Digital design and operation of robust continuous drug substance manufacture processes: Industry cases & value statements

In this presentation, we will describe applications demonstrating the use of mechanistic models for robust design of continuous drug substance manufacturing processes. This includes model calibration of relevant unit operations, development of dynamic integration flowsheet models and investigation of the impact of process disturbances and model uncertainties on Critical Quality Attributes (CQAs).

We will highlight approaches for characterizing residence time distributions and process dynamics to analyze disturbance rejection and material traceability (lot genealogy). We will present a novel modeling framework to track lot composition throughout a Continuous Drug Substance Manufacturing (CDSM) process, which can be useful in assessing regulatory quality and batch definition in production campaigns. Lastly, opportunities for mechanistic model-based digital operation will be described, including testing control strategies, soft sensing, operator training, and model predictive control.