The application of control charts in regulated bioanalysis for monitoring long-term reproducibility.

In regulated bioanalysis, the acceptance of results is batch-wise. When during clinical development derived pharmacokinetic or pharmacodynamic results from different studies will be combined or compared, it is recommendable to monitor the long-term reproducibility of bioanalytical assays. Long-term reproducibility can be evaluated by control charts generated from control samples included in each batch. We present a methodology for the implementation, construction and evaluation of control charts next to the regular batch acceptance of bioanalytical results. Decision rules can be set up for a statistical evaluation of the results. Violation of a decision rule may lead to a root-cause investigation and corrective actions to improve assay robustness. Three examples of control charts, for pharmacokinetic and pharmacodynamic analytes are presented.