2011-24431. Guidance for Industry on Reproductive and Developmental Toxicities-Integrating Study Results To Assess Concerns; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled “Reproductive and Developmental Toxicities—Integrating Study Results to Assess Concerns.” This guidance describes an approach to estimating possible human developmental or reproductive risks associated with drug or biological product exposure when a nonclinical finding of toxicity has been identified, but definitive human data are unavailable. The guidance is intended for drug developers planning to submit new drug applications (NDAs) and biologics licensing applications (BLAs), and who are assessing nonclinical toxicity information.

DATES:

Submit either electronic or written comments on Agency guidances at any time.

ADDRESSES:

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, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, 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.

Submit electronic comments on the 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:

Abigail Jacobs, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg 22, Rm. 6484, Silver Spring, MD 20993-0002, 301-796-0174.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance entitled “Reproductive and Developmental Toxicities—Integrating Study Results to Assess Concerns.” This guidance describes an approach to estimating possible human developmental or reproductive risks associated with drug or biological product exposure when a finding of toxicity has been identified, but definitive human data are unavailable. The guidance is intended for drug developers intending to submit NDAs and BLAs, and who are assessing nonclinical toxicity information. The recommendations included here will also help to ensure a consistent review of reproductive and developmental toxicity data among Center for Drug Evaluation and Research review staff.

This guidance does not: (1) Give detailed advice about labeling or placement of toxicity information in product labeling (for information on labeling, see 21 CFR 201.57); or (2) discuss clinical data, the integration of nonclinical and clinical data, or the clinical implications of these data.

The approach presented here for assessing nonclinical reproductive and developmental toxicity data involves the integration and careful consideration of a variety of different types of nonclinical information: Reproductive toxicology; general toxicology; and toxicokinetic and pharmacokinetic information, including absorption, distribution, metabolism, and elimination findings. The approach is used when there is a toxicity finding and focuses on assessing the likelihood that a drug will increase the risk of adverse human developmental or reproductive outcomes. The approach includes noting when studies were not conducted or when they were not performed using relevant model systems or at appropriate dose ranges.

On November 13, 2001 (66 FR 56830), FDA issued a draft of this guidance. Comments were received and carefully considered during the finalization of the guidance. Most changes to the document are editorial. However, one important change has been made. The description of a process that involved assignment of values of +1, −1 or 0 to the various factors was removed from the guidance.

This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the Agency's current thinking on integration of study results to assess concerns about human reproductive and developmental toxicities. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

II. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) either electronic or written comments regarding this document. It is only necessary to send one set of comments. It is no longer necessary to send two copies of mailed 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.

III. 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: September 19, 2011.

Leslie Kux,

Acting Assistant Commissioner for Policy.