Cambridge Healthtech Institute’s 12th Annual
Optimizing Cell Culture Technology
Enhancing Knowledge for Growing Cells
Part of CHI's 8th Annual The Bioprocessing Summit
August 15-16, 2016 | Westin Boston Waterfront | Boston, Massachusetts

The “Optimizing Cell Culture Technology” is the leading international conference focused solely on culturing cells. As industry demand increases, greater pressure is put on cell culture to meet growing needs. This meeting explores today’s evolving strategies and technologies for improving mammalian cell cultivation, including omics technologies and Synthetic Biology. Industry experts offer insights into optimizing conditions as well as cell biology in an effort to improve yield, while also addressing the future of cell culture in an expanding market where standards of quality continue to rise.

The agenda again features a session focused on CHO (Chinese Hamster Ovary cells), as well as small-group breakout discussions that provide the opportunity to discuss important topics with peers from around the world.

Final Agenda

Monday, August 15

8:00 am Short Course Registration

11:30 Main Conference Registration Opens

QUALITY & PRODUCTIVITY

1:00 pm Chairperson’s Opening Remarks

Richard Altman, M.S., Scientist, Protein Technologies, Amgen, Inc.

1:45 FEATURED PRESENTATION:
Analytical and Device Technologies for Bioprocess Engineering

James Piret, Sc.D., Professor, Michael Smith Laboratories, University of British Columbia

This presentation is focused on research to improve the understanding and performance of mammalian cell based processes. We have developed single-cell Raman spectroscopy methods for cell analysis to detect the types of Chinese Hamster Ovary cell death and to detect the early stages of apoptosis based on macromolecular changes in the cell composition. Also, we are addressing the increasing need for high cell concentration perfusion technology, including in scale-down bioreactors. 

2:15 Early Development Strategies for Innovative Therapeutic Molecules

Nicola Beaucamp, Ph.D., Head, Process Research, Large Molecule Research, Pharma Research and Early Development, Roche Innovation Center Penzberg 

A number of novel antibody formats have been advanced into clinics by Roche pRED. In order to discover and develop differentiated monoclonal antibodies Roche’s strategy is based on engineering technologies which bear several challenges for technical development. Examples on innovative therapeutic molecules for multi-pathway-inhibition and specific tumor-targeting will be given.

2:45 Refreshment Break

QUALITY & PRODUCTIVITY

3:15 Strategies for Optimizing the Productivity of a Cell Culture Platform without Impacting Product Quality

Nattu Vijayasankaran, Ph.D., Senior Engineer, Late Stage Cell Culture, Genentech Inc. – A Member of the Roche Group

Cell culture processes are generally simplified when needed as a robust platform technology. But both culture medium and process parameters are customized for specific cell lines when there is a need to achieve high titer. A case study will be used to demonstrate that changes made to the platform process to maximize productivity could alter the product quality profile. Strategies to minimize these product quality changes will be discussed.

3:45 Selected Poster Presentation
Development of a CHO Cell Culture Platform for Monoclonal Antibody Production: From Clone Generation to Pilot-Plant Scale-Up
Julien Robitaille, Research Council Officer, Cell Culture Scale Up, National Research Council Canada

4:00 Using High-Seeding Density to Improve Cell Culture Process Efficiency and Increase Manufacturing Facility Capacity

Ning Liu, Ph.D., Associate Senior Consultant Engineer, Bioproduct Research and Development, Eli Lilly and Company

A high-seeding density fed-batch process with N-1 perfusion culture was developed at Lilly that has significantly increased volumetric productivity. A case study will be presented to demonstrate that the new process could shorten the production time from 14 days to 7 days and achieve the same titer with comparable product qualities, or increase the titer by 50%. Considerations for implementation at manufacturing sites will also be discussed.

4:30 Interactive Small-Group Breakout Discussions

This session provides an 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 commiserate about persistent challenges. Then continue the discussion as you head into the lively Exhibit Hall for information about the latest technologies.

TABLE 1.

Scale-Down Model Development and Evaluation for Process Characterization Work

Moderator: Amanda M. Lewis, Ph.D., Scientist II, Biologics Development, Bristol-Myers Squibb

TABLE 2.

Requirements for Perfusion Media: Technology Gaps and Strategies Moving Forward

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

TABLE 3.

Translational Cell Cultures

Moderator: To be Announced

TABLE 4.

Product Quality Similarities and Differences When Going from Transient to Stable CHO

Moderator: Yashas Rajendra, Ph.D., Research Scientist, Bio-TDR Cell Culture, Eli Lilly and Company 

• How valuable is a transient platform that can accurately predict product quality in stable CHO platform?
• What are all the differences between your transient and stable expression platform?
• Have you seen correlation of titer between transient and stable expression platform?
• How often have you observed product quality surprises when moving a molecule from transient expression to stable expression
  • What kind of differences have been observed?
  • Is it across all molecule types, or more prevalent in complex formats of mAbs and/or other protein types?
   

Optimizing the Cell Culture Components of Transient Protein Production

Moderators: Richard Altman, MS, Scientist, Protein Technologies, Amgen, Inc.
Henry C. Chiou, Ph.D., Associate Director, Cell Biology, Life Science Solutions, Thermo Fisher Scientific
Chao Yan Liu, M.D., Senior Staff Scientist, Research & Development Cell Biology, Life Science Solutions, Thermo Fisher Scientific

• What cell lines are available for protein production and what are their advantages and disadvantages?
• Culture media and bioreactor culture conditions that achieve both high productivity and product quality
• Cell culture performance at different scales

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

CULTURING CHO CELLS

7:55 Chairperson’s Remarks

Jonathan Bones, Ph.D., Principal Investigator, National Institute for Bioprocessing Research & Training (NIBRT), University College Dublin

8:00 Using Quantitative Proteomics to Link Critical Quality Attributes to Critical Process Parameters

Jonathan Bones, Ph.D., Principal Investigator, National Institute for Bioprocessing Research & Training (NIBRT), University College Dublin

Quantitative proteomics is a powerful tool to understand cellular behavior at the molecular level. Quantitative proteomics of an IgG1 mAb producing CHO cell line was performed following systematic alteration of bioprocess conditions using a limited Plackett-Burman design of experiments approach. In addition to investigating changes in cellular behavior, complete characterization of the expressed mAb was also performed to investigate the link between product critical quality attributes and alterations in critical process parameters.

8:30 Harmonizing Transient and Stable CHO Expression Platforms for Early-Phase Drug Discovery

Yashas Rajendra, Ph.D., Research Scientist, Bio-TDR Cell Culture, Eli Lilly and Company

We describe the development of transient CHO system capable of rapidly (7 days) generating high titers, scalable up to 6L. Additionally, we describe the use of stable CHO pools (instead of master wells or clones) for generation of gram quantities of therapeutic protein. Using the same CHO cell line and media package for both platforms streamlines expression during early phase biologic drug discovery.

9:00 An ‘Omics’ Approach to Understanding Performance of a CHO-Fc Fusion Process at 5000-L Scale

Amanda M. Lewis, Ph.D., Scientist II, Biologics Development, Bristol-Myers Squibb

A CHO bioprocess, where the product is a sialylated Fc-fusion protein, showed significant variation of sialylation at large scale. Lower sialylation correlated with elevated mannose, a shift in glucose metabolism, and increased oxidative stress. This information was used to optimize a 5-L scale-down model able to reproduce the large-scale phenotypic profiles. Targeted transcriptomics and metabolomics were used to develop a proposed biological mechanism linking large-scale operation, oxidative stress, and sialylation.

9:30 Feed Optimization to Improve Productivity and Product Quality Enabled by Automated Sampling System

Linda Hoshan, Senior Scientist, Process Development & Engineering, Bioprocess Development, Merck Research Laboratories

A study in optimizing feed media and feeding strategies for a fed-batch CHO culture producing monoclonal antibody will be presented. Fully chemically defined feed medium was used to replace hydrosylate-containing feed in the original Phase I process. For better control of the nutrient levels in the bioreactor, a system developed for automatic bioreactor sampling and feedback control was integrated, enabling sampling and feed multiple times a day.

9:45 Coffee Break in the Exhibit Hall with Poster Viewing

EMERGING CELL CULTURE TECHNOLOGIES

10:30 Next-Generation Cellular Models for Drug Discovery

T. Oliver Chao, Ph.D., Head, Emerging Biomedical Sciences, Strategy & Innovation, Sanofi

How to improve cell culture technology for a more relevant and more translational models for drug discovery? From stem cells to artificial cells, from single cell platforms to organs-on-chips, from cultures derived from humanized animals to 3D cultures built by human cells. We will discuss several emerging approaches that hopefully would help us to achieve this goal.

11:00 Mammalian Cell Fluid Mechanics and Scale-Up Considerations for Cell Therapy

Peter Amaya, Ph.D. Candidate, Graduate Research Associate, William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University

The perception of “shear sensitivity” has historically put an arbitrary upper limit on agitation and aeration in bioreactor operation; however, as cell densities and productivities continue to increase, mass transfer requirements can exceed those imposed by these arbitrary low limits. This presentation will mainly focus on some recent experimental data on microcarrier cultures regarding the effect of hydrodynamic forces on industrially relevant animal cells, and on scale-up.

11:30 Genome-Scale RNA Interference Screen Identifies Key Pathways and Genes for Improving Recombinant Protein Production in Mammalian Cells

Joseph Shiloach, Ph.D., Director, Biotechnology Core Laboratory, Intramural Research, NIDDK/NIH

A high-throughput RNA interference screen was conducted using HEK293 cells expressing firefly luciferase. The gene encoding the ornithine decarboxylase antizyme1 was selected for detailed investigation, and our study shows that this gene is a novel target for improving expression of recombinant proteins. The genome-scale screening demonstrated in this work can establish the foundation for targeted design of an efficient mammalian cell platform for different biotechnological applications.

12:00 pm Use of a Scalable, Continuous Processing Platform to Solve Production Challenges in Mammalian Cell Cultures

Scott Waginer, Vice President, Bioservices, Cell Culture Company

Traditionally difficult-to-express proteins perform well in a continuous processing bioreactor system as it provides long-term sustainable homeostatic pH conditions, metabolite and waste levels, as well as continuous collection of the protein of interest for 3-9 months. This stable, in vivo like environment enables increased cell viability and a higher yield compared to typical fed-batch systems. This presentation will highlight the steady-state production of a monoclonal antibody and the scalability of an automated single-use, perfusion bioreactor.

 12:30 Luncheon Presentation: ExpiCHO: Latest Developments in High-Titer Transient CHO Expression

Jonathan Zmuda, Ph.D., Director, Cell Biology, Thermo Fisher Scientific

The Gibco Expi293 and ExpiCHO Expression Systems have become premier tools for protein expression in many pharma, biotech and academic laboratories, enabling high-titer recombinant protein production for a broad range of research applications. Here, we present the latest updates on the ExpiCHO Expression System with regard to optimizing protein expression, purification and characterization from 96 well plates up to 10L bioreactors.

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

IMPROVING & INNOVATING PROCESSES

1:55 Chairperson’s Remarks

James Piret, Ph.D., Professor, Michael Smith Laboratories, University of British Columbia

2:00 Strategies to Improve Process Robustness for Monoclonal Antibody Production: A Case Study

Jeffrey Ly, M.S., Senior Scientist, Process Development and Commercialization, Merck & Co., Inc.

During the manufacture of a monoclonal antibody, consistent product quality was maintained, but large variations in bioreactor harvest titer (>2X) were observed between lots. Investigations into this titer variation led us to identify correlations between cellular metabolism, feeding strategy and harvest titer. As a result, process modifications have successfully been developed to obtain a more robust production bioreactor process while maintaining product quality.

2:30 Challenges in Cell-Line, Process and Analytical Development of a Single-Chain Antibody and Solutions

Hanuman Mallubhotla, Ph.D., Research Director, Biopharmaceutical Development, Syngene International, Ltd.

Single chain antibodies are more difficult to express well than full-length antibodies, and have additional issues with their purification. Two clone systems have been developed. Using semi-empirical and DOE strategies, methods and processes were developed for both systems with quality and productivity targets. A titer of > 3 g/L was obtained for the single-chain antibody.

3:00 Production of Recombinant Biotherapeutic Proteins in Spodoptera frugiperda (Sf9) Insect Cells for Vaccine Development

Rajiv Gangurde, Ph.D., Associate Director, Protein Production, Genocea Biosciences

Therapeutic proteins used for the prevention or treatment of human diseases have been manufactured in a variety of different expression systems, with baculovirus-infected insect cells providing a solid platform for the production of glycosylated proteins. One of our lead programs, GEN-003, is a therapeutic HSV-2 vaccine containing two proteins expressed independently in insect cells. Here we discuss strategies, challenges and advantages of employing this system for the production of GEN-003.

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

OPTIMIZING CELL CULTURE CONDITIONS

4:15 Case Study: Evaluation of High Temperature-Short Time Treatment of Basal and Feed Media for Production of a Monoclonal Antibody

Amanda L. Carpenter, MS, Associate Scientist II, Drug Substance Manufacturing Sciences and Technology (Upstream), Bristol-Myers Squibb

In the biopharmaceutical industry, high temperature-short time (HTST) treatment of cell culture media and solutions is being implemented to mitigate the risk of potential viral or other contamination of the cell culture. As a proof-of-concept, the impact of HTST-treated basal and feed media was evaluated for a monoclonal antibody in scale-down production bioreactors. The results demonstrate that implementing HTST-treatment of basal and feed media into manufacturing for this monoclonal antibody is feasible.

4:45 Optimization, Simplification and Intensification of Cell Culture Processes 

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

Fed-Batch processes are the standard cultivation method for the manufacturing of biopharmaceuticals with CHO cells today. Besides the production organism, cell culture media and feeds have a great impact on process productivity optimization. Our recent introduction of chemically modified amino acids for cell culture media allow for a significant simplification of CHO fed-batch processes by eliminating the second, typically caustic feed. Furthermore, increases in productivity were observed, resulting in more productive fed-batch as well as highly intensified perfusion processes. 

5:15 End of Conference

5:15 Registration for Dinner Short Courses