Evaluating end‐to‐end continuous antibody manufacture with column‐free capture alternatives from economic, environmental, and robustness perspectives

Abstract

AbstractProcess intensification efforts have renewed interest in the potential of end‐to‐end continuous manufacture with column‐free capture alternatives. This article describes a decisional tool that encompasses mass balance and design equations, process economics, stochastic simulation and multi‐criteria decision‐making and enables the evaluation of different batch, and continuous flowsheets for monoclonal antibody (mAb) manufacture. The traditional batch process was compared with end‐to‐end continuous bioprocesses with either protein A capture or column‐free capture employing aqueous two‐phase extraction or precipitation from economic, environmental, and robustness perspectives. The cost of goods analysis predicted that continuous flowsheets could offer substantial cost savings (~20%–40%) over the batch process at low and medium annual commercial demands (100–500 kg); however, at tonnage demands they resulted in either comparable or higher costs. Comparing the continuous options, the continuous flowsheets with protein A or precipitation yielded similar COG/g values, while aqueous two‐phase extraction presented higher costs. The analysis of overall process mass intensities accounting for water and consumables suggested that the continuous flowsheet with protein A would result in the lowest environmental burden. When the economic, environmental, and operational criteria were reconciled using multi‐criteria decision‐making analysis, the continuous protein A‐based flowsheet was found to be the most favorable. A target analysis highlighted the need for process improvements in the following parameters to reduce the manufacturing costs of the continuous column‐free capture options below that of protein A: the perfusion volumetric productivity, the harvested cell culture fluid percentage in column‐free operations, the column‐free step yields along with the implementation of buffer concentrates.