E14 and S7B Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential-Questions and Answers; International Council for Harmonisation; Draft Guidance for Industry; Availability, 61753-61755 [2020-21624]
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Federal Register / Vol. 85, No. 190 / Wednesday, September 30, 2020 / Notices
ESTIMATED RECORDKEEPING COSTS
Instrument
Total number
of respondents
Total number of
responses per
respondent
50
1
NAC Recommendations and State Self-Assessment Survey .......................
Estimated Total Annual Burden
Hours: 2,000
(Authority: 42 U.S.C. 1314b)
John M. Sweet Jr.,
ACF/OPRE Certifying Officer.
[FR Doc. 2020–21617 Filed 9–29–20; 8:45 am]
BILLING CODE 4184–47–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Harmonisation; Draft Guidance for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announcing the availability of a draft
guidance for industry entitled ‘‘E14 and
S7B Clinical and Nonclinical Evaluation
of QT/QTc Interval Prolongation and
Proarrhythmic Potential—Questions and
Answers.’’ The draft guidance was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 of Technical
Requirements for Registration of
Pharmaceuticals for Human Use. The
draft guidance contains revised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
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SUMMARY:
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development when clinical data are
available. The draft guidance is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.
DATES: Submit either electronic or
written comments on the draft guidance
by November 30, 2020 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:
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
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Average
burden hours
per response
40
Total/annual
burden hours
2,000.
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
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
E:\FR\FM\30SEN1.SGM
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61754
Federal Register / Vol. 85, No. 190 / Wednesday, September 30, 2020 / Notices
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: David Strauss,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 64, Rm. 2072, Silver Spring,
MD 20993–0002, 301–796–6323; 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:
jbell on DSKJLSW7X2PROD with NOTICES
I. Background
FDA is announcing the availability of
a draft guidance for industry entitled
‘‘E14 and S7B Clinical and Nonclinical
Evaluation of QT/QTc Interval
Prolongation and Proarrhythmic
Potential—Questions and Answers.’’
The draft 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
VerDate Sep<11>2014
17:36 Sep 29, 2020
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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 consensusdriven 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 July 2020, the ICH Assembly
endorsed the draft guideline entitled
‘‘E14 and S7B Clinical and Nonclinical
Evaluation of QT/QTc Interval
Prolongation and Proarrhythmic
Potential—Questions and Answers’’ and
agreed that the guideline should be
made available for public comment. The
draft guideline is the product of the E14
and S7B Implementation Working
Group of the ICH. Comments about this
draft will be considered by FDA and the
ICH E14 and S7B Implementation
Working Group.
The draft 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-
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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 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 6.1). For ICH S7B, new 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 1.1 and
1.2); best-practice considerations for in
vitro (ICH S7B Q&As 2.1 to 2.5) and in
vivo (ICH S7B Q&As 3.1 to 3.5) studies;
and principles for proarrhythmia
models, including in silico (ICH S7B
Q&As 4.1 to 4.3). The draft 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. FDA seeks
public comment on all aspects of these
draft Q&As; of note, ICH E14 Q&A 6.1
encourages public comment on how to
define the lack of clinically relevant QT
prolongation in the context of this Q&A.
This draft guidance has been left in
the original ICH format. The final
guidance will be reformatted and edited
to conform with FDA’s good guidance
practices regulation (21 CFR 10.115) and
style before publication. The draft
guidance, when finalized, will represent
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.
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Federal Register / Vol. 85, No. 190 / Wednesday, September 30, 2020 / Notices
II. Paperwork Reduction Act of 1995
FDA tentatively concludes that this
draft guidance contains no collection of
information. Therefore, clearance by the
Office of Management and Budget under
the Paperwork Reduction Act of 1995 is
not required.
III. 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, or https://
www.fda.gov/vaccines-blood-biologics/
guidance-compliance-regulatoryinformation-biologics/biologicsguidances.
Dated: September 25, 2020.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2020–21624 Filed 9–29–20; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2020–N–1898]
Vaccines and Related Biological
Products Advisory Committee;
Amendment of Notice
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing an
amendment to the notice of meeting of
the Vaccines and Related Biological
Products Advisory Committee
(VRBPAC). This meeting was
announced in the Federal Register of
August 28, 2020. The amendment is
being made to reflect changes in the
ADDRESSES portion of the document.
FOR FURTHER INFORMATION CONTACT:
Prabhakara Atreya or Monique Hill,
Center for Biologics Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 71, Rm. 6306, Silver Spring,
MD 20993–0002, 240–506–4946,
Prabhakara.Atreya@fda.hhs.gov, or
301–796–4620, monique.hill@
fda.hhs.gov, respectively, or FDA
Advisory Committee Information Line,
1–800–741–8138 (301–443–0572 in the
Washington, DC area). Please call the
Information Line for up-to-date
information on this meeting.
SUPPLEMENTARY INFORMATION: In the
Federal Register of August 28, 2020, (85
FR 18985), FDA announced that a
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SUMMARY:
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meeting of the Vaccines and Related
Biological Products Advisory
Committee would be held on October
22, 2020. On page 53385, in the first
column, the ADDRESSES portion of the
document is changed to read as follows:
The online web conference meeting
will be available at the following link:
https://fda.yorkcast.com/webcast/Play/
c26e83a0f77a412296949f4f43af4c981d.
FDA is establishing a docket for
public comment on this meeting. The
docket number is FDA–2020–N–1898.
The docket will close on October 15,
2020. Submit either electronic or
written comments on this public
meeting by October 15, 2020. Please
note that late, untimely filed comments
will not be considered. Electronic
comments must be submitted on or
before October 15, 2020. The https://
www.regulations.gov electronic filing
system will accept comments until
11:59 p.m. Eastern Time at the end of
October 15, 2020. Comments received
by mail/hand delivery/courier (for
written/paper submissions will be
considered timely if they are
postmarked or the delivery service
acceptance receipt is on or before that
date.
Comments received on or before
October 15, 2020, will be provided to
the committee. Comments received after
that date will be taken into
consideration by FDA. In the event that
the meeting is cancelled, FDA will
continue to evaluate any relevant
applications or information, and
consider any comments submitted to the
docket, as appropriate.
You may submit comments 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.
PO 00000
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• 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–N–1898 for Vaccines and Related
Biological Products Advisory
Committee; Notice of Meeting;
Establishment of a Public Docket;
Request for Comments.’’ Received
comments, those filed in a timely
manner (see the ADDRESSES section),
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
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.’’ FDA
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 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 the 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
E:\FR\FM\30SEN1.SGM
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]]>Agencies
[Federal Register Volume 85, Number 190 (Wednesday, September 30, 2020)]
[Notices]
[Pages 61753-61755]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-21624]
-----------------------------------------------------------------------
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; Draft 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 draft guidance for industry entitled ``E14 and
S7B Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation
and Proarrhythmic Potential--Questions and Answers.'' The draft
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
of Technical Requirements for Registration of Pharmaceuticals for Human
Use. The draft 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
draft 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.
DATES: Submit either electronic or written comments on the draft
guidance by November 30, 2020 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:
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 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
[[Page 61754]]
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: David Strauss,
Center for Drug Evaluation and Research, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 64, Rm. 2072, Silver Spring, MD 20993-
0002, 301-796-6323; 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 draft guidance for industry
entitled ``E14 and S7B Clinical and Nonclinical Evaluation of QT/QTc
Interval Prolongation and Proarrhythmic Potential--Questions and
Answers.'' The draft 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 July 2020, the ICH Assembly endorsed the draft guideline
entitled ``E14 and S7B Clinical and Nonclinical Evaluation of QT/QTc
Interval Prolongation and Proarrhythmic Potential--Questions and
Answers'' and agreed that the guideline should be made available for
public comment. The draft guideline is the product of the E14 and S7B
Implementation Working Group of the ICH. Comments about this draft will
be considered by FDA and the ICH E14 and S7B Implementation Working
Group.
The draft 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 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 6.1). For ICH S7B, new 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 1.1 and 1.2); best-practice considerations for in
vitro (ICH S7B Q&As 2.1 to 2.5) and in vivo (ICH S7B Q&As 3.1 to 3.5)
studies; and principles for proarrhythmia models, including in silico
(ICH S7B Q&As 4.1 to 4.3). The draft 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. FDA seeks public comment
on all aspects of these draft Q&As; of note, ICH E14 Q&A 6.1 encourages
public comment on how to define the lack of clinically relevant QT
prolongation in the context of this Q&A.
This draft guidance has been left in the original ICH format. The
final guidance will be reformatted and edited to conform with FDA's
good guidance practices regulation (21 CFR 10.115) and style before
publication. The draft guidance, when finalized, will represent 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.
[[Page 61755]]
II. Paperwork Reduction Act of 1995
FDA tentatively concludes that this draft guidance contains no
collection of information. Therefore, clearance by the Office of
Management and Budget under the Paperwork Reduction Act of 1995 is not
required.
III. 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, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.
Dated: September 25, 2020.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2020-21624 Filed 9-29-20; 8:45 am]
BILLING CODE 4164-01-P
