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

点击翻译按钮获取中文摘要

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.