Bioreactors, Cell Culture, Commercial Production

Abstract

Various recombinant proteins expressed by animal cells and secondary metabolites produced by plant cells have significantly increased the demand for high‐value‐added (mainly biopharmaceutical) products in recent years. Without doubt, large‐scale efficient production of these compounds is very important to meet market requirements. As animal cells and plant cells are more sensitive to culture conditions than microorganisms, their bioreactor culture technique is critical to reduce the production cost. In order to favor the desired functions of the cells and achieve cost‐effective large‐scale manufacture, it is necessary to optimize and control the bioreactor environment via operating variables. In this article, the characteristics of various types of cell culture bioreactors including stirred‐tank bioreactors, pneumatically agitated bioreactors, membrane bioreactors, packed and fluidized‐bed bioreactors, and wave bioreactors are discussed. Details of basic bioreactor design principles such as shear force, oxygen supply, and mixing are introduced. The effects of process variables including oxygen and mass transfer, fluid mixing, temperature, pH, and light irradiation on cell cultures are described. Bioreactor operation strategies for cell cultures are compared. For commercial production scale‐up, different criteria are considered and industrial large‐scale examples are also illustrated.

Fungal pelleted reactors in wastewater treatment: Applications and perspectives

“…The main design criteria for reactors with fungal pellets should consider adequate transfer of oxygen and other nutrients, low shear stress and adequate mixing [95,96].…”

Design space definition for a stirred single‐use bioreactor family from 50 to 2000 L scale

“…For biopharmaceutical processes, the used bioreactor as well as its design is of major importance. The bioreactor is a key element for process optimization [1] as operations such as homogenization, dispersion, suspension of solid particles, and heat transfer [2] are performed. Due to the well-defined characteristics of stirred stainless steel and glass bioreactors, these cultivation platforms are the gold standard since many decades for biopharmaceutical requirements.…”

Recent advances in bioreactor engineering

“…Huang et al recently reported up to 13 g/L of final titer and high volumetric productivity of 800 mg/(L·d) in an 18-day fed batch process using a CHO cell line without anti-apoptosis gene [2]. It can be predicted that more companies can achieve this level in future, which will increase manufacture capability dramatically and put a positive pressure on downstream purification.…”

“…In general, the main criteria for designing bioreactor should consider adequate oxygen transfer, low shear stress and adequate mixing [1,2]. In considering the bioreactor design and selection, nutrients must be effectively provided to the cells, and waste products must be removed.…”