version of the guidance.
ADDRESSES: You may submit comments
on any guidance at any time as follows:
SUMMARY:
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,
PO 00000
Frm 00052
Fmt 4703
Sfmt 4703
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–
2022–D–1562 for ‘‘E11A Pediatric
Extrapolation.’’ Received comments will
be placed in the docket and, except for
those submitted as ‘‘Confidential
Submissions,’’ are publicly viewable at
https://www.regulations.gov or at the
Dockets Management Staff between 9
a.m. and 4 p.m., Monday through
Friday, 240–402–7500.
• 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
E:\FR\FM\29AUN1.SGM
29AUN1
]]>Agencies
[Federal Register Volume 87, Number 166 (Monday, August 29, 2022)]
[Notices]
[Pages 52786-52788]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-18515]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-1791]
E14 and S7B Clinical and Nonclinical Evaluation of QT/QTc
Interval Prolongation and Proarrhythmic Potential--Questions and
Answers; 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 for industry entitled ``E14 and
S7B Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation
and Proarrhythmic Potential--Questions and Answers.'' The guidance was
prepared under the auspices of the International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human
Use (ICH), formerly the International Conference on Harmonisation. The
guidance contains revised questions and answers (Q&As) for the ICH
guidance for industry ``E14 Clinical Evaluation of the QT/QTc Interval
Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs''
and new Q&As for the ICH guidance for industry ``S7B Nonclinical
Evaluation of the Potential for Delayed Ventricular Repolarization (QT
Interval Prolongation) by Human Pharmaceuticals'' that provide
recommendations on considerations for an integrated risk assessment
combining nonclinical and clinical data--in particular, at later stages
of drug development when clinical data are available. The guidance is
intended to provide a harmonized approach to integrate nonclinical and
clinical information for proarrhythmia risk assessment to streamline
drug development and provide clarity on regulatory decision making.
This guidance finalizes the draft guidance of the same title issued in
September 2020.
DATES: The announcement of the guidance is published in the Federal
Register on August 29, 2022.
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-2020-D-1791 for ``E14 and S7B Clinical and Nonclinical Evaluation
of QT/QTc Interval Prolongation and Proarrhythmic Potential--Questions
and Answers.'' 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, 240-402-7500.
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
[[Page 52787]]
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.govinfo.gov/content/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, 240-402-7500.
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: Devi Kozeli, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
22, Rm. 4183, Silver Spring, MD 20993-0002, 301-796-1128; 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: Jill Adleberg, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-5259.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``E14 and S7B Clinical and Nonclinical Evaluation of QT/QTc
Interval Prolongation and Proarrhythmic Potential--Questions and
Answers.'' The guidance was prepared under the auspices of ICH. ICH has
the mission of achieving greater regulatory harmonization worldwide to
ensure that safe, effective, high-quality medicines are developed,
registered, and maintained in the most resource-efficient manner.
By harmonizing the regulatory requirements in regions around the
world, ICH guidelines have substantially reduced duplicative clinical
studies, prevented unnecessary animal studies, standardized the
reporting of important safety information, standardized marketing
application submissions, and made many other improvements in the
quality of global drug development and manufacturing and the products
available to patients.
The six Founding Members of the ICH are FDA; the Pharmaceutical
Research and Manufacturers of America; the European Commission; the
European Federation of Pharmaceutical Industries Associations; the
Japanese Ministry of Health, Labour, and Welfare; and the Japanese
Pharmaceutical Manufacturers Association. The Standing Members of the
ICH Association include Health Canada and Swissmedic. Additionally, the
Membership of ICH has expanded to include other regulatory authorities
and industry associations from around the world (https://www.ich.org/).
ICH works by involving technical experts from both regulators and
industry parties in detailed technical harmonization work and the
application of a science-based approach to harmonization through a
consensus-driven process that results in the development of ICH
guidelines. The regulators around the world are committed to
consistently adopting these consensus-based guidelines, realizing the
benefits for patients and for industry.
As a Founding Regulatory Member of ICH, FDA plays a major role in
the development of each of the ICH guidelines, which FDA then adopts
and issues as guidance for industry. FDA's guidance documents do not
establish legally enforceable responsibilities. Instead, they describe
the Agency's current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory requirements
are cited.
In the Federal Register of September 30, 2020 (85 FR 61753), FDA
published a notice announcing the availability of a draft guidance
entitled ``E14 and S7B Clinical and Nonclinical Evaluation of QT/QTc
Interval Prolongation and Proarrhythmic Potential--Questions and
Answers.'' The notice gave interested persons an opportunity to submit
comments by November 30, 2020.
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 February 2022.
This guidance finalizes the draft guidance issued on September 30,
2020. The guidance contains revised Q&As about the ICH guidance for
industry ``E14 Clinical Evaluation of the QT/QTc Interval Prolongation
and Proarrhythmic Potential for Non-Antiarrhythmic Drugs'' and new Q&As
about the ICH guidance for industry ``S7B Nonclinical Evaluation of the
Potential for Delayed Ventricular Repolarization (QT Interval
Prolongation) by Human Pharmaceuticals'' that provide recommendations
on considerations for an integrated risk assessment combining
nonclinical and clinical data--in particular, at later stages of drug
development when clinical data are available. For ICH E14, revised Q&As
provide recommendations for how an integrated nonclinical and clinical
risk assessment can be particularly valuable under scenarios when a
sufficiently high multiple of maximum therapeutic exposure cannot be
achieved (ICH E14 Q&A Q12 (5.1)); and under scenarios where a placebo-
controlled comparison is not possible, safety considerations preclude
administering supratherapeutic doses to obtain high clinical exposures
and/or safety or tolerability prohibit the use of the product in
healthy participants (ICH E14 Q&A Q13 (6.1)). For ICH S7B, new
[[Page 52788]]
Q&As provide recommendations on an integrated risk assessment and how
it can inform the design of clinical investigations and the
interpretation of their results (ICH S7B Q&As Q17 (1.1) and Q18 (1.2));
best-practice considerations for in vitro (ICH S7B Q&As Q 19 (2.1) to
Q23 (2.5)) and in vivo (ICH S7B Q&As Q24 (3.1) to Q28 (3.5)) studies;
and principles for proarrhythmia models, including in silico (ICH S7B
Q&As Q30 (4.1) and 4.2). The guidance is intended to provide a
harmonized approach to integrate nonclinical and clinical information
for proarrhythmia risk assessment to streamline drug development and
provide clarity on regulatory decision making.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). This guidance represents the
current thinking of FDA on ``E14 and S7B Clinical and Nonclinical
Evaluation of QT/QTc Interval Prolongation and Proarrhythmic
Potential--Questions and Answers.'' 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. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information for submitting investigational new drug applications are
approved under OMB control number 0910-0014. The collections of
information for submitting new drug applications are approved under OMB
control number 0910-0001. The collections of information for submitting
biologics license applications are approved under OMB control number
0910-0338.
II. Electronic Access
Persons with access to the internet may obtain the draft guidance
at https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.
Dated: August 22, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-18515 Filed 8-26-22; 8:45 am]
BILLING CODE 4164-01-P
