CHORUS CyberSpeedCell Platform: CHORUS-CSCP

It is common knowledge that biopharmaceuticals using CHO production cell lines are the main growth force for the increase in revenue observed in biopharmaceuticals. Many of these blockbusters have in the meantime come of age, have lost patent protection, are produced in large quantities all over the world, and have made the transition from specialty medication to commodity medicines. This was made possible over the last decade by significant increases in Viable Cell Densities achieved in bioprocesses, however, the underlying technology has remained virtually the same. It is therefore time to set the stage for a revolutionary transition also with respect to the production process, including both cell line development and process optimisation, which have to be seen as a single and synergistic effort. We here present a research project that aims to establish such a technology within the next 5 years.

Goals: Establishment of a comprehensive, fast and efficient cell line development and production pipeline that allows:

  • Rapid Production of Material for the preclinic within 2 weeks
  • Establishment of a MCB of production clones within 6 weeks
  • Production of 5-10g/l commodity biologics in a standard process of 7 day duration


To achieve this goal several puzzle pieces need to come together:

  • optimised host cell line with fast growth, high production capacity
  • genomic stability of the host cell line
  • an optimised selection system that allows insertion of genes into pre-determined and preoptimised loci of the chromosome
  • rapid removal of cells that have not performed the gene exchange
  • Rapid generation of material for preclinical testing from the same cell lineage that is later used for production
  • optimised cloning procedure for fast clone recovery
  • maintained viability for high yields
  • process-regulated gene expression based on autologously regulated endogenous promoters
  • controlled switch to high qP phenotype


How to achieve these
Many of the above can only be achieved with a detailed knowledge on the molecular build-up of CHO cells, which, due to absence of genomic sequence information, has not been available so far. Recently, this information has become available, both for CHO cells and the Chinese Hamster, and will now set the stage for intelligent engineering and optimisation of the cell line for enhanced performance as well as for developing tools to monitor and control bioprocesses at a previously unavailable level of control.
The following paragraphs describe the different puzzle pieces in the order that they come into play during a typical cell line and process development campaign. During the development phase of this platform, the sequence will be in order of ease of realisation and availability. Thus the initial focus will be on achieving faster growth, a more stable phenotype and increased productivity.

Potential Partners
Potential partners of CHORUS-CSCP are pharmaceutical companies involved in research and/or production as well as Contract Manufacturing Organisations (CMO´s) interested in an optimised CHO cell line development and process platform.


Timeline:


Chorus Timeline