Method equivalence assessments should be considered when analytical methods are either modified or substituted. The TOST (two one sided tests) approach provides a sounder data driven method for testing equivalence than a simple comparative intermediate precision study which is typically performed as part of method validation. Prior to designing an equivalency study, an acceptance criterion (an acceptable bias between original and modified/changed method) must be chosen. The choice of acceptance criteria requires the identification of the smallest mean difference or bias between methods that is practically important. Equivalence testing in this manner is used to prove that the new method can generate data which continues to support previously established specifications. Once the acceptance criterion is decided, other aspects of the study can be designed following a set of design principles. When the design and acceptance criteria have been established, the collection of the data can commence. Demonstration of equivalence should not start until the validity of the observations has been confirmed such as assessment for outliers, normality, and comparison of variances. Once the suitability of the data is confirmed, the mean difference between the two data sets can be calculated along with a +/-90% confidence interval using the TOST approach. It can then be established whether equivalence of the two methods has been demonstrated.
In the pharmaceutical industry it is necessary to manage changes to processes or analytical methods to ensure that the quality of drug products is maintained. This often includes an assessment of similarity using data. Scientists may be asked to show that output before and after a change is or will be 'equivalent', without clarity on what exactly is required. In the area of analytical methods, the authors have found it useful to promote the differentiation between equivalence and a wider set of comparability approaches. This paper discusses equivalence and comparability, when such approaches should be applied and provides examples of applications to analytical methods. The discussion is then widened to other application areas such as processes including the appropriateness of the approaches and aspects to be considered when designing equivalence studies. Change management, the design of studies and appropriate statistical analysis can be challenging. However, use of the terminology and methodology exemplified here has enabled scientific project teams to focus on appropriate goals and the means to achieve them with great benefits. Copyright
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