Both the FDA and EMEA subscribe to the ICH guidelines

The Food & Drug Administration (FDA), Health Canada, the Japanese Ministry of Health and Welfare (MoHW) and the European Agency for the Evaluation of Medicinal Products (EMEA) subscribed fully to the ICH guidelines as pertains to safety pharmacology studies.

Nonetheless, in all cases, the current interpretation of ICH S7A allows some flexibility; for instance, endpoints can be measured during toxicology studies through the standard functional observation battery; cardiovascular as well as respiratory studies can and should be combined in order to maximize the use of each experimental subject.


Current position of each agency
As far as the issue of cardiovascular toxicity is concerned, there appears to be a welcomed consensus in the positions of the regulatory agencies of the world; all agree that the combined use of in vivo experimentation as well as in vitro investigations yield results that are considered to be more sensitive, and predictive, than the exclusive use of one or the other of these approaches.

The current approach preferred, as far as preclinical testing goes, involves the combined and coordinated design and execution of both in vivo cardiovascular and hemodynamic (telemetered) monitoring and in vitro hERG current inhibition.

It is understood that the best experimental designs will benefit from the coordinated efforts of in vivo and in vitro pharmacologists, working together to generate data that can be interpreted in an integrated context, as opposed to separate study designs.