83 FR 21782 - 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
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 91 (May 10, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 91 (May 10, 2018)
| Page Range | 21782-21784 | |
| FR Document | 2018-09930 |
[Federal Register Volume 83, Number 91 (Thursday, May 10, 2018)] [Notices] [Pages 21782-21784] From the Federal Register Online [www.thefederalregister.org] [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.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)). Submit written requests for single copies of this guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002, or the Office of Communication, Outreach and Development, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. The guidance may also be obtained by mail by calling CBER at 1-800-835-4709 or 240-402-8010. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document. FOR FURTHER INFORMATION CONTACT: Regarding the guidance: 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
![21782 Federal Register / Vol. 83, No. 91 / Thursday, May 10, 2018 / Notices
follows a systematic risk-based 2. For circumstances when DDI method in toxicokinetic studies and
approach for DDI assessment. assessments are necessary: acknowledges the benefits (and some
Two draft guidance documents, when a. What types of assessments can be limitations) of the use of microsampling.
finalized, which are intended to assist useful (e.g., in vitro studies, dedicated DATES: The announcement of the
drug developers in the planning and clinical studies, population guidance is published in the Federal
evaluation of the DDI potential of their pharmacokinetic analyses, Register on May 10, 2018.
drug during development were physiologically based pharmacokinetic ADDRESSES: You may submit either
published in October 2017 entitled analyses)? Please discuss the challenges electronic or written comments on
‘‘Clinical Drug Interaction Studies— and limitations with each type of Agency guidances at any time as
Study Design, Data Analysis, and assessment, and, as necessary, organize follows:
Clinical Implications,’’ and ‘‘In Vitro any discussions by the class of TP.
Metabolism- and Transporter-Mediated b. What are the study design Electronic Submissions
Drug-Drug Interaction Studies.’’ 2 These considerations (e.g., population, Submit electronic comments in the
two draft guidances replaced the 2012 analytes) for the types of assessments following way:
draft guidance entitled ‘‘Drug discussed in bullet 2a. above? Please • Federal eRulemaking Portal:
Interaction Studies—Study Design, Data describe the rationale for any design https://www.regulations.gov. Follow the
Analysis, Implications for Dosing, and considerations proposed. instructions for submitting comments.
Labeling Recommendations.’’ The 2017 FDA will consider all information and Comments submitted electronically,
draft guidance documents focus on comments submitted. including attachments, to https://
enzyme- and transporter-based DDIs; Dated: May 4, 2018. www.regulations.gov will be posted to
however, they do not discuss TPs. Leslie Kux, the docket unchanged. Because your
The 2012 guidance recommended DDI comment will be made public, you are
Associate Commissioner for Policy.
assessment for TPs in three scenarios: solely responsible for ensuring that your
(1) For cytokine or cytokine modulators, [FR Doc. 2018–09931 Filed 5–9–18; 8:45 am]
comment does not include any
(2) for a known or suspected mechanism BILLING CODE 4164–01–P
confidential information that you or a
of DDI not related to effects on third party may not wish to be posted,
Cytochrome P450 enzymes or such as medical information, your or
transporters, and (3) for when a TP is DEPARTMENT OF HEALTH AND
HUMAN SERVICES anyone else’s Social Security number, or
used in combination with another drug. confidential business information, such
The Agency now plans to revisit the Food and Drug Administration as a manufacturing process. Please note
previous framework for the assessment that if you include your name, contact
of DDIs for TPs that was included in the [Docket No. FDA–2016–D–2513]
information, or other information that
2012 draft guidance. We are seeking identifies you in the body of your
public input on the revision and S3A Guidance: Note for Guidance on
Toxicokinetics: The Assessment of comments, that information will be
development of a framework to address posted on https://www.regulations.gov.
DDIs for TPs with the goal of publishing Systemic Exposure in Toxicity Studies:
Focus on Microsampling—Questions • If you want to submit a comment
this framework in a short policy/ with confidential information that you
guidance document. and Answers; International Council for
Harmonisation; Guidance for Industry; do not wish to be made available to the
II. Additional Issues for Consideration Availability public, submit the comment as a
and Request for Information written/paper submission and in the
AGENCY: Food and Drug Administration, manner detailed (see ‘‘Written/Paper
Interested persons are invited to
HHS. Submissions’’ and ‘‘Instructions’’).
provide detailed information and
comments on the approach to the DDI ACTION: Notice of availability. Written/Paper Submissions
assessment of TPs. Please read the SUMMARY: The Food and Drug Submit written/paper submissions as
information above regarding the Administration (FDA or Agency) is follows:
submission of comments and announcing the availability of a • Mail/Hand delivery/Courier (for
confidential information. FDA is guidance entitled ‘‘S3A Guidance: Note written/paper submissions): Dockets
particularly interested in responses to for Guidance on Toxicokinetics: The Management Staff (HFA–305), Food and
the following overarching questions: Assessment of Systemic Exposure in Drug Administration, 5630 Fishers
1. In what scenarios/circumstances
Toxicity Studies: Focus on Lane, Rm. 1061, Rockville, MD 20852.
and for which classes of TPs should DDI
Microsampling—Questions and • For written/paper comments
assessment be performed? Please
Answers.’’ The guidance was prepared submitted to the Dockets Management
provide rationale for your suggestions
under the auspices of the International Staff, FDA will post your comment, as
including available data and scientific
Council for Harmonisation (ICH), well as any attachments, except for
principles to inform the considerations.
formerly the International Conference information submitted, marked and
2 ‘‘Clinical Drug Interaction Studies—Study
on Harmonisation. This question-and- identified, as confidential, if submitted
Design, Data Analysis, and Clinical Implications’’ answer (Q&A) guidance provides as detailed in ‘‘Instructions.’’
can be found at https://www.fda.gov/downloads/ additional information to facilitate Instructions: All submissions received
Drugs/GuidanceComplianceRegulatoryInformation/ interpretation of the guideline for must include the Docket No. FDA–
Guidances/UCM292362.pdf; provide comments to industry ‘‘S3A Toxicokinetics: The 2016–D–2513 for ‘‘S3A Guidance: Note
daltland on DSKBBV9HB2PROD with NOTICES
this guidance using docket number FDA–2017–D–
596. Assessment of Systemic Exposure in for Guidance on Toxicokinetics: The
‘‘In Vitro Metabolism- and Transporter-Mediated Toxicity Studies’’ (S3A guidance), Assessment of Systemic Exposure in
Drug-Drug Interaction Studies’’ can be found at especially to address the benefit and use Toxicity Studies: Focus on
https://www.fda.gov/downloads/Drugs/ of microsampling techniques in main Microsampling—Questions and
GuidanceComplianceRegulatoryInformation/
Guidances/UCM581965.pdf; provide comments to
study animals. The Q&A guidance is Answers.’’ Received comments will be
this guidance using docket number FDA–2017–D– intended to provide points to consider placed in the docket and, except for
5961. before incorporating the microsampling those submitted as ‘‘Confidential
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![21784 Federal Register / Vol. 83, No. 91 / Thursday, May 10, 2018 / Notices
This guidance is being issued Electronic Submissions with a heading or cover note that states
consistent with FDA’s good guidance Submit electronic comments in the ‘‘THIS DOCUMENT CONTAINS
practices regulation (21 CFR 10.115). following way: CONFIDENTIAL INFORMATION.’’ The
The guidance represents the current • Federal eRulemaking Portal: Agency will review this copy, including
thinking of FDA on ‘‘S3A Guidance: https://www.regulations.gov. Follow the the claimed confidential information, in
Note for Guidance on Toxicokinetics: instructions for submitting comments. its consideration of comments. The
The Assessment of Systemic Exposure Comments submitted electronically, second copy, which will have the
in Toxicity Studies: Focus on including attachments, to https:// claimed confidential information
Microsampling—Questions and www.regulations.gov will be posted to redacted/blacked out, will be available
Answers.’’ It does not establish any the docket unchanged. Because your for public viewing and posted on
rights for any person and is not binding comment will be made public, you are https://www.regulations.gov. Submit
on FDA or the public. You can use an solely responsible for ensuring that your both copies to the Dockets Management
alternative approach if it satisfies the comment does not include any Staff. If you do not wish your name and
requirements of the applicable statutes confidential information that you or a contact information to be made publicly
and regulations. This guidance is not third party may not wish to be posted, available, you can provide this
subject to Executive Order 12866. such as medical information, your or information on the cover sheet and not
anyone else’s Social Security number, or in the body of your comments and you
II. Electronic Access
confidential business information, such must identify this information as
Persons with access to the internet ‘‘confidential.’’ Any information marked
as a manufacturing process. Please note
may obtain the document at https:// as ‘‘confidential’’ will not be disclosed
that if you include your name, contact
www.regulations.gov, https://www. except in accordance with 21 CFR 10.20
information, or other information that
fda.gov/Drugs/GuidanceCompliance and other applicable disclosure law. For
identifies you in the body of your
RegulatoryInformation/Guidances/ more information about FDA’s posting
comments, that information will be
default.htm, or https://www.fda.gov/ of comments to public dockets, see 80
posted on https://www.regulations.gov.
BiologicsBloodVaccines/Guidance FR 56469, September 18, 2015, or access
• If you want to submit a comment
ComplianceRegulatoryInformation/ the information at: https://www.gpo.gov/
with confidential information that you
Guidances/default.htm. fdsys/pkg/FR-2015-09-18/pdf/2015-
do not wish to be made available to the
Dated: May 4, 2018. public, submit the comment as a 23389.pdf.
Leslie Kux, written/paper submission and in the Docket: For access to the docket to
Associate Commissioner for Policy. manner detailed (see ‘‘Written/Paper read background documents or the
Submissions’’ and ‘‘Instructions’’). electronic and written/paper comments
[FR Doc. 2018–09930 Filed 5–9–18; 8:45 am]
received, go to https://
BILLING CODE 4164–01–P Written/Paper Submissions www.regulations.gov and insert the
Submit written/paper submissions as docket number, found in brackets in the
DEPARTMENT OF HEALTH AND follows: heading of this document, into the
HUMAN SERVICES • Mail/Hand delivery/Courier (for ‘‘Search’’ box and follow the prompts
written/paper submissions): Dockets and/or go to the Dockets Management
Food and Drug Administration Management Staff (HFA–305), Food and Staff, 5630 Fishers Lane, Rm. 1061,
Drug Administration, 5630 Fishers Rockville, MD 20852.
[Docket No. FDA–2018–D–1562] You may submit comments on any
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments guidance at any time (see 21 CFR
Uncomplicated Urinary Tract
submitted to the Dockets Management 10.115(g)(5)).
Infections: Developing Drugs for
Staff, FDA will post your comment, as Submit written requests for single
Treatment; Draft Guidance for
well as any attachments, except for copies of the draft guidance to the
Industry; Availability
information submitted, marked and Division of Drug Information, Center for
AGENCY: Food and Drug Administration, identified, as confidential, if submitted Drug Evaluation and Research, Food
HHS. as detailed in ‘‘Instructions.’’ and Drug Administration, 10001 New
ACTION: Notice of availability. Instructions: All submissions received Hampshire Ave., Hillandale Building,
must include the Docket No. FDA– 4th Floor, Silver Spring, MD 20993–
SUMMARY: The Food and Drug 2018–D–1562 for ‘‘Uncomplicated 0002. Send one self-addressed adhesive
Administration (FDA or Agency) is Urinary Tract Infections: Developing label to assist that office in processing
announcing the availability of a draft Drugs for Treatment; Draft Guidance for your requests. See the SUPPLEMENTARY
guidance for industry entitled Industry.’’ Received comments will be INFORMATION section for electronic
‘‘Uncomplicated Urinary Tract placed in the docket and, except for access to the draft guidance document.
Infections: Developing Drugs for those submitted as ‘‘Confidential FOR FURTHER INFORMATION CONTACT:
Treatment.’’ The purpose of this draft Submissions,’’ publicly viewable at Joseph Toerner, Center for Drug
guidance is to assist sponsors in the https://www.regulations.gov or at the Evaluation and Research, Food and
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treatment of uncomplicated urinary a.m. and 4 p.m., Monday through Hampshire Ave., Bldg. 22, Rm. 6244,
tract infections. Friday. Silver Spring, MD 20993–0002, 301–
DATES: Submit either electronic or • Confidential Submissions—To 796–1400.
daltland on DSKBBV9HB2PROD with NOTICES
written comments on the draft guidance submit a comment with confidential SUPPLEMENTARY INFORMATION:
by August 8, 2018 to ensure that the information that you do not wish to be
Agency considers your comment on this made publicly available, submit your I. Background
draft guidance before it begins work on comments only as a written/paper FDA is announcing the availability of
the final version of the guidance. submission. You should submit two a draft guidance for industry entitled
ADDRESSES: You may submit comments copies total. One copy will include the ‘‘Uncomplicated Urinary Tract
on any guidance at any time as follows: information you claim to be confidential Infections: Developing Drugs for
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Document Created: 2018-11-02 09:47:06
Document Modified: 2018-11-02 09:47:06
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| Dates | The announcement of the guidance is published in the Federal Register on May 10, 2018. | |
| 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. | |
| FR Citation | 83 FR 21782 |
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