Simulation of Process Performance on Contaminant Removal Using Constant and Non-Constant Volume Diafiltration Modeling

by Renato Lorenzi, Bala Raghunath, PhD, Yanglin Mok, and Karen Chan
Volume 15, Issue 2 (Summer 2016)

Constant volume diafiltration (CVD) is commonly used in the biopharmaceutical industry for impurity removal or buffer exchange. The number of diavolumes is usually determined empirically or by theoretical analysis to achieve the target degree of impurity removal. There is, however, a lack of conclusive information about the effect of contaminant removal in variable volume diafiltration (VVD). VVD can occur when the diafiltration control mode is not functioning as intended. In this study, a mathematical model has been proposed to predict removal efficiency during VVD. Experiments were performed to compare the results to model calculations. A dilute concentration of bovine serum albumin solution was used as the feed solution to study variable volume effects. Study results demonstrate that the contaminant removal rate is higher when the diafiltration flow rate is lower than the permeate flow rate (flux). The simple analytical expression for contaminant removal presented in this article, developed and supported by the experimental results, serves as a guide for the optimization and troubleshooting of industrial diafiltration processes. The expression verifies the diafiltration process performance when it deviates from the traditional constant volume approach, with the assumption that the contaminant has no interactions with the product...

Lorenzi R, Raghunath B, Mok Y, Chan K. Simulation of process performance on contaminant removal using constant and non-constant volume diafiltration modeling. BioProcess J, 2016; 15(2): 30–7.

Posted online July 30, 2016.