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

基本信息

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

项目摘要

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.

不稳定生物药品的冷冻干燥是确保重要药品（例如单克隆抗体等治疗性蛋白质）可用性的重要过程。传统上，工艺设计基于经验基础，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很大程度上缺失。今年，建立了干燥步骤的初步小瓶规模模型来预测干燥时间。针对冷冻干燥过程中用作添加剂的标准材料，研究了不同工艺条件对工艺性能和产品质量的影响，例如滤饼塌陷现象。研究了确定过程参数的不确定性。正在建立一个包含产品质量的集成模型。预期的模型开发包括应用于冷冻干燥过程中用作添加剂的不同类型的材料。这可以促进积极干燥工艺的安全发展，从而显着节省时间和成本。该方法可以作为工业界和学术界组合工艺和材料开发/优化的系统基础。与各个实验和工业团体建立了合作，以进一步进行模型开发和验证。