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Joint Session

Protein Purification & Recovery and Protein Production

7:00am – 5:30pm Registration

7:30 Breakfast Workshop (Sponsorship Available)

Optimizing Processes

8:15          Chairperson’s Remarks

Selection to Large-Scale Production
Feng Li, Ph.D., Senior Engineer, Process Development, Genentech

9:20 Technologies to Improve Cell Line Development and Engineering
Susan Dana Jones, Ph.D., Vice President and Senior Consultant, BioProcess Technology Consultants, Inc.
One of the critical activities for decreasing the time for moving a biologic product from candidate selection to first in human clinical trials is the rapid generation of a stable high expressing production cell line. Technologies that can enable this rapid development include expression vectors with elements that increase transcription or translation of the linked recombinant gene, pre-adapted host cell lines,  and high throughput screening methods for optimizing media composition to improve bioreactor performance and increase volumetric productivity. Strategies for achieving rapid cell line development and reducing overall development costs will be addressed along with an assessment of the risks and strategic impact of short cuts taken early in development on later stage production, partnering opportunities, product valuation, and regulatory acceptance.

9:50 Coffee Break in the Exhibit Hall

Analytical Approaches

10:45 Global Biochemical Analysis for Cell Line Selection and Media Development
Michael Milburn, Ph.D., Chief Scientific Officer, Metabolon, Inc.
Maximizing production of biologicals from cultures is a stepped process often requiring multiple rounds of cause and effect experiments with analysis of production and quality as the end point drivers. From selection of clonal isolates to initial media formulations to scale up conditions there are many areas of experimentation which can be utilized for optimization of production.  There has been a striking uptake in the use of metabolomics technology in cell line development and bioprocessing. This technology has been shown to have the potential to truly impact the market and drive greater efficiencies.

11:15 Characterization of LucraTone Animal-Free Hydrolysates and the Impact of Ultra filtration on Mammalian Cell Culture Performance
Michael  Cunningham, Ph.D., Senior Scientist, Bioprocess Division, Millipore Corporation
Hydrolysates are used extensively in biopharmaceutical manufacturing to enhance efficient mammalian cell growth and protein production.  Ultrafiltration is an effective method for removing large molecular weight entities, including endotoxin, from hydrolysates.  While the necessity of hydrolysate ultrafiltration prior to use in cell culture media has not been adequately established, some data suggest that ultrafiltration negatively impacts hydrolysate performance of cell growth and protein production in cell culture media.  In this case study, multiple lots of ultrafiltered and non-ultrafiltered LucraTone Soy P hydrolysates were evaluated to determine their impact on cell culture performance (mammalian and microbial cultures).  Ultrafiltration of hydrolysate stock solutions by normal flow and tangential flow techniques were also analyzed.

11:45 Optimization of Cell Culture Conditions for Protein Production using Quantitative Targeted Metabolite Analysis
Denise Sonntag, Ph.D., Senior Scientist Biochemistry, Contract Research, BIOCRATES Life Sciences AG
Cell-based protein production requires optimal culture conditions to obtain a high yield of quality products. As the composition of the cell culture medium is a critical parameter in the fermentation process, efficient analysis methods that allow media control during fermentation are highly beneficial for culture optimization. Quantitative targeted metabolomic analysis of cell culture supernatants 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, glycerophospholipids, sphingomyelins, total fatty acids, mono- and oligosaccharides and 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 the optimization of cell-based protein production.

12:15 Technology Spotlight (Sponsorship Available)

12:30 Luncheon Workshop (Sponsorship Available) or Lunch on your Own

Higher Yields

1:45 Chairperson’s Remarks

2:20 Intensifying CHO Cell Based Fed-Batch Culture for High Yield Antibody Production
Thomas Ryll, Ph.D., Director, Cell Culture Development, Cell Culture Development, Biogen Idec Inc.
Production of antibody drugs using mammalian cell culture has made significant progress over the last 20 years. Fed-batch processing has evolved as the dominant production mode at industrial scales of up to 15 – 20,000L operating volumes. While product concentrations in the 0.5 - 1 g/L range were considered high productivity in the early 90ties product concentrations in the range above 1 g/L is nowadays standard expectation and are typically reached at the pre-IND stage applying platform process designs with little to no optimization. More optimized fed-batch processes typically reach 2-5 g/L and more recently titers in the 10 g/L range have been reported for CHO cell culture.
Intensification of mammalian cell culture has been accomplished over the last 10 or so years by optimizing media compositions and feeding strategies. A result is that using fed-batch technology nowadays cell concentration levels can be reached which have previously been more typical for perfusion culture but not fed-batch. The presentation will review some of the recent progress we have accomplished at Biogen Idec while implementing chemically defined process formats for high efficiency antibody production.

Intensification of mammalian cell culture has been accomplished over the last 10 or so years by optimizing media compositions and feeding strategies. A result is that using fed-batch technology nowadays cell concentration levels can be reached which have previously been more typical for perfusion culture but not fed-batch. The presentation will review some of the recent progress we have accomplished at Biogen Idec while implementing chemically defined process formats for high efficiency antibody production.

2:50 Embryonic Stem Cells for the Manufacturing of Biologics
Majid Mehtali, Ph.D., Chief Scientific Officer, Vice President, Research and Development, Vivalis SA
Primary cells and established continuous cell lines have been used since decades for the industrial production of vaccines and therapeutic proteins. However, such manufacturing systems are often limited by various drawbacks. Embryonic stem cells hold exceptional biological properties that could theoretically be exploited for the derivation of new generations of cell substrates that fulfil modern industrial and regulatory requirements. EBx® cell lines have been derived from avian embryonic stem cells using proprietary procedures. Such cells maintain most of the desirable features of ES cells (ie. long-term genetic stability, indefinite cell proliferation…) but display new industrial- and regulatory-friendly characteristics (ie. proliferation in stirred-tank bioreactors at high cell densities as suspension cells, growth in serum-free media, high susceptibility to various human and animal viruses, efficient genetic engineering and heterologous protein production…). EBx® cells constitute a unique alternative for the manufacturing of vaccines and therapeutic proteins, in particular monoclonal antibodies with enhanced ADCC (antibody-directed cell cytotoxicity) activity. Fully controlled master and working cell banks (MCB & WCB) are available and a biologic master file (BMF) was filed with the US. FDA. EBx® cells have already been licensed to over 22 Biotech and Pharma companies worldwide.

3:20 Production of Animal-Free Recombinant Serum Proteins from Yeast for use in Biopharmaceutical Manufacturing

Sponsored by

Chris Finnis, PhD. Molecular Biology Manager, Novozymes Biopharma UK Ltd. The use of animal-derived components in biomanufacturing carries a risk of contamination with pathogenic prions and viruses. Novozymes has used strains of the baker’s yeast, Saccharomyces cerevisiae, originally engineered for the commercial production of recombinant human albumin (Recombumin®) and albumin fusion proteins (e.g. Albuferon®), to produce the first high-level microbial expression system for an animal-free recombinant transferrin analogue. The transferrin product was functionally equivalent to human serum transferrin and superior to commonly used iron salts in a range of in vitro assays, including mammalian cell culture and IgG productivity. This expression system has been scaled up for the cGMP manufacture of an animal-free recombinant transferrin (CellPrime™ rTransferrin AF) from an FDA inspected facility, which is now available for industrial cell culture applications.

Production of Animal-Free Recombinant Serum Proteins from Yeast for use in Biopharmaceutical Manufacturing
Chris Finnis, PhD. Molecular Biology Manager, Novozymes Biopharma UK Ltd.
The use of animal-derived components in biomanufacturing carries a risk of contamination with pathogenic prions and viruses. Novozymes has used strains of the baker’s yeast, Saccharomyces cerevisiae, originally engineered for the commercial production of recombinant human albumin (Recombumin®) and albumin fusion proteins (e.g. Albuferon®), to produce the first high-level microbial expression system for an animal-free recombinant transferrin analogue. The transferrin product was functionally equivalent to human serum transferrin and superior to commonly used iron salts in a range of in vitro assays, including mammalian cell culture and IgG productivity. This expression system has been scaled up for the cGMP manufacture of an animal-free recombinant transferrin (CellPrime™ rTransferrin AF) from an FDA inspected facility, which is now available for industrial cell culture applications. 

3:35 Refreshment Break in the Exhibit Hall

4:15 Poster Awards in the Exhibit Hall

4:30 Rapid Cell Line Development by Direct Cloning Based on Cell Secretion Analysis, Growth Tracking, and Secretion Stability
Gary Bright, Ph.D., Senior Director, Applications Development, Cyntellect, Inc.
Development of highly-secreting mammalian cell lines is critical for efficient biopharmaceutical manufacturing of many important therapeutic proteins. Current approaches are low-throughput involving significant labor for clone tracking and analysis. A fundamentally new process (CellXpress™ powered by LEAP™) combines in situ measurement of individual cell protein secretion, laser-mediated elimination of all non- and poorly-secreting cells, real-time growth tracking and secretion stability tracking. CellXpress yields hundreds of highly-secreting clones per plate within 24 hours of initial plating. Verification of cloning and subsequent cell growth was automatically tracked using non-invasive brightfield cell counting within plates at various time points after cloning, allowing efforts to be focused on clonal wells containing cells with both the best secretion and growth properties. Secretion stability tracking was performed using the in situ secretion assay from as few as 100 cells, allowing poor clones to be discarded very quickly before significant cell culture efforts were expended for standard assays requiring millions of cells (e.g., ELISA and HPLC). The process resulted in rapid generation of clonal populations with significantly increased and homogeneous antibody secretion, at a frequency that was 10-fold greater than with standard methods.

5:00 Effective Early Stage Clone Screening Using Flow Cytometry
Christine T. DeMaria, Ph.D., Senior Scientist, Therapeutic Protein Expression, Genzyme Corporation
Flow cytometry was partnered with a non-fluorescent reporter protein for rapid, early stage identification of clones producing high levels of a therapeutic protein. A cell surface protein, not normally expressed on CHO cells, is co-expressed, as a reporter, with the therapeutic protein and detected using a fluorescently labelled antibody. The genes encoding the reporter protein and the therapeutic protein are transcribed in the same mRNA but are translated independently. Since they each arise from a common mRNA, the reporter protein’s expression level accurately predicts the relative expression level of the therapeutic protein for each clone. This method provides an effective process for generating recombinant cell lines producing high levels of therapeutic proteins, with the benefits of rapid and accurate 96-well plate clone screening and elimination of unstable clones at an earlier stage in the development process. Furthermore, because this method does not rely on the availability of an antibody specific for the therapeutic protein being expressed, it can be easily implemented into any cell line development process.

5:30 Close of Conference

6:00 PepTalk Dinner “BuzZ in the Pipeline”

8:00 Close of Day

Overview | Short Courses | Day 1 (Joint Session) | Day 2 | Day 3 | Download Brochure

For more information, please contact:
Mary Ruberry, Conference Director
Phone: 781-972-5421 
E-mail: mruberry@healthtech.com 

For exhibit and sponsorship information, please contact:
Suzanne Carroll, Manager, Business Development
Phone: 781-972-5452 
E-mail: scarroll@healthtech.com

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