Side-by-side comparability of batch and continuous downstream for the production of monoclonal antibodies.

Continuous processing is the future production method for monoclonal antibodies (mAbs). A fully continuous, fully automated downstream process based on disposable equipment was developed and implemented inside the MoBiDiK pilot plant. However, a study evaluating the comparability between batch and continuous processing based on product quality attributes was not conducted before. The work presented fills this gap comparing both process modes experimentally by purifying the same harvest material (side-by-side comparability). Samples were drawn at different time points and positions in the process for batch and continuous mode. Product quality attributes, product-related impurities, as well as process-related impurities were determined. The resulting polished material was processed to drug substance and further evaluated regarding storage stability and degradation behavior. The in-process control data from the continuous process showed the high degree of accuracy in providing relevant process parameters such as pH, conductivity, and protein concentration during the entire process duration. Minor differences between batch and continuous samples are expected as different processing conditions are unavoidable due to the different nature of batch and continuous processing. All tests revealed no significant differences in the intermediates and comparability in the drug substance between the samples of both process modes. The stability study of the final product also showed no differences in the stability profile during storage and forced degradation. Finally, online data analysis is presented as a powerful tool for online-monitoring of chromatography columns during continuous processing.

Band-broadening effects in preparative free-flow zone electrophoresis.

Recently, we proposed a novel preparative free flow zone electrophoresis cell with extremely short residence time, which does not require external cooling (Poggel, M., Melin, T., Electrophoresis 2001, 22, 1008-1015). Within the new cell the smallest chamber dimension is not orientated perpendicular but in direction of the electric field. This alteration provides straight forward scale up opportunities. In this paper, new experimental results are reported, from which the limits of stable flow can be determined. The data suggest that not density differences but electrohydrodynamic effects are responsible for the disturbance of the laminar flow pattern, which is observed above a critical field strength. To demonstrate the efficiency of the new system, a three-component mixture consisting of bovine serum albumin (BSA), myoglobin and cytochrome c is processed, resulting in relatively high recovery and purity values of the different proteins, although a complete separation is not achieved.