Cambridge Healthtech Institute’s Inaugural

Optimising Cell Culture Technology

Enhancing Knowledge for Growing Cells

20-21 March 2018 | Sheraton Lisboa Hotel & Spa | Lisbon, Portugal


The ubiquitous task of culturing cells might be considered an established technology; yet, meeting demands of industry pushes the need to increase titre, and decrease the time and resources necessary to meet project goals. The Optimising Cell Culture Technology conference examines strategies to streamline production while ensuring bottom-line quality, and will include a session focused on culturing CHO cells (Chinese Hamster Ovary cells). New technologies and protocols will be discussed in the effort to improve yield, while also addressing the future of cell culture in an expanding market where standards of quality continue to rise.

Final Agenda

Monday, 19 March

13.00 – 16.00 Recommended Short Course*

SC1: Optimizing Media for Culturing Cells

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.


Tim Beckmann, PhD, Director, Strategic Development & USP, Xell AG
Frederic Girard, PhD, Managing Director, Eurofins Spinnovation Analytical
Jochen B. Sieck, PhD, Head, Perfusion Systems and Cell Culture Media R&D, Merck Life Science

* Separate registration required.


7:00 Registration and Morning Coffee

Mammalian/CHO Cultivation

8:25 Chairperson’s Opening Remarks

Ralf Pörtner, PhD, Senior Research Associate, Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology

8:30 Protein Production Using Perfusion Processing of Human Cells

Véronique_ChotteauVéronique Chotteau, PhD, Researcher & Principal Investigator, Cell Technology Group, Biotechnology, KTH Royal Institute of Technology

CHO cells are the workhorses of the biopharmaceutical field. However, human cell-based systems might bring important advantages, such as production systems resulting in proteins with more human-like post-translational modifications and potentially alleviate the production of difficult-to-produce molecules. To evaluate the potential of HEK 293 cells for biopharmaceutical production, a high cell density perfusion process has been developed for EPO production, at a density up to 100 x 106 cells/mL. This process was developed in our novel scale-down perfusion bioreactor of 200 mL working volume.

9:00 Transcriptome Analysis of a Recombinant Antibody-Producing CHO Cell Line Cultivated in Feed-Spiked Medium

Renate_KunertRenate Kunert, PhD, Professor, Biotechnology, Austrian Center of Industrial Biotechnology, University of Natural Resources and Life Sciences (BOKU)

Feed spiking is the most commonly applied production processes in animal cell culture technology today. To investigate metabolic and transcriptomic changes in a feed spiked CHO cell culture, we defined a batch strategy with and without a single feed shot at the beginning of the process. Thereby we found two-fold higher cell concentrations and three-fold higher antibody titers which could be related to metabolic rates and reflected by transcriptomic changes.

9:30 Investigating Alterations in the CHO N-Glycome Following Exposure to Leachables from Single-Use Bioreactors

Jonathan_BonesJonathan Bones, PhD, Principal Investigator, Characterization and Comparability Laboratory, National Institute for Bioprocessing Research and Training (NIBRT)

The cellular N-glycome of CHO cells, characterized using two dimensional liquid chromatography with high resolution mass spectrometry, is highly complex, consisting of a dominant high mannose series and a broad range of complex N-glycans bearing varying degrees of sialylation and poly-lactosamine motifs. The dynamics of the CHO N-glycome is described following exposure to leachable compounds from single use bioreactors. Correlation with product quality attributes, including mAb glycosylation, were also investigated.

10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing



10:45 CHO: Optimizing Cell Culture Technologies for Manufacture of Recombinant Proteins - Past, Present and Future

Florian M. Wurm, PhD, Professor Emeritus, Swiss Federal Institute of Technology Lausanne (EPFL), and Founder & CSO, ExcellGene SA

CHO cells became THE dominant host for pharmaceutical protein production, because a convenient metabolic deficiency was found and explored by early biotech pioneers in the late 1970s to repair the defect with the help of plasmid vectors, dragging along any other gene of interest when transfected. Genentech and Amgen were the first to explore the DHFR deficient CHO cell lines to generate proteins that became the first large and complex protein products approved for therapy. The rest is history… which the speaker will try to convey with respect to important events, regulator issues, key insights into biology and processes, as well as achievements in terms of yield and quality.


11:15 Next Generation CHO

Nicole Borth, PhD, Professor, Biotechnology, Austrian Center of Industrial Biotechnology, University of Natural Resources and Life Sciences (BOKU)

With detailed sequence information now available for the most important production cell line for biopharmaceutics and new tools that enable efficient engineering approaches, the environment for CHO cell research and optimization has significantly changed over the last few years. The combination of computational prediction of cell behavior and efficient testing of multiplexed engineering strategies will thus lead to the next generation of cell lines with enhanced properties and capabilities.


11:45 ChemStress Fingerprinting: A Simple, Novel Platform Using Small Molecules to Control and Enhance CHO Cell Factories

Jerry CliffordJerry Clifford, PhD, COO, Valitacell

The utility of CHO cell factories derives from exploitation of their acquired genetic/functional variation, which enable industry to identify cell lineages with desirable manufacturing properties. Here we discuss novel technologies engineered to provide process control while at the same time enabling optimal leverage of the cell factory using ChemStress fingerprinting.


12:00 Demonstrate Monoclonality by Single-Cell Dispensing in Cell Line Development

Jonas SchoendubeJonas Schoendube, CEO, cytena GmbH
cytena’s single-cell printer uses an imaging system and object recognition algorithms to detect cells in a disposable dispenser cartridge. Cells are classified and dispensed into well plates. Images of the printing process enable assurance of clonality. High viability has been observed for several cell lines. Customer data will be presented.

12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Session Break

Optimising Cell Culture Processes

13:30 Chairperson’s Remarks

Renate Kunert, PhD, Professor, Biotechnology, Austrian Center of Industrial Biotechnology, University of Natural Resources and Life Sciences (BOKU)

13:35 Exploiting Process Knowledge to Perform More Meaningful Design of Experiments

Moritz_von_StoschMoritz von Stosch, PhD, Senior Manager, Fermentation, Technical Research and Development, GSK Vaccines

Understanding the impact of Critical Process Parameters (CPPs) on the Critical Quality Attributes (CQAs) is central to the Quality by Design (QbD) paradigm. Design of Experiment (DoE) methods can be employed to develop this understanding. However, for numbers of CPPs >3, the number of experiments in the design is usually too high to be executed. In this presentation it is shown how process knowledge can be used to structure the relation between CPPs, mapping their dependences, which can decrease the number of CPPs that are included in the design.

14:05 Monitoring and Controlling Critical Components in Cell Culture Processes Using Raman Spectroscopy

Carl Rafferty, PhD Student, Pharmaceutical Development and Manufacturing Sciences, Janssen Sciences Ireland

Development and use of Partial Least Squares (PLS) predictive models to monitor cell culture for critical components (glucose, lactate and ammonia) using a Raman spectroscopic probe. Monitoring is performed in parallel in reduced (5L) and manufacturing scale (2000L) bioreactors to obtain 48 times more data compared to the historical process. Also, demonstrated as part of this work is the automated control of a critical cell culture component (glucose) using PLS and Raman spectroscopy. This is performed using a feedback control loop with the aim of influencing metabolism which improved biotherapeutic production by 20%.

14:35 Embedding the Berkeley Lights Beacon – A Bright Future for Cell Line Development

Robyn_EmminsRobyn Emmins, PhD, Associate Fellow & Group Leader, Cell Line Development: Projects and Enabling Technologies Team, Biopharm Cell and Process Derisking, R&D Platform Technology & Science, GlaxoSmithKline

The Berkeley Lights Beacon system couples proprietary OptoSelect™ technology with the nano-fluidic culture of cells. This technology offers the potential to significantly reduce cell line development cycle times and to enable clonal cell line selection based on preferred cell phenotypes in addition to traditional cell growth and productivity measurements. The data presented will highlight initial observations as we embed the Berkeley Lights Beacon technology, and an overview of the impact that we anticipate it will have on our Cell Line Development platform process.

15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

15:45 Large-Scale Manufacturing of High-Titer Cell Culture Processes Using Advanced Process Controls

Nikolaj_Neerstrand_RasmussenNikolaj Neerstrand Rasmussen, MSc, EBA, Manufacturing Scientist II, Manufacturing Sciences, Biogen

To enable high-density and high-titer processes, Biogen has developed a next-generation manufacturing process with N-1 perfusion to allow high seed density at the production bioreactor stage. During production, advanced process control is applied by variable-volume feeding via dynamic biomass dependent nutrient feed control. This strategy has enabled Biogen to generate robust processes with titers in the 7-10g/L range.

16:15 Nip-Tuck the Next Gen Designer Cells for Drug Discovery

T_Oliver_ChaoT. Oliver Chao, PhD, Head, Emerging Biomedical Sciences, Sanofi

My talk will address the promise and liability of gene editing approaches, along with a discussion of the application of designer cells for translational drug discovery. I will also look at the prospect of integration of GM cells, and future potential.

16:45 Breakout Discussion Groups

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.

The Challenges of Modelling Cell Culture Processes Within Time and Budget Constraints

Moderator: Robert J. Thomas, PhD, Professor, Manufacturing for Cell and Gene Therapies, Centre for Biological Engineering (CBE), Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University

  • Determining parameters
  • Using models to design and improve processes
  • Using models to understand complex dynamics 

Model-Based Design Strategies

Moderator: Ralf Pörtner, PhD, Senior Research Associate, Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology

  • expectations from industry
  • available tools
  • application spectrum (development, process steps, process lifecycle)
  • where to go?
  • regulatory issues
  • requirements for applicability

Is a Cell Density of 200g/l Desirable or Do We Need Better Producers (>50 p/c/d) Which Keep Specific Productivity Over the Whole Process?

Moderator: TBA

  • Productivity
  • Improving processes to achieve greater cell density
  • How to make the entire process more productive

17:30 Welcome Reception in the Exhibit Hall with Poster Viewing

18:30 End of Day


8:00 Registration and Morning Coffee

Using Models To Enhance Cell Culture Processes

8:25 Chairperson’s Remarks

Jonathan Bones, PhD, Principal Investigator, Characterization and Comparability Laboratory, National Institute for Bioprocessing Research and Training (NIBRT)

8:30 Optimizing a Small-Scale (5L) Fermentation Model for Production of Monoclonal Antibodies

Eda_Bener_AksamEda Bener Aksam, PhD, Scientist, PDMS API LM (R&D), Janssen Biologics

At our research lab, we had a running small-scale model at 10L bioreactor which mimics the large scale well, but we were not able to mimic the production at 5L bioreactor model for this product. Dissolved oxygen and in connection to that viable cell density control was problematic. Through a series of analysis and experimentation of different configurations, we managed to get a good model at 5L. The mechanism between different bioreactor configurations (mixing speed, aeration parameters, etc.) and culture performance indicators are explained through our study.

9:00 Model-Assisted Design of Process Strategies for Cell Culture Processes

Ralf_PörtnerRalf Pörtner, PhD, Senior Research Associate, Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology

The potential of a model-assisted process design for a pharmaceutical production process will be discussed for three purposes: (1) coupling of statistical design of experiment (DoE) methods and mathematical models for the reduction of experimental effort as well as the model-assisted interpretation and evaluation of process management strategies, (2) a software tool for seed train modeling enabling seed train analysis, optimization and design, (3) operator-training tools.

9:30 Dynamic Mechanistic Modelling for Optimisation of Cell Therapy Process Development and Manufacture

Rob_ThomasRobert J. Thomas, PhD, Professor, Manufacturing for Cell and Gene Therapies, Centre for Biological Engineering (CBE), Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University

This talk will discuss the challenge of modelling cell therapy manufacture processes in a manner that is useful for understanding quality risk and efficiency but also compatible with constraints of process development (such as limited data and complex dynamics). A workflow and toolset to support definition of culture dynamics and optimisation of cell culture operation will be introduced supported by case studies of process improvement opportunities in hematopoietic lineage culture systems.

Resolution Spectra Systems10:00Fast and Robust Implementation Of Bioprocess Raman In-Line Monitoring

Christophe_BonnevilleChristophe Bonneville, President, RESOLUTION Spectra Systems

Bioprocess monitoring with Raman spectroscopy has been recently considered a state-of-the-art method after being validated by leading biopharma companies. However, multivariate model-building is still experienced as a rate-limiting step. In this presentation, we will describe a method and tools to efficiently reduce this step in terms of effort and timing. It will be illustrated by CHO cell culture experiments and a focus will be made on how to conduct robust multivariate calibration.


10:30 Coffee Break in the Exhibit Hall with Poster Viewing

Plenary keynote Session

11:15 Chairperson’s Remarks

Manuel Carrondo, PhD, Professor of Chemical and Biochemical Engineering, FCT-UNL, Vice President, IBET

11:20 Integrated Drug Substance-Drug Product Development for the Next Generation of Biologics

Hitto Kaufmann, PhD, Global Head, BioPharmaceutics Development & Platform Innovation, Global R&D, Sanofi-Aventis

The rise of next generation biologics brings with it new challenges. This presentation will examine how bioprocessing departments are adapting to evolving and diverse biological pipelines and the role of innovation as a key driver to deliver superior medicines to patients. The convergence of CMC technologies will also be examined using examples from Sanofi where relevant.

11:50 Next-Generation Processes, Technologies and Operations

Michael Pohlscheidt, PhD, Site Head & Head of Operations, Solothurn Manufacturing Facility, Biogen

A critical step in meeting the demand of biologic production worldwide involves implementing disruptive manufacturing technologies, processes and capabilities. This talk will evaluate Biogen’s new manufacturing site in Switzerland, due to go online in 2019, including the new processes, operational models and technologies being adopted to drive value through innovation and deliver new medicines in areas such as Alzheimer’s.

12:20 End of Conference