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TUESDAY, AUGUST 21
WEDNESDAY, AUGUST 22
This meeting will explore the process development strategies and computational tools for scaling up protein production, including representative scale-down models. Optimizing bioreactor engineering and design will also be addressed, along with single-use technologies and monitoring /analyzing processes to ensure optimal conditions and productivity. Join in the discussion with international experts who will share their important, innovative work and case studies with the shared goal of manufacturing protein-based products.
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Opening Remarks
» 8:30 OPENING KEYNOTE PRESENTATION:
What Scales Up Must Scale Down – Spinning Wheels?
Beth Junker, Ph.D., Senior Scientific Director, BioProcess Development, Merck Research Laboratories
Scale-down models have been and remain essential to process development, process performance qualification, and troubleshooting of scaled-up process operations. Practicality dictates that most process development experiments are conducted at the small scale. However, scale-down model fidelity varies considerably for different bioprocess steps, expression systems, and protein products. This talk presents the current state of scale-down models, offers an explanation about why this state exists despite decades of scale-up experience, and what advances need to be undertaken to "let the spinning wheel fly".
» 9:00 FEATURED PRESENTATION:
From Micro to Small Scale Fermentation – Combining Cell Line and Process Development
René Brecht, Ph.D., Vice President, Process Science & Manufacturing, ProBioGen AG
9:30 Consistent Fed-Batch Bioprocess Development in the µL to L-Scale
Stefan Junne, Ph.D., Group Leader, Process and Systems Biotechnology, Chair, Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin
From concept to market, it typically takes from 5 to 10 years for the development of biotechnological processes. The step from bench-scale to pilot- and production-scale is crucial, since multidisciplinary approaches are necessary to circumvent typical problems of the scale-up process. One factor causing issues is the inconsistency of the process mode. Therefore, we have developed in situ susbtrate delivery systems, which allow a fed-batch procedure in any scale. In combination with state-of-the-art experimental design approaches, a fast and consistent process development in well-plates on liquid-handling systems becomes possible. Therefore, also microsensor integration and scale-down reactor concepts in the L-scale are considered.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Qualification and Application of a Perfusion Bioreactor Scale-Down Model for Commercial Manufacturing Support
Caroline DiCesare, Process Engineer 1, Commercial Cell Culture Development, Genzyme Corp.
11:15 Computational Methods Supporting Process Intensification
Ulrich Krühne, Ph.D., Senior Researcher, Center for Process Engineering and Technology (PROCESS), Department of Chemical and Biochemical Engineering, Technical University of Denmark
The talk presents a number of case studies, where computational methods have been used for gaining a more detailed understanding of complex interactions in biochemical applications. The cases will comprise scenarios across scales reaching from microfluidic examples to pilot plant scale setups. Computational fluid dynamic (CFD) models coupled with biological models will be presented for shedding light on reactor design, determination of material properties and optimization routines.
11:45 Sponsored Presentation (Opportunity Available)
12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:55 Chairperson’s Remarks
2:00 Bioreactor Scaling Up and Down: How to Perform Successful Process Development
Aurore Lahille, Ph.D., Specialist, New Technologies and Manufacturing Support, Merck Serono
Manufacturing planning depends on performances derived from process development data. This presentation will provide guidelines to reach a successful bioreactor process scale-up and down. My talk will span either disposable or reusable small process development bioreactors (15mL to 3L) to more than 1000L bioreactor, illustrating Merck’s biodevelopment way forward.
2:30 Topology Optimized Bioreactors — A Design Example with Immobilized Yeast
Krist V. Gernaey, Ph.D., Associate Professor, Center for Process Engineering and Technology (PROCESS), Department of Chemical and Biochemical Engineering, Technical University of Denmark
This work exploits the increased design flexibility offered by microsystems for optimizing the operation of a microbioreactor. In this optimization project, the production of a recombinant protein in a continuous culture of immobilized Saccharomyces cerevisiae was used as a case study. A topology optimization methodology was applied to a mathematical model of the S. cerevisiae microbioreactor, in order to obtain the spatial distribution of immobilized yeast that maximizes protein concentration at the outlet. Compared to a stirred tank reactor, productivity improvements of up to a factor ten were predicted.
3:00 Insights into Large-Scale Bioreactors
Andreas Lübbert, Ph.D., Professor, Center for Bioprocess Engineering, Institute of Biochemistry and Biotechnology, Martin-Luther-University
In recent years we learned much about the transport properties of large bioreactors. Here we discuss the most important aspects, for instance, the improvements in our understanding of the oxygen mass transfer in stirred tank bioreactors, the problem of CO2 accumulation in large-scale cell culture bioreactors and its solution. We will focus on the mechanistic understanding of the effects and the validation of the corresponding engineering models by means of physical measurements.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Pilot Scale Fermentation
Kristie R. Apgar, Ph.D., Bioprocess Clinical Manufacturing and Technology, Merck Research Labs, Merck & Co., Inc.
4:45 Scaling-Down a Process: Lessons in Correcting Your Assumptions in Order to Create a Small Scale Bioreactor Model
E. Todd Sorensen, M.S., Development Associate 4, Alexion Pharmaceuticals, Inc.
The need for robust, reproducible large-scale cell culture bioreactor performance for the production of recombinant proteins and monoclonal antibodies led us to develop reliably predictable small-scale bioreactor models. During the exercise of creating a small-scale bioreactor model for our 10,000L Bioreactors, not only did we discover how to operate our bioreactors, we also learned that several of our initial assumptions were incorrect. Our approach started by defining requirements for our model such as retaining product quality attributes across scales and matching trends in growth and productivity. Next, we employed computational fluid dynamics (CFD) software in conjunction with a series of experiments to characterize each scale, focusing on: magnitude of shear forces, mixing time, bubble size distribution and liquid addition dispersion. We explored the impact of modifying a host of operating conditions including: agitation rate, pH setpoint, dissolved oxygen setpoint, sparge rate, location of liquid additions (i.e. feed and alkaline solution) and timing of liquid additions. Ultimately, we engineered our model to go from outperforming the large-scale by nearly 50% in terms of productivity to closely matching final titer while preserving product quality. We will discuss the lessons learned by going through this process.
5:15 Networking Reception, Last Chance for Exhibit and Poster Viewing
6:45 End of Day
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