Governance of advanced materials: Shaping a safe and sustainable future.

The past few decades of managing the uncertain risks associated with nanomaterials have provided valuable insights (knowledge gaps, tools, methods, etc.) that are equally important to promote safe and sustainable development and use of advanced materials. Based on these insights, the current paper proposes several actions to optimize the risk and sustainability governance of advanced materials. We emphasise the importance of establishing a European approach for risk and sustainability governance of advanced materials as soon as possible to keep up with the pace of innovation and to manage uncertainty among regulators, industry, SMEs and the public, regarding potential risks and impacts of advanced materials. Coordination of safe and sustainable advanced material research efforts, and data management according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles will enhance the generation of regulatory-relevant knowledge. This knowledge is crucial to identify whether current regulatory standardised and harmonised test methods are adequate to assess advanced materials. At the same time, there is urgent need for responsible innovation beyond regulatory compliance which can be promoted through the Safe and Sustainable Innovation Approach. that combines the Safe and Sustainable by Design concept with Regulatory Preparedness, supported by a trusted environment. We further recommend consolidating all efforts and networks related to the risk and sustainability governance of advanced materials in a single, easy-to-use digital portal. Given the anticipated complexity and tremendous efforts required, we identified the need of establishing an organisational structure dedicated to aligning the fast technological developments in advanced materials with proper risk and sustainability governance. Involvement of multiple stakeholders in a trusted environment ensures a coordinated effort towards the safe and sustainable development, production, and use of advanced materials. The existing infrastructures and network of experts involved in the governance of nanomaterials would form a solid foundation for such an organisational structure.

A roadmap to strengthen standardisation efforts in risk governance of nanotechnology.

A roadmap was developed to strengthen standardisation activities for risk governance of nanotechnology. Its baseline is the available standardised and harmonised methods for nanotechnology developed by the International Organization for Standardization (ISO), the European Committee for Standardization (CEN), and the Organisation for Economic Co-operation and Development (OECD). In order to identify improvements and needs for new themes in standardisation work, an analysis of the state-of-the-art concepts and interpretations of risk governance of nanotechnology was performed. Eleven overall areas of action were identified, each including a subset of specific topics. Themes addressed include physical chemical characterisation, assessment of hazard, exposure, risk and socio-economic factors, as well as education & training and social dialogue. This has been visualised in a standardisation roadmap spanning a timeframe of ten years and including key outcomes and highlights of the analysis. Furthermore, the roadmap indicates potential areas of action for harmonisation and standardisation (H&S) for nanomaterials and nanotechnology. It also includes an evaluation of the current level (limited, moderate, intense) of ongoing H&S activities and indicates the time horizon for the different areas of action. As the identified areas differ in their state of development, the number and type of actions varied widely amongst the different actions towards achieving standardisation. Thus, priority areas were also identified. The overall objective of these actions is to strengthen risk governance towards a safe use of nanomaterials and nano-related products. Though not explicitly addressed, risk-based legislation and policies are supported via the proposed H&S actions.

Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method.

Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients. In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability. Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease. Through a risk analysis and a Design of Experiments (DoE), we obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing.

Critical Considerations on the Clinical Translation of Upconversion Nanoparticles (UCNPs): Recommendations from the European Upconversion Network (COST Action CM1403).

The unique photoluminescent properties of upconversion nanoparticles (UCNPs) have attracted worldwide research interest and inspired many bioanalytical applications. The anti-Stokes emission with long luminescence lifetimes, narrow and multiple absorption and emission bands, and excellent photostability enable background-free and multiplexed detection in deep tissues. So far, however, in vitro and in vivo applications of UCNPs are restricted to the laboratory use due to safety concerns. Possible harmful effects may originate from the chemical composition but also from the small size of UCNPs. Potential end users must rely on well-founded safety data. Thus, a risk to benefit assessment of the envisioned combined therapeutic and diagnostic ("theranostic") applications is fundamentally important to bridge the translational gap between laboratory and clinics. The COST Action CM1403 "The European Upconversion Network-From the Design of Photon-Upconverting Nanomaterials to Biomedical Applications" integrates research on UCNPs ranging from fundamental materials synthesis and research, detection instrumentation, biofunctionalization, and bioassay development to toxicity testing. Such an interdisciplinary approach is necessary for a better and safer theranostic use of UCNPs. Here, the status of nanotoxicity research on UCNPs is compared to other nanomaterials, and routes for the translation of UCNPs into clinical applications are delineated.