Fig. 2 Instantaneous and average low rates measured during six filtration cycles. The flow rate is given as liters per square meter per hour (LMH), and the filtration pressure was 1.5 bar<\/figcaption><\/figure>\nCase study<\/h3>\n
Suspension growing Chinese Hamster Ovary (CHO) DP-12 cells, producing an Immunoglobulin (IgG)-1 antibody against Interleukin-8 (clone #1934, ATCC CRL-12445, provided by Prof Dr T. Noll, Bielefeld University, Germany), were cultivated in a chemically defined medium. At the time of the harvest, the total and viable cell densities were 22.3<\/sup> and 20.8 million cells per ml, respectively. The solids content was 49.3 g\/L and the viability was 93.2%. The pH was reduced from 6.75 to five prior to the harvest by adding diluted acetic acid, and 40% Celpure\u00ae C300 filter aid was added per wet cell weight. The experiments were performed at a pressure of 1.5 bar with an FDA certified filter media having a nominal pore size of 0.9 \u00b5m.<\/p>\nThe flow rates obtained over six cycles are shown in Fig. 2. In each cycle, the flow rate started high and decreased as the cake was growing. In conventional filtration systems, such as depth filters, the filtration is continued until the flow rates drop very low, at which point the filter is replaced. On the other hand, in the CONTIBAC\u00ae SU each filtration cycle is terminated once the flow rate drops significantly below the initial flow rate. In this case study, each cycle was terminated once the flow rate approached 1,000 LMH, at which point the filter was back-flushed, the filter media regenerated, and a new cycle was started.<\/p>\n
After the back-flush, the flow rate went back to the initial level, and a high average flow rate of around 2,000 LMH could be maintained over all six cycles. Therefore, there was no sign of fouling or dip in the performance, something that cannot be achieved with conventional filters. Depth filters, for instance, cannot be back-flushed and even experience severe fouling within a single filtration cycle. Cross-flow filters require high flow speeds and thereby induce cell damage, which inevitably causes fouling. Unlike in these two technologies, the filter media in the CONTIBAC\u00ae SU does not perform the actual filtration, but instead acts as a cake support, thereby being less susceptible to fouling. Moreover, the pH reduction agglomerates impurities such as cell debris, DNA, and host cell proteins (HCP) and facilitates their separation from the liquid.3<\/sup><\/p>\nThe high performance of the CONTIBAC\u00ae SU does not come at the cost of filtrate quality. The filter reduced the turbidity by 98-99% and the amount of deoxyribonucleic acid (DNA) content by up to 90%. The activity of lactate dehydrogenase (LDH), a measure of the amount of cell damage, only roughly doubled, which is an outstanding result compared to competing technologies.3<\/sup><\/p>\nConclusion<\/h3>\n
The innovative filtration technology by DrM exhibits exceptional performance while producing high filtrate quality. High average flow rates in combination with cyclic operation allows for using smaller filters, which in turn reduces the investment and operating costs, decreases the footprint, and reduces the amount of leachables and extractables.<\/p>\n
Moreover, the CONTIBAC\u00ae SU is highly suitable for larger batch volumes, higher cell concentrations and even continuous production, leading the biologics production into a brighter future.<\/p>\n