Bioequivalence and Drug Product Assessment: In Vivo

Introduction ............................................................................................................220 Objectives of Bioequivalence Studies ....................................................................220 History of Bioequivalence Evaluation in the United States ................................... 221

Drug Efficacy Study Implementation (DESI) ................................................... 221 Development of the FDA’s Bioavailability/Bioequivalence Regulations .......... 222 Creation of an Office of Technology Assessment (OTA) .................................. 222 Publication of the 1977 Bioavailability and Bioequivalence Regulations ........ 223 Availability of the Paper NDA Route for Duplicate Drug Products ................. 223 1984 Hatch-Waxman Amendments .................................................................. 223 1992 Revisions to the FDA’s Bioavailability/Bioequivalence Regulations .......224 Early Days of the FDA’s Bioequivalence Review Process ................................224

Two One-Sided Tests Procedure for Analyzing Bioequivalence Data ...................225 Logarithmic Transformation of Bioequivalence Data .......................................225

Reference-Scaled Average Bioequivalence Approach ...........................................226 Role of Tmax in Bioequivalence Analysis ................................................................228 Partial Auc ..............................................................................................................228 General Bioequivalence Study Design Recommendations .................................... 229