Scaling Up and Down Strategies for Protein Production


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TUESDAY, MAY 6

7:45 am Morning Coffee

 

Bioreactor PROCESSING & OptimizatioN 

8:25 Chairperson's Remarks

Hao Chen, Ph.D., Principal Scientist, Merck

8:30 Case Study: Improving the Comparability and Predictability of a Scale-Down Model for Monoclonal Antibody Production Processes

Scott Camberg, MS, Principal Scientist, Process Development, Amgen

9:00 Using Models to Address Scale-Related Challenges in Industrial Fermentation Technology

Krist GernaeyKrist Gernaey, Ph.D., Professor, Center for Process Engineering and Technology (PROCESS), Chemical and Biochemical Engineering, Technical University of Denmark

This lecture will focus on scaling problems, and on the tools – experimental methods and modeling tools – available to support scale-up. Reaction kinetics can be assumed constant across scales, and process development is based on exploiting knowledge on reaction kinetics obtained at small scale to predict performance at production scale. Mathematical models, validated with sufficient experimental data, can be a great help in this exercise.

9:30 A Comparative Study between Bench-Top Single Use Bioreactor Vessels and Their Counterpart Reusable Glass Vessels

Kamal RashidKamal Rashid, Ph.D., Director, Biomanufacturing Education and Training Center, Worcester Polytechnic Institute

Large scale single-use stirred-tank bioreactor systems have been on the market for a number of years now, but until recently single-use bench-scale stirred-tank bioreactors have not been commercially available. With the development of the New Brunswick CelliGen® BLU pitched-blade bioreactor in 2009 and other brands, single-use bench-top stirred-tank bioreactors have become a reality.  At present, few research based publications are available on the utility of these bioreactors for bench-scale production of recombinant products.   The objective of this study was to perform multiple comparisons with these single use bioreactors and the traditional glass vessel counterparts.

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

Pfenex10:30 Poster Award in the Exhibit Hall


 

DISPOSABLES 

10:45 Downstream Processing: Disposable Options in Processing of Complicated Feed Streams within Bioprocessing Operations

Michael JarpeMichael Jarpe, Ph.D., Vice President, Biologics Development, Allergan

The process development, scale-up and manufacture of vaccine candidates as well as the characterization and IND filing of vaccine or therapeutic products are currently the bottlenecks in bioprocesses. In this presentation, we will explore the different upstream and downstream options for the process development and manufacturing of products focusing on cost-effective disposable and flexible options for facility integration.

11:15 Benefits of Disposables in Non-Platform Manufacturing of Fusion Protein

Stefan SchmidtStefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology

In selected case studies, we demonstrate how to overcome the typical difficulties of processing fusion proteins such as low titer, lack of an affinity matrix, tendency to aggregate etc. Strategies in the context of fusion proteins are summarized, highlighting approaches such as utilization of disposable equipment or DoE to accelerate their process development and scale up for clinical applications.

11:45 Evaluation of Single-Use Bioreactors for Perfusion Processes

Richard Pearce, Commercial and Operations Director, Merck BioDevelopment

The aim of our study was to combine standard single use bioreactors with different perfusion technologies and to compare productivity and molecule quality. Without any modification of the Single Use Bioreactor, we were able to demonstrate the compatibility with a mAb perfusion process with a significant increase in productivity. This study demonstrates the flexibility of existing disposable bioreactors to new bioprocessing technologies.

12:15 pm Luncheon Presentation I: Automation of Small Scale Purification Enables Accelerated Process Development

Andrew Barry, MS, Director, Applications & Biology R&D, PerkinElmer

Small scale protein purification presents opportunities for accelerated process development of biotherapeutic molecules. The PerkinElmer Janus BioTx Pro and Pro-Plus Workstations were developed as intuitive, flexible, automated devices capable of performing parallel small-scale analytical protein purification. In order to understand the capabilities of a robotic platform to miniaturize chromatographic purification of proteins that is predictive of higher scale purification platforms while offering advantages in speed and number of samples processed, a series of experiments were performed comparing the Janus BioTx Pro Plus system with GE AKTA Express chromatography.

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

1:15-1:45 Ice Cream Break in the Exhibit Hall

 

SCALING UP 

2:00 Chairperson's Remarks

Yamuna Dasarathy, Ph.D., Director, Marketing, Pall Life Sciences

2:05  Case Studies on Scaling Up a Monoclonal Antibody Purification Process for Clinical Manufacturing at a CMO – The Good, Bad and Ugly

Yun Bai, Ph.D., Associate Director, Process Development, Ambrx, Inc.

Despite the fact that monoclonal antibody products have been around for a long time and a significant amount of effort has been made in developing platform processes for mAb production, each mAb product is unique and constantly challenges the platform process. An appropriate and effective PD strategy is, therefore, necessary to leverage the platform knowledge to the distinctiveness of the individual mAb molecule in order to minimize PD time and risk while maintaining process efficiency and robustness. This presentation will focus on several case studies from a mAb project which is currently in the clinical manufacturing stage. Detailed process development and scale-up data will be presented and discussed to demonstrate the challenges often encountered in mAb PD and manufacturing.

2:35  Large-Scale Automation of Plasmid DNA Purifications for Transient Mammalian Protein Expression

Mark NagelMark Nagel, Senior Research Associate, Protein Chemistry, Genentech

Advancing research projects require increased amounts of proteins and plasmid DNA. Here we describe the development of a preparative three series large-scale automated (LSA) plasmid DNA purification process utilizing the GE Akta Xpress. This new process includes physical modifications of the Xpress flow paths, incorporates unique Unicorn programs that isolate a single flow path for each of the serial purifications and has specialized cleaning programs.

3:05  Identification and Risk Mitigation of a Critical Process Parameter during Antibody Process Scale-Up

Susan Dana Jones, Ph.D., Vice President and Senior Consultant, BioProcess Technology Consultants
Jonathan Mitschelen, Ph.D., Vice President, Upstream Process Development, Cytovance Biologics

Rapid process development of a therapeutic monoclonal antibody was performed to enable production of Phase 1 clinical material at the 100 – 200 L scale.  Working against a tight timeline, process parameters were not rigorously defined during process development or Phase 1 production.  When the process was scaled to 1,000 L for Phase 2 production, cell growth was slower and productivity was much lower than anticipated.  A detailed review and risk assessment of available development and manufacturing data was performed and depletion of a single nutrient was identified as the most likely cause.  This talk will present the risk assessment and the successful outcome of an increased process control strategy on the performance of the scaled up process.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

 

Scaling Down  

4:15 Scaling Down with High Cell Densities: Evaluating the TAP AMBR250 Microbioreactor for High-Throughput Fermentation Process Development

Bob KuczenskiBob Kuczenski, Ph.D., Engineer II, Genentech

The majority of E. coli fermentation process development at Genentech is performed at the 10 L pilot scale, which while costly, scales well to production scale. We will present our evaluation of the TAP AMBR250 bioreactor and discuss how this automated platform could increase throughput and reduce cost in fermentation process development.

4:45 Mammalian Cell Culture Process Scale-Down Model Development in Single-Use Bioreactors

Hao ChenHao Chen, Ph.D., Principal Scientist, Merck

Despite the convenience of set-up and improved automation, Single-Use Bioreactors have unique challenges as scale-down models for mammalian cell culture. Here, we explored using Single-Use Bioreactors as scale-down models at four different scales (15 mL - 200 L). Multivariate Data Analysis (MVDA) tools are applied to establish effective models for fed-batch process up to 12,000 L scale.

 

 

5:15 End of Conference

 

Recommended Tuesday Dinner Short Course* 

Production Challenges for Complex Biologics – ADCs, Bispecifics & Fusion Proteins - View Detailed Agenda 

*Separate registration required. 

 

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