Prediction of the Performance of Capture Chromatography Processes of Proteins and Its Application to the Repeated Cyclic Operation Optimization

抄録

Improving the performance of capture chromatography is important for the purification of protein drugs such as monoclonal antibodies. Dynamic binding capacities (DBCs) of antibody (IgG) measured for various Protein A chromatography columns were described well with dimensionless plots of E* vs. F*, where E*=DBC/SBC and F*=d_p²/[D_s(Z/u)]. SBC is the static binding capacity, d_p is the particle diameter, D_s is the stationary phase (pore) diffusion coefficient determined by the pulse response experiment at non-binding conditions, Z is the column bed length, and u is the mobile phase velocity. With the E* vs. F* correlation, the repeated cyclic operation optimization method was developed. The total working time (t_tot), the total volume and the concentration of the feed were assumed to be fixed. Then, the number of runs n_c within t_tot was calculated to determine the chromatography column bed volume. It was found that multiple runs can reduce the bed volume significantly, which results in higher productivities.