It must be Nanotechnology Regulation week in Washington DC.  Yesterday, two federal agencies and the White House released documents that grapple with the effective regulation of products that depend on engineered nanomaterials.

In a joint memorandum, the Office of Science and Technology Policy, the Office of Management and Budget and the Office of the United States Trade Representative laid out Policy Principles for the U.S. Decision Making Concerning Regulations and Oversight of Applications of Nanotechnology and Nanomaterials.

On the same day, the US Environmental Protection Agency posted a prepublication notice on Policies Concerning Products Containing Nanoscale Materials.

And to cap it all, the US Food and Drug Administration released Draft Guidance for Industry on Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology.

A busy week for nanotechnology regulation!

White House Memo on Nanotechnology Regulation Policy Principles

The White House memorandum is the latest document to come out of the Emerging Technologies Interagency Policy Coordination Committee – ETIPC for short.  In part, it is a response to the 2010 review of the National Nanotechnology Initiative by the President’s Council of Advisors on Science and Technology, and in particular the concern expressed by PCAST that

“In the absence of sound science on the safe use of nanomaterials and of technologies and products containing them, the chance of unintentionally harming people and the environment increases.  At the same time, uncertainty and speculation about potential risks threaten to undermine consumer and business confidence.”

Correspondingly, this is a memorandum that is heavily focused on science-driven regulation, and the avoidance of knee-jerk responses to speculative concerns.

Reading through it, a number of themes emerge, including:

• Existing regulatory frameworks provide a firm foundation for the oversight of nanomaterials, but there is a need to respond to new scientific evidence on potential risks, and to consider administrative and legal modifications to the regulatory landscape should the need arise.
• Regulatory action on nanomaterials should be based on scientific evidence of risk, and not on definitions of materials that do not necessarily reflect the evidence-based likelihood of a material causing harm.
• There should be no prior judgement on whether nanomaterials are intrinsically benign or harmful, in the absence of supporting scientific evidence.
• Transparency and communication are important to ensuring effective evidence-based regulation.

Overall, this is a strong set of policy principles that lays the groundwork for developing regulation that is grounded in science and not swayed by speculative whims, and yet is responsive and adaptive to emerging challenges.  Gratifyingly, the memorandum begins to touch on some of the concerns I have expressed previously about approaches to nanomaterial regulation that seem not to be evidence-based.  There is a reasonable chance that they will help move away from the dogma that engineered nanomaterials should be regulated separately because they are new, to a more nuanced and evidence-based approach to ensuring the safe use of increasingly sophisticated materials.  Where it perhaps lacks is in recognizing the importance of other factors in addition to science in crafting effective regulation, and in handling uncertainty in decision making.  But it is undoubtedly a move in the right direction.  The principles are listed at the end of this post.

EPA Draft Pesticides and Nanomaterials Policies

The second piece in this triumvirate is a prepublication version of a document from EPA that should appear in the Federal Register next week, titled “Pesticides; Policies Concerning Products Containing nanoscale Materials; Opportunities for Public Comment.”

As the title makes very clear, this is a statement from the EPA that is setting out draft policies for dealing with nanomaterials in pesticide products – materials such as nanoscale silver particles – and asking for public comment.  This is the latest iteration in a process that has been going on for some time to address the use of nanoscale silver as an antimicrobial agent, together with other antimicrobial, fungicidal and pesticide uses of nanomaterials.

The crux of the proposed policy is a requirement for manufacturers to let EPA know when a pesticide product contains an engineered nanomaterial – irrespective of whether it is an active or passive ingredient in the product. EPA acknowledges that the presence of a nanoscale material in a product does not necessarily indicate the possibility that it will exhibit new or unusual risks – but the agency intends to use this information as a trigger for a more thorough evaluation of products that might raise concerns.

This is a long and somewhat convoluted document, that spends some time outlining what the agency considers is an engineered nanomaterial, and reviewing nanomaterial hazard data.

Reading the document, EPA still seems somewhat tangled up with definitions of engineered nanomaterials. After outlining conventional attributes associated with engineered nanomaterials, including structures between ~1 – 100 nm and unique or novel properties, the document states

“These elements do not readily work in a regulatory context because of the high degree of subjectivity involved with interpreting such phrases as “unique or novel properties” or “manufactured or engineered to take advantage of these properties” Moreover the contribution of these subjective elements to risk has not been established.”

This aligns with where my own thinking has been moving in recent years.  Yet following this statement, the document reverts back to considering nanoparticles between 1 – 100 nm as the archetypal nanomaterial, and intimates “novel” properties such as “larger surface area per unit volume and/or quantum effects” as raising new risk concerns.

I also found the background information on potential hazards somewhat lopsided, as a litany of studies were cited that indicate a number of potential hazards associated with a range of materials, but without clear information on how this might translate to plausible and quantifiable risk.

At the end of the day, I found this to be a mixed bag of a document – some useful information and some evidence of new thinking, but all surrounded by a rather unfocused assessment.   However, it is a draft that has been put out for public comment, which means that there is an opportunity here to tighten it up considerably in the final version.

I must also add that I was impressed by the final section on Questions for Comment – here you will find a list of highly relevant questions that are the clearest indication in the document that EPA understands many of the critical issues here, and is genuinely looking for expert input to address them.

Interestingly though, the EPA document does not reference the White House memorandum on Policy Principles published at the same time – unlike my third and final document in this set from FDA.

FDA Draft Guidance for Industry on Products and Nanotechnology

The FDA Guidance for Industry: Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology is a very different kettle of fish to the EPA document.  It is overtly responsive to the White House memo; it demonstrates a deep understanding of the issues surrounding nanotechnology and regulation; and it is mercifully concise.

To be fair, the scope of the draft guidance is limited to helping manufacturers understand how the agency is approaching nanotechnology-enabled products under their purview.  But this is something it does well.

One of the more significant aspects of the guidance is the discussion on regulatory definitions of nanomaterials.  Following a line of reasoning established some years ago, the agency focuses on material properties rather than rigid definitions:

“FDA has not to date established regulatory definitions of “nanotechnology,” “nanoscale” or related terms… Based on FDA’s current scientific and technical understanding of nanomaterials and their characteristics, FDA believes that evaluations of safety, effectiveness or public health impact of such products should consider the unique properties and behaviors that nanomaterials may exhibit”

Of course, this still begs the question “what is a nanomaterial in FDA’s eyes?”  The agency answer by stating:

At this time, when considering whether an FDA-regulated product contains nanomaterials or otherwise involves the application of nanotechnology, FDA will ask:

1. Whether an engineered material or end product has at least one dimension in the nanoscale range (approximately 1 nm to 100 nm); or
2. Whether an engineered material or end product exhibits 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 guidance goes on to state

“These considerations apply not only to new products, but also may apply when manufacturing changes alter the dimensions, properties, or effects of an FDA-regulated product or any of its components. Additionally, they are subject to change in the future as new information becomes available, and to refinement in future product-specific guidance documents.”

FDA is clearly aiming for responsive and adaptive regulation here.

Reading the first of the two criteria above and the associated justification in the guidance, I can’t help feeling that FDA is still trying to justify responding to sub-100 nm scale materials based on assumptions of risk rather than evidence.  But the second criteria is important, because it opens the door to considering physical form and structure as a factor in determining potential risk irrespective of scale – as long as a material can come into intimate biological contact with a person.  This is a significant move, as it supports evidence-based decision-making on materials and products under FDA’s jurisdiction, irrespective of what technological label is applied to them.

That said, there remains some confusion as to how this criteria will be applied, and the reasoning behind it. Clearly, there is an aim here to capture supra-100 nm materials that nevertheless exhibit biological behavior associated with a nanometer-scale structure – including agglomerates, coated materials and hierarchical structures.  Yet the criteria is also said to have been selected to “exclude macro-scaled materials that may have properties attributable to their dimension(s) but are not likely relevant to nanotechnology”.  This statement seems to hark back to an assumption that “nanotechnology” is something that needs to be regulated, rather than focusing on materials and products that run the risk of slipping through the regulatory net – no matter what they are called.

But like the EPA document, the FDA guidance is still in draft form, and open to public comment.  And so is still very much a work in progress.

Overall, all three of these documents seem to be heading in the right direction if evidence-based, responsive and responsible regulations are the end goal.  There is still a way to go for both FDA and EPA before regulatory policy escapes being mesmerized by “nanotechnology”. But with strong science-driven policy principles emerging from the White House, the odds of this occurring are looking decidedly more healthy.

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While House Policy Principles for the U.S. decision-Making Concerning Regulation and Oversight of Applications of nanotechnology and Nanomaterials:

In addressing issues raised by nanomaterials, agencies will adhere to the Principles for Regulation and Oversight of Emerging Technologies. Specifically, to the extent permitted by law, Federal agencies will:

• To ensure scientific integrity, base their decisions on the best available scientific evidence, separating purely scientific judgments from judgments of policy to the extent feasible;
• Seek and develop adequate information with respect to the potential effects of nanomaterials on human health and the environment and take into account new knowledge when it becomes available;
• To the extent feasible and subject to valid constraints (involving, for example, national security and confidential business information), develop relevant information in an open and transparent manner, with ample opportunities for stakeholder involvement and public participation;
• Actively communicate information to the public regarding the potential benefits and risks associated with specific uses ofnanomate rials;
• Base their decisions on an awareness of the potential benefits and the potential costs of such regulation and oversight, including recognition of the role of limited information and risk in decision making;
• To the extent practicable, provide sufficient flexibility in their oversight and regulation to accommodate new evidence and learning on nanomaterials;
• Consistent with current statutes and regulations, strive to reach an appropriate level of consistency in risk assessment and risk management across the Federal Government, using standard oversight approaches to assess risks and benefits and manage risks, considering safety, health and environmental impacts, and exposure mitigation;
• Mandate risk management actions appropriate to, and commensurate with, the degree of risk identified in an assessment.
• Seek to coordinate with one another, with state authorities, and with stakeholders to address the breadth of issues, including health and safety, economic, environmental, and ethical issues (where applicable) associated with nanomaterials; and
• Encourage coordinated and collaborative research across the international community and clearly communicate the regulatory approaches and understanding of the United States to other nations.