Freezing and thawing of biologics in bottles and downscale modelling evaluation

Freezing and thawing are critical steps in the manufacturing of biologics, as they help preserve product quality during storage and transport. However, these processes can also introduce stresses that affect protein stability. This study investigates the representativeness of a scale down device (SDD) developed by SmartFreez® in replicating the stress-time distribution and cryo-concentration profile of larger manufacturing containers (2-liter and 5-liter bottles) under slow freezing and thawing conditions. Additionally, the study evaluates the use of a surrogate solution to predict freezing kinetics, thawing kinetics, stress-time distribution, and protein concentration profiles. Computational fluid dynamics (CFD) simulations were used to design the SDD, and experimental validation was performed under low heat transfer regimes.