BACKGROUND AND CHALLENGE

The ongoing optimization of mammalian cell lines and fermentation processes leads to higher cell densities/titers and higher monoclonal antibody ( mAb ) yields. Due to this optimization also the biomass increases, including cell debris and other impurities, which challenges the clarification/harvest step. The traditional filtration approach as well as the single-use approach are shown below.

The typical clarification process for mammalian cells

and mAb involves a primary and a secondary clarification step. Centrifugation is the most common technology for large scales. Due to potentially high shear forces and the necessity of this step to remove submicron particles, depth filtration is a mandatory step before transferring the liquid into the downstream. The process combines low running costs with operating robustness. 

Another option is the use of two depth filtration steps. A coarse filtration followed by a fine filtration. Both approaches need time, in some cases extra equipment and have high investment costs.

The single-use approach for mammalian cells clarification

The use of single-use equipment becomes more and more state of the art, especially for smaller production scale and manufacturing sites with frequently changing productions. The FILTROX approach is the combination of depth filtration and alluvial filtration.

THIS TYPE OF DEPTH FILTRATION CAN REMOVE THE CENTRIFUGATION STEP AND REDUCE THE CLARIFICATION TO ONLY ONE STEP.

For alluvial filtration it is necessary to add filter aid, like diatomaceous earth (DE), to build a filter cake on top of the depth filter sheets. The DE is added to the fermentation broth, mixed for a couple of minutes and then pumped into the depth filtration unit PURADISC® BIO SD. For upscaling, the necessary space for the filter cake needs to be calculated. In comparison, for the standard calculation the filter area is the parameter of interest. Cells and cell debris remain in the filter cake and/or in the filter sheet. However, charged particles are being removed due to the electrokinetical potential of the filter sheet.

THIS TECHNOLOGY COMBINES THE ADVANTAGES OF ALLUVIAL AND DEPTH FILTRATION.

We offer both, depth filtration solutions for the traditional and the single-use approach. These flexible technologies fit all needs and applications for the purification of high value liquids e. g. mAb and mammalian cells.