Selection procedure production factors affecting

An aspect of matrix RMs which is of considerable importance is the question of commutability or horizontal traceability. This refers to the scope of the materials, i.e. the extent to which a matrix RM of a particular composition may reliably be used to evaluate a measurement procedure that is applied to a routine test sample of a different composition. The differences in composition between a reference matrix and a routine test sample matrix must not cause the two materials to behave differently when a particular analytical method is applied. At present, the extent to which this is true is largely a matter of expert judgement based on knowledge of the measurement application. A better and more systematic understanding of the factors affecting horizontal traceability will enable users to select appropriate matrix RMs more reliably and producers to target their production activities more efficiently. 

Method validation is often based on the combined use of validation procedures. The validation used can be direct or comparative. The selection of the validation procedures should also be justified on a cost-benefit basis as long as the fitness-for-purpose is maintained. Focusing the effort on the most critical factors affecting the test method will lead to a different solution for the validation of exact physical and chemical test methods as compared to that for product or subjective testing. For example, in the validation of ergonomics and sensory test methods not all possibilities are applicable. 

Analytical method validation has developed within the pharmaceutical industry over the years in order to produce an assurance of the capabilities of an analytical method. A recent text on validation of analytical techniques has been published by the international Conference on Harmonisation (ICH) [19]. This discusses the four most common analytical procedures (1) identification test, (2) quantitative measurements for content of impurities, (3) limit test for the control of impurities and (4) quantitative measurement of the active moiety in samples of drug substance or drug product or other selected components of the drug product. As in any analytical method, the characteristics of the assay are determined and used to provide quantitative data which demonstrate the analytical validation. The reported validation data for CE are identical to those produced by an LC or GC method [11] and are derived from the same parameters, i.e. peak time and response. Those validation parameters featured by the ICH (Table 1) are derived from the peak data generated by the method. Table 1 also indicates those aspects of a CE method (instrumentation and chemistry), peculiar to the technique, which can affect the peak data and highlights factors which can assist the user in demonstrating the validation parameters. 

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