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Key Sessions

David James

KEYNOTE PRESENTATION: New Parts and Systems for CHO Cell Synthetic Biology

University of Sheffield

Simon Fischer

How Novel Technologies can be Applied to Advance CHO-K1 Manufacturing Cell Lines

Boehringer Ingelheim Pharma GmbH & Co.KG

Apr 24
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08:00 - 08:50 50 mins
Registration and Morning Coffee
08:50 - 09:00 10 mins
Chairperson's Opening Remarks
  • Bjørn Voldborg - Director CHO Cell Line Development, Technical University of Denmark
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09:00 - 09:30 30 mins
Cell Line Development and Engineering
KEYNOTE PRESENTATION: New Parts and Systems for CHO Cell Synthetic Biology
  • David James - Professor of Bioprocess Engineering, Chemical and Biological Engineering, University of Sheffield
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Synthetic biology based on the “Design-Build-Test-Learn” cycle offers a new paradigm for CHO cell engineering, where it is possible to engineer the host cell factory in a product specific manner via combinatorial “tuning” of discrete cellular synthetic processes.  This approach permits “one-size-fits-all” genetic vectorology and mechanistically blind screening of transfected cells to be replaced with tailored design and construction of specifically fit-for-purpose cell factories.  This engineering design system relies upon a toolbox of synthetic parts with user-defined functionality that work in synchrony to enable product manufacturability.

09:30 - 10:00 30 mins
Cell Line Development and Engineering
Systems and Synthetic Biology: Next Generation Tools for Cell Line Development
  • Lin Zhang - Research Fellow, Pfizer
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10:00 - 10:30 30 mins
Cell Line Development and Engineering
Spotlight Presentation: A Representative from Lonza
10:30 - 11:15 45 mins
Cell Line Development and Engineering
Morning Coffee and Networking
11:15 - 11:45 30 mins
Cell Line Development and Engineering
Generation of Superior Host Cell Lines for Biomanufacturing
  • Holger Laux - Fellow, Novartis
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CHO cells are the most widely used host for large-scale production of recombinant therapeutic proteins. Using transcriptomic approaches we have identified target genes involved in productivity and product quality. Subsequently a variety of novel parental CHO cell lines were generated applying cell line engineering techniques. These novel knockout CHO cell lines are superior in respect to productivity and/or product quality.

11:45 - 12:15 30 mins
Cell Line Development and Engineering
How Novel Technologies can be Applied to Advance CHO-K1 Manufacturing Cell Lines
  • Simon Fischer - Head of Cell Line Development CMB, Boehringer Ingelheim Pharma GmbH & Co.KG
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Genome editing, next-generation sequencing (NGS) and cell line engineering using microRNAs (miRNAs) have emerged as key technologies towards successful biopharmaceutical process development. We have evaluated and integrated these innovative tools to enhance our state-of-the-art cell line development and characterization processes using our novel BI-HEX® CHO-K1GS manufacturing cell line. This talk will present an overview on our recent achievements in employing these technologies to provide solutions for future bioprocessing challenges.

12:15 - 12:30 15 mins
Cell Line Development and Engineering
ChemStress Fingerprinting: A Simple, Novel Platform using Small Molecules to Control and Enhance CHO Cell Factories
  • Hannah Byrne - Product Manager, Valitacell
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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 a desired level of process control while at the same time enabling optimal leverage of the cell factory using ChemStress Fingerprinting.

12:30 - 12:45 15 mins
Cell Line Development and Engineering
Difficult to Express Proteins: A Novel Plasmid Technology to Increase Product Yields in CHO Cells
  • Menzo Havenga - CEO & President, Batavia Biosciences
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Yield is still an area that requires significant improvement for many promising recombinant proteins and antibodies. Novel vector technology enables rapid generation of stable, CHO cell lines able to provide at least 10-fold more product per cell.

12:45 - 14:00 75 mins
Lunch in the Exhibition Hall and Live Labs
14:00 - 14:30 30 mins
Cell Line Development and Engineering
Applications of CRISPR-Mediated Genome Engineering Towards Improved CHO Cell Factories
  • Helene Faustrup Kildegaard - Senior Researcher, Technical University of Denmark
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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.

14:30 - 15:00 30 mins
Cell Line Development and Engineering
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15:00 - 15:30 30 mins
Cell Line Development and Engineering
cGMP-compliant Cell Engineering for Rapid Genome Modification, Protein Production & Stable Cell Line Generation
  • Peer Heine - Field Application Scientist, MaxCyte, Inc.
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The continued growth of biotherapeutics has created a critical need for technologies that facilitate scalable biomanufacturing and precise genome modification. In this presentation, we present recent data for a high-performance cell engineering technology that enables improved transient CHO productivity and streamlined stable cell line generation as well as custom CRISPR-mediated gene editing for construction of high-yield CHO cell lines.

15:30 - 16:00 30 mins
Cell Line Development and Engineering
Afternoon Coffee Break
16:00 - 16:30 30 mins
Cell Line Development and Engineering
Engineering the CHO Cell
  • Bjørn Voldborg - Director CHO Cell Line Development, Technical University of Denmark
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At CFB we have established a high throughput genome engineering pipeline using CRISPR-Cas9. The pipeline is being used to generate a panel of engineered CHO cells with improved properties for the production of recombinant therapeutic proteins. We now have a collection of cell lines generating predictable and tailormade glycoprofiles, better product quality and improved growth phenotypes.

16:30 - 17:00 30 mins
Cell Line Development and Engineering
A siRNA Screen Reveals Novel Engineering Targets in CHO Cells that Boost Productivity
  • Gerald Klanert - Post Doc, ACIB – The Austrian Centre of Industrial Biotechnology
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A whole genome mouse siRNA screening was applied to suspension CHO cells producing and secreting GFP. With this screen, two genes were identified, that, upon knockdown, boost the productivity in CHO cells. The effect of knockdown of these genes varied in different production clones producing either an antibody or an Erythropoietin-Fc fusion protein, indicating cell- and/or subclone specific limitations. However, in each cell line, at least one of the two knockdowns enhanced specific productivity.

17:00 - 17:15 15 mins
Plenary Change Over
17:15 - 17:45 30 mins
Scalable platform for reducing time to market of Intensified and Continuous Upstream Processes
  • Gerben Zijlstra - Platform Manager, Sartorius
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Despite their low costs, rapid deployment and flexibility, the current Single Use facilities are limited by their output, typically 500 kg/year for a 6 x 2000 L facility at 3 g/L Fed Batch titer. This also limits their usefulness for commercial scale manufacturing of multiple midsize portfolio products. Upstream process intensification can solve this limitation. With consistent effective titers of 10 g/L and beyond, annual outputs of 1500 kg/year can be realized from Single Use facilities so they become an even more attractive option for commercial manufacturing of multiple products.

To this point however the development and scale-up of intensified upstream has been cumbersome and time consuming. In this presentation a platform of upstream process intensification tools and technologies are shown, that can greatly speed-up and improve process development, scale-up and commercial scale process control.

Examples will be shown including an effective titer boost from 3 to 10 g/L in 12 days of culture, using commercially available platform tools, including cell line, media, process development tools and commercial scale manufacturing tools.

17:45 - 19:45 120 mins
End of Conference Day Two and Pre-Kings Day Party at the RAI Boathouse