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Informa
08:15 - 09:00

Registration

Showing of Streams
10:35 - 11:05

Morning Coffee

Showing of Streams
12:55 - 13:55

Lunch followed by Site Visit

13:55 - 17:55

NIBRT Site Visit

The National Institute for Bioprocessing Research and Training (NIBRT) is a global centre of excellence for training and research in bioprocessing. It is located in a new, world class facility in Dublin, Ireland. This facility is purpose built to closely replicate a modern bioprocessing plant with state of the art equipment. These facilities are all operated in a realistic GMP simulated, operational manufacturing environment. In 2012 NIBRT was awarded a Special Recognition Award for Novel Collaboration in the Facility of the Year Awards (FOYA) from ISPE.

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17:55 - 18:00
Return from Site Visit

Return from Site Visit

08:15 - 09:00 45 mins
Registration
09:00 - 09:05 5 mins
Cell Line Development & Engineering
Chairperson's Opening Remarks
  • Thomas Jostock - Group Head, Cell Line Development, Novartis Pharma AG
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09:00 - 10:35 95 mins
Continuous Manufacturing
Workshop by Ypso-Facto: Continuous Processing – Challenges, Technologies, Processes, Economics & Strategy
  • Roger-Marc Nicoud - Founder & CEO, Ypso-Facto, France
  • Margit Holzer - Scientific Director and Exclusive Consultant, Ypso-Facto, France
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Technologies & Processes

  • Motivations for continuous bioprocessing
  • Definitions
  • Process designs of a typical mAb production process
  • Landscape of continuous processing technologies
    • In-line dilution
    • Perfusion cultures
    • Continuous chromatography
    • Continuous TFF
    •  Continuous centrifugation, reactions; etc.
  • Process integration

From batch to continuous ... Is it the right question? The unit operation perspective

  • A few trivial considerations on reactions and chromatography in batch or continuous mode
  • Basic chemical engineering lessons for reactors, liquid-liquid extraction and chromatography
  • Further insights on chromatography


09:05 - 09:35 30 mins
Cell Line Development & Engineering
CHO Genome Stability and Heterogeneity
  • Nicole Borth, - Department of Biotechnology, , BOKU University and Austrian Center of Industrial Biotechnology (ACIB)
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With the availability of a new and much improved reference genome for the Chinese Hamster, more indepth studies on the genomic and phenotypic variation have become available. The talk will cover frequency and distribution of genomic variations across sequenced cell lines, their impact or lack thereof on the phenotype, the high degree of variation observed both in cell pools and subclones and our increased understanding of what controls gene expression level and thus phentoype in CHO cells.

09:35 - 10:05 30 mins
Cell Line Development & Engineering
CRISPR-Cas9-based Genome Engineering of CHO Cells
  • Shamim Rahman - Senior Research Scientist, Novo Nordisk
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Mammalian cell lines based on CHO are frequently used for the production of recombinant proteins. Cleaning up the cell by knocking out the genes which products contributes the most to the contaminating host cell proteins will be of high benefit for the production of recombinant proteins. CRISPR/Cas9 allows targeted modification of genomes with efficiencies that renders drug-based selection dispensable. We compared different genome engineering platforms to find the most efficient, fastest and with lowest toxicity associated protocol. We analysed the frequencies of monoallelic versus biallelic modified clones, compared knockout clones regarding their expression of host cell and recombinant proteins and defined quality parameters and show that CRISPR/Cas9 is an efficient tool to engineer next generation production cell lines.

10:05 - 10:35 30 mins
Cell Line Development & Engineering
Evolution of the Novartis CHO Expression Toolbox: Combining Novel Vector Technologies and Cell Line Engineering
  • Thomas Jostock - Group Head, Cell Line Development, Novartis Pharma AG
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10:35 - 11:05 30 mins
Morning Coffee
11:05 - 11:35 30 mins
Cell Line Development & Engineering
Ultra-deep Next Generation Mitochondrial Genome Sequencing Reveals Widespread Heteroplasmy in Chinese Hamster Ovary Cells
  • Colin Clarke, Ph.D. - Principal Investigator, National Institute for Bioprocessing
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11:05 - 12:55 110 mins
Continuous Manufacturing
Part 2: Continuous Manufacturing
  • Margit Holzer - Scientific Director and Exclusive Consultant, Ypso-Facto, France
  • Roger-Marc Nicoud - Founder & CEO, Ypso-Facto, France
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From unit operations to integrated processes & economical evaluations

  • Existing facilities
  • Design of new facilities
  • Example of cost studies of a mAb process

Day-to-day challenges during implementation of continuous processes

  • Batch definition
  • Process control strategy - PAT
  • Cleaning strategy
  • Process validation
11:35 - 11:55 20 mins
Cell Line Development & Engineering
Ensuring Clonality by Single-Cell Dispensing in Cell Line Development
  • Thomas Kretschmann - Field Application Specialist, cytena GmbH
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cytena’s single-cell printer uses an imaging system and object recognition algorithms to detect cells in a single-use dispenser cartridge. Droplets are produced similar to inkjet printing. Single cells are classified in the nozzle and subsequently dispensed directly into well plates. High viability has been observed for several cell lines (CHO: >90 %; HEK: >90 %; L292: >80 %).

11:55 - 12:25 30 mins
Cell Line Development & Engineering
Single Cell Cloning: Development, Application and Validation of a Fluorescent Assisted Single Cell Cloning Protocol
  • John Follit - Development Scientist III, ImmunoGen, Inc. USA
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Increased scrutiny from regulatory agencies in recent years regarding the origin of cell substrates used in the production of biologics has led to various techniques to calculate probability and provide assurance of “clonality”. Traditional methods relied on two rounds of cloning by limited dilution and resulted in lengthy timelines for cell line development. Recent advances in single cell cloning approaches provide the ability to perform cloning in a single step greatly reducing cell line development timelines. Here, we describe the development, application and validation of a high-throughput fluorescent assisted single cell cloning (FASCC) protocol combining fluorescent and bright-field microscopy with automated image processing. The FASCC protocol enables generation of single cell clones in a single step greatly increasing both our statistical probability and overall assurance of “clonality”, while significantly accelerating timelines.

12:25 - 12:55 30 mins
Cell Line Development & Engineering
Cell Line Development Platform Process for the Production of Blood Clotting Factors in a Human Cell Line
  • Ruth Wagner - Group Manager Cell Line Development, Octapharma Biopharmaceuticals
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Octapharma Biopharmaceuticals Is dedicated to develop and manufacture recombinant human therapeutic proteins, mainly for treating patients suffering from bleeding disorders. Octapharma’s mission is to provide patients with human-like therapeutics for maximizing drug tolerance and minimizing any adverse side effects, such as anti-drug antibody formation. Thus, our recombinant product portfolio – mainly consisting of highly glycosylated clotting factors - is expressed in a human cell line (HEK 293-F), thereby assuring well-tolerable proteins that display a human-like glycosylation pattern.

Using a combination of different genetic elements in our expression vector platform, we improved the generation of stable cell pools expressing complex glycoproteins. For assuring monoclonality and simultaneously shortening process timelines, we have integrated the Cytena single-cell printer as well as the Cell Metric cell imager to our clone selection platform process. The expression of proteins with complex PTMs requires an optimal supply of nutrients. To maintain a high product quality throughout the entire production process, our bioreactors are operated in perfusion mode. Consequently, we optimized the clone screening process by integrating the ambr15 bioreactor system operated in a perfusion-mimic mode. Using a combined bleeding and sedimentation strategy, we have developed an ambr15-scale model mimicking our lab scale perfusion process. For the final step of clone selection, we have integrated a parallelized multi-reactor system at lab scale operated in perfusion mode. In summary, our improved clone selection process links both, shortened timelines and increased focus on product quality of our complex glycoprotein products.

12:55 - 13:55 60 mins
Lunch followed by Site Visit
13:55 - 17:55 240 mins
NIBRT Site Visit
more

The National Institute for Bioprocessing Research and Training (NIBRT) is a global centre of excellence for training and research in bioprocessing. It is located in a new, world class facility in Dublin, Ireland. This facility is purpose built to closely replicate a modern bioprocessing plant with state of the art equipment. These facilities are all operated in a realistic GMP simulated, operational manufacturing environment. In 2012 NIBRT was awarded a Special Recognition Award for Novel Collaboration in the Facility of the Year Awards (FOYA) from ISPE.

17:55 - 18:00 5 mins
Return from Site Visit