[Federal Register Volume 82, Number 217 (Monday, November 13, 2017)]
[Notices]
[Pages 52306-52308]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-24483]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-D-5138]


S5(R3) Detection of Toxicity to Reproduction for Human 
Pharmaceuticals; International Council for Harmonisation; Draft 
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance entitled ``S5(R3) Detection of 
Toxicity to Reproduction for Human Pharmaceuticals.'' The draft 
guidance was prepared under the auspices of the International Council 
for Harmonisation (ICH), formerly the International Conference on 
Harmonisation. The draft guidance replaces the existing guidance 
entitled ``S5(R2) Detection of Toxicity to Reproduction for Human 
Pharmaceuticals.'' The draft guidance is intended to align with other 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.

[[Page 52307]]


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this draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by February 12, 2018.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     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 Office, 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 Toxicity to Reproduction 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 Office 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 Office. 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.
    Submit written requests for single copies of this draft 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 draft guidance 
document.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Abigail 
Jacobs, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6474, Silver 
Spring, MD 20993-0002, 301-796-0174; or Martin (Dave) Green, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 3270, Silver Spring, MD 20993-0002, 
301-796-2640. 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

    FDA is announcing the availability of a draft guidance for industry 
entitled ``S5(R3) Detection of Toxicity to Reproduction for Human 
Pharmaceuticals.'' In recent years, regulatory authorities and industry 
associations have participated in many important initiatives to promote 
international harmonization of regulatory requirements. FDA has 
participated in several 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 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

[[Page 52308]]

Swissmedic. Any party eligible to become 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 August 2017, the ICH Assembly endorsed the draft guidance titled 
``S5(R3) Detection of Toxicity to Reproduction for Human 
Pharmaceuticals'' and agreed that the guidance should be made available 
for public comment. The draft guidance is the product of the S5(R3) 
Safety Expert Working Group of the ICH. Comments about this draft will 
be considered by FDA and the S5(R3) Safety Expert Working Group.
    The draft guidance replaces the existing guidance entitled ``S5(R2) 
Detection of Toxicity to Reproduction for Human Pharmaceuticals.'' The 
guidance has undergone major 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.
    To support using alternative assays, compounds that are either 
positive or negative in their ability to induce embryolethality or 
malformations are used in the process of qualifying the assays. 
Although a number of compounds have been identified in the draft 
guidance's Annex, section 11.3.4, Tables 9-6 and 9-7, with the type of 
information for the compounds, the list is not complete; therefore, FDA 
is requesting data in the form of public comments to the docket for 
additional positive and negative reference compounds for potential 
inclusion into the list. These compounds can be either pharmaceuticals 
or non-pharmaceuticals and should be commercially available. For 
additional guidance, please refer to Endnote 3 in the S5(R3) guidance. 
This is not a request for data for the compounds already listed in 
Table 9-6, nor is this a request for examples of assays that could be 
used.
    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 ``S5(R3) 
Detection of Toxicity to Reproduction 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. This guidance 
is not subject to Executive Order 12866.

II. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
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: November 2, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-24483 Filed 11-9-17; 8:45 am]
BILLING CODE 4164-01-P


