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.
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