Capture and intermediate purification of recombinant antibodies with combined precipitation methods

•Combined precipitation methods with equal separation power as chromatographic methods.•Replacement of capture and intermediate steps by caprylic acid and PEG precipitation.•Combination of CEP, PEG, CA and CaCl2 precipitation to remove host cell impurities.•The final yield and purity of the antibodies nearly reached drug substance values.

A protocol for capturing recombinant antibodies was developed with a combination of different precipitation methods. This process comprised four different precipitations, including caprylic acid, polyethylene glycol (PEG), CaCl2, and cold ethanol. The final yield and purity of the antibodies nearly reached drug substance values, with a low host cell protein concentration (<300 ppm), no high molecular weight impurities, and a yield of 70%. In fact, only the combination of caprylic acid and PEG precipitations was needed to achieve purity similar to that produced with protein A affinity chromatography. Caprylic acid was used to remove the host cell proteins and high molecular weight impurities, and the PEG precipitation separated the IgG from the remaining impurities.