The launch of a novel drug to the market is preceded by clinical testing and validation both on animal in vitro and in vivo models. Animal models used in drug development have known methodological drawbacks leading to the failure of drugs. Further, animal tests are associated with ethical issues. Moreover, a strong bias in in-human testing still overlooks major population groups e.g. children, women, different ethical groups. It is estimated that 197,000 deaths per year in the EU are caused by Adverse Drug Reactions (ADRs) and the total cost to society of ADRs is €79 billion. The emerging Organ-on-Chip (OOC) field, an alternative to animal test, brings great potential for safe testing and validation: An OOC-systems consists of a 3D-microstructured channel network embedded on a small plastic device that simulates the mechanics and physiological response of an entire organ or organs. Project UNLOOC will develop, optimize, and validate a multitude of ECS-based tools to build OOC-models to replace animal and in-human testing. UNLOOC aims to combine three important characteristics for routine use of OOC models, i.e platforms that combine ECS-based technologies with established biological material, capitalize on AI, parallelized test set-ups allowing efficient high-throughput demands, and standardized procedures enabling reliable results. UNLOOC will develop ECS-based hardware and software tools and validate them in five Use Cases (UCs) performed in 10 European countries. The applications developed and validated will be used by academia and pharma industry to drive drug development, create cosmetics without animal test, personalized medicine and gain new insights into disease. Given the large OOC market, these solutions have great economic value, on average it would result in cost reduction of up to $169M and $706M per new drug reaching the market and will put Europe at the forefront of this booming research field (see impact section for details).