Big Concerns for Small Technology

29 March 2009 (Last Updated March 29th, 2009 18:30)

Although a potential goldmine for the future of medicine, nanotechnology is still not fully understood by many. Richard Moore of the Institute of Nanotechnology shares his thoughts with Lorrie Kelly on the future of nanomaterials within medicine and how regulations must evolve as innovation continues.

Big Concerns for Small Technology

Nanotechnology has captured our imaginations and many believe it holds the potential to revolutionise our lives, particularly in medicine. However, a recent report, "Novel Materials in the Environment: The case of nanotechnology" by the Royal Commission on Environmental Pollution (RCEP), warned that not enough research has been done to fully understand nanomaterials and how they interact with the environment.

At first glance, the report may seem a scathing commentary on nanotechnology and the regulatory agencies' ability to monitor its use in products and materials. However, the Institute of Nanotechnology's Richard Moore believes the report offers a balanced view that considers usefulness and the potential for harm.

"There is insufficient knowledge about nanomaterials properties and interactions, as well as the properties that you can get at the nanoscale."

"I think the Royal Commission's report recognises that there is a great deal of societal benefit to be gained from nanotechnology," says Moore.

"Where it may appear negative – and I think they are making a good point – is that we're talking about emerging technologies, where the rate of innovation and development may often exceed the ability of traditional governance models to keep up.

"The Commission has obviously looked at a number of factors, such as the knowledge gap in terms of understanding nanomaterials. There is insufficient knowledge about nanomaterials properties and interactions, as well as the properties that you can get at the nanoscale."

One example used by the RCEP noted that gold, in its bulk form, is inert. But at the nanoscale, gold becomes highly excitable. At present, the classification of nanomaterials is generic: anything that is 1–100nm on a one, two or three-dimensional scale. This method of classification completely ignores the function or interaction of such substances.

The report identified three primary areas of concern regarding governance and regulation of nanomaterials:

  • Profound ignorance and uncertainty about the behaviour of some types of nanomaterial in the environment and/or the risks that they pose for human health
  • The nanoform of an element or material may have significantly different properties to its bulk form
  • In the longer term, concern that more sophisticated third and fourth-generation nanoproducts may represent a further step change in functionalities and properties, which would be even more difficult to capture in a regulatory system primarily focused on bulk chemical properties.

Insufficient information and regulation concerns

According to Moore, it is the lack of knowledge on how nanomaterials interact in terms of toxicology that causes greatest concern. Well-established guidelines such as REACH legislation deal with substances on a bulk level and may be insufficient for regulating nanomaterials. "I think the Commission has come to the conclusion that we need to extend the range of scientific and technical methodologies currently being used to assess risk and toxicology, in order for legislation such as REACH to able to cover future developments in nanomaterials," he explains.

In the medical technology sector, Moore believes there is no reason why European directives couldn't be applied to nanomaterials. Similarly, pharmaceutical regulations could be expanded to incorporate these novel materials, especially since drug delivery systems will be a huge area of development.

"It is the lack of knowledge on how nanomaterials interact in terms of toxicology that causes greatest concern."

"Neither of those directives was written at a time when there was much knowledge about nanotechnology at all, let alone the range of materials we have now," he says. "The supporting methodologies underlying those directives are based on addressing risks. But those methodologies need to be extended to take into account the range of novel hazards that materials present at the nanoscale, together with their associated risks.

It is not a case of existing regulations not being able to deal with nanomaterials. Some additional tools need to be developed to enable them to address nanotechnology. It is about knowledge of the functionality, properties and characterisation of materials – what they are intended to be used for.

It is also important to look at what combinations of the main characteristics are likely to result in hazards and risks. A lot more work and research is needed to develop that kind of methodology, as the commission's report appears to have concluded.

Innovation requires workers

The report also recognises that existing regulatory structures and processes have the potential to stifle innovation, delaying life-saving devices and treatments for years while research data is gathered. "What kept jumping out at me throughout the report was that they are looking towards a system of adaptive governance; something that does not necessarily inhibit innovation or deal with things simply because they are nanoscale," says Moore.

"Looking at these materials in terms of functionality – what they actually do in the body or the environment – and then having quick-response regulation that can jump in if problems are identified at an early stage, is the ultimate goal. There's a lack of flexibility.

"If, for instance, you were to take a contrast imaging agent made from nanomaterials, it could take one of two paths to market. The contrast agent could fall under the Medical Device Directive which is a fairly quick route to market with a risk management-based process. People would be expected to characterise the materials, characterise the intended use and identify all the potential hazards that could arise from the use of that material. That could include new problems that arise because some of the materials may be nanoscale. From that, determine the likelihood of harm occurring, in order to formulate ways of reducing or mitigating the risk. This will be an essential part of the product development.

"Existing regulatory structures and processes have the potential to stifle innovation, delaying life-saving devices and treatments for years while research data is gathered."

"If the contrast agent went under a different regulatory regime, for instance, if some of these particles functionalise with antibodies, then the product might fall under pharmaceutical directives. Then you would have a more rigid type of regulation which will probably mean up to 12 years to market because of the preclinical trials and stages of clinical testing required. None of that would necessarily have been construed originally with knowledge of a nanoscale in mind. So there could be a long lead time to market. This points to the need for adapting or complementing regulations."

To complicate matters further, expansion of regulation and governance are likely to be hindered in the immediate future due to lack of qualified and skilled workers. Toxicology enrolment alone has been on the decline for a number of years. This means that companies seeking to implement nanomaterials in their novel product lines will need to recruit and train people to help with monitoring and development.

"Not only is there a shortage of toxicologists but also the whole paradigm of how you do toxicology is changing because you get different properties in nanomaterials than you do in bulk materials," says Moore. "There is a need to extend toxicology to cover the different ranges of properties, and the characteristics that impact toxicity that you get in those materials."

Material risks

Disposal of nanomaterials has been a cause for serious concern, especially in the wake of research findings that show materials such as some carbon nanotubes can pose health risks on a par with asbestos. Regulation of "end-of-life" practices is almost nonexistent in some industry sectors and Moore believes "entire lifecycle" regulations are needed across the board to help minimise risk.

"For example, wound dressing may have nanoparticulate silver in it," he says. "If you do a risk assessment on that, it's not just meant to apply to the manufacturing and point of use but covers the disposal of that product at end-of-life. In theory, risk management is based across the whole lifecycle of the product. But I think more supporting technologies and approaches may be needed for disposal aspects. There is certainly some regulatory development to be done, so that regulation applies from cradle to grave: from inception/concept through to disposal/end-of-life," says Moore.

"Some regulations could probably be adapted to cover specific products. But some other products are probably governed just by end-of-life. The WEEE directive will deal with disposal and has been concerned with nanoparticulate materials. There is a need for supporting risk management methodology to underpin all of that."

A functional nano future

Despite the unknown hazards and risks associated with nanotechnology, the development of nanomaterials in the medical devices sector is both central and crucial to industry's advancement. "Right across the board, whether it is in the development of new types of materials, properties, membranes, or diagnostics, and moving towards in vivo diagnostics and bio-sensing, you are talking about functionalising all sorts of materials at the nanoscale because they are interacting with biological molecules at the nanoscale," says Moore.

"Companies seeking to implement nanomaterials in their novel product lines will need to recruit and train people to help with monitoring and development."

There will be whole ranges of new types of sensing. For instance, a diagnosis will be able to pick out individual molecules and identify early markers for cancer and other diseases. When it comes to therapy and drug delivery systems, there are a couple of dozen nanoscale delivery systems available. It may be possible to use a lesser quantity of a drug, less toxic doses of drugs, more accurately targeted in the body – perhaps activated when they reach their site. These developments would have considerable medical benefits.

"Drugs, devices, diagnostics, biosensing – the implications run right across the whole range of medicine," says Moore. "The progression of disease and understanding that progression is all about what happens at a molecular level; knowledge that is handled by nanotechnology and nanoscale solutions, which will form a multi-billion-pound market in the next ten to 15 years.

"I think there's a chance that nanotechnology can move forward in a controlled way because the medical device industry is based on the idea that the risks and hazard of a product have to be characterised before you put something to market. You have to go through a process of risk management; controlling risks, documenting what you've done and so forth. If you are developing a product that is based on nanomaterials you cannot avoid this process."

The real challenge is that some of these materials have such novel properties and there is going to be quite a bit of characterisation and research to determine what these new hazards are at the nanoscale. Determining what risk is involved and how that can be controlled is a challenge. But the basic framework is there, at least in the medical device sector.