From theory to practice: action plan
To achieve our ambitious goals until January 2025, we structure our activities around several Work Packages that interact with each other and allow an efficient project implementation.
Challenging actions across different Work Packages
1. Taking access to and building further upon large databases with in vitro and in vivo hazard and exposure data for a wide variety of MCNM & HARNs (WP1, WP2, WP3)
2. Combining our knowledge and competencies to a sound understanding of existing data on the interplay of material properties with functionality-hazard-exposure (all WPs)
3. Generating extensive new data in case studies targeting AOP-driven IATA characterisation of materials with low hazard profiles and/or low release profiles while retaining intended functionality (WP2, WP3)
4. Leveraging the NAMs for reliable prediction of basic toxicological profiles and exposure magnitudes while fully embracing the entire product value chain (WP4, WP5)
5. Ensuring the realisation of the envisioned Safe Innovation Approach by industries, creating a user-friendly Safe-by-Design decision support system tool that is iteratively validated in case studies (WP4, WP5, WP6)
WP 1: Data Collection and Data Management, Lead IDEA
We build on existing high-quality databases such as eNanoMapper and NECID for nanoEHS and exposure data, respectively. In order to avoid time-consuming data uploading and extensive data curation, a dedicated intake layer will handle data input directly from instruments or electronic lab books. Text processing AI methods will be integrated to find gaps in existing ontologies, which will be annotated and updated to meet the requirements for advanced materials. Similarly, data quality will be assured based on objective criteria and data curation processes and quality upgrade methods are established to ensure that high quality data is available for risk assessment, modelling, and Safe-by-Design tool development. We will draft a Data Management Plan according to best practice and in compliance with the FAIR and OPEN principles, building on ongoing projects.
WP 2: Safety Assessment Strategies, Lead NRCWE
The purpose of WP2 is to provide a solid in vivo anchorage for the NAM development in WP2. For human toxicology, we will focus on inhalation (lung) but also include relevant secondary target organs such as liver, the cardiovascular and the immune system. For environmental safety assessment, we will focus on evaluation of persistency, bioaccumulation and toxicity with an onset in the water compartment. We make use and adapt existing hazard assessment strategies like Integrated Approaches to Testing and Assessment (IATAs) as developed. Subsequently, critical data gaps will be identified and filled to create large in vivo datasets of toxicity studies of MCNM & HARNs that will be used for training and validation for NAM development in WP3.
WP 3: New Approach Methodology - in vitro and in silico data generation, Lead KI
We transfer new approach methodologies (NAMs) with multi-omics approaches and modern in silico and bioinformatics data analysis, into logically structured IATAs and ultimately into Safe-by-Design tools. The purpose is to enable fast, reliable decision-making for different purposes (Screening, Ranking, Prioritization, Grouping). A NAM tool package covering safety and exposure assessment strategies will be utilized. 37 NAMs are reviewed that were indicated as potentially useful for Safeb-by-Design strategies. The in silico analysis includes new predictive computational tools and QSAR/read-across models based on nanomaterial-related (intrinsic) descriptors, system-related descriptors, additive descriptors and quantum-chemical descriptors, reflecting interactions between released elements of multi-component nanomaterials. In combination with information on release patterns (WP2) and their interaction of the multi-component elements with each other or other chemicals, this will improve our understanding of mixture toxicity.
WP 4: Safe Innovation Approach, Lead BfR
WP4 aims to develop a Safe Innovation Approach concept that meets the demands of MCNM & HARNs. The new framework will address the Agile Triple A innovation approach, based on regulatory needs applied at stages where regulatory bound testing (in vivo) generally does not apply, hence enabling users to apply novel and cost-effective testing strategies to screen for safety issues and anticipate them in good time. The different aspects of the framework will be validated under real-life conditions in WP6, while WP5 will translate the Safe Innovation Approach into a user-friendly, easy to implement software package.
WP 5: Tool Development, Lead TNO
The main objective of WP5 is to build a user friendly Safe-by-Design Decision Support System for MCNM & HARNs by applying bioinformatics tools, such as machine learning for purposes of ranking and prioritisation of available and newly generated data as well as modelling tools. WP5 integrates methods and components developed in WP2, WP3 and WP4 into a user-friendly decision support system. We use the data generated with NAMs to build and improve models. The decision support system provides innovators in industry guidance to devise Safe-by-Design at all stages of development of a new product. Further, in-depth testing of the developed tools, both with regard to prediction performance as well as user-friendliness, are carried out in case studies as well as other stakeholder events (WP6 & WP7). A user-friendly interface is developed with and for industrial partners to facilitate the computer-aided evaluation of new and complex materials.
WP 6: Safe-by-Design Case Studies, Lead BASF
Within WP6, we realise industrial case studies from various sectors: photovoltaic devices, catalysts, advanced facades, advanced manufacturing, and sustainable agriculture, represented by five different case studies. WP6 identifies the “safety concern”, “design space” and “intended functionality” of the SbD case studies and supplies both initial testing materials and SbD-targeted materials. We establish an iteration cycle with the developers in WP4 and WP5, and with the testing in WP2 and WP3. The case studies are thus seamlessly integrated in the development of the HARMLESS SbD strategy, but also serve as demonstration to stakeholders.
WP 7: Stakeholder Engagement, Dissemination and Exploitation, Lead BNN
Our Exploitation & Dissemination plan balances public interest, inventors’ interests and commercial interests. In addition, we put special focus on the collaboration with other projects and platforms, and ensure the necessary outreach and technology transfer to different stakeholders.
WP 8: Coordination & Management, Lead HMGU
For coordination, we add methods of modern agile management to a proven classical structure. This allows fast reaction to developments in the state of the art, unforeseen problems and new ideas.