80 FR 33526 - Assessment of Male-Mediated Developmental Risk for Pharmaceuticals; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 113 (June 12, 2015)

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Assessment of Male-Mediated Developmental Risk for Pharmaceuticals.'' This draft guidance provides recommendations to sponsors for assessing risks to embryo/fetal development resulting from administration of an active pharmaceutical ingredient (API) to males either through an effect on the male germ cell or from fetal exposure following seminal transfer of a potentially developmental toxicant to pregnant females. The need for measures to mitigate the risk to embryo/fetal development posed by males participating in clinical trials is also addressed.

[Federal Register Volume 80, Number 113 (Friday, June 12, 2015)]
[Notices]
[Pages 33526-33527]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-14363]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-D-2001]


Assessment of Male-Mediated Developmental Risk for 
Pharmaceuticals; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Assessment 
of Male-Mediated Developmental Risk for Pharmaceuticals.'' This draft 
guidance provides recommendations to sponsors for assessing risks to 
embryo/fetal development resulting from administration of an active 
pharmaceutical ingredient (API) to males either through an effect on 
the male germ cell or from fetal exposure following seminal transfer of 
a potentially developmental toxicant to pregnant females. The need for 
measures to mitigate the risk to embryo/fetal development posed by 
males participating in clinical trials is also addressed.

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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by August 11, 2015.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: Lynnda Reid, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5388, Silver Spring, MD 20993-0002, 301-
796-0984.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Assessment of Male-Mediated Developmental Risk for 
Pharmaceuticals.'' This guidance presents an overview of FDA's current 
approach to assessing potential risks associated with pharmaceutical 
use in male patients. Current regulatory guidance exists regarding the 
need to assess the genotoxic and embryo/fetal developmental toxicity 
potential of pharmaceuticals before their administration to pregnant 
women and females of reproductive potential. However, there is a lack 
of consistency in clinical trial protocol designs and labeling 
documents regarding pregnancy risk for sexual partners of men being 
administered an API. The conceptus of a female sexual partner may be 
subject to developmental risk associated with

[[Page 33527]]

pre- or post-conception exposure of a male to an API. Such male-
mediated developmental toxicity may result from an effect of the API on 
the male germ cell before conception or occur as a result of direct 
exposure of the conceptus to the pharmaceutical following seminal 
transfer and vaginal uptake in a pregnant partner.
    This draft guidance provides recommendations for addressing the 
potential for male-mediated adverse effects on pregnancy outcome for 
sponsors developing an investigational drug. Topics covered include: 
(1) Factors that investigators should consider when testing a new API 
in males, (2) nonclinical studies relevant to the assessment of male-
mediated developmental risks, and (3) measures to prevent pregnancy or 
seminal transfer to a pregnant sexual partner when risk is either 
unknown or anticipated.
    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 assessment 
of male-mediated developmental risk for 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.

II. The 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.

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: June 8, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-14363 Filed 6-11-15; 8:45 am]
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