Technological and methodical process integration in manufacturing of monoclonal antibodies

Background A steady increase of product titers and the corresponding change in impurity composition represent a challenge for development and optimization of antibody production processes [1,2]. Concentration and composition of impurities like host cell proteins (HCP) are critical for efficient process development. These impurities show significant variations, which primarily depend on cell culture conditions. They have a strong influence on the downstream processing (DSP) and costs [2]. It is already shown that not optimized changes of parameters in USP can change the impurity profile by a factor of 7 [3]. The resulting “bottleneck” in DSP requires new optimization, technology and development approaches. These include the optimization and adaptation of existing unit operations respective to the new separation task, the assessment of alternative separation technologies and the search for new methods in process development [2].