Sizing up the potential of nanotechnology: technology advances create opportunity for revolutionary medical applications, but not without some challenges.
Nanotechnology involves working with small particles at the molecular level--a nanometer is equal to one billionth of a meter. For scale purposes, a human hair is about 80,000 nanometers wide.
The concept of nanotechnology was introduced in 1959 by Nobel Prize-winning American physicist Richard Feynman, when he gave a famous talk ("There's Plenty of Room at the Bottom") on the subject. Fast forward a couple of decades to Eric Drexler, who, in the 1980s, explored his ideas on molecular manufacturing pertaining to machines building other machines down to a molecular level. From there, various industries took increased notice--including the medical device community.
"When it comes to materials science, nanotechnology of sorts has existed for some time--it just wasn't recognized as nanotechnology," said Simon Grant, a business development manager for Sandvik Materials Technology, based in Sweden. "In the '80s we started to better define nanotechnology, and we saw many possible applications within materials science--so it is within materials and surface coatings where much of the medical device nanotechnology occurs today."
According to research from the FDA, nanotechnology has been developing rapidly in recent years. In 1990, approximately 1,000 scientific publications on nanotechnology were published and approximately 200 patent applications were filed globally. By 2002, the number of publications had risen to more than 22,000, and the number of patent applications exceeded 1,900.
Lux Research found that governments, corporations and venture capitalists globally spent $12.4 billion in 2006 on research and development related to nanotechnology, a 30% increase from the year before. And growth will continue over the next decade. Overall, the market for nanotechnology is forecasted to increase 17.5% annually, reaching $53 billion by 2011, according to data from The Freedonia Group. Five years after that, the market will more than double in size. Within this market, the medical devices and supplies segment incorporating nanomaterials and technology is predicted to grow from $400 million in 2006 to $5.2 billion in 2011, reaching $16.2 billion by 2016.
According to data from the Woodrow Wilson International Center for Scholars (located in Washington, DC), at least 138 universities and government laboratories are working on some aspect of this technology today. They are doing so with good reason. Already in use in a variety of consumer applications such as nutraceuticads, textiles and cosmetics, nanotechnology is expected to play a greater role in medical areas such as surgery, implant technology, molecular imaging, biosensors, drug delivery and a variety of other applications. In these capacities, nanotechnology is expected to offer novel methods for preventing, diagnosing and treating a wide range of diseases.
The Nano-lnnovation Invasion
Many medical device companies already are jumping on the nano-bandwagon. For example, orthopedic giant Smith & Nephew (London, United Kingdom), whose wound dressing Acticoat uses nanocrystalline silver, recently joined the Nanocode Initiative, an international project launched in July by the Nanotechnology Industries Association, the Royal Society, Insight Investment and the Nanotechnology Knowledge Transfer Network. The working group will develop a code of conduct for businesses that are involved in emerging innovations featuring nanotechnology.
Most experts agree that in the device industry, the most prevalent uses of nanotechnology in the next few years will be in coatings and surface treatments. For example, the past few years have seen vast improvements in dental implants--particularly in surface treatments that promote bone adhesion as well as coatings that help inhibit infection--thanks to nanotechnology.
The desire for advances in medicalgrade materials also has led to a surge of interest from companies looking to improve device properties. Nanoscale materials often have properties that differ from those of their larger counterparts, with differences ranging from altered magnetic properties, altered electrical or optical activity, increased structural integrity or altered chemical or biological activity. With nanotechnology, new classes of materials can be made lighter, stronger and more precise than what's ever been introduced to the market.
Foster-Miller, a Waltham, MA-based engineering firm that works with a variety of medical device clients, has been exploring nanotechnology development within its materials division for more than five years. For example, the company has been looking to nanomaterials such as nanostructured clays and carbon nanotubes to help improve physical properties of existing materials.
"Right now, nanotechnology is being used in polymers and other materials,"said Bob Andrews, medical division manager for the commercial business at Foster-Miller." What you see coming out now are better solutions using nanotechnology for existing applications."
Sandvik Materials Technology, a developer of advanced alloys and ceramic materials, similarly is a leader within nanotechnology advancement for materials. The company's Nanoflex material incorporates nanotechnology to produce an alloy that is both tough and hard--two normally opposing characteristics, according to Grant. He said his company achieved this by altering structures at the nano level to create an alloy "reinforced" by very small and very hard quasicrystalline nanoparticles.
"As a result, Sandvik Nanoflex is formable but can be heat treated to reach high tensile strength and hardness--this makes it ideal for some medical applications such as surgical needles, drills and reamers," Grant said.
Along with materials and coatings developments, drug delivery is another burgeoning area in which nanotechnology is being incorporated, as it offers new ways to gain access to previously unreachable areas of the body--in fact, studies have shown that some forms of nanotechnology are capable of passing through the blood-brain barrier. Some manufacturers are developing pumps the size of molecules that could be implanted to deliver medications to cells and tissues precisely where they are needed.
"[In the] long term, there is considerable potential," Grant said. "Drexler's work raised the possibility of 'nanobots' working in vivo to repair the human body. This is some ways away, but we already see companies working with nanotechnology based targeted drug-delivery systems targeting tumor cells."
Also of interest in the medical community is the "lab on a chip" concept--that is, nano-size implants containing sensors or diagnostic tracers that, for example, can help medical professionals evaluate bone adhesion in and around an implant and report to the physician what's going on inside the body, or help evaluate how body tissue is reacting to a certain medication the patient is taking. These sensors could be available for use as soon as within the next five years, according to experts who spoke with MPO.
Complementing in vitro diagnostic efforts is medical imaging, which has the potential to transcend its current capabilities by employing nanoparticles, especially as R&D efforts in molecular imaging expand. Several companies currently are exploring (if not already developing) the use of nanotracers that can attach to different types of cells. The goal is to identify cellular problems at the earliest stage possible to precisely determine the optimal patient treatment.
"You now have the ability to miniaturize medical devices," Andrews explained. "For example, you could use a biopsy tool to sample tissue to determine whether the cells are benign or cancerous, and if cancerous, the treatment method might change from total removal of an organ or cells or chemotherapy to delivery of nanoparticles to treat the specific cancer."
Where is nanotechnology heading in the device sector? Even the experts are unsure at this point. One promising development cited by David Rejeski, director of the Woodrow Wilson Center's Foresight and Governance Project and Project on Emerging Nanotechnologies, is scaffolding--lattice material composed of nanomaterials--that could help nerve cells regenerate. "It's had some amazing impacts on tests conducted on mice by Dr. Samuel Stupp at Northwestern University," he noted. In mice, researchers severed the spinal cord and injected this material, and the mice begun to regain leg movement within a few days. "This could have a huge impact on people with spinal injuries," Rejeski added. He estimated that this technology could be available within the next five to 10 years.
"Everyone is waiting to see a killer application using nanotechnology, and I think that's going to happen in the device sector first," Rejeski concluded. "Nanotech applications on the market now--from wrinkle-free pants to better tennis rackets--don't strike most consumers as big breakthroughs, but if we can get someone who lost control of their legs to walk again, that's beyond exciting."
Navigating the Issues With Nanotechnology
As might be expected with any new technology, nanoparticles don't come without some challenges that medical device manufacturers must be aware of if interested in using this technology.
"When it comes ... to 'active' nanotechnology-based devices such as nanobots, in the future, the ethical, clinical and regulatory challenges will be complex and many," Grant cautioned.
Echoing his concern is John Monica, a partner with the Washington, DC law firm of Porter Wright Morris & Arthur LLP. Monica, who has been practicing product liability law for more than 15 years, is an industry expert on the topic whose interest was piqued a few years ago after reading materials discussing undetermined toxicology issues related to certain nanomaterials.
"What made me interested was that you see so many industries taken over by plaintiff interests," he explained."You start wondering, what would we have done differently in the legal defense community had we known more from the outset and had a clean slate? That's what intrigued me about nanotechnology."
What may work on a larger scale might react differently in the body at the nano scale, scientists have found. In addition, nanoparticles have the potential to accumulate in organs, creating a risk of toxicity over time.
"These nanoparticles could be longterm sites for growth for what's not desirable in the body," Andrews said.
With nanotechnology, companies are engineering "new forms of old matter" on a biological scale, Rejeski said, and it's not clear how these novel properties will affect humans and the environment. "One of the major concerns is, how will these particles move around in the body? The ability of nanoparticles to move across the bloodbrain barrier can be an advantage for the delivery of drugs or imaging agents, but it might have some unintended consequences, too, he explained.
Three years ago, the Woodrow Wilson Center received a grant from the Pew Charitable Trusts to examine emerging issues with nanotechnology. "The goal of our project is to make sure we can maximize the benefits of nanotechnologies and minimize the risks. That said, it's not an easy thing to do," Rejeski said.
"The federal government currently has allocated $1.4 billion to research this technology, but only around one percent, according to our calculations, is being dedicated to highly targeted research on the environmental, health and safety risks associated with nanotechnologies," Rejeski continued. "This simply is not enough and some agencies, like the FDA, are under-resourced, though they have a key role to play in the commercialization of innovations in the drug and device areas."
Recognizing the growing use of nanotechnology in cosmetics, food and, yes, medical products, in August 2006, the EDA announced the formation of an internal FDA Nanotechnology Task Force to will help determine regulatory approaches regarding products using nanotechnology materials. The agency released a report in July noting that nanoscale materials present regulatory challenges similar to those posed by products using other emerging technologies. However, these challenges may be magnified because nanotechnology can be used in, or to make, any FDA-regulated product and because, at this scale, properties of a material relevant to the safety and (as applicable) effectiveness of FDA-regulated products might change repeatedly as size enters into or varies within the nanoscale range. Furthermore, the emerging and uncertain nature of the science and potential for rapid development of applications for FDA-regulated products highlight the need for timely development of a transparent, consistent and predictable regulatory pathway.
The task force's initial recommendations relating to scientific issues focus on improving scientific knowledge of nanotechnology to help ensure the agency's regulatory effectiveness, particularly with regard to products not subject to premarket authorization requirements. The report also addresses the need to evaluate whether the tools available to describe and evaluate nanoscale materials are sufficient, and the development of additional tools where necessary.
Given the nature of nanotechnology-fortified products, they tend to span regulatory boundaries and, thus, often fall into the "combination products" category at present. Since the FDA regulates products--not technology--the stage at which the agency gets involved in regulating nanotechnology can vary. And since the agency only regulates claims made about a product, if no nanotechnology claims are made regarding the manufacture or performance of a product, the agency may not even know that nanotechnology was used, according to one article on the FDA's Web site.
In the FDA's report (which followed a public meeting held last October on the subject), the agency acknowledged that the general setup of clinical trials is a strength for the device industry as it moves forward into this newer scientific realm. Public perception will play a large role in shaping times to come, however.
The Woodrow Wilson Center has performed various public opinion polls on the topic and found that"the public still remains largely ignorant of nanotechnology, even though the government is paying considerable attention to it. How the public learns about nanotechnology, from whom and with what message will be critical to public acceptance. Unfortunately, many manufacturers aren't discussing their use of it, either," Rejeski reported.
"The public doesn't have enough knowledge to differentiate between nanotechnology in a drug, food or device. If there's some carelessness and there's bad press about nanotechnology, it could have a spillover effect on a wide range of products and industry sectors," Rejeski asserted.
Although medical devices are well regulated by the FDA, certain loopholes exist at present for regulation of nano-reinforced materials and surfaces. The FDA currently appears to be taking a wait-and-see approach to let more long-term results from the scientific community emerge.
"The FDA is still in the information-gathering mode. I think they have a good handle on it and I'm confident they can fill any gaps," Monica said. However, he also is studying how other FDA-monitored industries are using nanotechnology, since any problems that arise could have an impact on the public's perception of this new technology. For example, he said, "If you have an adverse incident in an areas like cosmetics, how will that affect public perception in more highly regulated areas? People may not be able to differentiate what happens in those areas and the medical device area," he explained.
"The public doesn't differentiate much between nanotechnology in a drug, food or device. If there's some carelessness and there's bad press about nanotechnology, it could have a spillover effect on all industries," Rejeski asserted.
From a litigation perspective, Monica believes any problems in consumer-oriented industries could pave a path spawning litigation over devices incorporating nanotechnology. "There's enough out there in general literature that can be seized and twisted to make it look like all nanoparticles may be dangerous," Monica said. "Plaintiffs' attorneys could take unrelated information and try to twist it for their own purposes."
With myriad issues to consider with using the technology, there's one other potential barrier: cost. Novel technologies often command a higher price tag, at least in the initial stages of introduction.
"With plastics [for example], you can be spending $20 to $30 dollars or more per pound for nanocomposite material. It's not a slam dunk that you may use nanomaterials in every application because the cost may be driven up. Therefore, I don't think it will be a commodity product in the near term," Andrews said.
Moving Forward With Nano-Initiatives?
With so many issues still not quite resolved, medical device manufacturers would be wise to temper their innovation with careful monitoring of the development and marketing process to be sure they are doing whatever possible to anticipate any type of backlash that could arise as nanostructures gain ground in device ideations. Monica advised medtech firms to perform extensive literature surveys (or hire an expert consultant to do so) regarding environmental health and safely issues with nanotechnology. (A good start is a visit to Rice University's Web site, http://icon.rice.edu/virtualjournal.cfm, which contains a database of most of the studies to date on this technology.) Companies also should stay abreast of the FDA's activities regarding the technology. Finally, although this is a tenet of any good medical device manufacturing operation, firms must be especially diligent about maintaining proper documentation.
Rejeski also believes that manufacturers probably need different types of "talent" in their staff, since nanotechnology falls into the intersection of organic and inorganic science. "It will require some tweaking of scientific and engineering staff. More expertise will be needed, especially with fabrication of these materials," he said.
Andrews of Foster-Miller also believes that in addition to tightly controlling the manufacturing process with this new technology, manufacturers also may find a need to isolate the production of products employing nanoparticles. "When working with pharmaceuticals, rooms are dedicated to use with specific compounds to prevent potential cross contamination of compounds used in future programs," he said. Therefore, device manufacturers may find themselves devoting an isolated space for working with nanocompounds.
"Obviously this industry is newer and not as mature as the pharmaceutical industry, but this could be a trend [in device manufacturing] in the future," he said. "Imagine if you got a compound in the vent and then it expelled later on when you're making something else. That could be catastrophic."
The lack of industry-standardized specifications for nanotechnology could present some challenges for device manufacturers taking the leap into this field, Monica said. "If you go to two companies that manufacture titanium nanospheres [for example], you might get two different qualities--there's no conforming standard for what you'll get," he explained. "The companies who end up with the purest product and who can market it as being 'pure' will be successful and the market will embrace that. And the companies using the technology Hill have to have the ability to analyze what they're getting to make sure it's up to their needs."
To that end, communication with the supplier is critical. Monica advises that OEMs fully disclose the intended use for the nanospheres, as the supplier may offer insight and recommendations that could help protect the OEM from future liability and ensure that the technology is being employed properly.
Jennifer Whitney, Editor
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|Title Annotation:||Advances in Nanotechnology|
|Publication:||Medical Product Outsourcing|
|Date:||Sep 1, 2007|
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