Acceptance Criteria for Method Equivalency Assessments

Abstract

Quality by design (ICH-Topic Q8) requires that process control strategy requirements are met and maintained. The challenging task of setting appropriate acceptance criteria for assessment of method equivalence is a critical component of satisfying these requirements. The use of these criteria will support changes made to methods across the product lifecycle. A method equivalence assessment is required when a change is made to a method which may pose a risk to its ability to monitor the quality of the process. Establishing appropriate acceptance criteria are a vital, but not clearly understood, prerequisite to deciding the appropriate design/sample size of the equivalency study. A number of approaches are proposed in the literature for setting acceptance criteria for equivalence which address different purposes. This perspective discusses those purposes and then provides more details on setting acceptance criteria based on patient and producer risk, e.g., tolerance interval approach and the consideration of method or process capability. Applying these to a drug substance assay method for batch release illustrates that, for the equivalence assessment to be meaningful, a clear understanding and appraisal of the control requirements of the method is needed. Rather than a single exact algorithm, the analyst's judgment on a number of aspects is required in deciding the appropriate acceptance criteria.