Pharmaceutical Analysis, Drug Discovery and Designing Chemistry

Analytical methods used in the characterization of combination products must be suffi ciently accurate, specifi c, sensitive and precise to ensure quality and reliability of the results, which in turn are crucial for ensuring quality, safety and efficiency of the products. Method validation is the process of proving that an analytical method is acceptable for its intended purpose. Validation is primarily concerned with the identifi cation of the sources of the potential errors in the method and their quantifi cation. It describes in mathematical and quantifi able terms the performance characteristics of a method. Performance is strongly connected with both the requirements and the design of the individual analytical procedure. Consequently, the analyst has to identify relevant parameters, which refl ect the routine performance of the given analytical procedure, to design the method validation studies accordingly and to defi ne acceptance criteria for the results generated. Setting acceptance criteria for the analytical methods used in the characterization of combination products is however much more complex than usually described. Criteria that are too wide may lead to unnecessary and incorrect out-of-specifi cation (OOS) cases, resulting in bad reject decision for the products. Th is study concentrates on analysis, through simulation, of the relation of method variability with specifi cation limits for the total loaded dose of the active substance on the drug eluting stents (DES). Th e fi ndings of this study point towards what levels of precision and accuracy are needed, in other words, what is the magnitude of the allowable total error from all possible eff ects (both systematic and random) in an assay method, in order to to achieve the level of performance required for the methods applied routinely for the evaluation of the total loaded dose of DES as part of lot release/ stability testing