Extension of Population Pharmacokinetic Models and Optimal Sparse Sampling Designs to Bioequivalence Study Designs

• Activity Number: 277
• Type: Topic Contributed
• Date/Time: Tuesday, August 5, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Junshan Qiu and Mark Fitzgerald*+
• Companies: FDA and Berry Consultants
• Keywords: Optimal Sparse Sampling ; Population Pharmacokinetic Models ; Bioequivalence

Abstract

Bioequivalence between an innovator and a generic drug is generally tested via comparison of area under the curve (AUC) and the maximum serum or plasma concentration (Cmax), both estimated by employing a noncompartment analysis (NCA) of the test article plasma or serum concentration versus time profile. Although traditionally, rich profiles have been generated, such sampling regimens include noninformative time points that add cost and additional noise especially from the observations that are close to the lower bound of the assay limit. Furthermore, a rich sampling approach may not be feasible if the available number of subjects and samples is limited due to ethical, technical, or financial constraints. This challenge is particularly problematic when evaluating product bioequivalence in some veterinary species (e.g., feline, fish, and swine). For this reason, we explore the use of a nonlinear mixed effects model coupled with an optimal sparse sampling design to demonstrate bioequivalence. Our strategy to achieve this goal is as follows: first, identify and assemble relevant prior knowledge for development of a population pharmacokinetic model; second, develop a population pharma