Nanoscale technologies and their resultant innovations have long captured the imaginations of scientists and inventors, the scrutiny of regulators, and the apprehension of nongovernmental organizations and consumer watchdogs. Over the past decade or so, however, a compelling case can be made that the scientific and regulatory communities have done a credible job of allaying these initial concerns and thus can claim victory over nay-sayers who portended global calamity occasioned by the commercialization of nano-enabled products.
October 03, 2019 Feature
Nanotechnology and Regulatory Certainty Closer Now Than Ever
By Lynn L. Bergeson and Carla N. Hutton
In the United States, the U.S. Environmental Protection Agency (EPA) is responsible for regulating chemical substances, including nanoscale substances, under the Toxic Substances Control Act (TSCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).1 The U.S. Food and Drug Administration (FDA) is responsible for regulating ingredients, including nanomaterials, in food, drugs, cosmetics, and related products. The core regulatory paradigms that have evolved over decades under these federal laws and calibrated to bulk materials have proved to be durable and effective in their application to nanoscale materials, despite the unique properties derivative of the nanoscale, such as stronger magnetic properties, improved conduction of heat or electricity, or better light reflection.2
This article provides an overview of how EPA and FDA are using their existing authorities (prudently and proactively) to ensure that nanomaterials do not pose a risk to human health and the environment.
TSCA
On June 22, 2016, President Obama signed the Frank R. Lautenberg Chemical Safety for the 21st Century Act (Lautenberg Act), and in so doing significantly revised TSCA for the first time since its enactment in 1976.3 Although the new TSCA dramatically changes how EPA evaluates and manages industrial chemicals, including nanoscale chemicals, the absence of words or phrases such as “nano” or “nanoscale” materials in the law means that there are no specific or additional requirements that apply explicitly to such materials. This was a significant shift from many of the earlier TSCA reform bills, which explicitly addressed nanoscale materials by proposing new definitions such as “substance characteristics” and “special substance characteristics” that included concepts such as size or size distribution, shape, surface structure, and reactivity. The new TSCA is noticeably silent on this subject and does not distinguish nanoscale materials or treat such materials differently from the other chemical substances regulated under TSCA. This relatively recent congressional action is a compelling statement that TSCA’s fundamental approach to defining and regulating unreasonable risk, honed over four decades, is equally applicable to conventional and nanoscale chemical substances.
Because new chemicals are subject to additional requirements under new TSCA section 5, an important task for chemical manufacturers, importers, and processors, including nanoscale chemical manufacturers, is identifying new chemical substances prior to its commercial activity. This has been an especially tricky area for the nano community, and the Lautenberg Act makes the new chemical review process much more demanding than under old TSCA. EPA’s prior development of a comprehensive section 5 new chemical review process for nanoscale chemicals under TSCA pre-Lautenberg had served the nano community well, and noticeably, the new law’s implementation has not materially impacted the commercialization of new nanomaterials.
In this regard, in January 2008, EPA published a document outlining its approach to determining whether a nanoscale substance is a new chemical for the purposes of TSCA section 5 Inventory requirements.4 EPA refers to TSCA section 3(2)(A), which defines a chemical substance as “any organic or inorganic substance of a particular molecular identity.” EPA states that for the purposes of the TSCA Inventory, it historically has not used particle size to distinguish chemical substances that have the same molecular identity. Thus, the nanoscale form of an existing chemical substance would also be considered an existing chemical substance. EPA has continued to apply this approach—using molecular identity rather than particle size—to determine whether a nanoscale chemical is an existing or a new chemical.
Since January 2005, EPA has received and reviewed more than 220 new chemical notices for nanoscale materials such as fullerenes, quantum dots, and carbon nanotubes.5 EPA has taken actions intended to control and limit exposure, including limiting the use of the nanoscale material; requiring the use of personal protective equipment and engineering controls; limiting environmental releases; and requiring testing to generate health and environmental effects data.
Under old TSCA, if EPA did not respond to a premanufacture notification (PMN) and take action within ninety days, a company could submit a notice of commencement and begin manufacture, processing, or import. New TSCA section 5(a)(3) requires EPA to review PMNs, make one of three affirmative “determinations,” and take the appropriate action depending upon the determination. EPA’s review may not consider costs or other nonrisk factors in determining that the new chemical presents an unreasonable risk. New TSCA also requires EPA to consider unreasonable risks to potentially exposed or susceptible subpopulations that are identified as relevant by EPA under the conditions of use in making determinations under section 5(a)(3)(A) and (C).
On January 12, 2017, EPA promulgated a final TSCA section 8(a) rule imposing reporting and recordkeeping requirements for certain chemical substances when they are manufactured or processed at the nanoscale.6 The rule excludes from the reporting requirement chemical substances manufactured at the nanoscale as part of a film on a surface; certain biological materials such as DNA, RNA, proteins, enzymes, lipids, carbohydrates, peptides, liposomes, antibodies, viruses, and microorganisms; and chemical substances that dissociate completely in water to form ions that are smaller than one nanometer. The final rule also requires manufacturers, importers, and processors to report the specific chemical identity, actual or anticipated production volume, methods of manufacture and processing, use, exposure and release information, and existing data concerning environmental and health effects. The rule imposes a one-time reporting requirement for discrete forms of existing chemical nanoscale materials manufactured or processed any time prior to May 12, 2017, the effective date of the final rule. It also imposes a reporting requirement for new discrete forms of existing chemical nanoscale materials 135 days before they are manufactured or processed. According to EPA, the information will facilitate evaluation of the nanomaterials and a determination of whether further action, including additional information collection, is needed.
FIFRA
Under FIFRA, EPA regulates the distribution, sale, and use of pesticides. This includes reviewing pesticide registrations to ensure that a pesticide product “will not generally cause unreasonable adverse effects on the environment.”7 The use of modern technologies could pose less risk to human health and the environment than conventional pesticides.8 Emerging technologies, such as nanotechnology, biotechnology, and synthetic biology, can be used in more targeted ways, reducing the use and cumulative impact of more conventional pesticides.
EPA acknowledged the potential benefits of nanoscale materials in its June 2011 proposed policy statement describing two possible approaches to obtain information about nanoscale materials used in registered pesticide products.9 Under the first approach, EPA would use FIFRA section 6(a)(2) to obtain information regarding nanoscale materials present in registered pesticide products and their potential effects on humans or the environment. Under the second approach, EPA would obtain information using a data call-in (DCI) under FIFRA section 3(c)(2)(B). EPA also proposed how it would determine whether a nanoscale active or inert ingredient is a new active or inert ingredient for purposes of FIFRA and the Pesticide Registration Improvement Act (PRIA), “even when an identical, non-nanoscale form of the nanoscale ingredient is already registered.”10
In December 2011, EPA announced its first conditional registration for a pesticide product containing nanosilver as a new active ingredient.11 As a condition of the conditional registration, EPA required additional data to confirm its assessment “that the product will not cause unreasonable adverse effects on human health or the environment.” On May 19, 2015, EPA announced a conditional registration for another nanosilver-containing antimicrobial pesticide product.12 This second nanosilver registration reflected EPA’s growing expertise in addressing, processing, and approving nanopesticide registration applications. EPA based its decision “on its evaluation of the hazard of nanosilver after reviewing exposure data and other information on nanosilver from the applicant, as well as data from the scientific literature.” According to EPA, these data show that plastics and textiles treated with nanosilver “release exceedingly small amounts of silver.” Based on its evaluation, EPA states that it determined not only that the nanosilver pesticide would not cause unreasonable adverse effects on people, including children, or the environment, but also “that it would be beneficial because it will introduce less silver into the environment than competing products.”13 EPA noted that it was requiring the company “to generate additional data to refine the Agency’s exposure estimates.”14
While EPA did not issue a final policy statement concerning products containing nanoscale materials, in 2015, EPA responded to a 2008 petition for rulemaking filed by the International Center for Technology Assessment (ICTA) requesting that EPA regulate products containing nanosilver as pesticides and assess products containing nanosilver as “new and different” products from products containing macro-silver.15 EPA granted ICTA’s request to use its authorities under FIFRA and the Federal Food, Drug, and Cosmetics Act (FFDCA) to address concerns related to the potential for different toxicity profiles for macro-silver and nanosilver ingredients that may be regulated under FIFRA and FFDCA and that have a pesticidal purpose.16 EPA stated that it would “use its discretion on how best to address these concerns under each of these authorities,” applying it to registration applications for products containing a new nanosilver active ingredient or to its review of existing registrations. EPA also committed to using its enforcement discretion on how best to address the distribution and sale of unregistered pesticides in the U.S.
In October 2018, EPA posted the Final Work Plan (FWP) for the nanosilver registration review process.17 The FWP explains what EPA’s Office of Pesticide Programs “knows about nanosilver generally, highlighting anticipated data and assessment needs for each unique nanosilver chemistry, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing review of the nanosilver case.”18 EPA anticipated issuing a DCI in 2018 requiring certain data anticipated as needed for the registration review of nanosilver, but it has not issued one to date.
FDA
In its approach to the regulation of nano-enabled products, FDA has noted that the application of nanotechnology “may result in product attributes that differ from those of conventionally-manufactured products.”19 As a result, when evaluating the safety or effectiveness of FDA-regulated products including nanomaterials or otherwise involving the application of nanotechnology, FDA acknowledges that it should consider the unique properties and behaviors that nanomaterials may exhibit. FDA stated that it “does not categorically judge all products containing nanomaterials or otherwise involving the application of nanotechnology as intrinsically benign or harmful,”20 however. FDA intends to regulate nanotechnology products under its existing statutory authorities, “in accordance with the specific legal standards applicable to each type of product under its jurisdiction.”21
FDA has issued many helpful guidance documents concerning the application of nanotechnology or the use of nanomaterials in FDA-regulated products, including cosmetic products, food ingredients, food contact substances, food for animals, and drug products:
- Guidance for Industry: Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology;22
- Guidance for Industry: Safety of Nanomaterials in Cosmetic Products;23
- Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients That Are Color Additives;24
- Guidance for Industry: Use of Nanomaterials in Food for Animals;25 and
- Guidance for Industry: Drug Products, Including Biological Products, That Contain Nanomaterials (Draft Guidance).26
These guidance documents are just that—guidance, not rules or regulations. They represent FDA’s current thinking on the above topics. Industry may use alternative approaches as long as the approach meets the requirements of the applicable statutes and regulations. In all cases, FDA recommends that manufacturers consult it to discuss an alternative approach or early in the development process.
More recently, FDA published a proposed rule on February 26, 2019, that would put into effect a final monograph that would establish standards for nonprescription, over-the-counter (OTC) sunscreen drug products.27 The proposed rule describes the conditions under which FDA proposes that OTC sunscreen monograph products are generally recognized as safe and effective (GRASE) and not misbranded. While FDA expressed concern regarding the safety of several sunscreen ingredients, noting that the public record has insufficient data to support their safety, FDA did not do so regarding the nanomaterial forms of zinc oxide and titanium dioxide. FDA states that “having examined the scientific information in the record, including for nanomaterial forms of zinc oxide and titanium dioxide, FDA is not now proposing conditions of use for these two active ingredients under the sunscreen monograph that distinguish nanomaterials from other forms of these ingredients.” FDA “also does not propose to categorically classify sunscreen products that are manufactured using nanotechnology or contain nanomaterials as GRASE or not, solely on that basis.”28
Discussion
While certain nanomaterials may be considered new chemicals under TSCA, or new active ingredients or inerts under FIFRA, or used in food, drugs, or cosmetics, EPA and FDA have demonstrated that the authority to regulate nanomaterials that each agency currently possesses is sufficiently durable and as effective as the authority to regulate more conventional industrial chemicals, pesticidal ingredients, or active ingredients. This level of certainty was absent a decade or so ago when early nano stakeholders were struggling with whether and, if so, how best to apply the then regulatory paradigms and frameworks that had evolved under these and other federal and international authorities to address potential risks from nano-sized materials. Nano advocates argued persuasively that with research, additional data, and suitable scaling methodologies, the core traditional approaches to identifying, classifying, and regulating risks could also apply to nanoscale materials. This was the unanimous view of the federal government, across party lines and over multiple administrations, and global authoritative bodies throughout Europe, Asia, and South America.29
When considering the broad arc of scientific developments, and the daunting complexity of evolving technologies, in hindsight the past decade or so seems relatively uncomplicated. Our more recent analysis of legal and regulatory challenges in regulating synthetic biology and products derivative of nano, synbio, and other technologies suggests many of the same issues arise. These issues include regulatory uncertainty regarding jurisdictional boundaries, limited technological literacy among regulators and legislators, and quantifying of potential risks from innovations that find no precedent—all of which lead to costly delays in commercialization.30 Innovators and manufacturers need to determine as soon as possible in which jurisdictional box their nanoscale innovation belongs and if none exists, help the legislator or regulator build a suitable one derivative of existing authority that will provide a glide path for landing the product on solid commercial footing. Any lesser effort will stall commercialization and deprive the marketplace of a newer, better, and more sustainable product.
Endnotes
1. 15 U.S.C. § 2601(c) (“It is the intent of Congress that the Administrator shall carry out this chapter in a reasonable and prudent manner[.]”); 7 U.S.C. § 136(a) (“To the extent necessary to prevent unreasonable adverse effects on the environment, the Administrator may by regulation limit the distribution, sale, or use in any State of any pesticide that is not registered[.]”).
2. What It Is and How It Works, Nat’l Nanotechnology Initiative, https://www.nano.gov/nanotech-101/what (last visited July 8, 2019).
3. Frank R. Lautenberg Chemical Safety for the 21st Century Act, Pub. L. No. 114-182, 130 Stat. 448 (June 22, 2016). The text of the Lautenberg Act is available at https://www.congress.gov/114/plaws/publ182/PLAW-114publ182.pdf (last visited July 8, 2019).
4. EPA, TSCA Inventory Status of Nanoscale Substances—General Approach (Jan. 23, 2008), available at https://www.epa.gov/sites/production/files/2015-10/documents/nmsp-inventorypaper2008.pdf.
5. Org. for Econ. Cooperation & Dev., Series on the Safety of Manufactured Nanomaterials No. 89, Developments in Delegations on the Safety of Manufactured Nanomaterials—Tour De Table: February 2018–March 2019, at 59 (May 27, 2019), available at http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono(2019)11&doclanguage=en.
6. Chemical Substances When Manufactured or Processed as Nanoscale Materials; TSCA Reporting and Recordkeeping Requirements, 82 Fed. Reg. 3641 (Jan. 12, 2017).
7. 7 U.S.C. § 136a(c)(5)(D).
8. Lynn L. Bergeson, Enlisting Modern Technologies to Ensure a Safe Food Supply, 31 Nat. Res. & Envt., no. 3, Winter 2017, available at http://www.lawbc.com/uploads/docs/00199887.pdf.
9. Pesticides; Policies Concerning Products Containing Nanoscale Materials; Opportunity for Public Comment, 76 Fed. Reg. 35383, 35388 (June 17, 2011).
10. Id. at 35384.
11. Press Release, EPA, Pesticide News Story: EPA Announces Conditional Registration of Nanosilver Pesticide Product (Dec. 1, 2011), available at https://archive.epa.gov/pesticides/news/web/html/nanosilver-2.html.
12. Press Release, EPA, EPA Pesticide Program Updates: EPA Announces Registration of Nanosilver Pesticide Product (May 19, 2015).
13. Id.
14. One of the conditional registrations was overturned because “EPA failed to support its finding that [the nanosilver product] was in the public interest,” not because of a finding that the product posed any adverse effects to human health or the environment. Lynn L. Bergeson & Timothy D. Backstrom, Appellate Court Vacates Conditional Nanosilver Registration, 18 ABA Sec. of Envt., Energy & Res. PCRRTK Newsl., no. 5, Aug. 2017, at 9, available at http://www.lawbc.com/uploads/docs/Appellate_Court_Vacates_Conditional_Nanosilver_Registration.PDF.
15. Letter from EPA to Int’l Ctr. for Tech. Assessment, EPA Response to “Petition for Rulemaking Requesting EPA Regulate Nano-Silver Products as Pesticides” (Mar. 19, 2015), available at https://www.regulations.gov/document?D=EPA-HQ-OPP-2008-0650-1406.
16. Id. at 2.
17. EPA, Dkt. No. EPA-HQ-OPP-2011-0370, Nanosilver Final Work Plan (FWP): Registration Review: Initial Docket Case Number 5042 (Oct. 2018), available at https://www.regulations.gov/document?D=EPA-HQ-OPP-2011-0370-0021.
18. Id. at 5.
19. FDA’s Approach to Regulation of Nanotechnology Products, FDA: Nanotechnology Programs at FDA, https://www.fda.gov/science-research/nanotechnology-programs-fda/fdas-approach-regulation-nanotechnology-products (last visited June 26, 2019).
20. Id.
21. Id.
22. FDA, Guidance for Industry: Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, Dkt. No. FDA-2010-D-0530 (June 2014), available at https://www.fda.gov/media/88423/download.
23. FDA, Guidance for Industry: Safety of Nanomaterials in Cosmetic Products (June 2014), available at https://www.fda.gov/media/83957/download.
24. FDA, Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients That Are Color Additives (June 2014), available at https://www.fda.gov/media/115075/download.
25. FDA, Guidance for Industry: Use of Nanomaterials in Food for Animals (Aug. 2015), available at https://www.fda.gov/media/88828/download.
26. FDA, Guidance for Industry: Drug Products, Including Biological Products, That Contain Nanomaterials (Draft Guidance) (Dec. 2017), available at https://www.fda.gov/media/109910/download.
27. Sunscreen Drug Products for Over-the-Counter Human Use, 84 Fed. Reg. 6204 (Feb. 26, 2019).
28. Id. at 6216.
29. For example, on September 20, 2013, the Organization for Economic Cooperation and Development (OECD) approved a recommendation that its Member Countries apply existing regulatory frameworks to manage risks associated with manufactured nanomaterials. OECD Countries Address the Safety of Manufactured Nanomaterials, OECD (Sept. 20, 2013), https://www.oecd.org/chemicalsafety/oecd-countries-address-the-safety-of-manufactured-nanomaterials.htm.
30. Lynn L. Bergeson et al., The DNA of the U.S. Regulatory System: Are We Getting It Right for Synthetic Biology? (Oct. 15, 2015) (Woodrow Wilson Int’l Ctr. for Scholars Synthetic Biology Project Report), available at https://www.lawbc.com/uploads/docs/0168960.pdf.