Process intensification refers to the improvement of volumetric production capacity by the use of novel technologies. To maximize the biomanufacturing output, there is an emerging trend of implementing process intensification in upstream bioprocesses. Reported applications include intensified perfusion cultures, concentrated fed-batch cultures, and high-density seed trains. Compared with conventional batch and fed-batch cultures, significantly higher cell densities and/or product yields can be achieved with intensified processes. However, for successful implementation of intensified cell cultures, challenges such as increased hardware and operational complexity need to be overcome.
With advantages such as ease of implementation and hardware simplicity, single-use systems are often applied in batch and fed-batch cell culture processes. Given these benefits, we evaluated the feasibility of running an intensified perfusion cell culture using a streamlined single-use WAVE Bioreactor™ system. Either an internal floating filter or an external hollow fiber cartridge was used as a retention device. Evaluation studies were performed using multiple cell lines at various scales. The results demonstrate the simplicity and flexibility of this single-use solution for intensified cell culture, where high cell density (200 × 106 cells/mL) and volumetric productivity of up to 2 g/L/d were achieved.
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Authors and Organizations:
Peggy Lio1; Zhou Jiang1; Véronique Chotteau2; Marie-Francoise Clincke2; Carin Mölleryd2; Ye Zhang2; Puneeth Samani2; Eric Fäldt3; Kieron Walsh1; Eva Lindskog3; and Christian Kaisermayer3.
1 GE Healthcare Life Sciences, Westborough, MA, USA; 2 The Royal Institute of Technology, KTH, Sweden; 3 GE Healthcare Life Sciences, Uppsala, Sweden