Criteria for selecting pharmacokinetic repeat study samples.

The pharmacokinetic (PK) repeat study sample, selected by the study pharmacokineticist, requires repeat bioanalysis because the concentration is incongruous with drug plasma concentration versus time profile. The inconsistency could be due to a number of reasons, including the detectable drug concentration in a predose sample or a sample from a placebo control group or a significant double peak in the terminal phase of an individual plasma concentration versus time profile that is not consistent with the profiles from other subjects in the same dose group. The justification for selecting the PK repeat sample should be clearly documented. The repeat analysis should be conducted in duplicate or triplicate as allowed by sample volume. To avoid subjectively selecting PK repeat samples, standard operating procedures should be prepared prior to the start of the study in order to define the criteria for selecting PK repeat study samples and also the procedure for conducting repeat analysis and reporting repeat assay values. The incurred sample re-analysis (ISR) assessment and the repeat analysis of pharmacokinetically anomalous samples are different in terms of purpose and conduct; the ISR assessment alone cannot accept or reject the results from a study for analytical reasons. Therefore, the results from the ISR assessment for assuring the reliability and reproducibility of a validated bioanalytical method in animal or human plasma or other biological matrices should not be used to substitute the results of repeat analysis of pharmacokinetically anomalous samples from a nonclinical or clinical study.