Cell culture process

Traditionally, the upstream fermentation and cell culture processes have been viewed as being distinct from the subsequent downstream processing and purification steps, and the two different sets of processes nave been optimized individually. In some instances, careful consideration of the conditions used in the fermentation process, or manipulation of the genetic makeup of the host, can simplify and even... 

Kyuchnicchenko V., Rodenbrock A., Thommes J., Kula M., Heine H., and Biselli M. (1998), Analysis of hybridoma cell culture processes by CE-SDS and MALDI-MS, Biotechnol. Appl. Biochem. 27, 181-188. 

Figure 12.7 Proton NMR spectrum of a typical polymer used in mammalian cell culture processes Pluronic F68.

The Lab Chip instruments/methods currently commercially available generally have less resolution and are less sensitive compared to conventional CE-SDS methods. However, the high throughput of the Lab Chip technique makes it attractive for in-process monitoring during process development. The Lab Chip method is generally used for process development activities such as clone selection, cell culture process development, and optimization of the downstream purification process. 

Anderson, L. A., Phillipson, J. D. and Roberts, M. F. 1987. Alkaloid production by plant cells. In Plant and Animal Cell Cultures, Process, Possibilities (Webb, C. and Mavituna, F. eds.), pp. 172-192. Chichester Ellis Horwood. 

As outhned earUer every single step of hematopoiesis is regulated and controlled in vivo by the cell s microenvironment. This not only includes the composition and concentration of growth factors, but also the local oxygen concentration, the pH, the osmolaHty, the supply of nutrients and the cellular and molecular surrounding of the cells (cell-cell contact, adhesion molecules and extracellular matrix). All these parameters affect the fate of the cell and, to estabUsh a cell culture process to cultivate or generate a specific subpopulation, the influence of all these factors has to be considered in the experimental set-up. In the following sections these parameters will be discussed in brief. 

Cell culture, particularly mammalian cell culture, processes enable the production of new, hitherto unknown drugs, the biopharmaceuticals. The year 2001 marked a turning point in the development of biopharmaceuticals, insofar as it was the first time that more new biological entities (NBEs) than... 

General Considerations in the Development and Scale-Up of Cell Culture Processes... 

Griffiths JB. Animal cell culture processes—batch or continuous J Biotechnol 1992 22 21-30... 

Adamson, S. R., Leonard, M., Drapeau, D., Harrison, S. A., O Connell, B. D., Charlebois, T. S. Process validation and characterization animal cell culture processes. In G. Sofer, D. W. Zabriskie, eds. Biopharmaceutical Process Validation. New York Marcel Dekker (2000). 

Wagner R (1997), Metabolic control of animal cell culture processes. In Hauser H, Wagner R (Eds), Mammalian Cell Biotechnology in Protein Production, Walter de Gruyter, Berlin, pp. 193-232. 

The advances attained in the last decades in the knowledge of the biological fundamentals underlying animal cell culture have enabled significant improvements in cell culture processes in vitro. In this chapter, the mechanisms that determine cell proliferation and cell death are discussed. Aspects concerning the kinetics and the mathematical description of cell growth and cell death are dealt with in Chapter 8. 

Sidoli FR, Mantalaris A, Asprey SP (2004), Modeling of mammalian cells and cell culture processes, Cytotechnology 44 27-46. 

Tziampazis E, Sambanis A (1994), Modeling of cell culture processes, Cytotechnology, 14 191-204. 

Since in animal cell culture processes the effects of mechanical stress are much more relevant than in microbial fermentations (Chisti, 1993), it is quite common to adopt scale-up criteria that are associated with cell damage (Joshi et al., 1996), such as constant peripheral impeller velocity, constant aeration rate, and constant integrated shear stress (Croughan et al., 1987). 

Pattison RN, Swamy J, Mendenhall B, Hwang C, Frohlich BT (2000), Measurement and control of dissolved carbon dioxide in mammalian cell culture processes using an in situ fiber optic chemical sensor, Biotechnol. Prog. 16 69-74. 

Sauer PW, Burky JE, Wesson MC, Sternard HD, Qu L (2000), A high yielding, generic fed-batch cell culture process for production of recombinant antibodies, Biotechnol. Bioeng. 67 565-597. 

The cell culture process was licensed in May 1995 by Bristol-Meyer Squibb, which in 1998 designated 25 million for development of an FDA-approved commercial process. Many academic and industrial research groups around the world are pursuing plant cell culture routes of production [76-86]. 

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