Effect of Freeze Dryer Design on Heat Transfer Variability Investigated Using a 3D Mathematical Model

Abstract

During the freeze-drying process, vials located at the border of the shelf usually present higher heat flow rates that result in higher product temperatures than vials in the center. This phenomenon, referred to as edge vial effect, can lead to product quality variability within the same batch of vials and between batches at different scales. Our objective was to investigate the effect of various freeze dryer design features on heat transfer variability. A 3D mathematical model previously developed in COMSOL Multiphysics and experimentally validated was used to simulate the heat transfer of a set of vials located at the edge and in the center of the shelf. The design features considered included the vials loading configurations, the thermal characteristics, and some relevant dimensions of the drying chamber geometry. The presence of the rail in the loading configuration and the value of the shelf emissivity strongly impacted the heat flow rates received by the vials. Conversely, the heat transfer was not significantly influenced by modifications of the thermal conductivity of the rail, the emissivity of the walls, or the geometry of the drying chamber. The model developed turned out to be a powerful tool for cycle development and scale-up.

Keywords: edge vial effect; freeze-drying/lyophilization; heat transfer; mathematical model; processing; simulations; vaccines.