Implementation challenges for designing Integrated In Vitro Testing Strategies (ITS) aiming at reducing and replacing animal experimentation

At the IVTIP (In Vitro Testing Industrial Platform) meeting of November 26th 2009 entitled ‘Toxicology in the 21st century (‘21C’) – working our way towards a visionary reality’ all delegates endorsed the emerging concept of the ‘21C’ vision as the way forward to enable a thorough, reliable and systematic approach to future toxicity testing without the use of animals. One of the emerging concepts focused on integrating a defined number of tests modelling in vivo-relevant and well-characterised toxicity pathways representing mechanistic endpoints. At this meeting the importance of Integrated Testing Strategies (ITS) as tools towards reduction and eventually replacement of the animals currently used for hazard identification and risk assessment was recognised.A follow-up IVTIP Spring 2010 meeting entitled ‘Integrated In Vitro Testing Strategies (ITS) – Implementation Challenges’ was organised to address pending questions about ITS. This report is not a review of the ITS literature, but a summary of the discussions triggered by presented examples on how to develop and implement ITS. Contrasts between pharmaceutical and chemical industry, as well as a list of general but practical aspects to be considered while developing an ITS emerged from the discussions. In addition, current recommendations on the validation of ITS were discussed.In conclusion, the outcome of this workshop improved the understanding of the participants of some important factors that may impact the design of an ITS in function of its purpose (e.g. screening, or early decision making versus regulatory), the context in which they need to be applied (e.g. ICH guidelines, REACH) and the status and quality of the available tools. A set of recommendations of best practices was established and the importance of the applicability of the individual tests as well as the testing strategy itself was highlighted.