Quality by design in the pharmaceutical industry: The role of multivariate analysis

摘要

Quality by Design (1) encompasses a wealth of concepts, among which are the Design Space and Control Strategy (2). To address these concepts, several scientific fields need be considered, among which are Process Modeling, Process Control, Multivariate Statistical Process Control, Fault Detection and Diagnosis, Model maintenance, Product Transfer, Multivariate Specifications. Multivariate Statistical Analysis has played a key role in all of the above fields, and relevant applications have been reported by diverse industries such as food, petrochemicals, pulp and paper, polymer, steel, semiconductor, mining, to name a few. It is therefore appropriate to see it as an integral part of the pharmaceutical industry's effort to address issues like process understanding, modeling for design space, establishing operating conditions for multivariate quality specifications, real time process monitoring, real time process control, continuous improvement of processes, and correct technology transfer. From determining the acceptability of raw material entering the plant to ensuring quality of the drug product that leaves the plant, the multivariate analysis philosophy should govern all the operations that take that raw material and convert it to a final drug product that assuresquality, patient safety and efficacy, in a cost efficient way, while meeting safety and environmental constraints. Multivariate analysis philosophy should also govern the lifecycle of the product, from development to manufacturing to site transfer. The pharmaceutical industry can benefit from the wealth of knowledge that has been accumulated and published over decades and applied to other industries, adapt and enhance this knowledge to meet its needs, and therefore achieve these goals in a speedy way.