Intensified capture of recombinant blood coagulation factors by continuous, integrated downstream processing

Abstract

AbstractBACKGROUNDThe biopharmaceutical community has realized the tremendous potential of continuous processing for process intensification. However, to date reports of continuous processes for monoclonal antibodies (mAb) represent the overwhelming majority, while integrated continuous processes for non‐mAb products are rare.RESULTSWe have developed an integrated, continuous process for capture of recombinant blood coagulation factors: Factor VIII (FVIII) and VonWillebrand factor (VWF). Due to their complex and diverse nature, tailored solutions beyond chromatographic separations are required for continuously producing non‐mAb products. Our integrated process consists of three continuous unit operations that include cell removal, product capture by precipitation and precipitate collection with a yield of 33% and 56% for FVIII and VWF, respectively. These unit operations were developed individually and then integrated into a continuous process at laboratory scale. Using prototype equipment, we have demonstrated continuous, integrated capture of recombinant blood coagulation factors over a duration of 24 h.CONCLUSIONThe continuous solutions employed were developed for FVIII and VWF, but may very well be applied to other molecules. These solutions to continuous solid–liquid separation and integration are important parts in the puzzle that is continuous downstream processing of biopharmaceuticals. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).