Continuous Protein Crystallization
Over the past three decades, protein-based biologics such as insulin and monoclonal antibodies have steadily gained significance in the pharmaceutical industry, accounting for a global market that is worth hundreds of billions US dollars. The production cost of protein-based biologics is significantly higher than traditional small-molecule pharmaceuticals due to the costly downstream processing steps that are centred on chromatography. In order to overcome this challenge, protein crystallisation has been developed to replace chromatography, but the crystallisation of proteins is significantly more difficult than small molecules due to the complex three-dimensional configurations of proteins. Nevertheless, the crystallisation of numerous proteins has been successfully performed at microlitre scale for structural determination, of which a small subset has even been scaled up to the millilitre and litre scales. The latest development in protein crystallisation is continuous protein crystallisation, which is advantageous over the batch mode in terms of product quality control and equipment size. This chapter discusses the general workflow for the development of continuous protein crystallisation, which consists of the screening of crystallisation conditions, the scale-up in batch mode and finally the conversion to the continuous mode.