Safety pharmacology in focus: new methods developed in the light of the ICH S7B guidance document.

'Safety' continues to be a growth area in 'Pharmacology'. This issue of Journal of Pharmacological and Toxicological Methods is the third to be focused on methods development in the safety pharmacology area. The unusual nature of safety pharmacology mandates that methods development be done with, not only scientific validation, but also, adherence to the mandates of legislation to the forefront. This focused issue draws on a broad range of global safety pharmacology experts, many of whom operate in the industrial milieu. They have reviewed and updated current models, validated modifications, and have also introduced novel methodology important to the conduct of non-clinical safety pharmacology studies. The contributors were all active participants at the 5th Annual Safety Pharmacology Society (SPS) meeting held in Mannheim, Germany September 25-28, 2005. The publications presented here describe in vitro and in vivo pharmacological methods development that has been informed by the S7A regulatory guidance document for pre-clinical safety testing of drugs. While S7A describes the 'core battery' of methods used to characterize the safety pharmacology profile of a compound, the most recent news in Safety Pharmacology involves ratification of the related S7B safety guidance document. Unlike the past, S7B heralds a new era for the pharmaceutical industry since it now sets out how to address safety concerns of a new chemical entity (NCE) in relation to adverse actions on ventricular repolarization, a topic that has vexed industry and regulatory authorities for many years. Unsurprisingly there are many papers in the present issue that address this specific aspect of safety pharmacology. These include results from the Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) initiative, in which non-clinical in vitro (hERG and Purkinje fiber) and in vivo (QT dog study) assays were found to be useful in the determination of drug-induced QT prolongation risk, and thus provide better characterization of a biomarker for the potential risk in humans for development of the torsades de pointes syndrome. However, safety methods development does not begin and end with ventricular repolarization. This focused issue also describes the re-evaluation and validation of a primate CNS model for evaluating orthostatic hypotension, and outlines a simple and rapid rodent object recognition task model that can be used to assess the amnesic potential of an NCE. Reviews of respiratory safety studies as well as both in vitro and in vivo aspects of cardiovascular function are also described. There are also papers that describe the pharmacology of vehicles and solvents used to solubilize study drugs and the applicability of voltage-sensitive dyes to optically record cardiac action potentials from single myocytes. Thus, this issue of the Journal of Pharmacological and Toxicological Methods remains a primary resource for industrial and academic pharmacologists interested in better understanding non-clinical safety pharmacology methods.