Evaluation of a continuous chromatography process through process modeling and resin characterization

Increased product yield at reduced cost and time has been the driving force of any manufacturing process. However, inevitable increase in future demand for biopharmaceutical drugs, along with intensified competition and stringent regulatory laws have exhibited an imperative need for established platform processes. In this regard, the implementation of continuous processing, in whole or in components, has demonstrated to increase the manufacturing productivity with key impact on speed, cost and facility implications. While, upstream operations have confirmed increased productivity by implementation of continuous processing components, such as perfusion culture, similar adaptation for downstream processes has been limited. We have evaluated a continuous process for separation of a mAb in a closed environment by employing a combined approach of process modelling for continuous chromatography column and characterization of the Protein A resin. The process model utilized several semi-empirical parameters namely Peclet number and effective diffusivity from previous batch processes for continuous separation mAbs, which were appraised for process efficiency. The resin characteristics were assessed for the impact of pH, temperature, pressure and shelf life using the Scanning Electron Microscope (SEM). The results and associated outcome confirmed that this model can be employed with significant impact on the process time. The approach elucidates the conditions required to perform the continuous unit operation for mAb capture step, with indications of alleviating the bottleneck posed by conventional batch processes. Overall, the outcomes of the evaluated approach supports the shift away from conventional fed batch processes to continuous processing for improved biomanufacturing