Operationalization of the safe and sustainable by design framework for chemicals and materials: challenges and proposed actions

Abstract

The production and use of chemicals and materials have both advantages and drawbacks for human and ecosystem health. This has led to a demand for carefully guided, safe, and sustainable innovation in the production of chemicals and materials, taking into consideration their entire life cycle. The European Commission's Joint Research Centre (JRC) has released the Safe and Sustainable by Design (SSbD) framework, which aims to support this objective. The SSbD framework consists of two components that are intended to be iteratively implemented throughout the innovation process: (1) the application of design principles phase, and (2) the safety and sustainability assessment phase. However, the operationalization of the framework is currently challenging. This article maps the challenges and proposes ways to address them effectively. The mapping, which is based on a literature review and stakeholder opinions, resulted in 35 challenges. The highest priority challenge is “integration of SSbD framework into the innovation process.” To begin addressing this issue, this article recommends conducting a scoping analysis to define the SSbD study. This can be achieved through implementing a tiered approach that aligns with the objectives of the innovation and the growing expertise that comes with it. The second priority challenge is “data availability, quality and uncertainty.” This can be supported by using Findability, Accessibility, Interoperability, and Reuse (FAIR) principles and by optimizing in silico methods at early stages of the innovation process. An infrastructure for data and communication is necessary to effectively engage with the entire value chain. The third priority challenge is “integration of safety and sustainability aspects,” which requires a clear definition of how to integrate those aspects in the SSbD context, and harmonization, as far as possible, of input data, assumptions, and scenario construction. This review is the first step in accelerating the operationalization of the novel SSbD concept and framework into industrial practice.

Key points  

• This review maps the challenges to operationalize the Safe and Sustainable by Design (SSbD) framework.

• Cooperation among the scientific community, policymakers, and industries is key to address those challenges.

• Possible actions accompany the mapped challenges in order to guide research toward the operationalization of the SSbD framework.

• Two priority actions are the addition of the scoping analysis in the SSbD framework, and the integration between risk assessment and life cycle assessment.

Introduction

Chemicals and materials play a pivotal role in the functioning and economic performance of current societies. But, unfortunately, chemical pollution is also part of the triple planetary crisis (climate change, pollution, and biodiversity loss) identified by the United Nations (United Nations Environment Programme, 2024). Chemical pollution is considered to exceed the planetary boundary of novel entities and poses a risk to human health and the environment (Persson et al., 2022; Richardson et al., 2023). Moreover, harmful chemicals in various applications are often discovered too late, when the environmental quality or human health are affected (Scher et al., 2018) or when environmental exposure problems increase over time, such as with polyfluoroalkyl substances (Kumar et al., 2020).

All of these factors indicate a need to anticipate their risk and impact on human health and the environment before these chemicals are on the market. This can be achieved through novel initiatives that focus more on innovation to replace chemicals that pose a risk to human health and the environment (UNEP, 2019). Some existing concepts, such as green chemistry, green engineering, sustainable chemistry, and circular chemistry, present design principles that relate, for example, to “prevention,” “atom economy,” and “use of renewable feedstock” (Anastas & Zimmerman, 2003; Blum et al., 2017; Keijer et al., 2019). Safe-by-Design (SbD) and the Safe and Sustainable Innovation Approach are proactive concepts that guide innovation towards not only safer but also more sustainable materials, chemicals, products, and production processes (Dekkers et al., 2016; OECD, 2021b, 2022). The Chemical Alternative Assessment (CAA) identifies safer chemicals that can be used as alternatives, and also takes into account life cycle considerations to a certain extent (National Research Council, 2014). Finally, the more recent Safer Choice and Design for the Environment (DfE) standard developed by the U.S. Environmental Protection Agency (USEPA) supports the identification of functional alternatives to specific priority chemicals (US EPA: 2011, 2024a).

At the European level, the European Commission’s (EC’s) Chemicals Strategy for Sustainability (European Commission, 2020) operating under the umbrella of the European Green Deal aims to promote innovation for safe and sustainable chemicals, ultimately leading to a toxic-free environment (European Commission, 2020). This resulted in the EC “Recommendation for the establishment of a European assessment framework for Safe and Sustainable by Design (SSbD) chemicals and materials” (European Commission, 2022). The EC recommendation is founded on the SSbD framework, developed by the EC’s Joint Research Centre (JRC; Caldeira et al., 2022a) based on a review conducted by the JRC on existing frameworks (Caldeira et al., 2022b). The SSbD framework is intended to serve as a voluntary approach for guiding the innovation process of chemicals and materials. It aims to: (a) steer the innovation process towards the green and sustainable industrial transition; (b) substitute or minimize the production and use of substances of concern, in line with, and beyond existing and upcoming regulatory obligations; and (c) minimize the impact on health, climate, and the environment during sourcing, production, use and disposal of chemicals, materials, and products.

The SSbD framework is an essential component of future chemical management, emphasizing prevention over remediation by considering the diverse potential impacts on human health and the environment. This process begins as early as possible in the innovation process (European Commission, 2021b). In comparison to the CAA designed in the United States, the SSbD widens the scope beyond the chemical substitution, encompassing any form of (re)design, such as improvement of synthesis processes. Furthermore, it integrates an assessment of environmental sustainability in conjunction with safety considerations to provide a comprehensive evaluation. In contrast, the CAA approach treats environmental sustainability as an optional subsequent step after the identification of safer alternatives.

The framework is currently undergoing extensive testing to assess both its conceptual consistency and practical applicability. Case studies (Caldeira et al., 2023) have identified several challenges related to SSbD, and various organizations have also highlighted the difficulties that companies face in implementing it (CEFIC, 2021, 2022; ChemSec, 2021; European Environment Agency, 2020). Finally, several researchers have identified and discussed the challenges related to assessing the sustainability and safety of chemicals and materials through SSbD. Among these challenges, there is the need to have an agreed terminology and a common understanding of SSbD criteria, assessment tools, data availability and quality, methods for scaling up process data from the laboratory to the industrial scale, assessment at the early stages of development, and evaluation of the functionality of the chemical or material (Hong et al., 2023; Pizzol et al., 2023). However, most challenges identified so far refer to specific case studies, applications, or sectors, and a comprehensive overview and analysis of the challenges and potential solutions is currently lacking.

The objective of this study is to fill this gap by conducting a thorough and systematic assessment of the scientific and practical challenges posed by the JRC SSbD framework (hereafter referred to as the SSbD framework). The goal is to propose actions that can effectively address these challenges. The extensive and systematic mapping analysis consisted of inputs from a literature review, a stakeholder workshop, an online questionnaire, and stakeholder interviews regarding seven value chains. The interviews were carried out by the Horizon Europe project IRISS (The InteRnatIonal ecosystem for accelerating the transition to Safe-and-Sustainable-by-design materials, products and processes, iriss-ssbd.eu).

The findings of our investigation are presented in this article, following a specific sequence. First, the Background information: the SSbD framework section provides a summary description of the general features of the SSbD. Then, the Methods section details the various methods for the mapping. The Mapping the challenges and the Suggestions for actions on the priority challenges sections provide a mapping of the challenges and the possible actions, respectively. The Conclusions and outlook section summarizes the key outcomes of the article.

Background information: the SSbD framework

This study examines the structure of the SSbD framework as outlined by Caldeira et al. (2022a). The description provided deviates slightly from the structure presented in the EC recommendation, particularly with regard to the inclusion or exclusion of Step 5, which involves a socioeconomic sustainability assessment. More details regarding this section are provided below. The general structure of the JRC SSbD framework, which is shown in the upper left of Figure 1, entails two components: the application of design principles for the innovation (re)design phase of a chemical/material and a safety and sustainability assessment phase. Both phases are implemented in an iterative and tiered way as data and information become available along the steps in innovation processes.

Figure 1.

Overview of the structure of the study. The left side of the figure shows the general structure of the Safe and Sustainable by Design (SSbD) framework adapted starting from Caldeira et al. (2022a). The right side describes the methods used to conduct the study and the outcomes.

Innovation processes are commonly structured in ways that can be described by the stage-gate method (Cooper, 2010), and the SSbD framework also adheres to this method. This method outlines the various stages of the innovation process, from ideation to the launch of the final product. These stages include idea generation, idea scoping, developing a business case, product development, testing and validation, and finally, product launch. At the end of each stage there is the “gate,” representing an evaluation of the findings of the preceding “stage,” to take a go/no-go decision, which steers continuation of or stopping the design of the new technology or selecting the best (subset of) candidate molecules or product (Cooper & Sommer, 2018).

The SSbD framework proposes several design principles. These include selecting and minimizing the use of raw materials, avoiding hazardous chemicals and emissions, redesigning production processes, and designing for end-of-life. The framework includes a description, examples of actions, and potential indicators for each design principle to ensure its proper implementation.

The assessment of safety and sustainability of chemicals/materials consists of the following five steps:

• Step 1: Hazard assessment of the chemical/material. This step focuses on examining the chemical/material's inherent properties and potential hazards. The SSbD framework establishes criteria based on existing EC legislation and initiatives (e.g., European Commission, 2017; European Parliament and the Council, 2006).

• Step 2: Human health and safety in production and processing phases. This step assesses the occupational safety concerns related to the production and processing of the chemical/material as well as its end-of-life implications.

• Step 3: Human health and environmental aspects in the final application phase. This step involves evaluating the safety and environmental impact of using the chemical or material in its final application. This assessment includes analyzing the potential exposure of consumers and the environment to the substance.

• Step 4: Environmental sustainability assessment. This step assesses the environmental sustainability of the chemical/material by means of life cycle assessment (LCA). It considers the 16 impact categories of the environmental footprint method (European Commission, 2021a), and it groups them into toxicity, climate change, pollution, and resources, according to the Chemicals Strategy for Sustainability (European Commission, 2020).

• Step 5: Socioeconomic sustainability assessment (not included in the recommendation). This step evaluates the social and economic aspects of the chemical or material being studied throughout its entire life cycle. For example, social life cycle assessment (SLCA) and life cycle costing (LCC) are two methods that can be used to perform these assessments.

The results generated in each step are aggregated to support the decision-making of the assessment. The framework recommends using multicriteria decision analysis (MCDA) to evaluate safety and sustainability factors, providing various options for aggregation. Although these specifications exist, the results from the SSbD practice tests indicate that there is room for improvement. This includes aligning the stage-gate model with the SSbD framework, evaluating safety and sustainability alignment and deriving intermediate and final conclusions.

Methods

The mapping and prioritization of the challenges considered the four sources of information (Figure 1): (a) literature review, (b) stakeholder workshop, (c) the online questionnaire, and (d) interviews with seven value chains (packaging, textiles, construction, automotive, electronics, energy, and fragrances). First, a literature review, described in detail in online supplementary material SM1, was conducted, covering scientific articles and technical reports. The SSbD framework combines various safety and sustainability aspects, methods, indicators, and tools in a unique and comprehensive manner. Because the concept and framework of SSbD are relatively new, the literature also includes studies on SbD and SSbD that do not explicitly refer to the SSbD framework but still highlight relevant operational challenges.

Second, stakeholders were asked to complement the challenges identified in the literature review and to prioritize them. This interactive approach also makes it possible to capture more practical issues encountered by industries or research centers. This was done through a stakeholder workshop (organized in February 2023 by the EC’s Research and Innovation [RTD] Directorate General and JRC) and an online questionnaire. The questions in the online questionnaire are reported in online supplementary material SM1.

The challenges were prioritized based on the results of the online questionnaire as well as the relevance highlighted in the literature review and stakeholder workshop. Finally, the author team had internal discussions to complement the analysis, primarily aimed at standardizing the terminology and grouping the challenges together. Online supplementary material SM1 provides a more detailed description of the methods used in the study.

The engagement with stakeholders also included interviews with technology platforms from seven different value chains to further map practical challenges and specific priorities regarding the implementation of the design principles proposed in the SSbD framework. This was performed with the contribution of the Horizon Europe project IRISS (iriss-ssbd.eu).

Mapping the challenges

Challenges in the safety and sustainability assessment phase

The challenges that were gathered here through the review of SbD and sustainable-by-design studies assisted in framing and anticipating potential practical obstacles that may arise when applying the SSbD framework. Nevertheless, the complementing interaction with stakeholders also further highlighted some challenges or added new ones. Stakeholders who have tested the framework experienced a lack of harmonized values on substances properties and parameters used for safety and sustainability assessment or terminology used among actors from different areas of expertise. This also suggests that additional challenges may arise in the future as the application of the SSbD framework becomes more widespread.

This study presents an extensive analysis of the challenges and potential solutions, which can be found in online supplementary material SM2 (refer to Tables S1–S7) for a detailed overview. A total of 50% of the 94 papers selected during the literature review focused on SbD and 24% on sustainable-by-design. Only 26% of papers focused on SSbD which is expected given the novelty of the SSbD concept. The stakeholder workshop collected information from approx. 300 participants (more information regarding the structure of the workshop and how the data were analyzed is presented in online supplementary material SM1-1.1.2). Due to the setting of the workshop, it was not possible to classify the insights from participants according to their field of expertise. The online questionnaire collected feedback from around 70 experts, 43% of whom were from universities and research centers and 57% from companies, regulatory agencies, industry associations, and consultancy. A total of 59% self-classified as having expertise in environmental aspects, 50% on chemicals/materials, 29% on safety aspects, and 12% on modeling. Further information on the results of the online questionnaire is reported in online supplementary material SM3.

Figure 2 shows the mapped challenges for the operationalization of the SSbD framework. Each challenge was categorized either as “general,” related to the entire framework or related to one of the five steps in the framework. The three columns of the figure (i.e., the literature review, stakeholder workshop, and questionnaire) represent the three main data sources used to map the challenges and generate outcomes. The percentage in each cell represents the relevance of each challenge according to each data source. The last column, as indicated by “Priority,” shows how the challenges have been prioritized based on the information obtained from the three data sources. The challenges were prioritized using the methodology outlined in online supplementary material SM1.

Figure 2.

Mapped challenges for the operationalization of the Safe and Sustainable by Design (SSbD) framework derived from the literature review and stakeholder engagement (stakeholder workshop and questionnaire). The challenges are subdivided into each step of the SSbD assessment (according to [Caldeira et al., 2022]). The bar graphs depict the occurrence percentage of the challenge in the literature review and stakeholder feedback. For the literature review, the percentage represents the count of articles mentioning the challenges. For the stakeholder workshop, it represents the count of questions raised for the challenges during the workshop. For the questionnaire, it represents the average of the importance given by the respondents (from 1 to 4). In the last column, the red circles highlight the priority challenges. NA corresponds to aspects not asked in the questionnaire, either because potential relevance from the literature review and the stakeholder workshop was not emphasized or because it is very specific.

The list of challenges shows 16 challenges that relate to the framework as a whole and 19 challenges related to the five steps of the SSbD framework. The challenge with the highest priority was “Integration of the SSbD assessment into the innovation process,” as confirmed by both the literature review and stakeholder engagement. Based on the experiences in case studies, it is clear that various assessments are required to accommodate the diverse range of uses and applications of chemicals and materials. This complexity is a major challenge for the design, especially at the early stage of innovation when the final application(s) of a chemical or material are rarely fully known (Chatty et al., 2022; Stoycheva et al., 2022). Also, the assessment at the early stage of designing a new chemical or material should consider uncertainties, both related to predicting the potential hazard (preferably without animal testing) and the sustainability impact metrics, as well as the associated decision-making processes (e.g., dealing with trade-offs among indicators; Furxhi et al., 2022; Gomes et al., 2022; van Dijk et al., 2022).

Other priority challenges are (in alphabetic order): “alignment with other policy and research initiatives,” “appropriate system for decision-making considering trade-offs,” “data availability, quality and uncertainty (for all steps),” “expertise,” “implementation resources,” “integration of the safety and sustainability assessments,” and “tools (for all steps).”

Figure 2 provides further insights that were not covered in the literature review alone. In particular, challenges related to Step 4, such as “from relative to absolute sustainability,” “integration of circularity into environmental sustainability,” “data scale-up,” “regionalized assessment,” “integration of additional impact categories,” and “availability of characterization factors of chemicals,” were rarely discussed in the literature review. This is probably because the challenges are not unique to SSbD and require addressing regardless of the operationalization of the SSbD framework. Because the search results mainly consisted of theoretical considerations, the addition of case studies experiences was crucial, as it highlighted the challenges directly associated with SSbD practices. The articles mostly focused on SbD without including the socioeconomic sustainability dimension, which may explain why challenges related to socioeconomic sustainability were mentioned less frequently than other aspects. Currently, the articles addressing sustainable design are mainly focused on environmental sustainability and do not fully address practical issues, such as assessing the life cycle at the early stages of the innovation process. These results were not surprising given the novelty of the SSbD framework as well as the few applications of the SSbD framework. The engagement with stakeholders via the questionnaire (third column in the figure) helped in covering the relevance of such challenges because the respondents had to indicate a level of importance for each challenge.

Challenges in the implementation of the SSbD (re)design principles

The IRISS project interviewed actors from different value chains to map their experiences with the implementation of the (re)design principles proposed in the SSbD framework. Figure 3 summarizes those challenges. Each row in the figure represents the challenges that were identified in the value chain interviews, taking into account the entire life cycle. The code SSbD + number from 1 to 8 in the second column refers to the SSbD design principles as reported in Caldeira et al. (2022a). This analysis resulted in two main points of discussion related to further improvement of the SSbD framework. First, the design principles proposed in the SSbD framework are strictly related to chemical/material innovation regardless of the sector. However, the analysis of the value chains shows that the characteristics of the specific application sectors also contextualize design principles. For example, in the automotive industry, functional safety is a design principle related to the final product for the safety requirements when the car is used. It is necessary to combine this concept with the SSbD approach to ensure chemical safety and sustainability. As generally recognized in the SSbD framework, there are several sector-specific design principles that must be considered in conjunction with safety and sustainability throughout the innovation process. This confluence of different requirement types needs attention.

Figure 3.

Preliminary analysis of the challenges for the implementation of the design principles proposed by the Joint Research Centre framework with specific examples of value chains. From the top to the bottom, the figure shows the life cycle stages, the applicable design principles for each stage, and the practical challenges for the implementation of the design principles obtained from input from the value chains in the Horizon Europe IRISS project (iriss-ssbd.eu). P = packaging; T = textiles; C = construction; A = automotive; E = electronics; En = energy; F = fragrance.

Second, another important outcome concerns social sustainability. The current structure of the SSbD framework and its use in case studies suggests that social aspects are so far rarely addressed because methods to characterize them are less mature compared with environmental sustainability. Nonetheless, the data indicate that the actors interviewed would take social indicators into account during the design phase. The traceability of the critical raw materials and the working conditions at the sites of suppliers’ raw materials were identified as specific key factors to be considered, especially in the textile, electronics, automotive, and energy sectors. Additional design principles reflecting those aspects would create a more holistic design, and the Sustainable Development Goals (SDGs) can be considered as starting points for the identification of such supply chain-specific key factors and the definition of their associated indicators (THE 17 GOALS; Sustainable Development [https://sdgs.un.org/goals]).

Suggestions for actions on the priority challenges

Figure 4 summarizes the priority challenges and describes the potential actions proposed to address them. The major aspects are discussed here, and online supplementary material, Tables S1–S7, provides further details on the proposed actions for all the identified challenges.

Figure 4.

Overview of the priority challenges identified via literature search and stakeholder interactions for the operationalization of the Safe and Sustainable by Design (SSbD) framework (left), with associated (nonexhaustive) bullets list with potential actions to address the challenges (right). Each group of actions is described in the dedicated subsection.

Adding a scoping analysis for the definition of the SSbD study

The SSbD framework's current structure stipulates that an SSbD assessment must be determined based on various factors, including its objectives, scope, and aspects related to (re)design. It also groups the wide range of possible applications into the following three (re)design levels: chemical/material (re)design, product (re)design, and process (re)design. The chemical/material (re)design considers actions such as the substitution of the chemical/material with new or existing ones, or the assessment of a new chemical/material; the product/application (re)design entails, for example, the exploration of other applications, and the process (re)design involves improving the production processes of the chemical/material, for instance, by using different raw materials or reducing energy consumption.

Although it is crucial to specify those aspects from the beginning, the current structure of the SSbD framework does not offer specific guidance on this matter. The proposed scoping analysis is intended to aid in identifying the starting points for various assessments that can be conducted when applying the SSbD framework. The results (reported here) have been accommodated already in the recent methodological guidance on the SSbD framework (Abbate et al., 2024).

These assessments could focus on a single chemical or material, or on a range of candidate chemicals or materials for a comparative evaluation, such as comparing candidate molecules for a particular intended use. We derived the content of the proposed scoping analysis for SSbD from the well-established preliminary steps conducted in life cycle assessment (i.e., goal and scope definition), in risk assessment (i.e., problem definition or problem formulation), and CAA (i.e., scoping and problem formulation). These starting points can include the essential scoping analysis, which should be conducted before applying the safety and sustainability assessment of the SSbD framework. This will help to more precisely outline the goals of the particular SSbD study from the beginning.

Figure 5 displays the overall structure for defining an SSbD study, and a brief explanation is given below. At the top of the figure, the scoping analysis starts with the optional selection of the chemical/material to be assessed through the SSbD framework. This is especially true for industries that have a desire to innovate but lack a clear pathway to do so. The suggestions provided in online supplementary material SM4 can assist in prioritizing the assessment of certain chemicals and materials. After selecting the chemicals/materials for an SSbD assessment, the scoping analysis begins by describing the initial system being studied. The online supplementary material SM4 includes a series of questions that aid in comprehending and identifying pertinent information for framing the system being studied. Some questions relate to the name of the chemical(s)/material(s), the (current or foreseen) application(s) and function(s), etc.

Figure 5.

Overview of the structure of the proposed scoping analysis for the definition of the Safe and Sustainable by Design (SSbD) study. From the top, if the chemical/material is not defined, this analysis can help in the selection. After, the chemical/material is defined by collecting preliminary information on its properties, its application and function, etc. Then, according to the goal of the study following the three levels of (re)design, the definition of the study is completed by including information on, for instance, alternatives, process improvement, and potential hot spots. An example for each type of (re)design is provided.

When assessing the chemical or material throughout its entire life cycle, it is important to take into account the intended function(s) and application(s) listed. However, this has been flagged in this study as a challenge: “multiple uses and applications of the chemical/material.” This challenge refers to the plethora of potential applications of a chemical/material. Through an example shown in Figure 6, the logical links in the definition of the SSbD study, along with the data collection and flow tasks, are highlighted. This is done by displaying hypothetical production chains and demonstrating how chemicals can be alternatively used in various end products.

Figure 6.

Visualization of the logical links on data collection and flow tasks regarding data requirements in the context of the Safe and Sustainable by Design (SSbD). If we assume that Company 1 performs the SSbD assessment of one of its chemicals/materials, it needs to collect data to perform the study. Company 1 will be facilitated in selecting a product(s) for a cradle-to-grave assessment or a cradle-to-gate assessment. The cradle-to-grave for all the applications is challenging, and the information on this might be unavailable to Company 1. On the contrary, Final producer 1, which is at the end of the manufacturing stage, is able to perform cradle-to-grave assessment having more data on the final application.

To address the issue of either multiple uses of the chemical/material or uncertainty regarding its final application, one option is to assess selected scenarios of applications or to choose a single application to focus on, for instance, a worst-case scenario. The least desirable option could be to omit the requirement of a defined application of a chemical/material, only at the beginning of the innovation stage (i.e., low technology readiness level [TRL]) by performing cradle-to-gate assessments. This is usually done in a simplified LCA for intermediate producers (Oguzcan et al., 2019). However, in the case of the SSbD framework, this challenge also refers to the safety assessment based on the chosen system boundaries. Nevertheless, increasing the TRL, a real application would be necessary to obtain a comprehensive evaluation and comparison of the impacts, and hence, a cradle-to-grave assessment is necessary. This can be achieved by connecting with the end-use customers and gathering information on the ultimate application(s). Such engagements with downstream customers will be enhanced by the Digital Product Passport under the Ecodesign for Sustainable Product Regulation (ESPR) that promotes the traceability of data (European Commission, 2023b). This can also improve data sharing and data availability in the context of the SSbD, as further discussed in the Data availability, quality, and uncertainty section.

Tiered approach for the SSbD to guide the innovation process

Assessing safety and sustainability throughout the innovation process is quite challenging, mostly due to uncertainties during the innovation process itself (e.g., the applications and exposure scenarios), as well as the limited resources and data, especially at lower TRLs (details on this feedback are reported in online supplementary material SM3). The JRC has proposed a tiered assessment framework for evaluating the safety and sustainability aspects of a system or chemical being developed. This framework operates on the assumption that as the innovation process progresses, there is a greater abundance of knowledge and data available for studying the system and the materials being developed. However, the framework does not provide guidance on how to design and perform the tiered assessment. There is a need to expand on this by designing lower-to-higher tier methods (along with the stage-gate process) with clear decision points to enable going to the next tier.

Whereas lower tiers tend to focus on less precise and more conservative evaluations, higher tiers typically yield more accurate outcomes when compared to reality. The stakeholders have suggested using qualitative assessment approaches during the initial stages of the innovation process and switching to quantitative assessment as the process progresses to higher tiers. Alternatively, they proposed to only use quantitative assessment at the end of the innovation process or to focus on assessing more critical aspects while leaving the assessment of other aspects until the innovation has matured. The scoping analysis seeks to identify areas of high safety or sustainability concern, even with limited data, to guide early assessments and decisions on designing a tiered approach. This involves identifying potential hotspots that require further investigation and analysis. The authors of existing SbD and SSbD case studies have suggested that as the innovation process progresses, the accuracy of the outcomes increases along with the complexity of the assessment (Schmutz et al., 2020; Semenzin et al., 2019; van der Berg et al., 2020). Dekkers et al. (2020) followed a stage-gate method (Cooper, 2010), and/or proposed a list of questions to be answered at each stage in relation to safety. Tavernaro et al. (2021) combined functionality, SbD actions, information, and data gathering according to the stage of development. Pizzol et al. (2023) introduced a tiered approach for the evaluation of safety, functionality, and sustainability aspects following the stage-gate model for the innovation of new chemicals/materials.

Taking these ideas and practical challenges into account, we conclude that the design and implementation of a tiered system requires further attention. This might be more challenging for sustainability assessments than for safety assessments, where tiering is often applied. There are fewer studies exploring a tiered LCA. Haanstra et al. (2020) distinguished three levels of LCA, reflecting the increasing effort required, ranging from a matrix LCA to a full LCA. A simplified LCA can offer insights into hot spots and further strategies needed at an early stage, although the assessment would entail greater uncertainty (Chatty et al., 2022). Oguzcan et al. (2019) also explored simplified LCA in the context of substituting chemicals of concern. Other tiered LCAs were found in the literature, referred to, for instance, as streamlined (Calvo-Serrano et al., 2019) or predictive LCA (Fleitmann et al., 2021).

According to the existing studies, more research is needed to provide guidelines on developing and implementing a successful tiered assessment that takes into account safety, sustainability, and variations in data availability during the innovation process. In addition, there is the need to understand the innovation processes of chemicals and materials across different product value chains. This makes it possible to clarify methods, parameters, and decision tools currently being used and framed for the various product value chains.

Exploring the integration of safety and sustainability aspects

The SSbD framework's main objective is to evaluate the safety and environmental sustainability of a chemical/material life cycle. The joint evaluation led to several unexpected difficulties and challenges. The reason for this can be attributed to the distinct historical progression of chemical safety assessment and product sustainability assessment from a life cycle perspective. The former refers to a process that follows formalized and widely used protocols for risk assessment (RA). The aim is to determine whether the intended use of a chemical is considered safe for both the environment and human health. The assessment of toxicity aspects, along with other impact categories, is conducted through formalized and widely applied LCA protocols. Although RA and LCA both address toxicity in freshwater and human health, they differ in their approach. This can be an ideal situation if the results from RA and LCA are similar, but it can also be problematic if there are conceptual and practical differences between the two.

The SSbD framework combines both, so it is crucial to assess both ideal and nonideal RA and LCA evaluations. Several studies have highlighted that the options for integrating RA and LCA depend primarily on the intended purpose of the integration, as they play complementary roles. According to some authors, it is necessary to integrate the results of LCA and RA instead of integrating their methodologies (Linkov et al., 2017) to assess the benefits and to identify potential optimizations (Weyell et al., 2020). Other researchers have explored and discussed possible integrations (Bare, 2006; Csiszar et al., 2016; Hauschild et al., 2022; Sonnemann et al., 2004), for instance, introducing life cycle risk assessment (Breedveld, 2013; Harder et al., 2016) or defining the inclusion of the RA into LCA or the LCA into RA (Muazu et al., 2021).

Within the context of the SSbD framework, the two methods are being carried out separately, which may lead to less than optimal outcomes. This means that the two assessments will eventually need to be integrated, but there is a research gap in how this integration should be performed. Integration can be useful in assessing chemicals or materials during their early development stage, especially when there are limited available data and/or when multiple options are being considered. By effectively integrating both methods, the SSbD framework would be more feasible to implement and result in a more comprehensive assessment of chemical safety and sustainability. As examples of this, several studies have explored the possibility of integrating RA aspects into LCA. These include the integration of occupational and near-field exposure into LCA (Ansar et al., 2021; Csiszar et al., 2016; Fantke et al., 2016; Kijko et al., 2015), the spatialization of LCA results (De Luca Peña et al., 2022; Gargiulo et al., 2021; Megange et al., 2020), and the alignment of entry data for the construction of the characterization factors of LCA (Fantke et al., 2018; Milazzo & Spina, 2015; Saouter et al., 2020; Tian & Bilec, 2018).

Overall, it is important to first have a clear understanding of what “integration” means and determine which type of integration is most suitable in the context of early assessment along the innovation process of chemicals and materials. To achieve this, we should strive to harmonize input data, assumptions, and scenario construction as much as possible. To achieve this, the proposed scoping analysis, as described in the Addition of a scoping analysis for the definition of the SSbD study section, can assist in establishing a common understanding. Whenever possible, we aim to collect the same information regarding the chemical or material properties and exposure scenarios. However, we must also consider the unique aspects of each approach. Achieving comparability and harmonization between the two approaches requires the establishment and consistent use of terminology (Harder et al., 2015) as well as adopting a single database approach for each chemical (to avoid contrasting results of RA and LCA simply due to differences in using input data for both assessments). The rationale behind this is based on the uniform goal of achieving ultimate protection and the observation that higher levels of exposure should lead to comparable results in a quantitative risk assessment, as compared to a life cycle assessment.

Risk assessment and LCA can also be used interchangeably to detect potential hotspots in specific situations. For instance, when developing a material, performing an initial life cycle assessment can help identify areas of risk, using a life cycle thinking approach. This can be followed by a risk analysis (Subramanian et al., 2023). Conversely, RA can be initially performed for more specific analysis, followed by the LCA (Salieri et al., 2021).

The material flow analysis (MFA) approach could be a good starting point both for the RA and LCA to collect data and identify exposure pathways and the processes involved. Therefore, the regulatory outcome for the RA would identify any instances of noncompliance with the established protection goals. Material flow analysis follows the flows of a chemical/material (or product) from the extraction of its raw materials and production until the end of its life, and it is a useful tool that many researchers have used (Oguzcan et al., 2019; Pavlicek et al., 2021; Suhendra et al., 2020). Using the MFA technique, it is possible to map out all the components of a chemical/material (Guinée et al., 2022), which would be limited to the availability of data for RA and LCA (Shatkin, 2008).

Data availability, quality, and uncertainty

The challenges of safety and sustainability assessments extend beyond the operationalization of the SSbD framework due to well-known issues such as insufficient data or data with unknown variables and insufficient quality. Dealing with chemicals or materials in the early stages of development poses a significant challenge. This is due to three underlying reasons: (1) insufficient data generation, (2) inadequate data collection and management, and (3) limited data sharing.

The first issue relates to the insufficient generation of data for the new chemical or material. Chemical hazard identification in safety assessment follows a hierarchical approach that starts in silico and is followed by other experimental methods, e.g., in vitro studies. It is worth noting that generating new data through in vivo studies is typically a last resort. The SSbD framework supports and encourages the utilization of new approach methodologies (NAMs) for data generation, particularly in the initial phases of innovation. New approach methodologies provide information on chemical hazard and/or exposure, often as alternatives to animal testing; NAMs include methods such as in vitro methods, as well as in chemico or in silico methods (e.g., read-across, quantitative structure-activity relationships; ECHA, 2017), the use of combined and stepwise approaches, such as integrated testing strategies and integrated approaches to testing and assessment (OECD, 2020a). In silico approaches can predict data based solely on the chemical structure or properties of substances (such as bioaccumulation) and can provide support in generating the information necessary for early-stage hazard identification of new chemicals. There are already several types of software available applying these approaches and models (Danish EPA, 2024; ECHA, 2023; IRCCS, 2024; USEPA, 2024b) and the OECD (Q)SAR toolbox. These can be supported by physiologically based toxicokinetic models that predict absorption, distribution, metabolism, excretion properties (OECD, 2021a). Additionally, adverse outcome pathways investigate toxicodynamics (OECD, 2017) and in vitro tests. There are also exposure estimation tools based on exposure determinants or conditions of use (e.g., ART, Calendex, Cares, ChemSteer, Chesar, ConsExpo, E-FAST, EMKG-EXPO-TOOL, EUSES, OECD Emission Scenario Documents, and RAIDAR; Arnot et al., 2006). When using these tools in the early development stages, especially when the final application of a chemical/material is not always known, it is essential that scenarios are defined and modeled to estimate exposure. The creation and adoption of so-called (predicted) use maps would represent a useful opportunity to create scenarios to analyze possible situations of exposure for the different predicted uses (whether alone or in combination; ECHA, 2024b).

The lack of data for new chemicals or materials affects LCA studies both in the life cycle inventory (LCI) and in the life cycle impact assessment phases. In this context, implementing the LCI requires either scaling up laboratory data to an industrial level or using computational models such as quantitative structure-activity relationship to predict data based on molecular structures (Kleinekorte et al., 2023; Langhorst et al., 2023). The scale-up of laboratory data to industrial scale is a necessary procedure to estimate production-related data at the industrial scale, by using default data or equations (van der Hulst et al., 2020; Piccinno et al., 2016), with additional assumptions. The life cycle impact assessment lacks characterization factors (CFs) for (new or existing) emitted chemicals/materials in the existing databases and types of software (e.g., Ecoinvent, LCA for experts). Indeed, the LCA results are affected by the presence of the CF of the emitted chemical/material itself: if there is no CF, no impact related to that emission can be quantified in the LCA results. Machine learning techniques have been increasingly explored to expand the CF coverage of chemicals/materials (Algren et al., 2021; Hou et al., 2020; Von Borries et al., 2023).

The second cause is the inadequate collection and management of data in a company, specifically regarding energy and material consumption, production volumes, and other pertinent data. This information is crucial in conducting the LCA. If there is insufficient primary data available for LCI, it is recommended that the company enhance its data management practices. One solution is to establish a library that includes all the materials that enter the production site, along with a list of suppliers and the products that leave the production site. It has been demonstrated that data management can improve the execution, interpretation, and utility of the LCA (Rovelli et al., 2022). Similarly, although the inventory of the background system is usually performed by the use of secondary data (i.e., from external inventory database, literature analysis, proxies, etc.), companies need to promote engagement with suppliers in providing primary data. In the context of SSbD, it is crucial to accurately model the chemical processes with primary data to effectively capture the varying environmental impacts of different chemicals and materials. This is especially important when assessing the different suppliers of raw materials and/or production processes (e.g., starting from the FAIRification process).

The third cause is the lack of data sharing, which requires a collaborative effort from various stakeholders to be resolved. The scientific community's research data are not always suitable for the needs of companies, such as product standards, or easily accessible in a useful format. However, companies are often hesitant to share their data with stakeholders due to concerns about confidentiality. For instance, companies that have invested in testing and data collection for economic reasons may not want to share their data with “free riders” who have not made any investments.

At the scientific level, data sharing requires a shift towards ensuring ethical commitments to inclusion and trust (Soranno et al., 2015). Open Science initiatives can promote ethical commitment, for example, via recommendations on criteria for transparency and reliability of data to support regulation (Brock et al., 2021). At the regulatory level, the data collected under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation (and other legislation) on chemical properties are already shared via the International Uniform Chemical Information Database (IUCLID) portal (ECHA, 2024a), and also the OECD recognizes IUCLID and develops harmonized templates for data collection which can be integrated into IUCLID. The objective of the Findability, Accessibility, Interoperability, and Reuse (FAIR) data concept is to establish a community in which there is sufficient trust to use and provide data (GO FAIR International Support & Coordination Office; GFISCO, 2024). The concept of FAIR data emphasizes the importance of adhering to good practices when defining and sharing data. This involves ensuring that data possess essential characteristics that make them usable not only by humans but also by machines. Data ontologies are essential for maximizing the value of data and making machine learning and artificial intelligence tools applicable. This will help address data gaps and move towards more predictive in silico analysis, as suggested by Lin et al. (2020). In addition, digital repositories should adhere to the TRUST principles (transparency, responsibility, user focus, sustainability, and technology) to ensure reliability (Lin et al., 2020). These TRUST principles provide a common framework to facilitate the discussion and implementation of best practices. Efforts have been made to streamline the sharing of data where data are missing. This includes initiatives by platforms and databases (CERN & OpenAIRE, 2023; OpenAIRE, 2023). However, it is uncertain whether these voluntary initiatives are adequate for promoting data sharing or whether stricter measures by policymakers are necessary. An example of how the freedom to claim environmental information on products without any restrictions on data transparency can be misused is the phenomenon of “greenwashing.” In response, the EC has introduced the European Directive to guide environmental claims supported by transparent data (European Commission, 2023a).

Challenges related to data quality, completeness, and uncertainty must also be addressed. Data completeness refers to missing, incomplete, or incorrect information. Data completeness depends on several factors, including the quantity, quality, and relevance of the data, as well as the reliability and appropriateness of the models and inferences used to fill any data gaps. The term data quality encompasses factors such as data adequacy, relevance, and reliability, e.g., as defined by Klimisch et al. (1997) within the context of risk assessment for toxicological and ecotoxicological in vivo studies. Data uncertainty arises from uncertain parameter values and technical configurations that may change or be inaccurate during the chemical/material innovation process, resulting in potentially adverse effects on safety and environmental sustainability assessment outcomes. To identify the parameters that have the most significant impact on environmental performance, one could use techniques such as Monte Carlo simulation or scenario development by altering the parameter values. All the above need to be considered in the process of collecting the evidence and its weighting to reach a conclusion on a particular question with a defined degree of confidence. This aspect has been less often investigated in the SSbD context due to its increased complexity. On the one hand, SSbD prioritizes the use of NAMs to generate data, particularly in the initial stages of innovation. However, the question of how to manage data uncertainty and ensure quality in decision-making throughout the innovation process remains unresolved.

Decision-making support systems

As depicted in Figure 2, the challenge that arose regarding the decision-making aspects of the SSbD framework can be divided into two categories: the evaluation methodology and criteria for scoring at each assessment step, and the integration of multiple criteria to reach an overall decision on the SSbD results.

Evaluation methodology and criteria for the scoring

For each step of the assessment, the SSbD framework aims to include an evaluation methodology and criteria for the scoring to aid the decision-making. Regarding the safety assessment, the definition of its evaluation methodology and criteria has been widely discussed, particularly in the context of design where data are scarce (Baas et al., 2022; Gulumian & Cassee, 2021; Pavlicek et al., 2021). The main challenge of the evaluation methodology is devising a weighting system for multiple aspects. To understand the potential dangers of a chemical, various endpoints can be used to assess its hazard profile, including carcinogenicity, endocrine disruption, and aquatic toxicity. Given that RA (safety assessment) is a combination of the hazard of the chemical and the exposure of that chemical to receptors, the evaluation of the risk and decision-making should consider both levels (Packroff & Marx, 2022).

In the SSbD framework, the decision-making process takes into account the hazards associated with certain substances. This is done by using cut-off criteria for the most harmful substances, which includes substances that are deemed to be of very high concern. The criteria for excluding such substances should be established to ensure that they can be eliminated early in the innovation process. This approach follows the EU legislation, e.g., REACH and legislation for protecting workers (The Council of the European Union, 1998), which aims to minimize the use of hazardous substances through restrictions and authorization and encourages the search for safer alternatives. In addition to the cut-off criteria that eliminate the most harmful substances, various alternatives can be compared based on information regarding different endpoints using different weighting systems such as NRC (2014).

With regard to the evaluation methodology and criteria for the environmental sustainability, the difficulties primarily lie in the identification of the acceptable level of sustainability and the choice of indicators to be incorporated into the evaluation (Mech et al., 2022). As with the safety assessment, several aspects might need to be weighted, as it is unlikely that one option will perform better than the others in all impact categories. One challenge of this step is that the assessment is comparative and relative, which makes it difficult to make an absolute assessment of sustainability.

The SSbD framework currently transforms the results of the sustainability assessment for the different options into scores (Zanghelini et al., 2018; Kalbar et al., 2017). The weighting of the impact assessment results, as recommended by the Product Environmental Footprint method (European Commission, 2024), supports the interpretation by reflecting the relative importance of each impact category.

Decision-making among safety and sustainability dimensions

A decision-making system suitable for the innovation process should prioritize options based on both their sustainability and safety outcomes (Angeles et al., 2021; Di Martino et al., 2021). Innovation can result by improving some aspects of safety and sustainability where trade-offs need to be considered to avoid unintended consequences. Multicriteria decision analysis can be used to assess these trade-offs. There are up to 60 different methods described in the literature for MCDA (Taherdoost & Madanchian, 2023). The most commonly used and cited methods include the analytic hierarchy process, the data envelopment analysis, and the fuzzy set theory approach. Most rely on assigning weights to criteria/attributes (Odu, 2019).

Some approaches suggest prioritizing safety during the early stages of development and addressing other aspects of sustainability at a later stage (Bouchaut et al., 2021). Other approaches consider weights for each indicator competing to the final decision, following various existing methodologies, such as analytic hierarchy process or integrated weighting factor (Serna et al., 2016). Another approach establishes a minimum performance requirement taking into account safety and sustainability (European Environment Agency, 2020). For instance, the Safer Choice Program, which was developed by the USEPA, has toxicity thresholds that substances must meet as requirements (USEPA, 2023).

To reach a compromise, first, minimum requirements for each dimension such as safety, environmental sustainability, etc., or for each aspect, such as carcinogenicity, acidification, and child labor, could be established as a cut-off criterion in Step 1 of the SSbD framework. Second, only those options that meet the minimum requirements will be analyzed using the MCDA. The MCDA toolbox, which is currently available, can assist in selecting the most suitable MCDA approaches for specific situations (Dias et al., 2024).

Although various approaches have been proposed and tested specifically for the SSbD framework (Abbate et al., 2024; Caldeira et al., 2022a; Caldeira et al., 2023), the following needs should complement the use of the MCDA: expert judgement on the meaning and interpretation of the different indicators fed into the MCDA (Furxhi et al., 2022), data quality and uncertainty (Dias et al., 2024), and the definition of minimum requirements along the safety and sustainability dimensions.

Actions to address other priority challenges

This section briefly discusses the other “more practical” priority challenges that if addressed, can enhance the operationalization of the SSbD framework. These challenges include the need for a “transparent and harmonized terminology,” “implementation resources,” and the “communication to stakeholders.”

A transparent and harmonized terminology for SSbD has been discussed by the scientific community (Mech et al., 2022) and it could be addressed with the collaboration of scientific experts (Heinemeyer et al., 2021). In the context of SSbD, which involves various disciplines, the use of a consistent terminology is crucial to facilitate discussion and collaboration among experts from different fields (Guinée et al., 2022). As the SSbD framework seeks to integrate RA and LCA, terms might be well known and defined in one field but not in the other, or could be used in both fields, albeit with different meanings, or the terms could be new. Terms like “substance” (which has a precise definition in chemical regulations and is therefore subject to regulatory risk assessment), “chemical,” “material,” “product,” and “life cycle” are all examples. In LCA, the term “life cycle” usually refers to the quantity of a product or product system based on its performance in the end-use application(s). One initial chemical or material may have different life cycle perspectives depending on its intended uses. To address this, Guinée and colleagues have identified three types of life cycle that can be applied in the context of SSbD, namely the life cycle of a product system, a chemical, and a material (Guinée et al., 2022).

The need for communication among stakeholders and experts from different fields has been highlighted by audiences and stakeholders (Völker et al., 2024), also proposing interactive system of communication among stakeholders, especially between producers and regulators (Micheletti et al., 2017). The recent collaboration platform, which was launched by the IRISS project to share knowledge on SSbD in general and at the value chain level, aims to address the need to create a trusted environment by involving stakeholders in sharing results and in having open communication (OECD, 2020b; van der Berg et al., 2020; Tavernaro et al., 2021). Lectures and courses in this field in university programs (Mech et al., 2022; Muñoz et al., 2021), and pathways to guide young researchers in these topics are key to adding the SSbD concept into research. Finally, specific technical and economic incentives and support should be provided to small and midsize enterprises (Dekkers et al., 2020) in a broader perspective, also considering other current policies that include sustainability aspects of products (or processes).

Conclusions and outlook

This study identified the challenges and proposed actions for implementing the SSbD framework. The SSbD framework presents a methodology for proactively promoting innovation towards safer and more sustainable chemicals and materials. It unites diverse expertise, including product/process designers, engineers, and professionals specializing in risk and environmental sustainability assessment. As the concept of SSbD is still new and its applications are limited, this study contributes to shaping the concept and framing its challenges. By learning from existing methodologies and engaging with stakeholders to capture new elements, we hope to broaden our understanding of SSbD.

First, the proposal for additional scoping analysis of the SSbD framework aims to support the “integration of the SSbD assessment into the innovation process” by helping to define the SSbD system being studied based on the goal of the innovation. To facilitate the scoping analysis, a set of guidelines has been developed to support the SSbD assessment in alignment with the defined SSbD study. These guidelines, which were recently established by the JRC's methodological guidance for the SSbD framework, adopt a tiered approach that takes into account various innovation options or the TRL level of the chemical/material.

Second, regarding the “integration of the safety and sustainability aspects,” the SSbD framework requires the integration of the RA and LCA assessments. This ensures that a new chemical/material meets both safety and sustainability standards throughout its entire life cycle, while minimizing data needs, optimizing the impact of innovation strategies, and performing “hot spots” analyses. The iterative assessment of safety and sustainability in the development phases for a new chemical/material should lead to the early identification of issues or promising development. To achieve comparability and harmonization, it would be beneficial to have consistent terminology and utilize a single database approach for each chemical. This would prevent conflicting results between RA and LCA due to variations in the input data used for both assessments.

Third, we should focus on improving the availability of data by developing methodologies for generating data at the early stages of development. Solutions are needed, not only for technical data sharing but also regarding return on investment for companies financing the testing vis a vis free riders (which currently motivates no-share practices). Companies could improve cooperation throughout the product value chains to improve data generation and sharing. One way to do this is to adopt the FAIR approach for maximum valorization of data and the optimal use of in silico analyses with the aid of machine learning and artificial intelligence. To improve data collection, companies should focus on enhancing their own production processes as well as those of their suppliers.

This article provides an overview of the challenges that companies, scientists, and policymakers need to address given the current state of development of the novel SSbD approach. It identifies priority issues and proposes actions to address them, demonstrating that there is latitude to successfully address each challenge. This analysis confirms the outreach provided by the EC to member states through the recommendation for the establishment of a European assessment framework for SSbD chemicals and materials. There are several key requirements to ensure the assessment of safety and sustainability with regard to data. These include the need for high-quality FAIR data; the improvement of assessment methods, models, and tools; the development of new tools as necessary; and the support of educational curricula to teach the skills required for implementing the framework. This review can speed up the operationalization of the SSbD framework by identifying potential challenges and providing actionable solutions that can be applied as the use of SSbD continues to grow.

Supplementary material

Supplementary material is available online at Integrated Environmental Assessment and Management.

Data availability

Data are available as supporting information.

Author contributions

Elisabetta Abbate (Conceptualization, Formal analysis, Investigation, Methodology, Visualization, Writing—original draft, Writing—review & editing), Ad Ragas (Conceptualization, Methodology, Supervision, Writing—review & editing), Carla Caldeira (Conceptualization, Supervision, Writing—review & editing), Leo Posthuma (Conceptualization, Supervision, Writing—review & editing), Irantzu Garmendia Aguirre (Writing—review & editing), Anne Chloe Devic (Investigation), Lya G. Soeteman-Hernández (Investigation, Writing—review & editing), Mark A.J. Huijbregts (Conceptualization, Methodology, Supervision, Writing—review & editing), and Serenella Sala (Conceptualization, Methodology, Supervision, Writing—review & editing)

Funding

The present study has been conducted by the European Commission Joint Research Centre (JRC) as well as being financially supported by Directorate General for Research and Innovation (DG RTD) in the context of the Administrative Arrangement JRC 36058—DG RTD LC-01671974 “Criteria for Safe and Sustainable-by-Design advanced materials and chemicals” (SSBDCHEM). This work has been developed in the context of Collaborative Doctoral Partnership Agreement No 35334 between the European Commission Joint Research Centre and Radboud University. This work was also supported by the Horizon Europe project IRISS which receives funding from the European Union’s Horizon Europe research and innovation program under grant agreement no 101058245. UK participants in Project IRISS are supported by UKRI grant 10038816. CH participants in Project IRISS receive funding from the Swiss State Secretariat for Education, Research and Innovation (SERI).

Conflicts of interest

The authors declare no conflicts of interest.

Disclaimer

The peer review for this article was managed by the Editorial Board without the involvement of Serenella Sala.