Validation in pharmaceutical analysis. Part I: an integrated approach.

The ICH guidelines achieved a great deal in harmonising the definitions of the required validation characteristics and their basic requirements. However, they provide only a basis for a general discussion of the validation parameters, their calculation and interpretation. It is the responsibility of the analyst to identify parameters which are relevant to the performance of the given analytical procedure as well as to design proper validation protocols including acceptance criteria and to perform an appropriate evaluation. In order to fulfil this responsibility properly, the background of the validation parameters and their consequences must be understood. In this part, the general concept of an integrated validation is discussed. The interdependencies to other ICH guidelines and topics during drug development (e.g. impurities and degradants, stability and specification design) must be taken into account to define the required acceptance criteria. Evaluation of the results in order to prove the suitability of the analytical procedure must be based on the specification limits. Important parameters and aspects are discussed for the individual validation characteristics. In the following parts, these parameters will be discussed in detail. Examples will be given for their interpretation in order to facilitate the selection of parameters which are relevant to the performance and suitability of the given analytical procedure.