The freeze-drying of pharmaceuticals in vials nested in a rack system. – Part II: Primary drying behaviour

The distribution of biopharmaceuticals often requires lyophilisation. The drug product is first frozen and potentially exposed to stress conditions that can be detrimental to its quality. These stresses are also encountered when a drug product has to be distributed under ultra-cold conditions. Adjusting the formulation and/or freezing conditions allows for limiting the impact of these stresses on the final product. This paper investigates two loading configurations, vials directly resting on the shelf and nested in a rack system, and their impact on the freezing and drying behaviour of a sucrose-based formulation. First, two key freezing parameters, i.e., ice nucleation temperature and cooling rate, were studied as they can affect the product behaviour during drying. The product freezing rate and the ice nucleation temperature distribution were affected by the loading configuration, resulting in larger ice crystals in the case of vials nested in a rack system. The analysis was also extended to the drying phase, showing that the loading configuration impacted the product temperature during drying and the overall heat transfer coefficient between the equipment and the product.