REFINE proposes a Regulatory Science Framework for the risk-benefit assessment of medical products and medical devices that are based on nanomedicines and biomaterials. The heart of our framework is the development of a product-specific Decision Support System that identifies the most efficient way to deliver the data required by regulation by the best-fitting methods. The decision tree will explicate the product’s specific regulatory challenges and the priorities of both missing data and missing methods to match these challenges. It will thus allow planning a cost-and time efficient strategy both for necessary measurements and for the advancement of methods. Our approach is aligned with the industrial R&D practice of stage gating. We will demonstrate the relevance of the framework for the most pressing regulatory challenges, which are: borderline products, nanosimilars, and products combining several functionalities. In order to do so, we will identify the regulatory challenges with Regulation Authorities from Europe and abroad, and design methods for tiered decision tree, guided by the latest scientific knowledge. We will study/predict physiological distribution of nanomedicines and biomaterials, as well as develop and validate new analytical or experimental methods and assays requested by the regulators. These latter development will be performed in a quality management system, ensuring the possible standardisation of our assays. REFINE will gather a wide community of stakeholders in regulation, industry, science, technology development, patients, and end-users, into a Consortium for the Advancement of Regulatory Science in Biomaterials and Nanomedicine.

Inflammatory bowel diseases (IBD) are the second most common immune-mediated disorders in Europe, affecting more particularly young people. The current therapies, including antibodies, show three main drawbacks: efficacy, tolerability and convenience. NEW DEAL solution will offer radical therapeutic progress for all IBD patients, thanks to the improved efficacy and increased safety of the specific JAK3 inhibition, which has been proven in clinics to be a target of great interest, the better tolerability of siRNA in term of immunogenicity and the good convenience with oral administration. To achieve this challenge, we will address three objectives: i) Specifically inhibit JAK 3 in a highly selective and safer manner by the mean of siRNA carefully designed and validated, ii) Deliver the siRNA therapeutic locally to the inflamed gut, by combining innovative nanostructured lipid carriers enabling their transport across the mucus, the intestinal barrier and the plasma membrane of the target cells, with polymeric capsules for protecting siRNA nanotherapeutics during their transit along the GI tract, thus allowing an oral administration, and iii) Promote the clinical translation and the future industrial transfer of this new clinical product, by addressing manufacturing, safety and efficacy evaluation at the late preclinical stage, to generate a Regulatory Submission Package and a Clinical Development Plan. The NEW DEAL project brings together clinical experts on IBD, leading scientists in nanomedicine, RNAi biology and immunology, innovative SMEs with a strong background in nanosafety, design of capsules and regulatory issues and an established pharma company with historic expertise on gastroenterology medicinal products. If successful, NEW DEAL will open new avenues for siRNA-based therapy in IBD with oral administration.

The main goal of PlasticsFatE (Plastics Fate and Effects in the Human Body) is to improve our present understanding of the impact of micro- and nano-plastics (MP/NP) and associated additives/adsorbed contaminants (A/C) in the human body. Human exposure to MP/NP may result from the widespread use of plastic products and their release to the environment, where they degrade to MP/NP particles. But plastics particles reach natural systems also as secondary by-products, e.g., from tyre wear or abrasion of textiles. As a consequence, these particles are found in food, drinking water, air and environmental media (food chain, soils). Despite recent efforts to assess the real dimension of human risks associated with MP/NP, our current knowledge is still insufficient. One of the reasons is the lack of reliable and validated methods that are able to generate the science-based data we need. PlasticsFatE will address this challenge and associated uncertainties by implementing a comprehensive measurement and testing program ("test the test"), including inter-laboratory studies, to improve and validate the performance and applicability of available methods and tools to MP/NP. The tested and validated approaches will be used to (1) identify and detect MP/NP and A/C in a variety of complex matrices, such as food (vegetables, fruits, beverages, fish etc.), human tissues and consumer products (tooth paste, beauty products), as well as relevant environmental media (air, drinking water, soils), and to (2) assess their (also long-term) fate and toxicity in the human body by using advanced cell culture and organ models that simulate real exposure to MP/NP in the respiratory and gastro-intestinal tract. The newly developed innovative approaches will be integrated into a novel risk assessment strategy specifically designed for MP/NP to provide the policy relevant and scientifically sound data needed to support the health-relevant aims of European strategies for plastics. PlasticsFatE is part of the European MNP cluster on human health.

The main goal of SUNSHINE is to develop and implement S&SbD strategies for products enabled by multi-component (advanced) nanomaterials (MCNM), including high aspect-ratio nanomaterials (HARNs). To this end, the project will generate essential knowledge, tools and data on the exposure, hazard and functionality characteristics of these materials, especially those arising from their unique properties and interactions (e.g. mixture effects due to the multi-component nature of the materials). To facilitate the uptake and utilisation of the S&SbD strategies by industry, especially SMEs, we will deliver them as part of a user-friendly e-infrastructure designed to: (1) facilitate collaboration and information exchange between actors along nanotechnology supply chains (developers, producers, downstream users) to promote the development and implementation of S&SbD strategies for MCNM-based materials, products and processes; (2) support SMEs and large industries in the selection and application of simple, robust and cost-effective experimental, modelling and grouping/read-across approaches to acquire/generate the data needed to test the effectiveness of the S&SbD strategies; (3) enable risk-benefit analysis of the S&SbD-modified materials and products at each stage of the innovation process to ensure that they are safe for the human health and the environment without compromising their technical and/or commercial probability of success The S&SbD strategies that are effective in reducing the risks from MCNMs, while retaining product performance and economic viability, will be proposed for full scale industrial implementation. In addition, the project will contribute to Regulatory Preparedness by providing recommendations on improvement and adaptation of the current regulatory hazard, exposure and risk assessment guidance (e.g. REACH, Biocides, Consumer Products, Food and Feed, Medical Technologies) and standard guidelines (OECD, ISO, CEN) for MCNMs.