Cambridge Healthtech Institute’s 13th Annual
Optimizing Cell Culture Technology
Enhancing Knowledge for Growing Cells
Part of CHI's Ninth Annual The Bioprocessing Summit
August 21-22, 2017 | Westin Copley Place | Boston, MA
The Optimizing Cell Culture Technology is the leading international conference focused solely on culturing cells. As industry needs increase, greater pressure is put on cell culture to meet growing demands. This meeting explores today’s
evolving strategies and technologies for improving mammalian cell cultivation, including omics technologies and synthetic biology. Industry experts offer insights into optimizing conditions as well as cell biology in an effort to improve yield, while
also addressing the future of cell culture in an expanding market where standards of quality continue to rise.
The agenda again features a session focused on CHO (Chinese Hamster Ovary cells), as well as small-group breakout discussions that provide the opportunity to discuss important topics with peers from around the world.
Monday, August 21
8:00 am Short Course Registration Open
9:00 – 11:30 Recommended
Morning Short Courses*
SC1: Optimizing Cell Culture Media
* Separate registration required
11:30 Main Conference Registration Open
1:00 pm Chairperson’s Opening Remarks
Alan Dickson, Ph.D., Director, Centre of Excellence in Biopharmaceuticals (COEBP), and Professor, Biotechnology, The University of Manchester
1:10 OPENING KEYNOTE PRESENTATION:
Innovations in Process Science within an End-to-End Integrated Development Organization, Delivers on Speed, Cost and Quality Objectives for Biogen’s Biotherapeutic Pipeline
Rashmi Korke-Kshirsagar, Ph.D., Director, Cell Line and Cell Culture
Development for Proteins, Biogen
Biogen has developed platform approaches for our various unit operations. Investment in process sciences, innovation and technology development were enabling factors and will be discussed. This has allowed us to routinely deliver high-productivity
processes for early clinical programs. During late-stage process development and characterization of the processes and the quality attributes, we have realized the value of end-to-end integration of DS and DP development organization. Deep bioprocess
knowledge and understanding coupled with integrated analytical characterization and formulation development has delivered the optimal solution of high volumetric productivity, low-cost manufacturing, and desired product quality. Optimization of
this knowledge has translated into the end-to-end early and late-stage approach for our future pipeline.
1:45 Cell-Derived Extracellular Matrix: Isolation, Analysis and Functional Studies
Josephine C. Adams, Ph.D., Professor, Cell Biology, Biochemistry, University of Bristol
Metazoan extracellular matrix (ECM) consists of fibres and networks of collagens, glycoproteins and proteoglycans. The ECM micro-environment has important roles in cell survival, differentiation, motility and mechanical force-balance in tissues. Isolation
of ECM is complicated by its insoluble, cross-linked nature and the need to separate ECM from cellular proteins. I will discuss my laboratory’s approaches with a scaleable method to isolate ECM from adherent, cultured cells for downstream
2:15 Use of Multivariate Data Analysis to Improve Cell Culture Performance in a Commercial Process -- Case Study
Betty Agudelo-Rewey, M.S., Principal Engineer, Drug Substance Process Development,
Process variability can lead to poor process performance and can impact product quality attributes. Cell culture manufacturing processes are multivariate by nature which can make it more difficult to determine the sources of input variation and
therefore make it more difficult to diagnose and troubleshoot issues. The application of appropriate multivariate data analyses can significantly aid in signal identification, diagnosis, understanding of process shifts, as well as in the identification
of improvement opportunities. A case study will be presented to demonstrate the value of this approach to control variation for a critical quality attribute while maintaining process performance.
2:45 Refreshment Break
3:15 From CHO to hMSCs, Perceptions and Reality of “Shear Sensitivities”
Jeffrey Chalmers, Ph.D., Professor, Chemical and Biomolecular Engineering, The Ohio
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. The perception of “shear sensitivity” has historically put an arbitrary upper limit on agitation and aeration in bioreactor operation. 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.
3:45 ChemStress Fingerprinting: A Simple, Novel Process Control Strategy for CHO Cell Factories.
Jerry Clifford, Ph.D., MBA, COO, Valitacell
Valitacell is developing technologies that have been specifically designed to provide a desired level of process control while at the same time enabling optimal leverage of the cell factory for each individual product. Here we discuss new methodologies
to measure and predict clone-specific functional stability using rapid, multiparallel ChemStress fingerprinting.
4:00 Understanding and Modulating the Quality Attributes of a Novel Class of Therapeutic Proteins through Upstream Process Development -- Case Study &New, Unpublished Data
Ravindra Pangule, Ph.D., Associate Principal Scientist, Process Development & Engineering,
Merck Research Laboratories
Next-generation biotherapeutic proteins, engineered with unique and novel biology, have attracted more attention in recent years. However, understanding and controlling the quality attributes for those proteins are still in early stages. I will share our experience with two molecules from a novel class of therapeutic proteins as case studies. I will present the strategies designed and implemented to address product quality liabilities associated with these molecules. Specifically, media supplementation and process optimization approaches were taken to control post-translational modifications and product-related impurity levels.
4:30 Breakout Discussions
This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish
collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.
Biggest Challenges Today Limiting Scale-Up
Jeffrey Chalmers, Ph.D., Professor, Chemical and Biomolecular Engineering, The Ohio State University
- Clone selection?
- Optimized media?
- Different equipment/different sites?
Standardization versus Customization of Disposables
Stefan Schmidt, Ph.D., M.B.A., Senior Vice President, Process Science and Production, Rentschler Biotechnology
- Lead times
- Inventory cost
- Supplier sourcing
- Quality control
Cell Engineering to Optimize Therapeutic Protein Production
Helene Faustrup Kildegaard, Ph.D., Senior Researcher and Co-Principal Investigator, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark
- To which extent is cell engineering being applied to optimize protein production?
- What is the potential of applying cell engineering?
- Which technologies are being applied?
- What are the concerns, hurdles and successes?
5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
Tuesday, August 22
7:30 am Registration Open and Morning Coffee
7:55 Chairperson’s Remarks
Jeffrey Chalmers, Ph.D., Professor, Chemical and Biomolecular Engineering, The Ohio State University
8:00 Is It Time to Reinvent Basic Cell Culture Medium?
Svetlana V. Komarova, Ph.D., Associate Professor, Dentistry, McGill University
The quality of the cell culture media is critically important for the success of in vitro experiments. Four synthetic media formulations developed more than 50 years ago – DMEM, RPMI 1640, MEM, and Medium
199 (M199) – are used in ~90% of published in vitro studies. However, the levels of electrolytes and carbohydrates in these media formulations largely deviate from physiological values. The potential
consequences of such deviations will be discussed.
8:30 Systems Biology Approach in the Development of Chemically-Defined Media for Production of Protein Therapeutics in CHO Cells
Wai Lam W. Ling, Ph.D., Senior Principal Scientist and Group Director, Process Development
& Engineering, Biologics & Vaccines BioProcess Development, Merck Research Labs
9:00 Assessing Mycoplasma Contamination of Cell Cultures by qPCR using a Set of Universal Primer Pairs Targeting a 1.5 kb Fragment of 16S rRNA Genes
Denis Gerlier, M.D., Ph.D., Emeritus Director of Research, CNRS, International Center
for Infectiology Research (CIRI), SFR Bioscience, University of Lyon
Mycoplasma are a formidable threat both in fundamental research by perverting a whole range of cell properties and functions, and in the pharmacological use of cells and cell-derived products. I shall report a universal, sensitive, and
quantitative assay based on the amplification of a 1.5 kb fragment covering the 16S rDNA of the Mollicute class, and its usefulness to check mycoplasma contaminations in BSL2, BSL3 and BSL4 viral stocks.
9:30 Improve Efficiency and Eliminate Human Error with Automated Sampling and Feed Control
Frederick Schneider Jr., Director of Sales, Flownamics
What if you could reduce or completely eliminate the time spent sampling manually each day and or on weekends? In this technical seminar, you will learn how the Seg-Flow automated sampling platform will improve your process conditions
and performance, decrease sample volume requirements and save you both time and money.
9:45 Coffee Break in the Exhibit Hall with Poster Viewing
10:30 Quality by
Design Control or Why We Could use a Different Understanding of the Design Space
von Stosch, Ph.D., Senior Manager, Fermentation, GlaxoSmithKline Pharma GmbH
Real-time control of the critical product quality attributes via appropriate manipulation of the process parameters requires:
1) Understanding how the process parameters impact on the quality attributes
2) The quality attributes to be measurable in some form on-line.
Astonishingly (or not), the Quality by Design (QbD) roadmap, looks much like a guide to realize real-time product quality control, only that process
dynamics seem to be overlooked. In this contribution, the implications of considering the process dynamics in the QbD roadmap are discussed and a strategy for exploiting the dynamics in an intensified Design of Experiment method is
demonstrated, which can significantly reduce the number of experiments required to achieve process understanding.
11:00 SPR Biosensing of Monoclonal Antibody during Cell Culture
Gregory De Crescenzo, Ph.D., Professor, Chemical Engineering, Polytechnique
A surface plasmon resonance-based assay has been developed to quantify monoclonal antibody within the supernatant of a mammalian cell and confirm Mab binding to its antigen in a single biosensing experiment. Our results were in excellent
agreement with quantification performed by Protein-A HPLC. While the approach is of interest for off-line analysis, its application to at-line characterization will be discussed.
11:30 Softsensors: New Approach for Process Monitoring Cell Growth in Small-Scale Fermentation Systems --New, Unpublished Data
Wolfgang Paul, Ph.D., Group Leader, Cell Culture Research, Roche Innovation Center Munich,
Roche Diagnostics GmbH
The new approach is a soft sensor, which takes online signals of the bioreactor, which are correlated to cell growth to estimate the cell growth. The soft sensor based on multiple linear regression and on artificial neural network to estimate
the cell growth as online signal during cultivation time. The soft sensor was successful implemented in the multiple small scale bioreactor system and estimated values with high confidence and low root mean squared error below 15%.
12:00 pm Using Metabolomics to Understand Genetically Determined and Environmental Cell Culture Needs
Kendra Hightower, Ph.D., Study Director, Metabolon
12:30 Luncheon Presentation: “Difficult-to-Express” Proteins: Solutions for Clinical Manufacturing
Scott Waniger, Vice President, Bioprocessing, Cell Culture Company
Advances in protein engineering have made complex biologic therapeutics more prominent. These molecules are sometimes labeled as “difficult-to-express” proteins due to low protein titers and/or sensitivity to environmental
conditions, making clinical manufacturing slow and expensive. Acusyst perfusion systems provide an alternative to traditional fed-batch systems for clinical manufacturing, enabling efficient production of difficult-to-express proteins.
This talk presents case studies demonstrating the benefits of Acusyst systems including enhanced yields, reduced costs and improved scalability.
1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing
1:55 Chairperson’s Remarks
Shahram Misaghi, Ph.D., Senior Scientist, Early Stage Cell Culture, Genentech -- A Member of the Roche Group
2:00 FEATURED PRESENTATION:
Genome Editing of CHO Cells: Molecular Tinkering or Revolutionary Change?
Alan Dickson, Ph.D., Director, Centre of Excellence in Biopharmaceuticals (COEBP),
and Professor, Biotechnology, The University of Manchester
What’s new? Genome editing opens up the possibilities to revolutionise CHO cell platforms…or is it to discover that nature got there before us? In this case study, I will describe some of our recent work to engineer novel
CHO cell phenotypes and focus on factors that maximise the match between prediction and outcome.
2:30 POSTER SPOTLIGHT
Transposon-Based Technology Enhances the Generation of Stable and High-Producing CHO Clones for Industrial Production of Recombinant
Laura Strippoli, Ph.D., Research Scientist, DiaSorin Research Center of Gerenzano
3:00 CRISPR Tools for CHO Cell Engineering -- New, Unpublished Data
Helene Faustrup Kildegaard, Ph.D., Senior Researcher and Co-Principal
Investigator, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark
CHO cells are widely used in the industry as a host for the production of complex pharmaceutical proteins. Thus, accelerated genome engineering of CHO cell factories to improve product yield and quality is of great interest. In this
talk, our recent efforts in accelerating genome engineering of CHO cell factories will be presented. Topics will include targeted integration and multiplexing of gene knockouts.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Advanced Process Monitoring and Hybrid Modeling: A Basis for QbD/PAT Implementation in Mammalian Cell Culture Bioprocesses?
Gerald Striedner, Ph.D., Associate Professor, Biotechnology, University
of Natural Resources and Life Sciences (BOKU), and Principal Investigator, Austrian Center of Industrial Biotechnology (ACIB)
- Advanced on- and offline monitoring strategies
- Implementation of hybrid modeling approaches in mAB production processes
- Transferability of hybrid models along scales from shaker to laboratory and pilot scale
- Towards Model predictive control (MPC) in bioprocesses
4:45 BiP the Alarm; High Intracellular Seed Train BiP Levels Correlate with Poor Production Culture Performance, a Case Study of a DHFR-Deficient CHO Cell Line
Shahram Misaghi, Ph.D., Senior Scientist, Early Stage Cell Culture, Genentech
-- A Member of the Roche Group
Consistent cell culture performance is a prerequisite to ensure product quality consistency and achieve productivity goals to manufacture recombinant protein therapeutics, including monoclonal antibodies. To ensure a smooth transition
from seed train through inoculum train to the production culture, parameters such as viability, viable cell count (VCC), packed cell volume (PCV), glucose consumption, and pH are closely monitored. Here we report a peculiar observation
where high levels of intracellular BiP in seed train cultures are consistently predictive of poor cell culture performance in the subsequent inoculum and production cultures for a monoclonal antibody produced in CHO cells.
5:15 Close of Conference
6:00 – 8:30 Recommended
Dinner Short Course*
SC7: Analytical Strategies for Comparability in Bioprocess Development
Christine P. Chan, Ph.D., Principal Scientist/Technical Lead, Global Manufacturing Science & Technology, Specialty Care Operations, Sanofi
* Separate registration required