Monoclonal antibodies (mAbs) are among the most important therapeutic proteins for the treatment of cancer. They also find wide application in the field of diagnostics. The market for mAbs was US$ 5.4 billion in 2002 and is expected to triple by 2010 (1). MAbs are mainly produced in cell culture and purified by chromatography. Apart from the mAb, the downstream processing is confronted with a multitude of impurities from the upstream process. Some of these impurities bind strongly to the chromatographic stationary phase and can only be removed by separate cleaning solutions. Depending on the type of media used, e.g. affinity or ion exchange, differing cleaning regimes may have to be applied. In addition, sanitization is required to prevent microbial contamination. Both steps are closely tied to the mAb production step and need to be repeated in regular intervals. In this work, the impact of irreversible impurity adsorption on the separation performance is investigated experimentally; first for a batch column and then for a continuous chromatographic process. At first, the retention time of a model substance is established as a suitable measure to describe the degree of irreversible adsorption. The impact of the presence and the absence of cleaning-in-place (CIP) on the retention time of the model substance is demonstrated. Since the issue of column cleaning is particularly important if processes are operated in continuous mode, in the second part of this work the introduction of a CIP step in the continuous multicolumn countercurrent solvent gradient purification (MCSGP) process is investigated. The process purifies a mAb from a cell culture supernatant that also contains irreversibly adsorbing impuritiesor impurities that desorb in a later cycle of the process as a contamination. Following the same approach as for the batch experiments, the MCSGP process is operated in the presence and the absence of CIP in order to track prospective changes of the process performance caused by changes in the product retention time. Instead of the model substance, a cell culture supernatant, providing a real case impurity profile in an industrial application is used for the process. Although an impact of the product retention time change on the process yield is not observed it is shown that CIP is required for a stable long-term operation in terms of purity and system pressure drop. With the introduction of a CIP step the process was successfully operated for 9000min (6 days) without interruption.