“…There are only a few studies focusing on protein aggregation during USP (Fischer et al, 2015;Franco, Daniela, Fabrizio, Ilaria, & Detlev, 1999;Gomez et al, 2012;Jing et al, 2012;Paul et al, 2015;Paul, Schwab, & Hesse, 2014). Statistical Design of experiments (DoE) strategies have often been used for bioprocess optimization of cell culture processes producing mAbs, since DoE enables process characterization of parameter interactions and classification of parameters based on their impact to the bioprocess and product quality (Abu-Absi et al, 2010;Dong et al, 2008;Mandenius & Brundin, 2008;Montgomery, 2013;Moran et al, 2000). Astonishingly, the formation of large aggregate particles in cell culture was not investigated before, although such particles are known to induce nucleation-dependent aggregation processes (Wang, Nema, & Teagarden, 2010).…”