Relative equivalence of CNS safety (FOB) assessment outcomes in male and female Wistar-Han and Sprague-Dawley rats.

Abstract

In 2006 the National Toxicology Program (NTP) of the FDA shifted to the preferred use of Wistar-Han rats from the more commonly used Sprague-Dawley (SD) strain - and industry followed. While European laboratories preferred the Wistar-Han line, there was a paucity of relevant historical control data in many US research institutions for the new industry standard rat strain. In 2010 the NTP reversed its decision and shifted back to SD rats because of reproductive issues with the Wistar strain. For post hoc comparative analyses, we report minimal practical differences in Functional Observational Battery (FOB) data from a large sample of male and female Wistar-Han and SD rats. In summarizing data from the preclinical safety evaluations of the CNS effects of new drugs using the FOB, it is crucial to understand the value of not only how the functional expression of drug effects in the rat are predictive of the human response, but also how and why they differ. What we can predict from the behavioral and physiological response of the designated test system to drug administration is the foundation of generalizability to the human s response. Here, we conclude that the use of either SD or WH rat strains in standard CNS safety studies provide equivalent supportive data for CNS safety assessment required for IND approval under the harmonized guidelines.