Regulatory and Scientific Barriers to The Safety Evaluation of Medical Nanotechnologies

Abstract

Nanotechnology has permeated several key markets, with its fastest and highest rate of incorporation found in the development of medicinal products, medical device and other healthcare products. This has been achieved without reform of regulatory testing guidelines that were developed before nanotechnologies were even conceptualized. A number of medicinal products containing nanomaterials have already been authorized both in the EU and the USA. These nanotechnology-based products incorporate nanoscale liposomes (e.g., Caelyx/Doxil and MyocetTM), lipid micelles (e.g., Estrasorb), virosomes (e.g., Epaxal Berna) and pegylated proteins (e.g., Neulasta, Pegasys, PegIntron, Macugen and Somavert). Other products include CALAA-01 with its proprietary siRNApolymer delivery system, the synthetic amino acid polymer in Copaxone, protein conjugates (e.g., Abraxane), microemulsions (e.g., of cyclosporine) and nanocrystalline suspensions (e.g., Rapamune, Emend and Megace ES). Additional organic nanomaterials being investigated for drug delivery include carbon fullerenes and nanotubes, whilst inorganic nanoparticles are already incorporated into a number of in vivo diagnostic products (iron nanoparticles), wound care products (nanosilver) or dental and bone restoratives (calcium nanoparticles and composites) [1]. The fact that novel characteristics of nanomaterials, such as SilcrystTM and NanoOss, are conferred by their size, shape, surface and core chemistry have been long since recognized by organizations such as the US and European Patent and Trademark Offices and regulatory agencies such as the European Medicines Agency (EMEA) and the US FDA. These novel characteristics have met important medical needs, such as the ability to deliver therapeutic agents across biological membranes, improve their solubility, reduce their toxicity or allow their localized concentration at tumor sites. However, in spite of a growing body of evidence that many of the desirable properties of nanomaterials can also translate to risks, to date there is no specific guidance pertaining to the safety evaluation of nanotechnology-based products. One such risk is the ability of nanomaterials to cross biological barriers impervious to larger particles. In some cases, this may trigger neurotoxicity [2]. Furthermore, chemical composition does not necessarily correlate with risk. Indeed, last year it was reported that engineered carbon nanotubes, once thought to be no more toxic than graphite, trigger the formation of lesions akin to those seen in asbestosis in mice [3]. In light of such evidence, in April 2009, the EU Parliament called the Commission to task over its decision to allow single registration of nano and bulk equivalent materials under the EU Chemicals Policy after having already come to the conclusion that existing test methods are not adequate for assessing the risks associated with nanomaterials in foods and having earlier this year called upon the Commission to compile a database of nanomaterials used in the EU by 2011 and to review legislative measures to ensure the safety of nanomaterials for all uses.