TOWARDS A CORRECT RISK ASSESSMENT OF MEDICAL DEVICES CONTAINING NANOMATERIALS S.Tedesco, G. D’Avenio, C. Daniele, M. Grigioni Technology and Health Department, Istituto Superiore di Sanità, Rome, Italy Introduction Results Discussion The increasing diffusion of medical devices (MDs) containing nanomaterials (NMs) witnesses the great benefits given by the nanoscale’s unique properties. At the same time, it is necessary to define and to monitorate the associated risks, mainly associated to NMs themeselves. The common cathegory risks are: human, political, ecological, educational. In absence of proper guidelines for NMs, OECD has accepted as suitable the laws regulating chemical products, which should be taken as the reference for them. The document producted and used for chemical products is the safety data sheet (SDS), written in Switzerland by UFSP, and adopted by the Federal Council (FC) in April 2008, according to OPChim RS 813.11, art. 52, with the only aim to add some informations typical of NMs. What is currently lacking are standardised methods to determine those physical-chemical that could influence the behaviour of NMs in biological systems and in environment. A physical–chemical characterization exists nowaday only for raw materials (EN ISO 10992 18 e 19 ) but it contains a lot of data and informations to be extended to NMs. Specifically the better physical-chemical parameters chosen, with the help of the documents cited above, are reported in the table below:   In 2012 the FC decided to continue the impementation work until 2015 (Swiss “Action plan for synthetic nanomaterials”). This work aims to: -- Create a regulatory framework for responsible handling of synthetic NMs --Developing a precautionary matrix for synthetic NM, with the responsibility to apply the precautionary principle in a goal oriented and cost-effective manner. --Promoting public dialogue on opportunities and risks of nanotechnologies and NMs. --Implementing a guide for the correctly completing the SDS. --Dispose about industrial nanowaste The guidelines for risk evaluation of MDs containing NMs are still in a very preliminary phase, ought to a quantity of different problems. Below is shown only some example of them. The definition and delicate difference between MDs containing NMs and NM devices becomes extremely ambigous for novel nano-based drug delivery devices, as they can be considered either device (carrier) or drugs (effectors). In order to successfully do it a strong knowledge of the field is essential together with a better understanding of the potential risks . It is not clear if the traditional laboratory approaches to safety evaluations will supply a correct evaluation of the nano-technological risk for first in humans trials (FIT), because the nano-medical interventions present an higher level of uncertainty than more conventional biomedical intervention, and also more than the last in human trials. Definition of NMs or of nano-relevance is not the same in different part of the world. EU criterion (2011/696/EU) is based on size, FDA assess the safety of NMs as a new materials and of nanotechnology as it does any other emerging technology or significant change in manufacturing process ( see below in the table). Aim This study addresses the current status of risks assessment of MDs containing NMs Material and methods Physical-chemical parameters for risks of NMs Distribution Morphology Aggregation/agglomeration Specific surface area Composition ( chemical and structural) Surface charge Surface chemics solubility A risk is defined as the combined effect of product toxicity and exposure level (quantity, kind and time of the contact). Generally an adeguate risk assessment for a MD containing NMs have to undergo the next steps: Detailed description of DM Detailed description of physical-chemical properties of NMs involved in the life cycle of the DM Physical-chemical characterization of NMs above (incidental and intentional, and regarding production and use) Current guidelines for risk management of MDs (EN ISO 10993-1) are generally accepted also when they contain NMs but before standard testing, it is necessary to perform an adequate physical-chemical characterization of the NMs (intentional and incidental) involved in the entire life cycle of the MD. Actually, the toxicity of the same NMs may vary in different locations and forms (airborne, surface bound, suspended…), and also in different points of the product’s cycle of life. A full assessment of the effects of exposure to NMs would require a wealth of knowledge, currently not available. EU FDA Typeand state of NM Natural,incidental, manufactured; unbound, aggregate or agglomerate state Engineered or end state Dim. of NM 50% particles or at least one ext dim in 1nm-100nm At least one dim. in 1nm-100 nm or exhibits properties or phenomena attributable to it’s dimension(s) even if these fall out of nm scale up to μm Conclusions Current testing procedures are just a good start in view of attaining the level required for a correct risk management. A coordinated, international and multidisciplinary work is needed to improve knowledge, innovation and safety of MDs with NMs References FOPH, FOEN, Switzerland Confederation, Guidelines on Precautionary Matrix for Synthetic NMs, 2013. FDA, Considering Whether a FDA- Regulated Product Involves the Application of Nanotechnology,Guidance for industry, 2014. Contacts Silvia Tedesco, silviated@gmail.com. Exposed at the 41st annual ESAO congress European Society for Artificial Organs Rome, September 17-20, 2014