80_FR_42638 80 FR 42501 - Testicular Toxicity: Evaluation During Drug Development; Draft Guidance for Industry; Availability

80 FR 42501 - Testicular Toxicity: Evaluation During Drug Development; Draft Guidance for Industry; Availability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

Page Range42501-42502
FR Document2015-17557

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Testicular Toxicity: Evaluation During Drug Development.'' The draft guidance addresses nonclinical findings that may raise concerns of a drug- related adverse effect on the testes, clinical monitoring of adverse testicular effects early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 The draft guidance is intended to assist sponsors developing drugs to identify nonclinical signals of testicular toxicity and to evaluate the potential for such toxicity in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 Issue 137 (Friday, July 17, 2015) 
[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Testicular Toxicity: Evaluation During Drug Development; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Testicular 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 The draft guidance 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 The draft guidance is intended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

Federal Register / Vol. 80, No. 137 / Friday, July 17, 2015 / Notices 42501 comments should be received within 30 2014 to help coordinate technical information collection request to initiate days of this notice. assistance and control activities with multiple urgently needed information international partners and to deploy collections in West Africa, at U.S. ports Proposed Project teams of public health experts to the of entry, and within STL jurisdictions. National Disease Surveillance affected countries. These information collections allowed Program III—CDC Support for Case The operations turned to the United the agency to accomplish its primary Investigation, Contact Tracing, and Case States (U.S.) when the first imported mission on many fronts to quickly Reports—New—National Center for case of EVD was diagnosed in Texas on prevent public harm, illness, and death Emerging and Zoonotic Infectious September 30, 2014. In response, on from the uncontrolled spread of EVD. Diseases (NCEZID), Centers for Disease October 11, 2014, the CDC Quarantine This new collection of information is Control and Prevention (CDC). Stations and the Department of designed to allow CDC to conduct active Homeland Security Customs and Border disease surveillance in support of and at Background and Brief Description Patrol mobilized to screen, detect, and the request of STL authorities among The international outbreak of Ebola refer arriving travelers who were respondents that may include the virus disease (EVD) in West Africa potential persons at risk for EVD to general public, workers, and STL began March 10, 2014. The initial cases appropriate state, territorial, and local authorities. This should cut down on were from southern Guinea, near its (STL) authorities. The CDC also the need for multiple steps in rural border with Liberia and Sierra increased its commitment to support emergency requests that were Leone. Highly mobile populations STL public health authorities to combat experienced in the first year of the 2014 contributed to increasing waves of and control the spread of EVD within Ebola virus response. person-to-person transmission of EVD their jurisdictions. There are no costs to the respondents that occurred in multiple countries in Thus in 2014, the CDC requested and other than their time. The total West Africa. The CDC activated its received an expedited emergency annualized burden requested is 14,702 Emergency Operations Center on July 9, review and approval from OMB of an hours. ESTIMATED ANNUALIZED BURDEN HOURS Number of Avg. burden Number of Type of respondents Form name responses per per response respondents respondent (in hrs.) General Public—Case .................................... Ebola Virus Disease Case Investigation 15 1 30/60 Form—United States. General Public—Case .................................... Symptom Monitoring Form ............................. 15 42 5/60 General Public—Person Under Investigation Ebola Virus Disease Person Under Inves- 300 1 10/60 (PUI). tigation (PUI) Form. General Public—Person Under Investigation Symptom Monitoring Form ............................. 300 42 5/60 (PUI). General Public—Contact ................................ Ebola Virus Disease Contact Tracing Form— 105 1 10/60 United States. General Public—Contact ................................ Symptom Monitoring Form ............................. 105 42 5/60 Healthcare Workers ........................................ Ebola Virus Disease Tracking Form for 600 15 10/60 Healthcare Workers with Direct Patient Contact. Healthcare Workers ........................................ Symptom Monitoring Form ............................. 600 57 5/60 Laboratory Personnel ...................................... Ebola Tracking Form for Laboratory Per- 600 15 10/60 sonnel. Laboratory Personnel ...................................... Symptom Monitoring Form ............................. 600 57 5/60 Environmental Services Personnel ................. Ebola Tracking Form for Environmental 600 15 10/60 Services Personnel. Environmental Services Personnel ................. Symptom Monitoring Form ............................. 600 57 5/60 State, Territorial, and Local Public Health Au- White House Evening Report ........................ 15 42 10/60 thorities and Their Delegates. Total ......................................................... ......................................................................... ........................ ........................ ........................ Leroy A. Richardson, DEPARTMENT OF HEALTH AND SUMMARY: The Food and Drug Chief, Information Collection Review Office, HUMAN SERVICES Administration (FDA or Agency) is Office of Scientific Integrity, Office of the announcing the availability of a draft Associate Director for Science, Office of the Food and Drug Administration guidance for industry entitled Director, Centers for Disease Control and ‘‘Testicular Toxicity: Evaluation During Prevention. [Docket No. FDA–2015–D–2306] Drug Development.’’ The draft guidance [FR Doc. 2015–17554 Filed 7–16–15; 8:45 am] addresses nonclinical findings that may srobinson on DSK5SPTVN1PROD with NOTICES BILLING CODE 4163–18–P Testicular Toxicity: Evaluation During raise concerns of a drug-related adverse Drug Development; Draft Guidance for effect on the testes, clinical monitoring Industry; Availability of adverse testicular effects early in AGENCY: Food and Drug Administration, clinical development, and the design HHS. and conduct of a safety clinical trial assessing drug-related testicular ACTION: Notice. toxicity. The draft guidance is intended VerDate Sep<11>2014 20:59 Jul 16, 2015 Jkt 235001 PO 00000 Frm 00035 Fmt 4703 Sfmt 4703 E:\FR\FM\17JYN1.SGM 17JYN1

42502 Federal Register / Vol. 80, No. 137 / Friday, July 17, 2015 / Notices to assist sponsors developing drugs to If a concerning nonclinical signal is docket number found in brackets in the identify nonclinical signals of testicular identified, the draft guidance presents heading of this document. Received toxicity and to evaluate the potential for suggestions for clinical monitoring comments may be seen in the Division such toxicity in humans. when the drug is initially administered of Dockets Management between 9 a.m. DATES: Although you can comment on to humans. These suggestions aim to and 4 p.m., Monday through Friday, and any guidance at any time (see 21 CFR minimize the hazards to men while will be posted to the docket at http:// 10.115(g)(5)), to ensure that the Agency making possible the collection of data www.regulations.gov. considers your comment on this draft that will assist in evaluating the potential toxicity of the drug in the IV. Electronic Access guidance before it begins work on the final version of the guidance, submit target population. These early studies, Persons with access to the Internet either electronic or written comments however, are not intended to be a may obtain the document at either on the draft guidance by October 15, definitive evaluation of the potential for http://www.fda.gov/Drugs/ 2015. testicular toxicity of the drug. Rather, GuidanceCompliance they can provide clinical information RegulatoryInformation/Guidances/ ADDRESSES: Submit written requests for that, together with the nonclinical default.htm or http:// single copies of the draft guidance to the information, will support a judgment as www.regulations.gov. Division of Drug Information, Center for to whether the testicular toxicity signal Dated: July 13, 2015. Drug Evaluation and Research, Food warrants indepth evaluation in a and Drug Administration, 10001 New Leslie Kux, dedicated safety study. Hampshire Ave., Hillandale Building, If a reasonable basis for concern of Associate Commissioner for Policy. 4th Floor, Silver Spring, MD 20993– human testicular toxicity exists, a [FR Doc. 2015–17557 Filed 7–16–15; 8:45 am] 0002. Send one self-addressed adhesive dedicated clinical safety trial with a BILLING CODE 4164–01–P label to assist that office in processing primary objective of evaluating drug- your requests. See the SUPPLEMENTARY related testicular toxicity may be INFORMATION section for electronic warranted. The draft guidance provides DEPARTMENT OF HEALTH AND access to the draft guidance document. recommendations for the design of such HUMAN SERVICES Submit electronic comments on the a trial, including conduct, endpoints, draft guidance to http:// Food and Drug Administration and presentation of results. These are www.regulations.gov. Submit written general recommendations for the [Docket No. FDA–2007–D–0429 (formerly comments to the Division of Dockets purpose of defining the role of drugs in Docket No. 2007D–0496)] Management (HFA–305), Food and Drug testicular injury; however, the specific Administration, 5630 Fishers Lane, Rm. details of an individual trial may vary Agency Information Collection 1061, Rockville, MD 20852. depending on the context of use of the Activities; Proposed Collection; FOR FURTHER INFORMATION CONTACT: drug product. Comment Request; Guidance for Eufrecina Deguia, Center for Drug This draft guidance is being issued Industry on Questions and Answers Evaluation and Research, Food and consistent with FDA’s good guidance Regarding the Labeling of Drug Administration, 10903 New practices regulation (21 CFR 10.115). Nonprescription Human Drug Products Hampshire Ave., Bldg. 22, Rm. 5348, The draft guidance, when finalized, will Marketed Without an Approved Silver Spring, MD 20993–0002, 301– represent the current thinking of FDA Application as Required by the Dietary 796–0881. on the evaluation of testicular toxicity Supplement and Nonprescription Drug SUPPLEMENTARY INFORMATION: during drug development. It does not Consumer Protection Act I. Background establish rights for any person and is not AGENCY: Food and Drug Administration, binding on FDA or the public. You can HHS. FDA is announcing the availability of use an alternative approach if it satisfies a draft guidance for industry entitled ACTION: Notice. the requirements of the applicable ‘‘Testicular Toxicity: Evaluation During statutes and regulations. SUMMARY: The Food and Drug Drug Development.’’ This draft guidance Administration (FDA) is announcing an is intended to help sponsors identify II. The Paperwork Reduction Act of 1995 opportunity for public comment on the nonclinical signals that raise concern proposed collection of certain regarding the potential for human This draft guidance refers to information by the Agency. Under the testicular toxicity and to evaluate those previously approved collections of Paperwork Reduction Act of 1995 (the signals appropriately in human studies. information found in FDA regulations. PRA), Federal Agencies are required to The draft guidance describes the These collections of information are publish notice in the Federal Register standard battery of nonclinical studies subject to review by the Office of concerning each proposed collection of that are used to assess the effects of Management and Budget (OMB) under information, including each proposed pharmaceuticals on the male the Paperwork Reduction Act of 1995 extension of an existing collection of reproductive system. The draft guidance (44 U.S.C. 3501–3520). The collections information, and to allow 60 days for discusses findings in nonclinical studies of information in 21 CFR part 312 have public comment in response to the that may increase the level of concern been approved under OMB control notice. This notice solicits comments on for drug-related testicular toxicity. number 0910–0014. certain labeling statements for Examples of nonclinical studies that III. Comments nonprescription human drug products could be used to further evaluate initial srobinson on DSK5SPTVN1PROD with NOTICES marketed without an approved signals of testicular toxicity are also Interested persons may submit either application. described. The draft guidance then electronic comments regarding this provides a general approach on how to document to http://www.regulations.gov DATES: Submit either electronic or weigh the relevance of nonclinical or written comments to the Division of written comments on the collection of findings, taking into account factors that Dockets Management (see ADDRESSES). It information by September 15, 2015. can confound the interpretation of these is only necessary to send one set of ADDRESSES: Submit electronic findings. comments. Identify comments with the comments on the collection of VerDate Sep<11>2014 20:59 Jul 16, 2015 Jkt 235001 PO 00000 Frm 00036 Fmt 4703 Sfmt 4703 E:\FR\FM\17JYN1.SGM 17JYN1


Document Created: 2018-02-23 09:21:48
Document Modified: 2018-02-23 09:21:48
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice.
DatesAlthough 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.
ContactEufrecina 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.
FR Citation80 FR 42501 
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