CONCLUSION
Systematic feed medium development approaches were successfully used to enable the transition from a peptone-containing process
to a process using chemically-defined basal and feed media. An iterative process was used to increase titers based on the
metabolic needs of specific cell lines. In addition, we have successfully conducted filterability, medium preparation, and
scale-up studies. These CD formulations have the potential to increase process robustness, generate higher titer processes
with acceptable product quality, and be used for further medium optimization efforts.
ACKNOWLEGEMENTS
The authors would like to acknowledge the contributions of Gayle Derfus, Roberto Flores, Jennifer Autsen, Joana Caria, Dacia
Brooks, Masaru Shiratori, and Robert Shawley for their guidance, ideas, and support.
Efren Pacis is a senior research associate, Jincai Li is a senior engineer, Ashraf Amanullah is a director, and Feng Li is a senior engineer, all at Oceanside Pharma Technical Development, Genentech, Inc. Oceanside, CA, 760.231.2127, fengl@gene.com Natarajan Vijayasankaran is engineer II and Martin Gawlitzek is a senior scientist, both at late stage cell culture, US Biologics Pharma Technical Development, Genentech, Inc., South
San Francisco, CA.
REFERENCES
1. Fike R. Nutrient supplementation strategies for biopharmaceutical production, Part 1: Identifying a nutrient supplementation
formulation. BioProcess Int. 2009;7(10): 44–51.
2. Fike R. Nutrient supplementation strategies for biopharmaceutical production, Part 2 Feeding for optimal recombinant protein
production. BioProcess Int. 2009;7(11):46–52.
3. Vijayasankaran N Li J, Shawley R, Chen A, Shiratori M, Gawlitzek M, Li F, Kiss R, Amanullah A. Animal cell culture media.
In: Flickinger MC, ed. Encyclopedia of Industrial Biotechnology, Bioprocess, Bioseparation, and Cell Technology. New York:
John Wiley & Sons, Inc. 2010; p. 261–75.
4. Heidemann R, Zhang C, Qi H. Larrick Rule J, Rozales C, Park S, Chuppa S, Ray M, Michaels J, Konstantinov K, Naveh D. The
use of peptones as medium additives for the production of a recombinant therapeutic protein in high density perfusion cultures
of mammalian cells. Cytotechnol. 2000;32(2):157–67.
5. Merten, OW. Virus contaminations of cell cultures —A biotechnological view. Cytotechnol. 2002;39(2):91–116.
6. Grosvenor S. The role of media development in process optimization: an historical perspective. BioPharm Int Suppl. Guide
to Protein Production. 2008 Jun: pp 28–36.
7. Hodge G. Media development for cell Culture. Biopharm Int. 2005;18(5):54–57 .
8. Arunakumari A, Dai X, Goldstein J, Kloth C, Ghebremariam H, MacIsaac G, Wagner M. The impact of cell culture medium on
cell line and process development and timelines and strategies. BioPharm Int Suppl. Advances in Fermentation and Cell Culture:
the keys to upstream productivity; 2009 June: pp. 4–15.
9. Ishaque A, Al-Rubeai M. Role of vitamins in determining apoptosis and extent of suppression by bcl-2 during hybridoma
cell culture. Apoptosis 2002;7(3):231–9.
10. Ducommun P, Ruffieux PA, von Stockar U, Marison I. The role of vitamins and amino acids on hybridoma growth and monoclonal
antibody production. Cytotechnol. 2001;37(2):65–73.
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