Exxua: what flexibility did regulators accept, and why?

“The in vitro chromosomal aberration assay was inadequate because although gepirone was negative for 5-hour treatment, with and without metabolic activation, this negative finding (without activation) should have been followed up with a study using continuous treatment with gepirone (without activation) for ~ 24 hours (1.5 cell doubling times) in accordance with current guidelines.”

“Since the weight of evidence suggests that gepirone is neither genotoxic nor carcinogenic, we are not requiring that this study be repeated; however, it will have to be repeated if it is to be included in product labeling.”

“It is also noted that although the current practice is to express exposure multiples in the labeling based on AUC ratios, the pharmacokinetics and drug metabolism data provide a strong rationale for expressing exposure multiples in the toxicity studies on the basis of body surface area (Mg/M2”