ABSTRACT
As mentioned in the previous chapters, in a typical bioequivalence study for generic approval, the test product is said to be average bioequivalent with the reference product if the 90% confidence interval of the ratio of geometric means of the primary pharmacokinetic (PK) responses such as AUC and Cmax is within the bioequivalence limits of 80% and 125% (FDA, 2001, 2003). This one-size-fits-all ABE criterion ignores the variability associated with the responses although the number of subjects required for concluding ABE with a desired power depends upon the magnitude of the withinsubject variability of the product. One of the major criticisms is that the one-size-fits-all ABE criterion may penalize good products with smaller variability in the sense that they may fail to pass the one-size-fits-all ABE criterion if the intra-subject variability of the reference product is large. To overcome the problem, it is suggested to widen the bioequivalence limits for products with large variability in order to increase the probability of passing for those drug products with smaller variability.
