2013 Archived Content
August 19-20, 2013
Cambridge Healthtech Institute’s 9th Annual
Optimizing Cell Culture Technology
Enhancing Knowledge for Growing Cells
Day 1 | Day 2 | Short Courses | Download Brochure
Tuesday, August 20
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
Yuval Shimoni, Ph.D., Principal Engineer, Manufacturing Sciences, Bayer HealthCare LLC
8:30 Featured Presentation:
Karyotypic Profiling of Recombinant Gene Expression in Amplified CHO Cell Lines
Alan Dickson, Ph.D., Director, Centre of Excellence in Biopharmaceuticals (COEBP); Professor, Institute of Biotechnology, University of Manchester - Biography
This presentation will describe the heterogeneity and stability/instability of recombinant genes integrated into the chromosomes of CHO cell lines and is part of our developing understanding of CHO cell genomics. These data address the relationships between site of integration and expressibility and how genome structure changes in response to methotrexate amplification protocols.
9:00 Engineering a CHO Host for Improved Antibody Titer
Shirley Peters, Ph.D., Research Scientist, Protein Expression and Purification Group, UCB Celltech - Biography
A transient expression system has been developed at UCB. This system employs a number of culture conditions which have provided incremental increases to transient antibody yields. The most substantial impact on yield was observed when using a CHO host that was engineered to express exogenous XBP1-S and ERO1La. The generation of this CHO host (CHOS-XE) will be described and how this cell line and transient culture conditions have improved our antibody yields. Data will also be presented on the use of CHOS-XE in generating stable cell lines.
9:30 13C Metabolic Flux Analysis of an Industrial CHO Cell Culture
Jamey D. Young, Ph.D., Assistant Professor, Chemical and Biomolecular Engineering, Molecular Physiology & Biophysics, Vanderbilt University - Biography
Cell metabolism can vary considerably over the course of a typical fed-batch antibody production process. We performed 13C labeling experiments and metabolic flux analysis to characterize CHO cell metabolism during four separate phases of a fed-batch culture designed to closely represent industrial process conditions. Overall, we found that a highly oxidative state of metabolism corresponded with peak antibody production, whereas peak cell growth was characterized by a highly glycolytic metabolic state.
10:00 Increasing Viral Yields in the Corning HYPER (High Yield PERformance) Technology
Kate Strathearn, Ph.D., Cell Applications Scientist, Corning Life Sciences - Biography
Producers of vaccines and other biologics have used traditional technologies for a number of years. Corning offers a new breakthrough technology which allows greater yields in a smaller footprint. The HYPER Technology platform utilizes a gas permeable film as an attachment surface, eliminating the requirement for an air gap found in traditional cell culture vessels.
10:15 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Implementing Metabolomics in Bioprocessing Applications
Ulrike Rennefahrt, Ph.D., Senior Research Scientist, Metanomics GmbH - Biography
The metabolism of cells changes drastically during fed-batch culture due to environmental adaptation and transition from exponential to stationary growth. Metabolamics was utilized to evaluate key metabolic features of two CHO cell lines with respectively low antibody expression. Intra- and extracellular metabolites were investigated and hypotheses will be shared how to improve productivity by optimizing media formulation, feeding strategy and metabolic engineering.
11:30 Unfolded Protein Response (UPR) During CHO Cell Production Culture
Zhimei Du, Ph.D., Senior Scientist, Amgen
A UPR-specific monitoring system was created that can be used to detect and quantify endogenous UPR activation levels in real-time during production. Using this monitoring system, it was found that recombinant cells differed in their UPR induction patterns. It also revealed that cell culture conditions can also alter UPR levels without recombinant protein expression. A discussion of how a production process can be rescued by controlling the UPR in a live growing culture will be addressed.
12:00 pm Accelerating the Scale-Up of Cell Lines Through the Use of Integrated Platforms
Peggy Lio, Ph.D., Director, Process Science & Cell Culture, GE Healthcare - Biography
The development of scalable processes for cell lines is often challenging and is influenced by many process parameters. Multiple rounds of experimental studies are typically required to optimize process scale-up conditions to maximize the performance and productivity of a lead clone thereby lengthening timelines significantly. This presentation will explore media and technology platform approaches aimed at simplifying and accelerating the timeline from clone to manufacturing.
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:55 Chairperson’s Remarks
Patrick Hossler, Ph.D., Senior Scientist III, Process Sciences, AbbVie Bioresearch Center - Biography
2:00 High-Throughput Total Sialic Acid Assay (HT-TSA)
Lam Raga Anggara Markely, Ph.D., Scientist I, Biogen Idec, Inc. - Biography
In order to optimize and consistently control the qualities of proteins produced in bioprocesses, a high-throughput method for measuring sialic acid content of the proteins (HT-TSA) is required. Here, we present an HT-TSA that can accurately, precisely, rapidly (70 min), and specifically analyze 80 crude culture samples in parallel. Moreover, we found that sample protein denaturation is crucial to ensure complete cleavage of sialic acid by sialidase. The HT-TSA can be used for many applications in cell line and bioprocess development.
2:30 Mammalian Cell Fluid Mechanics and Scale-Up/Scale-Down Considerations
Jeffrey J. Chalmers, Ph.D., Professor Department of Chemical and Biomolecular Engineering, The Ohio State University - Biography
Suspension animal cell culture is now routinely scaled up to bioreactors on the order of 10,000 liters and greater to meet commercial demand. However, the concern of the “shear sensitivity” of animal cells still remains, not only within the bioreactor, but also in the downstream processing. This presentation will mainly focus on publications from both academia and industry regarding the effect of hydrodynamic forces on industrially relevant animal cells, and on the general observation with respect to scale-up.
3:00 Evaluation of UV-C Treatment Technology for Viral Inactivation of Cell Culture Media
Lada Laenen, Ph.D., Managing Principal Scientist, Head, Cell Culture and Microbiology, Technology Division, Genzyme, a Sanofi Company - Biography
Although raw material testing should be considered part of the overall strategy in developing barriers against viral contamination, the current testing strategies are not always effective by themselves given limitation by sample size to be tested, sensitivity and specificity of the assay, etc. Cell culture media poses one of the highest risks, and for that reason, an innovative UV-C technology was applied for treating cell culture media. Cell culture evaluation studies have been completed demonstrating feasibility of this technology for implementation in biomanufacturing. Challenges and innovation of this approach will be discussed.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Controlling On-Chip Gas Partial Pressure
Samuel P. Forry, Ph.D., Research Chemist, Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST)
Gas partial pressures (e.g. O2, CO2) are critically important in biology. For cell-based assays, carbon dioxide is tightly maintained at 5% to mimic the in vivo environment, and differences in oxygen levels can lead to varying experimental outcomes. We have developed on-chip strategies to simultaneously modulate gas partial pressures and mitigate pervaporation. This has allowed us to demonstrate long-term, stopped-flow microfluidic cell culture without requiring the use of bulky and expensive cell culture incubators.
4:45 Matrix-Free 3D Cell Spheroid System for Bioprocessing and Nanomaterials Evaluation
Mark DeCoster, Ph.D., Associate Professor, Biomedical Engineering, Louisiana Tech University - Biography
We have established a novel matrix-free 3D cell spheroid system that permits growth and maintenance of normal cells, stem cells, and cancer cells. In addition to processing of soluble drugs, we are also using our 3D system to evaluate bioprocessing of micro- and nano-materials. We have measured binding and internalization of these materials as well as toxicity of nanomaterials. It is anticipated that 3D systems will provide new information for materials bioprocessing compared to traditional 2D cell culture systems due to differences in diffusion and cell-cell communication.
5:15 End of Day & Registration for Dinner Short Courses
6:00 Dinner Short Courses*
*Separate registration required
Day 1 | Day 2 | Short Courses | Download Brochure