Bioequivalence and Bioavailability Forum

Dear both
A redosing study is acceptable for the FDA but not for the EMEA
Based on data from the pivotal study, an acceptance range for the ratios - mean ±3 standard deviations - should be calculated for AUC and Cmax using the log transformed data. For each subject, a ratio (test/reference) should be calculated for AUCt, and Cmax based on data obtained in the re-dosing study. The ratios should be compared to the acceptance range.
The following scenarios are possible:
• If the ratios of AUCt, and Cmax of the suspected outlier lie outside the corresponding acceptance range and all the ratios of AUCt and Cmax for the control subjects fall within the acceptance range, then the outlying subject will be confirmed as an outlier. The pharmacokinetic and statistical analysis for the pivotal study will then be performed without data for the outlying subject.
• If the ratios of AUCt and Cmax for the suspected outlier lie inside the corresponding acceptance range and all the ratios of AUCt and Cmax for the control subjects fall within the acceptance range, then the outlying subject from the pivotal study will not be confirmed as an outlier.
• If the ratios of AUCt and Cmax for one or more of the control subjects lie outside the corresponding acceptance range, then this re-dosing study will be inconclusive with regard to the outlying subject.
All subjects to be included in the redosing study have to have participated in the pivotal study. In the study protocol of the redosing study you have to describe how to select these subjects. A special rule how to select does not exist.
I hope this helps
Kind regards
Dan