Upstream Technologies
A. Advances in Biocatalysis
Biocatalyis is increasingly becoming a more prevalent and important technology. Enzymes offer unique advantages over traditional catalysts (high specificity, high selectivity, low environmental impact, etc.) and are also becoming more economically viable. Additionally, researchers are minimizing the challenges that enzymes present (minimal range of pH and temperature, low stability, etc.) through advances in genomics, proteomics, directed evolution, and rational design. Biocatalysts are important to industrial applications such as the production of specialty chemicals, polymers, and chiral intermediates. They are also vital to medical diagnostics and drug discovery, particularly with the increasing development of high-throughput screening assays. This session will focus on both theoretical as well as experimental achievements in biocatalysis research and applications. We encourage presentations that discuss recent successes in the optimization/engineering of biocatalysts and biocatalytic processes, and where the potential impact to industrial or medical applications is novel and significant.
Co-Chairs: Huimin Zhao, U Illinois Urbana-Champaign, (217) 333-2631, and Angela Lewandowski, Genzyme, (508) 271-2975,
B. Advances in Microbial Fermentation Process Development
The demand for fermentation products has increased in the past few years leading to an urgent requirement for industry and academia to focus on increases in production capacity and the improvement of existing yields for bio-processes. With huge investments involved in expanding production capacity, industries have to rely primarily on process improvements for net productivity gains. With current advances in molecular biology leading to a better understanding of cellular mechanisms and cutting edge technologies to optimize upstream processes, the biotech world has shown significant progress in bridging the gap between increasing demands and limited production capacity. This session focuses on the methods used to improve fermentation yields through strain engineering, novel methodologies and cutting edge technology for fermentation process optimization. This session will include topics related to advances in upstream process optimization, yield improvements through bioreactor design, process-monitoring and control techniques.
Co-Chairs: Mariajose Castellanos, UMBC, (410) 455-8151, and Swapnil Bhargava, Amgen, (805) 447-6241,
C. Advances in Metabolic Engineering
Metabolic Engineering includes the analysis and modification of metabolic pathways to optimize genetic and regulatory processes within cells to increase production of certain substances. Metabolic engineers commonly work to reduce cellular energy use (i.e., the energetic cost of cell reproduction or proliferation) and to reduce production of waste or undesirable by-products. Metabolic Engineering typically involves the redirection of cellular activities by the rearrangement of the enzymatic, transport, and regulatory functions of the cell through the use of recombinant DNA and other techniques. Much of this effort has traditionally focused on microbial organisms, but important advances are being made in cell cultures derived from plants, insects, and animals.
This session will cover recent experimental and modeling advances in the field of prokaryotic and eukaryotic metabolic engineering. Areas of possible interest include but are not limited to: models and expression tools for optimizing metabolic flux; development of new host organisms; tools for elucidation of functional needs; pathway development and/or optimization for novel drug, energy, or material production; and the application of cutting edge technologies to metabolic engineering and synthetic biology challenges.
Co-Chairs: Kristala Jones Prather, MIT, (617) 253-1950, and Nimish G. Dalal, Bristol-Myers Squibb, (315) 432-9561,
D. Advances in Cell Culture Process Development
As the number and quantity of recombinant proteins in development and commercial production has increased over the last few years, the demand on process development and manufacturing facilities has increased as well. While some of this demand can be met by building new infrastructures and facilities, a more efficient and less costly means of meeting these needs is by designing higher productivity processes that are well characterized and robust. This session will focus on recent developments in the field of cell culture process development and engineering with emphasis on enhancing yield and improving robustness of the culture process (i.e., excluding cell line manipulations). Topics include, but are not limited to, advances in clone screening and development, bioprocess optimization, bioreactor design and operation,novel control approaches, scale up/scale down methods, utilization of new technology and process analytical techniques for cell culture.
Co-Chairs: Sarah Harcum, Clemson, (864) 656-6865, and Jayanth Sridhar, Merck, (215) 652-0338,
E. Molecular and Cellular Approaches in Cell Culture Systems
Recent years have seen significant advances in molecular biology techniques as well as genomic tools. Advances in vector systems, especially with the integration of genetic elements to expression cassettes, have led to improvement in protein expression as well as streamlining of the process of cell line development and optimization. Tools such as microarray and proteomics are currently reaching a level of understanding and sophistication that they are starting to be applied directly to further our understanding of cell culture based expression systems both in a fundamental manner as well as to understand specific phenotypes and genotypes. Tools such as siRNA are allowing for results derived from microarray and genomics to be applied to engineering of cell culture systems to rapidly to test for functional validation of microarray and proteomics data. These tools are also being applied to understand the metabolism of cell culture systems as well as in the creation of designer cell culture systems, via significant host engineering. This session is intended to focus on application of recent advances in molecular and cell biology tools to further our understanding of both microbial and mammalian cell culture systems. Examples on host engineering are also invited for presentation. Particular consideration will also be given to papers that focus on application of cutting edge molecular tools to improve the properties of the proteins expressed using cell culture systems.
Co-Chairs: Eric Shusta,Wisconsin, (608) 262-1092, and Raghavan Venkat, MedImmune, (301) 398-5817,
F. Applications of Systems Biology to Upstream Process Development
Systems biology is a newly emerging discipline that combines traditional Chemical and Biochemical Engineering principles with systems-theoretic approaches and rapidly advancing analytical capabilities. A key component of Systems Biology is the integrated characterization of biological systems on organism-wide scales. Central to this integrated approach is (i) the ability to rapidly gather quantitative system-wide data on different length and time scales and (ii) the integration of large tracks of data into a coherent picture of the biological process.
The goal of this session is to explore the methods and technologies underlying Systems Biology and their application to process development and improvement. Experimental and theoretical papers are encouraged, with the ideal paper incorporating both. Areas of possible interest include but are not limited to: models and expression tools for optimizing metabolic flux, development of new host organisms for metabolite or protein production, tools for elucidation of the functional properties of networks and systems, and the development or improvement of pathways for novel drug, energy, or material production in both prokaryotes and eukaryotes.
Co-Chairs: Jeffrey Varner, Cornell, (607) 255-4258, and Ravi Radhakrishnan, Penn, (215) 898-0487,
Downstream Technologies
Downstream Processing: Impact of Product Properties on the Design and Optimization of Downstream Processes
Understanding how product properties drive design and optimization of downstream processes (bioseparations and formulation) and how downstream processes influence product properties are both critical issues for the biotech community. Therefore, this session will focus on new molecular insights, design principles and practical optimization considerations that reveal how downstream processes impact product properties and how specific product properties can influence the design of such processes. Products of interest to this session are proteins, peptides, vaccines, natural products and oligo- or polynucleotides. Product properties of interest include proper folding and minimization of aggregation, glycosylation and other post-translational modifications, pegylation and minimization of oxidation, cross-linking, deamidation and product-related impurities, such as truncated, extended and degraded biomolecules. Examples of topics well suited for this session:
· Approaches that guide optimal selection of specific unit operations and order of process steps to enhance product properties
· Studies of how operating conditions of downstream processes (e.g., mixing speeds, flow rates, temperature) influence product properties
· Novel separations or novel modes of carrying out existing separations that improve product properties and minimize impurities
· Theoretical and experimental insights into how solution environment, surfaces and other aspects of downstream processes impact the final properties of biomolecules
Co-Chairs:
Peter M. Tessier, Department of Chemical & Biological Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, (518) 276 2045, .
Arne Staby, Project Planning & Management, Novo Nordisk A/S, Nybrovej 90, DK-2820 Gentofte, Denmark, +45 4443 9989, .
Scale-up/Scale-Down
There has been a drive in the bioprocessing industries for more expedient development using less material at smaller scales, with the end goal of developing commercial processes at increasingly larger scales. This session will focus on principles and issues regarding the scale up or scale down of bioseparation unit operations. Papers on the scale up of various separation processes (chromatography, membrane, precipitation, etc.) could focus on the effect of scale, the operational adjustments needed to handle very large scales, or the use of disposable formats. Papers demonstrating improvements in scale down models, for the purposes of process validation, troubleshooting, or acceleration of development timelines, are also sought. This would include papers describing the use of high throughput screening formats (e.g., 96-well plate), particularly if theoretical and/or empirical connections between these screening formats and actual process performance can be established.
Session Chairs
Doug Frey. University of Maryland Baltimore County, Phone : (410) 455-3418, Email :
Scott Tobler, Wyeth, Phone : (978) 247-1078, Email :
Downstream processing – Emerging technologies for Downstream Processing
New drivers in the biotechnology industry have created a need for powerful new technologies in downstream processing. Included among these drivers are the development of high-yielding expression systems, products with projected multi-ton demands, new expression hosts and systems, novel therapeutic modalities and potential competition from generic biologics. The result has been an interest in novel, game-changing downstream technologies, with the potential to radically impact the protein production industry at a fundamental level. This session will focus on the development and application of cutting edge technologies, with emphasis on their impact in the changing world of bioprocess development. Topics of interest include, but are not limited to: development of new purification and primary recovery methods, disposable large-scale technologies, unconventional process configurations, purification challenges for new therapeutic modalities. Submissions that combine theory and practice, or relate one to the other, are particularly sought.
Co-chairs:
David Wood, Department of Chemical Engineering, Princeton University, Princeton, NJ 08544, (609) 258-5721,
Sanchayita Ghose, Process Sciences, Bristol-Myers Squibb, Syracuse, NY 13057, (315) 431-7930, email:
Non-Chromatographic Separations: Innovations and Advances
The increasing demand for lower-cost/higher-throughput recovery processes in the biotechnology industry has pushed our current process designs to the limits of their capability. The low cost and high throughput nature of non-chromatographic techniques provides an attractive avenue towards process intensification.
Non-chromatographic separation techniques have long been the workhorse of non-therapeutic large scale purification processes, while chromatography remains the workhorse of current biotherapeutic recovery processes. The challenge becomes tailoring these non-chromatographic techniques to a GMP environment for process consistency, impurity clearance as well as process “portability” to different manufacturing sites. Due to the strict requirements of therapeutic processes in terms of process impurity clearance and product quality attributes, new cutting-edge technologies may also be required to advance us beyond the landscape of our current chromatographic paradigms.
This session is intended to examine key advances in established separation processes such as centrifugation, depth filtration, membrane filtration, precipitation, crystallization, refolding, viral filtration and ultrafiltration, as well as provide a venue for novel separation technologies. We welcome presentations illustrating challenges and solutions to implementing these and other non-chromatographic techniques in processing of biotherapeutics and other biotechnology products. Presentations exploring methods of high-throughput screening of non-chromatographic separation methods are also encouraged.
Session Chairs
Chris Roberts , University of Delaware : Phone : 302-831-0838, email :
Tony Cano, Genentech : Phone : 650-467-1422, email :
Bioprocess Integration: Case studies
This session will cover case studies that highlight a more holistic approach to bioprocess development, optimization, implementation and change. The bioprocess could be at any scale ranging from lab to pilot to manufacturing. As an example, papers detailing how upstream bioprocess operations and performance impact the performance of downstream steps post harvest (isolation and purification steps further downstream) will be accepted.
Of particular interest would be the impact of a new technology – examples include a new bioprocessing step employed upstream, an in-line analytical tool (PAT) or off-line analytical tool. The session will focus on lessons learned during the implementation of the new technology or process change, regardless of whether the result was successful.
Session Chairs
Yuefeng Lu, Amgen, Phone : (805) 447-4897, Email :
William Kelly, Villanova University : Phone :(610) 519-4947, Email :
Downstream Process Modeling
Time-to-market pressure manifests directly in time-to-process pressure. Rapid development, scale-up, and validation of downstream purification processes with fewer resources is the norm. As a result of these development constraints, the amount of experimental data available to define, develop and characterize a downstream process can be limited. Process modeling can be used as an effective tool to aid in the development of biotechnology products, while cutting down on development time, resource requirements, and experimental data required. Downstream process modeling has been used as a predictive tool to streamline experimental work in several areas, including chromatographic separation and unit operation scale-up predictions. Additionally, it can be used to troubleshoot manufacturing deviations or used to gain further insight into complex separation phenomena. This session will focus on recent advances in process modeling, in particular those that use the latest technologies in modeling applications to speed up and/or improve downstream process development and process scale-up.
Topics of interest include both novel macroscopic modeling (such the integration of unit operations), as well as new microscopic modeling approaches that connect the behavior of biologics with process design and operation variables (such as interaction of proteins with surfaces in chromatographic and filtration environments). Contributions that use the latest in modeling technology are particularly sought in this session.