Single-Use Bioreactors for Animal and Human Cells

Abstract

Single-use (SU) bioreactors are being increasingly used in production processes based on animal (i.e. mammalian and insect) and human cells. They are particularly suitable for the production of high-value products on small and medium scales, and in cases where fast and safe production is a requirement. Thus, it is not surprising that SU bioreactors have established themselves for screening studies, cell expansions, and product expressions where they are used for the production of pre-clinical and clinical samples of therapeutic antibodies and preventive vaccines. Furthermore, recent publications have revealed the potential of SU bioreactors for the production of cell therapeutics using human mesenchymal stem cells (hMSCs).This chapter provides a perspective on current developments in SU bioreactors and their main applications. After briefly introducing the reader to the basics of SU bioreactor technology (terminology, historical milestones and characteristics compared to their reusable counterparts) an overview of the categories of currently available SU bioreactor types is provided. SU bioreactor instrumentation is then examined, before discussing well-established and novel applications of SU bioreactors for animal and human cells. This includes descriptions of the engineering characteristics of often-used types of SU bioreactors, covering wave-mixed, stirred, orbitally shaken systems and fixed-bed systems. In this context, the scaling-up of geometrically and non-geometrically similar SU bioreactors is also addressed.

Model uncertainty-based evaluation of process strategies during scale-up of biopharmaceutical processes

“…All investigated bioreactors were hydrodynamically characterized ( Meusel et al, 2016;Kaiser et al, 2015 ) and engineering parameters were compared with respect to cell growth, metabolism, and product titer during scale-up and in scale-down models (not part of this work). Based on this, a specific power input of 19 W m −3 was identified as the scale-up criterion, which was kept constant in this study at all investigated stirred bioreactor scales.…”

Mass Production of Mesenchymal Stem Cells — Impact of Bioreactor Design and Flow Conditions on Proliferation and Differentiation

“…The N S1U criterion is its lower limit and thus the impeller speed required to locate the particles at the bottom of the bioreactor with none of them at rest. Comparing different stirred SU bioreactors from small to pilot scale, the lowest impeller speeds, and, thereby power inputs required to lift up polystyrene-based microcarriers with solid fractions of up 0.2 % were found in the Mobius ® CellReady bioreactor [182]. However, the suspension criteria also strongly depend on the microcarrier type used.…”

“…It is worth mentioning that the majority of dynamic bioreactor types were originally developed for production processes aimed antibodies and vaccines. For this, genetically modified, continuous mammalian cell lines such as Chinese hamster ovary (CHO) cells are generally grown [180][181][182]. With the exception of spinner flasks (as simple stirred bioreactors), mechanically driven bioreactors are generally instrumented with sensors to enable monitoring and control of temperature, pH value, DO and carbon dioxide concentration, gas and liquid flow rates, impeller or rocking speed.…”

Efficient propagation of suspended HL-60 cells in a disposable bioreactor supporting wave-induced agitation at various Reynolds number

“…As fragile biomass, animal cells require gentle flow of liquid phase in culture vessel, which is characterized by low values of Reynolds number for liquid phase (Re L ), as well as low levels of hydrodynamic shear stress [1,2]. Feasibility of gently mixing in small-scale wave-type agitated single-use (disposable) bioreactors establishes applicability of such systems for in vitro scale-up of fragile biomass of both nonadherent and adherent animal cells [3][4][5].…”