The use of nanotechnology in medical products has been demonstrated at laboratory scale, and many resulting nanomedicines are in the translational phase toward clinical applications, with global market trends indicating strong growth of the sector in the coming years. The translation of nanomedicines toward the clinic and subsequent commercialization may require the development of new or adaptation of existing standards to ensure the quality, safety and efficacy of such products. This work addresses some identified needs, and illustrates the shortcomings of currently used standardized methods when applied to medical-nanoparticles to assess particle size, drug loading, drug release and in vitro safety. Alternative physicochemical, and in vitro toxicology methods, with the potential to qualify as future standards supporting the evaluation of nanomedicine are provided.

Appropriate documentary standards and reference materials are crucial building blocks for the development of innovative products. In order to support the emerging sector of nanomedicine, relevant standards must be identified and/or developed before the products will enter into the regulatory approval process. The anticipation of standardization needs requires a good understanding on the regulatory information requirements that can be triggered by the particularities of nanomedicines. However, robust datasets allowing firm conclusions on regulatory demands are not yet available due to a lack of regulatory experience with innovative products. Such a catch-22 situation can only be advanced in an iterative process by monitoring continuously the scientific evidence and by promoting intensive knowledge exchange between all involved stakeholders. In this study, we have compiled information requirements released by regulatory scientists so far and mapped it against available standards that could be of relevance for nanomedicines. Our gap analysis clearly demonstrated that for some endpoints such as drug release/loading and the interaction of nanomedicines with the immune system no standards are available so far. The emerging nanomedicine sector could benefit from cross-sector collaboration and review the suitability of standards that have been developed for nanomaterials used for other industrial applications. Only a concerted action of all parties can lead to a smooth translation of nanomedicines to clinical application and to the market. This is in particular important because nanotechnology-based drug delivery systems are key for the development and implementation of personalized medicine. This article is characterized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

The application of nanotechnology to emerging medicinal products is a crucial parameter for the implementation of personalized medicine. For example, sophisticated drug delivery systems can target the diseased tissue by recognizing patient-specific biomarkers while carrying pharmacologically active molecules. However, such nanomedicines can be recognized by the immune system as foreign triggering unexpected biological reactions. The anticipation of the immunogenic potential of emerging nanotechnology-based products in the preclinical phase is challenging due to high interspecies variations between the immune systems of laboratory animals and humans. A close monitoring of the scientific literature is required to better understand the relationship between various immune reactions and the diversity of nanomedicines currently in the development pipeline. We have reviewed the most frequent immune reactions induced by the nanomaterials in vivo and have identified the main effects triggered by lipid-based, polymer-based and inorganic nanoparticles, as the main categories of nanomaterials used in medicine. According to our results, almost 50% of the investigated nanomaterials induced effects related to the activation of the immune system. Among them, complement activation-related hypersensitivity reactions and activation of adaptive immune response were the most frequent effects reported for the lipid-based nanoparticles. However, many of these effects are not or are only partially covered by the current regulatory framework applicable for nanomedicines. In addition, we extracted the most relevant nanospecific properties responsible for the observed biological effects. Our analysis led to identification of the most prevalent measurement endpoints relevant for the assessment of the immunotoxic potential of the nanotechnology-based products and will support the smooth and safe translation of the new formulations to clinical applications.

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The application of nanotechnology in health care is widely accepted as a potential driver of biomedical innovation. By exploiting their unique physicochemical properties, nanomedicines can monitor, repair, and control biological systems in order to address diseases for which currently no or only insufficient diagnostic and therapeutic tools are available. Nevertheless, the opportunities of nanotechnologies in the health sector are accompanied by challenges in the regulation of these products. Sufficient knowledge on their quality, safety, and efficacy must be gained and standardised methods must be made available to support the regulatory decision making and allow a smooth translation towards clinical applications. We have conducted a survey among regulatory authorities with the aim to obtain a general overview on the status and regulatory needs of nanomedicines and to indicate some trends on future requirements. The outcome has demonstrated strong regional differences in the regulation of nanomedicines and confirmed the need for the harmonisation of information requirements on nano‐specific properties. In addition, a number of critical physicochemical properties that have already been proposed in the scientific literature were verified in the survey as relevant for regulatory decision making. Finally, the survey has demonstrated an interest of regulatory agencies in an independent nanomedicine characterisation facility that can support regulators in the evaluation of these systems and at the same time assess the performance of existing and new test methods for their application to the field of nanomedicine.