Pharmacelsus GmbH
Science Park 2
66123 Saarbrücken
Germany
Research & Development
Pharmacelsus focuses its R&D activities on innovative methods that are supposed to be commercialized in order to make them available to the Pharmacelsus clients. During the last years Pharmacelsus has been able to advance and expand its portfolio in a creative and innovative way.
Thus R&D at Pharmacelsus is considered as basis of future innovation and will provide the company with sustainability.
The objective of the project is to establish stable cell lines that reliably reflect human hepatic properties by the development of models derived from human embryonic stem cells. The aim is to deliver reliable in vitro models that could be used by the pharmaceutical industry to replace experimental animals in investigations on human drug metabolism, uptake and efflux properties of compounds in the drug discovery and development processes. In the pharmaceutical industry reliable in vitro cell models would replace current techniques and animal experimentation in the selection and optimisation of lead compounds and in documentation of a selected drug candidate before it enters clinical phases.
The means to accomplish the objective are in addition to new stable human embryonic stem (hES) cell derived hepatocytes, (1) 3D-hepatic cell culture and co-culture methods, (2) micro-cultivation monitoring systems for in vitro screening, (3) genomic and metabolomic characterization, and (4) a multi-micro-bioreactor platform for high-throughput screening of drug candidates. Comparative studies of hepatocyte derived from hES cells with established in vitro models will be carried out in order to validate the new models and methods.
The outcome of the project is new efficient in vitro pre-validation models which will significantly reduce the use of animal experimentation for prediction of human drug metabolism and disposition by 60-80%. In addition, the models will also increase safety and quality of compounds chosen as candidates in the different stages of the drug discovery and development process. Furthermore, it will strengthen the possibility for SMEs to market new potential products in the areas of cell assays and in vitro compound screening.
The clinical expertise in the project is manifested by the involvement of two renowned European university hospitals, one SME founded by another well-known European university hospital and the partnership with one of the leading European pharmaceutical companies. Also the coordinator has managerial background from an international pharmaceutical company as well as the project leader from one of the SME partners. Three partners represent a solid reputed bioengineering background. Other important partners are one SME focused on development of standardised assay conditions for drug testing, and the European Centre for Validation of Alternative Methods (ECVAM). Links to animal care institutes are also added to the project.
The objective of the proposal is to establish stable cell lines that reliably reflect human cardiomyocyte properties by the development of models derived from human embryonic stem cells. The aim is to deliver reliable in vitro models that could be used by the pharmaceutical industry to replace experimental animals in (2) investigations on pharmacological toxicity and safety of compounds in the drug discovery and development processes, and (2) the testing of toxic effects of chemicals according to the new system of the Community on the Registration, Evaluation and Authorisation of Chemicals (REACH). In the pharmaceutical industry reliable in vitro cell models would contribute to replace current techniques with animal experimentation in the selection and optimisation of lead compounds and in documentation of a selected drug candidate before it enters clinical phases. In the toxicity testing of chemical substances replacement of animal testing methods can be attained as well.
The means to accomplish the objective are in addition to new stable human embryonic stem (hES) cell derived cardiomyocytes, (1) state of the art methods for electrophysiological cardiac cell monitoring, (2) optical micro-sensor monitoring in micro-cultivation systems for in vitro screening, (3) a multi-micro-bioreactor platform for high-throughput screening of drugs and chemicals. Comparative studies of cardiomyocytes derived from hES cells with established in vitro models will be carried out in order to validate the new models and methods.
The outcome of the project is new efficient in vitro pre-validation models which will significantly reduce the use of animal experimentation for cardiotoxicity testing by 60-80%. Furthermore, it will strengthen the possibility for the participating SMEs to market new potential products in the areas of in vitro assay methods and in vitro compound screening. The SMEs part in this proposal is substantial and the share of the requested budget for the SMEs is 59%.
The clinical expertise in the project is represented by a leading European university hospital and a well-known European pharmaceutical company. The four established European SME companies, very experienced in life science and micro-sensor technologies, are the key providers of state of the art technology. Also the coordinator has managerial background from an international pharmaceutical company as well as the project leader from one of the SME partners. Two of the partners represent a solid reputed bioengineering background. Another important partner for the proposed project is the European Centre for Validation of Alternative Methods (ECVAM). Links to animal care institutes are also added to the project.
- German Federal Ministry for Education and Research (BMBF)
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3D-In vitro Model for Hepatic Drug Toxicity (HepaTox)
A major hurdle in preclinical drug testing is the existing lack in suitable in vitro models that allow the prediction of potentially toxic effects in humans. The project is aimed at providing a novel in vitro model to analyze human-specific hepatotoxic effects of drugs and of hepatic-generated intermediates in human liver cells.
Two models will be tested: a Petri-Dish 2D culture model and a 3D-multi- compartment bioreactor technology that allows the maintenance of human liver cells in a perfused, tightly controlled environment with high mass exchange and decentralized oxygenation, thereby creating physiological conditions for the cells similar to the situation within the liver in vivo. Readout parameters for assessing potential hepatotoxic effects in the models will be established based on a multi-level concept that includes parameters for basal toxicity, for general and specific functionality, morphological criteria and complex metabolic pathways. The response of the cultures to drug exposition in 3D bioreactor cultures will be modelled based on systems biotechnological analysis.
Data will be compared for validation to in vitro data from 2D culture models and to in vivo data available within the consortium and/or in public databases. In case of successful model development, commercial exploitation of the new methodology will be brought forwards by the industry partners.
- Lead Synthesis and Optimisation
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