Bioprocessing Technology for Production of Biopharmaceuticals and Bioproducts by Komives Claire;Zhou Weichang;
Author:Komives, Claire;Zhou, Weichang; [Komives, Claire]
Language: eng
Format: epub
Publisher: John Wiley & Sons, Incorporated
Published: 2018-11-24T17:55:51+00:00
Part II
Bioreactors
4
Bioreactors for Stem Cell and Mammalian Cell Cultivation
Ana FernandesâPlatzgummer*, Sara M. Badenes*, Cláudia L. da Silva, and Joaquim M. S. Cabral
Department of Bioengineering and Institute for Bioengineering and Biosciences, Insituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
4.1 Overview of (Mammalian and Stem) Cell Culture Engineering
The use of cultured cells for the production of viral vaccines was the first application of mammalian cell culture technology. In the midâ1950s, the need of mass cultivation techniques for vaccine production led to the development of largeâscale cell culture bioreactors (Fenge and Lüllau 2006). The hybridoma technology had been established in 1975 (Kohler and Milstein 1975), and in the 1980s, several companies started producing monoclonal antibodies for research and diagnostic purposes, using small hollowâfiber bioreactors (Papoutsakis 2009). Recombinant DNA technology enabled the production of several protein therapeutics in mammalian cell culture in the 1980s. Tolbert et al. (1980, 1982) pioneered the development of largeâscale mammalian cell culture technology identifying several important scaleâup issues. Since the midâ1990s, while mammalian cell culture was maturing, the available knowledge has also been applied to the design of bioreactors for stem cell culture. In recent years, the potential of stem cell research for Tissue Engineering and Cellular Therapies has become established, which will require cell production on a largeâscale using bioreactors.
In a biological system, extensive studies are required to understand cell needs concerning cell growth, metabolism, as well as focusing genetic manipulation, protein, or other product expression. Then, when choosing and scalingâup the appropriate bioreactor, strategy for a specific biological system is essential for the understanding of the influence of the complexity of the fluidâmechanical, nutritional, and physicochemical environment in the bioreactors in the cells, which depend on their intrinsic characteristics (Zhong 2010). Importantly, cells must be cultured in conditions compliant with current good manufacturing practice (cGMP) standards. There are several differences between biopharmaceutical production using mammalian cell culture and stem cell production schemes that are relevant for the bioreactor design. Of notice, in the latter case, the target product is a cell, rather than a protein or a vector.
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