With the biologics industry moving towards more diverse batch volumes and cell concentrations, the innovative CONTIBAC® SU Filter with cycling cake filtration, may be the solution the industry needs.
Throughout the past two decades, single-use (SU) components have been on the rise in the production of biologics, since they reduce the risk of cross-contamination and render costly equipment sterilisations and unnecessary validations. The shift towards SU components has been successful for many production steps, yet some challenges remain. Particularly in cell separations, current SU technologies are not capable of handling the high batch volumes that are the norm in non-SU plants.
The technologies that are most widely used for SU cell harvest (for extracellular applications) are depth filtration, centrifugation, and crossflow filtration. Depth filters are straightforward in concept and operation but have several drawbacks.
The major issue is the large footprint and the number of required modules, which becomes problematic as batch volumes and cell densities increase. Moreover, depth filters cannot be regenerated and are more susceptible to turbidity breakthrough. Centrifugation is widely used in production plants of biologics with working volumes over 2,000 L. Converting the technology from stainless steel to SU, however, requires complex equipment and intricate SU components, resulting in high investment and operating costs. Cross- flow filters have rather low filtration rates, while requiring a very high crossflow velocity, which is energy inefficient and can harm shear-sensitive mammalian cells.
The working principle of the CONTIBAC® SU Filter
As the industry is moving towards larger batches, higher cell densities, and continuous production, the aforementioned technologies are pushed to the limit, and there is a demand for innovative technologies. The CONTIBAC® SU of DrM, Dr. Mueller AG, introduced in this study, overcomes some of these limitations by using two novel concepts:
- Cake filtration: the filter media does not perform the actual filtration, but it acts as a support for the filter cake consisting of cells and filter aid. As a result, the filtration is much faster, and the filter media can be regenerated by being back- flushed from the opposite side; and
- Cyclic operation: since the filter media can be regenerated, the filter can be operated in a cyclic manner that is illustrated in Fig. 1 and explained in the following paragraph.
A cross-section of the filter is illustrated in Fig. 1; the filter consists of multiple vertically aligned elements, each containing a filter media around the circumference. These filter elements are connected with each other on the top, such that the filtrate from each element is collected in a horizontal register and can exit the filter through connector 2. The filter elements are completely encapsulated by a polyethylene bag, and there is an air-tight seal between the bag and the filter housing.
As shown in Figure 1, there are four steps in a complete filtration cycle. During the first step, the filter is filled through connector 1. Once filled (having allowed the air to escape through connector 3), the liquid pushes through the filter media into the vertical elements and exits the filter through connector 2. As the filtration is carried on a cake forms on each element. When the cake has grown to a degree that causes a significant drop in the flow rate, it is proceeded to the next step, the heel volume (HV) filtration. Air is pumped between the filter bag and the filter housing, squeezing all the remaining liquid out of the bag.
The benefit of this step is that all the product is harvested, unlike in-depth filters and crossflow filters where the heel volume cannot be filtered, resulting in a loss of yield. After completing the HV filtration, the filter elements are backflushed by pumping water for injection (WFI) or buffer through connector 2 (i.e. reversing the flow). As a result, the cake is removed from the filter elements and accumulates as a slurry on the bottom of the filter bag. This slurry is removed from the filter bag in the last step by opening the bottom pinch valve. The back-flush step completely regenerates the filter media for the next cycle, while the discharge step regenerates the whole filter bag for the next cycle.
The multi-cycle advantage
The advantage of using the aforementioned cyclic filtration technique is that a smaller filter volume can be used to perform the same task. Unlike conventional filters, whose capacity is limited by the filter area, the capacity of the CONTIBAC® SU filter is only limited by the number of cycles, or respectively, the time the user has allotted for the filtration.
A smaller filter also leads to a smaller footprint, a lower contact area (and hence less leachables and extractables), as well as lower investment and operating costs. Finally, the CONTIBAC® SU can be used for the quasi-continuous production of biologics that spans over several days or weeks, something that is rather challenging to achieve with conventional filters.
To download the full paper, head to our website: https://drm-lifescience.com/cell-harvest-with-contibac-su-filters/
DrM is an industry leader and manufacturer of high-quality solid-liquid separation systems, candle filters, single-use systems and vibratory mixing solutions.
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