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04: Biomedical and pharmaceutical engineering – key technologies of the 21st century

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Hauptschule
Breakout / Working Group
english language

The challenges in biomedical technology as well as in the development and production of modern therapeutics have risen drastically. An important indicator of this trend is the significant reduction in the approval of new medicines since 1995.
This working group will deal with modern methods to counteract this development, e.g. by using modern “high-throughput methods” like “lab-on-a-chip”, nanotechnology and modern quality and risk management in combination with predictive modelling approaches. Computational medicine’s aim, for example, is to better analyze age-related diseases like atherosclerosis or osteoporosis. This approach to digitalize and personalize data will lead to better health care.

Speakers

Consultant; retired Head, Technology Liaison, Global Quality Operations, Novartis Pharma AG, Dornach Abstract
The pharmaceutical Industry has significant problems with innovation. Drug discovery is lacking product innovation that should lead to new products. Development and manufacturing use old technologies that produce quality levels that need significant end product testing and elimination of non conforming products.
The new possibilities of Quality by Design for pharmaceutical development and manufacturing are discussed. The ICH initiative on global harmonization (International Conference on Harmonization ICH) has changed the vision of how development, manufacturing and control of drug products should be performed. The implementation of ICH guidelines on Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Quality Systems (Q10) will open new possibilities for manufacturing flexibilities, cost reduction and regulatory flexibility.
The lack of innovation in development and manufacturing are highlighted. The possibilities of the new concepts are discussed and expectations to stakeholders are defined.
Professor of Engineering Science; Director, Auckland Bioengineering Institute, The University of Auckland Abstract
The Physiome Project of the International Union of Physiological Sciences (IUPS) is attempting to provide a comprehensive framework for modelling the human body using computational methods that can incorporate the biochemistry, biophysics and anatomy of cells, tissues and organs. A major goal of the project is to use computational modelling to analyse integrative biological function in terms of underlying structure and molecular mechanisms. It is also establishing web-accessible physiological databases dealing with model-related data at the cell, tissue, organ and organ system levels. A newly formed EU Network of Excellence for the Virtual Physiological Human (VPH) is also contributing and, in particular, addressing clinical applications of the project.
The application of this framework to modeling the heart, lungs, musculo-skeletal system and other organ systems will be discussed, including some clinical applications of the models. The talk will also briefly describe current progress in the development of XML markup languages for standardised encoding of models, and the model repositories, graphical user interfaces and the open source computational software being developed under the IUPS Physiome Project for computational physiology.
References
1. Hunter, P.J. and Borg, T.K. Integration from proteins to organs: The Physiome Project. Nature Reviews Molecular and Cell Biology. 4, 237-243, 2003.
2. Hunter, P.J. and Nielsen, P.M.F. A strategy for integrative computational physiology. Physiology. 20,316-325, 2005.
3. Hunter, P.J., Crampin, E.J. and Nielsen, P.M.F. Bioinformatics, multiscale modelling and the IUPS Physiome Project. Briefings in Bioinformatics. 9 (4), 333-343, 2008.
Direktor, Institut für Biomechanik, Eidgenössische Technische Hochschule Zürich Abstract
Aging is on the verge of a new era. Humans are approaching old age in unprecedented numbers as a result of large baby boom cohorts born in the middle of the 20th century that are approaching traditional retirement ages. Increases in the prevalence of age-related disease, frailty, and disability are visible signs of the potential costs and social burdens arising from this historic demographic shift. One disease that will be affected dramatically by this shift will be osteoporosis and with it there will be marked increase in osteoporotic bone fractures. With recent advances in molecular medicine and disease treatment in osteoporosis, the development of diagnostic and monitoring tools must therefore be in the focus of aging and health-related research in order to allow early detection and control of the disease.
A number of new microstructural imaging modalities have been put forward recently allowing quantification with high precision and accuracy. Biomedical imaging technology such as MRI or CT is readily available, but few attempts have been made to expand the capabilities of these systems by integrating quantitative analysis tools as an integrative part of biomedical information technology and by exploring structure-function relationships in a hierarchical fashion over the different length scales. Nevertheless, such quantitative endpoints have become an important factor for success in basic research and the development of novel therapeutic strategies in biomedicine and clinical practice. Where the 20th century was the century of image formation, success in the 21th century will be judged by our ability to extract meaningful quantitative information from these images. Micro- and nano-computed tomography is key to these developments being an approach to image and quantify trabecular bone in three dimensions and providing multi-scale biological imaging capabilities with isotropic resolutions ranging from a few millimetre (clinical CT), to a few micrometers (microCT) down to one hundred nanometers (nanoCT).
As part of the presentation, new strategies for advanced hierarchical quantification of bone and their structure function relationship will be presented. The focus will be on hierarchical micro- and nano-imaging as well as image-guided biomechanics. At the microscopic level, bone microstructure is known to influence bone strength and failure mechanisms significantly. Biomechanical imaging allows direct time-lapsed visualization and computation of local displacements and strains for better quantification of bone fracture initiation and progression. Recent introduction of highly brilliant synchrotron radiation X-ray sources now permits to explore bone on the nanoscopic level to uncover the ultrastructure of bone including vascular and cellular structures and to investigate their role in the development of bone failure.
In conclusion, hierarchical microimaging is well suited to investigate quantitative structure function relationships in both trabecular and cortical bone. The procedure can help improve predictions of bone failure, clarify the pathophysiology of skeletal diseases, and define the response to therapy. We expect these findings to improve our understanding of structure function relationships in bone and with that to also allow improved quality control and more successful outcomes in studies dealing with pharmacological treatment of bone.
James M. and Marsha McCormick Chair of Biomedical Engineering; Samuel B. Eckert Professor of Chemical Engineering, School of Chemical and Biomolecular Engineering, Cornell University, Ithaca Abstract
We seek to understand the response of the human body to various pharmaceuticals. Our platform technology is an in vitro system that combines microfabrication and cell cultures and is guided by a computer model of the body. We called this in vitro system a micro cell culture analog (microCCA) or a "Body-on-a-Chip". A microCCA device contains mammalian cells cultured in interconnected micro-chambers to represent key body organs linked through the circulatory system and is a physical representation of a physiologically based pharmacokinetic model. MicroCCAs can reveal toxic effects that result from interactions between organs as well as provide realistic, inexpensive, accurate, rapid throughput toxicological studies that do not require animals. The advantages of operating on a microscale include the ability to mimic physiological relationships more accurately as the natural length scale is order of 10 to 100 microns. The basic concept has been described. (1,2)
We have done "proof-of-concept" experiments to evaluate combination therapy for cancer. Multidrug resistant (MDR) cancer often occurs after initial success with a chemotherapeutic drug. MDR cancer cannot be treated with the original drug as well as many other drugs. A form of MDR is overexpression of P-glycoprotein at levels 50 to100 fold over normal. P-glycoprotein is a pump protein that intercepts drugs and pumps them back out of the cell. Here we test a possible combination treatment using a chemotherapeutic drug, doxorubicin, and two MDR suppressors (cyclosporine and nicardipine). The microCCA (with "liver", "bone marrow", "uterine cancer", "slowly perfused" and "rapidly perfused" compartments) shows an unexpected synergistic response to certain drug combinations not observable in traditional assay systems. The toxic response is selective to the MDR resistant cancer cells; the MDR suppressors do not alter toxicity in the "bone marrow" compartment. (3) We have also used a microCCA to test potential combination therapies (Tegafur and uracil) for colon cancer. (4) Tegafur is a prodrug for 5-FU and uracil an inhibitor of DPD, an enzyme which deactivates 5-FU. Simple microwell plates cannot probe this system, but the microCCA predicts the types of responses observed experimentally. We have coupled these body modules with a micro model of the GI tract to examine the response to oral exposure of drugs, chemicals, or nanoparticles.
Overall, we believe that in vitro, microfabricated devices with cell cultures provide a viable alternative to animal models to predict toxicity and efficacy in response to pharmaceuticals.
References
1. Sin, A., K.C. Chin, M.F. Jamil, Y. Kostov, G. Rao, and M.L. Shuler. The Design and Fabrication of Three-Chamber Microscale Cell Culture Analog Devices with Integrated Dissolved Oxygen Sensors. Biotechnol. Prog. (2004), 20:338-345.
2. Khamsi, R. Meet the Stripped Down Rat. Nature (2005), 435(5 May):12-13.
3. Tatosian, D.A. and M.L. Shuler. A Novel System for Evaluation of Drug Mixtures for Potential Efficacy in Treating Multidrug Resistant Cancers. Biotechnol. Bioeng. (2009), 103:187-198.
4. Sung, J.H. and M.L. Shuler. A Micro Cell Culture Analog (microCCA) with 3-D Hydrogel Culture of Multiple Cell Lines to Assess Metabolism-Dependent Cytotoxicity of Anti-Cancer Drugs. Lab Chip (2009), 9:1385-1394.
Full Professor and Chair of Biomechanics, Graz University of Technology; Adjunct Full Professor and Chair of Biomechanics, Department of Solid Mechanics, School of Engineering Sciences, Royal Institute of Technology (KTH), Stockholm; Visiting Professor, Department of Mathematics, University of Glasgow, Graz Abstract Chair
Mechanics regulates biological processes at the molecular, cellular, tissue, organ, and organism levels. Biomechanics is the development, extension, and application of mechanics to answer questions of importance in biology and medicine. Nowadays, biomechanics is a multi-disciplinary, growing area in research and development with challenges of academic, industrial and clinical importance.
This presentation aims to show the variety, richness and beauty of biomechanics to increase our understanding of a critical human health concern. We are focusing here on "state-of-the-art" in vascular biomechanical simulation and modeling. In particular, a multi-disciplinary approach in the context of biomedical engineering, biochemistry and biophysics presents a special opportunity to build integrated computational and predictive models. Such models are able to couple the mechanics of, for example, the vascular wall with the biofluid mechanics by including cell-mediated changes in wall structure, properties, and geometry. Moreover, they can incorporate 3D patient-specific geometries, thus providing the basis for the fusion of clinical imaging/diagnostics and computational biomechanics. This fusion leads to better computational tools that represent a reliable basis for the optimization of biomedical engineering designs for tissue engineering or of coatings and stent platforms for drug delivery. It is the biomedical industry which benefits from such tools.
Computational and predictive models have the potential to better understand pathological changes due to biomechanical factors, to prevent injuries, to improve clinical diagnostics, surgical planning and intervention, to help predict the rupture risk of aneurysms or the effects of specific pharmacologic interventions on stent-grafts. The range of possible applications is huge. Of course, the goal of such efforts are improving health care delivery and decreasing the financial burden of our aging society.
References
1. G.A. Holzapfel and R.W. Ogden (eds.): "Biomechanical Modelling at the Molecular, Cellular and Tissue Levels", CISM Courses and Lectures No. 508, Springer: Wien, New York, 2009.
2. D.E. Kiousis, A.R. Wulff and G.A. Holzapfel: Experimental studies and numerical analysis of the inflation and interaction of vascular balloon catheter-stent systems. Annals of Biomedical Engineering, 37 (2009) 315-330.
3. J. Stålhand, A. Klarbring and G.A. Holzapfel: Smooth muscle contraction: mechanochemical formulation for homogeneous finite strains. Progress in Biophysics & Molecular Biology, 96 (2008) 465-481.
Head, Institute of Process- and Particle Engineering, Graz University of Technology; Scientific Director, Research Center Pharmaceutical Engineering GmbH, Graz Abstract Chair
As our understanding of the bio-molecular origin of many diseases, such as cancer, rapidly increases, it raises the prospect for developing new and effective therapeutic compounds or gene-based therapies in the next decades. This requires new technologies, such as multi-drug controlled-release vehicles, nanotechnology-based delivery systems, drug targeting and nano-structured drug products, that are a prerequisite for delivering the highly potent and specific pharmaceutical agents of the future. In addition, personalized medicine, i.e., drug products that are designed to fit the individual needs of patients, is becoming a driver for pharmaceutical innovation. Clearly, drugs of the future are "intelligent" products that consist of many different components with diverse functionality, similar to a cell phone or an airplane. Often these components have to be structured on the nano-level, making the drug of the future a true "high-tech" product.
In order to make new drugs available to patients worldwide, they need to be manufactured on a large scale, i.e., millions of doses per year, while maintaining the highest quality standards of all industries in order to avoid contamination or undesired effects. This, however, is a major problem, since no production technology for new high-tech medicines simply exists at present. Even for today's standard drug products, manufacturing is a challenge, and in some cases up to 20% of all batches produced need to be reworked, discharged or recalled.
The scientific area of pharmaceutical engineering focuses on the development of a new robust and scalable production technology for novel high-tech drug products, both for small molecules and biopharmaceuticals. This requires expertise in the fields of chemical engineering, material science, chemistry, biotechnology, nano-technolgy and pharmaceutics. Thus, pharmaceutical engineering, while being a key to the development of modern drugs and therapeutics, is truly an interdisciplinary endeavour.
Ph.D. Researcher, Institute of Process and Particle Engineering, Graz University of Technology Coordination

Dr. Fritz ERNI

Consultant; retired Head, Technology Liaison, Global Quality Operations, Novartis Pharma AG, Dornach

 Started his career in Japan in research at Hitachi Ltd.
1969 Ph.D. from the Swiss Federal Institute of Technology (Dr. sc.nat. ETH) in Zurich
1974-1986 Several positions in the analytical research and development of new drug substances and products at Sandoz in Basel
1986-1995 Head of Analytical Research and Development at Sandoz in Basel
1995-2000 Several management positions in Quality Assurance/Control at Sandoz and after the merger within Novartis
2000-2002 Director of Novartis Pharmanalytica SA in Locarno, Switzerland
 Since 2009 Consultant (retired from Novartis after 35 years in the pharmaceutical Industry)
2002-2009 Head of Technical Liaison, Global Quality Operations of Novartis in Basel (responsible for the establishing of Novartis Global activities on Process Analytical Technologies (PAT) and Quality by Design)

Ph.D. Peter J. HUNTER

Professor of Engineering Science; Director, Auckland Bioengineering Institute, The University of Auckland

1971 B.E. in Engineering Science (1st Class Hons) at Auckland University, NZ
1971-1972 Master s research in the Dept. of Theoretical & Applied Mechanics at Auckland University
1973-1975 Postgraduate research for D.Phil. in Physiology at Oxford University
1975-1977 Research Fellow and tutor at St. Catherine's College, Oxford University
1975-1977 Research Fellow at Rutherford Laboratory, UK
1977-1978 Engineering Lecturer at Keble College, Oxford
since 1979 Lecturer to Professor in Engineering Science at Auckland University
1998-1999 Associate Dean of Research in the School of Engineering
1999-2000 James Cook Fellow of the Royal Society of New Zealand
2001 Distinguished Professor, University of Auckland
since 2001 Director of Bioengineering Institute at Auckland University
since 2003 Director, Computational Physiology, University of Oxford

Dr. Ralph MÜLLER

Direktor, Institut für Biomechanik, Eidgenössische Technische Hochschule Zürich

 Anschließend arbeitete er als Mikrotomographie Projektmanager für die BIOMED1 Concerted Action der Europäischen Union.
1994 Promotion in Elektrotechnik, Eidgenössische Technische Hochschule Zürich
1996 Wechsel an die Harvard Medical School in Boston, wo er als tenure-tracked Assistant Professor of Orthopedic Surgery und als stellvertretender Direktor des Orthopedic Biomechanics Laboratory tätig war.
2000-2006 SNF Professor für Bioingenieurwissenschaften am Institut für Biomedizinische Technik der Universität und ETH Zürich
seit 2006 Professor für Biomechanik am Departement für Maschinenbau und Verfahrenstechnik und der Direktor des Instituts für Biomechanik an der ETH Zürich

Ph.D. Michael L. SHULER

James M. and Marsha McCormick Chair of Biomedical Engineering; Samuel B. Eckert Professor of Chemical Engineering, School of Chemical and Biomolecular Engineering, Cornell University, Ithaca

1969 B.Sc., Chemical Engineering, University of Notre Dame (Notre Dame, IN)
1973 Ph.D., Chemical Engineering, University of Minnesota (Minneapolis, MN)
1974-1979 Assistant Professor of Chemical Engineering, Cornell University
1979-1983 Associate Professor of Chemical Engineering, Cornell University
1980-1981 Visiting Scholar, Department of Chemical Engineering, University of Washington, Seattle
1984-1991 Professor of Chemical Engineering, Cornell University
1985-1988 Founding Editor, Biotechnology Progress (Board since 1988)
1986-2006 Editorial Board, AIChE (American Institute of Chemical Engineers) Journal
1988-1989 Visiting Prof., Dept. of Chemical Engineering, University of Wisconsin, Madison
since 1990 Editorial Board, Biotechnology and Bioengineering
1991-2001 Board of Directors, Phyton
since 1992 Samuel B. Eckert Professor of Chemical Engineering, Cornell University
since 1993 Director, Bioengineering Program
since 1994 Editorial Board, Enzyme and Microbial Technology
1995 Guest Professor, Institute for Biotechnology, ETH Zurich, Switzerland
1996-2008 Editorial Board, Cambridge University Press
1998-2002 Director, Chemical and Biomolecular Engineering
2001-2003 Board of Directors, American Institute of Chemical Engineers
2002-2004 Director, Biomedical Engineering Program
  Scientific Advisory Board, HuRel
since 2004 James and Marsha McCormick Chair of Biomedical Engineering
2005-2008 Scientific Advisory Board, Institute of Chemical and Engineering Sciences, Singapore

Dipl.-Ing. Dr. techn. Gerhard A. HOLZAPFEL

Full Professor and Chair of Biomechanics, Graz University of Technology; Adjunct Full Professor and Chair of Biomechanics, Department of Solid Mechanics, School of Engineering Sciences, Royal Institute of Technology (KTH), Stockholm; Visiting Professor, Department of Mathematics, University of Glasgow, Graz

1985 MSc. Civil Engineering (with distinction), Graz University of Technology (TU Graz), Austria
1986-1987 National Service at Red Cross
1987-1997 Assistant and Docent at the Institute of Strength of Materials, TU Graz
1990 PhD in Mechanical Engineering (with distinction), TU Graz
1991 Visiting Scholar at University of Shenyang, P.R. China
1993-1995 Post-Doctoral Fellow at the Division of Applied Mechanics, Department of Mechanical Engineering, Stanford University; with late Prof. JC Simo
1996 Habilitation in "Mechanics" Vienna University of Technology
1998-2004 Associate Professor and Head of the Research Group "Computational Biomechanics", Institute of Structural Analysis, TU Graz
2003 Visiting Professor, Universidad Politécnica de Cataluña, Barcelona, Spain
2003 Offer of a Chair (C4) in Continuum Mechanics, University of Kassel, Germany (not accepted)
2004-2007 Full Professor and Chair of Biomechanics, Royal Institute of Technology (KTH), Stockholm, Sweden
2007 Visiting Professor, University of Zaragoza, Spain
since 2007 Full Professor and Chair of Biomechanics, Graz University of Technology; Adjunct Full Professor and Chair of Biomechanics, Department of Solid Mechanics, School of Engineering Sciences, Royal Institute of Technology (KTH), Stockholm
since 2009 Visiting Professor, Department of Mathematics, University of Glasgow, Scotland

DI Dr. techn. Johannes KHINAST

Head, Institute of Process- and Particle Engineering, Graz University of Technology; Scientific Director, Research Center Pharmaceutical Engineering GmbH, Graz

1991 DI in Chemical Engineering (highest distinction), Graz University of Technology
1995 Ph.D. in Chemical Engineering (highest distinction), Graz University of Technology
1996-1998 Post Doc in Chemical Engineering, University of Houston, Houston (TX)
1998-2003 Assistant Professor, Rutgers University, Piscataway (NJ)
since 2003 Tenured Professor, Rutgers University, Piscataway (NJ)
2003-2006 Director of the Rutgers Catalyst Consortium, Rutgers University, Piscataway (NJ)
since 2005 Professor of Pharmaceutical and Process Engineering
2005-2008 Marie Curie Chair of the European Union
since 2006 Head of the Institute for Process Engineering, Graz University of Technology
since 2008 Scientific Director of the Research Center for Pharmaceutical Engineering GmbH

Technology Forum

show timetable

27.08.2009

10:00 - 12:30Technology brunch of the Tiroler ZukunftsstiftungSocial
13:00 - 13:10Opening by the European Forum AlpbachPlenary
13:10 - 14:00Welcome statementsPlenary
14:00 - 16:00Pathways out of the crisis - new perspectives through research and innovation?Plenary
16:30 - 18:00The future of stem cell researchPlenary
20:00 - 21:30A look at the past - the secrets of our originPlenary
21:30 - 23:30Evening reception hosted by Forschung Austria in cooperation with GFF and BMVITSocial

28.08.2009

09:00 - 18:00Junior Alpbach - Science and technology for young peopleBreakout
09:00 - 15:00Technology Workshop: Trend radar of developments in societyBreakout
09:00 - 15:30Working Group 01: Can we trust in feed and food?Breakout
09:00 - 15:30Working Group 02: An international comparison of research, technology and innovation-policy (RTI) strategiesBreakout
09:00 - 15:30Working Group 03: "Sowing and harvesting" in bio(techno)logical research: From the atomic structure of proteins to the discovery of new drugs and their clinical applicationBreakout
09:00 - 15:30Working Group 04: Biomedical and pharmaceutical engineering - key technologies of the 21st centuryBreakout
09:00 - 15:30Working Group 05: Infratech - a chance in crisisBreakout
09:00 - 15:30Working Group 06: Creativity - fuel for the knowledge society?Breakout
09:00 - 15:30Working Group 07: Creative industries vs. old economy: where is the economy headed?Breakout
09:00 - 15:30Working Group 08: Universities: responsibility for the futureBreakout
09:00 - 15:30Working Group 09: Trust in the future - investment in researchBreakout
09:00 - 15:30Working Group 10: Digital Government - citizens and administration in a conflict areaBreakout
09:00 - 15:30Working Group 11: E-Mobility AustriaBreakout
09:00 - 15:00Ö1 Children's University Alpbach - Science and technology for kidsBreakout
10:00 - 15:00Special Event: Positioning Austria in the international knowledge areaBreakout
16:30 - 17:45Creativity. How kids learn - learning like kids do?Plenary
18:15 - 20:00Innovative research locations - regions in competitionPlenary

29.08.2009

09:30 - 10:45Can we trust in science? Integrity in scientific researchPlenary
10:45 - 11:30The future of the universe - perspectives for astrophysics and cosmologyPlenary
12:00 - 13:00I-Brain - the technological evolution of the brain?Plenary
13:00 - 13:15Closing statementPlenary
13:15 - 14:00Snack receptionSocial