Predicting the phase behavior during freeze-drying of biopharmaceuticals

Freeze-drying (lyophilization) remains one of the dominant strategies for long-term stabilization of biopharmaceuticals. The biopharmaceutical is thereby embedded in an amorphous phase of several excipients (e.g. cryoprotectants such as sugars), preserving its native state and activity during storage. Aside protein stability, choice of the excipients also defines process parameters of the lyophilization process, e.g. drying time. Choice of excipients and determination of these process parameters is usually performed through costly and time-consuming experiments. Within this work, we developed a hybrid (predictive) approach to facilitate the excipient choice and give easy access to the aforementioned process parameters.