A continuous precipitation-based capture step for recombinant monoclonal antibodies (mAbs) has been developed using polyethylene glycol (PEG) in a sequential precipitation approach. In the first step, impurities are removed by precipitation at low pH and low PEG concentrations. After removing the precipitate, mAbs are precipitated by pH adjustment and PEG supplementation. Yields of 86-94% and a reduction in host cell proteins (HCPs) to 7200-15,000 ppm were reached depending on the mAb. Host cell DNA was removed to 18-29 ng/ml, which was independent of the starting DNA concentration. The secondary structure and isoform distribution of mAbs are unaltered compared with the chromatographically purified reference material. The method was then shifted to a continuous operating mode in a single-use tubular reactor by converting the time to reach equilibrium into residence time. Tangential flow filtration (TFF) has been used as an alternative precipitate capture step to centrifugation. The yield was not compromised with the use of TFF (>92%), and impurity removal was even enhanced compared with centrifugation. Concentration of the mAb precipitate by TFF and washing by diafiltration preserves the floc structure of the precipitate, thereby accelerating the subsequent resolubilization. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).