CFD for Characterizing Standard and Single-use Stirred Cell Culture Bioreactors (2011)

Driven by global competition and rising cost pressure in the pharmaceutical industry, over the last ten years single-use bioreactors have been increasingly used for animal cell cultivations in screening experiments, seed inoculum and seed train productions as well as in small and medium scale production processes of proteins (in particular, antibodies and vaccines). In contrast to re-usable bioreactors made of glass or stainless steel, single-use bioreactors consist of a flexible or rigid cultivation vessel which has been gamma-sterilized and made ready for the purchaser to use. After harvest, the cultivation vessel is discarded, which results in a lower risk of cross-contamination, and eliminates the need for steam sterilization and cleaning Nowadays a multitude of single-use bioreactors are commercially available, which can be categorized according to the type of power input into static and dynamic systems. The latter can be further subdivided into hydraulically, pneumatically and mechanically driven bioreactors and their combinations, the so-called hybrid systems Mechanically driven single-use bioreactors represent the largest group and are mixed by either orbital-shaken, wave-induced or stirrer motion. While wave-mixed bioreactors (e.g. from GE Healthcare, Sartorius Stedim Biotech, Applikon Biotechnology) were initially dominant, nowadays stirred bag systems (such as Hyclone Single Use Bioreactor S.U.B., BIOSTAT CultiBag STR, XDR-DSTB animal) are more frequently used, mainly due to the broad experience already obtained with conventional stirred cell culture bioreactors The flexible cultivation bags are fixed and shaped by a temperature-controlled stainless steel container. This design is also used in the BIOSTAT CultiBag STR from Sartorius Stedim Biotech, which is available at different scales from 50 to 1,000 L. The bag geometry, the impellers and the aeration system are designed in a similar way to Sartorius Stedim's re-usable stirred cell culture bioreactors to ensure comparability of single-use and classical processes, and thus facilitate integration of singleuse bioreactor technologies into modern cultivation processes Until summer 2009, stirred bag bioreactors were available only at working volumes exceeding 50 L for manufacturing and cost reasons. The introduction of the first single-use stirred bioreactors with a rigid cultivation vessel (Mobius CellReady 3L bioreactor and CelliGen BLU SUB) bridged the gap for stirred systems between laboratory and pilot scale www.intechopen.com With the recent development of the UniVessel single-use, Sartorius Stedim Biotech have extended their portfolio of the BIOSTAT product family at bench scale. This novel cell culture bioreactor comes as close as possible to the conventional UniVessel , but differs slightly in geometry due to the manufacturing process. Furthermore, the positioning of installations, such as harvest tubes or probes, are customized in the reusable bioreactor, but fixed in the single-use alternative. Comparability of single-use and conventional cell culture bioreactors is essential for process development, especially when both systems have to be used side by side in hybrid solutions. A need for single-use bioreactors with design and set-up comparable to the reusable alternative is therefore evident. Hence, the aim of this case study is a comparison of the UniVessel 2L single-use bioreactor with its conventional counterpart made out of glass (in the following, also referred to as 'small scale'). For this purpose, fluid flow investigations using computational fluid dynamics (CFD) are carried out for the single-use and conventional bioreactor to show that the small changes in the geometry of the single-use UniVessel have no significant effect on its fluid flow. The commercial CFD software package ANSYS Fluent (version 12.1.3) is applied and engineering parameters, such as power input, mixing time and oxygen mass transfer, are determined for the first time. With regard to scale-up, the results are compared with those of the disposable BIOSTAT CultiBag STR at 50 L scale (in the following, also referred to as 'large scale').