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Nanotechnology: Europe risks lagging behind

A peer-review system for nanomedicine which fails to produce entrepreneurial researchers is curbing development, so academics need schooling in what makes a drug marketable

Nanotechnology in healthcareThe development of nanotechnology-based medicines in Europe is being inhibited by a disconnection between academic research and the pharmaceutical industry, according to the European Technology Platform on Nanomedicine (ETPN) group.

A September 2011 white paper, 'Improving Translation of Public Healthcare Nano-Research in Europe', from the industry-led organisation, suggests that a lack of entrepreneurial culture among academics in Europe is blocking the translation of nanomedicine research from 'bench to bedside', while industry is failing to appreciate the challenges of being a 'solo performer in academia'.

ETPN defines the nanomedicine universe as spanning diagnostics and imaging, nano-pharmaceuticals and regenerative medicines.

"The problem lies in part with the academic culture in Europe, where there is an emphasis on academic freedom and a resistance to being held to commercial objectives," according to ETPN's chairman Mike Eaton, who believes this is a much more serious issue than the oft-cited problem of access to funding.

"There is a separation between scientists in academia and those in industry within Europe that is not seen elsewhere in the world, including the US and particularly China," he says.

The result of this is that academics in Europe working in the nanotechnology area often work in silos, without tapping into the drug industry's drug development expertise. That has led to poor choice of research area; for example, wasting resources in undevelopable projects and suboptimal selection of therapeutic agents. Eaton believes the problem is not confined to academia, with some small and medium-sized enterprises suffering from similar ailments.

Part of the problem is the current peer review process, according to Eaton, who questions why academic experts should know what makes a drug marketable or not. What is needed is insight into areas such as the competitive landscape, regulatory affairs, analytical methods and instruments, and manufacturing, process and scale-up – knowledge which is often unpublished and sequestered within pharmaceutical companies, he states in the article 'How do we develop nanopharmaceuticals under open innovation?' (Nanomedicine: Nanotechnology, Biology and Medicine 7, 371–375).

One example of the disconnect can be seen among those academic groups which have developed complex, exotic nanomedicines that are hard to profile in terms of the excretion and metabolism of their constituents. It is impossible to get approval for drugs whose in vivo fate is unknown or impossible to quantify, notes Eaton.

"Expect research and you get research. Expect products and you get products! The peer-review system looks at quality of research, not whether products are likely to come out of it."

Artificial definitions
Part of the problem is that nanotechnology in healthcare remains such a nebulous concept. Many proposed definitions of the sector rely on the sizes of particles in medicines, something which the US Food and Drug Administration (FDA) has also alluded to in its recently-published draft guidance on the application of nanotechnology in regulated products: 'Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology', from June 2011.

The guidance explores the often-used threshold of a 100nm dimension for engineered nanoparticles and whether particle size has an importance in the interaction between nanoscale materials and biological systems.

These artificial definitions have no relevance to industry, however, as it makes little distinction between products based on size, only in the context of clinical efficacy and patient safety, according to the ETPN paper.

That view is backed up by comments submitted to the FDA by the US Consumer Healthcare Products Association, which argues that including nanoscale active ingredients or excipients in a drug product does not by itself determine a product's safety and efficacy. It notes that widely-used techniques in pharmaceutical manufacturing, such as milling, already produce particles in the 1-100nm range, with no evidence that these have different properties.

Political label
"Nano is more of a political label than a scientific one in the present nano-pharmaceutical context," Eaton points out.

Eaton has developed a slightly different definition of nanomedicine using the concept of drug space, rather than one based rather arbitrarily on a specific particle size. He defines them as synthetic entities bigger than biologicals (around 5nm) – a group including, for example, antibody-drug-conjugates and protein-polymer-conjugates – and extending up to regenerative medicines such as therapies based on stem cells, transfected cells and engineered tissues.

While not universally accepted, Eaton's definition is interesting, as it renders nanomedicines as part of a continuum in pharmaceuticals, from small-molecule through biologics and beyond, which would render them subject to the same established safety and efficacy criteria as any other candidate medicines.

That is important, as it could allow nanomedicines to side-step the continually rumbling debate about safety, first emerging in the 1980s when nanotechnology researcher Eric Drexler published a book warning of self-replicating nanorobots that could run out of control – creating what has now become the infamous 'grey goo'.

The safety debate continues. For example, the paper, 'Nanoparticles can hinder intracellular transport', published in August 2011, found that uptake of nanoparticles in the 30-100nm range into cells can disrupt intracellular transport pathways, 'causing undesirable changes in the cell's physiology and disrupting normal cell functioning'.

Eaton believes that there are always concerns with any new technology, but in the particular application of nanotechnology in medicines and diagnostics these concerns are without merit. There are lots of different types of nanoparticles – cellular components such as proteins are nanoparticles, after all – and studies that find toxicity associated with one type based on size alone are not sound science.

"That may not be the case with other sectors such as domestic products like washing powders, but the high level of regulation and requirements to prove safety and efficacy for drugs make it a different situation for nanomedicines."

Nevertheless, the safety debate has meant that companies developing nanomedicines have become almost polarised, with some branding their products as 'nano' while others avoid use of the term altogether.

Reticence
Examples of the former include Celgene (formerly Abraxis BioScience) with its Abraxane nano-pharmaceutical, an albumin-bound form of the anticancer drug paclitaxel, and also Germany's MagForce which uses nanoparticles containing iron oxide to treat solid tumours. MagForce was the first company worldwide to receive European approval for a medical product using nanoparticles. Others are, however, more reticent.

"It's very similar to the situation with genetically-modified foods," Eaton said. "Some companies have tried to avoid the nanotechnology connection altogether for fear of damaging their brands."

Europe has made great strides in preclinical nanomedicine research thanks, in part, to hundreds of millions of euros in central EU funding via the EU Framework Programme six and seven (FP6/7). However, the sector has struggled to convert these into drug development projects and a sizeable chunk of the funding has gone towards nanoparticle safety studies, rather than new nanomedicines.

Culture shock
To improve its competitive advantage in nanomedicine, Europe needs to implement a dedicated, translation-orientated funding programme, to make research in this area more commercially-orientated and advance projects beyond proof-of-concept, the ETPN says. This will 'de-risk' the research and make it more appealing to industry.
That could be achieved under the umbrella of the EU's Horizon 2020 Framework Programme in the form of a public-private-partnership, according to the white paper.
Meanwhile, ETPN recommends establishing a novel translational nanomedicine infrastructure based on federating the existing distributed nanomedicine research and clinical centres of excellence, with a central management facility to "guarantee [the] sustainability and quality of efforts".

That effort will be supported by industrial 'catalysts': industrially-experienced individuals acting as advisers to research projects who should be able to provide guidance on topics such as scalability of production processes.

Full integration
Ultimately, ETPN would like to see a fully-integrated facility for the translation of nanomedicine-based solutions housed under the same roof as the central management office and "perhaps run as a company-orientated business, as Genentech was in its early days".

In addition, change must be implemented from the top down, with industrial and clinical translation experts taking a key role in the development of EU funding programmes.

'This is, in many ways, the hardest issue to resolve, as it requires industry to reveal its wish-lists!' the white paper notes, while academic and clinical groups will need to identify unmet needs that can be met with nanomedicines.

'Universities will look to industry to be funded, but do not actively ask companies – nor clinicians and patients – what they need,' it adds.

Looking to the future, Eaton notes that important translational hurdles for nanomedicine will come as regenerative medicines and therapies based on nucleic acids start to reach the market.

For regenerative medicines, the problems will be logistical as much as technical, relating to transport issues – for instance, live cells or tissues – the cost of goods, maintaining sterility, overcoming injection challenges and separating the therapeutic elements from stabiliser substances and so on. Nucleic acid-based therapies still have a number of barriers to overcome, mainly related to delivery into cells, but once these are mastered, they will form a major new category within nanomedicine.

As the pharmaceutical industry continues to embrace the open innovation concept and places greater emphasis on research partnerships with SMEs and academic groups, drug development expertise and, to an extent, supporting costs are being transferred to those partners."It is vital to improve communication between the stakeholders dramatically if this field is to fulfil its potential," Eaton concludes.


Phil Taylor
The Author

Phil Taylor is a freelance journalist specialising in the pharmaceutical industry

To comment on this article, please use the commenting feature below.

16th November 2011

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