MATTAWAN, MI September 14, 2005:

In May of 2005 the International Conference on Harmonization (ICH) recommended for full adoption and implementation the long discussed and debated S7B guidelines for the preclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals. These guidelines will be accepted and put into practice by the tripartite of regulatory bodies of the USA, Europe and Japan. Europe will be the first to require these assessments be done as GLP components of an IND submission in November 2005, followed soon by the regulatory bodies of the United States and Japan.

The new guidelines state that the effects of new drug candidates on prolongation of the QT interval be assessed using an “integrated risk assessment…which should be scientifically based and individualized for each test substance.” This comprehensive approach to evaluate the potential clinical problem of QT interval prolongation should include in vitro and in vivo studies (ICH S7A) which precede or follow up on clinical evaluations. The in vitro assays suggested place particular emphasis on the hERG related K+ channel current inhibition assay and potential follow up tests such as the cardiac action potential duration (APD), Purkinje fiber assay, and the Langendorff isolated heart assay. Section 1.2 of the new guidelines state, “Prolongation of the action potential can result from… [Effects on ion channels other than just hERG (Ikr)]. Using tools such as the APD Purkinje fiber, isolated cardiac myocyte or the Langendorff isolated heart assay to evaluate possible drug effects on other ion channels and aspects of cardiac physiology can yield important and timely information.

MPI CardIon Laboratories is a leading electrophysiology company whose strength is utilizing the key tools necessary to offer a true “integrated risk assessment” for the cardiac safety evaluation of new drugs. The experienced staff offers GLP whole cell patch clamp hERG assays as well as GLP Purkinje fiber assays to assess effects on cardiac action potential duration and morphology. Recent additions to the MPI CardIon armamentarium to evaluate potential clinical cardiac safety issues of new drugs include; non-GLP high throughput via true voltage clamp screening with the “Ion Works®” platform and the Langendorff isolated heart assay. The Ion Works HTS platform allows for rapid functional evaluation of hERG related currents using multiple compounds and concentrations in a single assay. The talented staff at MPI CardIon can also offer customized protocols to functionally evaluate multiple ion channels (Ca++, Na++, Cl- and other K+) when the need arises.

Dr. James Laveglia, Executive Vice President for MPI Research commented, ”MPI Research and MPI CardIon Laboratories are proud to be the only leading North American CRO to offer the full regimen of preclinical assays to address the regulatory requirements concerning QT interval prolongation. No other CRO offers all the key studies soon to be required to effectively evaluate cardiac safety for an IND submission; i.e. hERG, APD, and in vivo telemetry studies in a fully GLP compliant environment. Combine this with our new Ion Works® high throughput screening platform, and we are uniquely positioned to address QT interval prolongation from early drug discovery stages to the IND submission of a new drug candidate for our Sponsors. We have led the industry for many years addressing the in vivo ICH S7A guidelines and are pleased to offer critical solutions to meet the new cardiac in vitro safety specific S7B guidelines.”

For details concerning MPI CardIon services please visit our page on www.mpiresearch.com. To review the ICH S7B guidelines in their entirety, please visit www.ich.org.

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