Freeze-Drying of Pharmaceuticals in Vials Nested in a Rack System-Part I: Freezing Behaviour.

The distribution of biopharmaceuticals often requires either ultra-cold conditions or lyophilisation. In both cases, the drug product is frozen and, thus, exposed to similar stress conditions, which can be detrimental to its quality. However, these stresses can be inhibited or mitigated by a suitable formulation and/or an appropriate freezing design. This paper addresses how the key freezing parameters, i.e., ice nucleation temperature and cooling rate, impact the freezing behaviour of a sucrose-based formulation. The analysis included two loading configurations, vials directly resting on the shelf and nested in a rack system. The loading configuration affected the product freezing rate and the ice nucleation temperature distribution, resulting in larger ice crystals in the case of vials nested in a rack system. SEM micrographs and specific surface area measurements confirmed the different product morphology. Eventually, the different product morphology impacted the bioactivity recovery of lactate dehydrogenase.