International Harmonization of Regulatory Requirements for Average Bioequivalence and Current Issues in Individual Bioequivalence

International harmonization of regulatory requirements for average bioequivalence has made major progress during the last years, particularly with regard to the bioequivalence range and statistical analysis. The multiplicative model and hence the logarithmic transformation of the primary extent and rate characteristics AUC and C_max and—consistent with this—the bioequivalence range of (0.80, 1.25) are now accepted by all major health authorities including the European Committee for Proprietary Medicinal Products (CPMP), the United States Food and Drug Administration (FDA), and the Canadian Health Protection Branch (HPB). Such a consensus is missing for the concept of individual bioequivalence. The selection of an appropriate methodology and suitable operative procedures for assessing individual bioequivalence must be addressed in the future by biostatisticians, biopharmaceutical scientists, and regulatory authorities.