Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process based on the process characterization

Abstract

AbstractA continuous downstream process of monoclonal antibody was developed based on the process characterization. Periodic‐counter current chromatography (PCCC) with two protein A columns was used for the capture step. For low pH virus inactivation (VI), a batch reactor was employed, which can work as a surge (buffer) tank. Flow‐through chromatography (FTC) with two connected columns of different separation modes (anion‐mixed mode and cation exchange) was designed as a polish step. After 24 h PCCC run, the collected pool was processed for VI. After adjusting pH and electric conductivity, the solution was fed to the two connected FTC columns for 24 h. Virus filter was also connected to the exit of the connected‐column. PCCC and FTC were run in parallel. Six runs of different feed rates (0.5–10 L/day) and feed concentrations (1–3.2 g/L) were performed with protein A columns of 1–5 mL and FTC columns of 3–10 mL. The largest run (feed rate 10 L/day, feed concentration 2 g/L) was carried out at a GMP facility with 15 mL protein A columns and 100 mL FTC columns. Good recovery and purity values were obtained for all runs. The process was found to be flexible and stable for feed fluctuations. Only three surge or pool tanks were needed in addition to the final product pool tank.