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 challenges. 

Wednesday, August 5

7:00 am Registration and Morning Coffee

CONTINUOUS PROCESSING AS A DISRUPTIVE INNOVATION IN BIOPROCESSING

8:05 Chairperson’s Remarks

Massimo Morbidelli, Ph.D., Professor, Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich

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, MassBiologics

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

CONTINUOUS PROCESSING VS. FED-BATCH: ECONOMIC AND REGULATORY PERSPECTIVES

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 Healthcare

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 environment.

11:45 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 needs.

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Session Break

INTEGRATION OF UP- AND DOWN-STREAM PROCESSING

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

Jean-Marc 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 working well?

·      Knowledge: the community has not the knowledge today, either from not enough published information or not enough trained 'perfusion people'   

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

PLENARY SESSION

4:45 Chair’s Remarks

Sam Ellis, Vice President, Biochemist, Thomson Instrument Co.

5:20 INTERACTIVE PANEL DISCUSSION:

How to Innovate Product Development

• Technologies
• Strategies
• Cutting Costs
• Meeting needs
• Utilizing creativity
• Lessons Learned

Panelists:

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
Stefan 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

IMPLEMENTATION CHALLENGES IN UPSTREAM PERFUSION AND DOWNSTREAM CHROMATOGRAPHY

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?

Andrew 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

Todd 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

.

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