[Federal Register Volume 81, Number 174 (Thursday, September 8, 2016)]
[Notices]
[Pages 62141-62142]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-21552]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-2513]


ICH S3A Guidance: Note for Guidance on Toxicokinetics: The 
Assessment of Systemic Exposure in Toxicity Studies--Questions and 
Answers; International Council for Harmonisation; Draft Guidance for 
Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is 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the availability of a draft guidance entitled ``ICH S3A Guidance: Note 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 The draft guidance was 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 ``S3A 
Guidance: 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: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by December 7, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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 ``ICH S3A Guidance: Note for Guidance on 
Toxicokinetics: The Assessment of Systemic Exposure in Toxicity 
Studies--Questions and Answers; International Council for 
Harmonisation; Draft Guidance for Industry; Availability.''
    Received comments will be placed in the docket and, except for 
those submitted as ``Confidential Submissions,'' publicly viewable at 
http://www.regulations.gov or at the Division of Dockets Management 
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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the

[[Page 62142]]

docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of this guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research 
(CDER), 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, 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. 4025, 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. 1128, Silver Spring, MD 20993-0002, 301-796-4548.

SUPPLEMENTARY INFORMATION: 

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory Agencies.
    ICH was organized 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; the Japanese Ministry of 
Health, Labour, and Welfare; the Japanese Pharmaceutical Manufacturers 
Association; CDER and CBER, FDA; 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. In 
May 2016, the ICH Assembly endorsed the draft guidance entitled ``ICH 
S3A Guidance: Note for Guidance on Toxicokinetics: The Assessment of 
Systemic Exposure in Toxicity Studies--Questions and Answers'' and 
agreed that the guidance should be made available for public comment. 
The draft guidance is the product of the Safety Expert Working Group of 
the ICH. Comments about this draft will be considered by FDA and the 
Safety Expert Working Group.
    The draft 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 draft 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 with 
the small sample volumes available.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ICH ``S3A 
Guidance: Note for Guidance on Toxicokinetics: The Assessment of 
Systemic Exposure in Toxicity Studies--Questions and Answers.'' It does 
not establish any rights for any person and is not binding on FDA or 
the public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.

II. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://www.regulations.gov, http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

    Dated: September 1, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-21552 Filed 9-7-16; 8:45 am]
 BILLING CODE 4164-01-P