Millistak+HC AppGd_textC.qxd - Millipore

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Post-TFF Microfiltration Mammalian cell cultures clarified by means of crossflow (TFF) microfiltration will typically utilize a membrane in the 0.45–0.65 µm range. Even at this high degree of separation, the treated effluent (permeate) frequently requires further clarification in order to achieve acceptable capacities in subsequent sterile filtration. The preferred Millistak+ HC prefilter for these low solids fluids is the A1HC. When applied to a post-TFF process stream, this prefilter will ordinarily develop little pressure build-up, yet will provide a remarkable improvement in downstream sterile filter throughput. Sterile Filter (0.22 µm) Capacity (L/m2 ) 10 700 600 500 400 300 200 100 0 CHO Cell Culture: TFF/MF Permeate Competitor A Single Layer Media Competitor A Dual Layer Media Figure 7. Competitive Prefilter Analysis: Sterile Filter Protection In one example, a fed-batch CHO cell culture was first processed using a 0.65 µm TFF/MF (Prostak ) filter system with Durapore membrane and the permeate was batch-filtered through the A1HC, followed by a 0.22 µm Durapore sterilizing filter (prefilter flux = 150–160 LMH). The A1HC was able to achieve a process capacity of over 500 L/m 2 , while never exceeding a pressure differential of 5 psid. The throughput on the trailing sterile filter was greater than 3000 L/m 2 . Figure 7 illustrates the performance benefit of Millistak+ HC filters over competitive products, in side-by-side trials on a mammalian cell culture Competitor B Single Layer Media Millistak+ A1HC Prefilter Flux: 37 LMH Sterile Filter Flux: 200 LMH www.millipore.com
after microfiltration (0.65 µm). The competitive products represent similar stacked-disk prefilters, based on both single- and double-layer cellulosic media. In all tests, the prefilter exhibited little or no pressure build-up— performance was measured according to the volume of filtrate that could be processed subsequently through a sterilizing-grade (0.22 µm) filter. As shown, the A1HC outperformed all other products tested, demonstrating that the proper design of depth filter media and bi-layer configuration will result in superior sterile filter protection. Perfusion Bioreactor Biomass 300 – 400 NTU Depth Filter Figure 8. Processing of Perfusion Bioreactor Product Perfusion Bioreactor A side-by-side test of Millistak+ HC filters and several competitive single and multilayer stacked-disk products was conducted on a mammalian cell (CHO) perfusion process. As shown in Figure 8, the perfusion process generates two types of material, which are accumulated and batch-processed. The majority of the process fluid (~70%) is a crude product, harvested from the bioreactor through a screening mechanism, which must be further clarified before final filtration through a 0.45 µm membrane. In addition, the bioreactor is periodically purged Spin Filter Cell Harvest 40 NTU 0.45 µm Sterile Filter Millistak+ HC Filters Application Guide 11
Page 1: A P P L I C A T I O N G U I D E Â
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Page 6 and 7: types present in the process stream
Page 8 and 9: Proven Performance for Mammalian Ce
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Page 16 and 17: Summary of Application Test Results
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Page 20 and 21: Figure 13. Effect of Flux on Capaci
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Page 26 and 27: Manual Procedure The configuration
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Millistak+HC AppGd_textC.qxd - Millipore

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