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A novel single‐use bioreactor was recently introduced to the market that is agitated by impellers suspended on flexible ropes rather than a rigid shaft. Computational fluid dynamics (CFD) models were created and validated by particle image velocimetry (PIV) to predict the bioreactor's fluid flow and mixing. The data were then used to scale‐up a Spodoptera frugiperda, subclone 9 (Sf9) insect cell‐based production of recombinant adeno‐associated virus (AAV) from a benchtop glass bioreactor to the single‐use system with 30 L working volume. This viral vector is one of the most commonly used in gene therapies. The volumetric power input was kept constant while maintaining reasonable mixing times and shear stresses between the scales. Peak cell densities of up to 7.2 × 106 cells mL−1 and maximum virus titers of 1.7 × 1011 vg mL−1 were achieved. Similar cell growth and metabolite profiles further proved the successful process transfer between the two geometrically non‐similar bioreactor systems. The pilot bioreactor yielded between 3.3 and 4.8 × 1015 vg that, depending on the therapy, can be sufficient for the treatment of a single patient. [ABSTRACT FROM AUTHOR]

The innovative travelling wave bioreactor (TWB), an orbitally shaken system, developed specifically for cell culture applications, is investigated. In this study, engineering parameters covering power input, mixing time and oxygen mass transfer obtained in two TWB prototypes are presented for the first time. Based on the results, cultivation parameters for CHO suspension cell cultivations were defined. Cell growth and substrate consumption were comparable with a wave-mixed reference bioreactor, which demonstrates the bioreactor's applicability for cultivations of mammalian cell cultures for the first time. [ABSTRACT FROM AUTHOR]

A multitude of heterologous proteins is needed in pharmaceutical research. These have to be produced in robust and flexible cultivation systems to allow a fast and cost-effective handling. Moreover, these systems should be scalable and meet quality and regulatory requirements. The baculovirus expression vector system propagated on High Five insect cells is a popular choice for this purpose. For this expression system an efficient, robust and scalable process was developed based on a single-use technology and a medium replacement strategy with cell retention. It is shown that a medium replacement in the Wave bioreactor is feasible and can be scaled up to a 10-L scale without much effort. [ABSTRACT FROM AUTHOR]

During the past five years, the number of single-use bioreactors used in biopharmaceutical research and production has increased tremendously. This increase has been particularly associated with mammalian cell culture processes from small- to medium-scale volumes. Even though nowadays customers can choose from a multitude of 2nd and 3rd generation single-use bioreactors, ranging from mL- up to m3-scale, there is a lack of knowledge of their engineering parameters. Different approaches have been applied to characterization investigations, resulting in an inability to compare different single-use bioreactors with each other and their reusable counterparts, creating an obstacle to a systematic approach to scaling-up the process. This article describes parametric, experimental and computer-based numeric methods for biochemical engineering characterization of single-use bioreactors, which have already been used successfully for the characterization of their reusable counterparts. For the first time, these methods have been evaluated in terms of their practical application. [ABSTRACT FROM AUTHOR]

Contamination-free process measurement is essential for efficient monitoring of fermenters. This contribution introduces the use of high-frequency sensors for the contactless measurement of the permittivity and conductivity of fermentation media. As microwaves can penetrate through plastic materials without much attenuation, it is possible to achieve measurement setups that can measure the media under test without any direct contact and with long-term stability. The sensor can be installed directly to the outer surface of the fermenter or can be clamped onto tubing. [ABSTRACT FROM AUTHOR]

This study presents the concept of the travelling wave single-use bioreactor, based on an orbitally shaken, annular-shaped vessel. A numerical model was developed for early design studies in order to reduce the number of prototypes. The flow characteristics in two different vessel shapes were investigated. It was shown that the orbital motion combined with the toroidal shape of the bioreactor create the desired wave characteristics in the contents of the vessel. [ABSTRACT FROM AUTHOR]

Although vertical column, flat-plate, tubular, bubble column and airlift photobioreactors are widely used for the cultivation of diatoms, it has been shown that bubble-induced hydrodynamic stress created in these types of bioreactor can damage cells. Therefore, three single-use surface-aerated bag bioreactors, known for their outstanding results in cultivating shear-sensitive mammalian cells, were for the first time investigated for their suitability in growing the model microalgae Phaeodactylum tricornutum. All of the systems, which were additionally aerated with CO2 and equipped with illumination systems providing different light qualities, guaranteed a 22- to 43-fold increase in cell density within seven days, without any addition of cell protection agents or changes in cell morphology. Maximum cell density and dry biomass were achieved in the orbitally shaken 2D-bag by using cool-white fluorescent tubes. [ABSTRACT FROM AUTHOR]