We present case studies on the application of flowsheet models, systematically escalating the complexity and utilization. To start, flowsheet models are used at a unit-operation level to explore various design options, using chromatography for biologics purification as the representative example. Thereafter, we develop an end-to-end flowsheet representation of a biologics process train, comprised of multiple interconnected unit operations. We use the end-to-end model to explore and define the design space, as well as study the sensitivity to perturbations. This is a key application of the flowsheet which can lead towards a more robust process design and wider operating ranges while maintaining quality attributes. When used in this fashion, the flowsheet model effectively serves as a digital twin that enables model-driven control strategy in future regulatory narratives.
Finally, we augment the flowsheet models with information pertaining to equipment capacities, schedules for unit operations, and utility/resource constraints. Now, the augmented flowsheet can be used to optimize business outcomes, such as minimizing batch cadence or reducing costs, in addition to improving the scientific quality attributes (e.g., increasing yields). We demonstrate how the flowsheet model can be used to de-risk facility fit decisions during technology transfers. This flowsheet model can be used as a true digital twin in a manufacturing plant, driving real-time decisions to continuously improve quality, robustness, costs, and cadence for bioprocesses—this work summarizes our progress towards this vision.