Sustainable by design: A first attempt on bioprocessing

The growing commitment of the biopharmaceutical sector to transition to Net Zero is driving the industry to embed sustainability principles across its entire pipeline of operations from early-stage process development to manufacturing. In this context, a key challenge for process design is the prediction of the impact of upstream variability on downstream process performance and, therefore, design, with effects on process economics and sustainability. In this work, we focus on the economic and sustainability analysis of antibody-producing bioprocess designs in the presence and absence of downstream process performance constraints. Specifically, we introduce a kinetic model of upstream processing that predicts the profile of critical cell-derived and product-associated impurities and their variability based on culture conditions. Upstream model simulation results are then used to inform a superstructure optimization that maximizes monoclonal antibody (mAb) throughput under purity constraints. Flowsheet simulation models of the candidate designs are developed and process performance is evaluated through techno-economic and life cycle assessment. As expected, results show that purity constraints can lead to more complex downstream configurations, with higher nominal costs and footprint, and improved capacity to withstand feedstock variability. Although intuitive, the results highlight the significance of uncertainty quantification and impurity modeling for informing end-to-end process design. The digitally-enabled holistic approach proposed herein comprehensively enables cost-effective, eco-efficient, and uncertainty-aware design decisions in bioprocessing.