[Federal Register Volume 83, Number 207 (Thursday, October 25, 2018)]
[Notices]
[Pages 53882-53883]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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draft guidance of the same name issued on July 17, 2015.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.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. 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