Monitoring of product temperature and cycle duration in multi-vial lyophilization

The implementation of an in-line control strategy for primary drying relies on the availability of the product temperature and sublimation front position. Such measurements are often inaccessible or difficult to obtain directly without interfering with the drying trajectory, thus motivating the design of in-line estimators. This article specifically addresses this issue, taking advantage of a global mass loss measurement and spatial characterization of vials along the chamber. The estimator proposed uses a least square algorithm and simplified models to recalibrate the heat transfer coefficient related to different vial locations. Results allow comparing the quality of the estimations with regard to the product temperature and cycle time predictions under parametric disturbances and plant/model mismatch.