In its newly released guidance to industry, FDA indicates that “agglomerates and aggregates” of materials that exceed the oft-cited ceiling of 100 nanometers may still warrant consideration as nanotechnology based on their “properties,” a position that could impact the cosmetics sector.

Capping the nanotech realm at 100 nm has become popular practice because the National Nanotechnology Initiative does so in its definition offered online.

However, avoiding such a narrow delineation of nanotechnology is “probably a good idea,” according to Todd Kuiken, senior research associate at the Project on Emerging Nanotechnologies, a Woodrow Wilson International Center for Scholars initiative.

“Once you set a specific definition, then you get into these arguments – ‘What if it’s 110 or 150 or 200 [nanometers]?’ A material still may be displaying some of the properties [of nanotechnology], which is really what you want to be focusing on,” Kuiken asserted in a June 15 interview with “The Rose Sheet.”

Where pre-market review is not required, as in the case of cosmetics, "the agency urges manufacturers to consult with the agency early in the product development process." – FDA nanotech guidance

He noted that formulators use nano-sized ingredients specifically because of the different behavior they frequently exhibit compared with their macroscale counterparts, which enables novel product applications. Such innovations are being seen increasingly in sunscreens and cosmetics as well as dietary supplements and certain foods.

FDA still uses the popular 1 nm-100 nm scale as a reference and indicates that in its regulatory deliberations the agency will consider whether an engineered material or end product has “at least one dimension” that measures in that range.

But the agency may also take into account whether a product or material “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,” according to the guidance, published June 9.

FDA recognizes that larger agglomerates and aggregates of nanoscale substances up to the 1-µm mark "may exhibit dimension-dependent properties or phenomena relevant to nanotechnology and distinct from those of macro-scaled materials."

This language suggests that firms "won't be able to hide behind agglomerates" of nanomaterials when FDA evaluates product safety, said Kuiken.

Aggregates Count

FDA’s inclusion of aggregates within the purview of its nanotechnology oversight could have implications for personal care, Kuiken suggested.

“Previously,” he said, “if you listened to some of the talks from the cosmetics industry, particularly at FDA meetings, they have hinted that, ‘Well, in the final products the size of the nanomaterials is actually larger than the 100-nm barrier because they’re actually agglomerates. ... Therefore they’re not really new nanomaterials, so we don’t have to look at them any differently.’”

The Nanodermatology Society has pointed out nanoparticles’ tendency to “group together to form larger clusters” in its defense of nanotech-based sunscreen formulations (Also see "“Physician-Led” Nanodermatology Society Endorses Nano-Sunscreens" - HBW Insight, 9 May, 2011.).

In many cases, “the reality is it’s still portraying the properties of the nanomaterial in the agglomerated form,” said Kuiken. “So what’s good about this new FDA policy is that they call out the properties they are concerned about and not necessarily the size.”

Properties FDA highlights as potentially attributable to a material’s dimensions include increased bioavailability, increased potency of a drug product, decreased toxicity of a drug product or, generally, any that affect safety, effectiveness, performance, quality or public health impact.

The agency says both formal and informal pre-market product review can help the agency and applicant firms understand the properties of products with nanoscale components.

Where pre-market review is not required, as in the case for cosmetics and nutritional supplements, "the agency urges manufacturers to consult with the agency early in the product development process," the guidance says.

Regulatory Process Still Unclear

Comments on the guidance are due by Aug. 15. Kuiken said he will be interested to see how industry reacts to the agency’s behavior- or property-based approach.

Firms may view it as problematic and overly burdensome, he suggested. “How are you going to distinguish the properties from the nanomaterial [they] may have used from other properties that are being incorporated into the product?” he asked.

Stretching the nanoscale to 1,000 nm rather than 100 nm could also provoke comment, Kuiken said, as companies may wonder if every material they use that falls under that ceiling qualifies as nanotechnology in the regulator’s eyes.

“That’s something I think the guidance lacks,” he said. “It’s still sort of unclear about what the actual regulatory process is going to be. At the end of the day the guidance still basically says, ‘Just come talk to us first and we’ll work it out.’”

The agency acknowledges that the document, published for comment June 9, is only a starting point in the regulation of engineered nanomaterials.

"These points to consider are intended to be broadly applicable to all FDA-regulated products, with the understanding that additional guidance may be articulated for specific product areas as appropriate in the future," the guidance says.

In a same-day release, FDA Commissioner Margaret Hamburg reiterates that the guidance is merely a first step that offers no regulatory definition of nanotech.

"We want to narrow the discussion to these points and work with industry to determine if this focus is an appropriate starting place," the commissioner says.

Guidance Is “Good Step Forward”

Kuiken called the guidance “a good step forward,” adding: “It’s taken a while for [FDA] to get to this point, but they have clarified a little bit the direction that they’re probably going to be going.”

To date, some manufacturers have eschewed nanoscale ingredients, despite the advantages they pose, due to regulatory uncertainty and concerns raised by consumer and environmental groups that claim nano-sized substances are inherently unpredictable (Also see "Badger Reformulates Sunscreens To Meet Consumer Demand For Nano-Free" - HBW Insight, 9 May, 2011.).

Meanwhile, the U.S. government's stated interest in nanotechnology remains high.

FDA published its guidance in conjunction with a memo from the White House heralding the work of the National Nanotechnology Initiative, which has invested nearly $14 billion in nanotech research and development over the past decade, and establishing an interagency working group to harmonize nanotech regulation and oversight.

Nanotech investments at FDA remain modest. The agency sought $7.3 million for nanotech research in 2012, matching its prior-year request (Also see "Nanotech Programs In U.S., EU, Move Regs Closer To Global Model" - HBW Insight, 28 February, 2011.).

By Dan Schiff, Ryan Nelson

FDA Takes “Property”-Based Approach To Nanotech, Raises Roof To 1 Micron

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