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

用于生物制药制造中冷冻干燥工艺设计和操作的多尺度混合建模

• 批准号: 22K14535
• 负责人: バドラ サラ・サミール・レヤド
• 金额: $ 2.91万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K14535/
• 关键词: freeze-drying; process optimization; mechanistic modelling; Biopharmaceuticals; cake collapse; Process design; Hybrid modelling; Freeze drying

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.

冻结不稳定的生物药物的干燥是确保重要药物（例如单克隆抗体）的重要药物的重要过程。传统上，过程设计基于经验基础，因此使用保守的过程条件。将与质量相关的属性与过程条件相关联的模型在很大程度上缺少。在今年，建立了干燥步骤的初步小瓶尺度模型，以预测干燥时间。在冻干过程中，研究了不同过程条件对过程性能和产品质量的影响，例如，蛋糕倒塌现象，用于冻干过程中用作添加剂的标准材料。研究了确定过程参数的不确定性。建立一个集成模型以包括产品质量。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。这可以导致积极干燥过程的安全开发，这可以提供大量的时间和成本节省。该方法可以作为行业和学术界的组合过程和材料开发/优化的系统基础。与各种实验和工业团体建立了合并，以进一步建模和验证。

项目成果

The role of data-driven and hybrid modelling in biopharmaceutical manufacturing

数据驱动和混合建模在生物制药制造中的作用

• 发表时间: 2023
• 作者: Shuji Ohsaki;Akito Teranishi;Hideya Nakamura;Satoru Watano;Sara Badr
• 通讯作者: Sara Badr