Model Based Robustness Analysis of An Industrial Ion Exchange Step

The application of mechanistic models for process development and optimization has been a topic of discussion in the Pharmaceutical industry for many years. Mechanistic models are considered as an alternative to a standard DoE type empiric approach. Most often the DoE approach is preferred based on a cost-benefit evaluation where the time consumption and the complexity are found to extensive when using a mechanistic modelling. In our company we use mechanistic models for the development of selected downstream process steps. In the purification of peptides and proteins it is of great advantage to have the ability to predict the behaviour of the purification steps i.e. retention of the product and various closely related impurities as a function of variables like salt concentration, gradient and loading conditions. The ability to simulate the chromatographic process facilitates fast development and optimization, and it assists robustness analysis of the purification step. The present work demonstrates how simulation, using a mechanistic model of ion exchange chromatography, can be applied for robustness analysis of a process step.