부산대학교 도서관

The quality of biopharmaceutical proteins is strongly affected by a manufacturing process employed to produce it, and thus validation of the manufacturing bioprocess is a very important issue. Chromatography is probably the most widely used bioprocess unit operation for protein purification. In this study, a miniaturized automatic chromatography system was designed and constructed for scale-down studies for process chromatography validation. This system, named MiniValChrom, has the following features: automatic and repeated operation, flexible sequences and intervals among the steps, on-line and real-time monitoring and control, method files savings, etc. Using the MiniValChrom, we performed a case study of an abbreviated experiment to estimate chromatographic resin lifetime. BSA (bovine serum albumin) and Cibacron Blue 3G-A were used as the model protein and the resin, respectively. The resin deterioration was evaluated by determining and monitoring the HETP and NTP values from the chromatograms every 5 cycles. It was observed that the HETP and the NTP values were changed by 9% after 15 cycles. The resin lifetime validation could be completed by repeating this experiment until the HETP value reached a predetermined value. The MiniValChrom's concept and the protocol suggested in this study can serve as a rapid and economical tool for the validation studies of bioprocess chromatography system.