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Asymmetric dialysis, a novel one?step continuous process combining ultrafiltration and diafiltration, achieves high product concentrations (up to 200?g/L) with low pressures and reduces buffer consumption by 75% compared to conventional methods. This sustainable, low?cost technology demonstrates significant potential for integration into continuous biopharmaceutical manufacturing.ABSTRACTBiopharmaceutical manufacturing has been using ultrafiltration (UF) and diafiltration (DF) for buffer exchange, desalting, and formulation of biologics. The legacy UF/DF is commonly a two?step batch process that is challenging to integrate into end?to?end continuous biomanufacturing. Here, we introduce asymmetric dialysis, a novel one?step continuous process that combines UF and DF. It works by utilizing asymmetric flow between the inlet and outlet of the retentate and complementary flow of the dialysate solution, achieving product concentration, buffer exchange, and salt removal using a commercially available hollow fiber device. Asymmetric dialysis can achieve product concentrations of 105 (3.8×), 200 (10×), and 64?g/L (9.4×) starting from feed concentrations of 30, 20, and 7?g/L, respectively, with modest pressures of 6–7?psi. The interplay between feed and exchange buffer flow rates was exploited to make the process sustainable by reducing buffer consumption by 75% (25?L/kg mAb) compared to conventional batch UF/DF (100?L/kg, mAb). We successfully processed 7?kg of mAb at 20?g/L feed using 5?day asymmetric dialysis with a daily productivity of 0.8?kg/m2/day to product concentration of 200?g/L. These results demonstrate the potential of asymmetric dialysis, a simple, sustainable, and low?cost bioprocessing technology for continuous bioprocessing.