The Bioprocessing Summit
The Bioprocessing Summit

Cambridge Healthtech Institute’s 8th Annual
Optimizing Cell Line Development
Enhancing Expression
Part of CHI's 8th Annual The Bioprocessing Summit

August 18-19, 2016 | Westin Boston Waterfront | Boston, Massachusetts


The “Optimizing Cell Line Development” meeting brings together experts in cell line development and protein expression who share their real-world strategies for achieving cell lines that meet bottom-line goals faster and at lower expense. Their practical and detailed insights will illustrate how to best optimize codons, construct vectors, and how to select and engineer clones and host systems. Gaining a greater understanding of cells through sequencing and the omics sciences will also be addressed, including the CHO genome research, metabolomics, assays, and QPCR. In addition, challenges for introducing new technologies, such as in silico modeling, will be discussed, along with an overview of industrial trends and regulatory perspectives.

Final Agenda

Day 1 | Day 2 | Short Courses | Download Brochure


Thursday, August 18

11:30 am Registration Opens

12:15 pm Lunch Available for Purchase in the Exhibit Hall

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


INNOVATING CELL LINE DEVELOPMENT PROCESSES

1:55 Chairperson’s Opening Remarks

Nathan E. Lewis, Ph.D., Assistant Professor, Department of Pediatrics, University of California, San Diego


2:00 KEYNOTE PRESENTATION:
Tilting at Windmills: Cell Line Development Impacts on Quality, Time and Costs

Steve_LangSteven Lang, Ph.D., M.B.A., Director, Early Stage Cell Culture, Genentech, Inc., a member of the Roche Group

Advances in technology and processes have made significant improvements in cell line development efficiency. However, the continued pressure to reduce timelines and costs while delivering on quality has created imaginary giants. This talk will discuss cell line development challenges and how focusing on real issues can improve the value of clinical programs.


2:45 Technology Toolbox for Cell Line Development – Next-Generation Cell Line Development Technologies

Holger_LauxHolger Laux, Ph.D., Fellow, Novartis

A novel toolbox of vector elements and novel engineered CHO cell lines were developed which results in significant increase of titer and improved product quality. We have evaluated novel vector elements with a variety of antibody projects resulting in an increase of titer. Especially the combination of the recently published CHO genome in combination with screening methods and cell line engineering tools has enabled the development of a superior CHO cell.

3:15 What is Your Cell Line Really Translating? Enhancing Protein Production with Ribosomal Profiling and Systems Biology Analysis

Nathan_LewisNathan E. Lewis, Ph.D., Assistant Professor, Department of Pediatrics, University of California, San Diego

Mammalian cells channel their resources to produce recombinant protein drugs, but it is unclear how recombinant genes impact global translation and if they are translated as efficiently as host genes. To answer these questions, we gained a global view of mRNA translation in IgG-producing CHO cells using ribosomal profiling. We demonstrate how these data can be harnessed to guide cell line development for protein production.

3:45 Sponsored Presentation (Opportunity Available)

4:00 Refreshment Break


CELL LINE SCREENING

4:15 A Novel Platform for High Throughput Cell Line Screening & Development

Christoph Freiberg, Ph.D., Senior Scientific Consultant, Biologics, Genedata

Co-developed with leading biopharmaceutical companies, we have implemented a dedicated cell line development platform for fully automating the clone line selection and assessment process to increase process efficiency and quality. It supports the entire cell line development workflow including seeding, selection, incubation, passaging, analyzing, and cryo-conservation and tracks the full history of all clones along with product quality and analytics data. It directly integrates with instruments, such as pipetting robots, colony pickers, and bioanalyzers.

4:45 Alleviate the Downstream Burden of Harvest Filterability through Upstream Process Optimization and Cell Line Screening

Sheng (Sam) Zhang, Ph.D., Senior Scientist, Process Sciences, AbbVie

In this study, instead of looking into alternate harvest clarification approaches, we are exploring other options in upstream processing. These approaches are designed to enhance the harvest filterability by significantly reducing the cell mass, debris and/or other impurities while boosting productivity. To move a step further, we are implementing the same upstream condition(s) in the early stage of cell line screening to preferentially select line(s)/clone(s) that may not encumber the platform downstream process.

5:15 End of Day

5:15 Registration for Dinner Short Courses


6:00 – 8:30 Recommended Dinner Short Course*
SC11: Regulatory and Scientific Base of Monoclonality for Generating Protein Expression Cell Banks

* Separate registration required


Day 1 | Day 2 | Short Courses | Download Brochure


Friday, August 19

8:00 am Registration Opens and Morning Coffee


CHO CELL LINE DEVELOPMENT

8:25 Chairperson’s Remarks

Susan Sharfstein, Ph.D., Associate Professor, Nanobioscience, Nanoscale Science and Engineering, SUNY Polytechnic Institute

8:30 Accelerated Genome Engineering of CHO Cell Factories for Improved Protein Production

Helene_KildegaardHelene Faustrup Kildegaard, Ph.D., Senior Researcher and Co-Principal Investigator, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark

Chinese hamster ovary (CHO) cells are widely used in the biopharmaceutical industry as a host for the production of complex pharmaceutical proteins. Thus, accelerated genome engineering of CHO cell factories to improve product yield and quality is of great interest. Here, our recent efforts in generating desirable CHO cell factories with predicted performance using genome engineering, systems biology data and high-throughput screening, will be presented.

9:00 Cell Line Development: Glycoengineering of Chinese Hamster Ovary Cells for Improving Biotherapeutics’ Efficacies

Andrew_Chengyu_ChungAndrew Chengyu Chung, MSE, Researcher, Chemical and Biomolecular Engineering, Johns Hopkins University

Many biotherapeutics include post-translational modifications such as glycosylation. The chemical composition of these glycans can influence drug effectiveness. Sialylation is one of the most important glycan modifications due to its negative charge and terminal location. In this study, we applied genetic engineering strategies to modulate the level of sialylation content on various potential biotherapeutics.

9:30 Epigenetic Effects on Antibody Production in CHO Cells

Susan_SharfsteinSusan Sharfstein, Ph.D., Associate Professor, Nanobioscience, Nanoscale Science and Engineering, SUNY Polytechnic Institute

Identifying characteristics of high productivity cell clones is critical for rapid cell line development. We evaluated epigenetic differences between parental clones and DHFR-amplified progeny including transcription factor activation and DNA methylation. These studies suggest that transcription factor binding is altered in different families of parental cell lines and progeny, providing possible strategies for cell line engineering.

10:00 Networking Coffee Break


CELL LINE AUTHENTICATION

10:30 Know Thy Cells: Improving Biomedical Research Reproducibility

Leonard_FreedmanLeonard P. Freedman, Ph.D., President, Global Biological Standards Institute

Sources of irreproducibility are often magnified by the explosion of high-throughput technologies, genomics, and other data-intensive disciplines. This presentation will use examples of biological materials and reagents, specifically cell lines and antibodies, on the impact of irreproducibility in basic/preclinical research and development, and how the implementation of consensus-based standards to authenticate and certify these reagents will lead to both increased rates of reproducibility and dramatic returns on research funding investments.

11:00 Cell Line and Biospecimen Authentication: Challenges and Solutions for Biomedical Science

Richard_NeveRichard M. Neve, Ph.D., Senior Research Scientist I, Gilead Sciences, Inc.

The use of cell lines and biosamples are widespread in biomedical research. Contamination of stocks and confusion of cell line/sample origin frequently occur, resulting in wasted research funds and delaying development of important medicines for patients. This presentation outlines solutions for these issues by defining a framework of quality controls and best practices to prevent and detect the most common forms of cross-contamination.

11:30 Authentication of Mouse, CHO, and Rat Cell Lines

Jamie_AlmeidaJamie Almeida, Microbiologist, Biochemical Science Division, Bioassay Methods Group, NIST

Cell line authentication has never been more necessary in the current environment. Currently, there are no standards for cell line authentication for nonhuman cell lines. We have developed rapid, sensitive, and specific multiplex PCR assays targeting short tandem repeat markers for mouse and Chinese hamster cell lines, and we have identified STR markers specific to rat. Use of these assays provide assurance in cell line identity for the validation of downstream products.

12:00 pm Sponsored Presentations (Opportunities Available)

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

1:15 Session Break


EMERGING TECHNOLOGIES

1:25 Chairperson’s Remarks

Christoph Freiberg, Ph.D., Senior Scientific Consultant, Biologics, Genedata

1:30 Greater Predictability in Establishing Optimal Biologic Production Systems Using Integrated Synthetic Biology Approaches

Ian_FotheringhamIan Fotheringham, Ph.D., Managing Director, Ingenza, Ltd.

In this talk, I will describe how Ingenza develops and applies various synthetic biology tools to enable us to more predictably achieve efficient, soluble and stable expression of active biologics using both mammalian cell lines and microbial strains. I will describe scaled commercial examples that solved customer problems and illustrate the utility of our approach.

2:00 Switchable Membrane Reporter (SwiMR) Technology for Facile Cell Line Development

Bo_YuBo Yu, Ph.D., Co-Founder & CSO, Larix Bioscience

Switchable Membrane Reporter (SwiMR) technology is the most efficient technology available today for the isolation of production cell lines. It utilizes a unique switchable reporter system to facilitate FACS-based enrichment and isolation of high producing cells. This eliminates the requirement for gene amplification and reduces cell line screening time from 4-8 months to 2-3 months. The SwiMR technology has been used to generate production CHO cells for multiple antibodies.


CLONE STRATEGIES

2:30 Towards a Novel Site-Specific Integration System for Cell Line Development

Mara C. Inniss, Ph.D., PostDoc Fellow, Cell Line Development, Pfizer, Inc.
The growth of the biopharmaceutical market in recent years has prompted dramatic improvements in recombinant protein production. Pfizer’s site-specific integration (SSI) platform, based on the Flp/FRT recombinase-mediated cassette exchange (RMCE), promises unparalleled ease and consistency in generating CHO cell lines. To further advance our mammalian expression technology, we are developing a novel site-specific integration system which is comparable and orthogonal to the Flp/FRT system, offering flexibility and user-defined capability in generating recombinant cell lines for biopharmaceutical production.

3:00 Towards One Round of Cloning in Cell Line Development

Nathalie Veith, Ph.D., Senior Scientist, Upstream Development, Synthon Biopharmaceuticals

Regulatory guidelines state that production cell lines need to be derived from one cell progenitor. In order to guarantee this with a high probability, biopharmaceutical industries use two rounds of limiting dilution, FACS-based procedures and/or imaging techniques to ensure clonality of a cell line. Since time lines play an important role for CMC projects, many efforts are undertaken to decrease the effort and time to prove clonality of a cell line. Synthon Biopharmaceuticals want to present their approach using two different devices to support their strategy ensuring clonality of a cell line.

3:30 Close of Conference



Day 1 | Day 2 | Short Courses | Download Brochure