Cambridge Healthtech Institute’s 3rd Annual

Cell Culture to Bioproduction

Accelerating Productivity

New Dates - 21-22 JULY 2020

 

Cambridge Healthtech Institute’s Cell Culture to Bioproduction conference examines the strategies that lead to greater productivity when cultivating cells and scaling up production. Emerging research and technologies are breathing new life into bioproduction, especially with genomic research and CRISPR engineering. Also, predictive technologies, such as PAT and DoE, have changed the way scientists develop methods and assess risks. In all, the conference explores how to increase productivity, while minimizing time and cost in order to provide the materials needed to create tomorrow's biopharmaceuticals.

TUESDAY, 21 JULY

8:55 Welcome Introduction

IMPROVING PROCESSES

9:00 Chairperson’s Opening Remarks

Mark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU); Co-Founder and CEO, Novasign GmbH


9:05 KEYNOTE PRESENTATION:
Schmidt_StefanProcess Intensification Strategies Based on Single-Use Equipment

Stefan R. Schmidt, PhD, MBA, COO, Head, Operations, BioAtrium AG

Reducing plant occupancy time and optimizing capacity utilization are the drivers for innovations in the field of process intensification. Many unit operations from cell banks to final fill can benefit from intensification through single-use solutions. This presentation gives a comprehensive overview of strategies on where and how to implement process intensification and quantifies the benefits based on successful examples and case studies.

 

9:25 Machine Learning in Bioprocess Development: What Can We Do Now & What Is Waiting for Us?

von_Stosch_Moritz

Moritz von Stosch, PhD, Head, Process Systems Biology and Engineering Center of Excellence of Technical R&D, GSK Biologicals

Machine Learning is believed to be a game changer for industry, especially by big Pharma reflected by significant investments. Starting from 101 in machine learning, this contribution outlines the current machine learning status for process development with examples, provides future directions towards more global high-value machine learning-centric development, concepts to engage people in the digital evolution, and ideas for machine learning-centric business models.

9:45 Presentation to be AnnouncedCatalent-Biologics

10:05 Q&A, Session Wrap-up

10:20 Break Time to View our Virtual Exhibit Hall

PROCESS OPTIMIZATION

10:50 Chairperson’s Remarks

Mark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU); Co-Founder and CEO, Novasign GmbH

10:55 Towards Improved Efficiency by Cell-Line Engineering and Process Optimization

Pieper_Lisa_AlexandraLisa Alexandra Pieper, PhD, Associate Director, Cell Culture, Bioprocess and Analytical Development, Boehringer Ingelheim Pharma GmbH & Co. KG

In an effort to improve the performance of a manufacturing clone expressing a complex therapeutic protein, we investigated cell-line engineering, as well as directed modulations of the cell culture process. Applying a pro-productive small RNA in combination with process optimization, we successfully enhanced specific productivity and final product titer, proving the superiority of this integrated approach.

11:15 Expression of Anti-Apoptotic Genes to Enhance the Performance of CHO Cell Cultures for Protein Production

Martinez-Monge_IvanIván Martínez-Monge, PhD, Postdoctoral Researcher, The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

One of the most relevant limitations of CHO cells in culture is apoptosis, which can be triggered by nutrient depletion or by-product accumulation. In this work, the impact of 8 anti-apoptotic genes was tested in terms of anti-apoptotic effect, changes in metabolism and productivity in batch and fed-batch. To this end, targeted integration of those genes combined with a recombinant protein has been used to generate isogenic cell lines that only differ in the anti-apoptotic gene inserted.

11:35 Rapid Generation of Production Cell Lines with Superior Titers and >99% Monoclonality for Complex Antibody MoleculesBerkeley_Lights_Stacked

Proctor_JohnJohn Proctor, PhD, Senior Vice President, Marketing, Berkeley Lights

The dev of next-gen therapeutics requires rapid workflows to generate production cell lines secreting wide range of complex antibody molecular formats.  Berkeley Lights will show how the Beacon enables users to generate cell lines secreting traditional and non-traditional antibody molecules.  Cell lines are generated with >99% monoclonality assurance in under 1 week removing lengthy rounds of cloning. Showing how Beacon users are generating cell lines with titers superior to clones selected with alternative CLD methods.   

11:55 Q&A, Session Wrap-up

12:10 Lunch Break - Come and View our Virtual Exhibit Hall

BIOPROCESS MONITORING

12:40 Chairperson’s Remarks

Moritz von Stosch, PhD, Head, Process Systems Biology and Engineering Center of Excellence of Technical R&D, GSK Biologicals

12:45  

High-Resolution Optical and Dielectric Methods for Monitoring Cells in Bioprocesses

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

We have established 0.25 S/m as a threshold cytoplasmic conductivity below which cells cannot be recovered from apoptosis. This point occurs at a time when there are observable changes in the cell membrane that can be observed by high-resolution optics. These changes can be observed up to 20h before cells stain with trypan blue. This allows dielectrics and high-resolution optics to be offered as a means of monitoring a bioprocess and maintaining cell viability over prolonged time periods.

13:05  Enabling PAT in Insect Cell Processes for rAAV Production

Isidro_InesInês Isidro, PhD, Scientist, Computational Biotechnology, Animal Cell Technology, iBET Instituto de Biologia Experimental Tecnologica

Insect cells with recombinant baculoviruses constitute a well-established production system for viral vectors for gene therapy and vaccines. As a lytic production system with released proteases likely to affect product quality attributes, the ability to track culture progression is especially important. This talk will explore how monitoring can be used to detect deviations, improve process understanding and support the critical time-of-harvest decision, enabling an information-based approach that aligns with PAT principles.

13:25 Q&A, Session Wrap-up

13:40 Break Time to View our Virtual Exhibit Hall

ENHANCING PRODUCTIVITY

13:55 Chairperson’s Remarks

Moritz von Stosch, PhD, Head, Process Systems Biology and Engineering Center of Excellence of Technical R&D, GSK Biologicals

14:00  Making Cell Culture More Physiological: Considering the Secretome and Extracellular Matrix

Adams_JosephineJosephine Adams, PhD, Professor, Cell Biology, Biochemistry, University of Bristol

Research involving culture of mammalian cells depends extensively on conditions devised in the mid-twentieth century that do not well-replicate the physiological microenvironment. There remains a huge research need for cell culture to expand fundamental knowledge of cellular functions and to facilitate preclinical drug discovery. Culture conditions that more closely reproduce physiological milieus are important to enhance biological relevance. I will discuss recent research investigating the effects of extracellular matrix and soluble secreted proteins, the secretome.

14:20  Process Intensification and Real-Time Monitoring Technologies to Accelerate Upstream Bioprocess Development

Wirth_JohannesJohannes Wirth, MSc, Scientist, BioProcess Science, Rentschler Biopharma SE

The application of intensified and dynamic strategies has widely been used for the improvement of bioprocess performance. In line with this, we present case studies where the application of an intensified seed train and dynamic feeding strategies led to reduced timelines, as well as higher product yields. The implementation of these approaches in combination with online monitoring technologies enables real-time process insights and holds the opportunity to facilitate bioprocess operation through automation.

14:40 Q&A, Session Wrap-up

14:55 Virtual Happy Hour in our Virtual Exhibit HallPurolite_Life_Sciences

15:15 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.

Making Cell Culture More Physiological 

Moderator:  Josephine Adams, PhD, Professor, Cell Biology, Biochemistry, University of Bristol

  • Laboratory cell culture is a central technology for investigating cell structure, physiology and the cellular basis of disease processes
  • But many cell culture reagents and procedures remain the same as used in the 1950s!
  • How can researchers embrace new resources to improve biological relevance and reproducibility of cell culture, along with the challenges that need to be overcome?

Industry 4.0 and Process Analytical Technology: Where are We and Where Can We Go?

Moderator:  Mark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU); Co-Founder and CEO, Novasign GmbH

 

  • Data storage, availability and integrity
  • Latest automation implementations
  • QbD strategies
  • Latest sensor technologies – soft sensors
  • Machine Learning for process development and optimization
  • Model Predictive Control and real time release

 

Day 1 | Day 2 |  Download Brochure

WEDNESDAY, 22 JULY

HARNESSING PREDICTIVE TECHNOLOGIES – MODELLING, PAT, AND DoE

9:00 Chairperson’s Remarks

Stefan R. Schmidt, PhD, MBA, COO, Head, Operations, BioAtrium AG

9:05 Hybrid Modeling and Intensified DoE Enabling Faster Process Understanding and Model Predictive Control

Duerkop_MarkMark Dürkop, PhD, Project Leader, Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU), and Co-Founder and CEO, Novasign GmbH

One of the bottlenecks in the development of innovative biopharmaceuticals is found in endless process development and characterization times. Within this work, we compared classical Design of Experiments (DoE) with an intensified DoE approach applied on an E. coli fed-batch process. While the screening of a classical DoE required 29 weeks, the intensified characterization could be finished within 10 weeks while still uncovering the best process conditions. The generated model will further be used for the process control showcase.

9:25  Advanced Control Strategies in Upstream Processing

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

Implementation of QbD/PAT concepts in biopharmaceutical production asks for advanced process control concepts to put the idea of in-process product quality control into practice. Today, a set of PAT tools is available that can be used to develop such concepts. In this talk, one example based on use of a hybrid modeling approach and a second showcase exploiting process information directly delivered by complex analyzers will be presented.

9:45 A Quality-by-Design Approach to Upstream Bioprocess Interrogation and IntensificationEppendorf

David BittnerDavid Bittner, Bioprocess Center, Eppendorf AG

Efficient process development in biotechnology relies on the Quality-by-Design (QbD) paradigm. QbD is a scientific, risk-based proactive approach to drug development that aims to have a full understanding of how the process and product are related. Within this talk, we provide approaches and tools to apply this principle. 

10:05 Q&A, Session Wrap-up

10:20 Break Time to View our Virtual Exhibit Hall

 

REFINING CHO ENGINEERING

10:40 Chairperson’s Opening Remarks

 

10:45  KEYNOTE PRESENTATION:

Engineering of Multiple Metabolic Pathways Mediates Improved Productivity in CHO Cells

Mermod_NicolasNicolas P. Mermod, PhD, Professor & Director, Biology & Medicine, University of Lausanne

We uncovered numerous cellular genes that are overexpressed in CHO cell lines that produce high levels of therapeutic proteins. While some were the consequence of heterologous protein overexpression, others appeared to limit the expression and secretion of heterologous proteins. This was assessed by overexpressing these genes, resulting in increased expression of various therapeutic proteins. Interestingly, several CHO cell metabolic activities were simultaneously limiting in pathways as diverse as cell signaling, response to cellular stress, cytoskeleton organization, and lipid metabolism.

11:05  Cell and Vector Engineering for Biologics Production by CHO Cells: Evaluating Diverse Strategies 

James_DavidDavid C. James, PhD, Professor, Bioprocess Engineering, Chemical and Biological Engineering, University of Sheffield


11:25  Novel Cell Retention Device and System for N-1 Perfusion ProcessesMERCK

Savary_LenaigLénaïg Savary, Upstream Biomanufacturing Engineer, MSAT, MERCK

Adoption of perfusion in N-1 bioreactors yields a reduction in process time and/or increase in manufacturing capacity without increasing volume capacity. Due to recent advances in cell retention technologies, cell line and media development, perfusion becomes a more viable alternative to expand performance beyond what traditional platforms can attain.  This presentation explores the benefits of a pre-sterilized, high-throughput perfusion filtration systems in an N-1 perfusion application and demonstrates scalability from 3 L to 50 L.    

11:45 Q&A, Session Wrap-up

12:00 Lunch Break - Come view our virtual Exhibit Hall

PLENARY SESSION:

NEXT-GENERATION PROCESSES AND PRODUCTS

12:25 Chairperson’s Remarks

Jarka Glassey, PhD, Professor, Chemical Engineering, Engineering, Newcastle University

12:30 Continuous Processing for Vaccine Manufacturing: Challenges and Opportunities

Yang-PingYangYan-Ping Yang, PhD, Head of Bioprocess Research & Development, North America, Sanofi Pasteur

Over the last decade, there have been significant investments in continuous manufacturing in the pharmaceutical industry, as it holds great promise to lead the reduction of process steps, smaller footprint, higher product quality, and better pharmaceuticals for patients. While it’s still in its early stage, the vaccine industry has embraced this concept and is ready to explore the full advantages associated with this approach. This presentation explores the challenges and opportunities to make continuous vaccine manufacturing a reality.

12:55 Gene Therapy Manufacturing and Technical Development

Blumenthal_DianeDiane Blumenthal, PhD., Head, Technical Development, Spark Therapeutics

In the past few years, several cell and gene therapy products have gained regulatory approval in the US and EU with many more in the pipeline. Manufacturers of cell and gene therapy products must tackle technological challenges under the pressure of short timelines resulting from streamlined clinical development. This presentation will focus on the key technical development challenges facing the industry as product development programs move the into the later stages of process development and scale-up, process performance qualification and ultimately commercialization.

13:20 Q&A, Session wrap-up, Host Intro to Special Virtual Features

 

Day 1 | Day 2 | Download Brochure

BPDE Brochure RC