S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies: Focus on Microsampling-Questions and Answers; International Council for Harmonisation; Guidance for Industry; Availability, 21782-21784 [2018-09930]
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Federal Register / Vol. 83, No. 91 / Thursday, May 10, 2018 / Notices
follows a systematic risk-based
approach for DDI assessment.
Two draft guidance documents, when
finalized, which are intended to assist
drug developers in the planning and
evaluation of the DDI potential of their
drug during development were
published in October 2017 entitled
‘‘Clinical Drug Interaction Studies—
Study Design, Data Analysis, and
Clinical Implications,’’ and ‘‘In Vitro
Metabolism- and Transporter-Mediated
Drug-Drug Interaction Studies.’’ 2 These
two draft guidances replaced the 2012
draft guidance entitled ‘‘Drug
Interaction Studies—Study Design, Data
Analysis, Implications for Dosing, and
Labeling Recommendations.’’ The 2017
draft guidance documents focus on
enzyme- and transporter-based DDIs;
however, they do not discuss TPs.
The 2012 guidance recommended DDI
assessment for TPs in three scenarios:
(1) For cytokine or cytokine modulators,
(2) for a known or suspected mechanism
of DDI not related to effects on
Cytochrome P450 enzymes or
transporters, and (3) for when a TP is
used in combination with another drug.
The Agency now plans to revisit the
previous framework for the assessment
of DDIs for TPs that was included in the
2012 draft guidance. We are seeking
public input on the revision and
development of a framework to address
DDIs for TPs with the goal of publishing
this framework in a short policy/
guidance document.
II. Additional Issues for Consideration
and Request for Information
daltland on DSKBBV9HB2PROD with NOTICES
Interested persons are invited to
provide detailed information and
comments on the approach to the DDI
assessment of TPs. Please read the
information above regarding the
submission of comments and
confidential information. FDA is
particularly interested in responses to
the following overarching questions:
1. In what scenarios/circumstances
and for which classes of TPs should DDI
assessment be performed? Please
provide rationale for your suggestions
including available data and scientific
principles to inform the considerations.
2 ‘‘Clinical Drug Interaction Studies—Study
Design, Data Analysis, and Clinical Implications’’
can be found at https://www.fda.gov/downloads/
Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM292362.pdf; provide comments to
this guidance using docket number FDA–2017–D–
596.
‘‘In Vitro Metabolism- and Transporter-Mediated
Drug-Drug Interaction Studies’’ can be found at
https://www.fda.gov/downloads/Drugs/
GuidanceComplianceRegulatoryInformation/
Guidances/UCM581965.pdf; provide comments to
this guidance using docket number FDA–2017–D–
5961.
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16:29 May 09, 2018
Jkt 244001
2. For circumstances when DDI
assessments are necessary:
a. What types of assessments can be
useful (e.g., in vitro studies, dedicated
clinical studies, population
pharmacokinetic analyses,
physiologically based pharmacokinetic
analyses)? Please discuss the challenges
and limitations with each type of
assessment, and, as necessary, organize
any discussions by the class of TP.
b. What are the study design
considerations (e.g., population,
analytes) for the types of assessments
discussed in bullet 2a. above? Please
describe the rationale for any design
considerations proposed.
FDA will consider all information and
comments submitted.
Dated: May 4, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–09931 Filed 5–9–18; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2016–D–2513]
S3A Guidance: Note for Guidance on
Toxicokinetics: The Assessment of
Systemic Exposure in Toxicity Studies:
Focus on Microsampling—Questions
and Answers; International Council for
Harmonisation; Guidance for Industry;
Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
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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
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a
guidance entitled ‘‘S3A Guidance: Note
for Guidance on Toxicokinetics: The
Assessment of Systemic Exposure in
Toxicity Studies: Focus on
Microsampling—Questions and
Answers.’’ The guidance was prepared
under the auspices of the International
Council for Harmonisation (ICH),
formerly the International Conference
on Harmonisation. This question-andanswer (Q&A) guidance provides
additional information to facilitate
interpretation of the guideline for
industry ‘‘S3A Toxicokinetics: The
Assessment of Systemic Exposure in
Toxicity Studies’’ (S3A guidance),
especially to address the benefit and use
of microsampling techniques in main
study animals. The Q&A guidance is
intended to provide points to consider
before incorporating the microsampling
SUMMARY:
method in toxicokinetic studies and
acknowledges the benefits (and some
limitations) of the use of microsampling.
DATES: The announcement of the
guidance is published in the Federal
Register on May 10, 2018.
ADDRESSES: You may submit either
electronic or written comments on
Agency guidances at any time as
follows:
Submit written/paper submissions as
follows:
• Mail/Hand delivery/Courier (for
written/paper submissions): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, FDA will post your comment, as
well as any attachments, except for
information submitted, marked and
identified, as confidential, if submitted
as detailed in ‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2016–D–2513 for ‘‘S3A Guidance: Note
for Guidance on Toxicokinetics: The
Assessment of Systemic Exposure in
Toxicity Studies: Focus on
Microsampling—Questions and
Answers.’’ Received comments will be
placed in the docket and, except for
those submitted as ‘‘Confidential
E:\FR\FM\10MYN1.SGM
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daltland on DSKBBV9HB2PROD with NOTICES
Federal Register / Vol. 83, No. 91 / Thursday, May 10, 2018 / Notices
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.
• 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.gpo.gov/
fdsys/pkg/FR-2015-09-18/pdf/201523389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852.
You may submit comments on any
guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single
copies of this guidance to the Division
of Drug Information, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10001 New
Hampshire Ave., Hillandale Building,
4th Floor, Silver Spring, MD 20993–
0002, or the Office of Communication,
Outreach and Development, Center for
Biologics Evaluation and Research
(CBER), Food and Drug Administration,
10903 New Hampshire Ave., Bldg. 71,
Rm. 3128, Silver Spring, MD 20993–
0002. Send one self-addressed adhesive
VerDate Sep<11>2014
16:29 May 09, 2018
Jkt 244001
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: Aisar Atrakchi,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 22, Rm. 4118, Silver Spring,
MD 20993–0002, 301–796–1036; or
Anne Pilaro, Center for Biologics
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 4023,
Silver Spring, MD 20993–0002, 240–
402–8341.
Regarding the ICH: Amanda Roache,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 1176, Silver Spring,
MD 20993–0002, 301–796–4548.
SUPPLEMENTARY INFORMATION:
I. Background
In recent years, regulatory authorities
and industry associations from around
the world have participated in many
important initiatives to promote
international harmonization of
regulatory requirements under the ICH.
FDA has participated in several ICH
meetings designed to enhance
harmonization, and FDA is committed
to seeking scientifically based
harmonized technical procedures for
pharmaceutical development. One of
the goals of harmonization is to identify
and reduce differences in technical
requirements for drug development
among regulatory agencies.
ICH was established to provide an
opportunity for harmonization
initiatives to be developed with input
from both regulatory and industry
representatives. FDA also seeks input
from consumer representatives and
others. ICH is concerned with
harmonization of technical
requirements for the registration of
pharmaceutical products for human use
among regulators around the world. The
six founding members of the ICH are the
European Commission; the European
Federation of Pharmaceutical Industries
Associations; FDA; the Japanese
Ministry of Health, Labour, and Welfare;
the Japanese Pharmaceutical
Manufacturers Association; and the
Pharmaceutical Research and
Manufacturers of America. The
Standing Members of the ICH
Association include Health Canada and
Swissmedic. Any party eligible as a
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21783
member in accordance with the ICH
Articles of Association can apply for
membership in writing to the ICH
Secretariat. The ICH Secretariat, which
coordinates the preparation of
documentation, operates as an
international nonprofit organization and
is funded by the Members of the ICH
Association.
The ICH Assembly is the overarching
body of the Association and includes
representatives from each of the ICH
members and observers. The Assembly
is responsible for the endorsement of
draft guidelines and adoption of final
guidelines. FDA publishes ICH
guidelines as FDA guidance.
In the Federal Register of September
8, 2016 (81 FR 62141), FDA published
a notice announcing the availability of
a draft guidance entitled ‘‘ICH S3A
Guidance: Note for Guidance on
Toxicokinetics: The Assessment of
Systemic Exposure in Toxicity
Studies—Questions and Answers.’’ The
notice gave interested persons an
opportunity to submit comments by
December 7, 2016.
After consideration of the comments
received and revisions to the guideline,
a final draft of the guideline was
submitted to the ICH Assembly and
endorsed by the regulatory agencies in
November 2017.
The Q&A guidance provides
additional information to facilitate
interpretation of the S3A guidance. The
S3A guidance has been successfully
implemented since 1994, and in recent
years, analytical method sensitivity has
improved, allowing microsampling
techniques to be used in toxicokinetic
assessment. This Q&A guidance focuses
on points to consider before
incorporating the microsampling
method in toxicokinetic studies,
acknowledges the benefits (and some
limitations) of the use of microsampling
for assessing toxicokinetics in main
study animals, and acknowledges the
overall important contribution of
microsampling to the 3Rs benefits
(replacement, reduction, and
refinement), by reducing or eliminating
the need for toxicokinetic satellite
animals.
The Q&A guidance is intended to
apply to the majority of pharmaceuticals
and biopharmaceuticals; however, for
all types of molecules, consideration
should be given on a case-by-case basis
as to whether the sensitivity of the
measurement method is appropriate for
the small sample volumes available. The
guidance on microsampling provided in
the Q&A can be used in any type of
toxicology study, as well as in rodents
and nonrodents.
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21784
Federal Register / Vol. 83, No. 91 / Thursday, May 10, 2018 / Notices
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 ‘‘S3A Guidance:
Note for Guidance on Toxicokinetics:
The Assessment of Systemic Exposure
in Toxicity Studies: Focus on
Microsampling—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. This guidance is not
subject to Executive Order 12866.
II. Electronic Access
Persons with access to the internet
may obtain the document at https://
www.regulations.gov, https://www.
fda.gov/Drugs/GuidanceCompliance
RegulatoryInformation/Guidances/
default.htm, or https://www.fda.gov/
BiologicsBloodVaccines/Guidance
ComplianceRegulatoryInformation/
Guidances/default.htm.
Dated: May 4, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–09930 Filed 5–9–18; 8:45 am]
BILLING CODE 4164–01–P
Food and Drug Administration
[Docket No. FDA–2018–D–1562]
Uncomplicated Urinary Tract
Infections: Developing Drugs for
Treatment; Draft Guidance for
Industry; Availability
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
‘‘Uncomplicated Urinary Tract
Infections: Developing Drugs for
Treatment.’’ The purpose of this draft
guidance is to assist sponsors in the
development of new drugs for the
treatment of uncomplicated urinary
tract infections.
DATES: Submit either electronic or
written comments on the draft guidance
by August 8, 2018 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:
daltland on DSKBBV9HB2PROD with NOTICES
SUMMARY:
VerDate Sep<11>2014
16:29 May 09, 2018
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
AGENCY:
Electronic Submissions
Jkt 244001
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–
2018–D–1562 for ‘‘Uncomplicated
Urinary Tract Infections: Developing
Drugs for Treatment; Draft Guidance for
Industry.’’ 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.
• 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
PO 00000
Frm 00023
Fmt 4703
Sfmt 4703
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.gpo.gov/
fdsys/pkg/FR-2015-09-18/pdf/201523389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852.
You may submit comments on any
guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single
copies of the draft 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. Send one self-addressed adhesive
label to assist that office in processing
your requests. See the SUPPLEMENTARY
INFORMATION section for electronic
access to the draft guidance document.
FOR FURTHER INFORMATION CONTACT:
Joseph Toerner, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6244,
Silver Spring, MD 20993–0002, 301–
796–1400.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a draft guidance for industry entitled
‘‘Uncomplicated Urinary Tract
Infections: Developing Drugs for
E:\FR\FM\10MYN1.SGM
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]]>Agencies
[Federal Register Volume 83, Number 91 (Thursday, May 10, 2018)]
[Notices]
[Pages 21782-21784]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-09930]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-D-2513]
S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment
of Systemic Exposure in Toxicity Studies: Focus on Microsampling--
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 guidance entitled ``S3A Guidance: Note for
Guidance on Toxicokinetics: The Assessment of Systemic Exposure in
Toxicity Studies: Focus on Microsampling--Questions and Answers.'' The
guidance was prepared under the auspices of the International Council
for Harmonisation (ICH), formerly the International Conference on
Harmonisation. This question-and-answer (Q&A) guidance provides
additional information to facilitate interpretation of the guideline
for industry ``S3A Toxicokinetics: The Assessment of Systemic Exposure
in Toxicity Studies'' (S3A guidance), especially to address the benefit
and use of microsampling techniques in main study animals. The Q&A
guidance is intended to provide points to consider before incorporating
the microsampling method in toxicokinetic studies and acknowledges the
benefits (and some limitations) of the use of microsampling.
DATES: The announcement of the guidance is published in the Federal
Register on May 10, 2018.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2016-D-2513 for ``S3A Guidance: Note for Guidance on
Toxicokinetics: The Assessment of Systemic Exposure in Toxicity
Studies: Focus on Microsampling--Questions and Answers.'' Received
comments will be placed in the docket and, except for those submitted
as ``Confidential
[[Page 21783]]
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.
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.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002, or the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. The guidance may also be obtained by mail by calling
CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Aisar
Atrakchi, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4118, Silver
Spring, MD 20993-0002, 301-796-1036; or Anne Pilaro, Center for
Biologics Evaluation and Research, Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 71, Rm. 4023, Silver Spring, MD 20993-0002,
240-402-8341.
Regarding the ICH: Amanda Roache, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 1176, Silver Spring, MD 20993-0002, 301-796-4548.
SUPPLEMENTARY INFORMATION:
I. Background
In recent years, regulatory authorities and industry associations
from around the world have participated in many important initiatives
to promote international harmonization of regulatory requirements under
the ICH. FDA has participated in several ICH meetings designed to
enhance harmonization, and FDA is committed to seeking scientifically
based harmonized technical procedures for pharmaceutical development.
One of the goals of harmonization is to identify and reduce differences
in technical requirements for drug development among regulatory
agencies.
ICH was established to provide an opportunity for harmonization
initiatives to be developed with input from both regulatory and
industry representatives. FDA also seeks input from consumer
representatives and others. ICH is concerned with harmonization of
technical requirements for the registration of pharmaceutical products
for human use among regulators around the world. The six founding
members of the ICH are the European Commission; the European Federation
of Pharmaceutical Industries Associations; FDA; the Japanese Ministry
of Health, Labour, and Welfare; the Japanese Pharmaceutical
Manufacturers Association; and the Pharmaceutical Research and
Manufacturers of America. The Standing Members of the ICH Association
include Health Canada and Swissmedic. Any party eligible as a member in
accordance with the ICH Articles of Association can apply for
membership in writing to the ICH Secretariat. The ICH Secretariat,
which coordinates the preparation of documentation, operates as an
international nonprofit organization and is funded by the Members of
the ICH Association.
The ICH Assembly is the overarching body of the Association and
includes representatives from each of the ICH members and observers.
The Assembly is responsible for the endorsement of draft guidelines and
adoption of final guidelines. FDA publishes ICH guidelines as FDA
guidance.
In the Federal Register of September 8, 2016 (81 FR 62141), FDA
published a notice announcing the availability of a draft guidance
entitled ``ICH S3A Guidance: Note for Guidance on Toxicokinetics: The
Assessment of Systemic Exposure in Toxicity Studies--Questions and
Answers.'' The notice gave interested persons an opportunity to submit
comments by December 7, 2016.
After consideration of the comments received and revisions to the
guideline, a final draft of the guideline was submitted to the ICH
Assembly and endorsed by the regulatory agencies in November 2017.
The Q&A guidance provides additional information to facilitate
interpretation of the S3A guidance. The S3A guidance has been
successfully implemented since 1994, and in recent years, analytical
method sensitivity has improved, allowing microsampling techniques to
be used in toxicokinetic assessment. This Q&A guidance focuses on
points to consider before incorporating the microsampling method in
toxicokinetic studies, acknowledges the benefits (and some limitations)
of the use of microsampling for assessing toxicokinetics in main study
animals, and acknowledges the overall important contribution of
microsampling to the 3Rs benefits (replacement, reduction, and
refinement), by reducing or eliminating the need for toxicokinetic
satellite animals.
The Q&A guidance is intended to apply to the majority of
pharmaceuticals and biopharmaceuticals; however, for all types of
molecules, consideration should be given on a case-by-case basis as to
whether the sensitivity of the measurement method is appropriate for
the small sample volumes available. The guidance on microsampling
provided in the Q&A can be used in any type of toxicology study, as
well as in rodents and nonrodents.
[[Page 21784]]
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 ``S3A Guidance: Note for Guidance on
Toxicokinetics: The Assessment of Systemic Exposure in Toxicity
Studies: Focus on Microsampling--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. This guidance
is not subject to Executive Order 12866.
II. Electronic Access
Persons with access to the internet may obtain the document at
https://www.regulations.gov, https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
Dated: May 4, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-09930 Filed 5-9-18; 8:45 am]
BILLING CODE 4164-01-P
