Abstract
Vial-based lyophilization for biopharmaceuticals has been an indispensable cornerstone process for over 50 years. However, the process is not without significant challenges. Capital costs to realize a lyophilized drug product facility, for example, are very high. Similarly, heat and mass transfer limitations inherent in lyophilization result in drying cycle on the order of several days while putting practical constraints on available formulation space, such as solute mass percentage or fill volume in a vial. Through collaboration with an external partner, we are exploring microwave vacuum drying (MVD) as a faster drying process to vial lyophilization wherein the heat transfer process occurs by microwave radiation instead of pure conduction from the vial. Drying using this radiative process demonstrates greater than 80% reduction in drying time over traditional freeze-drying times while maintaining product activity and stability. Such reduction in freeze-drying process times from days to several hours is a welcome change as it enables flexible manufacturing by being able to better react to changes either in terms of product volume for on-demand manufacturing scenarios or facilities for production (e.g., scale-out over scale-up). Additionally, by utilizing first-principle modeling coupled with experimental verification, a mechanism for faster drying times associated with MVD is proposed in this article. This research, to the best of our knowledge, forms the very first report of utilizing microwave vacuum drying for vaccines while utilizing the power of simplified models to understand drying principles associated with MVD.