The Bioprocessing Summit

Cambridge Healthtech Institute’s 6th Annual
Optimizing Cell Line Development
Enhancing Expression
Part of CHI’s 6th Annual The Bioprocessing Summit

August 21-22, 2014 | Renaissance Waterfront Hotel | Boston, Massachusetts


Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios 

Friday, August 22

8:00 am Registration and Morning Coffee


CELL LINE DEVELOPMENT

8:25 Chairperson’s Remarks

Howard Clarke, Ph.D., Director, Upstream Process Development, CMC Biologics


8:30 FEATURED PRESENTATION

Cell Line Development Approaches for Speed, Titer and Product Quality

Till WengerTill Wenger, Ph.D., Associate Director, Cell Biology & Cell Culture II, Process Sciences, Boehringer Ingelheim Pharma

In developing NBEs, speed, titer and an excellent product quality is key. For biosimilars, the essential target is matching the originator product quality. Here, we show how the use of a platform based on well characterized cell lines and thorough process understanding can be used to achieve fast and reliable development of high-titer cell lines, how cell line development can be accelerated, and how specific host cells and processes parameters can be used to influence product quality attributes.

9:00 Antibody Membrane Switch (AMS) Technology for Facile Cell Line Development

Bo YuBo Yu, Ph.D., Co-Founder and CSO, Larix Bioscience, LLC

Antibody Membrane Switch (AMS) technology is the most effective and time efficient technology available today for the isolation of production cell lines. AMS technology utilizes a unique switch mechanism of alternative splicing and site-specific DNA recombinase to turn cells from expressing membrane-anchored antibodies into production cells secreting the antibody. This enables screening of hundreds of millions of cells per day by FACS, eliminating the requirement for gene amplification. Utilizing AMS technology can reduce cell line screening time from 6-8 months to 2-3 months.

9:30 Innovative Cell Line Development for the Expression of Glenmark’s Novel Bispecific BEAT Format

PierreMorettiPierre Moretti, Ph.D., Staff Scientist and Head, Cell Line Development, Glenmark Pharmaceuticals

Glenmark’s BEAT bispecific antibody format is based on engineered IgG scaffolds and maintains key antibody properties such as thermostability, low immunogenicity and pharmacokinetics. Production and purification are achieved using established platform technologies. This presentation will focus on the cell line development. Innovative solutions were found in order to rapidly generate and select high producing, stable cell lines and to drive the optimal pairing of heterologous heavy and light chains while minimizing unwanted side products.


EARLY ANALYSIS OF CELL LINES TO PREDICT DEVELOPABILITY

10:45 Early Pre-Process Risk Assessment: Alternatives to One-Size-Fits-All Process Development to Reduce Product Attrition and Streamline Development

Jesús ZurdoJesús Zurdo, Ph.D., Head, Innovation, Biopharma Development, Lonza Biologics plc

Biomanufacturing processes are still complex, largely unpredictable, and very much linked to the nature of the product to be made. In most cases, uncertainty is managed with extensive screening, testing and analysis, which is tremendously costly and time-consuming. We present some alternative approaches to development that have a greater emphasis in the design and selection of the therapeutic candidate for optimal safety, stability and formulability, combined with faster approaches for early material generation. Potential impact in streamlining clinical development will be discussed.

11:15 High-Throughput Imaging during Cell-Line Development to Increase the Assurance of Clonality

David ShawDavid Shaw, Ph.D., Group Leader, Early Stage Cell Culture, Pharma Technical Development, Genentech, Inc.

Current methodologies to create monoclonal cell lines include limiting dilution or single-cell sorting at conditions that offer statistical assurance of monoclonality. We have implemented a fluorescent high-throughput automated imaging workflow that can provide evidence on whether the cell line originated from one cell during the cloning step. We will discuss some of the challenges, solutions and characterization experiments that were conducted during the development of this protocol and provide case study data.

11:45 Omics Analyses of Antibody Producing Cell Lines to Improve Productivity and Product Quality

Sohye Kang, Ph.D., Senior Scientist, Product Attribute Sciences, Amgen, Inc.

We examined various production cell lines expressing different therapeutic monoclonal antibodies and investigated their intrinsic properties associated with culture performance and phenotypes. 17 different cell lines displaying a wide spectrum of productivity range were chosen and treated with the same media and process conditions to keep the external factors constant. Microarray-based transcriptomics and LC-MS/MS shotgun proteomics technologies were utilized to obtain expression landscape of different cell lines and reveal cellular mechanisms associated with different culture phenotypes, including productivity, proliferation rate and cell size.

 12:15 pm Capabilities of Full Bioprocess Control in Micro Bioreactors for Cell Line Development
Kensy_FrankFrank Kensy, Ph.D., Managing Director, m2p-labs, Inc.
A new micro bioreactor platform with microfluidic control will be presented. The new BioLector Pro owns a unique microfluidic plane fused on a microplate to realize continuous pH-control and feeding in up to 32 parallel fermentations at 1ml scale. This single-use microfluidic system was designed to perform cell line development already under process conditions.  


12:30 pm Sponsored Presentation (Opportunity Available)

12:45 Luncheon Presentation (Sponsorship Opportunity Available)


OPTIMIZING PRODUCTIVITY & YIELD

1:25 Chairperson’s Remarks
Frank Kensy, Ph.D., Managing Director, m2p-labs, Inc. 

1:30 Optimization of Biologics Yield in Microbial and Mammalian Expression Systems

Ian FotheringhamIan Fotheringham, Ph.D., President & Co-Founder, Industrial Biotechnology, Ingenza, Ltd.

E. coli-based expression systems can be unsuitable for the production of certain mammalian proteins/enzymes often yielding insoluble, inactive product. We have developed optimized microbial and mammalian cell lines and expression systems for the production of protein biologics that consistently yield active soluble protein. Our systems are free of third party IP encumbrance, enable manufacturing to GMP standards and facilitate straightforward protein purification.

2:00 Improving Yields in a Novel Drosophila S2 Expression System

Wian de JonghWian de Jongh, Ph.D., CSO, ExpreS2ion Biotechnologies

ExpreS2ion Biotechnologies is responsible for the process development of two malaria vaccines in collaboration with The Jenner Institute, Oxford University, and the Centre for Medical Parasitology, Copenhagen University. It is vitally important to reduce cost-of-goods for these vaccines due to the geographic location of endemic areas and the philanthropic funding sources involved in vaccine distribution. ExpreS2ion has therefore focused on improving yields through cell line selection and process improvement strategies, which will be presented in this talk.

2:30 Highly Multiplexed Subcellular RNA Sequencing in situ 

Jehyuk LeeJehyuk Lee, M.D., Ph.D., Genetics, Wyss Institute for Biologically Inspired Engineering, Harvard University

We describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked cDNA amplicons are sequenced within a biological sample. Using 30-base reads from >8000 genes in situ, we examine RNA expression and localization in primary fibroblasts during wound healing in vitro. Our platform enables massively parallel detection of genetic elements, including gene transcripts and molecular barcodes, for studying cellular phenotype, gene regulation, and environment in situ.

3:00 Refreshment Break


CELL LINE DEVELOPMENT INNOVATIONS

3:15 A Vector-Free Microfluidic Platform for Intracellular Delivery and Manipulation of Cell Function

Armon ShareiArmon Sharei, Ph.D., Research Associate, Chemical Engineering, Massachusetts Institute of Technology (MIT); Co-Founder, SQZ Biotech

Intracellular delivery of macromolecules is a challenge in research and therapeutic applications. Existing vector-based and physical methods have some limitations, including their reliance on exogenous materials or electrical fields. We describe a microfluidic approach to delivery in which cells are mechanically deformed as they pass through a constriction 30-80% smaller than the cell diameter. By enabling the delivery of RNA, DNA, proteins, and nanoparticles, this technique has demonstrated effective manipulation of cell behavior in a range of applications.

3:45 High-Throughput Automation Solutions in Bioprocess Development

Gregory KeilGregory Keil, M.S., Senior Scientist, Merck

Automation and high-throughput techniques have become increasingly more important throughout bioprocess development for therapeutic proteins.  Within Merck’s Bioprocess Development organization, we have implemented a fully automated approach to cell line development involving multiple automation systems designed to streamline many of the activities involved in cell line and process development.  Here, we will demonstrate how a modular approach to automation allows for increased functionality, flexibility, and overall throughput.  With these automation solutions in place, bioprocess development has observed both increased efficiency and productivity across the entire platform.
 

4:15 Applicability of Readily Grown Mice Cell Lines in Culture for Melanoma Research

Molly Jenkins, Ph.D., Research Fellow, Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine, Dartmouth College

Transgenic mouse models allow the study of melanoma in vivo, however in vitro models are necessary to better understand the molecular mechanisms underlying disease progression and therapy resistance. We have established melanoma cell lines (Dartmouth Murine Mutant Malignant Melanoma; D4M cells) from a conditional mouse model of metastatic melanoma. Here, we report the characterization of these lines, and demonstrate their unique ability to correlate in vitro studies on molecular mechanisms of melanoma with in vivo investigations on pathology and immunology.

4:45 End of Conference



Day 1 | Day 2 | Short Courses | Download Brochure | Speaker Bios