(543d) Novel Concepts for Processing and Automation of Pharmaceutical End-to-End Manufacturing

While the production of solid dosage forms is gradually converting from batch to continuous mode, the manufacturing of the drug substance and the drug product are performed at different sites. The consequences are not just long cycle times, but also a strong dependence on the availability of active pharmaceutical ingredients (API) from overseas. Recent crises like the last pandemic drastically show the vulnerability of the actual supply chains.
This study demonstrates an integrated process from the API synthesis to the final tablet at one single production site. A novel concept has been developed for process simplification: After API synthesis in continuous flow followed by crystallization and purification, the time- and energy-intensive drying step is eliminated. The API is re-suspended instead and fed to a hot melt extrusion (HME) step. The strand consisting of polymer and API is pelletized and tableted in a direct compaction (DC) line. Additionally, an advanced control concept was developed based on process models of all units combined to a digital twin. The digital twin is supplied with real-time process information from an in-line monitoring strategy. An intelligent operating concept coordinates all process units according to defined objectives. The new approaches are demonstrated with Salbutamol free-base as model API.