Harvest and recovery of monoclonal antibodies from large-scale mammalian cell culture

The objective of harvest and clarification unit operations is the removal of cells and cell debris to enable product capture on a chromatographic column. The first step in the harvest of monoclonal antibodies from mammalian cell culture is cell removal, followed by filtration unit operations for additional clarification. Centrifugation and microfiltration have been the primary harvest techniques adopted industrially. Although depth filtration can be used as a primary harvest method, it is more common to see this unit operation follow the primary harvest step to provide additional clarification. Flocculants are sometimes added before harvest to improve harvest and clarification operations. Filtration through absolute pore size membranes is typically the final clarification step before capture chromatography. Expanded bed chromatography has been developed as an integrated unit operation that combines harvest with product capture, but to date, practical limitations have kept this technique from being adopted In commercial-scale operations.