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Optimizing Cell Line Development conference - Day 1

Optimizing Cell Line Development 

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TUESDAY, AUGUST 21


6:00 - 9:00 pm Recommended Dinner Short Course* 

SC6 Transient Protein Production in Mammalian Cells: A Short Story 


*Separate registration required 


WEDNESDAY, AUGUST 22


Gene expression in mammalian cells is the foundation for protein production. As more protein-based products, such as antibodies, head into development, the need to refine processes for optimizing cell line development increases. Reducing the time needed to develop cell lines and identify high-expressing clones is essential for trimming a project’s overall costs.

This meeting features experts sharing their protocols and case studies illustrating the steps they have taken to reach enhanced expression. Their insights and experiences will provide real-world details to help you conquer the challenges of cell line development. As you seek to enhance your skills and knowledge, make time to join the information exchange and network with colleagues from around the world who share common cellular goals on the path to protein abundance.

8:00 am Registration and Morning Coffee

 

FACILITATING THE SUCCESS OF BIOLOGICS 

8:25 Chairperson’s Opening Remarks

Dieter C. Gruenert, Ph.D., Professor, Department of Otolaryngology - Head and Neck Surgery, Professor, Department of Laboratory Medicine, University of California, San Francisco, and Head and Neck Cancer Lab, Mt. Zion Cancer Center

» 8:30 OPENING KEYNOTE PRESENTATION:Evolution of Cell Line Development Technologies

James FandlJames P. Fandl, Ph.D., Vice President, Protein Expression Sciences, Regeneron Pharmaceuticals, Inc. - Biography 

Flow cytometry presents unparalleled capabilities for cell line development and is the basis for Regeneron’s VelociMabTM suite of technologies. These technologies will be described with special emphasis on how they evolved from each other in response to the changing resource-limited demands of a growing biotechnology company.
 

» 9:00 FEATURED PRESENTATION: 

Jesús-ZurdoOptimizing Development Before Starting the “Process“:  Addressing Key Challenges in the Development of Biopharmaceuticals

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

The extremely high attrition rate observed in pharmaceutical development, linked to dwindling R&D productivity and spiralling development costs, are putting pressure on how process development is conducted.  New strategies aimed to reduce risks in the manufacturing process, as well as clinical development, are being introduced in early stages of development.  These approaches need to be combined with innovative ways of developing host cells that can facilitate the transition into the clinic. Finally, the new paradigm for biopharmaceutical development needs to incorporate a more holistic definition of product design, in which elements of administration and delivery are incorporated alongside mode of action or safety.

9:30 Efficient Cell Line Selection Strategy to Anticipate for Optimal Cell Line Development

Kirsten HegmansKirsten Hegmans, M.S., Scientist and Team Leader, Cell Technology, Protein Sciences, Crucell - Biography 

The seeds for a successful cell line development program are already planted in the early phase of a cell line generation approach. The success rate can be managed by implementing a cell line selection strategy that considers parameters key for optimal production, such as stability of production and compatibility of the cell lines in the anticipated production process. For the PER.C6® platform, we have turned the traditional paradigm from selecting only high producing cell lines, to deselecting cell lines based on harsh criteria which are crucial in the foreseen production process.
 

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

 

CHO CELL LINE DEVELOPMENT 

10:45 Engineering Novel Lec1 Glycosylation Mutants in CHO-DUKX Cells: Molecular Insights and Effector Modulation of N-Acetylglucosaminyltransferase I

Xiaotian-ZhongXiaotian Zhong, Ph.D., Principal Scientist/Lab Head, Global Biotherapeutics Technologies, Pfizer Biotherapeutics Research and Development - Biography 

The complexity and heterogeneity of glycosylation modification offers both an opportunity and a challenge to biotherapeutics drug discovery. Glyco-engineering through cell line engineering has provided a new approach to facilitate the development of next-generation of biotherapeutics with optimized glycoforms and therapeutic utilities. The presentation will talk about a study utilizing chemical mutagenesis and lectin selection strategy to engineer new Lec1 mutants in dhfr- host cells. The resulting cell lines allow an effective methotrexate selection for a quick stable pool expression of recombinant proteins such as antibodies with relatively homogenous Man5GlcNAc2 glycans modification for biotherapeutic and structural purpose. The data has revealed some molecular insights into these novel mutations as well as new mechanistic details and potential effector modulation function of the GnTI enzyme.

11:15 Proteomic Analysis of a Sustained Productivity (SQp) Phenotype in mAb-Secreting CHO Cells

Niall-BarronNiall Barron, Ph.D., Program Leader, Mammalian Cell Engineering, National Institute for Cellular Biotechnology, Dublin City University - Biography 

The ability of mammalian cells to sustain cell specific productivity (Qp) over the full duration of bioprocess culture is a highly desirable phenotype, but the molecular basis for sustainable productivity has not been previously investigated in detail. In order to identify proteins that may be associated with a sustained productivity phenotype, we have conducted a proteomic profiling analysis of two matched pairs of monoclonal antibody-producing Chinese hamster ovary (CHO) cell lines that differ in their ability to sustain productivity over a 10-day fed-batch culture.
 

Pall_LifeSciences 11:45 Bio-layer Interferometry (BLI): Instant Dip and ReadTM Label-Free Protein Quantitation and Binding Kinetics
Sriram Kumaraswamy, Ph. D., Director, Marketing Field Applications, Pall ForteBio
The presentation will describe the use of label-free binding assays on the Octet and BLItz platforms for cell line development. These systems are used routinely to perform titer assays for primary and secondary screening of cell lines, scale-up culture and cell line stability monitoring, and bioreactor titer performance monitoringforMAbs, as well other Protein A binding protein drug candidates.  Assay results, turnaround time and labor will be compared with HPLC titer assay as well as ELISA. 

MaxCyte12:00 The Reality of Fully Scalable Transient Gene Expression (TGE) in CHO Cells for Gram-Scale Antibody ProductionJames Brady, Ph.D., Director of Technical Applications, MaxCyteTransient gene expression in CHO cells greatly shortens the time line of antibody development by eliminating the need for transient HEK systems.  Data is presented demonstrating rapid gram-scale antibody production using the MaxCyte® STX™.   Titers exceeding 400 mg/L allow for production of over a gram of antibody from a total culture volume of only two liters.
 

 

12:15 Luncheon Presentation (Sponsorship Opportunity Available)
or Lunch on Your Own
 

 

CELL LINE DEVELOPMENT 

1:55 Chairperson’s Remarks

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

2:00 Cell Line Development of Multiple Molecules to De-Risk Programs

Marguerite Campbell, Scientist, Biologics Research, Janssen Research & Development

Advances in molecule selection, cell line development technology and platform processes have not eliminated the risk of project failure in pre-clinical development. This talk will discuss a front-loaded and flexible strategy to increase success rates by developing cell lines for multiple molecules and delay the selection process until adequate data is available to intelligently select the molecule and clone. Decision processes and case studies will be presented to demonstrate the effectiveness of this approach.

2:30 Tailoring Product Quality Attributes Though Cell Line Development and Process Optimizaton

Anne TolstrupAnne B. Tolstrup, Ph.D., Director, Cell Culture II, Process Science, Boehringer Ingelheim Pharma GmbH & Co. KG - Biography 

Boehringer-Ingelheim is faced with the multi-faceted challenge of developing CMC processes for therapeutic proteins, both for NBEs and for biosimilar molecules.  The desired product quality attributes of a given therapeutic molecule vary depending on its desired effector function. For example, antibodies aimed at targeting cancer cells should typically exhibit high ADCC activity, while a biosimilar molecule should match the profile of its originator molecules. The BI-HEX platform comprises several elements allowing efficient tailoring of the product quality in a given direction, such as CHO host cell lines varying in their glycoprofiles, automated screening and analytics procedures during cell line development, and DoE-based cell culture process development. Examples will be given on how these elements are combined to select production clones generating optimal molecules.

3:00 Immortalization of Tissue/Organ-Specific Human Cells: Airway, Bone Marrow, Parotid, Mammary, Thyroid, and Parathyroid Cell Line Development

Dieter GruenertDieter C. Gruenert, Ph.D., Professor, Department of Otolaryngology - Head and Neck Surgery, Professor, Department of Laboratory Medicine, University of California, San Francisco, and Head and Neck Cancer Lab, Mt. Zion Cancer Center

The development of human cell culture systems has been an integral component of understanding normal cell function and disease mechanisms, as well as the screening and development of therapeutic interventions (pharmacological and genetic) and protein production. While primary cell systems have a certain appeal, they have a limited lifespan and are often difficult to manipulate. The immortalization of human cells, in particular epithelial cells, has proven to be a significant contribution to the repertoire of reagents for the development of novel human therapies and for the generation of human proteins. To further this technology, cells from specific tissues/organs (airway, bone marrow, parotid gland, mammary gland, thyroid and parathyroid) have been immortalized. These immortalized cells display tissue-specific features in terms of gene expression, protein/ hormone production, and function that will be beneficial for tissue-specific drug screening and therapeutic development.

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

 

HIGH THROUGHPUT CELL LINE DEVELOPMENT 

4:15 A Fully Automated Approach to Cell Line Development

Gregory KeilGregory Keil, Scientist I, Protein Expression Technologies, MRL Bioprocess Development, Merck - Biography 

Production cell line development for manufacturing therapeutic recombinant proteins involves screening hundreds or thousands of transfected cells to ultimately select the best clone with the desired protein productivity and quality attributes. Traditionally, this process was mostly conducted manually, was very labor intensive, and was limited in throughput. Here, we have streamlined the process by fully automating most of the steps to increase the operational efficiency and accuracy.  First, we used surface-capture technology and FACS to isolate high producers into 96 well plates. Then, we used a Genetix Clone Select Imager™ integrated with a robotic arm to automatically monitor and select wells with colonies grown from a single cell with documented monoclonality. The population data derived from this microscopic screening are fed into a TECAN™ system to perform fully automated sampling and ELISA assay for product levels.  The selected clones based on growth and titer are then harvested and scaled up into 24-well plates.  Productivity and binding affinities of the product in 24 well plates are then confirmed by the use of a ForteBio Octet™.  Cells from selected 24 wells were transferred into 50 ml conical spintubes for growth and productivity evaluation in agitated suspension culture. A custom designed TECAN™ system was then employed to automatically perform long-term semi-continuous suspension culture for evaluating stability of the clones. Fed-batch evaluations were carried out at different cell ages by using AMBR 48 microbioreactor system™ under more controlled conditions for mimicking large-scale production conditions. By orchestrating process instruments, this automatic cell line development scheme has drastically increased the efficiency and throughput of cell line development.  It also provides better traceability, documentation of cell line history and reduced error-prone steps.

4:45 High-Throughput Cell Line Development Using Deep-Well Screening and Product Quality Assessment

Brian-MajorsBrian S. Majors, Ph.D., Scientist, Cell Engineering, Biogen Idec, Inc.

The biopharmaceutical industry has made great strides to increase productivity on recombinant protein expression, decrease cell line development timelines, and improve the product quality of complex biotherapeutic proteins. At Biogen Idec, we have implemented a high-throughput cell line development workflow that allows improved efficiency and shortened timelines, without compromising the quality of cell line generation. Implementation of deep-well culture technology into the cell line development workflow allows for screening of cell lines in a suspension system that more closely reflects the eventual manufacturing process. In addition, deep-well screening in 24-well plates allows for both analysis of culture growth and production characteristics, but also sufficient cell culture supernatant for purification and product quality analysis. Such early information about the characteristics of the cell lines and the protein they produce leads to more informed decisions when it comes to choosing cell lines for downstream processes. This presentation will give an overview of the cell line development process at Biogen Idec and the challenges we have faced in the implementation of high-throughput technologies.

5:15 Networking Reception, Last Chance for Exhibit and Poster Viewing

6:45 End of Day



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