Cambridge Healthtech Institute’s 3rd Annual

Cell Culture to Bioproduction

Accelerating Productivity

24-25 March 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.

Final Agenda

 

Monday, 23 March

Recommended Short Course*

13:00 - 16:00 SC1: Continuous and Integrated Bioprocessing Masterclass

Instructor: Margit Holzer, PhD, Owner, Ulysse Consult

*Separate registration required.

Tuesday, 24 March

7:00 Registration and Morning Coffee

IMPROVING PROCESSES

8:25 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


8:30 KEYNOTE PRESENTATION: There’s Still a Place for People in Technology & AI

David Stewart, MSc, Senior Director, Site Quality Lead, Next Generation Manufacturing, Biogen

There are a lot of questions about what the rise of artificial intelligence means for the future of biotech – and humans in general. The potential of AI to transform many industries, including biopharmaceuticals, and accelerate life-changing discoveries is thrilling. But remember “HAL,” the murderous, rogue computer in the film 2001: A Space Odyssey? It’s human nature to fear the new and unknown. And it’s terrifying to think a machine might replace or outsmart us. As AI advances, where do people fit in?

9:00 Machine Learning in Bioprocess Development: What Can We Do Now & What Is Waiting for Us?

von_Stosch_MoritzMoritz 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.

9:30 Process Intensification Strategies Based on Single-Use Equipment

Schmidt_StefanStefan 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.

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

10:45 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 Know Your Bioreactors: From Computational Fluid Dynamics to a Digital Process Twin

Gernaey_KristKrist Gernaey, PhD, Professor and Head, Process and Systems Engineering Center (PROSYS), Chemical and Biochemical Engineering, Technical University of Denmark (DTU)

Mathematical modelling plays an increasingly important role in bioprocess research, and also in industrial development. Computational Fluid Dynamics (CFD) is generally accepted as a tool for description of bioreactor hydrodynamics at large scale. Apart from addressing CFD-based generation of scale-down models, this talk discusses challenges with CFD model validation, including potential solutions. As future perspective, efforts to produce digital twins of bio-based production processes are presented and discussed in detail.

11:45 Presentation to be Announced

 

 

12:00 Quality by Control Implementation to Bioprocesses Using an Advanced Software Platform

Sommeregger_WolfgangWolfgang Sommeregger, PhD, Research & Development, Bilfinger Industrietechnik Salzburg GmbH

We are introducing Qubicon, a tool for advanced process monitoring and control, ultimately enabling the implementation of the QbC approach to bioprocesses. Through a few examples, we will demonstrate how the software can be applied for the improvement of mammalian cell culture processes.

12:15 LUNCHEON PRESENTATION: Rapid Generation of Production Cell Lines with Superior Titers and 99% Monoclonality for Complex Antibody Molecules

Singhal_AnupamAnupam Singhal, PhD, Technology Development, Marketing, Berkeley Lights, Inc.

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.   

13:00 Session Break

BIOPROCESS MONITORING

13:30 Chairperson’s Remarks

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

13:35 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.

14:05 Toward Biotherapeutic Product Real-Time Quality Monitoring

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

In order to improve process control and increase product quality assurance, online and real-time monitoring of product CQAs is most relevant. Recent analytical techniques used for assessment of product-related CQAs of mAbs are considered in light of the analytical speed and ability to measure different CQAs. Furthermore, the state-of-the-art modeling approaches for CQA estimation in real time are presented as a viable alternative for real-time bioproduct CQA monitoring under the process analytical technology and quality-by-design frameworks in the biopharmaceutical industry, which have recently been demonstrated.

14:35 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.

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

ENHANCING PRODUCTIVITY

15:45 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.

16:15 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.

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.

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

Advanced Monitoring and Control of Bioprocesses

Moderator:  Wolfgang Sommeregger, PhD, Research & Development, Bilfinger Industrietechnik Salzburg GmbH

 

  • Monitoring and control objectives
  • Mathematical models for control purposes
  • Data management and processing
  • Implementation challenges and benefits

 

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

18:30 End of Day

 

Wednesday, 25 March

8:00 Registration and Morning Coffee

HARNESSING PREDICTIVE TECHNOLOGIES – MODELLING, PAT, AND DoE

8:25 Chairperson’s Remarks

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

8:30  Data Science or PAT as Control Strategies for Continuous Biomanufacturing

Herwig_ChristophChristoph Herwig, PhD, Professor and Head, Biochemical Engineering, Chemical Environmental and Bioscience Engineering, Technical University of Vienna (TU Wien)

Continuous Biomanufacturing (CBM) needs a closer control strategy at the process. But are CPP and CQA measurements available and timely for feedback control? This contribution presents current PAT solutions along the process chain for CBM, and proposes alternative and complementary control strategies using data science approaches, such as fingerprint analyses, integrated process modelling, and equivalence testing.

9:00  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.

9:30  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.

10:00 New Generation of Intelligent Sensors to Minimize Bioprocess Variability

Campolongo_GiovanniGiovanni Campolongo, Market Segment Manager Process Analytics, Hamilton Bonaduz AG

In the biopharmaceutical industry, government initiatives, such as the PAT, push the implementation of real-time bioprocess monitoring and control by using process sensors. This challenge is best addressed by “intelligent sensors.” This contribution will introduce the newer generation of Intelligent Sensors for monitoring Dissolved Oxygen, Cell Density, and more.

10:15 Presentation to be Announced

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

PLENARY SESSION:

NEXT-GENERATION PROCESSES AND PRODUCTS

11:15 Chairperson’s Remarks

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

11:20 Current Opportunities and Challenges in Biotherapeutic CMC

Ralf Schumacher, PhD, Global Head, Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG

As biologic pipelines continue to grow and diversify, there is an increasing need to standardize, automate, and find efficiencies along the entire value chain. This presentation will discuss the current challenges and opportunities in biotherapeutic CMC and the impact new modalities are having on upstream and downstream processing, analytics, and formulation. The advantages of predictive process parameters in early-stage development and digital development concepts to speed up the CMC development will also be discussed.

11:50 Gene Therapy Manufacturing and Technical Development

Diane Blumenthal, PhD, Head, Technical Development, Spark Therapeutics, Inc.

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 into the later stages of process development and scale-up, process performance qualification, and ultimately, commercialization.

12:20 Session Break

12:30 Bridging Luncheon
          Presentation to be AnnouncedMERCK(1)

13:00 End of Cell Culture to Bioproduction