Juvenile animal toxicity study designs to support pediatric drug development.

The objective of juvenile animal toxicity studies of pharmaceuticals is to obtain safety data, including information on the potential for adverse effects on postnatal growth and development. Studies in juvenile animals may assist in identifying postnatal developmental toxicities or other adverse effects that are not adequately assessed in the routine toxicity evaluations and that cannot be safely or adequately measured in pediatric clinical trials. Unlike the traditional reproductive and developmental toxicology studies that have been discussed in the accompanying reports, the design requirements for toxicity studies in juvenile animals are not explicitly defined in regulatory guidance.

Embryo-fetal developmental toxicity study design for pharmaceuticals.

Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the International Conference on Harmonization (ICH) S5(R2) document (available at http://www.ich.org).

Hematology and clinical chemistry values in pregnant Wistar Hannover rats compared with nonmated controls.

Background: The Wistar Hannover rat has been considered as an alternative animal model to the Sprague-Dawley rat in the safety evaluation of candidate pharmaceuticals for potential reproductive and developmental toxicity. Hematology and clinical chemistry results may provide useful evidence of maternal toxicity in the absence of fetal effects.

Objective: The purpose of this study was to evaluate differences in routine laboratory values between nonmated and pregnant (near-term)Wistar Hannover rats during a control developmental study.