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Eur J Pharm Biopharm. 2018 Jul;128:363-378. doi: 10.1016/j.ejpb.2018.05.005. Epub 2018 May 5.

Predictive models of lyophilization process for development, scale-up/tech transfer and manufacturing.

Author information

School of Aeronautics and Astronautics, Purdue University, West Lafayette, IN, United States.
Drug Product Development, AbbVie Inc, North Chicago, IL, United States.
Drug Product Development, AbbVie Inc, Ludwigshafen, Germany.
Science and Technology, AbbVie Inc, North Chicago, IL, United States.
Process Research and Development, AbbVie Inc, North Chicago, IL, United States.
Drug Product Development, AbbVie Inc, North Chicago, IL, United States. Electronic address:


Scale-up and technology transfer of lyophilization processes remains a challenge that requires thorough characterization of the laboratory and larger scale lyophilizers. In this study, computational fluid dynamics (CFD) was employed to develop computer-based models of both laboratory and manufacturing scale lyophilizers in order to understand the differences in equipment performance arising from distinct designs. CFD coupled with steady state heat and mass transfer modeling of the vial were then utilized to study and predict independent variables such as shelf temperature and chamber pressure, and response variables such as product resistance, product temperature and primary drying time for a given formulation. The models were then verified experimentally for the different lyophilizers. Additionally, the models were applied to create and evaluate a design space for a lyophilized product in order to provide justification for the flexibility to operate within a certain range of process parameters without the need for validation.


Computational fluid dynamics; Design space; Freeze-drying; Heat and mass transfer; Lyophilization; Modeling; Process scale-up

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