(328g) Material Tracking in a Fully Continuous Drug Substance Process

This work summarizes a recent experience that uses a residence time distribution (RTD) model to track material across 12 unit operations of a drug substance process. The process features 48 feed tanks, several PAT points, 3 divert stations, and 3 surge points. This also corresponds to the first GMP campaign run in the new small volume continuous (SVC) facility and it resulted in 200 Kg of active pharmaceutical ingredient produced.

Application of flowsheet modeling to simulate the aforementioned continuous process, as well as the importance of event tracking (e.g., startups, diversion, stoppages, flow rate changes, feed composition changes, heel in surge vessels, complex schedule, etc.) will be highlighted. Of major importance were model linkage to process data (historian, batch records), modular approach, and challenges faced during development.