Process for Continuous Fab Production by Digestion of IgG

Abstract

Intensified processing and end-to-end integrated continuous manufacturing are increasingly being considered in bioprocessing as an alternative to the current batch-based technologies. Similar approaches can also be used at later stages of the production chain, such as in the post-translational modifications that are often considered for therapeutic proteins. In this work, a process to intensify the enzymatic digestion of immunoglobulin G (IgG) and the purification of the resulting Fab fragment is developed. The process consists of the integration of a continuous packed-bed reactor into a multicolumn chromatographic process. The integration is realized through the development of a novel multicolumn countercurrent solvent gradient purification (MCSGP) process, which, by adding a third column to the classical two-column MCSGP process, allows for continuous loading and then straight-through processing of the mixture leaving the reactor.