The impact of host cell-derived chromatin was investigated on the performance and productivity of cation exchange chromatography as a method for capture-purification of an IgG monoclonal antibody. Cell culture supernatant was prepared for loading by titration to pH 6.0, dilution with water to a conductivity of 4 mS/cm, then microfiltration to remove solids. DNA content was reduced 99% to 30 ppm, histone host cell protein content by 76% to 6300 ppm, non-histone host cell protein content by 15%

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... 321,000 ppm, and aggregates from 33% to 15%. IgG recovery was 83%. An alternative preparation was performed, adding octanoic acid, allantoin, and electropositive particles to the harvest at pH 5.3, then removing solids. DNA content was reduced to < 1 ppb, histones became undetectable, non-histones were reduced to 24,000 ppm, and aggregates were reduced to 2.4%. IgG recovery was 95%. This treatment increased dynamic capacity (DBC) of cation exchange capture to 173 g/L and enabled the column to reduce non-histone host proteins to 671 ppm. Step recovery was 99%. A single multimodal polishing step further reduced them to 15 ppm and aggregates to <0.1%. Overall process recovery was 89%. Productivity at feed stream IgG concentrations of 5-10 g/L was roughly double the productivity of a same-size protein A column with a DBC of 55 g/L.