MACRAMÉ’s Central Objective is to: • detect, characterise and quantify Advanced Materials during their processing and product-life-cycle (incl. recycling/end-of-life) to assess (e.g. ecotox-/tox-test) the resulting impact on (human) health and the environment if/when they pose (intended or unintended) exposures to humans and/or the environment and to • advance (i.e. prepare for standardisation & harmonisation/’regulatory validation’) the wide-spread applicability and application of the developed test- and characterisation methods, by demonstrating their effectiveness and efficiency in the context of existing, market-relevant industrial materials, processes and products. In alignment with the EU strategies to secure the safety and sustainability of enabling and emerging technologies (incl. those based on chemicals and materials, as addressed in the EU’s Chemical Strategy for Sustainability (2020), and in the European Green Deal (2021)), the MACRAMÉ Project focusses on the development of methodologies that are applicable to ‘Advanced Materials (AdMas)’ - a categories that includes, but surpasses that of ‘nanomaterials’ (EU, ‘Definition of a Nanomaterial’), and that is aligned with the future-oriented innovation, safety and sustainability considerations at the OECD (OECD (2020)), the EU (EU (2022)), and several of its Member States (e.g. Germany (2021)); this will be achieved by focussing the development and demonstration of novel methods and methodologies, as well as the advancement of their harmonisation and standardisation on (planned inhalable carbon-based AdMas in a variety of morphologies and dimensions, moving beyond spherical particles: (a) graphene-related material (GRM), (b) carbon fibres (CNTs), and (c) Poly Lactic-co-Glycolic Acid (PLGA). The focus on carbon-based AdMa is due to unsolved detection and characterisation issues especially in complex media.

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.

In order to accelerate the development of the nanomedicine business in Europe, EU-NCL interconnects 8 European and 1 American key reference facilities with a proven expertise in physical, chemical, in vitro and in vivo biological characterisation of nanoparticles for medical applications. The objective is to reach a level of international excellence in nanomedicine characterization for all medical indication, and make it accessible to all organisations developing candidate nanomedicines prior to their submission to the regulatory agencies in order to get the approval for clinical trials and later the marketing authorization. EU-NCL is partnered with the sole international reference facility namely the Nanotechnology Characterisation Lab of the USA to get a faster international harmonization of analytical protocols. EU-NCL is closely connected to national medicine agencies and to the European Medicine Agency in order to permanently adapt its analytical services to the need and requests of the regulators. EU-NCL is designed, organized and operated according to the highest EU regulatory and quality standards in order to provide a full analytical cascade of 42 assays. Within EU-NCL, 6 analytical facilities will offer a Trans National Access to their existing analytical services but they will also develop new or improved analytical assays under the Joint Research Activities in order to keep EU-NCL at the cutting edge of the nanomedicine characterisation. A complementary set of networking activities will make EU-NCL able to deliver to the European academic or industrial scientists the best analytical services they dramatically require for accelerating the industrial development of their candidate nanomedicines. An exploitation and business plan will be proposed at the end of the project in order to submit a sustainable development plan beyond the initial period of 4 years.

ENATRANS’ main objective is to network and support SMEs in translation of nanomedicine in Europe by providing a one-stop-shop service to interact and share information, experience and advice with up-to-date information and interactive tools, but also enabling personal contacts. To be successful SMEs need to understand the requirements of the complex ecosystem made up of regulatory and reimbursement agencies, as well as the requirements of large industrial companies and clinical needs. ENATRANS will gather and provide information about approval processes, regulatory authorities and agencies, clinical and market data, and specific nanomedicine value chain analysis, relevant SME support projects and organisations. ENATRANS will convert this critical information in dedicated learning programs and tools dedicated to translation of nanomedicine. ENATRANS aims at implementing the concept of a Translation Advisory Board (TAB) as central element of the ETPN White Paper. A TAB will be set-up with senior experienced translation experts to guide R&D teams (in SMEs and research institutes) along the translation process to successfully make it to clinical trials and later to the market. Promising projects identified and supported by the TAB need access to clinical centers for first studies in patients, which are able to handle the specificity of new nanotechnology based therapeutics. In addition, financial resources are needed to go pass the regulatory and scale-up processes, which often require funding from investors and/or large companies. ENATRANS will build bridges to clinical trial centers, investors and large companies. Promising projects need guidance to successfully master privileged contacts with the medical, the business or the investment community. ENATRANS will deliver special coaching sessions prior to showcasing of promising projects. Partners in ENATRANS are VDI/VDE-IT, Nanobiotix, CEA, bioanalytik-muenster, Tel Aviv University, Fondazione Don Gnocchi, TecMinho.