13/14 September 2023
A new Ph. Eur. chapter 5.27. Comparability of alternative analytical procedures has been proposed in Pharmeuropa 34.2. The commenting deadline is 30 June 2022. The general chapter describes how the comparability of an analytical procedure may be demonstrated. However, the use of an alternative procedure is subject to authorization by the competent authority. "The final responsibility for the demonstration of comparability lies with the user and the successful outcome of the process needs to be demonstrated and documented to the satisfaction of the competent authority." Previously, the new Ph. Eur. chapter 5.26. Implementation of pharmacopoeial procedures has already been adopted at the November 2021 session of the European Pharmacopoeia Commission. The chapter will be published in the 11th Edition of the Ph. Eur. and will apply as of 1 January 2023.
The purpose of the comparability study is to evaluate whether the results and performance of an analytical procedure are comparable to those of the pharmacopoeial procedure. This evaluation typically involves an equivalence testing that generates comparable data for the analytical procedure performance characteristics (APPCs) of the two procedures. In the case of quantitative tests, the accuracy and precision across the measurement range may be evaluated. Other APPCs, e.g. specificity / selectivity, may also be evaluated, depending on the intended use. A study protocol (containing the tests and acceptance criteria that will be used to compare the relevant APPCs) is established on the basis of the study design.
The acceptance criteria are defined prior to running the study. An example is to decide that the confidence intervals of the mean results (e.g. of an assay) of two procedures differ with an acceptable confidence level by no more than a defined amount (i.e. the confidence interval is within the defined equivalence margins). The equivalence testing approach may also be used for biological assays. When the equivalence as part of the comparability study is accepted, the alternative procedure may be considered statistically equivalent to the pharmacopoeial procedure.
More information can be found after registration on the Pharmeuropa website.