Cambridge Healthtech Institute’s Inaugural

Bioproduction: Scale, Bioreactors & Disposables

Making It Work

21-22 March 2018 | Sheraton Lisboa Hotel & Spa | Lisbon, Portugal

 

The inaugural Bioproduction conference examines biologics production, including scale-down models, scaling up production, engineering bioreactors, single-use systems, and ensuring quality, within the context of increasing productivity. A holistic review of bioprocessing will be explored, as well as practical details, such as monitoring and analyzing processes, and looking in-depth into how bioreactors process cells. The conference will address robust manufacturing processes and next-generation technologies, while improving manufacturing platforms and ensuring product quality.


Final Agenda

Wednesday, 21 MARCH

10:00 Registration and Morning Coffee

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

Plenary keynote Session

11:15 Chairperson’s Remarks

Manuel Carrondo, PhD, Professor of Chemical and Biochemical Engineering, FCT-UNL, Vice President, IBET

11:20 Integrated Drug Substance-Drug Product Development for the Next Generation of Biologics

Hitto Kaufmann, PhD, Global Head, BioPharmaceutics Development & Platform Innovation, Global R&D, Sanofi-Aventis

The rise of next generation biologics brings with it new challenges. This presentation will examine how bioprocessing departments are adapting to evolving and diverse biological pipelines and the role of innovation as a key driver to deliver superior medicines to patients. The convergence of CMC technologies will also be examined using examples from Sanofi where relevant.

11:50 Next-Generation Processes, Technologies and Operations

Michael Pohlscheidt, PhD, Site Head & Head of Operations, Solothurn Manufacturing Facility, Biogen

A critical step in meeting the demand of biologic production worldwide involves implementing disruptive manufacturing technologies, processes and capabilities. This talk will evaluate Biogen’s new manufacturing site in Switzerland, due to go online in 2019, including the new processes, operational models and technologies being adopted to drive value through innovation and deliver new medicines in areas such as Alzheimer’s.

12:20 Session Break

Process Development Strategies

13:40 Chairperson’s Remarks

Jarka Glassey, PhD, Professor, Engineering, Newcastle University

KEYNOTE PRESENTATION:

13:45 Current and Future Challenges in Developing and Producing Biopharmaceuticals

Jan Visser, PhD, Vice President, Process Development, Boehringer Ingelheim Pharma GmbH & Co. KG

The need to bring high-quality biopharmaceutical products to market quicker and more cost effectively is a key trend in biomanufacturing. This presentation will discuss the current challenges, technologies and strategies being adopted to meet this need using examples from the Boehringer Ingelheim development and manufacturing network.

14:15 From Cell to Product: Multivariate Data Analysis (MVDA) of Biopharmaceutical Manufacturing

Ornella_PreisnerOrnella Preisner, PhD, Senior QbD Specialist, CPI Biologics, The Centre for Process Innovation (CPI)

Biopharmaceutical production is a challenging field. To continue to meet market expectations processes must evolve beyond their current capabilities. Process optimisations such as medium design, feeding regimens and continuous culture have been successfully implemented to boost productivity. Cell line development is achieved through various methodologies, and can overcome expression bottlenecks. Such work uses large, parallel data sets from high-throughput screening systems. MVDA can be used as a tool to explain the biology underlying the observations.

14:45 Liquid Engineering: CHO Cell Culture Performance Enhancement Using Small Molecules

David_JamesDavid James, PhD, Professor, Bioprocess Engineering, Chemical and Biological Engineering, and Director, Advanced Biomanufacturing Center, University of Sheffield

In contrast to genetic engineering of CHO cells to enhance their functional performance, bioactive small molecule (SM) additives are relatively simple to utilise. They can be screened, titrated, combined and deployed during culture with comparative ease. We describe the development of a medium to high-throughput platform that enables rapid quantitative assessment of SM additives as a tool to create bespoke media environments designed to engineer cell factory function for optimal manufacturing performance.

 

15:15 The Arc Concept – Simplifying Life with Intelligent Sensors and Wireless Communication
Knut GeorgyKnut Georgy, Market Segment Manager, Process Analytics, Hamilton Bonaduz AG 
Intelligent Arc sensors eliminate the need for external transmitters. The integrated micro-transmitter communicates directly with the process control system via 4-20 mA or a digital Modbus protocol. Now with the new ArcAir App the workload for operators can be reduced and transcription errors can be avoided. Live demo.


Labor Dr Merk 15:30 Adherent Versus Suspension Bioreactors for Viral Therapeutics Production
Rolf G. Werner, Professor, Labor Dr. Merk & Kollegen 
A number of host cells for propagation of viral vectors are adherent cell cultures, growing in FCS. There is a limitation in scale up for these cells in Cell Factory, micro carriers and in iCELLis 500. Alternatively viral vectors are propagated directly in suspension cells in serum free media, avoiding potential contamination with adventitious viruses, with unlimited scale up.

15:45 Refreshment Break in the Exhibit Hall with Poster Viewing

USING MODELING TO SUPPORT PROCESS DEVELOPMENT

16:25 Hybrid Modeling and Intensified DoE Strategies Providing a Base for Efficient Implementation of the Quality by Design Approach in Biopharmaceutical Production

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

Implementation of QbD is a challenging and cost intensive task gaining more and more importance in biopharmaceutical industry. However, there is a still ongoing discussion on which methods (wet-lab, experimental design, data analysis) should be used and which combinations thereof are most meaningful. We will present the concept of intensified DoE in fermentation processes and hybrid modeling approaches and how these strategies can contribute to QbD implementation.

16:55 Hybrid Metabolic Modelling in Upstream Process Development

Inês_IsidroInês A. Isidro, PhD, Scientist, Computational Biotechnology, Animal Cell Technology Unit, iBET - Instituto de Biologia Experimental e Tecnológica

Hybrid models combine mechanistic descriptions with data-driven statistical models. They take advantage of (and complement) what is known about the system while also accounting for the effect of phenomena that are not fully understood. This talk will show how hybrid models can be leveraged to incorporate metabolic knowledge into upstream process development. Case studies will include culture media development for Pichia pastoris and bioprocess control of baby hamster kidney (BHK) cultures.

17:25 Predictive Modelling of Fed-Batch Monoclonal Antibody Production in CHO Cells for Scaling Up

Elmar_HeinzleElmar Heinzle, PhD, Professor, Biochemical Engineering, Saarland University

The acceleration of the development of cell culture processes for the production of biologicals like monoclonal antibodies is of great interest. It has significant impact on the development and on time-to-market of such products. We developed a procedure that allows the systematic development of predictive macroscopic models that are applicable for scale-up and optimization of fed-batch processes of interest.

17:55 End of Day

18:00 Dinner Short Course Registration

18:30 Dinner Short Course

18:0021:00 Recommended Dinner Short Course*

SC3: At the Heart of PAT Lies the QBD Approach

The QbD Roadmap provides a conceptual structure for the development activities of the drug manufacturing process. Coming from the Target Product Profile and subsequent determination of the Critical Quality Attributes (CQAs), the criticality of the process parameters that might have an impact on the CQAs are assessed using risk analysis. Subsequently, the impact of the critical process parameters (CPPs) on the CQAs is typically evaluated using a combined Design of Experiment and Data-driven process modeling strategy.

Instructors:

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

Moritz von Stosch, PhD, Senior Manager, Fermentation, GlaxoSmithKline Pharma GmbH

* Separate registration required. Dinner Included.

Thursday, 22 MARCH

8:00 Registration and Morning Coffee

Overcoming Production Challenges

8:25 Chairperson’s Remarks

Inês A. Isidro, PhD, Scientist, Computational Biotechnology, Animal Cell Technology Unit, iBET - Instituto de Biologia Experimental e Tecnológica

8:30 Manufacturing a Therapeutic Fab for High Concentrations - Filtration and Viscosity Challenges

Marc_PompiatiMarc Pompiati, Dipl.-Ing., Senior Scientist, Roche Diagnostics

It is critical in the production of ophtalmological therapeutics from E. coli to formulate proteins at very high concentrations. The applicable volume into the eye is limited, therefore, high protein concentrations are common. One of the challenges we encountered during the process of concentrating a Fab were high viscosity and the Donnan effect. In this presentation, we will show our method for developing a novel clarification method of periplasmatic extract, and a suitable tangential flow filtration and concentration step.

9:00 Enabling Continuous Upstream Bioprocessing - Using Tunable Promoters and Model Based Control Tools

Christoph_HerwigChristoph Herwig, PhD, Professor, Biochemical Engineering, Institutes of Chemical, Environmental and Biological Engineering, ICEBE, Technical University of Vienna

Robust downstream processing needs a robust upstream process also. Only to prolong a culture by perfusion techniques, for example, does not necessarily lead to continuous bioprocessing. More importantly, steady-state conditions in terms of productivity and product quality are needed. This contribution focuses on tunable promoters allowing continuous processing without perfusion and reaching steady-state conditions in the induced state. We use mixed feed systems which need multiparametric model based control strategies to accomplish this task.

Hovione9:30 Spray Drying - a Viable Alternative to Biopharmaceuticals?

Marcio_TemtemMarcio Temtem, Associate Director, PD & Pharmaceutical Development, Hovione SA

Spray drying is explained by the fact it is a scalable drying process suitable to convert liquid streams into dry powders with a broad range of properties. In this talk the authors will present examples of such processes and the advantages of spray drying over conventional technologies.

Flownamics9:45 Presentation to be Announced

10:00 Streamlining mAb Platform Processes: Integrating Single-Use Adsorptive Filtration as a Unit Operation for Virus Clearance

Anja_TrappAnja Trapp, MSc, Scientist, Bioprocessing Technology & Innovation, Rentschler Biopharma SE

Our goal was to take the full advantage of positively charged depth filters by addressing the removal of process-related impurities and viral contaminants. Results of our extensive virus spiking studies demonstrate the capability of anion exchange (AEX) filtration as an adsorptive unit operation for virus removal. Charged single-use filters are an excellent alternative to AEX resins and adsorbers. Key process economic advantages include higher flow rates, reduced process time, disposability and lower buffer consumption while ensuring virus safety of two-column mAb processes.

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

OPTIMISING BIOREACTORS

11:15 Accelerating Cell Culture Process Development with the Help of a 24-Well Miniature Bioreactor

Frank_BaganzFrank Baganz, PhD, Senior Lecturer/Associate Professor, Biochemical Engineering, University College London (UCL)

The need to bring new biopharmaceutical products to market more quickly and to reduce final manufacturing costs is driving early stage, small-scale bioprocess development. This presentation will cover the engineering characterisation of a single-use 24-well parallel miniature bioreactor (MBR) in terms of power input, liquid phase mixing and oxygen mass transfer. Examples will be given for the application of this MBR to rationally scale cell culture processes.

11:45 Bioreactor-Based Optimization and Scale-Up Issues for Large-Scale Manufacture with Suspension Culture of Animal Cells

Maria_WurmMaria Joao Wurm, PhD, CEO and Co-Founder, ExcellGene SA

The biology of CHO cells or others is highly complex and poorly understood. Manufacturing processes need to be addressed from a chemical engineering perspective, but by far more challenging are biological issues, such as the diversity of physiology, genetics, and product quality requirements. This talk will focus on topics facing the scientist/engineer when the work at small scale is trying to establish a process to be scaled up into stainless steel, or more frequently now, into “disposable” bioreactors of different shapes and performance.

12:15 Impact of Bioreactor Design on Human Stem Cell Bioprocessing

Serra_MargaridaMargarida Serra, PhD, Senior Scientist, Cell Bioprocesses Laboratory, Health & Pharma Division, Animal Cell Technology Unit, iBET
Human pluripotent and adult stem cells constitute an extremely attractive tool for cell therapy. However, flexible platforms for the large-scale production of these cells in tightly controlled conditions are necessary to deliver high quality cells in clinically relevant quantities. This presentation will focus the main principles for the bioprocessing of stem cells, highlighting the impact of environmental factors, novel 3-D culturing approaches and bioreactor design for controlling stem cell fate and culture outcome.

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:15 Session Break

Scaling Down and Up

13:45 Chairperson’s Remarks

Maria Joao Wurm, PhD, CEO and Co-Founder, ExcellGene SA

13:50 Developing Robust Scale-Down Models for Bioreactor Processes while Bridging the Gap between Single-Use and Stainless Steel Systems

Ashley_WitmerAshley Witmer, Associate Director, Bioreactor Scale-Up and Development, Regeneron Pharmaceuticals
Combining traditional and novel scale-down approaches to characterize pilot bioreactors has resulted in enhanced process knowledge and better predictability of manufacturing scale performance for production of monoclonal antibodies. In addition to defining scale-up parameter setpoints for transfer, statistically-designed, pilot-scale studies applying Quality by Design principles are employed to bridge the gap between bioreactor types ensuring robust process performance across scales.

14:20 Bioprocess Development – Moving through the Scales with More Confidence

Jarka_GlasseyJarka Glassey, PhD, Professor, Engineering, Newcastle University

Speed to market is essential in the biopharmaceutical sector, and while Quality by Design approaches marked progress in process and product understanding and more rapid and structured process development, scale-up still represents a significant challenge in introducing new biopharmaceuticals to market. This contribution will explore the use of scale-down models and the benefits of multivariate data analysis methods in combination with high-throughput/single-use technology to facilitate rapid bioprocess development.

14:50 Feedback on Single-Use Manufacturing and New Approach for Scale Transfer

Flavien_ThuetFlavien Thuet, MEng, CoE Team Leader, Operation, Merck Biodevelopment

The aim of this presentation is to share feedback after 2 years of using large-scale single-use systems (SUS). First, the benefits offered by these systems will be discussed under an organizational/plant management perspective. As a case study, the Merck Biodevelopment GMP plant organization will be discussed. Then, recent results obtained at 2KL scale will be shared. The process involves a new challenging cell line, and the quality results obtained will be discussed.

15:20 Close of Conference