Early4AdMa is an early awareness and action system for identifying emerging issues of advanced materials. Its first application on nanocarriers has revealed several potential issues for nanocarrier materials. These include the applicability of current regulations regarding nanocarriers. In various chemical domains this needs to be critically assessed in more detail. Further, research activities should focus on the carrier’s influence on the active ingredient. What happens to the carrier itself after its work is done also requires attention. Overall, the workshop results demonstrate that the Early4AdMa system may help to identify potential issues with safety, sustainability, and regulation. Provided that these issues are addressed through follow-up actions, this may help regulatory preparedness and contribute to safer materials.

Early4AdMa: the nanocarrier case study

The Organisation for Economic Co-operation and Development (OECD) hosted a workshop to identify and describe potential safety, sustainability, and regulatory issues on a case-study on nanocarriers. The Early4AdMa system was applied to gain relevant insights. Early4AdMa is a system developed to help regulators, risk assessors, and innovators address safety and sustainability issues early in the innovation process. The German Environment Agency (UBA) and the German Federal Institute for Risk Assessment (BfR) organised the workshop with support from the EU European Union (European Union) project ASINA. Attendees included regulators, policymakers, and experts from industry and academia.

Nanocarriers: materials of interest to multiple industries

Nanocarriers are complex materials designed to deliver a substance to a specific site of action. They are of increasing interest to the pharmaceutical, agriculture, food and cosmetics industries. They help to prevent the degradation of active ingredients, improve solubility and reduce the amount of active ingredient needed.

UBA published recent developments in nanocarriers. While they are currently mainly used in medicine, developments are expanding to other industries. For example, nanocarriers can deliver pesticides and fertilisers more precisely to the action site while reducing the amount of active substance needed.

According to the report by UBA, non-medicine applications are close to reaching the market. The authors expect a significant increase in the use of nanocarriers in the coming years. They stress the need to assess regulations to ensure that any potential risks are adequately addressed.

Early4AdMa identifies potential safety and regulatory issues for nanocarriers

During the workshop, three example applications of nanocarriers (i.e., cosmetics, pesticides and medicines) were screened for potential issues. The Early4AdMa system identified multiple potential safety, sustainability, and regulatory issues for nanocarriers. The workshop participants concluded that specific additional aspects in the risk assessment may be needed for nanocarriers. These are mainly related to the release of the active ingredient from the carrier (in time and space).

To improve regulatory risk assessment, it must be determined how to address the carrier system as a whole in a regulatory context. This includes testing the carrier’s influence on the fate and kinetics of the active ingredient that it is transporting. In addition, guidelines are needed to assess the persistence of the nanocarrier in the human body and the environment.

Reflections by RIVM

The Early4AdMa case study demonstrates that the system can help identify potential issues in the early stages of material innovation. Early awareness of potential issues is crucial in taking timely actions. In this case, regulations need to sufficiently address the specific risks of nanocarriers and the active ingredient they transport.

Generally, nanocarriers fall within the scope of existing legislation and regulation. However, the workshop results indicate that the applicability of current regulations regarding nanocarriers needs a critical look. In various chemical domains regulating agencies need to critically assess the regulations in more detail.

Some regulatory domains, such as medicinal products and food and feed, already consider the kinetics of nanocarriers. For medicine, the entire product forms the starting point in the risk assessment. This is the nanocarrier in combination with the active ingredient. Nanocarriers are also specifically addressed in EFSA guidance on risk assessment of nanomaterials in food and feed. This guidance says that the safety assessment of nanocarriers should consider the active ingredient, the encapsulating material, and the encapsulate/nanocarrier as a whole.

Even when current regulation includes nanocarrier specific provisions, the definition of nanomaterials may be an issue. The EU recommendation for a definition of nanomaterials may be too narrow for nanocarriers. According to the recommendation, the term nanomaterial is used for solid particles where 50% or more of the particles are 100 nm in size or smaller. Nanocarriers may be larger than 100 nm and are not necessarily solid particles. Accordingly, nano-specific requirements may not apply to nanocarriers, despite their relevance for safety assessments.

In addition to addressing these potential issues, research activities are needed by nanocarrier developers and the research community as a whole. These activities should focus on how transport via carriers influences the fate and effects of active substances. Also, the sustainability issues of nanocarrier systems are largely unknown and need further study.

Overall, the workshop results demonstrate that the Early4AdMa system may help to identify potential issues with safety, sustainability, and regulation. Provided that these issues are addressed through follow-up actions, this may help regulatory preparedness and contribute to safer materials.