Bioreactor (bioreactor) refers to any plant or engineering equipment that provides bioactive environment. It is a biological function simulator, such as fermentor, immobilized enzyme or immobilized cell counter, using the biological function of enzyme or organism.
The key to large-scale industrialization and commercialization of animal cell culture technology is whether we can design suitable bioreactors. Because of the great difference between animal cells and microbial cells, the traditional microbial reactor is obviously not suitable for large-scale cultivation of animal cells. First of all, we must satisfy enough oxygen under low shear force and good mixing state to provide enough oxygen for cell growth and cell product synthesis.
Then what types of bioreactors are commonly used in the laboratory? According to the material of the reactor, they can be divided into glass tank reactor, stainless steel reactor and disposable reactor.
(1) glass tank reactor
At present, most of the reactors used for the research of process development are mainly glass tanks. The glass tank bioreactor has the characteristics of flexible configuration, powerful function, simple operation and easy to upgrade. It is the best choice for developing animal cell culture and microbial fermentation research and development projects, and can be used in animal cells and coliform rods. Bacteria, yeast, fungi, insect cells and plant cell culture.
(2) stainless steel reactor
So far, the antibody drugs approved by FDA are basically produced in stainless steel reactors. Because the early antibody production is relatively low, the scale of production is mostly around 10000 L. Stainless steel reactor usually involves CIP module, SIP module, storage module and so on. Therefore, pipeline connection is very complex, which requires higher requirements for operators. Once there is pollution, we need to check and sterilize the whole system. Meanwhile, the stainless steel reactor is also facing high initial equipment investment and operation cost.
(3) one time reactor
In recent years, disposable reactors quickly occupy the market at home and abroad with the advantages of no cleaning, no sterilization and flexible operation. Shire company's trade name is VPRIV EMA, which is produced by disposable reactor and has been approved by EMA. Compared with the traditional stainless steel reactor, whether it is cell growth, antibody production or antibody quality, the use of a one-time reactor can achieve high similarity, at the same time, it can significantly reduce production costs and shorten production cycle.
With the rapid development of cell line construction technology and culture medium development technology, cell density and antibody production have been greatly improved, which poses a severe challenge to large-scale cell culture.
The rapid rise of the disposable reactor has brought a great impact to the traditional stainless steel reactor. Because the disposable reactor reduces CIP, SIP and related verification work at the same time, it significantly improves operation flexibility and reduces pollution risk. In the future, it will be possible to replace the stainless steel reactor and become the mainstream reactor for the production of antibody, if it can solve the problem of dissolving substance / precipitate and production scale well. In addition, the main basis for the amplification of the reactor is still based on the empirical amplification principle, and there are still some disputes, such as the leaf tip rate as the suitability of the amplification principle. These factors will undoubtedly increase the difficulty and risk of the industrialization of antibody drugs in the future.
