Cambridge Healthtech Institute’s 15th Annual

Optimizing Cell Culture Technology

Enhancing Knowledge for Growing Cells

August 12-13, 2019


Optimizing Cell Culture Technology” has long been considered the ‘must attend’ international conference focused solely on culturing cells. This leading meeting explores today’s evolving strategies and technologies for improving mammalian cell cultivation, including genome engineering, CRISPR, modeling and computational insights and analysis in the continuing efforts to improve yield. The conference will include a session focused on culturing CHO cells (Chinese Hamster Ovary), as well as discussions of breakthrough technologies and analytical approaches that support the tasks at hand and lead to greater productivity. Industry experts provide insights into optimizing conditions as well as cell biology in the effort to improve yield, while also addressing the future of cell culture in an expanding market where demand continues to increase.

Final Agenda

Monday, August 12

7:30 am Short Course Registration Open and Morning Coffee

Waterfront 1C

8:30-11:00 Recommended Short Course*

SC1: Optimizing Cell Culture Media


Jana Mahadevan, PhD, Jana has a accountSenior Scientist, Cell culture Perfusion Media & Bioprocess Development, MilliporeSigma, Merck KGaA

Ana Luz Quiroga Campano, PhD, Postdoctoral Fellow, The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology 
Michael Butler, PhD, CSO, Cell Technology, National Institute for Bioprocessing Research and Training (NIBRT)


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 as well as a look at how media development is being innovated. Cell Culture Media experts will also tailor a portion of the course for interactive discussion per the concerns and challenges faced by workshop participants.

11:00 Main Conference Registration Open


Harborview 1

12:30 pm Chairperson’s Opening Remarks

Alan G. Ryder, PhD, Professor, Nanoscale Biophotonics Laboratory, Chemistry, National University of Ireland Galway

12:40 KEYNOTE PRESENTATION: Know What You Know – Cross-Project Knowledge Management

Bechmann_JanJan Bechmann, PhD, Associate Director, Late-Stage Upstream Process Development, Boehringer Ingelheim Pharma GmbH & Co. KG

Developing biopharmaceutical processes is a knowledge-intensive endeavor that is constantly challenged by growing market demands, competition and increasing regulatory requirements. In upstream process development, detailed a priori knowledge about how process performance and product quality are affected by cell systems and process designs is required throughout all development stages. Case studies ranging from clone selection to late-stage process risk assessment demonstrate that cross-project knowledge management is key in this context.

1:10 FEATURED PRESENTATION: Very High Cell Density Perfusion Culture for the Production of Biologics Using CHO Cells or HEK293 Cells

Chotteau_VeroniqueVéronique Chotteau, PhD, Researcher Principal Investigator, Cell Technology, Industrial Biotechnology, KTH Royal Institute of Technology

These last years, we have carried out various studies of very high cell density perfusion processes for different CHO and HEK293 cells, among others, in our new small-scale 200 mL perfusion stirred tank bioreactor now integrated with down-stream process. Very high cell density enables fantastic intensification in small footprint but requires a better understanding of these new processes. We will review what we have learned from phenotypic and omics characterization of these intensified processes.

1:40 On-Line and Off-Line Monitoring of Cells for Growth and Productive Capacity during a Bioprocess

Butler_MichaelMichael Butler, PhD, CSO, Cell Technology, National Institute for Bioprocessing Research and Training (NIBRT)

Maintenance of cell viability during a bioprocess is crucial for productivity and product quality. The traditional approach involves off-line testing using dye exclusion at fixed points throughout the process. Novel methods of on-line digital holography, dielectric spectroscopy and impedance flow cytometry can provide a more complete picture of the state of cells during a bioprocess. Such methods compare well with off-line dye exclusion methods and conventional flow cytometry.

2:10 Refreshment Break


Harborview 1

2:30 Towards Model Predictive Control of Cell Culture Bioprocesses

Striedner_GeraldGerald Striedner, PhD, Associate Professor, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU)

Today, quality by testing is still the gold standard in bioprocesses. The production process is fixed and tightly specified to guarantee a constant product quality. However, out-of-specification events often result in batch rejections. Therefore, we applied intensified Design of Experiment (iDoE) to quickly screen a defined design space of a CHO fed-batch process. Hereby, a hybrid model is created that is enhanced by the data. This model will be used in the future for model predictive control to avoid batch rejections.

3:00 Leaving behind Static Process Descriptions – Using Hybrid Modeling and Intensified Design of Experiments to Better Describe Bioprocesses

Duerkop_MarkMark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU)

Process development and characterization is a very time and resource intense work. Most of the times only the endpoints of the processes are described, neglecting process dynamics. As an alternative approach we used intensified Design of Experiments, model-based Design of Experiments and hybrid models to not only overcome the endpoint evaluation problem of bioprocesses, but to present a solution for a better and robust design space description.

3:30 Talk Title to be Announced

Tan_KevinKevin Tan, PhD, Senior Scientist, FUJIFILM Irvine Scientific Inc.

3:45 Session Break

3:55 Plenary Keynote Session View details

5:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

6:30 End of Day

Tuesday, August 13

7:30 am Registration Open and Morning Coffee


Harborview 1

7:55 Chairperson’s Remarks

Uwe Jandt, PhD, Senior Research Associate, Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology (TUHH)

8:00 FEATURED PRESENTATION: A Reference Genome for the Community and Application to Understanding and Predicting Quality

Lee_KelvinKelvin Lee, PhD, Professor, NIIMBL, University of Delaware

Recently, there has been a significant shift in the community towards the development of community-wide resources such as in the develop of reference genomes. In this presentation, we will discuss the latest version of the CHO genome community’s reference genome and present applications to predicting product quality attributes such as glycosylation.

8:30 Developing a Transient CHO Expression Platform with N-Glycan Compositions Consistent with Stable CHO

Zhong_XiaotianXiaotian Zhong, PhD, Senior Principal Scientist & Lab Head, BioMedicine Design, Pfizer Research Labs

Developing a robust transient expression platform in CHO, the preferred host for many clinical and commercial products, offers a start-to-end quality alignment advantage for therapeutic protein discovery. This talk will present our recent efforts in developing a transient CHO platform to enabled efficient sialylation of N-glycans. The talk will also describe new strategies in optimizing transient CHO system with N-glycan compositions consistent with those from stable CHO production.

9:00 Strategies for the Generation of Difficult-to-Express Protein Targets

Rana Sidhu, PhD, Protein Expression Lead, UCB Biosciences

UCB is a global biopharmaceutical company that develops therapeutics for severe diseases in neurology and immunology therapeutic areas.  The Protein Expression group within the New Medicines team generates protein targets for gene to structure analysis and biochemical assays.  In this presentation I will describe strategies for the expression of difficult-to-express proteins with case studies using Flow Electroporation and BacMam-mediated protein expression as tools for gene delivery. 

9:30 Optimizing Yield and Improving Overall Culture Performance with Metabolomics

Keppler_BrianBrian Keppler, Director, Discovery and Translational Sciences Metabolon, Inc.

Global biochemical profiling provides an informative assessment of the metabolome, which is reflective of active biology.  Through metabolomics, expanded opportunities for culture performance improvements can be identified across the bioprocess lifecycle.  Such a data stream enables the interrogation of genetic, environmental and process design factors which influence the final product.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)


Harborview 1

10:30 Application of 13C Flux Analysis to Identify High-Productivity CHO Metabolic Phenotypes

Young_JameyJamey Young, PhD, Associate Professor, Chemical and Biomolecular Engineering, Vanderbilt University, and  Co-Founder and Chief Scientific Officer, Metalytics LLC

Identifying metabolic phenotypes that promote high expression is a major goal of the biotech industry. We conducted a series of 13C flux analysis studies to examine the metabolic response to IgG expression during early stationary phase of CHO cell cultures. Lactate consumption and citric acid cycle fluxes were most strongly associated with specific IgG productivity. These studies indicate that enhanced oxidative metabolism is a characteristic of high-producing CHO cell lines.

11:00 Glycosylation Flux Analysis of CHO Cell Culture Production of Monoclonal Antibodies

Gunawan_RudiyantoRudiyanto Gunawan, PhD, Associate Professor, Chemical and Biological Engineering, University at Buffalo - SUNY

The glycosylation of therapeutic monoclonal antibodies (mAbs) has functional and structural significance, and is a critical quality attribute. There exists naturally occurring heterogeneity in mAb glycosylation during fermentation, which is affected by numerous process parameters. In this talk, I will describe in silico flux analysis of N-glycosylation, its application to fed-batch and perfusion CHO cell culture production of immunoglobulin-G, and insights into the controlling factors of N-glycosylation from the analysis.

11:30 Cell-Cycle-Dependent Metabolism in CHO Cell Cultures: From Identification to Targeted Cell-Cycle Control

Jandt_UweUwe Jandt, PhD, Senior Research Associate, Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology (TUHH)

The influence of process parameters on the formation of heterogeneous cell populations, and correspondingly changing productivities, is still poorly understood. We identify metabolic variations depending on cell-cycle specific populations using a model-assisted workflow and statistical analysis. Further, a framework for the online measurement and control of cell-cycle distribution is introduced and demonstrated in repeated-batch and fed-batch cultures. This novel approach to control population heterogeneities provides potential to improve process stability and efficiency.

12:00 pm The Latest Innovation in Automated Sampling with Rapid Titer Results


Introducing the SegFlow S3, the latest innovation in automated sampling.  One of the most crucial components of your culture is the titer.  The Seg-Flow integrated with the Tridex Protein Analyzer provides titer concentrations on-line and in less than 5 minutes.  

BerkeleyLights12:30 Luncheon Presentation: Generating Production Cell Lines with Superior Titers and 99% Monoclonality in Under 1 Week

Singhal_AnupamAnupam Singhal, PhD Sr. Manager, Technology Development Berkeley Lights

Currently, clone selection is hampered by the lack of titer and stability measurements that are predictive of the downstream production environment. The Beacon® platform enables rapid selection of cell lines with titers superior to clones selected with alternative CLD methods. We will present case studies that demonstrate how the Beacon has accelerated CLD timelines and improved the yield of top-secreting clones.

1:15 Cake Break in the Exhibit Hall with Poster Viewing


Harborview 1

1:55 Chairperson’s Remarks

Rudiyanto Gunawan, PhD, Associate Professor, Chemical and Biological Engineering, University at Buffalo - SUNY

2:00 Combining Multi-Dimensional Fluorescence Spectroscopy with Chemometric Data Analysis for Routine and Effective Raw Material & Cell Culture Media Analysis

Ryder_AlanAlan G. Ryder, PhD, Professor, Nanoscale Biophotonics Laboratory, Chemistry, National University of Ireland Galway

Multi-dimensional fluorescence spectroscopy (MDFS) offers a convenient and inexpensive method for routine analysis of cell culture media and complex hydrolysates. MDFS provides information about both the presence of particles and changes in media composition. MDFS and multivariate analysis can be used for lot-to-lot variance analysis, process (filtering, sterilization, storage) validation, and in some cases as a predictive process model. Here we describe multiple cases studies and how MDFS can be effectively implemented.

2:30 Multi-Omics Analysis to Enhance Bioprocess Performance and Robustness

Hima Bindu Yalamanchili, PhD, Postdoctoral Fellow, Pharmaceutical Operations and Technology, Biogen

Each cell culture process is considered largely independent, and each product quality investigation thus requires significant resources to identify root causes. -Omics data (such as RNA, protein, and metabolite measurements) can provide a bridge between processes and enable us to develop effective application strategies to improve recombinant protein production with desired product quality. In addition, we can use the multi-omics database to generate hypotheses and to develop targeted solutions for cell culture processes trouble-shooting.

3:00 Multivariate Exo-Metabolome Analysis: A Tool for Cell-Culture Understanding and Optimization

Grilo_Antonio_LimaAntónio Lima Grilo, MSc, Early Stage Researcher, Chemical Engineering, Imperial College London

We will show how bioreactor monitoring could be used to predict cell culture performance. We have used a simple set-up involving at-line monitoring of energy production and off-line exo-metabolome analysis acquiring data for 24 metabolites. Multivariate analysis of these data has allowed to predict culture age, growth kinetics and productivity and to understand important metabolic changes occurring in culture. Information obtained from this analysis can be used for culture optimization including through the development of predictive mathematical models that can be used for control, feeding optimisation and medium design.

3:30 Biocapacitance for Improved Process Control and Consistency in Cell Culture Process Development

Forte_TaylorTaylor Forte, Engineer I, Cell Culture Development, Biogen

Process Analytical Technology (PAT) tools such as biocapacitance have been developed to monitor biomass in situ, to further automate bench-scale bioreactor systems, and to generate real time feedback control to decrease batch-to-batch variation. This talk will present a case study in which the application of in-line biocapacitance measurements can improve the accuracy of multiple steps in the upstream manufacturing process and transform a fixed process to a dynamic one, increasing robustness, consistency and product quality control in both CHO and non-CHO processes.

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

4:15 - 4:30 Stretch Break

4:45 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.

5:45 End of Conference

Waterfront 2

6:00-8:30 pm Recommended Dinner Short Course*

SC10: Phase-Appropriate Analytical and Process Control Strategies


Christine P. Chan, PhD, Principal Scientist, Global Manufacturing Science & Technology, Sanofi

Biotherapeutics are challenging to develop due to complexity of the molecular structure as well as the manufacturing process. The establishment of an integrated control strategy for robust manufacturing is an iterative process based on sound science and quality risk management. In this short course, we will discuss key considerations in evolving the analytical and process control strategies through the course of product development.