Precision of the reportable value-Statistical optimization of the number of replicates

Due to the usually rather low number of series/runs in precision studies, the uncertainty of the reportable value precision is often dominated by the factor runs. For a statistical evaluation of the precision of the reportable value (in case of three precision levels), the authors recommend a minimum of six runs, two preparations per run, and two injections/analyses per preparation, in order to provide sufficient precision of the variance estimates. However, a risk-based approach is recommended for the decision to apply a statistical evaluation of the precision of the reportable value. In case of low patient risk such as for an assay of a well-characterized drug substance with tightly controlled manufacturing and analytical variability dominating the specification range, a point estimator will usually be adequate to demonstrate the suitability of the analytical procedure.