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A Complete Mammalian Expression System
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| Lonza has developed a highly efficient mammalian expression system which makes use of selection, via glutamine metabolism, and powerful viral promoters. The GS System™ is well established with over 85 companies using the technology worldwide. Currently there are over 50 products in clinical trials and 5 products in-market that use the GS System™. |
Productivity
The high manufacturing cost of protein products, particularly for therapeutic proteins, means that maximising volumetric productivity is essential if economic processes are to be established. Use of the GS System™ reliably results in high-producing cell lines early in cell line construction programmes. Maximum expression levels attainable depend on the product but cell lines producing over 5 g/L of recombinant antibody have been created, with specific production rates in the range 15-65 pg/cell/day. |
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Productivity in chemically defined, animal compotent-free GS-CHO bioreactor process |
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Productivity in chemically defined, animal compotent-free GS-NS0 bioreactor process |
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Speed
Speed at the development stage of any biotechnology project is crucial to success. The GS System™ allows for rapid selection of high-producing cell lines. Product concentrations can be increased further through media and process optimization. This significantly reduces the time required to generate a cell line suitable for cGMP manufacture. Construction of full length antibodies with human constant regions is rapid and easy using Lonza’s GS constant region vectors which enable the addition of any variable region in a single ligation step. Lonza’s proprietary CHOK1SV host cell line is pre-adapted to growth in chemically defined animal component free (CDACF) media and suspension culture. Its pre-adaptation to suspension culture aids adaptation of GS cell lines back to growth in suspension culture after transfection. |
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Timeline of steps performed to select high-yielding uncloned GS-CHO cell lines adapted to chemically defined, animal component-free media |
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Stability
GS cell lines that are "consistent" in terms of product concentration, growth and product characteristics can be easily created. For unamplified, GS negative cell lines, such as NS0, the selective agent and inhibitor of GS activity methionine sulphoximine is not required for stability. For unamplified, GS positive cell lines, such as CHO, methionine sulphoximine is typically required to maintain volumetric productivity at a consistent level. |
Familiarity
The GS System™ is successfully used by over 85 global pharmaceutical and biotechnology companies and by academic laboratories leading to a large body of published information that new users can draw upon. In addition, Lonza has accumulated a considerable amount of expertise, which is shared with users. Currently there are over 50 products in clinical trials and 5 products in-market that use the GS System™, including Zenapax® (Roche) and Synagis® (Medimmune) so the system is well known to all regulatory authorities. |
Extensive Experience
Lonza has itself created hundreds of cell lines using the GS System™. Many of these cell lines have been grown at large scale and have produced product for use in clinical trials and for in market supply. Other GS users have accumulated experience with a diverse range of products. In most cases high harvest product concentrations were achieved. Many investigators use GS, not only to develop a manufacturing process, but as a tool to create recombinant proteins for biological studies. In these cases the reliability of GS, as a consistent means of generating high-producing cell lines quickly, is invaluable. |
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