Stochastic simulation model development for biopharmaceutical production process risk analysis and stability control

In this paper, we develop a stochastic simulation model for biomanufacturing risk analysis by focusing on the production process from raw materials to finished drug substance. By exploring biotechnology domain knowledge, we model how the properties or attributes of each batch dynamically evolve along the production process. We consider main sources of uncertainty leading to batch-to-batch variation, such as raw material biomass, cell culture, and target protein purification. The proposed simulation model allows us to incorporate the underlying physical chemical interactions and also the no-wait constraint in the purification process. It can be used to facilitate biomanufacturing risk management and guide coherent operational decision making (i.e., production scheduling and quality control) so that the stability of bio-drug quality can be improved while efficiently utilizing the resources and speeding up the time to market.