(126f) A Virtual Plant for Synthetic Continuous Manufacturing Via Integrated Systems-Based Modeling

The biopharmaceutical industry is moving towards continuous manufacturing to enable a smaller manufacturing footprint, improved environmental sustainability, improved control strategy, flexibility to meet changing demand and safer operations. Despite these benefits, the transition from batch to a continuous mode of operation significantly expands the number of parameters that require evaluation for optimal process design and process characterization, which directly translate to the need for a large and resource intensive experimental data set. These resource requirements can be reduced significantly by augmenting empirical design with modeling.

Here we present a ‘Virtual Plant for Synthetic Continuous Manufacturing’ via integrated systems-based modelling. As a part of this methodology, process characterization was executed to enable mechanistic understanding and modeling of the physical and chemical phenomena and to obtain quality data that are fed into model development. Those model components were integrated to form the end-to-end process model, with which in silico studies (sensitivity analysis, uncertainty propagation, etc.) are performed to identify the key process parameters. The systems-based model enables the subsequent development and testing of an integrated advanced process control strategy, which is envisioned to support regulatory filings for CM processes. The complete Virtual Plant enables identification and evaluation of other requirements and policies related to equipment, facility, automation, and operations. Development of a virtual plant for synthetic CM enables us to predict process performance and product quality in a real plant environment.