(641c) Applying Poisson-Boltzmann Theory to Predict Excipient Concentration in Ultrafiltered Therapeutic Protein Formulations

The final bulk drug substance manufacturing step for most therapeutic monoclonal antibodies is a buffer exchange and concentration through an ultrafiltration membrane into a final formulation buffer.  Properties such as pH and concentration of excipients in the resulting product solution are important, because they impact the stability of the frozen drug substance as well as the final product formulation composition.

Preferential rejection or retention of buffer components is commonly observed in this final production step; leading to a requirement to bias specific buffer components to higher or lower concentrations in order to achieve the targeted final composition.  Here, we assess the applicability of a Poisson-Boltzmann model for prediction of the final product composition and pH as a function of protein charge, diafiltration buffer composition, and final product concentration.