(588ck) Integrated Modeling and Optimization of Secondary Drying for Pharmaceutical Freeze-Drying Processes

Freeze-drying, or lyophilization, is a critical process in the pharmaceutical industry for the preservation of sensitive biological products. The secondary drying phase, where residual moisture is removed from the product, plays a crucial role in ensuring product stability and quality. Traditional design methods for lyophilization use conservatively low temperatures and long drying times to avoid product quality failures such as cake collapse. These designs not only limit throughput but also result in significant energy consumption due to the sustained low temperatures required. Model-based design and online optimization can bridge the gap to optimal operation while ensuring that enumerated failure modes are avoided through more detailed control.

In this work, we describe the practical application of enhanced models for the secondary drying phase. We reference 0-D and 1-D models for cake moisture and cake & vial temperature from literature. The resulting model is applied to the optimization of operational recipes, with the goal of reducing drying cycle times for improved throughput and energetic efficiency.

Our implementation is written in Python for agile deployment on modern containerized infrastructure and integration with live measurements for future work in online state estimation and continuous validation. Coupled with our existing digital twin assets for primary drying, this improved model can be used to optimize freeze-drying cycles and significantly reduce processing times, while maintaining product quality.