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Host Cell Protein and Host Cell DNA reduction using 3M™ Zeta Plus

Depth filtration is widely used in process scale clarification of cell culture harvests for the removal of cells and cell debris. However, in addition to their effective particulate filtration capabilities, 3M™ Zeta Plus depth filter media having electrokinetic charge can adsorb soluble impurities. This feature can be exploited to remove both host cell protein and host cell DNA from bioprocessing streams containing recombinant monoclonal antibody if this a process step requirement.

The presence of host cell protein increases turbidity in Protein A column eluate which can result in both unpredictable precipitation and sporadic plugging of sterile membrane filtration. High cell densities and low viabilities typically increase host cell protein levels and a reduction for a process step can become a key criteria for success. The use of Zeta Plus filters for host cell protein removal is most likely effected by electrostatic interaction, as lowering the conductivity of load prior to filtration has been shown to decrease turbidity in Protein A column eluate.

3M™ Zeta Plus ranges

Zeta Plus media is cellulosic impregnated with silicates and binder resin which can present a positively charged media to uniform process stream flow. This media is available as lenticular cartridges and as single-use capsules, containing the same lenticular format, fully disposable, for use in an 3M™ Encapsulated Zeta Plus System. These can provide high capacity depth filter systems for cell harvest clarification with concomitant or alternatively, separate adsorptive removal of host cell proteins.

Following a centrifugation step, filtration of harvest through a Zeta Plus system with 3M™ Zeta Plus EXT ZA series formulation media upstream of Protein A can reduce turbidity levels in the column eluate containing the monoclonal antibody product. The effectiveness of the reduction will depend on harvest cell culture viability. Two stages of dual layer 3M™ Zeta Plus EXT series depth filters can offer a high adsorptive capacity system to provide robust scale-up performance for variable feed streams. The use of multiple stages of depth filtration before Protein A column can reduce the amount of protein product precipitated during acidic elution. To maximize the flow rate and throughput, an open grade EXT filter is recommended as the first stage depth filter followed by a tighter grade EXT filter as the second stage depth filter.

The disruptive primary recovery stages used after cell culture harvest can result in cell lysis with a high release of host cell DNA. As the level of DNA has to be reduced throughout the downstream purification process to meet Regulatory requirements, consistent removal during early stages is beneficial and can be achieved using Zeta Plus depth filter media. This reduction is largely effected through exploiting the combined electrokinetic and physical properties of either 3M™ Zeta Plus SP EXT and 3M™ Zeta Plus ZA EXT formulations in lenticular EXT format. The clarifications of many mammalian and bacterial cell lysates are at neutral pH, where DNA retention is enhanced. The removal of DNA from bioprocess streams may, in some instances, be complicated by the presence of cell debris and proteins which compete for adsorptive sites. However, field application data has shown greater than 3 log DNA removal can be achieved prior to Protein A column. The Zeta Plus lenticular cartridges or capsules can conveniently be incorporated as modular column load step for large scale production.

To discuss any of these applications or your specific requirements with one of our trained technicians contact us