High-performance tangential flow filtration (HPTFF) is shown to successfully enable concentration, purification and formulation in a single unit operation. This is illustrated with feedstreams comprising recombinant proteins expressed in Escherichia coli (E. coli). Using positively charged cellulosic membranes of 100 kDa molecular weight cut-off and operating under a selected range of buffer pH and ionic strength at a filtrate flux of 100 L m(-2) h(-1), a 10-fold removal of E. coli host cell proteins (HCP) was obtained with an overall process yield of 98%. The HPTFF performance was shown to be robust and reproducible. In addition, the novel charged membrane was regenerated and re-used seven times without loss of selectivity or throughput. When compared with a conventional purification scheme, the proposed process results in the elimination of one chromatographic step, a 12% yield improvement and a significant reduction in purification cost of goods.

Inline ultrafiltration (UF) can significantly increase the recoverable mass of biopharmaceutical products when pool tank volumes are limiting. Using relatively small commercially available ultrafiltration cassettes, a proof-of-concept study demonstrates that inline UF can significantly increase recoverable mass in an antibody purification process. With ever-increasing cell culture titers pushing product masses to higher levels, inline UF offers a relatively easy-to-implement and less disruptive alternative to installing larger pool tanks and enables more cost-effective production utilizing facilities designed for smaller bulk sizes.

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