Randomized-field microwave-assisted pharmaceutical lyophilization with closed-loop control.

The current lyophilization technology for biopharmaceuticals and vaccine products is capital and energy-intensive, largely due to the use of indirect, conductive heat transfer. The heat removal and input in freezing, primary drying, and secondary drying are via contact between the product and shelves cooled or heated by a circulating working fluid such as silicone oil. This is slow, inefficient, and leads to non-uniform freezing and drying, especially in large-scale production systems. To address the current throughput limitations of conventional lyophilization, this collaborative project by Purdue University, Merck and IMA Life develops the next generation of tunable randomized-field microwave lyophilization system demonstrating significant acceleration over conventional freeze-drying processes. The system uses a microwave source delivering electromagnetic energy to the lyophilization chamber at frequencies between 8 GHz and 18 GHz at power levels below 400 W and mechanical stirrers for field randomization to achieve uniform heating. The frequency range is selected due to its greater efficiency for heating ice relative to traditional industrial microwave frequencies of 915 MHz and 2.45 GHz. During operation, temperature is measured directly using optical sensors, providing robust real-time product data. Closed-loop control algorithms enable direct control of the product temperature throughout the drying process, ensuring the material is dried at an optimal rate. The results of quasi-Random Field (qRF) microwave drying for several benchmark formulations, including an attenuated live virus vaccine, are presented and compared with the corresponding conventional lyophilization processes. A model for the product temperature and primary drying time is developed and validated against experimental cases.