ABSTRACT
Therapeutic proteins have revolutionized medical treatment for addressing a broad array of new targets and diseases, and represent a large fraction of new medicines being brought to the market. Production of commercial therapeutic proteins or biologics is an expensive process, and to optimize bioreactor capacity utilization, production is typically conducted in campaign mode. Freezing of an aqueous solution is a dynamic process that results in significant changes in the bulk properties of the solution. Presence of solutes adds to the complexity of the phenomenon. As the solute freeze concentrates into a supersaturated solution of high viscosity, it undergoes a transition into a vitreous or glassy state. The glass is a nonequilibrium metastable amorphous solid of extremely high viscosity (>108 Pa s) whereby the mobility of molecules by diffusion is extremely restricted. The relevance of the glass formation to the storage of a frozen biologic arises from several protective mechanisms that may be active.
