Cambridge Healthtech Institute’s 10th Annual
Optimizing Cell Culture Technology
Enhancing Knowledge for Growing Cells
Part of CHI's 6th Annual The Bioprocessing Summit
August 18-19, 2014 | Renaissance Waterfront Hotel | Boston, Massachusetts
Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios
Tuesday, August 19
7:30 am Registration and Morning Coffee
7:55 Chairperson’s Remarks
Jörg von Hagen, Ph.D., Director, Global Cell Culture R & D, Merck
8:00 Cell Culture Media Improvements – Considerations from a Powder Perspective
Jörg von Hagen, Ph.D., Director, Global Cell Culture R&D, Merck
To improve the batch-to-batch consistency of dry powder cell culture media, and narrow the variations arising from chemically defined media, different strategies will be presented to control impurities in complete formulations and single ingredients that are important to understand to control cQA of biopharmaceuticals and allow the reproducible regulation of the bioprocess by simplification of, e.g, feed strategies and simpler powder handling. We will present the correlation of the media dissolution coefficient [dc] and the impact on powder solubility and homogeneity as end points depending on the formulation as a result of the concentrations of hygroscopic molecules.
8:30 An Inflatable Chamber for Cell Culture under Hypoxia
Hua Zhong, M.D., Ph.D., FCAP, Assistant Professor, Pathology and Lab Medicine, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School
Tissue hypoxia is a common pathophysiological process. Since the 1990s, numerous studies have focused on investigating cellular adaptation to experimental hypoxia. An inflatable chamber was created for cell culture under hypoxic conditions. It yielded reproducible results in experiments detecting hypoxia-induced accumulation of hypoxia-inducible factor 1 a (HIF-1 a ) and hypoxia-induced expression of HIF-1-regulated genes. Basic properties and additional utilities of the chamber will be discussed and compared to pre-existing ones.
9:00 New Approach to Release Critical Raw Materials: Risk Versus Testing-Based Approach
Lada Laenen, Ph.D., Head, Cell Culture and Microbiology, MSAT, Genzyme, a Sanofi company
Regulatory guidelines require for testing to be conducted in order to confirm safety and consistency. Conducting raw material analysis by selection of appropriate risk assessment tools and identifying test methods, to successfully meet the challenges of testing, can prevent costly production issues and possible delays. Throughout the case studies, approaches and results will be presented in order to address potential risk, impact and remediation plans when introducing new raw materials. Furthermore, control strategies and managing risks will be discussed.
9:30 POSTER HIGHLIGHT
Impact of Light Exposure on Cell Culture Performance and Product Quality
Jan Ressl, Late Stage Cell Culture Engineer I, Genentech, Inc.
9:45 Coffee Break in the Exhibit Hall with Poster Viewing
10:30 Predicting Maximal Viable Cell Density and Cell Sustainability in CHO Fed-Batch Cultures
Yung-shyeng Tsao, Ph.D., Senior Principal Scientist, BioProcess Technology and Expression, Biologics Bioprocess Development, Merck & Co.
The metabolic profiles of 14 CHO-DXB11 clones in fed-batches were studied. During the exponential growth phase their total cell density were found to be linearly proportional to their respective combined glutamine and glutamate consumption rate. The CHO clones with higher efficiency in converting glutamine and glutamate into cell mass were found to reach higher maximal total cell density as well as higher integral of viable cell concentration (IVCC) in fed-batches. This principle may be useful for clone selection.
11:00 Towards Metabolic Engineering of Mammalian Cells using 13C-Metabolic Flux Analysis
Woo Suk Ahn, Ph.D., Research Associate, Bioinformatics and Metabolic Engineering, Massachusetts Institute of Technology (MIT)
Metabolic engineering of mammalian cells can be performed due to the recent development of molecular design tools. However, selection of target genes is still one of hurdles for metabolic engineering. Currently, 13C-Metabolic flux analysis (13C-MFA) draws interests in quantifying intracellular metabolism using stable isotopic tracer and mass spectrometry. This technology enables us to identify bottleneck metabolic genes and evaluate engineered cells.
11:30 Metabolic Flux Analysis of Amino Acid Pathways in CHO Cell Culture
Véronique Chotteau, Ph.D., Researcher, CETEG Cell Technology Group, Industrial Biotechnology, KTH Royal Institute of Technology
The determination of the metabolic fluxes occurring in the cell and in interaction with its environment is key for a better knowledge of the cell metabolism in culture. Models of the metabolic fluxes provide very powerful tools to understand and simulate the cell metabolism in culture, eventually leading to process optimization. We have developed approaches to model the amino acid metabolism based on their extracellular measurement. Our strategy is to obtain a single model that includes different cell states generating a powerful tool for process optimization.
12:00 pm GPEx® Cell Line Engineering Case Studies using Multiple Mammalian Cell Lines
Andrew Sandford, Vice President, Global Business Development, Biologics, Catalent Pharma Solutions
Through case study examples, attendees will gain an understanding of how GPEx® Cell Line Engineering was incorporated into several cell line expression/ product development projects. The presentation will discuss the challenges of the overall projects, procedures completed, analysis of data, insights gained, and final conclusions that demonstrate how GPEx® technology was used to generate mammalian cells with high yields and stability, which will help speed the drug to clinic.
12:15 Enjoy Lunch on Your Own
1:15 Session Break
1:55 Chairperson’s Remarks
Michael R. Dyson, Ph.D., Senior Research Associate, Biochemistry, University of Cambridge, and Group Leader, IONTAS, Ltd.
2:00 AMBR™ 48 as a Tool for Process Development and Characterization for the Manufacture of a Biosimilar in CHO Cells
Matthew Zustiak, Ph.D., Principal Scientist, Cell Culture Development, Gallus Biopharmaceuticals
A QbD approach is effective in the process development for the development of a biosimilar since the exact critical quality attributes are known. A high-throughput method of process development and characterization is desired. We used the Ambr™ 48 system as a scale-down model for process development and as a tool for key process parameter identification and characterization in the upstream process for the manufacture of a biosimilar. The results of this development will be discussed.
2:30 Scalable Transient Transfection for Antibody & Vaccine Production in Multiple CHO, Insect, and Other Mammalian Cells
James Brady, Ph.D., Director, Technical Applications, MaxCyte, Inc.
Flow electroporation streamlines biotherapeutic and vaccine development by enabling large-scale transient gene expression directly in the cells of interest including multiple CHO strains, insect cells and other mammalian cell lines. Flow electroporation produces significantly higher yields for a variety of proteins including antibodies, antibody-like molecules, and vaccines, when compared to other transfection methods. Data will be presented demonstrating the versatility, scalability, and multi-gram production capacity of flow electroporation.
3:00 Mammalian Cell Fluid Mechanics and Scale-Up/Scale-Down Considerations
Jeffrey Chalmers, Ph.D., Professor, Chemical and Biomolecular Engineering; Director, Analytical Cytometry Shared Resource, Comprehensive Cancer Center, The Ohio State University
The perception of “shear sensitivity” has historically put an arbitrary upper limit on agitation and aeration in bioreactor operation; however, as cell densities and productivities continue to increase, mass transfer requirements can exceed those imposed by these arbitrary low limits. This presentation will mainly focus on publications from both academia and industry, and some recent experimental data on microcarrier cultures regarding the effect of hydrodynamic forces on industrially relevant animal cells, and on the general observation with respect to scale-up.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Raman Spectroscopy as a PAT Tool
Sofie Goetschalckx, Head, Cell Culture Manufacturing Science Team, MSAT, Cell Culture and Microbiology, Genzyme, a Sanofi Company
To better understand critical quality attributes of manufactured biologics, and apply the FDA’s process analytical technology (PAT) initiative, industry increasingly seeks means by which critical process parameters can be monitored and controlled in real-time. Raman spectroscopy can be a very interesting tool as it is useful for PAT and QbD applications and allows for real-time, quick, in situ monitoring and bioprocess control. Data presented outlines the use of Raman spectroscopy in monitoring cell culture performance in recombinant protein production.
4:45 Comprehensive, Quantitative Bioprocess Productivity Monitoring Using Fluorescence EEM Spectroscopy and Chemometrics
Alan G. Ryder, Ph.D., Senior Lecturer, Nanoscale Biophotonics Laboratory, School of Chemistry, National University of Ireland, Galway
Fluorescence excitation-emission matrix (EEM) spectroscopy is used for quantitative predictive analysis of glycoprotein production in a CHO cell fed-batch process. EEM spectra of complex solutions are very sensitive to compositional change and as cultivation progressed, the emission of tyrosine, tryptophan, and the glycoprotein product showed significant differences, and this was used to follow culture progress via chemometrics. A second aspect of the study involved developing quantitative predictive models of process performance based on glycoprotein yield. This methodology opens the possibility of early-stage intervention for poorly performing lots.
5:15 End of Conference
Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios