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.