Multiscale hybrid modeling for design and operation of freeze-drying processes in biopharmaceutical manufacturing

冷冻干燥不稳定的生物药物是确保重要药物产品的可获得性的重要过程，例如治疗蛋白，如单抗。传统上，工艺设计是以经验为基础的，因此使用保守的工艺条件。将质量相关属性与工艺条件相关联的模型在很大程度上是缺失的。在这一年里，初步建立了干燥步骤的小瓶规模模型来预测干燥时间。针对冷冻干燥过程中作为添加剂的标准原料，研究了不同的工艺条件对工艺性能和产品质量的影响，如滤饼崩塌现象。研究了工艺参数测定的不确定度。建立一个包含产品质量的综合模型正在进行中。预期的模型开发包括在冷冻干燥过程中用作添加剂的不同类型的材料的应用。这可以导致安全地开发积极的干燥工艺，从而节省大量的时间和成本。该方法可作为产业界和学术界联合工艺和材料开发/优化的系统基础。与各种实验和工业团体建立了合作关系，以进一步开发和验证模型。

Freeze drying of unstable biopharmaceuticals is an important process for ensuring the availability of important drug products such as therapeutic proteins like monoclonal antibodies. Process design has traditionally been based on an empirical basis and therefore using conservative process conditions. Models correlating quality-related attributes to process conditions had been largely missing.During this year, preliminary vial-scale models for the drying step were established to predict drying time. The impact of varying process conditions on process performance and product quality, e.g., the cake collapse phenomenon, was investigated for standard materials used as additives during the freeze-drying process. The uncertainty in determining process parameters was studied. Building an integrated model to include product quality is ongoing. The intended model developments include the application to different types of materials used as additives during freeze-drying. This can lead to the safe development of aggressive drying processes, which can offer significant time and cost savings. This method can serve as a systematic basis for the combined process and material development/optimization by industry and academia.Collaborations were established with various experimental and industrial groups for further model development and validation.