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

不稳定生物制药的冷冻干燥是确保重要药物产品（如单克隆抗体等治疗性蛋白质）可用性的重要过程。工艺设计传统上是基于经验基础的，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。在这一年中，建立了干燥步骤的初步小尺度模型来预测干燥时间。针对冻干过程中使用的标准原料作为添加剂，研究了不同工艺条件对工艺性能和产品质量的影响，如饼塌现象。研究了工艺参数确定的不确定度。构建包含产品质量的集成模型正在进行中。预期的模型发展包括在冷冻干燥期间用作添加剂的不同类型的材料的应用。这可以导致侵略性干燥过程的安全开发，这可以提供显着的时间和成本节约。该方法可作为工业界和学术界联合开发/优化工艺和材料的系统基础。与不同的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.