End-to-end process flowsheet modeling for biopharmaceutical production: current state and future potential

As the biopharmaceutical industry advances to meet the pressures of an expanding product portfolio and global demand, it will continue to face new challenges while concurrently implementing Quality-by-Design principles. At this forefront, flowsheet modeling frameworks will become increasingly important in silico decisional tools during the process design phase. Flowsheet models further enable screening of process configurations, evaluation of technological alternatives, and identification and alleviation of potential bottlenecks within the context of technoeconomic and environmental impact studies. This review summarizes the recent literature on flowsheet methodologies within the monoclonal antibody sector. Key gaps and assumptions, primarily in the simulation of upstream production, present in current flowsheet approaches are examined. Strategies to overcome the identified assumptions are presented, involving the integration of higher resolution unit operation models to improve the accuracy of process assessments by incorporating biologically relevant constraints while maintaining computational feasibility.