Periodic Reporting for period 3 - ID-EPTRI (Infradev - European Paediatric Translational Research Infrastructure) Reporting period: 2020-01-01 to 2020-04-30 Summary of the context and overall objectives of the project Evidence exists that children receive new and innovative therapies with huge delays with respect to other populations, or in many cases are excluded from any improved treatments. Moreover, the use of existing therapies that have not been studied in children results in an off-label use for approximately 30% to 80% of all cases, depending on the children’s age and the therapeutic category of the drug. This situation exposes children to serious risks and also discriminates this vulnerable population, thus representing a social and ethical issue.Children and young patients cannot be compared with adults as they are growing up and their metabolism is different. EPTRI is aimed to facilitate basic, preclinical and translational research in paediatric medicines discovery and development, providing access to key technologies (from biological, technological and data science advancements), standardised models and analytical tools, implemented for or adapted to the paediatric setting. The ID-EPTRI project involved 29 partners from 21 EU and non-EU countries, including established RIs, non-profit research organisations, top-level universities, scientific and clinical centers of excellence.EPTRI key objectives are:o to extend the knowledge of the normal and pathological human development process in order to move from the current approach based on adult drugs that are administered off label to children to a new approach characterised by medicines studied and marketed for children o to involve multiple experts and competences to create multidisciplinary scientific and technology groups working to integrate basic science with key technologies (from biological, technological and data science advancements) to drive innovative medicines and health products discovery and developmento to enhance clinical research and paediatric medicines availability contributing to creating a unique paediatric research frameworko to accelerate the paediatric drug development processes from medicines discovery, biomarkers identification and preclinical research to developmental pharmacology, age tailored formulations and medical devices. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far During the ID-EPTRI project, the EPTRI concept has been designed and tested and has allowed to create the base for research excellence that is the added value of the EPTRI proposal. In particular, a large community has been identified during the Context analysis phase through several surveys, willing to cooperate in order to standardise models and approaches and to produce validated knowledge useful for drug development. The EPTRI scientific community survey has allowed to identify a total of 259 Institutions, often grouping more than one research group, distributed across 29 countries in the European area and encompassing a total of 330 research units (RUs), which have provided description of scientific competences, human resources, tools, facilities, services they are available to provide in the future European Paediatric Translational Research Infrastructure. The users’ survey, with 337 responders, allowed to identify the user community, that is widely distributed in the European area but also includes several extra-EU users. The survey showed that a total of 2207 paediatric research projects were planned for the next 3 years and identified 2780 paediatric projects performed over the past 5 years. Responders have been asked the number of times they have been blocked or delayed during the conduction of their projects. The following analytical tools and models have been identified as those with the highest incidence of blocks: PBPK Modelling and Simulation; Target identification; Preformulation; In vitro/in vivo pre-clinical test of the medical devices; Placental platforms.A survey conducted within the existing Biomedical RIs helped to identify areas for collaboration and differentiate from the general description of standard analytical methods and the specific requirements. Some analytical approach resulted to be totally unique to EPTRI as the use of placenta to assess drug sensitivity and distribution, organoid for foetal to adult maturation and juvenile animal models. EPTRI has been designed as a Hub and Spoke organisation with a Central Hub and several Spokes, represented by the Thematic Research Platforms (TRPs) and the national nodes in each member country participating of EPTRI.The following four TRPs have been created grouping RUs in each specific scientific domain and able to act as providers of cutting-edge services that are unique for paediatric research on medicines setting.• PAEDIATRIC MEDICINES DISCOVERY, dedicated to basic research and preclinical studies aimed to identify and validate druggable molecular targets specific to paediatric disease, as well as discover new drugs, using models reproducing specific paediatric ontogenetic stages. • PAEDIATRIC BIOMARKERS AND BIOSAMPLES, focused on the identification, characterisation and validation of paediatric biomarkers and on the evaluation of the paediatric variability with respect to adult biomarkers. • DEVELOPMENTAL PHARMACOLOGY, consisting on the identification and application of ad hoc innovative methods to study paediatric pharmacological variability due to ontogeny. • PAEDIATRIC MEDICINES FORMULATIONS, mainly devoted to perform preformulation and formulation studies for preterm neonates, infants, toddlers, children and adolescents.The the organisation of National Nodes in Italy, Belgium, Germany, The Netherlands, Spain, Hungary, Czech Republic, Cyprus, Ukraine and Israel has been started. The need to establish a dedicated RI for paediatric research was recognized as a priority by the 17 EU and non-EU Ministries (Albania, Cyprus, Finland, Greece, Hungary, Ireland, Israel, Italy, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Russia, UK and Ukraine) and several Foundations, Patients Associations, Hospitals, Research Institutions and Universities providing their expression of political support letters. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) EPTRI will bring a positive impact on the scientific community, by integrating the different research units within the new establishing RI, so to increase the scientific relevance of the paediatric research at international level.EPTRI will bring together scientists, researchers, regulators, and industry to support smarter paediatric medicines development in an atmosphere of innovation and collaboration for the benefit of the patients, the life science, the economy and ultimately the society. It will also benefit children’s and future generations’ health as it will establish the framework to speed-up the drug development process in paediatrics including the top-level research innovations. EPTRI will have the following expected impacts: improve the health of the paediatric population and reduce the serious delay to provide children with new and innovative therapies; change the paradigm to develop paediatric medicines focusing on all the innovative methodologies in life science and digital science that are continuously evolving, by applying them in age-tailored contexts and correctly considering the paediatric specificities; enhancing and widely implementing the Key Enabling Technologies (KET) for drug development that have been poorly used in paediatrics so far EPTRI logo
