The validation of analytical methods for drug substances and drug products in UK pharmaceutical laboratories

Results of a survey on method validation of analytical procedures used in the testing of drug substances and finished products, of most major research based pharmaceutical companies with laboratories in the UK, are presented. The results indicate that although method validation shows an essential similarity in different laboratories (in particular, chromatographic assay methods are validated in a similar manner in most laboratories), there is much diversity in the detailed application of validation parameters. Testing procedures for drug substances are broadly similar to finished products. Many laboratories validate methods at clinical trial stage to the same extent and detail as at the marketing authorization application (MAA)/new drug application (NDA) submission stage, however, only a small minority of laboratories apply the same criteria to methodology at pre-clinical trial stage. Extensive details of method validation parameters are included in the summary tables of this survey, together with details of the median response given for the validation of the most extensively applied methods. These median response details could be useful in suggesting a harmonized approach to method validation as applied by UK pharmaceutical laboratories. These guidelines would extend beyond the recommendations made to date by regulatory authorities and pharmacopoeias in that minimum requirements for each method validation parameter, e.g. number of replicates, range and tolerance, could be harmonized, both between laboratories and also in Product Licence submissions.