New bioequivalence studies: individual bioequivalence and population bioequivalence.

Abstract

The bioequivalence study which is currently conducted in different countries is the so-called average bioequivalence approach; this approach has been indicated to be insufficient for assessing switchability between two formulations (i.e., from the reference formulation to the test formulation). In the U.S., therefore, the population bioequivalence approach and the individual bioequivalence approach were recently proposed as the studies which would replace the current average bioequivalence approach. The average bioequivalence approach compares only the mean parameters of the test and reference formulations in the subject groups which received them. In contrast, the population bioequivalence approach guarantees prescribability by assessing the total variances of bioavailability values of the test and reference formulations in addition to the average bioequivalence. The individual bioequivalence approach guarantees switchability from the reference formulation to the test formulation by assessing the intrasubject variance and subject-by-formulation interaction in addition to the average bioequivalence. We introduce the individual bioequivalence approach and the population bioequivalence approach in comparison with the current average bioequivalence approach and have discussed the characteristics and issues of each of these three bioequivalence approaches.