Cambridge Healthtech Institute’s Inaugural
Continuous Processing in Biopharm Manufacturing
Economics, Regulatory, Integration and Practical Implementation
August 5-6, 2015
Part of CHI's 7th Annual The Bioprocessing Summit
August 3-7, 2015 | Westin Copley Place Hotel | Boston, Massachusetts
One of the most exciting developments in the bioprocessing field today is Continuous Processing. As a transplanted concept from pharma and food industry, Continuous Processing holds promise for increasing product throughput and ameliorating downstream
bottleneck in biopharm processing. Coupled with disposables technology and advances in continuous chromatography, the dream of a scalable, flexible and high productivity facility of the future is fast becoming a reality. However, before we get there,
there are hurdles in the Continuous Processing field that need to be addressed, from the simplest question of the definition of a “batch” in continuous mode, to the complex issues of column scale, the variations in continuous technology,
and the feasibility of migrating from batch to continuous.
At CHI's Continuous Processing in Biopharm Manufacturing, we bring to light the questions and uncertainties and put them in front of the audience to discuss and debate, and find out if continuous processing is the right solution to your manufacturing
Wednesday, August 5
7:00 am Registration and Morning Coffee
8:05 Chairperson’s Remarks
Massimo Morbidelli, Ph.D., Professor, Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich
8:15 KEYNOTE PRESENTATION:
Continuous Processing – Rewrite of the Rules?
Wayne Froland, Ph.D., Associate Vice President, Center for Biopharmaceutical Manufacturing
Sciences, Merck Manufacturing Division
9:00 The Future State of Bioprocessing
Lawrence Weiner, Senior Director, Strategic Innovation, Biogen
Disruptive innovation is required to deliver game changing improvements demanded by the market and industry. We will discuss Biogen’s approach to implementing near term sustaining and long term disruptive technologies. The discussion will include
how technologies are selected and driven forward to implementation. We will also discuss a few opportunities for innovation within existing technologies and share thoughts on continuous manufacturing as an alternate route to maximize productivity.
9:30 The Old Is New Again: A Fair and Balanced Assessment of Continuous Bioprocessing
Sadettin S. Ozturk, Ph.D., Assoc Deputy Director, Process & Analytical Development,
Although it is somehow branded as new, continuous bioprocessing has been utilized over 25 years that has resulted in more than 15 licensed biopharmaceuticals. Recent attempts of re-popularizing the continuous bioprocessing receive mixed reactions
form the industry: great enthusiasm, confusion, and skepticism. This talk will present an assessment of continuous bioprocessing against well-established fed-batch platform and provide a historical and futuristic perspective.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Economics of Continuous Processing Vs. Traditional Batch
Jeff Johnson, New Technology Lead, Merck & Co. Inc.
Opportunities for applying new technologies integrated with continuous processing and enabled by single use will be discussed for monoclonal antibody production. The combined efficiencies gained by continuous processing will be compared by economic
criteria to current manufacturing methods. In addition the impact of the new approaches to multi product manufacturing facilities will be described.
11:15 The Regulatory and Quality Perspective on Continuous Processing
Robert Kozak, Ph.D., Senior Regulatory Science Advisor, Global Regulatory Affairs, Bayer
Continuous perfusion production has enabled flexible manufacturing of rFVIII, a large complex biotech product, for over two decades. Continuous improvement has driven frequent process, equipment and facility changes supported by comparability exercises
assessing the impact to quality product attributes throughout the entire fermentation campaign which can be months in duration. Examples of process changes implemented and non-implemented will be reviewed along with the impact of a changing regulatory
Simplifying Continuous Chromatography Process Development - Optimisation Parameters to Fit Business Need
René Gantier, Ph.D., R&D Director, Biopharm Applications, Pall Life Sciences
Continuous capture multicolumn chromatography (MCC) is a key unit operation in the development of continuous, integrated processes. But how are continuous capture MCC processes developed and optimized using only small quantities of feedstock? We have
developed and tested a new method to accurately translate data from a minimal number of single column runs into a low cost multicolumn process. This new simple process transfer from batch to continuous enables process optimization to fit business
12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:30 Session Break
1:55 Chairperson’s Remarks
Andrew Sinclair, FREng, MSc, President & Founder, Biopharm Services Ltd.
2:00 Integration of Up- and Downstream Continuous Processing
Massimo Morbidelli, Ph.D., Professor, Institute for Chemical and Bioengineering,
Department of Chemistry and Applied Biosciences, ETH Zürich
We discuss here a series of experiments where a perfusion reactor with CHO cells for the production of a monoclonal antibody has been operated in the continuous mode and connected to a two column continuous protein A chromatographic unit for product
capture. A few steady states are examined and the use of simulation models for process design and control is illustrated.
2:30 Continuous Manufacturing: Upstream vs. Downstream Issues and the Drivers
Andrew Sinclair, FREng, MSc, President & Founder, Biopharm Services Ltd.
Our experience of modelling continuous bioprocess operations allow us to provide insights into the status of continuous bioprocessing. This allows us to identify those factors that require optimization/development and to understand the potential now
and for the future. In particular we focus on the influence of upstream versus downstream and the implication of technology trends on the value proposition for continuous operation.
3:00 Continuous Operations in Biopharm Manufacturing: Back to the Future
Bielser, MSc. (Eng), Assistant Scientist, BioProcess Science, Merck Serono Switzerland
At early stage of bioprocess science, continuous operations were the workhorse in the industry. Then, for the past 10 years, we moved towards fed-batch operations. Recently, continuous operations is considered again as a lever to boost process
productivity and control product quality. Looking at bioprocess history, this presentation will discuss the reasons of those “back and forth” trends. It will also present results obtained at EMD-Serono using continuous operations
in cell-culture and also in purification of biopharmaceuticals. Finally, it will discuss the challenges and opportunities of continuous operations versus current established fed-batch platform.
3:30 Breakout Discussions
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 explore potential solutions to persistent challenges.
Table: What are the impediments for perfusion process expansion today and how should we tackle these?
Moderator: Veronique Chotteau, Ph.D., Principal Investigator, Cell Technology Group, School of Biotechnology, KTH, Royal Institute of Technology
Material: such as equipment for perfusion, scale-up or scale-down
Cultural and pragmatic: why change something, which is legacy and
Knowledge: the community has not the knowledge today, either from not
enough published information or not enough trained 'perfusion
Table: An Examination of Barriers to the Commercial Adoption of Continuous Processes for Production of Biologicals
Todd Przybycien, Ph.D., Professor, Chemical Engineering and Biomedical Engineering, Carnegie Mellon University
- Regulatory hurdles – who goes first?
- Critical path hurdles – how long to develop and validate?
- Process development hurdles – are scale-down models available for development efforts?
- Process hurdles – how robust are integrated processes to fluctuations?
- Equipment hurdles – how robust is the equipment – particularly for single use formats?
- Monitoring and control hurdles – is the available PAT sufficient to support the necessary level of automated control?
- Economic hurdles – what are the current rosy economic predictions missing?
Table: The Challenges of Keeping Pharmaceutical Aging Facilities Fit for Purpose
Moderator: Morten Munk, Senior Technology Partner, Global Business Development, NNE PharmaPlan
- Aging facilities are a major concern for industry and regulators, due to the risk of supply of suboptimal quality products and possibly drug shortage situations
- Share insights on the challenges and what might hold the industry back from implementing up-to-date solutions
- Discussion on the facilities, processes, analytical methods and manufacturing control strategies
- Special focus on the regulatory impact and strategy for implementing the needed changes in all the mentioned areas
Table: Implementing Continuous Bioprocesses in GMP Manufacture
Moderator:Peter R. Levison, Ph.D., Senior Marketing Director, Downstream Processing, Pall Life Sciences
- Assuming the purification technologies and materials used in both batch and continuous processes are identical are these processes interchangeable during design, development, scale-up and production?
- Large fed batch culture is today's start point for DSP. Does the future include a series of staged smaller fed batch bioreactors and/or perfusion cell culture processes
- What other platforms and/or continuous processes are required for non-Mab applications?
4:00 Refreshment Break in the Exhibit Hall with Poster Viewing
4:45 Chair’s Remarks
Sam Ellis, Vice President, Biochemist, Thomson Instrument Co.
4:50 PLENARY KEYNOTE PRESENTATION:
Meeting the Needs of Patients with Rare Diseases: Innovation in Product Development
Joanne T. Beck, Ph.D., Senior Vice President, Pharmaceutical Development,
At Shire, where the delivery of innovative medicines to patients with rare diseases and other specialty conditions is a fundamental component of the business model, creative solutions are critical to our success. Starting with the transition
of drug candidates from discovery research to the clinic, followed by late phase development and eventually commercial product lifecycle management, scientists and engineers focus on both technology innovation and creative business approaches
to deliver high quality therapies to the patients while decreasing development timelines and costs.
5:20 INTERACTIVE PANEL DISCUSSION:
How to Innovate Product Development
- Cutting Costs
- Meeting needs
- Utilizing creativity
- Lessons Learned
Joanne T. Beck, Ph.D., Senior Vice President, Pharmaceutical Development, Shire Pharmaceuticals
Wayne Froland, Ph.D., Associate Vice President, Center for Biopharmaceutical Manufacturing Sciences, Merck Manufacturing Division
Schmidt, Ph.D., M.B.A., Vice President, Process Science & Production, Rentschler Biotechnologie GmbH
Haripada Maity, Ph.D., Research Advisor, Eli Lilly and Company
6:00 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
Thursday, August 6
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Remarks
Andrew Zydney, Ph.D., Distinguished Professor, Chemical Engineering, The Pennsylvania State University
8:30 Perfusion Process for Very High Cell Density of CHO Cells
Veronique Chotteau, Ph.D., Principal Investigator, Cell Technology
Group, School of Biotechnology, KTH, Royal Institute of Technology
Perfusion processes at high cell densities are perceived as a viable solution for the production of biopharmaceuticals, allying small volume bioreactors, compatibility with disposable equipment and continuous manufacturing concept reclaimed
by the Health Authorities. We will review our strategy for the development of high cell density processes looking in particular at the medium renewal rate minimization using cell separation by Alternating Tangential Flow filtration.
9:00 Continuous Chromatography – Why, When and How?
Zydney, Ph.D., Distinguished Professor, Chemical Engineering, The Pennsylvania State University
There is growing interest in the use of continuous unit operations for bioprocessing with the ultimate goal of developing an integrated continuous process. This talk will focus on the opportunities for continuous chromatographic separations,
including both the challenges and the potential advantages of this approach. Specific examples will be shown for the application of periodic (multi-column), simulated moving bed, and countercurrent tangential flow chromatography to
the purification of monoclonal antibodies.
9:30 Continuous Multi-Column and Integrated Purification Strategies for Enveloped Virus-Like Particles and Non-Enveloped Viruses
Ricardo Silva, Ph.D., Downstream Processing Research, iBET - Instituto
de Biologia Experimental e Tecnológica
The growing interest on enveloped virus-like particles and non-enveloped viruses for vaccines and gene therapy applications led to the development of new purification strategies capable of coping with the challenges presented by these
new products. Innovation in downstream processing should therefore aim not only at productivity increase but also at process economy whilst complying with regulatory requirements. Evaluation of integrated purification strategies and
two-column semi-continuous chromatographic systems for virus and enveloped virus-like particles will be reported. Significant improvements in yield and product quality thus obtained will be highlighted.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 A Continuous Precipitation Process for High-Titer Recombinant Protein Capture and Purification
Przybycien, Ph.D., Professor, Chemical Engineering and Biomedical Engineering, Carnegie Mellon University
Coupled precipitation-filtration operations can form the basis of a continuous, scalable, economical and generalizable platform process for the primary recovery of high titer recombinant proteins. We have used synergistic combinations
of precipitants to selectively precipitate target proteins, spanning a broad range of physical properties, against backgrounds of complex contaminants. We have evaluated the performance of the proposed process with simulations and
reduced it to practice with an industrial partner.
11:15 Behavior of a Ceramic Membrane-based Perfusion CHO Culture System for Production of IgG1
Jean-Francois Hamel, Ph.D., BPEC Core Laboratory Supervisor, MIT
11:45 Continuous Chromatography in Downstream Processing – How to Make It a Reality
Kathleen Mihlbachler, Ph.D., Global Director, Separations
Development, LEWA Process Technologies
Multi-column continuous chromatography has recently become an enabling technology that will “break the bottleneck” in downstream processing of biopharmaceuticals. Continuous chromatography has shown promises in reduction of
manufacturing cost. However, up to today there has not been a reported case at the production scale. What are the remaining technical barriers when implementing the technology in the GMP environment? This presentation highlights how
to overcome the major barriers when developing this technology platform.
12:15 pm What is Holding the Industry back from Implementing Continuous Processing More Broadly?
Morten Munk, Senior Technology Partner, Global Business Development, NNE PharmaPlan
Based on a survey among industry peers on continuous processing, this presentation will address various concerns around continuous processing, and real concerns are distinguished from perceived concerns. This presentation will not be another
presentation on the financial benefits of continuous processing or a report on the newest equipment on the market. The aim of the presentation is to discuss and illustrate other elements which make the difference between success and
failure when a continuous processing strategy is evaluated and implemented.
12:45 Close of Conference