Disposable bioreactors: the current state-of-the-art and recommended applications in biotechnology

Abstract

Disposable bioreactors have increasingly been incorporated into preclinical, clinical, and production-scale biotechnological facilities over the last few years. Driven by market needs, and, in particular, by the developers and manufacturers of drugs, vaccines, and further biologicals, there has been a trend toward the use of disposable seed bioreactors as well as production bioreactors. Numerous studies documenting their advantages in use have contributed to further new developments and have resulted in the availability of a multitude of disposable bioreactor types which differ in power input, design, instrumentation, and scale of the cultivation container. In this review, the term "disposable bioreactor" is defined, the benefits and constraints of disposable bioreactors are discussed, and critical phases and milestones in the development of disposable bioreactors are summarized. An overview of the disposable bioreactors that are currently commercially available is provided, and the domination of wave-mixed, orbitally shaken, and, in particular, stirred disposable bioreactors in animal cell-derived productions at cubic meter scale is reported. The growth of this type of reactor system is attributed to the recent availability of stirred disposable benchtop systems such as the Mobius CellReady 3 L Bioreactor. Analysis of the data from computational fluid dynamic simulation studies and first cultivation runs confirms that this novel bioreactor system is a viable alternative to traditional cell culture bioreactors at benchtop scale.

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

“…These systems can be used with disposable and/or standard online sensors for process monitoring. But compared to the reusable systems, the commercial availability of sensors or other reactor components is restricted [16]. In contrast to the static systems, cells in these systems reach much higher surface-to-volume ratios.…”

“…Problems arise due to the lack of experience in disposable systems concerning material quality [14] or potential interactions with the products [15]. In addition, there is also an increase in costs concerning waste disposable [16]. In the following, available cultivation concepts for hMSC are briefly summarized and details on disposable reactor concepts are provided.…”

Optimization of Insect Cell Based Protein Production Processes - Online Monitoring, Expression Systems, Scale Up

“…Overall, an acceptable equilibrium between the parameters in question has to be found for the specific process and equipment used (see Figure 11). [115,129]. Regardless of the specific system employed, the basic principles for scale up and transfer of a BEVS process into such a system are the same as for the standard stainless steel stirred tank equipment.…”

Cell Culture Processes for Biopharmaceutical Manufacturing

“…Single-use bioreactors comprising simplistically of plastic bags as reactor vessels are available commercially from several vendors up to scales of 2000 L (refs 101,102). The first among these was the WAVE bioreactor 103 where mixing takes place by virtue of a rocking motion resulting in formation of 'waves' within the reactor.…”