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Safety is paramount

Regulatory authorities require pharmaceutical companies to carry out clinical trials as well as preclinical, safety pharmacology tests when they are applying for marketing authorisations. Of key importance are electrophysiological tests on ion channels. The new drug screening and safety pharmacology laboratory at NMI Technologie Transfer GmbH (NMI TT GmbH) in Reutlingen, with its standardised and special test systems complies fully with these requirements.

“Safety pharmacology is a hurdle all drugs have to take before marketing authorisation can be applied for,” said Professor Dr. Hugo Hämmerle speaking at the official opening of the new laboratory. Hämmerle is director of the NMI Natural and Medical Sciences Institute in Reutlingen and managing director of the NMI’s subsidiary NMI TT GmbH. The new rooms have been equipped with the devices and know-how of the former Nycomed GmbH laboratory in Constance and of NMI TT GmbH. The laboratory offers extended safety pharmacology and drug screening services to clients from the pharmaceutical and biotechnology industries.

On behalf of Nycomed, Guido Hanauer, Director Global Pharmacology, outlined the effects of new developments on safety pharmacology and the significance for the company’s own products. The most important abbreviations are: ICH S 7A (ICH: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) and ICH S 7B, which specify the requirements for safety systems. ICH S 7A specifies the fundamentals and ICH S 7B refers to the cardiovascular system and provides a strategy for the implementation of guidelines.

hERG potassium channel tests are mandatory

The workshop on safety pharmacology and drug screening attracted a large number of people.
The guidelines of the American and European regulatory authorities, FDA and EMEA, require drugs to be tested for their potential to block potassium channels in the heart. The potassium channels are encoded by the human-ether-a-go-go-related-gene (hERG) and play a very important role in the repolarisation of the heart. Many substances have been shown to have adverse effects on cardiac rhythm, which is often mediated by the blockage of the hERG-encoded potassium channels.

The patch clamp technique is the gold standard of such measurements. In the electrocardiogram, life-threatening cardiac disorders are often associated with the prolongation of the QT interval. In view of the increasing financial risk associated with drug development, Hanauer asked the workshop audience “to start patch clamp investigations as early as possible during the drug discovery process”.

The new laboratory can conduct many different tests

The new laboratory is well equipped for such tests. “We offer established safety pharmacology and drug screening tests, and we are unique in the broad range of services we offer,” said Elke Guenther, head of Pharma Services at the NMI TT GmbH and head of Cell Biology at the NMI. The laboratory offers numerous established assays for the measurement of voltage-controlled and ligand-controlled ion channels.

Portrait of professor doctor Elke Guenther
Professor Dr. Elke Guenther takes the workshop participants on a tour around the new laboratory © NMI
The tests can also be adapted to client requirements. The new laboratory covers the entire range of assays, starting from single cell assays to cell cultures and even tissues and organs. The assays measure ion channels and action potential. In vitro test systems imitating in vivo conditions are used to measure ion channel interactions and signal transmission. The microelectrode array (MEA) cardiosensor, for example, is a quick and efficient drug screening system that complies with the requirements of drug studies. Based on the MEA, the company Multi Channel Systems GmbH developed an automated version, the QT-Screen. Another automated solution is Multi Channel System’s Robocyte for the testing of individual cells and a patch clamp automate. These systems allow the repeated readout of a single parameter as well as the readout of several parameters. “We can therefore respond to the clients’ need for more rapid and comprehensive test systems in the drug discovery process,” summarised Guenther.

New drug targets thanks to high throughput and automation

Preclinical research depends on the knowledge of cellular processes. Dr. Michael Pawlak, head of Protein Profiling/Assay Development at the NMI, uses high-throughput methods to identify cellular proteins and investigate their functions and interactions inside the cell. Pawlak offers a broad spectrum of tests for the pharmaceutical and biotechnology industries, which have become 10 times quicker than Western blots and which contain 50 times more information and consume 50 times less material.

Drug discovery would be impossible without automation. Hansjürgen Volkmer, head of Molecular Biology at the NMI, develops automated systems for the validation of targets in the drug discovery process. Protein microarrays are used to identify genes that are specifically expressed in certain diseases and hence are perfect targets for new drugs.

kp - 30th June 2008
© BIOPRO Baden-Württemberg GmbH
NMI Technologie Transfer GmbH was established in 2002 as a fully owned subsidiary of the NMI. The establishment of NMI TT GmbH became necessary due to a high demand for services that the NMI research institute was no longer able to meet. NMI TT GmbH offers services and products at standard market prices. NMI TT GmbH is divided into the following areas: contract peptide synthesis, coating, bio- and drug analytics, protein profiling, preclinical safety pharmacology, drug screening and consulting services. The new drug screening and safety pharmacology laboratory started operations at the beginning of 2008 and is headed up by Professor Dr. Elke Guenther. The following test systems are on offer: (1) manual and automated patch clamp analysis of heterologously expressed cell lines and primary cells, (2) automated QT screen measurements on cardiomyocytes, (4) Langendorff heart preparations, (5) papillary muscle preparations and (6) isolated organs for receptor interactions. There are plans to establish a certified GLP laboratory for hERG investigations.

Further information :

NMI Technologie Transfer GmbH

Markwiesenstraße 55
72770 Reutlingen
Prof. Dr. Hugo Hämmerle
Managing Director
Tel.: +49 (0)7121 51530-45
Fax: +49 (0)7121 51530-16
E-mail: haemmerle@nmi.de


Prof. Dr. Elke Guenther

Head of Pharma Services

Tel.: +49 (0)7121 51530-54
Fax: +49 (0)7121 51530-16

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/safety-is-paramount