Advances in mammalian expression systems have resulted in increased monoclonal antibody titers link to high density cell cultures with corresponding elevations in cellular debris and cellular impurities. In such cases, the performances of classical unit operations such as centrifugation or depth filtration are drastically reduced. <br/>Although the effectiveness of flocculation has been frequently demonstrated, adoption at large scale is not yet common.<br/>In this study from bench scale up to 2000 L single-use bioreactor scale, we could implement and witness the benefit of combining cell harvest pretreatment with a polycationic flocculating agent (polydiallyldimethylammonium chloride or pDADMAC), followed by specific depth filters, able to handle very large particle sizes (&gt; 20 µm). This robust process has not only allowed for reaching higher filtration capacity and yield with enhanced impurity removal, it has also exhibited its linear scalability and great flexibility with limited foot print and investment.  We also demonstrate how easy the implementation is as such scale, since pre-treatment is done directly in the Bioreactor. The area requirement of the subsequent depth filtration is reduced compared to classical depth filters.

Clarification by floculation: A promissing solution for high cell density

253rd National Meeting (2017)

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