Pharmacokinetics and Pharmacodynamics of ... - GMP

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GMP
Grou
p
e de Métabolisme
et de Pharmacocinéti
q
ue
Association loi du 1er Juillet 1901 n° 22/2781
www.gmp.asso.fr
gmp@cines.fr





Pharmacokinetics
and
Pharmacodynamics
of
macromolecules


10
th
and 11
th
of January 2008

Maison de la Chimie, 28 rue Saint-Dominique, 75007 PARIS




SHORT BIOGRAPHIES

SHORT BIOGRAPHIES

THURSDAY 10 JANUARY 2008


Session I - Macromolecules : the bases
9h30-10h00 Macromolecules : definition and particularities
Pr J.M. BIDART (Paris XI)
Jean-Michel Bidart is Professor of Biotechnology at the Faculty of Pharmacy, University Paris-
Sud 11. He is also Associate Director of the Department of Laboratory Medicine and Pathology,
and Head of the Translational Research Laboratory at Institut Gustave-Roussy, Villejuif, a
leader comprehensive cancer center in France. Since the early 80s, Jean-Michel Bidart has been
involved in the development of monoclonal antibodies directed against tumor biomarkers for
the improvement of cancer diagnosis and follow up.
His research interest focuses on the identification of genetic alterations and of new molecular
therapeutic targets for the treatment of thyroid carcinomas.

10h00-10h30 Macromolecules immuno-analysis: the example of therapeutic antibodies
Pr Gilles PAINTAUD (CHRU Tours)
Gilles Paintaud est professeur de Pharmacologie à la Faculté de Médecine de Tours et
responsable du laboratoire de pharmacologie-toxicologie du CHRU de Tours. Après des études
de Médecine à Nancy et un internat à Besançon, durant lequel il se spécialise en Hépato-
Gastroentérologie, il intègre en 1989 le service de pharmacologie de Pierre Bechtel. Un séjour
de 18 mois à Stockholm, dans le service de Folke Sjöqvist, lui permettra de débuter des travaux
de recherche dans le domaine de la modélisation pharmacocinétique et pharmacocinétique-
pharmacodynamique (PK-PD), sous la direction de Gunnar Alván, et il obtiendra un Ph.D de
l’Institut Karolinska en 1993. A son arrivée à Tours en 1997, G. Paintaud intègre une équipe de
recherche qui deviendra en 2004 l’EA 3853 “Immuno-Pharmaco-Génétique des Anticorps
thérapeutiques” (IPGA), dirigée par Hervé Watier. Il est actuellement responsable de l’équipe 7
« Pharmacologie des anticorps thérapeutiques et investigations cliniques » de l’UMR CNRS
6239 « Génétique, Immunothérapie, Chimie et Cancer » dirigée par Yves Bigot. Dans ce cadre,
il étudie la variabilité interindividuelle de l’effet des anticorps thérapeutiques grâce à la
modélisation pharmacocinétique et PK-PD. Parallèlement, il met en place un centre pilote de
suivi thérapeutique des anticorps monoclonaux s’appuyant notamment sur leur dosage sérique et
leur analyse pharmacocinétique.

Groupe
de Méta
bolis
m
e et de Ph
arma
cocinétique
– PK/P
D of macromole
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es – 10
-11 Janu
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8
, Paris



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11h00-11h30 LC/MS quantification of mAbs
Olivier HEUDI (Novartis, Basel )
Olivier Heudi obtained his diploma of advanced studies in physiology at Pasteur Institute,
France (1995) and his Ph.D. in life Sciences from the University of Angers (1999). He
previously gained experience in the analytical field at GSK stevenage (UK) where he has
implemented LC-ICPMS and LC-MS/MS for the quantification of peptide in biological fluids
and at Nestlé Lausanne (CH) where he developed LC-MS/MS methods for the identification
and quantification of vitamins and natural ingredients in food products. Then he joined Novartis
Institute for Tropical Diseases (Singapore) where he was in charge of the bioanalytical
activities. In December 2006, Olivier was appointed as Lab Head at Novartis Basel in the
DMPK group where he is now working on LC-MS/MS method development and
implementation for the quantification of monoclonal antibodies, oligonucleotides and SiRNA in
biological matrixes. Olivier is active as reviewer in several analytical papers and has great
interest in new technologies with special attention on large molecules.

11h30-12h15 Overview of the macromolecule pharmacokinetics
Joe BALTHASAR (Buffalo University)
Dr. Balthasar is Associate Professor of Pharmaceutical Sciences at the State University of
New York at Buffalo. Dr. Balthasar received a B.S. in Pharmacy (1991) and a Ph.D. in
Pharmaceutics (1996) from the University at Buffalo. Prior to joining the faculty of the
University as an Assistant Professor in 1999, Dr. Balthasar served as a Clinical Assistant
Professor of Pharmaceutics at the University at Buffalo from 1996-1997 and, from 1997-
1999, as an Assistant Professor of the Department of Pharmaceutics and Pharmaceutical
Chemistry at the University of Utah. Dr. Balthasar’s research, which is funded by the
National Institutes of Health, utilizes pharmacokinetic and pharmacodynamic analyses to
guide the development of new therapies. Current research focuses on the development of
drug targeting strategies to improve the selectivity of cancer chemotherapy and on the
development of new immunotherapies for the treatment of humoral autoimmune diseases.
2007 - Director, Center for Protein Therapeutics, University at Buffalo, State University of New
York
Groupe
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– PK/P
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Session II - Disposition and metabolism of macromolecules
14h15-14h45 Immunogenicity for biologics
Annette ZAAR (Novartis, Basel )
University Freiburg, Germany
∙ PhD in Microbiology
Roche-Vitamins, Basel, Switzerland:
∙ Postdoc 1
Novartis Pharma, Basel, Switzerland:
∙ Postdoc 2
∙ Lab Head Marker and Assay Development, Biomarker Development
∙ Group Head Immunogenicity, Biomarker Development

14h45-15h15 Dispositional features of pegylated antibodies
Ted PARTON (UCB Celltech, Slough)
With a background in analytical chemistry, I joined the Upjohn Company in 1985, in
bioanalysis and drug metabolism, both in development and in discovery support. I joined
Celltech in 1993 to build a DMPK team in drug discovery, and subsequently became part of the
UCB Research DMPK team. My current interests are in the use of modelling and simulation
techniques to improve our understanding of PBPK and pharmacometrics.

15h15-15h45 Pragmatic approaches to target-mediated disposition of monoclonal antibodies
Hans Peter GRIMM (Hoffman la Roche, Basel)
Hans Peter GRIMM is trained physicist with a PhD in applied mathematics (dynamical systems,
pattern formation) which he both obtained at ETH in Lausanne, Switzerland. After a first post-
doc at Northwestern University (Evanston, IL, USA) he returned to Lausanne to build
mathematical models for cell motility in close collaboration with cell biologists. He then joined
the small start-up company GiMS mbH in Basel (Switzerland) specialized in modeling and
simulation in a variety of fields ranging from fluid dynamics to PK/PD, most of them applied to
projects for the pharmaceutical industry. Since 2005 he works for F. Hoffman la Roche Ltd. in
Basel where he is member of the preclinical modeling and simulation group and is now
specialized in PK/PD for CNS projects and protein PK.

Groupe
de Méta
bolis
m
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cocinétique
– PK/P
D of macromole
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16h15-16h45 Target-mediated disposition of monoclonal antibodies: Implications for Mab development
Donald MAGER (Buffalo University)
Dr. Mager is an Assistant Professor of Pharmaceutical Sciences at the University at Buffalo,
State University of New York (UB). He received his BS degree in Pharmacy from UB in 1991,
followed by the PharmD (2000) and PhD (2002) degrees. He then completed two years of post-
doctoral training as an IRTA Fellow at the National Institute on Aging of the NIH, where he
continues to serve as an IPA investigator. He has been a fellow of the American Foundation for
Pharmaceutical Education (2000-2002), was recognized in the Eli Lilly Graduate Symposium at
the AAPS annual meeting in Toronto (2002), and was given the Buffalo Pharmaceutics Scholar
Award in 2001. He has also received the University at Buffalo Young Investigator Award in
2006 and the New Investigator Award in Pharmacokinetics, Pharmacodynamics, and Drug
Metabolism from AAPS in 2007. Dr. Mager served as a Visiting Professor at the Université
René Descartes – Paris V in January 2007. He is a current member of AAPS, AAAS, ASCPT,
ASPET, AACP, and ACCP and serves on the Editorial Advisory Board of Biochemical
Pharmacology. His research invokes PK/PD systems analysis to characterize drug effects, with
particular interest in anti-platelet, anti-cancer, and immunomodulatory pharmacotherapy.

16h45-17h15 Evaluation of FcRn as a determinant of IgG absorption, distribution and elimination
Joe BALTHASAR (Buffalo University)

17h15-17h45 Oligonucleotides metabolism
Camille PERRET (Novartis, Basel )
Dr Camille Perret is currently working as laboratory head at Novartis in the Drug Metabolism
group in Development (DMPK). Since March 2005, her work mainly focused on in vitro and in
vivo metabolism studies of small molecule drugs during the development phase. Recently, she
partially transitioned to the field of oligonucleotides where she is performing in vitro metabolic
stability studies as well as implementing new analytical methods.
After receiving her PhD, she worked for 3 years as an Application Chemist at Waters and then
Spectronex (ThermoFinnigan Switzerland). From both her studies and work experience, she has
acquired extensive expertise in mass spectrometry, especially LC-MS.
Camille Perret received her Chemist Diploma in 1998 and PhD in 2002 from the University of
Neuchâtel, Switzerland (Prof R. Tabacchi).

~~~~~

Groupe
de Méta
bolis
m
e et de Ph
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– PK/P
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-11 Janu
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FRIDAY 11 JANUARY 2008

09h15-9h45 Development of biologics versus small molecules
Wolfgang RICHTER (Hoffman la Roche, Basel)
Wolfgang F. Richter, Ph.D., is DMPK project leader at F. Hoffmann-La Roche Ltd. in Basel,
Switzerland. He did his undergraduate studies in pharmacy at the University of Marburg,
Germany, from where he also received his Ph.D. degree in pharmaceutical chemistry. Thereafter
he was postdoctoral fellow at the Department of Pharmaceutical Chemistry of the University of
Kansas, Lawrence, USA. In 1989 he joined F. Hoffmann-La Roche Ltd. in Basel, where he held
various positions within the drug metabolism department since then. He has been involved in
the development of numerous compounds, both small molecules and therapeutic proteins. His
major research interests are in the areas of pharmacokinetics of therapeutic proteins, tissue
distribution of drugs and whole-body autoradiography.

9h45-10h15 Macromolecules: specific requirements for regulatory agencies
Pr Jean-Hugues TROUVIN
Professor Jean-Hugues Trouvin graduated in Pharmacy and received his Doctorate in
Pharmacology from the University of Paris. Professor at the Faculty of Pharmacy, University of
Paris he has been working as assessor and expert for the French Health authorities since 1986,
in charge of reviewing the biological and pharmaceutical quality aspects of biological and
biotechnology-derived medicinal products. In France, he was chairman of the French
biotechnology working party from 1989 to 1993. He was Director of the Directorate for
Evaluation of Medicinal products and Biologics at the French medicine agency (AFSSAPS)
from 2001 to July 2007. He is currently professor at the Faculty of Pharmacy, Université Paris
Descartes, and head of the Pharmaceutical establishment set up at the Assistance-Publique-
Hôpitaux de Paris (AP-HP).
At the European level, he has been working in the biotechnology/pharmacy working party as
French representative, since 1986. He was appointed as French CPMP member from 1995 to
2004. In January 2001 he has been elected as Chairman of the Biologics Working Party (BWP)
and reelected in 2005. With the BWP he contributed to the drafting and implementation of
many concept papers and guidelines on the Quality and pharmaceutical/biological development
of biological products (including gene and cell therapy). He was one of the rapporteurs of the
guidelines and regulatory approach for comparability issues and biosimilar medicinal products.
Since 1992, he has been involved in the ICH (International Conference on Harmonisation)
process for the Biotechnology topics including the CTD documentation, for biotechnology
aspects.
Groupe
de Méta
bolis
m
e et de Ph
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cocinétique
– PK/P
D of macromole
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-11 Janu
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, Paris



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Session III – PK/PD of macromolecules
10h45-11h15 Physiologically-based modeling of monoclonal antibody disposition
Joe BALTHASAR (Buffalo University)

11h15-11h45 Saturable elimination versus TMDD
Elisabeth ROUITS (UCB SA, Belgium)
Elisabeth Rouits is working since November 2005 as a clinical pharmacokinetics modeling &
simulation specialist at UCB Pharma S.A. (Belgium) where she is implicated in epilepsy and
oncology projects.
During her PhD and the two following years, she has taken part in clinical studies in oncology
in the anti-cancerous centers of Angers (under the direction of Pr E. Gamelin) and Toulouse
(under the direction of Pr E. Chatelut). There, she has developed non linear population PK
models with NONMEM for oncology drugs such as irinotecan. She has also worked in the
bioanalysis (HPLC) and the pharmacogenomic fields to routinely detect biomarkers which are
critical in the individualization of anti-cancer treatments.
Elisabeth Rouits received her PharmD in 1998 and PhD in 2003 from the University of Angers,
France (Prof. E. Gamelin).

11h45-12h15 A PK/PD example on mAb
Phil LOWE (Novartis, Basel)
Dr Lowe first studied the physiology and biochemistry of bile secretion at Birmingham UK &
San Diego Universities. The work focussed on how bile acids, phospholipids, cholesterol &
various hepatocyte plasma membrane and serum proteins enter bile via transcytosis & tight
junctional permeation. He joined Ciba-Geigy’s Advanced Drug Delivery Research Unit in 1988
to study protein uptake from the intestine. Since then, he has worked on protein formulation,
research & clinical pharmacokinetics & pharmacodynamics, before moving full time into
modelling and simulation. After a spell as head of the Preclinical Safety M&S group, including
working on physiology based pharmacokinetic models & probabilistic risk assessments, he is
now enjoying life working on & overseeing projects for new biopharmaceutics. This involves
developing greater understanding of how proteins distribute throughout the body, quantifying,
through models, their subsequent effects on (patho)physiology & clinical endpoints.

14h15-14h45 PK/PD analysis of VEGF Trap, a potent angiogenesis inhibitor
Paul CHEVALIER (Sanofi-Aventis, Vitry sur Seine)
Paul Chevalier is currently senior clinical pharmacokineticist in Sanofi-Aventis. He has a
background in analytical chemistry, as immuno-analyst.
Groupe
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m
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– PK/P
D of macromole
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-11 Janu
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14h45-15h15 Exposure-response modeling of biologicals
Brigitte LACROIX (UCB SA, Belgium)
Brigitte Lacroix has been working for almost 2 years at UCB Pharma (Belgium) in the Clinical
Pharmacokinetics Modeling and Simulation group. During this period, she mainly performed
population PK and PK/PD analyses. Since about 1 year, she also started a PhD program, in
collaboration with Uppsala University (Sweden), under the supervision of Lena Friberg,
associate professor of Pharmacometrics.
After receiving her Pharmacy degree and Master degree in Pharmacokinetics from University
Paris XI in 2004, she worked for 1.5 years as a clinical pharmacokineticist for Servier, in Paris.
During this period, she acquired experience in population PK modeling.

15h15-15h45 Exposure-effect population model of inolimomab, a monoclonal antibody
Pascal GIRARD (Faculté de Médecine Lyon Sud)
Pascal Girard, PhD, is currently INSERM researcher working at Lyon University in a clinical
oncology team. His research interest is population pharmacokinetic-pharmacodynamic (PK-PD)
modelling and non compliance to oral treatment. He has successively been working as
researcher at Lyon Clinical Pharmacology Unit with Prof. Boissel, then visiting assistant
Professor at UCSF with Prof. Lewis Sheiner and as senior scientist at Pharsight Corp, applying
PK-PD to various domains as cardiology, endocrinology and now oncology. He is one of the
historical founding members of the Population Approach Group in Europe (PAGE).



Groupe
de Méta
bolis
m
e et de Ph
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cocinétique
– PK/P
D of macromole
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-11 Janu
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