83 FR 53882 - Testicular Toxicity: Evaluation During Drug Development; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 207 (October 25, 2018)

Page Range		53882-53883
FR Document		2018-23304

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled ``Testicular Toxicity: Evaluation During Drug Development.'' The guidance addresses nonclinical findings that may raise concerns of a drug-related adverse effect on the testes, clinical monitoring of adverse testicular effects early in clinical development, and the design and conduct of a safety clinical trial assessing drug-related testicular toxicity. The guidance is intended to assist sponsors developing drugs and therapeutic biologics regulated within the Center for Drug Evaluation and Research to identify nonclinical signals of testicular toxicity and to evaluate the potential for such toxicity in humans. This guidance finalizes the draft guidance of the same name issued on July 17, 2015.

Federal Register, Volume 83 Issue 207 (Thursday, October 25, 2018)

[Federal Register Volume 83, Number 207 (Thursday, October 25, 2018)]
[Notices]
[Pages 53882-53883]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2018-23304]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-2306]

Testicular Toxicity: Evaluation During Drug Development; 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 final guidance for industry entitled ``Testicular
Toxicity: Evaluation During Drug Development.'' The guidance addresses
nonclinical findings that may raise concerns of a drug-related adverse
effect on the testes, clinical monitoring of adverse testicular effects
early in clinical development, and the design and conduct of a safety
clinical trial assessing drug-related testicular toxicity. The guidance
is intended to assist sponsors developing drugs and therapeutic
biologics regulated within the Center for Drug Evaluation and Research
to identify nonclinical signals of testicular toxicity and to evaluate
the potential for such toxicity in humans. This guidance finalizes the
draft guidance of the same name issued on July 17, 2015.

DATES: The announcement of the guidance is published in the Federal
Register on October 25, 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-2015-D-2306 for ``Testicular Toxicity: Evaluation During Drug
Development.'' 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 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. Send one self-
addressed adhesive label to assist that office in processing your
requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Jennifer Mercier, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 5390, Silver Spring, MD 20993-0002, 301-
796-0957.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry
entitled ``Testicular Toxicity: Evaluation During Drug Development.''
This guidance is intended to help sponsors identify nonclinical signals
that raise concern regarding the potential for human testicular
toxicity and to evaluate those signals appropriately in human studies.
The guidance describes the standard battery of nonclinical studies
that are used to assess the effects of

[[Page 53883]]

pharmaceuticals on the male reproductive system. The guidance discusses
findings in nonclinical studies that may increase the level of concern
for drug-related testicular toxicity. The guidance provides a general
approach on how to weigh the relevance of nonclinical findings,
considering factors that can confound the interpretation of these
findings. If a concerning nonclinical signal is identified, the
guidance presents suggestions for clinical monitoring when the product
is initially administered to humans.
If a reasonable basis for concern of human testicular toxicity
exists, a trial with a primary objective of evaluating drug-related
testicular toxicity may be warranted. The guidance provides
recommendations for the design of such a trial, including study
conduct, endpoints, and presentation of results. These are general
recommendations for defining the role of drugs in testicular injury;
however, the specific details of an individual trial may vary depending
on the context of use of the drug product.
This guidance finalizes the draft guidance of the same name issued
on July 17, 2015 (80 FR 42501). Changes made to the guidance took into
consideration written and verbal comments received. In addition to
editorial changes primarily for clarification, the major changes in the
guidance include revision of information on nonclinical study design
(including species selection, chronic study design, histopathology
assessment, sperm quality, and findings that increase concern for
impaired fertility) and revision of information that, to the extent
possible, subjects enrolled in the dedicated clinical safety trial
represent the intended population.
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 the evaluation of testicular toxicity during
drug development. 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. Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of
information that are subject to review by the Office of Management and
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The collections of information in 21 CFR part 312 have been
approved under OMB control number 0910-0014. The collections of
information in 21 CFR parts 50 and 56 (``Protection of Human Subjects:
Informed Consent and Institutional Review Boards'') have been approved
under OMB control number 0910-0755.

III. Electronic Access

Persons with access to the internet may obtain the guidance at
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or
https://www.regulations.gov.

Dated: October 19, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-23304 Filed 10-24-18; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 83, No. 207 / Thursday, October 25, 2018 / Notices 53883

pharmaceuticals on the male II. Paperwork Reduction Act of 1995 New-30D and project title for reference,
reproductive system. The guidance This guidance refers to previously to Sherrette.funn@hhs.gov, or call the
discusses findings in nonclinical studies approved collections of information that Reports Clearance Officer at 202–795–
that may increase the level of concern are subject to review by the Office of 7714.
for drug-related testicular toxicity. The Management and Budget (OMB) under
guidance provides a general approach SUPPLEMENTARY INFORMATION: Interested
the Paperwork Reduction Act of 1995 persons are invited to send comments
on how to weigh the relevance of (44 U.S.C. 3501–3520). The collections
nonclinical findings, considering factors regarding this burden estimate or any
of information in 21 CFR part 312 have
that can confound the interpretation of other aspect of this collection of
been approved under OMB control
these findings. If a concerning information, including any of the
number 0910–0014. The collections of
nonclinical signal is identified, the following subjects: (1) The necessity and
information in 21 CFR parts 50 and 56
guidance presents suggestions for utility of the proposed information
(‘‘Protection of Human Subjects:
clinical monitoring when the product is collection for the proper performance of
Informed Consent and Institutional
initially administered to humans. the agency’s functions; (2) the accuracy
Review Boards’’) have been approved
If a reasonable basis for concern of of the estimated burden; (3) ways to
under OMB control number 0910–0755.
human testicular toxicity exists, a trial enhance the quality, utility, and clarity
with a primary objective of evaluating III. Electronic Access of the information to be collected; and
drug-related testicular toxicity may be Persons with access to the internet (4) the use of automated collection
warranted. The guidance provides may obtain the guidance at either techniques or other forms of information
recommendations for the design of such https://www.fda.gov/Drugs/Guidance technology to minimize the information
a trial, including study conduct, ComplianceRegulatoryInformation/ collection burden.
endpoints, and presentation of results. Guidances/default.htm or https:// Information Collection Request Title:
These are general recommendations for www.regulations.gov. 0990–0279—Extension—Institutional
defining the role of drugs in testicular Review Board Registration Form.
Dated: October 19, 2018.
injury; however, the specific details of
an individual trial may vary depending Leslie Kux, Abstract: Assistant Secretary for
on the context of use of the drug Associate Commissioner for Policy. Health, Office for Human Research
product. [FR Doc. 2018–23304 Filed 10–24–18; 8:45 am] Protections is requesting an extension
This guidance finalizes the draft BILLING CODE 4164–01–P
on a currently approved information
guidance of the same name issued on collection by the Office of Management
July 17, 2015 (80 FR 42501). Changes and Budget, on the Protection of Human
made to the guidance took into DEPARTMENT OF HEALTH AND Subjects, on the Institutional Review
consideration written and verbal HUMAN SERVICES Board (IRB) Form. The purpose of the
comments received. In addition to IRB Registration Form is to provide a
[Document Identifier: OS–0990–0279] simplified procedure for institutions
editorial changes primarily for
clarification, the major changes in the Agency Information Collection engaged in research conducted or
guidance include revision of Activities; Proposed Collection; Public supported by HHS to satisfy the (1) HHS
information on nonclinical study design Comment Request regulations for the protection of human
(including species selection, chronic subjects at 45 CFR 46.103((b), 45 CFR
study design, histopathology AGENCY: Office of the Secretary, HHS. 46.107, and 45 CFR 46, subpart E,
assessment, sperm quality, and findings ACTION: Notice. Registration of Institutional Review
that increase concern for impaired Boards; and, the Food and Drug
SUMMARY: In compliance with the Administration (FDA) regulations for
fertility) and revision of information requirement of the Paperwork
that, to the extent possible, subjects institutional review boards at 21 CFR
Reduction Act of 1995, the Office of the 56.106.
enrolled in the dedicated clinical safety Secretary (OS), Department of Health
trial represent the intended population. and Human Services, is publishing the Likely Respondents: Institutions or
This guidance is being issued following summary of a proposed organizations operating IRBs that review
consistent with FDA’s good guidance collection for public comment. human subjects research conducted or
practices regulation (21 CFR 10.115). supported by HHS, or, in the case of
DATES: Comments on the ICR must be
The guidance represents the current FDA’s requirements, each IRB in the
received on or before November 26,
thinking of FDA on the evaluation of United States that reviews clinical
2018.
testicular toxicity during drug investigations regulated by FDA under
development. It does not establish any ADDRESSES: Submit your comments to sections 505(i) or 520(g) of the Federal
rights for any person and is not binding Sherette.Funn@hhs.gov or by calling Food, Drug and Cosmetic Act; and each
on FDA or the public. You can use an (202) 795–7714. IRB in the United States that reviews
alternative approach if it satisfies the FOR FURTHER INFORMATION CONTACT: clinical investigations that are intended
requirements of the applicable statutes When submitting comments or to support applications for research or
and regulations. This guidance is not requesting information, please include marketing permits for FDA-regulated
subject to Executive Order 12866. the document identifier 0990–0279 products.

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IRB Registration Update .................................................................................. 5,650 2 30/60 5,650

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Document Created: 2018-10-25 01:44:43
Document Modified: 2018-10-25 01:44:43

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 October 25, 2018.
Contact		Jennifer Mercier, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 5390, Silver Spring, MD 20993-0002, 301- 796-0957.
FR Citation		83 FR 53882

83 FR 53882 - Testicular Toxicity: Evaluation During Drug Development; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 83, Issue 207 (October 25, 2018)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration