frameworks
Contract Agreement: 646221 Website: http://www.nanoreg2.eu/
Coordinator: Dr. Hab. Emeric FREJAFON / INERIS / FRANCE
Table 1 Consortium List.
Nr Name of partner Acronym Country type
1 (co) Institut National de l'Environnement Industriel et des Risques INERIS FR RES 2 European Virtual Institute for Integrated Risk Management EU-VRi DE SME
3 Nanotechnology Industries Association AISBL NIA BE IND
4 TEMAS AG Technology and Management Services TEMAS CH SME
5 Bundesinstitut fuer Risikobewertung BfR DE GOV
6 Rijksinsituut voor Volksgezondheid en Milieu RIVM NL RES
7 Det Nationale Forskningscenter for Arbejdsmiljo NRCWE DK GOV
8 Fundacion Gaiker Gaiker ES RES
9 Instituto Superiore di Sanità ISS IT GOV
10 University Utrecht UU NL RES
11 University of Gdansk UG PL RES
12 Institute of Occupational Medicine IOM UK RES
13 Leibniz Institut für neue Materialien INM DE RES
14 Joint Research Centre, Ispra JRC BE GOV
15 Nordic Quantum Computing Group AS NQCG NO SME
16 Norsk Institutt for Luftforskning NILU NO RES
17 Veneto Nanotech S.C.p.A. VN IT RES
18 Centre National de la Recherche Scientifique, CEREGE CNRS FR RES
19 Institute of Physical Chemistry "Ilie Murgulescu" of the Romanian Academy IPC RO RES 20 Roumen Tsanev Institute of Molecular Biology - Bulgarian Academy Sci. IMB-BAS BG RES
21 Aristotle University of Thessaloniki AUTh GR RES
22 Avanzare Innovación Tecnológica S.L. Avanzare ES SME
23 Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria INIA ES RES
24 Karolinska Institut KI SE RES
25 Fondazione Istituto Italiano di Tecnologia IIT IT RES
26 Nederlandse Organisatie voor Toegepaste Natuurwetenschappelijk
Onderzoek TNO NL RES
27 Commissariat à l’Energie Atomique et aux Energies Alternatives CEA FR RES
28 Association Francaise de Normalisation AFNOR FR RES
29 HiQ-nano HiQ-nano IT SME
30 Grupo Antolin Antolin ES IND
31 l'Association Saint Yves, Université Catholique de l’Ouest UCO FR RES
32 NANOGAP SUB-NM-POWDER, S.A NanoCap ES SME
33 IdeaConsult Ltd. IDEA BG SME
34 PINEXT BV Pub-Imp NL SME
35 DSM DSM NL IND
36 New Media Design s.r.o. NANOCOMO CZ SME
37 NANOMAKERS (EU Validation under progress to become a partner) Nanomakers FR SME
Contents
1 Summary ... 78 2 Background ... 78 3 Scientific and technological challenges ... 78 4 Objectives ... 79 5 Organisation ... 80
6 Progress to date ... 80 7 Expected Impact ... 81 8 Directory ... 81 9 Copyright ... 82
1 Summary
Project Duration: 36 months, starting on September 2015 Project Funding: 10 M€
One of the greatest challenges facing regulators in the ever changing landscape of novel nano-materials is how to design and implement a regulatory process which is robust enough to deal with a rapidly diversifying system of manufactured nanomaterials (MNM) over time. The challenge is to build a regulatory system which is flexible enough to be able to deal with new targets and requirements in the future, and this can be helped by the development and introduction of Safe by Design (SbD) principles.
The credibility of such a regulatory system, underpinned by the implementation of SbD, is essential for industry, who while accepting the need for regulation demand it is done in a cost effective and rapid manner. The NANoREG II project, built around the challenge of coupling SbD to the regulatory process, will demonstrate and establish new principles and ideas based on data from value chain implementation studies to establish SbD as a fundamental pillar in the validation of a novel MNM.
2 Background
As stated by the European Economic Forum in their reporting on the Innovation Principle . Innovation is the single most important driver of societal prosperity and is indispensable for sustainable development and economic growth. Without innovation European industry will lose competitive advantage and attractiveness for investment and steadily fall behind other economies”.
Despite efforts of innovators and despite regulations that require safe products at market, innovations with high economic potential are faced with questions about their safety for man and its environment. Too often these questions pop up after or around market penetration. The questions are merely related to the innovative aspects of the product or technology and appear not
easy to be answered. At that time investments have been done by innovators and interests are thereby established. On the other hand, regulators act in a reactive way which implies that regulations are tuned to innovations rather than giving clear guidance to innovations. At a more abstract level regulations are of course in place by stating that products should be safe when entering market, but for innovations the devil is in the details. For innovative products it is sometimes not clear which regulations are appropriate for the product, sometimes the validity of the testing methods might be absent whereas in others regulations do not cover the required test methods to prove safety. On the other hand, innovators tend to approach the safety issues of their innovations in a conservative way. In the end, when products near market, regulatory dossier requirements appear not to cover the information needed to address the question whether a product can be regarded safe or not. This makes the discussion about safety of innovative products a discussion about uncertainty whether there is a risk or not, rather than about the exact height of the risk.
The situation as described above makes clear that the pace of innovations reaching market is much higher than the pace of developing regulatory requirements tailored to innovative nanomaterials. This leads to conclusions that taking risks is unavoidable to come to innovations, as stated by CEO’s of large European companies in their letter to the European Commission and European Parliament last year. On the other hand, there is awareness among the regulatory community that the regulatory system should evolve to a system that is improved to absorb new safety aspects in a more proactive way and thereby facilitating innovation processes better.
3 Scientific and technological challenges
Nanosafety is expected to improve significantly following acceptance of SbD as a tool to guarantee safety at work, for
consumers and in the environment. In this sense SbD is not an aim in itself. SbD is an appealing concept, although it currently lacks agreed procedures, data collection along the R&D and innovations processes. Also acceptance of e.g. registration dossiers by ECHA to simplify the registration processes for SbD MNMs has not been discussed or agreed, and therefore, currently the SbD processes are not integrated in any legal framework and associated procedures such as REACH.
The challenge is therefore to devise a system which will channel the process of new nanomaterial acceptance through a number of interlinked regulatory steps in a rapid and effective manner.
Currently industry needs to generate data to demonstrate safe use of their products; either by performing risk assessment prior to product release (e.g. for drug dossiers or for REACH non-phase-in chemicals) or after materials have been placed on the market (REACH, for phase-in chemicals). We have to progress from rules to processes: now regulators check that the rules are followed, while in the future a procedure focusing on how to confirm the safety of new products and materials along their value chains could be envisaged.
A large consortium of partners has been formed to address this call, comprising regulators, researchers, and industry. Since it is industry who must take up this (SbD) challenge in future, it is essential to have industrial involvement, so that industrial concerns can be identified and addressed. Industry is placing nano-enabled products on the market in exponentially increasing numbers, with more than 500% growth from 2006 to 2011 registered in the USA.
There is a strong industrial participation, and clear commitment with an estimated 6.5 Million Euro own contribution by the consortium partners, in addition to the H2020 funding.
To achieve the above, the NANoREG II approach combines experts from different disciplines such as material scientists, toxicologists, engineers, market experts and regulators.
4 Objectives
OB-1 Identify and define regulatory requirements, build safe-orientated grouping approaches linked with Intelligent Testing and non-testing strategies (ITS). “Grouping approaches” are well established for chemicals, for example through the identification of chemical categories (“category approach”) or analogues (“analogue approach”). It can largely reduce the amount of tests and furthermore should strongly facilitate Regulatory Risk Assessment and Management. For MNMs, as reported recently, grouping concepts are mostly unavailable and their development pose additional (i.e. nano-specific) challenges as MNMs are defined according to their physical size and synthesized in a huge variety of different chemistries, sizes, shapes and surfaces which might change during their life cycle, influencing their behaviour and toxicological effects. Thus, identifying grouping needs and possibilities for current and future regulations, defining criteria addressing physical and chemical descriptors and toxicological end-points and evaluating results from a socio-economic point of view should be done. Such approach will be place in a global Intelligent non-Testing (eg. grouping and prediction tools) and Testing (eg. high throughputs screening, in-vitro models, short term in-vivo) Strategies (ITS) designed for toxicological, eco-toxicological and physical hazards.
OB-2 Identify and select materials as candidates for value chain demonstrators in collaboration with industry, then develop life cycle maps and identify existing and potential exposure scenarios (based on work carried out in other projects). A structured approach will be developed and applied that allows for grouping of similar release and exposure scenarios, taking into account the nanomaterial, the product, the process and environmental conditions. This will help to define the framework for evaluating changes in environmental and human health risk and to identify
“hot spots” where exposure and/or risks appear relatively high.
OB-3 Evaluate the relative change in environmental and human health risk, following implementation of the SbD process (for occupational and product (consumers and environment) safety), estimate any residual risk following SbD and recommend additional risk mitigation/management measures as appropriate.
OB-4 Develop and adapt supportive technical and organizational tools for Safe by Design, based on regulatory orientated grouping approaches. Based on grouping approaches placed in a general ITS, and based on a defined value chain, develop a comprehensive model supporting SbD principles to reduce uncertainties regarding safety along the value chain and therefore promoting safer innovations. This will be relevant when marketing should be balanced with competitiveness and social constraints.
Develop supportive tools for identifying and integrating efficient hazard and functionality testing during the innovation process that aims to minimize uncertainty on health risks for workers, consumers and the environment, analyze present SbD approaches applied in the processes extending from basic research to the market and illustrate added value of experimentally obtained safety data during the innovation process; Adapt currently applied stage-gate innovation models for use between organizations/actors wanting to facilitate the introduction of safety aspects for nanomaterials, nanoproducts at an early stage thereby supporting responsible innovation, and at the same time evaluate options to share information between players; Develop an action plan to achieve dedicated multi-stakeholder interactions (in any form) and define required actions aiming to facilitate responsible innovation.
OB-5 Identify and overcome barriers to the application of SbD concepts, including development of approaches to adequately address such barriers, taking into consideration grouping approaches and Risk Management (RM) requirements, with a view to ultimately eliminate the barriers and provide examples of guidance towards achieving SbD.
OB-6 Disseminate Safe by Design tools and SOPs, promoting regulatory orientated guidelines. The final objective is to establish viable grouping and SbD approaches, through the provision of industrial SbD-tools and Standard Operation Procedures (SOPs) that can become standards, the development of specific tools to help sharing knowledge between stakeholders (e.g. Newsletters, training support, web platform, helpdesk and public-private-partnership based platforms), and the provision of Grouping approaches that can become regulatory tools or guidelines for regulators. More precisely, standardization can support the regulatory process by providing the necessary measurement procedures and appropriate guides and specifications for products and processes. Public-private partnerships (PPP) such as helpdesk on SbD or such as pre-validation platform on non-testing and testing methods are techniques promoting innovation by developing instruments to anticipate regulations.
5 Organisation
WP 1: Regulatory orientated activities establishing a framework of grouping approaches will: 1- identify, define and harmonize current and prospective regulatory requirements and needs for MNM risk assessment, in order to implement grouping approaches and SbD.
Information requirements in different regulatory frameworks such as REACH, biocides and pesticides regulations, cosmetics directive and SCCS, and feed and food regulations will be reviewed. 2- develop and apply grouping concepts for MNM and ultimately provide tools applicable for regulatory purposes. First grouping concepts from different sources will be compiled and reviewed.
Through co-operations and partner’s contributions, information on data management, testing protocols and MNM characterization will be shared and grouping criteria and concepts will be defined, taking also into account regulatory needs including Analyses of Alternatives and Socio-Economic Analysis. A minimum number of tests will be performed only if important data gaps need to be addressed. Grouping criteria will be verified using various datasets, including those collected and made available to the project by industry. 3- combine grouping concepts with other non-testing concepts such as Read-across and QSARs or QSPRs under development in several on-going projects or European initiatives.
Then to associate these non-testing concepts with already existing testing concepts like High Throughputs screening, In-vitro models and in-vivo short term assays. All these testing and non-testing concepts will be associated in a general principle named as an Intelligent non-Testing and testing Strategy (ITS). 4 - build on a data management on well-established expertise developed in NANoREG and the ISA-TAB-Nano template approach.
WP 2: Nanomaterials for industrial markets and their corresponding value chains will 1 - Identify and select existing and new materials as candidates for value chain demonstrators in collaboration with WP1, WP3 and WP4. For each of the selected existing and new nanomaterials, develop life cycle maps, identifying existing and potential exposure scenarios. 2 - develop where possible a structured approach allowing grouping approaches of similar release and exposure scenarios, taking into account the nanomaterial, the product, and the process and environmental conditions. 3 - evaluate any relative change in environmental and human health risk following process of Safe-by-design (for production process safety and product safety) and carry out risk profiles of selected materials and/or products before and after application of SbD approaches in the case studies, to evaluate the impact of the SbD applied on the product and/or production process in terms of (potential) health and environmental risk and estimate any residual risk following SbD and recommend additional risk mitigation/management measures.
WP3: Safe by Design (SbD) aims of define a system of tools, guidance and checklists – which in its coherence is referred to as the safe innovation approach - to be used by various actors along innovation chains, supporting improved dealing with new safety issues of innovative nanomaterials and products on one hand but also supporting improved regulatory preparedness on the other hand. The safe innovation approach envisages a future proof approach, able to deal with upcoming generations of nanomaterials. Ultimately, safe innovation should also benefit to the public by improved warranting of safety of new products.
WP4: Demonstration and verification of Safe by Design concepts, will 1- -identify barriers to the application of Safe-by-Design (SbD) concepts and adequate address such barriers under consideration
of grouping principles and Risk Management (RM) requirements, with a view to ultimately eliminate/reduce the barriers and provide examples of guidance towards achieving SbD, 2 - demonstrate the integration of the SbD approaches to the innovation process of the industrial partners. 3 - establish commercially viable grouping and Safe-by-Design concepts, through the provision of industrial SbD-Tools and SOPs.
WP 5: Liaisons and network activities, will establish and strengthen the strategic and operational liaisons with: a) Member States and Associate Countries, inclusive regulation authorities; b) International organisations; c) EU and related organisations, d) FP7 and H2020 project consortia; e) Industries and industry associations. f) Public laboratories. These liaisons will be formalized by agreements and memorandums. The objective is to exchange actual information and future needs with regulation authorities, industry and the society as well as the research community with respect to actual and future needs about SbD. The close collaboration with experts of the ongoing NANoREG project, CSA ProSafe, and future H2020 projects, will guarantee complementary activities and prevent focusing on the same topics.
WP 6: Knowledge management, dissemination and exploitation, is addressing the management of the knowledge and the dissemination of new knowledge from external sources into the project and from the project to its relevant stakeholder groups.
Partners participating in WP6 have been selected due to their strong background in knowledge management and dissemination, their experience in the strategic planning and conduct of dissemination activities, and their existing liaisons and partnerships with external stakeholder that are central to the furthering of knowledge dissemination in the nanotechnology community and the provision of training to the community, where the impact of this workpackage will be evaluated. While the general public is not amongst the immediate target groups of the NANoREG II project, the public face of NANoREG II will be created and maintained with issues of societal awareness in mind: true to its name, NANoREG II will highlight the safety-aspect of nanotechnology and thus strengthen the societal awareness of nanotechnology as a ‘key enabling solution’ to grand societal challenges.
WP 7: Project Management and Scientific coordination, will provide the project coordination as defined in the Grant Agreement, the relations with EC, the project administration, regular reporting, financial management, quality assurance and impact monitoring. An Executive Board will ensure an effective information flow and knowledge exchange within the consortium and with coordinators of other relevant FP7 or H2020 research projects, a high quality and timely reporting, and management of risks and resolution of problems.
6 Progress to date
The progress within NanoReg II to date is summarised according to the main themes of the project, as follows:
Grouping strategies:
• An International Advisory Panel (IAP) was established.
Regulatory Needs for implementing grouping were identified.
• A Report on existing Grouping Strategies (NANoREG, OECD, ECHA or others) and available datasets from other projects
(e.g. NANoREG, NanoTEST, MARINA) State of the Art Analysis has been made.
• A Report on MNM selection, criteria for grouping was also finalized.
• An overview on available methods expertise was collected as a basis for the validation of the grouping approach.
• A solution team of database experts has been established.
Nanomaterials for industrial markets and their corresponding value chains
• The selection of a set of materials for case studies was realised.
More than 450 nano-enabled products have been identified.
• The definition of a group of relevant risk assessment (RA) tools for preliminary RA to suit each case study has been
accomplished.
• LCA activities have thereby been split into two distinct elements within the Nanoreg2 project: the development of necessary interfaces in order to be able to integrate LCA into the SbD approach and its related tools, and the development of various, currently missing elements for a comprehensive application of the LCA framework in the area of NM applications (development of adequate characterisation factors, CFs, for releases of NMs and the establishment of comprehensive and transparent inventory data covering the production of ENMs).
Safe by Design:
• A first description of a conceptual and operational framework of the Safe Innovation Approach (SIA).
• A literature search was also performed of the current available
• A literature search was also performed of the current available