S5(R3) Detection of Reproductive and Developmental Toxicity for Human Pharmaceuticals; International Council for Harmonisation; Guidance for Industry; Availability, 26048-26050 [2021-10017]
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26048
Federal Register / Vol. 86, No. 90 / Wednesday, May 12, 2021 / Notices
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: Scott Goldie,
Center for Drug Evaluation and
Research, Food and Drug
Administration, Bldg. 21, Rm. 3557,
Silver Spring, MD 20993–0002, 301–
796–2055, scott.goldie@fda.hhs.gov; or
Stephen Ripley, Center for Biologics
Evaluation and Research, Food and
Drug Administration, 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:
khammond on DSKJM1Z7X2PROD with NOTICES
I. Background
FDA is announcing the availability of
a guidance for industry entitled ‘‘E9(R1)
Statistical Principles for Clinical Trials:
Addendum: Estimands and Sensitivity
Analysis in Clinical Trials.’’ 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
VerDate Sep<11>2014
17:58 May 11, 2021
Jkt 253001
industry associations from around the
world (refer to 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 the Federal Register of October 31,
2017 (82 FR 50433), FDA published a
notice announcing the availability of a
draft guidance entitled ‘‘E9(R1)
Statistical Principles for Clinical Trials:
Addendum: Estimands and Sensitivity
Analysis in Clinical Trials.’’ The notice
gave interested persons an opportunity
to submit comments by April 30, 2018.
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 2019.
This guidance finalizes the draft
guidance issued on October 31, 2017.
The guidance provides clarification on
statistical principles for clinical trials
and an update on the choice of estimand
to describe a framework for planning,
conducting, and interpreting sensitivity
analyses of clinical trial data. The focus
of the guidance is on statistical
principles related to estimands and
sensitivity analysis for confirmatory
clinical trials. The guidance provides
recommendations for aligning the
choice of statistical methods with the
goals of a clinical trial; on
communicating the rationale for such
choices to FDA; and on using sensitivity
analysis to characterize the robustness
of the conclusions to plausible
deviations from the assumptions of the
main analysis. Revisions made
following the public comment period
are intended to clarify content within
the guidance; however, no new concepts
are presented in the revised version.
This guidance is being issued
consistent with FDA’s good guidance
PO 00000
Frm 00051
Fmt 4703
Sfmt 4703
practices regulation (21 CFR 10.115).
The guidance represents the current
thinking of FDA on ‘‘E9(R1) Statistical
Principles for Clinical Trials:
Addendum: Estimands and Sensitivity
Analysis in 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.
II. Electronic Access
Persons with access to the internet
may obtain the 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: May 7, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for
Policy.
[FR Doc. 2021–10066 Filed 5–11–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2017–D–5138]
S5(R3) Detection of Reproductive and
Developmental Toxicity for Human
Pharmaceuticals; 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 ‘‘S5(R3)
Detection of Reproductive and
Developmental Toxicity for Human
Pharmaceuticals.’’ 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 of Technical
Requirements for Registration of
Pharmaceuticals for Human Use. The
guidance provides key considerations
for developing a testing strategy to
identify hazard and characterize
reproductive risk for human
pharmaceuticals. The guidance is
intended to align with other ICH
guidances, elaborate on concepts to
SUMMARY:
E:\FR\FM\12MYN1.SGM
12MYN1
Federal Register / Vol. 86, No. 90 / Wednesday, May 12, 2021 / Notices
consider when designing studies, and
identify potential circumstances in
which a risk assessment can be made
based on preliminary studies. It also
clarifies the qualification and potential
use of alternative assays. This guidance
finalizes the draft guidance issued on
November 13, 2017.
DATES: The announcement of the
guidance is published in the Federal
Register on May 12, 2021.
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’’).
khammond on DSKJM1Z7X2PROD with NOTICES
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–
2017–D–5138 for ‘‘S5(R3) Detection of
Reproductive and Developmental
Toxicity for Human Pharmaceuticals.’’
VerDate Sep<11>2014
17:58 May 11, 2021
Jkt 253001
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
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,
PO 00000
Frm 00052
Fmt 4703
Sfmt 4703
26049
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: Ronald Wange,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 22, Rm. 3342, Silver Spring,
MD 20993–0002, 301–796–1304; 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,
Jill.Adleberg@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled ‘‘S5(R3)
Detection of Reproductive and
Developmental Toxicity for Human
Pharmaceuticals.’’ 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
E:\FR\FM\12MYN1.SGM
12MYN1
khammond on DSKJM1Z7X2PROD with NOTICES
26050
Federal Register / Vol. 86, No. 90 / Wednesday, May 12, 2021 / Notices
Canada and Swissmedic. Additionally,
the Membership of ICH has expanded to
include other regulatory authorities and
industry associations from around the
world (refer to 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 the Federal Register of November
13, 2017 (82 FR 52306), FDA published
a notice announcing the availability of
a draft guidance entitled ‘‘S5(R3)
Detection of Toxicity to Reproduction
for Human Pharmaceuticals.’’ The
notice gave interested persons an
opportunity to submit comments by
February 12, 2018.
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 agency
members in January 2020.
The guidance finalizes the guidance
issued on November 13, 2017. The
guidance has undergone revisions to
align with other ICH guidances,
elaborate on concepts to consider when
designing studies, and identify potential
circumstances in which a risk
assessment can be made based on
preliminary studies. It also clarifies the
qualification and potential use of
alternative assays.
The purpose of this guidance is to
provide key considerations for
developing a testing strategy to identify
hazard and characterize reproductive
risk for human pharmaceuticals. The
guidance informs on the use of existing
data and identifies potential study
designs to supplement available data to
identify, assess, and convey risk.
General concepts and recommendations
are provided that should be considered
when interpreting study data and
assessing reproductive risk in support of
VerDate Sep<11>2014
17:58 May 11, 2021
Jkt 253001
clinical development and marketing
approval.
This guidance applies to
pharmaceuticals, including
biotechnology-derived pharmaceuticals;
vaccines (and their novel constitutive
ingredients) for infectious diseases; and
novel excipients that are part of the final
pharmaceutical product. It does not
apply to cellular therapies, gene
therapies, and tissue-engineered
products. The methodological
principles (e.g., study design, dose
selection, and species selection)
outlined in this guidance can also apply
to all compounds for which the conduct
of reproductive and/or developmental
toxicity studies is appropriate,
including vaccines for other indications
(e.g., cancer). (see ICH guidance for
industry ‘‘S9 Nonclinical Evaluation for
Anticancer Pharmaceuticals’’ (March
2010), available at https://www.fda.gov/
media/73161/download).
The guidance reflects revisions made
in response to comments received on
the draft guidance. These include
reorganization of the guidance to
improve readability and clarity, to
introduce discussion of conventional
assessment strategies earlier in the
document, and to clarify which
elements of the guidance are more
appropriate for biotechnology-derived
therapies. To accommodate the rapidly
evolving nature of alternative assay
development, the discussion of
alternative assays was placed in an
Annex, subject to a maintenance
procedure, to allow for more frequent
updating of this material.
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 ‘‘S5(R3) Detection of
Reproductive and Developmental
Toxicity for Human Pharmaceuticals.’’ 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
This guidance contains no collection
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.
However, this guidance refers to
previously approved FDA collections of
information. These collections of
information are subject to review by
OMB under the PRA. The collections of
information in 21 CFR part 58 have been
approved under OMB control number
PO 00000
Frm 00053
Fmt 4703
Sfmt 4703
0910–0119; the collections of
information in 21 CFR part 314 have
been approved under OMB control
number 0910–0001; the collections of
information in 21 CFR part 312 have
been approved under OMB control
number 0910–0014; and the content and
format requirements for pregnancy and
lactation labeling of human prescription
drug and biological products have been
approved under OMB control number
0910–0624.
III. Electronic Access
Persons with access to the internet
may obtain the 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: May 6, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for
Policy.
[FR Doc. 2021–10017 Filed 5–11–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2020–D–1370]
COVID–19: Developing Drugs and
Biological Products for Treatment or
Prevention; 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 ‘‘COVID–
19: Developing Drugs and Biological
Products for Treatment or Prevention.’’
This guidance describes FDA’s current
recommendations regarding phase 2 or
phase 3 trials for drugs or biological
products under development for the
treatment or prevention of COVID–19.
Given the public health emergency
presented by COVID–19, this guidance
document is being implemented
without prior public comment because
FDA has determined that prior public
participation is not feasible or
appropriate, but it remains subject to
comment in accordance with the
Agency’s good guidance practices. This
final guidance revises and replaces the
final guidance of the same name issued
SUMMARY:
E:\FR\FM\12MYN1.SGM
12MYN1
]]>Agencies
[Federal Register Volume 86, Number 90 (Wednesday, May 12, 2021)]
[Notices]
[Pages 26048-26050]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-10017]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2017-D-5138]
S5(R3) Detection of Reproductive and Developmental Toxicity for
Human Pharmaceuticals; 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 ``S5(R3)
Detection of Reproductive and Developmental Toxicity for Human
Pharmaceuticals.'' 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 of Technical Requirements for Registration
of Pharmaceuticals for Human Use. The guidance provides key
considerations for developing a testing strategy to identify hazard and
characterize reproductive risk for human pharmaceuticals. The guidance
is intended to align with other ICH guidances, elaborate on concepts to
[[Page 26049]]
consider when designing studies, and identify potential circumstances
in which a risk assessment can be made based on preliminary studies. It
also clarifies the qualification and potential use of alternative
assays. This guidance finalizes the draft guidance issued on November
13, 2017.
DATES: The announcement of the guidance is published in the Federal
Register on May 12, 2021.
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-2017-D-5138 for ``S5(R3) Detection of Reproductive and
Developmental Toxicity for Human Pharmaceuticals.'' 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 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: Ronald Wange,
Center for Drug Evaluation and Research, Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 22, Rm. 3342, Silver Spring, MD 20993-
0002, 301-796-1304; 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,
[email protected].
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``S5(R3) Detection of Reproductive and Developmental Toxicity
for Human Pharmaceuticals.'' 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
[[Page 26050]]
Canada and Swissmedic. Additionally, the Membership of ICH has expanded
to include other regulatory authorities and industry associations from
around the world (refer to 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 November 13, 2017 (82 FR 52306), FDA
published a notice announcing the availability of a draft guidance
entitled ``S5(R3) Detection of Toxicity to Reproduction for Human
Pharmaceuticals.'' The notice gave interested persons an opportunity to
submit comments by February 12, 2018.
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 agency members in January 2020.
The guidance finalizes the guidance issued on November 13, 2017.
The guidance has undergone revisions to align with other ICH guidances,
elaborate on concepts to consider when designing studies, and identify
potential circumstances in which a risk assessment can be made based on
preliminary studies. It also clarifies the qualification and potential
use of alternative assays.
The purpose of this guidance is to provide key considerations for
developing a testing strategy to identify hazard and characterize
reproductive risk for human pharmaceuticals. The guidance informs on
the use of existing data and identifies potential study designs to
supplement available data to identify, assess, and convey risk. General
concepts and recommendations are provided that should be considered
when interpreting study data and assessing reproductive risk in support
of clinical development and marketing approval.
This guidance applies to pharmaceuticals, including biotechnology-
derived pharmaceuticals; vaccines (and their novel constitutive
ingredients) for infectious diseases; and novel excipients that are
part of the final pharmaceutical product. It does not apply to cellular
therapies, gene therapies, and tissue-engineered products. The
methodological principles (e.g., study design, dose selection, and
species selection) outlined in this guidance can also apply to all
compounds for which the conduct of reproductive and/or developmental
toxicity studies is appropriate, including vaccines for other
indications (e.g., cancer). (see ICH guidance for industry ``S9
Nonclinical Evaluation for Anticancer Pharmaceuticals'' (March 2010),
available at https://www.fda.gov/media/73161/download).
The guidance reflects revisions made in response to comments
received on the draft guidance. These include reorganization of the
guidance to improve readability and clarity, to introduce discussion of
conventional assessment strategies earlier in the document, and to
clarify which elements of the guidance are more appropriate for
biotechnology-derived therapies. To accommodate the rapidly evolving
nature of alternative assay development, the discussion of alternative
assays was placed in an Annex, subject to a maintenance procedure, to
allow for more frequent updating of this material.
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 ``S5(R3) Detection of Reproductive and
Developmental Toxicity for Human Pharmaceuticals.'' 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
This guidance contains no collection 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.
However, this guidance refers to previously approved FDA
collections of information. These collections of information are
subject to review by OMB under the PRA. The collections of information
in 21 CFR part 58 have been approved under OMB control number 0910-
0119; the collections of information in 21 CFR part 314 have been
approved under OMB control number 0910-0001; the collections of
information in 21 CFR part 312 have been approved under OMB control
number 0910-0014; and the content and format requirements for pregnancy
and lactation labeling of human prescription drug and biological
products have been approved under OMB control number 0910-0624.
III. Electronic Access
Persons with access to the internet may obtain the 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: May 6, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-10017 Filed 5-11-21; 8:45 am]
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