The convergence of nanotechnology and biotechnology has led to substantial advancements in nano-biomaterials (NBMs) used in medical devices (MD) and advanced therapy medicinal products (ATMP). However, there are concerns that applications of NBMs for medical diagnostics, therapeutics and regenerative medicine could also pose health and/or environmental risks since the current understanding of their safety is incomplete. A scientific strategy is therefore needed to assess all risks emerging along the life cycles of these products. To address this need, an overarching risk management framework (RMF) for NBMs used in MD and ATMP is presented in this paper, as a result of a collaborative effort of a team of experts within the EU Project BIORIMA and with relevant inputs from external stakeholders. The framework, in line with current regulatory requirements, is designed according to state-of-the-art approaches to risk assessment and management of both nanomaterials and biomaterials. The collection/generation of data for NBMs safety assessment is based on innovative integrated approaches to testing and assessment (IATA). The framework can support stakeholders (e.g., manufacturers, regulators, consultants) in systematically assessing not only patient safety but also occupational (including healthcare workers) and environmental risks along the life cycle of MD and ATMP. The outputs of the framework enable the user to identify suitable safe(r)-by-design alternatives and/or risk management measures and to compare the risks of NBMs to their (clinical) benefits, based on efficacy, quality and cost criteria, in order to inform robust risk management decision-making.

The SAbyNA platform supports value chain actors in developing safe-by-design nano-enabled products early in their development phases. The potential of digital guidance is exemplified in a case study on carbon nanotube-based 3D-printed products.

Personalized nanomedicine has rapidly evolved over the past decade to tailor the diagnosis and treatment of several diseases to the individual characteristics of each patient. In oncology, iron oxide nano-biomaterials (NBMs) have become a promising biomedical product in targeted drug delivery as well as in magnetic resonance imaging (MRI) as a contrast agent and magnetic hyperthermia. The combination of diagnosis and therapy in a single nano-enabled product (so-called theranostic agent) in the personalized nanomedicine has been investigated so far mostly in terms of local events, causes-effects, and mutual relationships. However, this approach could fail in capturing the overall complexity of a system, whereas systemic approaches can be used to study the organization of phenomena in terms of dynamic configurations, independent of the nature, type, or spatial and temporal scale of the elements of the system. In medicine, complex descriptions of diseases and their evolution are daily assessed in clinical settings, which can be thus considered as complex systems exhibiting self-organizing and non-linear features, to be investigated through the identification of dynamic feedback-driven behaviors. In this study, a Systems Thinking (ST) approach is proposed to represent the complexity of the theranostic modalities in the context of the personalized nanomedicine through the setting up of a stock-flow diagram. Specifically, the interconnections between the administration of magnetite NBMs for diagnosis and therapy of tumors are fully identified, emphasizing the role of the feedback loops. The presented approach has revealed its suitability for further application in the medical field. In particular, the obtained stock-flow diagram can be adapted for improving the future knowledge of complex systems in personalized nanomedicine as well as in other nanosafety areas.

The development of new materials that are inherently safe and sustainable has become a critical objective in the context of the green transition. This challenge is especially significant for plastics, which often contain complex mixtures of chemicals that may be released during various stages of their life cycle and that can pose risks to human health and the environment. Within this context, the Safe and Sustainable by Design (SSbD) framework was followed to support the design of an innovative epoxy–vitrimer composite that integrates non-releasable fire-retardant functionalities, aiming to produce safer, sustainable, and recyclable materials suitable for railway applications. A simple methodology was developed to identify release hotspots potentially affecting workers, consumers, and environmental species and organisms. Based on this, experimental simulations were conducted to evaluate the release of materials such as flame retardants, non-intentionally added substances, and microplastics at hotspots and to compare release profiles between a benchmark material and an SSbD alternative. The results demonstrate that the newly developed recyclable and less hazardous composites can also reduce material release under weathering and abrasion conditions.

The safety-by-design approach is a decision process that aims to minimize the risks of nanoforms in a context of high uncertainty.

The development of new chemicals and materials that are inherently safe and sustainable throughout their entire life cycle has become a critical objective in the context of the green transition. This challenge is especially significant for plastics, which often contain complex mixtures of chemicals that may be released during various stages of their life cycle, from manufacturing to use and end-of-life management. Such releases can pose risks to human health and the environment. Within this context, the Safe and Sustainable by Design (SSbD) framework was followed to support the design of an innovative epoxy-vitrimer composite that integrates non-releasable fire-retardant functionalities, aiming to produce a safer, recyclable materials suitable for railway applications. This study presents the identification and quantification of potential releases as part of Steps 2 and 3 of the SSbD framework. A dedicated methodology was established to evaluate the potential release of materials such as flame retardants, non-intentionally added substances, and microplastics throughout the product’s life cycle. A systematic template was developed to identify release hotspots potentially affecting workers, consumers, and environmental species and organisms. Based on these findings, experimental simulations were conducted to compare release profiles between a benchmark and the SSbD alternative.