Concept: NanoFASE will deliver an integrated Exposure Assessment Framework, including methods, parameter values, model and guidance that will allow Industry to assess the full diversity of industrial nano-enabled products to a standard acceptable in regulatory registrations. Methods to assess how use phases, waste streams and environmental compartments (air, soil, water biota) act as “reactors” in modifying and transporting ENMs will be developed and used to derive parameter values. Our nanospecific models will be integrated with the existing multi-media fate model SimpleBox4Nano for use in EUSES and also develop into a flexible multi-media model for risk assessment at different scales and complexities. Information on release form, transformation and transport processes for product relevant ENMs will allow grouping into Functional Fate Groups according to their “most probable” fate pathways as a contribution to safe-by-design based on fate. Methodology: Inventories of material release forms along the product value chain are established. We then study how released ENMs transform from initial reactive states to modified forms with lower energy states in which nanospecific properties may be lost. Transport studies assess material fluxes within/between compartments. The experimental work underpins models describing ENM transformation and transport. Open access is provided to the models suitable for incorporation into existing exposure assessment tools (e.g. SimpleBox4Nano) and for more detailed assessment. Framework completeness is validated by case studies. Impact: Identified links between ENM material properties and fate outcome (e.g. safe-by-design). Improved representation of nanospecific processes in existing key fate and exposure assessment tools (e.g. SimpleBox4Nano in EUSES). Contribution to standardization. GIS framework to support predictive assessment, catchment and point source management of ENM releases.

An increasing number of nanomaterials (NMs) are entering the market in every day products spanning from health care and leisure to electronics, cosmetics and foodstuff. Nanotechnology is a truly enabling technology, with unlimited potential for innovation. However, the novelty in properties and forms of NMs makes the development of a well-founded and robust legislative framework to ensure safe development of nano-enabled products particularly challenging. At the heart of the challenge lies the difficulty in the reliable and reproducible characterisation of NMs given their extreme diversity and dynamic nature, particularly in complex environments, such as within different biological, environmental and technological compartments. Two key steps can resolve this: 1) the development of a holistic framework for reproducible NM characterisation, spanning from initial needs assessment through method selection to data interpretation and storage; and 2) the embedding of this framework in an operational, linked-up ontological regime to allow identification of causal relationships between NMs properties, be they intrinsic, extrinsic or calculated, and biological, (eco)toxicological and health impacts fully embedded in a mechanistic risk assessment framework. ACEnano was conceived in response to the NMBP 26 call with the aim to comprehensively address these two steps. More specifically ACEnano will introduce confidence, adaptability and clarity into NM risk assessment by developing a widely implementable and robust tiered approach to NM physico-chemical characterisation that will simplify and facilitate contextual (hazard or exposure) description and its transcription into a reliable NMs grouping framework. This will be achieved by the creation of a conceptual “toolbox” that will facilitate decision-making in choice of techniques and SOPs, linked to a characterisation ontology framework for grouping and risk assessment and a supporting data management system.

The aim of the MOlecular-Scale Biophysics Research Infrastructure (MOSBRI) is to enable ambitious integrative multi-technological studies of biological systems at the crucial intermediate level between atomic-resolution structural descriptions and cellular-scale observations. Its consortium of 2 companies and 13 academic centres of excellence from 11 countries gathers a wide complementary panel of cutting-edge instrumentation and expertise, leveraging barriers that currently hinder the optimal exploitation of molecular-scale biophysical approaches in the fields of biomedicine, biotechnology, biomaterials and beyond. MOSBRI provides European academic and industrial researchers with a one-stop shop Trans-National Access to the latest technological developments in advanced spectroscopies, hydrodynamics, thermodynamics, real-time kinetics and single molecule approaches. It will play a major role in standardization and policy-making in the field by: i) carrying out Joint Research Activities to develop innovative methodologies; ii) designing robust quality control guidelines and FAIR-compatible archiving formats and databases; iii) engaging with instrumentation, pharma, biotech and CRO SMEs. Networking activities will multiply the impact of MOSBRI, by efficiently sharing and disseminating theoretical and practical knowledge through training events in Europe, contributing to: i) the emergence of a highly qualified new generation of scientists; ii) outreach to scientific communities currently unaware of the full potential of the integrated use of molecular-scale biophysics tools. MOSBRI is complementary to related infrastructures including INSTRUCT-ERIC and iNEXT-Discovery, and will help creating a strong cross-fertilizing ecosystem with leveraging effects for European science. It represents a unique opportunity for Europe to remain at the forefront in this competitive field, thereby contributing significantly to the acceleration of discoveries beneficial for OneHealth.

The overall objective of B-SMART is: 1. to design modular nanoparticles, 2. to manufacture them via a quality-by-design protocol, 3. to achieve delivery of therapeutic RNAs to the brain and treat neurodegenerative diseases. I. To design modular nanoparticles consisting of o an active RNA payload o established (lipid-based), emerging (trigger-responsive polymer-based) or exploratory (extracellular vesicle-based) nanoparticles o a targeting ligand consisting of the variable domain of heavy chain only antibodies (also known as VHHs or nanobodies), which are coupled to the carrier platform II. To manufacture the modular nanoparticles using a microfluidic assembly system that will ensure quality-by-design: uniform nanoparticles across research sites and excellent control over the physico-chemical parameters. III. To test pre-clinical activity of formulations with promising in vitro activity with good cell/blood compatibility and to select the best RNA-formulation for clinical translation to treat neurodegenerative diseases. Pre-clinical efficacy is tested after o local injection o nasal administration o systemic administration The neurodegenerative diseases carry a high burden for patients since they are without exception progressive. But they also carry a substantial socio-economic burden with estimated costs of 130 billion euro. per year (2008). IV. The technical work in B-SMART will be supported by project management. It ensures that the project is coordinated in a clear, unambiguous and mutually acceptable manner and that the project achieves its objectives, within the given financial and time constraints. in B-SMART we expect to arrive at a scale-able nanoparticle formulation with uniform characteristics that shows strong pre-clinical evidence of therapeutic efficacy and is ready for clinical translation.

PAT4Nano offers an integrated, end user-driven, approach to develop and deploy different, yet complementary particle size measurement technologies for in- and online real-time monitoring. These will quantify particle size distribution and chemical composition in nanosuspensions. With the consortium end user partners (Agfa-Gevaert, Janssen Pharmaceutica, and Johnson Matthey), PAT4Nano will focus on applications in pharmaceuticals, inks/pigments, and materials for catalysis, batteries, and glass manufacture. Continuous, rapid, and reliable real-time data from PAT4Nano tools will provide more comprehensive process information than current offline measurements enabling manufacturers to obtain insights into the fundamental dynamics of nanoparticle-based processes. Furthermore, this information can enable continuous process feedback, opening new opportunities to implement real-time process control and feed-forward loops to correct for process variances, leading to better end product consistency and higher process efficiencies. Multi-PAT solutions, where several complementary measurement methods are combined, together with advanced data processing, will further enhance capability by increasing the information that can be extracted from measurements, extending the application range further. PAT4Nano solutions will improve process control and efficiency, and the quality of nanosuspension products. The increased quantity and quality of the real-time data will enhance the efficiency and quality of nanomaterial production. Increased reliability and repeatability will result in more efficient R&D which can produce savings of €3.2M per nanomaterial pharmaceutical product development, for advanced materials it could bring annual savings of >€3M and help advance sustainability, while for Agfa the PAT4nano tools can facilitate new business opportunities leading to local investments (mostly employment) of ~€15 M within 10 years.