Drug safety assessment is a knowledge-intensive process that demands advancement in data handling methods and tools for facilitating data sharing, mining, analysis and predictive modelling. This need is not restricted to any specific type of data and real advancement requires integrating information of different types and from different sources (e.g. publicly available biomedical knowledge, proprietary preclinical and clinical data, evidence from post-marketing studies) for addressing drug safety assessment from a holistic perspective. The eTRANSAFE project will address these needs by developing a powerful data integration infrastructure (Knowledge Hub) and a collection of computational tools (exploitation modules) for making optimal use of these data. The proposed system will be a flexible and expandable framework, built on previous experience and applying state-of-the-art methods and technologies for providing the most advanced solutions for data sharing, interoperability and exploitation. An experienced honest broker will guarantee the confidentiality of any proprietary data. The project will develop in silico tools for data mining, visualisation, and prediction of potential toxicity, with specific attention to the assessment of the preclinical to clinical predictivity and the discovery of safety biomarkers. The CDISC-SEND format will be supported, facilitating the preparation of regulatory-compliant documentation. This infrastructure will be underpinned by development of open standards and guidelines recognised by regulatory agencies and international organisations. The eTRANSAFE consortium brings together 13 organizations that mobilize an unprecedented capacity and resources, uniquely placed to leverage the experience of eTOX and other EU projects and initiatives. The project partners are six prestigious academic institutions, six highly skilled small-medium enterprises (SME) and one European infrastructure (ELIXIR), bringing in this way a perfect balance.

VICT3R, a public-private partnership running under the European Innovative Health Initiative, aims to significantly reduce the number of animals used in experimental studies performed during the nonclinical drug and chemical safety evaluation by replacing the animals of the concurrent controls groups (CCGs) with Virtual Control Groups (VCGs). These VCGs will be generated by means of state-of-the-art statistical or artificial intelligence (AI) approaches that optimally exploit the wealth of historical data from control animals accumulated over decades by pharmaceutical companies and other relevant industrial and academic sectors. The VCG concept was conceived and prototyped during the recently finished eTRANSAFE IMI2 project for its application in the nonclinical safety assessment of the pharmaceutical industry. A preliminary evaluation of the VCG concept carried out in the eTRANSAFE project demonstrated that it is generally feasible, yet scientifically and operationally challenging and must therefore be refined before its adoption for regulatory hazard and risk assessment. The main challenges consist of adequate data collection and curation, identification of key variables to achieve optimal matching between VCGs and CCGs, and validation of procedures including compliance with Good Laboratory Practice (GLP). These challenges will be systematically tackled in VICT3R for achieving the full development and regulatory acceptance of the VCG concept. VICT3R will collect, curate and analyse large data sets of control animals from different species to produce a large high-quality database. The database will be made available to VICT3R partners, regulators, and policy makers with the purpose to allow maturation of the VCG concept and to prove its validity, reproducibility and robustness. While VICT3R will be primarily focused on repeated dose toxicity studies, the extension of the VCG concept to other types of studies involving animals will also be tackled. VICT3R will promote that its database and software platform is maintained and expanded long term.

The vision of the RISK-HUNT3R consortium is to develop a reliable, efficient and cost-effective chemical safety assessment approach. It will be based entirely on non-animal methods and provide improved protection of the human population against systemic health effects caused by (chronic) chemical exposure. The major innovation provided by RISK-HUNT3R is a complete and truly human-centric risk assessment strategy. RISK-HUNT3R will establish, optimize and assemble all essential safety testing elements: exposure assessment, information on chemical distribution in the body, hazard characterization, adverse outcome prediction and determination of actual risk in defined scenarios. RISK-HUNT3R integrates cutting-edge in silico (computational) and in vitro (experimental testing) technologies. Human (disease) genetics and exposome data will ensure anchoring of test results to the human situation. The project will ensure regulatory relevance by testing the applicability of the critical test systems integrated in the next generation risk assessment strategy. The ambitious overall deliverable will be a comprehensive computational framework for the prediction of human adverse outcomes, and a set of stringently evaluated assays to feed the required data into this framework. RISK-HUNT3R will engage with all key stakeholders from different industry sectors and international regulatory agencies to critically evaluate and warrant genuine acceptance of the novel safety testing framework. This unique interaction of these key stakeholders working together on real-world case studies, will result in a ready-to-apply strategy to ensure societal protection against hazardous chemicals fully in concordance with the European Commission’s “Green Deal”. Importantly, the project will push commercial exploitation of the validated safety assessment approaches, thereby ensuring sustainability of the project outcomes and fortifying the innovation capacity of the industry sectors involved.