Issue Date: March 17, 2008
FDA Confronts Nanotechnology
AS PRODUCTS made with engineered nanomaterials find their way into the marketplace in greater numbers, the federal agency most responsible for ensuring the safety of these products will be the Food & Drug Administration. From cosmetics to food packaging, and from drug components to implantable devices, FDA is where nanomaterials will have to get approval.
But is FDA ready for this responsibility? Does it even have the legal authority to make judgments on nanomaterials? And are the resources and expertise available to make these assessments?
A search for answers to these questions was the subject of a conference late last month in Washington, D.C, sponsored by the nonprofit Food & Drug Law Institute. In the words of FDLI President and Chief Executive Officer James J. Kelly, "law, regulations, and policy are going to have to take a giant leap if they are to keep up with the pace of nanotechnology development."
FDA knows it faces a daunting task. "Nanoengineered materials may become part of any or all of the products that are regulated by the agency," Norris E. Alderson, associate commissioner for science at FDA, said at the conference. Alderson noted that FDA released a comprehensive policy paper on nanomaterial regulations in July 2007. Prepared by a special FDA task force, the report states the agency's current thinking on nanotechnology and describes the myriad scientific and legal issues facing the agency in trying to regulate products that use nanomaterials.
The science questions related to nanotechnology, as laid out by Alderson, are reflected in concern over understanding the bioavailablity of these very small particles. "How do the changing properties of these materials change the toxicity?" he asked. "We don't even have the standards yet for measuring or detecting these materials."
The FDA report makes several recommendations relating to scientific questions, focusing on improving knowledge about nanotechnology to ensure the agency's regulatory effectiveness. The report stresses the need to evaluate whether the scientific tools available to the agency to describe and evaluate nanoscale materials are sufficient and whether the development of new tools is necessary. Public input and close communication with industry are also recommended as important for the agency to stay abreast of this fast-moving technology.
Alderson and other speakers at the conference noted that a major problem FDA and other regulatory agencies have is that these nanomaterials have different toxicity characteristics than the same chemical composition has in bulk forms. This is changing the paradigm for how toxicity is measured, according to several speakers. For nanomaterials, it is not only the mass of the dose that determines the toxicity, but also probably the surface area of the particles, the particles' surface charges, and even their solubility, the speakers explained.
These differences are not just theoretical, Scott E. McNeil said at the conference. McNeil, director of the Nanotechnology Characterization Laboratory for the National Cancer Institute, said his group is studying nanomaterials that might be used against cancers because of their interesting surface chemistry and the multifunctional capabilities of multiple surface charges on particles.
McNeil added that his lab is working on the characterization of several nanomaterials and is collaborating with researchers at the National Institute for Standards & Technology for information on the physical attributes of these materials. FDA has immediate access to all the data the lab generates, he noted. "This provides an interface at the policy level, where the nanoscience can influence policy decisions," he said.
There is still much to learn about how these nanoparticles react, McNeil said. "It is a daily occurrence in our labs that one of our standard assays doesn't work because of the unusual properties of these materials."
This unusual behavior is one of FDA's concerns because the agency relies on bioassays to determine a product's safety, Alderson said. One of FDA's major questions is about the biocompatibility of nanomaterials and whether the in vitro and in vivo tests the agency relies on will remain valid.
Despite the lack of knowledge about specifics of nanomaterials' actions, the agency is confident that it can effectively determine which products are likely to be safe and which are not. "This is because we regulate the product for safety, not the whole technology," Alderson said.
ALTHOUGH FDA contends it can regulate these products and grow in expertise and ability as the commercial field grows, some are not so sure. "These new scientific challenges are coming along at a time of dire resource constraints at FDA," Michael R. Taylor said at the conference. Taylor is a professor at the George Washington University School of Public Health & Health Services and previously served in several posts at FDA.
"Late last year, a subcommittee of FDA's Science Board issued a scathing report on the state of science at FDA," Taylor said. "It cited a combination of rapidly growing demands on the agency and lack of investment in the agency's basic scientific infrastructure. It concluded that FDA cannot fulfill its mission because its science base is eroded, its staff lacks the needed scientific capacity and capability, and its information technology infrastructure is inadequate."
FDA's Alderson argued that the agency is up to the task of regulating nanomaterials, pointing out that the agency staff is continually going through training to keep them current on the latest science. Building internal and external expertise in nanomaterials was one of the main recommendations in the FDA task force report.
The conference also included much discussion of FDA's legal authority to regulate nanomaterial products and whether additional authority is required. The basic conclusion is that no new laws are needed for the agency to do its job, but some gaps in coverage could cause problems.
"We have some reasonably robust authorities already," said Jeffrey M. Senger, FDA deputy chief counsel. "When FDA determines that a new product is in the nanoscale range, we can require submission of a lot of data, including particle size data for new drugs and biological materials."
This premarket authority applies to new drugs, biological products, devices, and color and food additives under review by FDA. Such products cannot be sold unless they meet specific statutory requirements of safety and effectivity. Agency officials contend that the challenges presented by nanomaterials are similar to those arising from other new technologies FDA has dealt with in the past-for example, products from genetically modified organisms. "We have done this before," Senger commented.
FDA also monitors over-the-counter drug ingredients, and their use is authorized in regulatory monographs, which specify the conditions of ingredients that are used. "We can require that particle size data be included for these [nanomaterial bearing] products as well," Senger said.
Some questions are being raised regarding regulatory authority for the use of nanomaterials in cosmetics and dietary supplements. The agency does not generally receive any safety data on these products before they are marketed, and there are no postmarketing reporting requirements for cosmetics.
"These supplements and cosmetics pose a problem for FDA," said Susan D. Brienza, an attorney in the Denver office of the law firm Patton Boggs LLP. She pointed out that the enormous surface area of nanomaterials means greater absorption by the body and therefore presents a greater risk, even if applied topically as cosmetics are. "The current regulatory scheme for nanotechnology supplements and cosmetics does not provide a solution to the problem. The result is that many people believe that these are not regulated enough," she said.
If a health or safety problem from one of these nanotechnology products ever happened, the effect on marketability would be immediate. "If a safety issue should arise about a marketed nanotech product, the impact on consumer confidence and acceptance of the technology would go well beyond the particular product involved," Taylor said. He suggested that the regulation of cosmetics and supplements is an area where Congress might want to give FDA more authority "so the agency will have the legal tools it needs to get companies to supply information on the safety of their products."
Other federal agencies are also facing up to the regulatory challenges of nanomaterials. James Willis, director of the Chemical Control Division of the Environmental Protection Agency's Office of Pollution Prevention & Toxics, said that the Toxic Substances Control Act, which regulates new chemicals in commerce, does not consider particle size as part of the identification of a chemical entity. This means that producers of nanoscale particles of existing chemicals are not required to file premanufacture notifications. Even so, about 30 manufacturers have submitted to EPA notices for review of new nanomaterials, Willis said.
WORKPLACE EXPOSURE is where many expect health and safety issues involving nanomaterials to first appear. Paul A. Schulte, an epidemiologist at the National Institute of Occupational Safety & Health, said, "NIOSH has field teams out to start trying to assess plant processes and types of exposures. As of now, exposures to bulk nanomaterials appear to be quite low."
Schulte added that NIOSH is concerned about the capability of existing control technologies in plants to remove nanoparticles. "We know we can capture some nanoparticles with conventional control methods, but there may be limits in these controls, and we are doing more research on this," he said.
The public's perception of the safety of products with nanomaterials is going to be key to their commercial acceptance. The experts at the FDLI conference agree that the role FDA plays in this acceptance is very important. There is consensus that FDA has the legal tools it needs to regulate nanotechnology products, but no one yet knows whether the agency is capable of responding to the scientific challenges of this broad technology.
- Chemical & Engineering News
- ISSN 0009-2347
- Copyright © American Chemical Society