2017-20906. Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations; Draft Guidance for Industry; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice of availability.

SUMMARY:

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled “Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations.” The purpose of this guidance is to assist sponsors in reproductive toxicity assessments (mainly of embryo-fetal development) for oncology pharmaceuticals and to provide recommendations for product labeling on duration of contraception following cessation of therapy to minimize potential risk to a developing embryo/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 provide for more consistent labeling for oncology pharmaceuticals and to reduce the conduct of nonclinical studies that are not informative on product use.

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comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by November 28, 2017.

ADDRESSES:

You may submit comments 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 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): Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Division of Dockets Management, 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; Draft Guidance for Industry; Availability.” 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 Division of Dockets Management 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 Division of Dockets Management. 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 Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

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.

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, 301-796-0750; 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, 301-796-0750.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry entitled “Oncology Pharmaceuticals: Reproductive Toxicity Testing and Labeling Recommendations.” This guidance presents FDA's current approach to assessing potential risks to embryo-fetal development associated with oncology pharmaceutical use in male and female patients. The term pharmaceutical in this guidance refers to small molecules, therapeutic proteins, antibodies, and related products such as conjugated products. The guidance describes when embryo-fetal developmental studies for oncology pharmaceuticals may be warranted for different types of pharmaceuticals, such as cytotoxic, biological, and conjugated pharmaceuticals, or pharmaceuticals used in combinations. The guidance also discusses other aspects of a nonclinical reproductive toxicity evaluation, such as fertility and pre- and postnatal evaluation. The guidance addresses the need for a reproductive toxicity evaluation when pharmaceuticals are used in specific populations (e.g., pediatric, males-only, or postmenopausal women).

Although current regulatory guidances exist regarding the need to assess the embryo-fetal developmental toxicity potential of pharmaceuticals and the overall design of the studies, this guidance provides additional recommendations on specific types of products and for specific populations, which are not covered under other guidances. In addition, this guidance provides recommendations on the use of contraception and the duration of its use to minimize the potential risks associated with the use of oncology pharmaceuticals.

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 reproductive toxicity testing and labeling recommendations for oncology 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. This is not a significant regulatory action subject to Executive Order 12866.

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 parts 312 and 314 have been approved under OMB control numbers 0910-0014 and 0910-0001, respectively. The collections of information in 21 CFR 201.56, 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 draft guidance at either https://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm or https://www.regulations.gov/​.

Dated: September 22, 2017.

Anna K. Abram,

Deputy Commissioner for Policy, Planning, Legislation, and Analysis.