National Resilience, Inc. (Resilience) is a first-of-its-kind manufacturing and technology company dedicated to broadening access to complex medicines and protecting biopharmaceutical supply chains against disruption. As a part of this vision, Resilience is developing an advanced end-to- end continuous drug substance manufacturing platform for biological molecules using Siemens gPROMS Formulated Products mechanistic and hybrid modelling platform. To enable robustness, facilitate in silico process characterization, and enable an efficient process control strategy, we are developing a mechanistic model with uncertainty analysis for an integrated and continuous biomanufacturing (ICB) process at Resilience. Described herein are the steps for the development of ICB model. The individual unit operation process models were built separately and then integrated into an end-to-end flowsheet simulation. The model is being used to determine the impact of expected disturbances, deviations, and provide a disturbance divergence strategy to maintain the product quality attribute. With uncertainty analysis, the model can provide the critical level analysis of process parameters along with the identification of failure boundaries on product quality.