Optimizing Cell Culture Media – Achieving Super Soup
MONDAY, AUGUST 21, 2017 | 9:00 – 11:30 AM
To grow mammalian cells, researchers need to provide an optimal in vitro environment. The key feature of successful cell growth is the culture medium. ‘Achieving Super Soup’ requires finesse and know-how in order to combine the right ingredients at the right times under the right conditions to achieve high titers. This workshop will provide a foundation for optimizing cell culture media presented by real-world experts who will also tailor a portion of the course to fit concerns and challenges faced by the workshop participants.
9:00 Chemical Aspects of Optimizing Cell Culture Media
Jochen B. Sieck, Ph.D., Head, Perfusion Systems Laboratory, Perfusion Systems and Cell Culture Media R&D, Merck KGaA
Optimization of mammalian cell culture media (CCM) is often limited by chemical aspects. For example, nutrients can only be increased to an (un)certain concentration, which depends on the solubility of the component itself but also various other components in the medium. The stability of CCM is affected by light, temperature and oxygen sensitive components. Variability in quality of single components can dramatically impact overall performance of the CCM. This talk will present a couple of case studies how these topics could be addressed successfully and give an outlook what aspects remain to be studied further.
9:45 Development of Optimized Basal Media for Novel Cell Lines
Sven Loebrich, Ph.D., Senior Development Scientist, Upstream Process Engineering, Immunogen, Inc.
Classical fed-batch culture of Chinese Hamster Ovary (CHO) cells for the production of humanized monoclonal antibodies (IgGs) relies on optimized basal and feed media to support cell growth and productivity. Ideally, a single platform formulation of chemically defined basal media is used to support different cell lines across a multitude of programs. However, given the complexity of media formulations and the large spectrum of metabolic idiosyncrasies seen in different cell lines, designing a singular formulation that is optimized for all processes poses a formidable challenge. Here, we report a strategy for blending numerous deliberately imbalanced parental media using different mixing algorithms to identify formulations that sustain greater integrated viable cell density (IVCD) and productivity. We employ an automated liquid handler to assemble 40 new blends, and test these media in a 24-well deep well batch assay, screening for improved IVCD and IgG productivity. We find that designing imbalanced parental media in which any of >100 components is varied by one or more orders of magnitude, followed by rigorous blending and robust screening, is a viable approach to identify novel formulations capable of sustaining greater cell mass for the production of monoclonal antibodies. Multi-variate analysis can be employed to identify key components which are positively or negatively associated with cell growth, viability, and IgG productivity. This approach is theoretically capable of generating an infinite number of novel formulations, supporting production cell lines with greatly differing backgrounds.
10:15 Break
10:45 Impact of Media Components, Toxic Metabolites and Metabolic Pathways on Cellular Productivity During Bioprocess Operations
Kamal A. Rashid, Ph.D., Director, Biomanufacturing Education & Training Center, and Research Professor, Biology and Biotechnology, Worcester Polytechnic Institute
Media composition plays a significant role in cell yield and viability in the culture. Yield and viability are critical for a successful biologics production in a mammalian cell system. Cell culture media contains a mixture of amino acid, vitamins, glucose, salts and other nutrients such as growth hormones and growth factors. The requirements for these nutrients vary from one cell line to another making optimization studies a necessity for individual cell lines.
This presentation will highlight:
- Media composition and some approaches to media optimization for increased cellular productivity.
- Media development from serum supplementation to chemically defined media
- Toxic metabolites in the super soup and how to reduce/eliminate their impact
- Understanding the cell cycle and the metabolic pathways during media optimization studies
11:30 End of Short Course
Speaker Biographies:
Jochen B. Sieck, Ph.D., Head, Perfusion Systems Laboratory, Perfusion Systems and Cell Culture Media R&D, Merck KGaA
Jochen is a Biotechnologist by training. He got his PhD from ETH Zurich in Bioprocess Engineering. He worked in Novartis Bioprocess R&D before moving to become a lab head in cell culture media R&D in Merck KGaA, Darmstadt, Germany. He has more than 10 years of experience in bioreactor characterization, scale-up and scale-down of mammalian cell culture processes, perfusion and medium development.
Sven Loebrich, Ph.D., Development Scientist III, Upstream Process Engineering, Immunogen, Inc.
Sven is the Leader of the media development group where he optimizes chemically defined media to support internal development programs. He designed basal media and feed formulations and built platform processes; and has comprehensive experience with glycosylation profile tuning through media additives. Sven has also designed and executed bioreactor studies using glass 4L vessels, as well as disposable 2L and 50L models. And he’s discovered and characterized media additives for improved harvest robustness. Sven is also the Leader of a cross-functional team for an internal development program with experience as a project manager in the CMC space, closely coordinating internal and CMO teams. Sven received his Ph.D. in Biology from the Center for Molecular Neurobiology at the Hamburg University in Germany.
Kamal A. Rashid, Ph.D., Director, Biomanufacturing Education & Training Center, and Research Professor, Biology and Biotechnology, Worcester Polytechnic Institute
Dr. Kamal A. Rashid has over thirty-five years of academic experience in both research and biotechnology program development. During his career, he has developed, directed and implemented biotechnology and biomanufacturing training courses at Worcester Polytechnic Institute, Utah State University, Penn State University and internationally. He has delivered bioprocessing training programs on-site in numerous countries, including, China, Dominican Republic, Egypt, Indonesia, Iraq, Korea, Malaysia, Philippines, Puerto Rico, Vietnam, Thailand, Taiwan, and Singapore. His present research emphasis is on bioprocessing utilizing mammalian cell systems for production of recombinant proteins and vaccines. He received his Ph.D. from Penn State University with an emphasis on toxicology and genotoxic effects of environmental pollutants on human health.