Cambridge Healthtech Institute’s Inaugural
Bioreactor Design and Engineering

Finesse and Control of Bioprocesses

4-5 November 2015

The inaugural “Bioreactor Design & Engineering” conference examines how bioreactors are designed and operated to ensure safety and quality. Engineering details will be examined through Case Studies that address varying production scales and project goals. Issues of safety, online monitoring and risk management strategies will be discussed. How delicate cells are processed through fluid mechanics will be revealed with an eye to mitigating shear and streamlining processes.

Final Agenda

Day 1 | Day 2 | Speaker Biographies | Download Brochure  

: Unpublished Data | : Case Study

Wednesday, 4 November

07:45 Registration and Morning Coffee

NEXT-GENERATION BIOREACTOR STRATEGIES

08:45 Chairperson’s Opening Remarks

Trevor Deeks, Ph.D., QA and QC Consultant, Teva Biopharmaceuticals USA, Inc.

09:35 Large-Scale Production of Phage Antibody Libraries Using a Bioreactor

Andrew Bradbury, MBBS, Ph.D., Group Leader and Research Scientist, B Division, Los Alamos National Laboratory

One limitation of high-throughput phage antibody library selections is the production of sufficient phage antibody library at the appropriate quality. This talk will describe the adaptation of a bioreactor-based protocol for the production of phage peptide libraries to the production of phage antibody libraries. Titers obtained in the stirred-tank bioreactor are higher than a standard shake flask procedure, and phage antibody library quality is indistinguishable to that produced using standard procedures.

10:15 The Bolt-On Bioreactor Project – Perfusion Bioreactor Design for Efficient Adherent Cell Culture

Marcos Simón, Ph.D., Founder, Bolt-on Bioreactor Project

Efficiency of bioreactors for the culture of adherent cells lags behind that of their suspension cells counterparts. The Bolt-on Bioreactor project has studied each of the four major challenges that preclude adherent cells from becoming the biopharmaceuticals production system of choice in industry. The result is an efficient and scalable system for the perfusion culture of adherent cells.

10:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:30 Miniature Bioreactor Technologies for Rapid Cell Culture Process Development

Frank Baganz, Ph.D., Senior Lecturer, Biochemical Engineering, University College London

The need for greater speed during bioprocess development has focused much attention onto the development and application of miniaturised and high-throughput devices. This presentation will focus on shaken microwell-based systems and miniature stirred tank reactors and will cover the engineering characterisation in terms of power input, liquid phase mixing, and oxygen mass transfer. Examples will be given for the application of these technologies to rationally scale-up/down cell culture processes.

12:00 Bioengineering Strategies for ex vivo Cultivation and Purification of Stem Cells

Joaquim M.S. Cabral, Ph.D., Professor and Head, Bioengineering, Instituto Superior Técnico, University of Lisbon

The development of reliable in vitro systems for stem cell growth is a valuable tool to study the mechanisms controlling the expansion and differentiation of stem cells. This lecture presents bioprocess concepts towards the ex vivo expansion of adult mesenchymal and pluripotent stem cells in bioreactors, while maintaining their functional characteristics, including the ability to differentiate into appropriate tissues. Additionally, recent developments are also described and discussed.

12:30 Enjoy Lunch on Your Own

DISPOSABLE BIOREACTORS

14:00 Chairperson’s Remarks

Andrew Bradbury, MBBS, Ph.D., Group Leader and Research Scientist, B Division, Los Alamos National Laboratory

14:05 Single-Use versus Stainless Steel Bioreactors – Quality Factors for Consideration When Selecting a Suitable System

Trevor Deeks, Ph.D., QA and QC Consultant, Teva Biopharmaceuticals USA, Inc.

The relative merits of single-use as compared to stainless steel bioreactors has been widely covered in the literature and in conference presentations. Relative cost, convenience and capabilities have been the main areas for discussion, but there has been relatively little debate about quality considerations. Quality considerations are not often part of the decision-making process to determine the type of system to select. This presentation discusses these quality factors and how they might influence the decision.

14:35 Extractables from Single-Use Bioreactors and Impact on Cell Culture Performance

Yasser Nashed-Samuel, Ph.D., Principal Scientist, Attribute Sciences, Process Development, Amgen, Inc.

Biopharmaceuticals are drugs manufactured by growing genetically engineered cells in bioreactors to produce a therapeutic protein. Plastic single-use bioreactors are of interest to biopharmaceutical drug manufacturers due to its significant environmental and cost benefits and flexibility over stainless steel bioreactors. Effect of plastics on the bio-manufacturing process is not yet completely understood. A case study on extractables from single-use bioreactors and impact on cell culture performance will be presented.

15:05 Scaled-Up Manufacturing of Recombinant Antibodies Produced by Plant or Animal Cells in a 200-L Orbitally Shaken Disposable Bioreactor

Stefan Schillberg, Ph.D., Head, Molecular Biology, Plant Biotechnology, Fraunhofer Institute for Molecular Biology

The cultivation of suspended cells in disposable bioreactors for production of recombinant proteins is a useful alternative to conventional stainless steel stirred-tank reactors, and orbitally shaken bioreactors could provide further advantages such as simple bag geometry, scalability and predictable process settings. We carried out a scale-up study, using a 200-L orbitally shaken bioreactor holding disposable bags, and plant or animal cells producing human monoclonal antibodies. Antibodies secreted to the culture medium were purified by affinity chromatography resulting in high recovery and purity.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

SMALL-SCALE MODELING

16:15 Fed-Batch Operation in Small-Scale Bioreactors – Characterization of a Microtiter Plate-Based Feeding System

Clemens Lattermann, Dipl.-Ing., Scientific Staff, Biochemical Engineering, RWTH Aachen University

Fed-batch operating conditions in small-scale screening systems are essential for an efficient bioprocess development. In this work, first an overview about recently published fed-batch screening systems is given. Furthermore, a novel shaken fed-batch microtiter plate is presented and characterized. This microtiter plate is based on substrate diffusion through a hydrogel. A simulation model has been developed, to better understand the diffusion process and the hydrogel behavior during substrate diffusion. Finally, the simulation data are compared to experimentally determined substrate release data.

16:45 Which Outputs of a CFD Simulation Really Affect Process Performance? – A Two-Step Scale-Down Approach

Jens Fricke, Ph.D., Project Assistant, Bioprocess Engineering, Environmental Engineering and Technical Biosciences, Vienna University of Technology

In order to characterize existing processes in homogeneities in large-scale bioreactors CFD, simulations are usually performed. The questions that remain are: (1) Which of those gradients actually really affect cell physiology and thereby process performance? (2) How to anticipate those effects in small-scale in order to avoid surprises during scale-up? This contribution aims at answering those questions by proposing a link between the outputs of CFD simulations and the analysis of its physiological effects in a two-step scale-down approach.

18:15 Networking Reception in the Exhibit Hall with Poster Viewing

19:15 End of Day

Day 1 | Day 2 | Speaker Biographies | Download Brochure  

Thursday, November 5

08:00 Morning Coffee

MODELING & ANALYZING PROCESSES

08:30 Chairperson’s Remarks

Joaquim M.S. Cabral, Ph.D., Professor and Head, Bioengineering, Instituto Superior Técnico, University of Lisbon

        08:35  Lifelines of Single Cells and Populations in Large-Scale Bioreactors – Complex Dynamic Interplay Between Extracellular Environment and Cell Machinery

Matthias Reuss, Ph.D., Professor & Acting Senior Director, Stuttgart Research Center Systems Biology, University of Stuttgart

The purpose of strategies for the integration of computational fluid dynamics (CFD) and quantitative physiology is the development of more reliable simulation tools to accelerate the process of scale-up. The lecture aims at introducing an Euler-Lagrange approach to characterize the behavior of heterogeneous cell population in a stirred tank bioreactor with non-ideal mixing. It allows one to describe population behavior as the outcome of the interaction between the intracellular state of its individual cell and the turbulent flow field in the bioreactor.

09:05 Multivariate Analysis of Industrial Scale Fermentation Data

Krist Gernaey, Ph.D., Professor, Chemical and Biochemical Engineering, Technical University of Denmark

Historical process data is available for data mining, and can provide insight into process operation. Multivariate analysis is a powerful tool for investigating such large data sets as will be illustrated with an industrial case study. However, there are also many challenges associated with the application of multivariate analysis tools to batch process data. This is due to issues related to different batch lengths, different data sampling intervals, noise in the measurements, and availability of both online and offline data.

09:35 Rapid Intracellular Nucleoside Phosphate Monitoring in Fed Batch and Perfusion Cell Cultures using MALDI-TOF-MS

Robert Steinhoff, MSc, Scientist, Chemistry and Applied Biosciences, ETH Zurich

Monitoring intracellular levels of nucleoside phosphates in cell cultures allows for a very precise determination of cell viability and strongly supports process development. This interesting metabolite class is accessible using matrix-assisted-laser desorption/ionization mass spectrometry in combination with a rapid extraction protocol. The main focus of this talk is dedicated to method development steps and their application in (i) a hypothermia study in fed batch cultures and (ii) steady-state investigations in a perfusion cell culture.

10:05 Towards the Use of Micro-Toolboxes for Bioprocess Characterization
Marco Marques, Ph.D., Post-Doctoral Research Associate, Biochemical Engineering, University College London
Miniaturizing bioprocess unit operation steps is a well-established approach to find novel routes for process intensification and improved process economics. This contribution will focus on the steps taken to develop microfluidic up- and downstream unit operations with analytical methods, exploiting our knowledge of different physical phenomena at the microscale. Examples will be given for the application of these technologies for process characterization and understanding.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

INNOVATIVE APPROACHES TO ENSURE QUALITY

11:15 Orbital Shaking – The Next Generation Bioreactor System for High-Density Animal Cell Culture?

Maria De Jesus, Ph.D., Co-Founder, COO and Vice President, Sciences, ExcellGene SA

Impeller-free mixing of a liquid is possible. However, technical parameters of shaking processes, such as vessel geometry, direction and frequency of vessel displacement, gas transfer, power input, shear stress impact, etc. have only been explored by a few groups. For more than 10 years, we have established key engineering data and studied the culture performance of orbitally shaken cylinders from 5 ml to 50 L, to 250 L and eventually to 2500 L. This talk will cover the essentials of our research and will present surprising data of unpublished case studies with CHO cells and their performance.

11:45 Free Surface Oxygen Transfer in Unbaffled Bio-Reactors

Francesca Scargiali, Ph.D., Assistant Professor, Dipartimento di Ingegneria Chimica, Gestionale, Informatica e Meccanica, Università degli Studi di Palermo

Animal cell damage in aerated bioreactors is mainly related to the bursting of bubbles at the air–liquid interface. A viable alternative to sparged bioreactors may be represented by uncovered unbaffled stirred tanks, which have been found to be able to provide sufficient mass transfer through the deep free surface vortex which takes place under agitation conditions so avoiding bubble formation and bursting. Mass transfer performance of this kind of bioreactor is then presented and discussed.

12:15 Enjoy Lunch on Your Own

13:00 Dessert Break in the Exhibit Hall with Poster Viewing

13:30 End of Bioreactor Design & Engineering

Day 1 | Day 2 | Speaker Biographies | Download Brochure  

: Unpublished Data | : Case Study

Conference Programs

• Display of Biologics
• Engineering Antibodies
• Machine Learning - Part 2

• Antibody-Based Therapies
• Emerging Targets & Approaches
• Membrane Protein Targets

• Safety & Efficacy
• Advancing Bispecifics
• Engineering Bispecifics

• Modulating the TME
• Innovative CAR T Therapy
• Next-Gen Immunotherapies

• Optimisation & Developability
• Analytical Characterisation
• Protein Stability & Formulation

• Data Science & Engineering
• Optimising Expression
• Process Development

• Intro to Machine Learning
• Machine Learning - Part 1
• Machine Learning - Part 2

• Antibody-based Therapies
• Engineering Conjugates
• Next-Gen Immunotherapies