Cambridge Healthtech Institute’s 2nd Annual
Continuous Processing in Biopharm Manufacturing
Reinventing Process Architecture with Integration, Intensification and Automation
Part of CHI's 8th Annual The Bioprocessing Summit
August 15-16, 2016 | Westin Boston Waterfront | Boston, Massachusetts

The industry is just at the tip of the iceberg when it comes to continuous biomanufacturing. Companies are weighing the pros and cons, figuring out the regulatory requirements and quality impact, evaluating the technologies, assessing their internal product needs and facility-fit to determine if and when it makes sense to move from batch to continuous, and how. Meanwhile, on the technology side, many different concepts and models are emerging featuring semi- to fully integrated continuous manufacturing.

The 2nd Annual Continuous Processing in Biopharm Manufacturing conference brings together scientists and opinion leaders to share their perspectives and experiences, from evaluating the economic benefits to reinventing process architectures, from incorporating technology and automation to overcoming challenges and hurdles in integration and implementation.

Final Agenda

Monday, August 15

8:00 am Short Course Registration

11:30 Main Conference Registration Opens

CONTINUOUS UPSTREAM PROCESSING

1:00 pm Chairperson’s Opening Remarks

Andrew Sinclair, MSc., FREng., President and Founder, Biopharm Services Ltd.

1:45 Medium Development for Next-Generation Perfusion Processes

Jochen B. Sieck, Ph.D., Lab Head, Cell Culture Media R&D, Process Solutions R&D, Merck KGaA

Perfusion processes have fundamentally different requirements for cell culture media, compared to fed-batch processes. Desirable characteristics also depend on the type of perfusion process that is targeted. In this talk we will present how different manifestations of perfusion impact these requirements and present data on how they can be addressed in medium development.

2:15 Scalability of Growth Characteristics and Product Quality: Efficient Downscale Perfusion Bioprocess Development Using DOE Studies

Steffen Kreye, MSc, Scientist, USP Development, Glycotope GmbH

The sedimentation based down-scale perfusion system SAM (10mL reactor volume) has been developed to characterize the upstream process parameters and their influence on product quality. Using DoE studies we gain a highly efficient method for media development as well as process optimization to achieve higher cell densities and higher productivities. Scalability and reproducibility of perfusions bioreactors (10mL – 1000L) will be highlighted with data of the fully human, high yield production and glycooptimization platform GlycoExpress (GEX).

2:45 Refreshment Break

3:15 Perfusion Process Applicability

Jacob Jensen, Senior Manager, Global Program Management, Biogen

Perfusion processes extends the time in the manufacturing bioreactor and may not be directly applicable to conventional fed-batch processing. This talk will focus on how the benefits of perfusion can be integrated in a fed-batch process to increase product output.

3:45 Poster Highlight

Evaluation of Flow-VPE for In-Line Concentration Measurement of Monoclonal Antibodies during Chromatography

Pranali Shah, Ph.D., Senior Associate, Purification Process Development, Amgen, Inc.

Process analytical technology (PAT) has received considerable attention in recent years in the biopharmaceutical industry following the FDA's initiative on identifying PAT as a key element of the Pharmaceutical Current Good Manufacturing Practices (cGMPs). A desired goal of the PAT framework is to design and develop well-understood processes that will consistently ensure a pre-defined quality. There is also a critical need for the development of real-time PAT that is capable of identifying changes in key product quality attributes (e.g. aggregation and glycosylation) and process performance (yield) during continuous processing. In this study we integrated Flow VPE(TM) instrumentation with AKTA chromatography systems for in-line real time concentration measurement of monoclonal antibodies during Protein A and ion exchange chromatography unit operations. This study provides insight into the application of Flow-VPE(TM) technology for full peak characterization, novel load breakthrough detection, and improved peak cut criteria, which are important steps towards longer-term implementation of the technology for real-time applications. 

4:00 A Membrane-Less Cell Retention Device Based on Inertial Sorting for Perfusion Cultures

Taehong Kwon, MSc, Research Assistant, Electrical Engineering and Computer Science, MIT

Membrane-based cell retention technologies (e.g., hollow fiber membranes) are currently used in perfusion cultures despite the limitations of membrane fouling and clogging. We developed a membrane-less clog-free retention device based on inertial sorting, and used it for IgG-producing perfusion CHO cultures. This talk will introduce the novel cell retention device and discuss its challenges and promises for continuous processing in biopharmaceutical manufacturing.

4:30 Breakout Discussions

Challenges Faced in Validating Continuous Manufacturing on Your Own or Partnering With Suppliers on Validation Efforts for Continuous Manufacturing

Moderator: Michelle Bailey, Ph.D., Head, Validation of Continuous Manufacturing and Process Automation, Vertex Pharmaceuticals (invited)

• Where should the line be drawn to ensure the customer is able to assume required accountability for the validation and release of a system? To what extend should you leverage suppliers to provide validation deliverables?
• What should go into a Supplier-provided Quality Project Plan (QPP) vs the Validation Plan written under Customer procedures, and should Suppliers contribute to the Validation Plan and if so, how much? HOw should a Supplier QPP be leveraged?
• How would you envision the project to be managed and who should assume key responsibility for meeting milestones, particularly where there are a number of suppliers involved? 
• How would you envision breaking down the validation effort for such a highly integrated system such as that used in Continuous Manufacturing? Is it feasible to fully qualify each component separately and also as an integrated whole? What approach(es) might you take?

Adapting Manufacturing Options to Growing Production Needs

Moderator: Robert Dream, PE, CPIP, Managing Director, HDR Company, LLC.

5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day

Tuesday, August 16

7:30 am Registration Opens and Morning Coffee

CONTINUOUS DOWNSTREAM PROCESSING

7:55 Chairperson’s Remarks

Robert Dream, PE, CPIP, Managing Director, HDR Company, LLC

8:30 Continuous Manufacturing, Hybrid Options Transitioning from Batch to Continuous: Economics and Operational Implications

Andrew Sinclair, MSc., FREng., President and Founder, Biopharm Services Ltd.

This presentation will assess the reality of transitioning to the hybrid option by providing insights on where this makes practical and economic sense within a process. This allows us to identify those factors that require optimization/development in terms of the potential now and for the future. Here the focus is on describing the approaches to hybrid downstream processing in terms of the mode of operation, integrating batch processing into continuous operations and looking at the impact on buffer supply to the process.

9:00 Continuous Chromatography for Purification of Virus and Virus-Like Particles Targeting Vaccine and Gene Therapy Applications

Ricardo Silva, Ph.D., Researcher, Downstream Processing Lab, Animal Cell Technology Unit, iBET – Instituto de Biologia Experimental e Tecnologica

Novel biopharmaceutical products are a challenging task for downstream processing. Alternative purification strategies that can improve the purification yield, such as continuous chromatography, are regarded nowadays as enabling technologies to overcome the capacity bottleneck in biomanufacturing. The current talk will focus on the development of multi-column chromatographic systems aimed at the purification of gene therapy vectors and enveloped virus-like particles produced using insect cell-based expression system for vaccine applications.

9:30 Comparison of Batch and Continuous Multi-Column Protein A Capture Processes

Thomas Mueller-Spaeth, Ph.D., Professor, Institute for Chemical and Bioengineering, ETH Zurich

Protein A affinity chromatography is used as a powerful purification platform in industry for capture of a number of therapeutic proteins including mAbs and fusion proteins from cell culture harvest. In the last years, the stationary phase capacity utilization and productivity of affinity chromatography has been significantly improved by newly introduced multi-column sequential loading processes for continuous mAb purification. This presentation provides a side-by-side comparison Protein A capture processes with 1 to 4 columns based on a chromatographic simulation model that was calibrated and validated using experimental capture data. The processes were compared in terms of resin costs, productivity, buffer consumption and equipment complexity. The study shows significant advantages of the twin-column process over batch chromatography and other multi-column processes.

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

MONITORING, CONTROL & VALIDATION OF CONTINUOUS PROCESSES

10:30 Implementation of Model Predictive Fermentation Process Control Strategies - Experienced Challenges and Strategies on How to Solve These Problems

Gerald Striedner, Ph.D., Assistant Professor, Biotechnology, University of Natural Resources and Life Sciences

We established data driven models for real time prediction of relevant process variables as basis for an advanced process control strategy. We used the predicted biomass in the process to calculate the inducer feed profile that allowed for setting a constant inducer to biomass ratio and thereby indirect control of the product formation rate. During implementation and evaluation of this advanced process control strategy we experienced various challenges and we also identified strategies on how to further advance this concept.

11:00 PAT Strategies in Support of Process Monitoring and Control to Enable Rapid Product Release

Jeffrey Doyle, Manager, PAT Projects, Pfizer, Inc.

Continuous bioprocessing offers potential to enhance productivity and product quality uniformity while simultaneously decreasing facility footprint and associated operational overhead. Advances in technology and increasing commercial pressures are leading to an increased interest in continuous processing across the biopharmaceutical sector. The advancement of continuous bioprocessing presents a range of opportunity and challenges, including the use of Process Analytical Technology (PAT) for process characterization, process control, and process robustness, in support of a Rapid Product Release (RPR) strategy.

11:30 Validation, Continuous Verification and Compliance of Continuous Manufacturing Operations

Michelle Bailey, Ph.D., Head, Validation of Continuous Manufacturing and Process Automation, Vertex Pharmaceuticals

The pharmaceutical industry is adopting continuous manufacturing models to drive efficiency and higher quality. These new technologies require effective approaches for validation. This presentation discusses challenges encountered and approaches taken to validate continuous manufacturing for multiproduct solid dosage product and preparing for a successful regulatory inspection.

12:00 pm A High Performance Integrated and Disposable Clarification Solution for Continuous Bioprocessing

Mike Collins, Principal Research Engineer, Pall Life Sciences

There is a growing interest within the biopharmaceutical industry in adopting continuous processing in place of current batch processing for biological molecules and primarily monoclonal antibodies (mAbs). Expectations from this transition are multiple including reduced product cost of goods, capital expenses and facility foot print while process productivity and flexibility is increased. But the adoption of continuous bioprocessing requires first to achieve a smooth transition for each process step from batch to continuous. The clarification is a key early step within the process which poses the challenge of reducing the cost and foot print of filtration in the context of a continuous mAb purification process.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing

INTEGRATED UP- AND DOWN-STREAM CONTINUOUS BIOMANUFACTURING

1:55 Chairperson’s Remarks

Todd Przybycien, Ph.D., Professor, Chemical Engineering and Biomedical Engineering, Carnegie Mellon University

2:00 Manufacturing Technologies to Enable Process Intensification

Jim Neville, Director, Technology Management- Americas', MilliporeSigma

The biopharmaceutical industry is adopting a more strategic view toward manufacturing, seeking solutions that offer increased productivity and improved economics without sacrificing process robustness. The industry addresses these challenges through process intensification efforts including unit operation optimization, linked and continuous processing. This presentation provides insight into upstream and downstream intensification approaches to improve processes. Examples include high producing and stable cell lines, column size reduction, product purity improvement and enabling a continuous process.

2:30 Building an Integrated Continuous Manufacturing Platform

Jonathan Souquet, Ph.D., Head, Biotech Process Sciences Technology & Innovation, Biopharma Global Manufacturing & Supply, Merck Serono

The objective of this presentation will be to provide invaluable insight into the design and development of a fully integrated platform manufacturing process operated in continuous mode. Challenges of integrating discrete unit operations to create a compact continuous processing drug substance manufacturing solution will be reviewed. Process design considerations and enabling technologies required to monitor, control and optimize the process will be discussed.

3:00 Integration of Single-Use Technologies and Continuous Processing for the Manufacturing of Therapeutic Proteins

Jorgen Magnus, Ph.D., Project Manager, R&D, Bayer Technology Services

Bayer is developing a novel production concept for monoclonal antibodies within the Mobidik project. All surfaces in contact with the product are in single-use technology and the downstream processing is run as a truly continuous process without intermediate storage. A process control system and on-line / at-line PAT are developed to give a high level of automation. GMP related issues are addressed at an early stage.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Challenges in the Development of Continuous Processes for Vaccines

Daniel C. Vellom, Ph.D., Senior Director, Global Technology Innovation, Sanofi Pasteur Biologics

Vaccine developers pursuing continuous manufacturing need to consider the nature of the batch production process and the economics supporting the transition to a new mode of manufacturing. Will the “new” product be comparable to the existing vaccine, or be considered a next-generation product in the eyes of the regulatory agencies? This presentation will outline these challenges and propose a general approach to development of a continuous vaccine production process, and new tools that can enable such development.

4:45 Closing Presentation: Integrated Continuous Biomanufacturing Enables More Efficient Cost-Effective Drug Manufacturing and Improved Process Safety

Robert Dream, PE, CPIP, Managing Director, HDR Company, LLC

The importance and value of continuous bioprocessing has economic and sustainability advantages and due to the modular nature of continuous bioprocesses it means that the industry is able to adapt more rapidly to changing market demands. Continuous manufacturing is as productive and with a much smaller footprint of the manufacturing plant, avoiding multiple non-value added unit operations. In essence, the investment for a continuous plant is much smaller compared to a batch-operated one.

5:15 End of Conference

5:15 Registration for Dinner Short Course