Biochemical Engineering Journal 17 (2004) 217–223 TubeSpin satellites: a fast track approach for process development with animal cells using shaking technology Maria J. De Jesus a,* , Philippe Girard a , Michaela Bourgeois a , Gwendoline Baumgartner a , Barbara Jacko b , Hanspeter Amstutz c , Florian M. Wurm a a Center of Biotechnology, LBTC, EPFL DC, CH-1015 Lausanne, Switzerland b BioWhittaker Inc., Walkersville, MD, USA c ZLB Bioplasma AG, Berne, Switzerland Received 1 November 2001; accepted after revision 17 June 2003 Abstract Process development with mammalian cells is often limited by the lack of resources and assay capacity to deal with the multiplicity and complexity of interrelated parameters in culture technology. Multi-component analysis, an issue in media development and in screening of newly established production cell lines, is subject to the same limitations. We therefore developed a high throughput system for the culture of mammalian cells in suspension. Our scale-down reactor system called “TubeSpin” allows many experiments to be run in parallel with a minimum of resources and labor. Reactor conditions were readily simulated using 50 ml centrifugation tubes as culture vessels mounted on a rotational shaker installed in a warm room. This system was applied to the development work for a number of CHO based processes for the production of a human recombinant IgG. We show here how such a system can increase process development speed and efficiency. The results presented illustrate the improvement of volumetric productivity using butyrate and temperature shifts. © 2003 Elsevier B.V. All rights reserved. Keywords: Monoclonal antibody; High throughput; Process development; Optimization; Small-scale bioreactor; Screening; Scale-down; Shaking technology 1. Introduction Progress in process development in animal cell culture is often limited by the lack of information about the response of cells to different process conditions, the addition of sup- plements or productivity enhancers. Commonly, to achieve a reliable and robust process, spinner flasks or small biore- actors must be used. These experiments are time consuming and demanding in resources. The limited availability and the high cost for spinner and reactor runs limit the advance- ment of the process development to a considerable extent. Certainly, for some parameters, such as pH, pO 2 , pCO 2 , and aeration method there is a need for a controlled environment and hence an obligation to use small-scale bioreactors. How- ever, identification of promising conditions, such as optimal medium composition, productivity enhancers, osmolality and temperature shifts, do not need a set of bioreactors, and so the use of smaller-scale and simpler equipment can be envisaged. The major difficulty for the use of such small- or micro-scale systems lies in their correlation (or lack * Corresponding author. Tel.: +41-21-693-6136; fax: +41-21-693-6140. E-mail address: maria.dejesus@epfl.ch (M.J. De Jesus). thereof) to the large-scale industrial process. Ideally, experi- ments should be executed in conditions resembling as close as possible those found in a bioreactor in order to achieve reasonable correlation. Limitations of the scale-down sys- tems have to be studied carefully, well understood and eventually anticipated in terms of the conclusions drawn. If done properly, a large amount of useful information can be obtained that dramatically reduces the need for work in bioreactors and thus the time spend for the identification of sets of parameters improving productivity and/or cell growth. Until now shaking technology was used mainly for micro- bial or yeast cultivation [1]. For the culture of mammalian cells several shaken cultivation systems have been proposed [2,3]. In these systems, shaking the whole culture vessel with an external device provides the power input necessary for agitation. Several systems based on this principle were proposed for different culture scales. Starting with small de- vices, for volumes for up to 3 ml based on microtiter plates [2], up to larger shaken rigid containers [3] for superior vol- umes up to 10 l, and finally to culture systems where cells grow in flexible bags [4], many different shaken cultivation systems were developed. In wave bioreactors, the cells are 1369-703X/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/S1369-703X(03)00180-3