Mechanistic Modelling of Chromatographic Processes: Its Trends, Development, Challenges and Applications

In biopharmaceutical manufacturing chromatography technique has been the backbone of purification process. As bioprocessing has advanced, a growing trend has emerged toward gaining a thorough understanding of the fundamental principles underlying the pertinent unit operations, which for some operations includes the use of mechanistic modelling in a manner similar to how it is used in the chemical industry. Due to the complexity of the impurity kinds and contents originating from high titer cell culture harvest, developing and optimizing chromatography processes is a time-consuming task. Mechanistic modelling is one such approach that aids in depth understanding of the process step, underlying physicochemical processes. A model that is well calibrated and has an acceptable predictability can be of great help in process optimization as well as characterization. Mechanistic models for process optimization have continued to bloom for almost 10 decades now, yet only a very little of it has been understood. Though the simpler and essential features of the models have received a thorough investigation, the complex parameters and specialization of the simpler models into biopharmaceutical processing requires greater clarifications. The purpose of this review is to encompass the modelling approaches that have been used before and are currently in use, estimation of model parameters, their application and evolution over time.