Evaluation of an alternating tangential flow system as a retention device in comparison to a continuous flow centrifugation system in repeated batch process mode
Matjaž Tisu¹, VatroslavSpudić¹, Matjaž Brinc¹, Petra Malovrh², Jan Visser^1
1Technical Development, ²Analytical Development
Address: Sandoz Biopharmaceuticals, Lek Pharmaceuticalsd.d., Kolodvorska 27, SI-1234 Mengeš
Email: matjaz.tisu@sandoz.com

INTRODUCTION

The demand for animal cell culture derived recombinant proteins for therapeutic and diagnostic applications is rising constantly, increasing the interest in a more efficient technology to meet demands in quality, purity and safety for these products, preferably at a reduced cost. Since animal cells grow substantially slower than most microorganisms, scale-up of a traditional batch culture has several practical and economical limitations resulting in a low cell concentration, low product titer and poor volumetric productivity. As an alternative method, recycling of cells in the bioreactor was established. Beside the well established and widely used perfusion process mode, where cells can be maintained at high density through a retention system that allows cells to be perfused with fresh medium while withdrawing spent medium at the same time, sever alvariations on a classical perfusion system have been developed. One of these variants is a repeated-batch process, enabling to concentrate cells outside (e.g., continuous flow centrifugation) or inside the vessel (e.g., alternating tangential filtration), while changing the complete volume of spent medium (harvest) with fresh medium. Growth, productivity and product quality of CHO cells expressing a sialylated recombinant glycoprotein was evaluated in a classical stirred tank bioreactor using either an alternating tangential flow system (ATF) or a continuous-flow centrifuge as a cell recycling device.

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