[Federal Register Volume 84, Number 91 (Friday, May 10, 2019)]
[Notices]
[Pages 20634-20636]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-09691]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-D-2165]


Oncology Pharmaceuticals: Reproductive Toxicity Testing and 
Labeling Recommendations; 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 ``Oncology 
Pharmaceuticals: Reproductive Toxicity Testing and Labeling 
Recommendations.'' The purpose of this guidance is to assist sponsors 
in evaluating reproductive toxicity (mainly related to embryo-fetal 
development (EFD)) for anticancer pharmaceuticals and to provide 
recommendations to applicants for pharmaceutical labeling on duration 
of contraception following cessation of therapy to minimize potential 
risk to a developing embryo or fetus. The guidance also clarifies FDA's 
current thinking on when nonclinical studies for reproductive 
toxicology assessment may not be needed (e.g., for pharmaceuticals 
intended for use in postmenopausal women only). The intended outcome of 
this guidance is to facilitate the development of oncology 
pharmaceuticals while avoiding unnecessary use of animals, in 
accordance with the 3R (reduce, refine, replace) principles, and to 
provide a consistent approach to labeling recommendations for the 
duration of contraception after completion of therapy. This guidance 
finalizes the guidance of the same name issued September 29, 2017.

DATES: The announcement of the guidance is published in the Federal 
Register on May 10, 2019.

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

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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-2017-D-2165 for ``Oncology Pharmaceuticals: Reproductive Toxicity 
Testing and Labeling Recommendations.'' 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: John Leighton, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 2204, Silver Spring, MD 20993-0002, 301-
796-7550; or Haleh Saber, Center for Drug Evaluation and Research, Food 
and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2117, 
Silver Spring, MD 20993-0002, 301-796-7550.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Oncology Pharmaceuticals: Reproductive Toxicity Testing and 
Labeling Recommendations.'' This guidance represents FDA's current 
approach to assessing potential risk to a developing embryo or fetus 
associated with the use of anticancer pharmaceuticals in male and 
female patients. The term oncology pharmaceutical in this guidance 
refers to small molecules, biotechnology-derived products, and related 
compounds such as conjugated products. This guidance describes: (1) How 
to evaluate EFD toxicity for various types of pharmaceuticals, such as 
for genotoxic, biological, conjugated, and combination products; (2) 
whether reproductive toxicity assessment is warranted for specific 
patient populations, such as pharmaceuticals being developed for use in 
male patients only or in postmenopausal women only; and (3) 
recommendations for the duration of contraception after completion of 
therapy to minimize risk to a developing embryo or fetus.
    Although, current regulatory guidances exist regarding the need to 
assess the EFD toxicity potential of pharmaceuticals and the overall 
design of the studies, this guidance provides additional 
recommendations for evaluation of EFD toxicity for specific types of 
pharmaceuticals and for specific populations, which are not covered 
under other guidances. This guidance also expands on the weight of 
evidence approaches that could be utilized to substitute for dedicated 
EFD toxicology studies and hence facilitate the development of oncology 
pharmaceuticals while avoiding unnecessary use of animals, in 
accordance with the 3R principles. Moreover, this guidance provides 
labeling recommendations on the duration of contraception after 
completion of therapy, not previously addressed in other guidance 
documents. This guidance finalizes the guidance of the same name issued 
on September 29, 2017 (82 FR 45593).
    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 ``Oncology Pharmaceuticals: Reproductive 
Toxicity Testing and Labeling Recommendations.'' 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 parts 312 and 314 have 
been approved under OMB control numbers 0910-0014 and 0910-0001, 
respectively. The collections of

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information in 21 CFR 201.56 and 201.57 and the final rule ``Content 
and Format of Labeling for Human Prescription Drug and Biological 
Products; Requirements for Pregnancy and Lactation Labeling'' have been 
approved under OMB control numbers 0910-0572 and 0910-0624.

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: May 7, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-09691 Filed 5-9-19; 8:45 am]
BILLING CODE 4164-01-P


