Cell culture process development

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. 

Table 1.1 Volumetric productivities from cell culture processes developed for the production of recombinant proteins for clinical use observations over a 20-year period...

Gramer, M.J. (2014) Product quality considerations for mammalian cell culture process development and manufacturing. Adv. Biochem. Eng. Biotechnol, 139, 123-166. 

AmanuUah A, Otero JM, Mikola M, Hsu A, Zhang J, Aunins J, Schreyer HB, Hope JA, Russo AP. 2010. Novel micro-bioreactor high throughput technology for cell culture process development Reproducibility and scalabihty assessment of fed-batch CHO cultures. Biotechnol Bioeng 106 57-67. 

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... 

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]. 

Ozturk, S.S. 2005. Batch versus perfusion A real case comparison of highly developed cell culture processes for the production of monoclonal antibodies. 229th National Meeting American Chemical Society, Mar 13-17, San Diego, CA. 

To date, progress achieved clearly demonstrates the potential of cultured plant cells for secondary metabolite production. Use of concurrent immobilization/permeabilization procedures, as well as precursor and elicitor treatments, may open new avenues of increasing product yields and will consequently affect the economic aspects of plant cell culture in a positive manner. However, our understanding of the many biosynthetic pathways of desired secondary metabolites is incomplete and successful industrial scale plant cell culture processes are still limited. Results of research in the area of plant cell culture will increase our understanding of the biosynthesis of plant metabolites, enhance our knowledge of plant-microorganism or plant-plant interactions and can lead to entirely new products or product lines of desirable compounds currently not available to use. Such work can also lead to development of industrial scale production processes for products now produced and recovered by conventional methods. Also, the genetic variety of the 250,000 to 750,000 plant species available remains to be explored. Presently only 5 to 15% of these species have been subject to even... 

The osmolarity of the cell suspension increases during a fermentation process as a result of metabolic events (0yaas, 1989). The influence on the cells and the product is still unclear. Therefore, with each development of a new cell culture process, a study on the importance of this parameter must be performed. Unfortunately, there is no on-line measurement system commercially available, although sterile installation of a membrane osmometer should be possible. 

Blackie J, Dean A, Konstantinov K Naveh D (1998) Real-time imaging for monitoring of mammalian cell culture processes. In Merten OW Griffiths B (eds) Animal Cell Technology New Developments and New Applications. Kluwer, Dordrecht, in press. 

Wurm FM. Development of High-Yielding Cell Culture processes for medical applications How to meet the challenge. Presented at Scale-Up of Biopharmaceutical Products, NL-Amsterdam, IBC Life Science UK, 26-27 January, 2004. 

Chemists at Sigma-Aldrich have developed a process to synthesize cholesterol from plant sources. Some plants, such as the Mexican yam, are excellent sources of specific steroids, which, through a sequence of chemical reactions, can be converted into cholesterol. Cosmetics manufacturers can use this cholesterol in their products, and pharmaceutical researchers can exploit its growth-promoting properties in cell culture. The development of a synthetic process to produce cholesterol from raw materials in plants is another example of problem solving through the appropriate use of chemistry. 

In view of the above conditions, cell culture has been proposed as a promising alternative method to obtain paclitaxel. Cell culture processes can be adapted to produce paclitaxel as well as the taxane precursor bacca-tin. However, the yield of paclitaxel or baccatin obtained using cell cultures is too low to be sufficient for industrial application. Therefore, there is an urgent need to develop effective means to increase paclitaxel production on an industrial scale. 

Major cell culture process changes such as a change in the cell line used or the development of a new master cell bank and different media such as a switch to chemically defined media to reduce contamination problems from adventitious agents and/or to provide a more consistent medium ... 

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