80 FR 33526 - Assessment of Male-Mediated Developmental Risk for Pharmaceuticals; Draft Guidance for Industry; Availability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

Page Range		33526-33527
FR Document		2015-14363

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Assessment of Male-Mediated Developmental Risk for Pharmaceuticals.'' This draft guidance provides recommendations to sponsors for assessing risks to embryo/fetal development resulting from administration of an active pharmaceutical ingredient (API)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 Issue 113 (Friday, June 12, 2015)

[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Pharmaceuticals; Draft Guidance for Industry; Availability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.

-----------------------------------------------------------------------

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the availability of a draft guidance for industry entitled ``Assessment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 This draft
guidance provides recommendations to sponsors for assessing risks to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draft guidance before it begins work on the final version of the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]
BILLING CODE 4164-01-P

33526 Federal Register / Vol. 80, No. 113 / Friday, June 12, 2015 / Notices

510(k) of the FD&C Act (21 U.S.C. GuidanceDocuments/UCM080199.pdf. male germ cell or from fetal exposure
360(k). Section 510(k) of the FD&C Act Send an email request to dsmica@ following seminal transfer of a
and the implementing regulations, 21 fda.hhs.gov to receive an electronic potentially developmental toxicant to
CFR part 807, require persons who copy of the document or send a fax pregnant females. The need for
intend to market a new device to submit request to 301–847–8149 to receive a measures to mitigate the risk to embryo/
a premarket notification (510(k)) hard copy. Please use the document fetal development posed by males
containing information that allows FDA number 159 to identify the guidance participating in clinical trials is also
to determine whether the new device is you are requesting. addressed.
‘‘substantially equivalent’’ within the DATES: Although you can comment on
III. Proposed Class II Device
meaning of section 513(i) of the FD&C any guidance at any time (see 21 CFR
Exemptions
Act to a legally marketed device that 10.115(g)(5)), to ensure that the Agency
does not require premarket approval. FDA has received the following
considers your comment on this draft
On November 21, 1997, the President petition requesting an exemption from
guidance before it begins work on the
signed into law FDAMA (Pub. L. 105– premarket notification for a class II
final version of the guidance, submit
115). Section 206 of FDAMA, in part, device: Brian Orwat, Stryker Medical,
either electronic or written comments
added a new section, 510(m), to the 3800 East Centre Ave., Portage, MI
on the draft guidance by August 11,
FD&C Act. Section 510(m)(1) of the 49002 for its electric positioning chair
2015.
FD&C Act requires FDA, within 60 days classified under 21 CFR 890.3110.
after enactment of FDAMA, to publish ADDRESSES: Submit written requests for
IV. Comments single copies of the draft guidance to the
in the Federal Register a list of each
type of class II device that does not Interested persons may submit either Division of Drug Information, Center for
require a report under section 510(k) of electronic comments regarding this Drug Evaluation and Research, Food
the FD&C Act to provide reasonable document to http://www.regulations.gov and Drug Administration, 10001 New
assurance of safety and effectiveness. or written comments to the Division of Hampshire Ave., Hillandale Building,
Section 510(m) of the FD&C Act further Dockets Management (see ADDRESSES). It 4th Floor, Silver Spring, MD 20993–
provides that a 510(k) will no longer be is only necessary to send one set of 0002. Send one self-addressed adhesive
required for these devices upon the date comments. Identify comments with the label to assist that office in processing
of publication of the list in the Federal docket number found in brackets in the your requests. See the SUPPLEMENTARY
Register. FDA published that list in the heading of this document. Received INFORMATION section for electronic
Federal Register of January 21, 1998 (63 comments may be seen in the Division access to the draft guidance document.
FR 3142). of Dockets Management between 9 a.m. Submit electronic comments on the
Section 510(m)(2) of the FD&C Act and 4 p.m., Monday through Friday, and draft guidance to http://
provides that 1 day after date of will be posted to the docket at http:// www.regulations.gov. Submit written
publication of the list under section www.regulations.gov. comments to the Division of Dockets
510(m)(1), FDA may exempt a device on Management (HFA–305), Food and Drug
Dated: June 9, 2015.
its own initiative or upon petition of an Administration, 5630 Fishers Lane, Rm.
Leslie Kux, 1061, Rockville, MD 20852.
interested person if FDA determines Associate Commissioner for Policy.
that a 510(k) is not necessary to provide FOR FURTHER INFORMATION CONTACT:
[FR Doc. 2015–14434 Filed 6–11–15; 8:45 am] Lynnda Reid, Center for Drug
reasonable assurance of the safety and
effectiveness of the device. This section BILLING CODE 4164–01–P Evaluation and Research, Food and
requires FDA to publish in the Federal Drug Administration, 10903 New
Register a notice of intent to exempt a Hampshire Ave., Bldg. 22, Rm. 5388,
DEPARTMENT OF HEALTH AND Silver Spring, MD 20993–0002, 301–
device, or of the petition, and to provide
HUMAN SERVICES 796–0984.
a 30-day comment period. Within 120
days of publication of this document, Food and Drug Administration SUPPLEMENTARY INFORMATION:
FDA must publish in the Federal
[Docket No. FDA–2015–D–2001] I. Background
Register its final determination
regarding the exemption of the device FDA is announcing the availability of
Assessment of Male-Mediated a draft guidance for industry entitled
that was the subject of the notice. If FDA
Developmental Risk for ‘‘Assessment of Male-Mediated
fails to respond to a petition under this
Pharmaceuticals; Draft Guidance for Developmental Risk for
section within 180 days of receiving it,
Industry; Availability Pharmaceuticals.’’ This guidance
the petition shall be deemed granted.
AGENCY: Food and Drug Administration, presents an overview of FDA’s current
II. Criteria for Exemption approach to assessing potential risks
HHS.
There are a number of factors FDA ACTION: Notice. associated with pharmaceutical use in
may consider to determine whether a male patients. Current regulatory
510(k) is necessary to provide SUMMARY: The Food and Drug guidance exists regarding the need to
reasonable assurance of the safety and Administration (FDA or Agency) is assess the genotoxic and embryo/fetal
effectiveness of a class II device. These announcing the availability of a draft developmental toxicity potential of
factors are discussed in the guidance the guidance for industry entitled pharmaceuticals before their
Agency issued on February 19, 1998, ‘‘Assessment of Male-Mediated administration to pregnant women and
mstockstill on DSK4VPTVN1PROD with NOTICES

entitled ‘‘Procedures for Class II Device Developmental Risk for females of reproductive potential.
Exemptions from Premarket Pharmaceuticals.’’ This draft guidance However, there is a lack of consistency
Notification, Guidance for Industry and provides recommendations to sponsors in clinical trial protocol designs and
CDRH Staff.’’ That guidance is available for assessing risks to embryo/fetal labeling documents regarding pregnancy
through the Internet at http:// development resulting from risk for sexual partners of men being
www.fda.gov/downloads/ administration of an active administered an API. The conceptus of
MedicalDevices/ pharmaceutical ingredient (API) to a female sexual partner may be subject
DeviceRegulationandGuidance/ males either through an effect on the to developmental risk associated with

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Federal Register / Vol. 80, No. 113 / Friday, June 12, 2015 / Notices 33527

pre- or post-conception exposure of a GuidanceCompliance regulatory review period forms the basis
male to an API. Such male-mediated RegulatoryInformation/Guidances/ for determining the amount of extension
developmental toxicity may result from default.htm or http:// an applicant may receive.
an effect of the API on the male germ www.regulations.gov. A regulatory review period consists of
cell before conception or occur as a Dated: June 8, 2015. two periods of time: A testing phase and
result of direct exposure of the Leslie Kux, an approval phase. For human drug
conceptus to the pharmaceutical products, the testing phase begins when
Associate Commissioner for Policy.
following seminal transfer and vaginal the exemption to permit the clinical
[FR Doc. 2015–14363 Filed 6–11–15; 8:45 am]
uptake in a pregnant partner. investigations of the drug becomes
This draft guidance provides BILLING CODE 4164–01–P
effective and runs until the approval
recommendations for addressing the phase begins. The approval phase starts
potential for male-mediated adverse with the initial submission of an
DEPARTMENT OF HEALTH AND
effects on pregnancy outcome for application to market the human drug
HUMAN SERVICES
sponsors developing an investigational product and continues until FDA grants
drug. Topics covered include: (1) Food and Drug Administration permission to market the drug product.
Factors that investigators should Although only a portion of a regulatory
consider when testing a new API in [Docket No. FDA–2013–E–1656]
review period may count toward the
males, (2) nonclinical studies relevant to actual amount of extension that the
Determination of Regulatory Review
the assessment of male-mediated Director of USPTO may award (for
Period for Purposes of Patent
developmental risks, and (3) measures example, half the testing phase must be
Extension; XELJANZ
to prevent pregnancy or seminal transfer subtracted as well as any time that may
to a pregnant sexual partner when risk AGENCY: Food and Drug Administration, have occurred before the patent was
is either unknown or anticipated. HHS. issued), FDA’s determination of the
This draft guidance is being issued ACTION: Notice. length of a regulatory review period for
consistent with FDA’s good guidance a human drug product will include all
practices regulation (21 CFR 10.115). SUMMARY: The Food and Drug of the testing phase and approval phase
The draft guidance, when finalized, will Administration (FDA) has determined as specified in 35 U.S.C. 156(g)(1)(B).
represent the current thinking of FDA the regulatory review period for
FDA has approved for marketing the
on the assessment of male-mediated XELJANZ and is publishing this notice
human drug product XELJANZ
developmental risk for pharmaceuticals. of that determination as required by
(tofacitinib citrate). XELJANZ is
It does not establish any rights for any law. FDA has made the determination
indicated for the treatment of adult
person and is not binding on FDA or the because of the submission of an
patients with moderately to severely
public. You can use an alternative application to the Director of the U.S.
active rheumatoid arthritis who have
approach if it satisfies the requirements Patent and Trademark Office (USPTO),
had an inadequate response or
of the applicable statutes and Department of Commerce, for the
intolerance to methotrexate. Subsequent
regulations. extension of a patent which claims that
to this approval, the USPTO received a
human drug product.
II. The Paperwork Reduction Act of patent term restoration application for
ADDRESSES: Submit electronic XELJANZ (U.S. Patent No. RE41,783)
1995
comments to http:// from Pfizer Inc., and the USPTO
This guidance refers to previously www.regulations.gov. Submit written requested FDA’s assistance in
approved collections of information that petitions (two copies are required) and determining this patent’s eligibility for
are subject to review by the Office of written comments to the Division of patent term restoration. In a letter dated
Management and Budget (OMB) under Dockets Management (HFA–305), Food March 26, 2014, FDA advised the
the Paperwork Reduction Act of 1995 and Drug Administration, 5630 Fishers USPTO that this human drug product
(44 U.S.C. 3501–3520). The collections Lane, Rm. 1061, Rockville, MD 20852. had undergone a regulatory review
of information in 21 CFR part 312 have Submit petitions electronically to http:// period and that the approval of
been approved under OMB control www.regulations.gov at Docket No. XELJANZ represented the first
number 0910–0014. FDA–2013–S–0610. permitted commercial marketing or use
III. Comments FOR FURTHER INFORMATION CONTACT: of the product. Thereafter, the USPTO
Beverly Friedman, Office of requested that FDA determine the
Interested persons may submit either
Management, Food and Drug product’s regulatory review period.
electronic comments regarding this
Administration, 10001 New Hampshire FDA has determined that the
document to http://www.regulations.gov
Ave., Hillandale Campus, Rm. 3180, applicable regulatory review period for
or written comments to the Division of
Silver Spring, MD 20993, 301–796– XELJANZ is 3,947 days. Of this time,
Dockets Management (see ADDRESSES). It
7900. 3,564 days occurred during the testing
is only necessary to send one set of
comments. Identify comments with the SUPPLEMENTARY INFORMATION: The Drug phase of the regulatory review period,
docket number found in brackets in the Price Competition and Patent Term while 383 days occurred during the
heading of this document. Received Restoration Act of 1984 (Pub. L. 98–417) approval phase. These periods of time
comments may be seen in the Division and the Generic Animal Drug and Patent were derived from the following dates:
of Dockets Management between 9 a.m. Term Restoration Act (Pub. L. 100–670) 1. The date an exemption under
mstockstill on DSK4VPTVN1PROD with NOTICES

and 4 p.m., Monday through Friday, and generally provide that a patent may be section 505(i) of the Federal Food, Drug,
will be posted to the docket at http:// extended for a period of up to 5 years and Cosmetic Act (the FD&C Act) (21
www.regulations.gov. so long as the patented item (human U.S.C. 355(i)) became effective: January
drug product, animal drug product, 18, 2002. FDA has verified the
IV. Electronic Access medical device, food additive, or color applicant’s claim that the date the
Persons with access to the Internet additive) was subject to regulatory investigational new drug application
may obtain the document at either review by FDA before the item was became effective was on January 18,
http://www.fda.gov/Drugs/ marketed. Under these acts, a product’s 2002.

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Document Created: 2018-02-22 10:16:04
Document Modified: 2018-02-22 10:16:04

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.
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.
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.
FR Citation		80 FR 33526

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

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration