Animal component free cell culture media development: The approach from the North
January 27-31, 2019
Cell therapies have been recognized as a promising treatment for various diseases including a wide range of malignancies. Hundreds of studies investigating the efficacy of cell infusions in terms of response level, duration and survival are currently in Phase1-2 clinical trials. Several research groups have developed successful protocols for the ex vivo expansion of therapeutic progenitor cells. However, upon the establishment of good manufacturing practice (GMP) standards, most established protocols are problematic mainly due to the presence of xenogeneic or human-derived components which introduce another level of product variability and regulatory complexity. At CCRM, we established a top down process for the development of cGMP-compliant, animal component free (ACF) cell culture media using a combination of mass spectrometry based multi-omics media interrogation and a DOE based, fully automated, high-throughput cell culture screening. Briefly, our media development pipeline can be described in three phases. Firstly, we define the solution space by interrogating a complete, fully supportive, serum-containing cell medium. Mass spectrometry based, open profile proteomics and metabolomics analyses is what allows us to identify the components that are available to the cells. We then reduce the solution space by utilizing the same multi-omics approach on depleting media during a time series interrogation of batch cell cultures. Based on the concentration fluctuations of the different media components, we identify the ones that are possibly correlated with key outcomes, such as cell growth. Finally, once we identify the correlated components, we design a multifactorial DOE based high-throughput screening (HTS) experiment that allows us to pick the critical media components and optimise their concentrations using a cutting edge, entirely enclosed, liquid handling robot.
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Panos Chrysanthopoulos, Anthony Eiliazadeh, and Sagar Kokal, "Animal component free cell culture media development: The approach from the North" in "Advancing Manufacture of Cell and Gene Therapies VI", Dolores Baksh, GE Healthcare, USA Rod Rietze, Novartis, USA Ivan Wall, Aston University, United Kingdom Eds, ECI Symposium Series, (2019). http://dc.engconfintl.org/cell_gene_therapies_vi/101