According to European Medicines Agency (EMA), “Nanotechnology is the use of tiny structures – less than 1,000 nanometres across – that are designed to have specific properties” and “Nanotechnology is an emerging field in science that is used in a wide range of applications, from consumer goods to health products”. Concerning medicine, Nanotechnology has so far been utilized for the improvement of certain drug molecule properties, such as their solubility and stability, altering their pharmacokinetic profile and biodistribution, but also for creating new ways to diagnose diseases, target pathological tissues and support cell and tissue regeneration. A number of nanotechnology-based medicines or nanomedicines have been approved by EMA, after recommendation from the Committee for Medicinal Products for Human Use (CHMP). Such formulations utilize the field of innovative excipients, like liposomes (e.g. Caelyx and Myocet) or are nanoparticles of previously used active substances (e.g. Abraxane and Rapamune). Nanomedicines are considered as a “multidisciplinary” subject in the EMA “human regulatory” issues.

Especially in the field of anticancer therapy, nanotechnological carriers have offered many advantages. Tumor-targeted delivery of cytotoxic drugs is achieved with a gamut of nanosystems, vesicular or particulate, such as liposomes, micelles, dendrimers or lipid, polymeric and protein nanoparticles, as well as polymer-drug and protein-drug conjugates. Many of these products are present in the market or currently undergoing clinical investigation (Phase I-III).¹ An example of the added value that Nanotechnology has offered in anticancer therapy, is the improved safety profile of liposomal doxorubicin, compared with conventional anthracyclines.² The co-delivery of imaging and therapeutic agents is also enabled, bringing forth the Nanotheranostics concept.³

Nanosimilars are a very recently emerged issue in the field of nanomedicines, since the first generation of nanomedicines have already started to come off patent. They are the follow-on copies of nanomedicines, whose approval process differs from that of generic and biosimilar products, but incorporates elements from both. Their regulatory framework is still not well-defined, since simple bioequivalence studies are not sufficient for their approval.⁴

Discussion concerning nanomedicines and nanosimilars is open in EMA, with the agency requesting new analytical tools for their investigation, as well as the scientific contribution of experts on the field, so as to form an integrated regulatory approach on this matter. For this purpose, peer-reviewed articles have been published, highlighting the regulatory challenges and opportunities⁵ and four reflection papers have been adopted by CHMP, which provide guidance to nanomedicine developers. The latter regard block copolymer micelles⁶ and coated nanomedicinal products⁷, as well as intravenous liposomal⁸ and intravenous iron-based nano-colloidal products⁹, which are to be developed with reference to an existing innovator product. There is also an ad hoc CHMP expert group on nanomedicines, which held its first meeting on nanomedicines in London 2009 and the first “European Medicines Agency’s workshop on nanomedicines”, which was held in London 2010.

References

1. Estanqueiro et al., 2015: http://dx.doi.org/10.1016/j.colsurfb.2014.12.041
2. Rafiyath et al., 2012: http://www.ehoonline.org/content/1/1/10
3. Muthu et al., 2014: http://www.thno.org/v04p0660
4. Demetzos and Pippa, 2015: http://dx.doi.org/10.1016/j.ijpharm.2015.02.008
5. Ehmann et al., 2013: http://www.futuremedicine.com/doi/10.2217/nnm.13.68
6. EMA/CHMP/13099/2013 (EMA Reflection Paper)
7. EMA/325027/2013 (EMA Reflection Paper)
8. EMA/CHMP/806058/2009/Rev. 02 (EMA Reflection Paper)
9. EMA/CHMP/SWP/620008/2012 (EMA Reflection Paper)

Selected Publications from the Laboratory of Pharmaceutical Nanotechnology of the Department of Pharmacy, National and Kapodistrian University of Athens

1. Demetzos and Pippa, 2013: http://dx.doi.org/10.3109/10717544.2013.844745
2. Pippa et al., 2016: https://doi.org/10.2174/1381612822666160217141232
3. Naziris et al., 2016: https://doi.org/10.2174/2468187306666160712232449
4. Demetzos, 2013: http://link.springer.com/article/10.1208%2Fs12249-015-0321-1
5. Naziris et al., 2017: https://www.novapublishers.com/catalog/product_info.php?products_id=62467&osCsid=5c086307d4ddb51ff5cfbe6d8498ee99
6. Pippa et al., 2013: https://doi.org/10.1016/j.ijpharm.2013.08.087
7. Demetzos and Pippa, 2014: https://doi.org/10.1016/j.ijpharm.2014.07.015