Historically, various industries such as petroleum, steel, automobile and fast moving consumer goods shifted from batch to continuous processing. The major motivation behind this shift has been the ability to meet increasing demands, reduce processing costs and most importantly produce products with consistent quality and higher productivity. Biotherapeutics industry presently is undergoing a similar transition from batch to continuous processing by investing in novel continuous processing technologies. In this study, we propose the use of a novel coiled flow inversion reactor (CFIR) for continuously performing biotech unit operations that require reaction and mixing. Coiled flow inverter (CFIR) has been proposed as a configuration consisting of helical coils bent at equidistant right angles to cause flow inversion for improved cross sectional mixing in the tube. The configuration can be appropriately utilized to provide a sharper residence time distribution along with good cross-sectional mixing, better emulating a plug flow than a simple straight tube or a helix. The novel reactor has been explored for continuously performing protein refolding and precipitation in two different case studies. The refolding and precipitation conditions were optimized in the continuous mode in CFIR using a design of experiments (DOE) study. The performance of the continuous protocol has been compared with an optimized batch protocol. It has been demonstrated that enhanced mixing in CFIR allows for operation at higher protein concentrations during refolding. In case of continuous precipitation improved clearance of host cell proteins (HCP) and DNA was obtained compared to batch. In both the case studies the continuous configuration demonstrated a 10-20X increase in productivity and a 30-70% decrease in the manufacturing cost with no adverse effect on product quality. Effectively, the configuration can significantly contribute towards creation of an integrated continuous bioprocessing platform.

Continuous processing of biotherapeutics through application of a novel Coiled Flow Inversion Reactor (CFIR)

253rd National Meeting (2017)

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