STRATEGIC PERSPECTIVES: Tiny particles with big implications: Nanotechnology and the FDA

by | Sep 23, 2014 | Articles, News, Uncategorized

By Danielle H. Capilla, JD, September 23, 2014

Nanomaterials, materials measured in nanometers or approximately one-billionth of a meter, are so small they cannot be seen with a regular microscope. Their tiny size hasn’t stopped the Food and Drug Administration (FDA) from putting them under their microscope, however, as concerns have been raised about their application in all FDA-regulated products including food, drugs, devices, and cosmetics. With different chemical, physical, or biological properties than their typically scaled counterparts, both the industries using nanotechnology and the FDA are taking a long hard look at its applicability and safety.

Nanotechnology potential can be overwhelming in its scope. A 2012 Federal Bureau of Investigation workshop tackling the complex “dual-use” aspect of nanotechnology research led to a report on scientific efforts to use nanoparticles to breach the blood-brain barrier to deliver medicine to diseased parts of the brain. With great clinical potential this effort could also constitute a threat, “for example, it is theorized that ‘aerosol delivery’ of some nano-engineered agent in a ‘crowded indoor space’ could cause serious harm to many people at once.”

Nanotechnology use in food and food packaging has almost infinite potential, including antimicrobial packaging, nano-encapsulation of vitamins and other important nutrients, green packaging, a reduction in pesticide use, nano-barriers to keep oxygen-sensitive food fresh, and bacteria identification and elimination. Nanobarcodes could be created to tag individual food products, leading to enhanced outbreak tracking and detection.

Nanotechnology is at the heart of a new malaria vaccine, which has been traditionally hard to develop due to malaria’s ability to transform itself to avoid immune system detection. Malaria is estimated to have killed 627,000 individuals in 2012. The scientists behind the vaccine are working to get human clinical trial approval from the FDA. Scientists experimenting with gold nanoparticles and cancer treatment found a more effective treatment for hepatocelleular carcinoma by utilizing the gold nanoparticles in conjunction with an antibody and chemotherapy drug.

Nanotechnology emerges

In 2006, the FDA began its foray into the world of nanotechnology by forming a Task Force that 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 identifies and recommends ways to address knowledge and policy gaps so the FDA can evaluate potential health risks from regulated products using nanotechnology. In 2007, the Task Force issued a report that incorporated information from public meetings and public comment. The report, which noted that the FDA’s control was much greater for products requiring premarket approval (drugs, biologicals, medical devices, and food and color additives) than for those that do not require premarket approval (dietary supplements, cosmetics, and food ingredients generally recognized as safe (GRAS)), made recommendations to address regulatory challenges with a focus on challenges relating to products not subject to premarket authorization. In 2008, policy experts at the Project on Emerging Nanotechnologies urged the FDA to issue guidance regarding nanotechnology as it related to food additives and GRAS materials. “Failure by the FDA to issue any guidance for nano food additives leaves the door open to manufacturers to enter the market without FDA clearance, despite having a material with novel properties,” stated David Rejeski, the director of the Project on Emerging Nanotechnologies.

White House response

In 2011, the White House issued a memorandum related to President Obama’s Executive Order 13563 which stated “our regulatory system must protect public health, welfare, safety and our environment while promoting economic growth, innovation, competitiveness, and job creation. It must be based on the best available science.” The memorandum, addressed to the heads of executive departments and agencies on “policy principles for the U.S. decision-making concerning regulation and oversight of applications of nanotechnology and nanomaterial,” stated, among other things, that agencies should continue their science-based approaches subject to rules governing areas of regulatory oversight and existing statutory authority. Furthermore, agencies with regulatory responsibility must “continue to implement sound policies to protect public health, safety, and the environment.” The White House also stated that “nanomaterials should not be deemed or identified as intrinsically benign or harmful in the absence of supporting scientific evidence, and regulatory actions should be based on scientific evidence.”

In the same year, a senior strategist at As You Sow, a shareholder advocacy group, noted that some larger food manufacturers were wary of nanotechnology. Specifically, he found that McDonald’s Corporate Responsibility website stated that the famous Golden Arches were working to understand the technology, but given the uncertainty, did not support its use. Similarly, Kraft stated it did not use nanotechnology although it was exploring its use in food packaging. Pepsi reportedly informed shareholders it was not looking to use or develop nanotechnology in relation to its products.

Current agency approach

In 2013, the FDA released its nanotechnology regulatory science research program to “foster the responsible development of FDA-regulated products that may contain nanomaterials or otherwise involve the application of nanotechnology.” The plan outlines research needs, research categories, and research goals for the agency.

Although pressure mounted on the FDA to provide guidance on nanotechnology, it did not do so until June of 2014 when the agency released four guidances addressing nanotechnology in relation to various products the FDA controls or regulates. The guidances are:

The agency also released two draft guidances that touch on nanotechnology:

Although none of these guidances contain binding standards on the industry, they provide an important look into the agency’s thoughts on nanotechnology. The guidances provide the industry with the two questions the FDA will ask when it determines if a product involves nanotechnology: (1) whether a material or end product is engineered to have at least one external dimension or an internal surface structure in the nanoscale range; and (2) whether a material or end product is engineered to exhibit properties or phenomena, including physical or chemical properties or biological effects, that are attributable to its dimension(s), even if these dimensions fall outside the nanoscale range, up to one micrometer. The term “engineered” is deliberate so the FDA can focus on products that are purposefully designed to have nanoproperties, rather than those that are naturally occurring, which the agency sees as having a greater potential for harm.

The FDA has stated that its current regulatory approach to nanotechnology includes the following attributes:

  • maintaining its product-focused, science-based regulatory policy;
  • respecting variations in legal standards for different product-classes;
  • where premarket review authority exists, incorporating attention to nanomaterials in standing procedures;
  • where statutory authority does not provide for premarket review, encouraging consultation to reduce the risk of unintended harm to humans or animal health; (5) the FDA will continue post-market monitoring;
  • requiring the industry to remain responsible for ensuring that its products meet all legal requirements, including safety standards;
  • collaborating, as appropriate, with domestic and international counterparts on regulatory policy issues; and
  • both for products that are not subject to premarket review and those that are, offering technical advice and guidance, as needed, to help the industry meet its regulatory and statutory obligations.

Generally nanotechnology is seen as an exciting new industry with infinite possibilities, but with them, the potential for risks is equally feasible. Michael Swit, Special Counsel at Duane Morris told Wolters Kluwer that it is vital that companies keep a critical eye on the safety and utility of nanotech products. Furthermore, for products such as cosmetics that lack a premarket approval process, companies should ensure their products undergo robust testing to ensure that another set of “regulators”—plaintiff’s attorneys—don’t have reason to “pounce with fury” if technology turns out to have risks that result in injury.

Adriana Vela, chief executive officer (CEO) of NanoTecNexus told Wolters Kluwer, that although risks exist, it is likely the market will react as they did to Bisphenol A (BPA) and the products will eventually phase out. She also noted that many products on the market today are discovered to be harmful after empirical data and additional testing is done and that risks are not inherent to nano products alone.

Rulemaking on the horizon?

With the FDA’s recent foray into nanotechnology, some might believe this a precursor to the proposed rulemaking. Daniel Kracov, Partner at Arnold & Porter LLP, however, echoed the popular sentiment that the development of rulemaking is unlikely when speaking with Wolters Kluwer. “Rather the FDA’s approach to nanotechnology has been to focus on what is necessary within the context of each product category; …the FDA will apply the relevant existing frameworks to the product and its use.” Similarly, Swit stated that when looking back at the FDA’s approach to biotechnology in the 1980s, the agency did not pursue a rulemaking process. instead, it fit the products into the existing framework. “There is no reason to question that nanotech products can’t be approached the same way,” he added.

Adopting nanotechnology

Swit had five pieces of advice for companies interested in adopting nanotechnology to mitigate risks. First, he suggested, “know your science better than anyone else.” Second, he suggested seeking help through the FDA and others who have undergone nanotechnology testing. Third, “assume that you will eventually have to explain what you did in developing a nanotech product to a jury in litigation in which you are a defendant and assess what you have done from the perspective of would you be fully comfortable reading about what you did on the front page of The Washington Post.” Fourth, he recommended always challenging what you are doing to ensure if it is good enough. Finally, he recommended that companies assume that a nanotech version of a product will function differently than the conventional version, and the typical approaches to testing might not work.

Similarly, Kracov provided three steps to manufacturers planning on adopting nanotechnology. First, he suggested fully understanding the nature of the available regulatory pathways, including the standards and processes that are applicable to the product. This includes looking to previous FDA guidance on the testing requirements. Second, he recommended conducting an initial assessment of the risks, to the extent possible, “and form a basis for resolving key questions relating to physiochemical properties, toxicology, and environmental effects.” This will answer questions about whether the necessary basic data has been compiled, and whether or not a draft development plan that incorporates relevant studies, Kracov explained. Finally, like Swit, Kracov suggested determining whether it would be prudent to interact with the FDA to discuss the development program for the product. This also will allow a company to determine whether it is prepared to have that interaction in a manner that will allow the FDA to understand the product plans and provide concrete feedback. Kracov emphasized that companies should avoid providing the FDA with open-ended questions, and added that “the better approach is to both frame the questions and present what you believe are the most appropriate—but hopefully, the least burdensome—methods for answering key regulatory questions and meeting applicable standards for putting the product on the market.”

Further encouragement to work with the FDA came from Vela, of NanoTecNexus, who suggested that companies “engage with the appropriate agencies and resources early on to gain a better understanding of the process and factors that need to be taken into consideration related to the product development cycle.”

Finally, Swit noted that companies engaging in nanotechnology should be cautious about nanotechnology changing the inherent definition of a product. “It is possible that a change to nanoscale might take a product such as hyaluronic acid—which is typically regarded as inert and, therefore, while it looks like a drug, is regulated as a medical device for most uses—and so change its properties that it becomes active in the chemical sense so that it is no longer a device under the federal Food, Drug and Cosmetic Act, but now meets the definition of a drug.” This issue, according to Swit, is best dealt with by early meetings with the FDA to address these concerns.

Conclusion

Nanotechnology has great potential in a multitude of uses—medicine, food, cosmetics, and devices. The potential for good also comes with great risks, both clinically and socially if nanoparticles are misused. Vela, of NanoTecNexus, noted “It is widely recognized that nanotechnologies have the potential to address many of society’s problems from medicine to clean drinkable water to energy. To achieve this we need more scientific knowledge and not innovation blockers if they are predominately fear-based and not scientific-based. It is our hope that the community at large does not lose sight of this and that responsible approaches are taken by both the industry and the scientific community as well as within groups and agencies driving policy and regulation.” Furthermore, Kracov noted that “there are already marketed drugs and medical devices incorporating nanotechnology that clearly produce a benefit that outweighs risks.” With this in mind, manufacturers would be prudent to go forward hand in hand with the FDA and other regulatory bodies to ensure the strongest level of safety and efficacy, while the community should remain aware of nanotechnology’s vast potential risks and benefits.

Attorneys: Michael Swit (Duane Morris); Daniel Kracov (Arnold & Porter LLP)

Companies: NanoTecNexus

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