United States: Risk Mitigation Strategies For Manufacturers Of Nanomaterials

Despite regulatory uncertainties and the lack of safety data, companies are rushing nanomaterials to market in a wide variety of FDA-regulated product categories. A public inventory of products that claim to contain nanomaterials includes products such as foods (including dietary supplements), food packaging and other food contact products, cosmetics, devices and drugs.¹ Food and food contact products listed in the inventory include oils, tea, nutritional and sports supplements, food storage containers, plastic wrap and kitchenware. Some of these products are claimed to help control weight, slow aging, reduce viral loads or destroy bacteria. The inventory includes a number of cosmetic products (77) and sunscreen products (27), as well as products classified as "personal care" products that include toothpaste, wound dressings, pregnancy tests, hearing aids, antiseptic sprays for cuts and scrapes, and pain relief products.

Although products such as foods and cosmetics generally are not subject to premarket approval, political and regulatory pressures may yet be brought to bear on nanotechnology as more information is gathered about possible toxicological, human health, and environmental effects of nanomaterials. This article suggests a number of risk mitigation strategies broadly applicable to the manufacture of all FDA-regulated products that contain nanomaterials.

There has not been a single lawsuit filed where someone claimed injury because they were exposed to engineered nanomaterials. That said, even the threat of litigation can adversely affect a company’s bottom line and its marketability. Large, established companies entering the nanotech field, either as developers or end-users, recognize the value of a good name. If one of their products composed of nanomaterials injures, or even kills, someone, they may suffer losses far greater than the cost of defending the inevitable lawsuit. Startups face different, yet similar, pressures. As many nanotech companies are in fact start-ups, their fate and future success will depend on the perceptions that their customers and potential investors have about the product’s worth and its associated risks.²

But, how real are the risks? Will engineered nanomaterials become the next asbestos, costing companies billions of dollars and resulting in dozens of bankruptcy filings?³ No one can say. However, one thing is clear: the plaintiffs’ bar is already looking for the next asbestos, the next toxic tort. In its search, the plaintiffs’ bar assiduously reads the conclusions drawn by scientists in peer-reviewed papers; it reviews the statements made by regulatory bodies; and it evaluates the steps taken by public interest groups who historically have paved the way for private litigation through oftentimes creative and expansive interpretations of science and law.

Maybe the most significant such event is the recently filed petition by a coalition of environmental Non-Government Organizations (NGO’s), asking the FDA to, among other things, force manufacturers of sunscreens that use nanoparticles to cease production and to recall their products.⁴ The petition discusses at length the possibly increased toxic properties of nanomaterials, citing various scholarly articles and reports.⁵ It is not known how FDA will respond to the petition. The agency currently appears unlikely to categorically curtail emerging uses of nanomaterials, but FDA has acknowledged the potential risks that they pose. FDA formed a Nanotechnology Task Force in 2006 to consider what safety and efficacy data and information the agency should require to review and approve a nanomaterial-containing product, and held a public meeting in October of that year to solicit input. The Task Force then issued a report on July 25, 2007, that acknowledges significant data gaps and potential weaknesses in its regulatory authorities, particularly with respect to products that are not subject to premarket approval.⁶

Whether the petition filed with FDA simply marks the beginning of private lawsuits is unknown. Certainly, if the science on nanomaterials more conclusively raises human health concerns, the risk of litigation increases dramatically.

The principles of products liability and toxic tort litigation are premised on the notion that some risks are acceptable and some are unacceptable; some conduct is appropriate, some conduct is not. Core questions that affect a company’s exposure to a nano tort lawsuit include:

• Has the company designed the product with safety in mind?
• Has the company educated its workers and consumers about known exposure risks?
• Has the company tracked what scientists, regulators and other members of industry are saying and doing about the product’s risk and ways to reduce that risk?
• Has the company itself evaluated, or collaborated with others to evaluate, risks that are still unknown?
• Are the company’s public pronouncements about the risks associated with its products consistent with its own internal evaluations and assessments of its products?
• Has the company taken affirmative steps to implement recommended controls to reduce exposures?
• Has the company taken steps to monitor the health of its workforce and its consumers that are exposed to its product?

If the answer to these questions is "yes," it is less likely that a company’s product will be deemed unreasonably dangerous, that its warnings and instructions will be found deficient, that its products will actually cause harm, or that it will incur punitive damages or be found liable to its workers above and beyond what worker’s compensation laws provide.

These same principles also define what are good product stewardship activities and good risk management strategies in the design and manufacturing of products made with engineered nanomaterials. If a company follows the basic tenets of product stewardship and implements risk management strategies, it will also reduce its liability exposure. The question then becomes what specific risk management strategies should companies implement?

For FDA-regulated products, the thoroughness with which these questions are addressed during product development, production and marketing are likely to depend on the product category. Some product categories, such as new drugs and higher risk medical devices, are subject to premarket approval and relatively stringent postmarket oversight, which helps to ensure that questions of safety associated with a product are comprehensively addressed. For other product categories, such as foods, cosmetics and lower risk devices, FDA regulatory oversight is far more limited.⁷ Nevertheless, for all FDAregulated products, the following risk mitigation strategies should prove to be instructive.

Whatever the product category involved, a company bears the responsibility of ensuring that its FDAregulated product meets the applicable safety standard for its specified use. Even the safety standard applicable to dietary supplements, which arguably is weakest, requires that a product not present a significant or unreasonable risk of illness or injury. Thus, in all cases, the measures that a company implements to control risks should be based on a full appreciation of what the risks are; typically, that information is made available through scientific study. For a new drug, a company will have to conduct extensive studies that ferret out potential risks associated with that particular product. In other contexts, extensive, independent safety research is not required. Complicating things is the fact that the human health effects from exposure to nanomaterials are not yet known, although numerous studies are being published monthly.⁸

Effective product stewardship requires monitoring this scientific literature. There are dozens of peerreviewed articles that address, either directly or indirectly, the environmental, health or safety risks associated with exposure to engineered nanomaterials, and the number of such articles is expanding. To help separate the chaff from the wheat, the "junk" science from the "real" science, companies should find ways of accessing databases that provide state of the art assessments relating to their products. An example might include NIOSH’s Web-based Nanoparticle Information Library.

The theoretical risks associated with nanomaterials relate to what makes nanomaterials different than their macro-sized cousins. Nanomaterials have a much greater surface area per unit mass compared with larger particles of the same chemical composition. Because chemical reactions occur at the surfaces, this means that a given mass of material in nanoparticulate form may be much more reactive than the same mass of material made up of larger particles. However, some studies have shown that modifying the surface of nanomaterials with biocompatible polymers reduces their toxicity in vitro and alters tissue deposition in vivo.⁹

A company interested in minimizing risk should therefore evaluate the feasibility of modifying the surface of nanomaterials if it can be done without altering the utility of the product. In conducting such an evaluation, the company should carefully balance the additional costs incurred by adopting the safer design against the level of risk and likelihood of harm if the design is not altered. Consultation with risk managers, lawyers and scientists is recommended when making those decisions.

Monitoring Products

Once a product enters the market, monitoring any harmful effects on workers and consumers is the best and most direct source of information about the product’s risk profile. Monitoring of adverse events involving consumers is generally required for drugs and devices, and will be required starting next year for dietary supplements when FDA’s rule prescribing industry-specific good manufacturing practices begins to take effect.

For their workers, companies may want to consider generally monitoring employee health to identify trends that may disclose previously undetected risks. At this stage, however, nanospecific monitoring mechanisms may be impractical given the dearth of toxicological and, of course, epidemiological data, by which to spot nano-engendered worker health issues. NIOSH is well aware of these challenges and is working on developing guidance on occupational health surveillance for nanotechnology workers.

FDA-regulated companies should, and in some cases must, have data on acceptable dose levels for consumers. For drugs and higher risk devices, data on acceptable dose levels must be gathered early in their development. For food additives, including food contact substances, such data generally must be included in a food additive petition or food contact notification to establish the conditions of use under which the food additive or food contact substance is safe.

For workers or downstream customers who may be occupationally exposed to nanomaterials, companies typically will not have defined, recognized permissible exposure levels by which to gauge their conduct because very little toxicological information exists about most nanomaterials. Notwithstanding the data gaps, companies will still be expected to reduce exposures for workers, particularly for those higherrisk activities that, based on experiences with other substances (such as asbestos or benzene), are well known and well understood.¹⁰

As for measures that companies should take to reduce exposures generated by these riskier activities, the data gaps again present significant hurdles. Nevertheless, because regulatory bodies and research groups are beginning to provide interim guidance, companies would be wellserved to track what is being said, and seriously consider adopting what is proposed. As just one example, NIOSH has written that, for most processes and jobs, control of airborne exposure to nanomaterials may be accomplished using engineering control techniques used for aerosols. This would include use of a well-designed exhaust ventilation system with high-efficiency particulate air (HEPA) filters, as well as source enclosures.¹¹ Protective clothing, gloves, goggles and respirators may also be required.

Because there are currently no definitive standards for any given type of nanomaterial, companies may also want to consider taking part in any processes to set those standards. Regulatory bodies are inviting such participation and stakeholders are regularly making their opinions known. For example, EPA has begun the first steps in considering development of a voluntary stewardship program, by which companies are asked to implement basic risk management practices and share information with EPA on what those practices are and how effective they are at minimizing risks associated with exposure to nanomaterials.¹² Although this process will take time—upwards of 2-3 years based on current EPA estimates—the EPA could ultimately (or in the interim) implement regulations that require certain controls or designate certain nanomaterials as presenting an unreasonable risk of injury to human health or the environment under the Toxic Control Substances Act (TSCA).¹³

Finally, in its recently issued Nanotechnology Task Force Report, FDA signals that it intends to issue guidance to industry on the types of information on nanomaterials that FDA may expect submission of in the course of its approval processes. Agency representatives have stated that such guidance is expected to issue in a matter of months.

Good manufacturing practice regulations mandate many practices that are geared toward prevention of adulteration, but that have the collateral benefit of enhancing worker safety, thereby helping to reduce a company’s legal liability. These include worker training in the handling of materials, and the provision of adequate handwashing facilities.

Although data gaps prevent a particularized listing of strategies relevant to the nanotechnology manufacturing environment, additional generalized principles are recognized and accepted: Keep work areas clean; avoid dry sweeping or the use of air hoses; prevent food or beverage consumption in workplaces where nanomaterials are being handled; encourage workers to use hand-washing facilities before eating, smoking or leaving the facility; and provide facilities for showers and changing clothes so as to avoid or minimize takehome exposures.

Companies need to evaluate whether (or what) to tell consumers about the presence of nanomaterials in the products they use. Presently, a number of companies appear eager to tout the presence of nanomaterials in their products, and to ascribe benefits to those materials. Other companies may prefer to promote the benefits or functionality of a product without revealing that those benefits or functionality are derived from the use of nanomaterials. The more conservative, risk-mitigating strategy would be to divulge that a product contains nanomaterials.¹⁴ Failure to disclose such information could easily become the basis for legal liability should anyone be (or claim to be) injured by a product that contains nanomaterials. However, FDA’s Nanotechnology Task Force Report suggests that labeling claims regarding the use of nanomaterials could misbrand a product, and recommends that manufacturers consult with FDA with respect to such claims.

As for warnings, not surprisingly, no nano-specific information for hazard communication exists in the literature. That said, NIOSH reported at a recent EPA conference that it had already received some proposals for a warning label, and a Canadian NGO currently has a competition for the design of a "Nano-Hazard Symbol."¹⁵ Such warnings, however, as opposed to mere statements of disclosure, are likely to be counter-productive in the absence of greater risk information. Warnings should only be issued after a company learns that there exists a quantifiable risk, and that the potential harm is actually preventable through the issuance of a warning.

Today there is little known about whether individuals are at risk due to exposures to nanomaterials. Under such circumstances, precedent tells us that industry practices and procedures play a large and important role in whether a company eventually finds itself in trouble when individuals bring claims alleging that a product caused them harm. Thus, a company manufacturing products with nanomaterials should be proactive and vigilant to demonstrate that it is a "good company."

Consistent with applicable regulatory requirements, a company should design its products with safety in mind; employ basic risk management strategies to protect workers, customers and consumers; institute processes by which to monitor any health effects associated with the use of its products; ensure its public announcements about the risks are consistent with its own internal evaluations and assessments; and monitor what is known, what is said, and what is being done, about nanotech risks within the scientific and regulatory communities, as well as within industry.

A company that ensures its awareness of what safety issues are known internally and externally and demonstrates that it is responsive to this knowledge will always have stronger arguments on its side should litigation strike.

1 http://www.nanotechproject.org/index.php?id=44&a ction=advanced (last visited on July 19, 2007).

15 www.etcgroup.org/nanohazard (last visited on July 24, 2007).

This article is presented for informational purposes only and is not intended to constitute legal advice.