Article

The effect of temperature shift on product titer and viability in the development of a CHO platform

Developing a platform process to accelerate the development of other therapeutic proteins

The production of recombinant therapeutic proteins requires the use of a host organism. The host organism that are commonly used for therapeutic proteins include CHO, E.coli, P. Pastoris, and S. Cerevisiae (1). The popularity of CHO for mammalian cell-based production is mainly due to its capacity for efficient post-translational modifications and ability to produce recombinant proteins with glycoforms compatible with humans at large manufacturing scales (2).

CHO cells have been demonstrated as safe hosts for recombinant therapeutic proteins for over three decades (2). There are many therapeutic proteins approved by the FDA that are produced in various CHO cells such as CHO-S, CHO-K1, CHOK1SV, CHO DG44 (3).

There is a lot of interest in decreasing time and effort required in process development of therapeutic products (4). One method that is used to decrease time and effort is the development of a platform process (5).

Authors:

Frank Agbogbo, PhD, MBA

Senior Director, Process Development
Cytovance Biologics

 

Sierra Bailey
Research Associate II
Cytovance Biologics

 

...performing the bioreactor run at 37°C throughout leads to a higher titer and a higher cumulative specific productivity.  


Read about the effect of temperature shift on product titer and viability in the development of a CHO platform. 

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References

  1. Ferrer-Miralles, N, Domingo-Espin, J, Corchero, J. L., Vazquez, E., Villaverde, A (2009). Microbial factories for recombinant pharmaceuticals. Microb Cell Factories (2019) 8:17
  2. Kim, J. Y., Kim Y-G, Lee, G. M (2011). CHO cells in biotechnology for  production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol (2012) 93:917-930
  3. Solfa, G., Smonskey M. T., Boniface, R, Hachmann, P. G., Joshi, A. D., Pierce, A. P., Jacobia, S. J., Campbell, A (2018). CHO-Omics Review: The impact of current and emerging technologies on Chinese Hamster Ovary based bioproduction. Cell Line Engineering (2018) 13:1-14
  4. Kennard, M. L., Goosney, D. L., Monteith, D, Roe, S., Fischer, D., Mott, J (2009). Auditioning of CHO host cell lines using the Artificial Chromosome Expression (ACE) technology. Biotechnology and Bioengineering (2009) 104:526-539
  5. Ha, T, K., Lee J. S., Lee, G M (2020). Platform technology for therapeutic protein production. In Cell Culture Engineering, Recombinant Protein production, Volume 9 (2020), Pages 1-22.