Comparisons of outlier tests for potency bioassays

摘要

Summary Potency bioassays are used to measure biological activity. Consequently, potency is considered a critical quality attribute in manufacturing. Relative potency is measured by comparing the concentration‐response curves of a manufactured test batch with that of a reference standard. If the curve shapes are deemed similar, the test batch is said to exhibit constant relative potency with the reference standard, a critical requirement for calibrating the potency of the final drug product. Outliers in bioassay potency data may result in the false acceptance/rejection of a bad/good sample and, if accepted, may yield a biased relative potency estimate. To avoid these issues, the USP1032 recommends the screening of bioassay data for outliers prior to performing a relative potency analysis. In a recently published work, the effects of one or more outliers, outlier size, and outlier type on similarity testing and estimation of relative potency were thoroughly examined, confirming the USP1032 outlier guidance. As a follow‐up, several outlier detection methods, including those proposed by the USP1010, are evaluated and compared in this work through computer simulation. Two novel outlier detection methods are also proposed. The effects of outlier removal on similarity testing and estimation of relative potency were evaluated, resulting in recommendations for best practice.