Digital Twin Enabled Process Development, Optimization and Control in Lyophilization for Enhanced Biopharmaceutical Production.

Digital twins have emerged as a powerful concept for real-time monitoring and analysis, facilitating Quality by Design integration into biopharmaceutical manufacturing. Traditionally, lyophilization processes are developed through trial-and-error, incorporating high security margins and inflexible process set points. Digital twins enable the integration of adaptable operating conditions and implementation of automation through Advanced Process Control (APC) with Process Analytical Technology (PAT) and validated physicochemical models that rely on heat and mass transfer principles, allowing us to overcome the challenges imposed by the lyophilization process. In this study, a digital twin for freeze-drying processes is developed and experimentally validated. Using the digital twin, primary drying conditions were optimized for controlled nucleation and annealing methods by carrying out a few laboratory tests beforehand. By incorporating PAT and modeling, the digital twin accurately predicts the product's temperature and drying endpoint, showing smaller errors than the experiments. The digital twin significantly increases productivity by up to 300% while reducing the costs by 74% and the Global Warming Potential by 64%. [ABSTRACT FROM AUTHOR]