by Martin E. Rock, P.E., J.D.
Substances with dimensions less that 100 nm often act quite differently from larger materials with the same chemical or elemental composition. (For reference, a nanometer is one billionth of a meter; a human hair is about 80,000 nm wide.) Nanomaterials are, by definition, designed and produced to have at least one dimension that is 100 nm or less and include an array of engineered materials already in commercial applications as more than 350 nanoproducts are already on the market. Such products range from deodorant to dishwashing liquid and from toothpaste to tanning lotion.
The application of nanotechnology to the life sciences has been termed nanobiotechnology (Mazzola 2005). The very small size and high surface-to-volume ratio of several types of nanomaterials make them ideal candidates for drug delivery (Bianco et al. 2005; Colvin 2003; Hardman 2006; LaVan et al. 2003). The transition from calculating the size of very small objects to manipulating them as needed defines the emerging field of nanotechnology. The things that can be seen and done with nanometer-size objects are the subjects of nanotechnology research and development, and a growing community of researchers is beginning to call themselves nanotechnologists.
By using nanotechnology, fundamental changes in drug production and delivery are expected to affect about half of the $380 billion worldwide drug production in the next decade. Some examples of nanotech applications within the life sciences and pharmaceutical industries include the following:
In addition, nanotechnology is rapidly emerging as an innovative answer to pharmaceutical industry formulation challenges, including:
All of this is good news for cancer therapy. According to Dr. M.C. Roco, head of the National Nanotechnology Initiative, “it’s conceivable that by 2015, our ability to detect and treat tumors in their first year of occurrence might totally eliminate suffering and death from cancer.”
Others claim that nanotechnology will account for over $1 trillion in economic activity with employment for over a million people by the year 2010. While not all of this investment would occur in the life sciences sector, the importance of nanotechnology to the pharma and biotech industries is expected to be an important driver of growth.
The Role of the FDA
The following are issues anticipated by FDA pertaining to nanotechnology development:
FDA has also formed an internal Nanotechnology Task Force. The new task force is charged with determining regulatory approaches that encourage the continued development of innovative, safe and effective FDA-regulated products that use nanotechnology materials. The task force will identify and recommend ways to address any knowledge or policy gaps that exist so as to better enable the agency to evaluate possible adverse health effects from FDA-regulated products that use nanotechnology materials. According to FDA Commissioner Andrew von Eschenbach:
As this exciting new area of science develops, FDA must be positioned to address both health promotion and protection challenges that it may present. Through this task force, we are leveraging our expertise and resources to guide the science and technology in the development of nanotechnology-based applications.
Nanotechnology has been included under FDA’s Critical Path Initiative designed to facilitate review of innovative science and technologies (Sadrieh 2006). The FDA has previously reviewed products containing nanoscale materials, such as sunscreens and cosmetics. Whether a new NM submission is categorized as a drug-device, drug-biologic or device-biologic product will determine which FDA Center will have jurisdiction regarding regulation. General considerations for NM product approval include characterization, safety issues related to specific delivery route (ie. inhalation, dermal, ingestion, injection), and environmental impact.
Environmental Health & Safety Issues
Investigators know relatively little about the hazards people may face if they eat food, breathe air, touch objects, or drink fluids containing nanoparticles. A number of universities are researching these issues. Regulatory agencies such as the Environmental Protection Agency, the Food and Drug Administration and the Occupational Health and Safety Administration are closely examining whether new regulations are needed to guard against “potentially harmful but currently unknown” effects, said Kevin Powers, associate director of the University of Florida, National Science Foundation Particle Engineering Research Center.
The Toxic Substances Control Act (TSCA) is the federal statute presently receiving the most attention by EPA as it considers how best to regulate engineered nanoscale materials. TSCA governs the manufacture of new chemical substances and regulates uses of existing chemical substances that EPA has determined to be “significant new” uses. A “significant new” use of a chemical substance that is already listed on the
TSCA Inventory is treated much like a new chemical substance and the new use is subject to EPA review in much the same way EPA reviews a new chemical.
Nick Katov, associate professor of chemical engineering at the University of Michigan has stated that stable nanocolloids and titanium dioxide “do exist currently in nature. However, we don’t know what their circulation path is and how it is affected by the influx of new materials.” A key question is, “Can they become concentrated in humans or animals?”
The total amount of research on nanotechnology issues is growing very quickly (see figure below) as the torch is being passed from government-sponsored research to corporate and privately funded research for commercial purposes.
Trends in the growth of nanotechnology research at the National Science Foundation (NSF), 1991-2005.
According to the National Nanotechnology Initiative (NNI), the “understanding and control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications,” is expanding rapidly. During the next 5-10 years, the challenges of nanotechnology will increase in new directions. While expectations of nanotechnology may be overestimated in the short term, the long-term implications on healthcare, productivity, and environment appear to be underestimated.
The potential for nanobiotechnology and innovative nanoparticle/drug combinations as medical treatments is certainly exciting. Clearly, those who work in this emerging field should have up-to-date information about related toxicology issues, potential health and safety risks, and the regulatory environment that will impact patient use. Understanding both the benefits and the risks of these new nanotech applications will be essential to good decision-making for drug developers, regulators, and ultimately the consumers and patients who will use this new drug delivery technology.
Martin E. Rock, P.E., J.D., is a registered professional engineer (PE) with an M.S. in Environmental Engineering; he is also a licensed attorney with a Juris Doctor in law. He is a graduate of the University of Michigan (Ann Arbor), College of Engineering and of the Lumpkin School of Law at the University of Georgia (Athens). Rock serves as President & Senior Principal with OMNI Professional Environmental, based in Research Triangle Park, North Carolina. He served as President and Board Chairman of the ISPE Carolina-South Atlantic Chapter during 2006-07, and he has been a member of ISPE for over 10 years.