Monitoring of a Pharmaceuticals Freeze-Drying Process by Model-Based Process Analytical Technology Tools

Pharmaceuticals freeze-drying requires a careful monitoring to preserve product quality. This is a challenging task as it is not possible to measure inline the variables of interest, i.e., temperature and residual amount of ice in the product in the primary drying stage and residual unfrozen water in the secondary drying stage. Various sensors are available to estimate the state of the product, coupling experimental measures and a model of the process. Methods based on the measure of product temperature and on the pressure rise test are discussed and compared by means of experimental investigations. The former is a local intrusive method, as it requires placing thermocouples in various vials, but allows monitoring the batch taking into account its non-uniformity, while the latter is a global and non-intrusive method which permits a partial insight into process dynamics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.