Inroads to Predict in Vivo Toxicology—An Introduction to the eTOX Project

Abstract

There is a widespread awareness that the wealth of preclinical toxicity data that the pharmaceutical industry has generated in recent decades is not exploited as efficiently as it could be. Enhanced data availability for compound comparison (“read-across”), or for data mining to build predictive tools, should lead to a more efficient drug development process and contribute to the reduction of animal use (3Rs principle). In order to achieve these goals, a consortium approach, grouping numbers of relevant partners, is required. The eTOX (“electronic toxicity”) consortium represents such a project and is a public-private partnership within the framework of the European Innovative Medicines Initiative (IMI). The project aims at the development of in silico prediction systems for organ and in vivo toxicity. The backbone of the project will be a database consisting of preclinical toxicity data for drug compounds or candidates extracted from previously unpublished, legacy reports from thirteen European and European operation-based pharmaceutical companies. The database will be enhanced by incorporation of publically available, high quality toxicology data. Seven academic institutes and five small-to-medium size enterprises (SMEs) contribute with their expertise in data gathering, database curation, data mining, chemoinformatics and predictive systems development. The outcome of the project will be a predictive system contributing to early potential hazard identification and risk assessment during the drug development process. The concept and strategy of the eTOX project is described here, together with current achievements and future deliverables.

Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments

“…In recent years, numerous initiatives have sought to improve the reliability, interpretability, generalizability, and connectivity of laboratory investigations of new drugs. These include the establishment of preclinical data repositories [20], minimum reporting checklists for biomedical investigations [21], biomedical data ontologies [22], and reporting standards for animal studies [15]. Our review drew upon another set of initiatives—guidelines for the design and conduct of preclinical studies—to identify key experimental operations believed to address threats to clinical generalizability.…”

The STEP (Safety and Toxicity of Excipients for Paediatrics) database. Part 1—A need assessment study

“…If data sharing is encouraged then all companies will have easier access to the information that will help them make the best decisions about product safety. In fact, the European Innovative Medicines Initiative (IMI), a public-private partnership of the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA), launched a call for a project to be funded to achieve this goal of data sharing and building of new in silico safety models (Briggs et al, 2012). The main objectives of this project are: to identify and implement ways for data sharing while safeguarding intellectual property; to build a harmonized toxicological database for the development of predictive models.…”

Improving R&D productivity of pharmaceutical companies through public–private partnership: experiences from the Innovative Medicines Initiative

“…If accepted, this could have a profound effect on future clinical trials in this area. The eTOX consortium is building a toxicology information database utilizing toxicology legacy reports from the participating pharmaceutical companies to develop better in silico tools for toxicological profile prediction of new chemical entities [12][13][14][15][16].…”