INTRODUCTION
Nanotechnology is a rapidly advancing field that enables the synthesis, engineering, and application of nanomaterials. Over the past two decades, numerous engineered nanomaterials have been developed for use in diagnostics and therapeutics within the medical field. These innovations show great potential for enhancing healthcare, particularly in areas such as cancer treatment.[1]
This episode explores the transformative impact of nanomaterials in medical devices and implants, showcasing how these tiny materials are revolutionising healthcare. However, as with any technological breakthrough, there are challenges to overcome. Without a robust and comprehensive legal framework, the widespread use of nanomaterials in medical devices could pose unforeseen health and environmental risks.
CONTEXTUALISATION
I. TECHNICAL
Nanomaterials are derived from nanotechnology, which enables engineers to create materials at nanoscale level. Nanomaterials are playing an increasingly important role across a variety of sectors, including cosmetics, environmental, sports equipment, sensors, and energy storage devices. Nanomaterials possess unique properties that differ significantly from their bulk counterparts, such as enhanced chemical reactivity and an increased capacity for nanoparticle internalisation. This makes them especially useful in medical device applications, where they can trigger specific cellular responses and offer enhanced functionality.
II. LEGAL
The legal definition of nanomaterials specifies that they are solid particles that exist naturally, incidentally or as a result of manufacturing. They can exist independently or as part of aggregates or agglomerates. At least 50% of these particles, by number, must meet one of these criteria:
– One or more of the external dimensions ranges from 1 to 100 nm.
– The particle has an elongated shape, with two dimensions smaller than 1 nm and one dimension larger than 100 nm.
– The particle has a plate-like shape, with one dimension smaller than 1 nm and the others larger than 100 nm.
Nanomaterials are regulated across various industries. In this article, we will focus on their application and regulation in the context of medical devices. The MDR aims to ensure the proper functioning of the internal market for medical devices while maintaining a high level of protection for users. MDR defines the concept of medical devices and includes specific considerations for those incorporating nanomaterials. The regulation emphasises that manufacturers must take special precautions when designing and producing such devices, including minimising the risks associated with the size and properties of particles that may be released into the body of the patient or user.
HAZARDS
Conducting a legal risk assessment is essential to minimise potential hazards. While nanomaterials generally fall within existing regulatory frameworks, their unique properties may require adaptations to these frameworks and associated testing methods, ensuring a comprehensive hazard and risk evaluation.
I. USER’S HEALTH RISKS
Nanostructured medical devices pose potential health risks, particularly due to the possibility of nanoparticle release. The most widely discussed issues are pulmonary toxicity and suppression of pulmonary inflammatory responses. The respiratory system is a critical target for toxicity assessment, as it serves as both the entry point for inhaled particles and a recipient of particles entering the bloodstream.
Researchers have also highlighted how engineered nanomaterials may disrupt haemostatic balance by interfering with the coagulation system.
Given the seriousness of these potential impacts, legislation must impose stringent obligations to mitigate the associated risks. The current legal framework demonstrates an awareness of these issues. According to the MDR, medical devices containing nanomaterials fall under the highest risk classification – Class III.
Furthermore, the MDR mandates heightened caution in the design and manufacture of devices that incorporate nanomaterials. To comply with these requirements, manufacturers must thoroughly assess the associated risks. In support of this, the EC and the SCENIHR published an opinion in 2015 outlining guidelines for the risk assessment of medical devices that incorporate nanomaterials.
Article 8 of the MDR states that compliance with relevant harmonised standards is presumed to mean that the regulation is being complied with. However, these standards are insufficient in addressing the unique properties and risks of nanomaterials. Harmonised standards, such as the widely used ISO 10993 series for the biological evaluation of medical devices, do not adequately account for nanomaterials. Scholars have emphasised the need for updates to these standards, with a particular focus on:
– a comparison of results obtained using different testing techniques.
– the evaluation of nanomaterials independently from the devices in which they are integrated.
– a more detailed characterisation of the impact of nanomaterials on the safety and functionality of medical devices.
In addition to updating technical standards, attention must be given to the lack of mandatory traceability and systematic labelling of nanomaterials. This regulatory gap fosters public mistrust regarding the safety and transparency of such devices. In our view, mandatory labelling and traceability requirements should be implemented to enhance transparency in producer-consumer relationships.
WORKER’S HEALTH RISKS
The properties of nanostructured medical devices pose unique risks to workers involved in their manufacture, handling, and disposal. These risks are further amplified by prolonged exposure to these materials over time. While existing legal frameworks, such as REACH, mandate the assessment of risks associated with nanomaterials and impose specific obligations on employers to ensure a safe working environment, there are still gaps in the provision of adequate protection for workers.
The ECʼs guidelines (2014) offer an overview of nanomaterials-related risks, outline preventive measures and provide tools for compliance with OSHA legislation. However, these frameworks fall short of establishing specific regulations, such as permissible exposure limits, clear safety measures to be followed in the event of an incident and penalties for employers who fail to ensure adequate protections. Furthermore, the absence of clearly defined regulations, combined with the varying levels of risk throughout the supply chain, leaves workers exposed to potential hazards at every stage of the process.
As it stands, the legal framework does not provide adequate protection for workers handling nanomaterials in the medical device sector. The lack of detailed, enforceable regulations means potential risks remain inadequately addressed, placing workers at risk and increasing the likelihood of legal and safety failures.
ENVIRONMENTAL RISKS
Beyond the health risks associated with nanomaterials, there are significant concerns about their potential release into the environment. Nanostructured medical devices pose risks to both the physical and biological components of ecosystems. The interaction of nanomaterials with the environment̶, particularly with regard to their bioavailability, bioaccumulation, biodegradation and changes to their physicochemical properties, requires careful monitoring and management.
Industries face challenges in achieving compliance with the regulatory requirements established by REACH. According to the ECHA, a key obstacle is the lack of validated tools and methodologies for characterising, testing, and assessing the risks posed by the physicochemical properties of nanomaterials. This gap significantly contributes to the low level of compliance with legal obligations in this area.
The guidelines on this topic provide enhanced rules and recommendations for assessing the environmental risks of medicinal products, with a particular focus on the physicochemical properties of nanomedicines. While the updated guideline offers more detailed instructions, its effectiveness will depend on its enforcement. Key factors include the ability of regulatory bodies to reject applications with incomplete or insufficientassessments, and to require applicants to address the risks identified in ERA adequately.
CONCLUSION
Scientific uncertainty remains regarding the advantages and risks posed by nanomaterials, particularly in the context of medical applications. While they play a critical role in advancing healthcare and offering new treatments, nanomaterials also present significant risks, such as potential carcinogenic effects on the health of workers involved in their production. Given the dual nature of these developments, it is essential to establish specific regulations that balance the positive impacts of innovation with the need to protect human and environmental health. Furthermore, ensuring the effective enforcement of these regulations is crucial. The legal framework must strike a balance between empowering companies to innovate and preventing potential fraud or negligent practices that could undermine public safety. The aim should be to design regulations that do not stifle innovation but also provide adequate safeguards to protect the well-being of workers and the environment.
[1] See for example, episode 25 of the podcast Discover with Infinita.
