Commercializing therapeutic proteins involves a series of processes aimed at maintaining safe and efficient protein drug solutions before final patient administration. Common operations include important steps such as pre-formulation, drug product formulation, sterile filtration, freezing, thawing, and freeze-drying intended to stabilize the protein drug before fill-and-finish, and during storage and transportation. Freeze–thaw operations used in the biotechnology industry still are generating debates regarding safety problems because methods to freeze and thaw samples can affect the purity, activity, safety, and efficacy of the final product. This article presents a Quality by Design (QbD) approach to define a safe freeze–thaw space where a protein's quality is not affected by the freezing or thawing method used.
To limit the cryoconcentration effect, Sartorius Stedim Biotech has developed the Celsius Control Freeze Thaw (CFT) technology: a single–use system for controlling the freezing and thawing rate at manufacturing- and laboratory-scale.7 With this system, the ice crystal growth rate in the direction of the heat flux is sufficient to prevent back-diffusion of solutes from inter-crystalline space into the liquid bulk, thus minimizing the bulk-scale cryoconcentration.9
In this article, we evaluate the suitability of the laboratory-scale Celsius S3 system as a screening tool for determining a safe freeze–thaw space where a protein's quality is not affected by the freezing or thawing method used.