(701d) Application of a Mechanistic Model for Ultrafiltration and Diafiltration for Process Troubleshooting and Design Space Exploration

Ultrafiltration and diafiltration (UF/DF) unit operations are a common process step in the generation of a final formulation for monoclonal antibodies. However, UF/DF process dynamics are complex considering factors such as mass transfer, chemical equilibrium, charge interactions, and volume exclusion. Additionally, material for UF/DF experimentation is of high value due to the need for large protein quantities. In silico simulation via a mechanistic model provides the ability to reduce the time, effort, and expense necessary to develop and refine UF/DF operations during process development. This study describes the application of the model developed by Ladwig et al. (2020) for the development of a two-stage diafiltration process. In this work, we describe the use of this high-fidelity model to identify the design space for buffer composition and UF/DF operating parameters in order to generate the desired final formulation conditions. Several in silico design iterations will be presented to describe common questions and elucidate design trade-offs. Sensitivity analysis results will be used to understand model parameters and process variable uncertainties.

References:

Ladwig, JE, Zhu, XX, Rolandi, P, Hart, R, Robinson, J, Rydholm, A. Mechanistic model of pH and excipient concentration during ultrafiltration and diafiltration processes of therapeutic antibodies. Biotechnol Progress. 2020; 36:e2993. https://doi.org/10.1002/btpr.2993