8:00am Morning Coffee (Sponsorship Available, Contact Ilana Schwartz at 781-972-5457 for more information)

OPTIMIZING PROCESSES

8:30 Chairperson’s Remarks

8:35 KEYNOTE PRESENTATION: Towards a “Bioprocess-on-a-Chip”
Michael L. Shuler, Ph.D., Samuel B. Eckert Professor, and J & M McCormick Chair, Chemical & Biomedical Engineering, Cornell University
Optimization of suspended animal cell culture processes for production of therapeutic proteins requires evaluation of volumetric productivity and protein quality (e.g. completeness of N-linked glycosylation) in response to a large number of genetic, host cell, and process permutations. Standard culture equipment is not practical for exploring large experimental spaces. Here we propose a system with three integrated components: (1) a mini-bioreactor; (2) a recovery/purifi cation module; (3) and a module to characterize the amount of sialic acid per protein. This talk will focus on the mini-bioreactor component with mixing and mass transfer characteristics similar to larger reactors. This mini-bioreactor uses pressure pulses to achieve oscillating fl ow of cells and medium between two chambers. Volumetric oxygen transfer coeffi cients up to 15 h-1 can be obtained. Model protein production from suspended insect (S. frugiperda) and mammalian cells (CHO) will be discussed.

9:05 Combination of Sequential and DOE Approaches for Cell Culture Process Development
Robin Ng, Ph.D., Scientist, Upstream Process Development, Goodwin Biotechnology, Inc.
Improving cell culture performance is a complex process that requires a broad understanding of the influencing factors. A systematic process development approach is, therefore, needed in order to effectively improve the cell culture performance. In this presentation, we demonstrate the use of combinational traditional sequential and design of experiment (DOE) approach. This approach is not only time-effective, but also labor and resources intensive.

9:35 A High-Throughput MicroBioreactor System for Rapid Bioprocess Development
Seth Rodgers, Ph.D., Chief Technology Officer, BioProcessors
We present a system capable of running several hundred cell cultures under conditions varied according to a factorial DOE. The control of key bioprocess parameters such as pH and DO is demonstrated. Because process controls are maintained in the microbioreactor, the quality of data obtained is shown to be generally comparable to that obtained in conventional scale-down models.

10:05 Technology Spotlight Sponsored by Kyowa Hakko U.S.A., Inc.
Five Decades of Cell Culture
George R. Erie, Tissue Culture Consultant, Kyowa Hakko USA, Inc.
A summary of over 50 years of using cell culture for Research, R&D, and Production of Therapeutics is presented. The progress made during these years with respect to facilities, culture media, and raw materials will be discussed. The talk will feature the evolution in the use of L-glutamine in culture media to the current availability of the L-alanyl-L-glutamine dipeptide to enhance stability of cell growth and yield of final product.10:20 Networking Coffee Break with Poster and Exhibit Viewing

OPTIMIZING CELL LINES

10:50 Chairperson’s Remarks

10:55 A New Genetic Element that Reduces the Variability in Expression Resulting in Rapid Production of Proteins
Igor Fisch, Ph.D., Chief Executive Officer, Selexis
An analysis of the integration pattern of the new synthetic element shows a single site of insertion within the chromosome that leads to high levels of stable protein production from a pool of cells. Sub-cloning is no longer required to obtain high stable levels of protein production. Due the lack of heterogeneity between clones, this system allows for the selection of clonally cell lines within 12 weeks of transfection. Our case study data, gathered in concert with Merrimack Pharmaceuticals, will include data on protein production from 96 wells to 2 liters and finally at 1000 liters scale.

11:25 Reconstructing Human Skin to Better Understand Melanoma Development and Progression
Meenhard Herlyn, Ph.D., Professor, Dermatology, The Wistar Institute
Human melanocytes cultured in monolayer have a phenotype similar to melanoma cells. However, when co-cultured with keratinocytes for three days, they down-regulate all markers associated with transformation and invasion. Thus the keratinocytes through cell-cell interactions control the expression of cell surface molecules on the melanocytes and they also regulate their growth. We can reconstruct normal human skin using the individual cellular components including fibroblasts embedded in collagen that form the ‘dermis’ with melanocytes and keratinocytes establishing the ‘epidermis.’ The model system also allows reconstructing a microcapillary network, in which the fibroblast induce differentiation of the endothelial cells through both cell-cell contacts and soluble factors. These models are superbly suited to investigate the mechanisms of cell-cell and cell-matrix interactions and to determine how in transformation of inflammation the normal tissue homeostasis is dysregulated.

 11:55  Technology Spotlight Sponsored by Novozymes Biopharma UK Ltd.
Advances in Animal-Free Media Supplements Leads to Enhanced Cell Performance
Sally Grosvenor, Scientific Communications Manager, Novozymes Biopharma AU Ltd.
With over 60 years experience in microbial protein expression Novozymes delivers a range of animal-free recombinant supplements, designed and manufactured exclusively for industrial cell culture, that allows developers to Rethink their media strategy. During the presentation we will briefly describe these products and their ability to stimulate cell growth and productivity in a variety of commercial cell lines.

12:10 pm Precision Genome Editing in Mammalian Cells Using Engineered Zinc Finger Proteins
Trevor Collingwood, Ph.D., Team Leader, Cell Line Engineering, Sangamo BioSciences
Improving the quality of cell lines used in therapeutic protein production is important to the biologics industry. The technology we present provides a powerful method to achieve customized cell engineering at the genetic level. Rational genome engineering in mammalian cells has enormous potential across basic research, drug-discovery and cell-based medicines. To this end, we have developed a novel technology that enables high-frequency genome editing via the application of designed zinc finger protein nucleases (ZFNs). By this method we can rapidly achieve targeted gene knockout and site-specific gene integration into native loci - without the need for selection strategies. Drawing from our work with transformed cell lines, primary human cells, and multi-potent stem cells, we will present several examples of single, double and triple gene knockout, as well as targeted gene insertion into native chromosomal loci.

12:40 Lunch on Your Own (Sponsorship Available, Contact Ilana Schwartz at 781-972-5457 for more information) 

OPTIMIZING CELL DEVELOPMENT USING METABOLOMICS

2:00 Chairperson’s Remarks

2:05 Application of Metabolomics for Cell Culture Optimization
Mike Milburn, Ph.D., Chief Scientific Officer, Metabolon
Metabolomics provides a snapshot into the metabolic state of cells. This global analysis of metabolites allows scientists to monitor hundreds of metabolites at once and can easily find rate limiting media components as well as cytotoxic metabolites accumulating in the cell and/or the media. Numerous case studies with several biopharmaceutical groups will show the utility of this approach.

2:35 Quantitative Targeted Metabolomics – Innovative Tool for Cell Culture Optimization
Denise Sonntag, Dr. rer. nat., Senior Scientist, Biochemistry, BIOCRATES Life Sciences
Quantitative targeted metabolomic analysis of cell cultures constitutes a rapid and comprehensive method to monitor changes in media composition that are relevant for cell growth and vitality. Consumption of supplied nutrients or accumulation of defined growth- inhibitory metabolites can be quantitatively recorded using sensitive and specific mass spectrometry methods (API-MS/MS). The enormous potential of a mass spectrometry-based approach to cell culture optimization, which covers several hundred metabolites of different classes, e.g. amino acids, acylcarnitines, phospholipids, sugars, biogenic amines, will be highlighted. As an example of application, we will present data from mammalian cell fermentation to point out the feasibility and significance of metabolomics for cell culture development.

3:05 (Sponsorship Available, Contact Ilana Schwartz at 781-972-5457 for more information) 

3:20 Networking Refreshment Break with Poster and Exhibit Viewing

OPTIMIZING YIELD & PRODUCTION

3:45 The Development, Evaluation, and Implementation of a Flow Cytometric Method for the Rapid Detection of Bacteria in Large-Scale Cell Culture Production
Irene McHugh, M.S., S.M., Senior Manager, Environmental/Microbiology/Molecular, Genentech

Outline of presentation:
• The flow cytometer technology
• Background and rationale for the development of the method
• Methodology
• Microbial challenge studies
• Problems encountered and method optimization
• Parallel study
• Results
• Implementation
• Future development

4:15 Adapting Cell Culture Development to Increase Throughput and Shorten Timelines
Gerald Carson, M.S., Principal Scientist, Biologics, Abbott Bioresearch Center
The drive to increase the efficiency of pharmaceutical discovery places higher demands on the development organization. Frequently these demands include bringing more candidates into GMP production more rapidly, often without a proportional increase in resources. The presentation will focus on improvements in technology and methodology that increase the efficiency and reliability of the cell line development process.

4:45 Single-Batch Production of a Recombinant Human Polyclonal Antibody
Anne B. Tolstrup, Ph.D., Director, Antibody Expression, Symphogen A/S
Symphogen has developed a single batch manufacturing platform, Sympress, for consistent production of target-specific recombinant human polyclonal antibodies. Simultaneously, a characterization strategy for analysis of the polyclonal products has been designed and developed, to gain regulatory acceptance of this new drug class. The first drug product manufactured by use of Sympress has now succesfully completed a clinical phase I study.

5:15 End of Conference