Analytical method transfer using equivalence tests with reasonable acceptance criteria and appropriate effort: Extension of the ISPE concept

A method development process is commonly finalized by a method transfer from the developing to the routine laboratory. Statistical tests are performed in order to survey if a transfer succeeded or failed. However, using the classic two-sample t-test can lead to misjudgments and unsatisfying transfer results due to its test characteristics. Therefore the International Society of Pharmaceutical Engineering (ISPE) employed a fixed method transfer design using equivalence tests in their Guide for Technology Transfer. Although it was well received by analytical laboratories worldwide this fixed design can easily bring about high β  -errors (rejection of successful transfers) or high workload (many analysts employed during transfer) if σˆAN (error due to different analysts) exceeds 0.6%. Hence this work introduces an extended concept which will help to circumvent this disadvantage by providing guidance to select a personalized and more appropriate experimental design. First of all it demonstrates that former t-test related acceptance criteria can be scaled by a factor of 1.15, which allows for a broader tolerance without a loss of decision certainty. Furthermore a decision guidance to choose the proper number of analysts or series at given percentage acceptance limits (%AL) is presented.