Planned launches of generic versions of first-generation nanomedicines and the emergence of a second generation of more-complex
nanotechnologies in healthcare are now becoming a big challenge for licensing agencies. Unsurprisingly, the pharmaceutical
industry has its doubts about the exact regulatory requirements for approval of innovative nanosubstances in medicinal products.
The uncertainties are not only confined to Europe but also other developed regions such as North America, mainly due to the
gaps in knowledge about the safety of nanomedicines derived from recent advances in nanotechnologies.
"The industry wants greater clarity among regulators, more uniform standards, and more harmonization," Beat Loeffler, chief
executive of the European Foundation for Clinical Nanomedicine (CLINAM), Basel, Switzerland, told Pharmaceutical Technology. "There is a feeling that the regulators do not know what they want." An annual international conference on clinical nanomedicines,
organized jointly at Basel in June 2013 by CLINAM and the European Technology Platform on Nanomedicine (ETPN), called for
greater consistency among regulators in dealing with new nanopharmaceutical products.
In Europe, the safety rules on nanosubstances in medicinal products can be particularly perplexing because in many cases,
the nanotechnologies are applied to drug-delivery systems, carriers, and imaging agents. As a result, the products have been
categorized as combination products or medical devices rather than medicines. In the European Union (EU), this categorization
has given much more scope for the regulatory authorities of the 28 EU member states to approve nanomedicines rather than the
European Medicines Agency (EMA), whose main responsibility is the approval of pharmaceuticals.
Some national governments have been taking their own regulatory initiatives on the management of nanosubstances in medicines
and other products because of the reluctance of the European Commission (EC) to tighten up EU rules in the area. Last year,
after a regulatory review on controls of nanomaterials, the EC decided to leave EU legislation on nanotechnology unchanged.
Instead, the EC stated that the safety of nanomaterials should be assessed on a case-by-case basis on the grounds that they
are similar to normal substances in that some may be toxic and some may not.
In an earlier recommendation, made in October 2011, the EC provided leeway for national governments to apply their own controls
on nanomaterials by recommending a broad definition of "nanomaterial." A material was defined as "nano" when it contained
50% or more particles in the size range of 1–100 nm. The EC also acknowledged that because of "special circumstances" in the
pharmaceutical sector, the recommendation of an upper limit of 100 nm should "not prejudice the use of the term nano when
defining certain pharmaceuticals and medical devices."
France has been among the most ambitious EU member states in introducing a new nanotechnology legislation, which came into
effect in May this year, but which has, so far, not raised any significant opposition among French pharmaceutical companies.
Its main requirement is that manufacturers, importers, and distributors of engineered nanosubstances make annual declarations
to the French government of the amounts they are placing on the national market with details of their uses.
"This legislation is not a hurdle and the provision for annual declaration encourages transparency, which is a desirable objective,"
explains Laurent Levy, chief executive of Nanobiotix, Paris, a nanomedicine company and a member of the biotechnology committee
of the French Pharmaceutical Companies Association. The increase in new nanomaterial legislation at the national level in
Europe is, however, causing some nanomedicine companies to see regulation as being an obstacle to innovation.
"Small and medium enterprises (SMEs), in particular, are regarding regulation in nanotechnology as a barrier," Levy, who is
also vice-chairman of the ETPN, an EU-funded research organization, said in an interview with Pharmaceutical Technology. "But once they start interacting with the regulatory authorities about their new products, they become much less concerned
because they are in a dialogue with the authorities during the development of their nanoproducts, and therefore, will know
what is expected of them."
Nanobiotix has been keeping in close contact with the French National Agency for the Safety of Medicines and Healthcare Products
(ANMS) in the development of a nanoparticle-enhanced radiotherapy technology. In June 2013, ANMS authorized the company to
start a clinical trial of the technology for the treatment of head and neck cancer.
The Nanobiotix technology, however, is an example of disparities outside Europe in the international classification of nanomedicines.
In Europe, it has been categorized as a medical device, while in the US, FDA considers it to be a drug. As a result, Nanobiotix
reckons its first products will reach the market more quickly in Europe than in the US because European national authorities
responsible for licensing medical devices require fewer clinical trials than with pharmaceuticals.
"There may be a bit of a difference in the time to market between Europe and the US, but in the end, you have to meet the
same regulatory requirements of demonstrating an acceptable benefit-to-risk ratio," explained Levy.