80 FR 42501 - Testicular Toxicity: Evaluation During Drug Development; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 137 (July 17, 2015)

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Testicular Toxicity: Evaluation During Drug Development.'' The draft guidance addresses nonclinical findings that may raise concerns of a drug- related adverse effect on the testes, clinical monitoring of adverse testicular effects early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 The draft guidance is intended to assist sponsors developing drugs to identify nonclinical signals of testicular toxicity and to evaluate the potential for such toxicity in humans.

[Federal Register Volume 80, Number 137 (Friday, July 17, 2015)]
[Notices]
[Pages 42501-42502]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-17557]


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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Testicular Toxicity: Evaluation During Drug Development; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Testicular 
Toxicity: Evaluation During Drug Development.'' The draft guidance 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 The draft guidance is intended

[[Page 42502]]

to assist sponsors developing drugs to identify nonclinical signals of 
testicular toxicity and to evaluate the potential for such toxicity in 
humans.

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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by October 15, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
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 draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Eufrecina Deguia, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5348, Silver Spring, MD 20993-0002, 301-
796-0881.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Testicular Toxicity: Evaluation During Drug Development.'' 
This draft 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 draft guidance describes the standard battery of nonclinical 
studies that are used to assess the effects of pharmaceuticals on the 
male reproductive system. The draft guidance discusses findings in 
nonclinical studies that may increase the level of concern for drug-
related testicular toxicity. Examples of nonclinical studies that could 
be used to further evaluate initial signals of testicular toxicity are 
also described. The draft guidance then provides a general approach on 
how to weigh the relevance of nonclinical findings, taking into account 
factors that can confound the interpretation of these findings.
    If a concerning nonclinical signal is identified, the draft 
guidance presents suggestions for clinical monitoring when the drug is 
initially administered to humans. These suggestions aim to minimize the 
hazards to men while making possible the collection of data that will 
assist in evaluating the potential toxicity of the drug in the target 
population. These early studies, however, are not intended to be a 
definitive evaluation of the potential for testicular toxicity of the 
drug. Rather, they can provide clinical information that, together with 
the nonclinical information, will support a judgment as to whether the 
testicular toxicity signal warrants indepth evaluation in a dedicated 
safety study.
    If a reasonable basis for concern of human testicular toxicity 
exists, a dedicated clinical safety trial with a primary objective of 
evaluating drug-related testicular toxicity may be warranted. The draft 
guidance provides recommendations for the design of such a trial, 
including conduct, endpoints, and presentation of results. These are 
general recommendations for the purpose of 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 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 the evaluation 
of testicular toxicity during drug development. It does not establish 
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. The Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
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.

III. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

IV. Electronic Access

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

    Dated: July 13, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-17557 Filed 7-16-15; 8:45 am]
 BILLING CODE 4164-01-P