Complementary to direct contact initiation with regulatory agencies, a deep analysis of the regulatory challenges reported in publications, conferences and reports have been conducted. Identifying, mapping, and matching of open regulatory challenges / needs together with the rationalisation of testing strategies resulted in the extraction and categorization of regulatory requirements. These results are explained and presented in the White Paper and updated with collected feedback from the communities to be additionally published in a peer-reviewed journal. To identify methodological gaps, the regulatory information needs were mapped against available methods resulting in the identification of five areas where an insufficient number of methods are available to respond to these regulatory needs. Further work in REFINE on the methods identification and experimental work was performed based on these results. In line, the regulatory validation requirements were elaborated as a base for assay development and a pathfinder to standardisation. To harmonise this process, the SOP for in silico, biodistribution and biological response assays were refined and standardised. They are stored on the open access repository Zenodo for optimised accessibility. The biological response assays were tested in interlaboratory comparison to evaluate their liability, transferability, and stability. Results were published and peer-reviewed in the REFINE special issue in DDTR to be accessible for different stakeholders. Results of REFINE were discussed and shared with other communities in the three Knowledge Exchange Conference (KEC) which bridged different communities beside medical field such as Food, Cosmetic, Chemicals, Medicinal product, Medical Devices. All three KECs aimed for the dissemination of achieved knowledge in REFINE, in collected feedback from the invited communities on trans regulatory challenges and of knowledge sharing, e.g. by a knowledge sharing platform (Research Gate for REFINE), joint events (Joint session between REFINE and Gov4Nano) to overcome regulatory silos. Based on the compiled information with the goal to support developers in the identification of the best fitting testing strategy for their respective material, we developed a user-friendly web-based Decision Support System (DSS). The DSS is intended to inform on pre-clinical safety testing for the market approval of medicinal products and medical devices. The scope of the DSS was mainly focussed on physicochemical characterisation of NBMs with the elaboration of an additional immunotoxicology characterisation module.
