Accounting for the Donnan Effect in Diafiltration Optimization for High-Concentration UFDF Applications
The biopharmaceutical industry is targeting high-concentration protein formulations to enable subcutaneous administrations. Such administration can provide better patient convenience than intravenous administration. One challenge associated with high-concentration formulations is increased electrostatic interaction between proteins and excipients. That is a result of increased protein-charge density at high protein concentrations. Such interactions can create an offset between excipient levels in final products and diafiltration buffers in ultrafiltration processes. The effect of such electrostatic interactions in a membrane process is known as the
The Donnan effect on excipient levels has received significant attention in recent years. Theoretical modeling has been developed to predict excipient and pH changes as a result of the Donnan effect in monoclonal antibody (MAb) processes. One model based on the Poisson–Boltzmann equation provided good prediction of excipient levels in the final retentate pool. A second model developed by Bolton et al. demonstrated to be predictive for basic MAb and acidic Fc-fusion proteins. The latter study also included several mitigation strategies to achieve target levels of excipients at the end of an ultrafiltration–diafiltration (UFDF) process. Both publications provide tools for understanding the influence of the Donnan effect on target formulation excipients. By contrast, our study focuses on the influence of the Donnan effect on removal of starting buffer excipients during diafiltration.
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