(165a) Multi-Scale Modeling in Pharmaceutical Drug Substance Manufacturing

The role of modeling in pharmaceutical drug substance manufacturing is becoming increasingly more important as the regulators push to the use of more sophisticated methods and tools to address process development and manufacturing. Those who adopt the best modeling approaches benefit from such decision in terms of right-first-time and confidence resulting from enhanced process understanding.

This work presents a multi-scale modeling paradigm applied to drug substance manufacturing. Starting at the molecular level, it is shown how Ab initio modeling (Density Functional Theory) can be useful for determining the IR spectra of the molecules that in specific cases can facilitate analytical work. As the modeling scale is increased, CFD simulations are shown to be key to study in detail the flow patterns inside a reactor. At the unit operation level, Dynochem is used to model the reaction kinetics and crystallization steps, as well as the work-up part of the process. Process trains are then addressed resorting to SuperPro Designer flowsheet software that can be useful for determining bottleneck and COGs. In the next modeling scale scheduling of a multi-process train facility is simulated with SchedulePro, that includes details also on operators and stocks. Finally, company-wide capacity (multi-site) is assessed by making use of Monte-Carlo stochastic simulations.