Use of a multi-vial mathematical model to design freeze-drying cycles for pharmaceuticals at known risk of failure

Freeze-drying is a dehydration method suitable for the stabilization of heat-labile pharmaceutical products, such as vaccines. Due to the vial-to-vial variability of heat and mass transfer during the process, the value of the critical process parameters (e.g., product temperature, sublimation rate) may be different between vials and batches often present significant product quality heterogeneity. The aim of this work was the development of a dynamic, multi-vial mathematical model making it possible to predict risk of failure of the process, defined as the percentage of vials potentially rejected by quality inspection. This tool could assist the design of freeze-drying cycle. Keywords: lyophilization; vaccines; heat and mass transfer; mathematical modeling; design space