Virtual Thermocouple: A Non-Invasive Multipoint Product Temperature Measurement for Lyophilization

Monitoring product temperature during lyophilization is of critical importance, especially during the process development stage, as the final product may be jeopardized if its process temperature exceeds a threshold value. While conventional thermocouples can track product temperature, they are invasive and can significantly alter the freezing and drying behavior. In this work, a new methodology for non-invasive product temperature monitoring and drying behavior during the entire lyophilization process is proposed and experimentally validated. The method is based on a new flexible wireless multi-point temperature sensing probe that is attached to the outside of the vial. Combining the wirelessly-collected data with advanced multi-physics simulations allows the accurate extraction of the product temperature non-invasively.