Journal of Bioequivalence & Bioavailability

Abstract

Use of Reverse Blood Grouping to Identify Plasma Samples Switched between Subjects in a Pharmacokinetic Study

Sandeep Shah, Hiren Mehta, Charles E. DiLiberti and Keith D. Gallicano*

Background: Inadvertent switching of plasma samples between two subjects is a leading cause of implausible pharmacokinetic profiles in bioequivalence studies, and may cause erroneous bioequivalence conclusions. Such events typically go unnoticed until review of the pharmacokinetic data. A key objective was to find an in vitro test that, in lieu of real-time documentation, and independent of the drug plasma concentrations themselves, could provide definitive evidence of such a putative sample swap.

Methods: We present a case of a post-hoc analysis of two plasma samples from a bioequivalence study using a Reverse Blood Grouping (RBG) procedure to demonstrate unequivocally that a sample switch had occurred between two study subjects with different ABO blood types.

Results: The bioequivalence study failed with the original incorrect assignment of subject identities, but passed following correction of subject assignments based on RBG analysis and the statistical re-analysis of the data.

Conclusion: RBG testing can support correction of aberrant pharmacokinetic data when there is no real-time documentation demonstrating a protocol violation during the clinical and/or analytical phase of the study.

Published Date: 2024-02-19; Received Date: 2024-01-17