Long-term operation of depth filter perfusion systems (DFPS) for monoclonal antibody production using recombinant CHO cells: Effect of temperature,pH, and dissolved oxygen

Recombinant CHO cells of DG44 origin (CS*13-1.00), expressing a chimeric antibody against the S surface antigen of the Hepatitis B virus, were cultivated in single-stage and two-stage depth filter perfusion systems (DFPS) under varying temperature, pH, and oxygen tension conditions to determine their effects on recombinant antibody production. A long-term culture was carried out in a single-stage depth filter for 81 days, during which an occasional clog interrupted the experiment. However, this problem was solved via trypsin injection. The DFPS showed a steady production of monoclonal antibody at a concentration of 100∼150 mg/L. As the cultivation temperature was increased from 33 to 37°C, the monoclonal antibody (Mab) concentration increased from 80.33 to 133.47 mg/L. Likewise, the glucose uptake rate (GUR) and lactate production rate (LPR) also increased. With an increase in pH from 6.95 to 7.61, the Mab concentration increased from 61.64 to 94.31 mg/L. When the oxygen tension was increased from 60 to 80%, the Mab concentration increased from 93.78 to 128.30 mg/L.