A contract research organization's response to the new FDA guidances for bioequivalence/bioavailability studies for orally administered drug products

The new FDA Guidance for Industry BA and BE Studies for Orally Administered Drug Products - General Considerations and Average, Population, and Indivi dual Approaches to Establishing Bioequivalence imply significant changes in the areas of enrollment, cost, ethics, time, entry validation applications (EVAs), and statistical and pharmacokinetic methods. The changes from thre e-period to two-period design for food effect studies, the elimination of m ost steady state studies, and the analyses of only the active moiety or ing redient are welcome. However, if the current guidances are adopted, additio nal time will be needed far participants, and more participants will be nee ded, resulting in higher costs to drug developers. The PK parameters needed to assess BE and the need for replicate designs for drugs with long t(1/2) are still unclear. Finally, the advantages of the aggregate property of th e FDA metric versus the disaggregate criteria are challenged, and four bioe quivalence criteria are proposed.