WEISS'S NOTEBOOK

Nanoparticles Get Nanoregulation

Little Particles are Big Business, but Safety Could Slip Through FDA Sieve

No one expects the federal bureaucracy to move quickly. To paraphrase the old Willie Dixon song, the government is built for comfort, not for speed. And okay, the bureaucracy is bound to appear especially sluggish when compared to the speed of scientific progress.

But there was something especially stultifying last week about the Food and Drug Administration’s latest effort to figure out how to protect the public from foods, drugs, cosmetics, and other products spiked with nanotech ingredients. A sleepy fog suffused the Rockville, MD meeting rooms where agency officials listened all day to scientists, policy experts, and consumer advocates. One could not help but wonder how many new nano-laced products had made their way onto supermarket shelves that day while the grinding wheels of the federal oversight machine ground around in their grinding grindiness.

Nanotechnology, as the general public increasingly knows, refers to the science of the very small. It involves the engineering of materials on the order of a billionth of a meter, or a few ten-thousandths the diameter of a human hair. The cool thing about such minuscule materials is that they take on novel properties that the very same chemical substances do not exhibit when made in chunkier dimensions. Substances that normally don’t conduct electricity suddenly do when made on the nanoscale. Things that are normally opaque become transparent. Matter normally weak becomes strong.

The not-so-cool thing about nanoscale materials is that they can be far more toxic to cells and other biological systems than macro versions of the same stuff. When it comes to safety, size matters.

That’s relevant to the FDA because the products that it regulates are increasingly being made with nanoscale ingredients. Nanoparticulate medicines can be absorbed faster. Cosmetics with nanoparticles penetrate the skin’s outer layers better. Nanoscale food additives can improve flavor, texture, and “mouth feel.” The problem is, it is not at all clear that conventional testing methods long relied upon by the agency to assure that foods, drugs, and cosmetics are safe can discern the unique risks that may be posed by nanoingredients.

The number of consumer products on the market containing nanoparticles or nanofibers now exceeds 800 and is growing rapidly.

The FDA has been struggling for years to come up with an approach for figuring this out. It determined back in 2007 that it ought to release at least a general guidance for manufacturers—a far cry short of actual regulation, but at least a start—that would lay out the kinds of safety standards manufacturers ought to apply as they seek to market products with nanoscale ingredients. At a follow-up meeting earlier this summer, agency advisors hedged on that modest commitment, suggesting it may be premature to produce even a general guidance document.

At the latest meeting, agency officials at least appeared to recommit themselves to producing some kind of document that might assure consumers that someone is looking out for their safety. But at the risk of practicing medicine without a license, let me give you a bit of advice: Don’t … hold … your … breath.

Admittedly, the problem is complex. The science of nanotoxicology is still young. Definitive safety tests for nanoscale materials are far from perfect. And too heavy a regulatory hand could stifle innovation in a fast-paced and potentially revolutionary field of science. But entrepreneurs, who see big dollar signs in small stuff, are not showing restraint.

According to conservative estimates by the Washington-based Project on Emerging Nanotechnologies, the number of consumer products on the market containing nanoparticles or nanofibers now exceeds 800 and is growing rapidly. That includes 125 cosmetic products, which already as a class are barely regulated by the FDA, even though most of them are meant to be applied directly to the skin; and 44 dietary supplements, which, thanks to Congressional action back in 1994, can today be marketed to consumers not only without first having to prove they are safe or effective, but without even having to prove that they actually contain what they say they contain.

Unfortunately, FDA is still at Nano Square One, debating how to define the term “nanotechnology”—a question most expert groups got past several years ago.

“Nanotechnology has the potential to blur the boundary between cosmetics and drugs.”

At the Rockville meeting, manufacturers and their trade-group representatives leaned on FDA to let them self-regulate. Many of their nanoproducts, they said, are not really nano, because those nanoparticles tend to clump together into larger agglomerates. That raised a question: So why make those ingredients nanoscale to begin with? Because, it turns out, even after they clump together, they exhibit many of the properties conferred upon them by virtue of their essential nano-ness. Well, doesn’t that suggest that the peculiar toxicities of nanoscale materials might also persist, even after agglomeration?

There is “no evidence” of any unique toxicities associated with drugs made this way, said Daniel Caldwell of Johnson & Johnson. Of course, there is pretty much “no evidence” of anything, one way or the other, because there is virtually no research going into this question.

As I’ve written before, drugs, at least, do have to pass reasonably rigorous tests for overall safety and efficacy before being marketed. So although I worry that regulators might not be using the best tests to actually detect novel (and perhaps long-term) toxicities associated with nanotech, at least there is something of a safety net there. Not so for foods, food additives, cosmetics and dietary supplements, which effectively only get regulated after evidence arises that they are making people sick. That’s especially worrisome because one of the reasons nanotech is being increasingly incorporated into these kinds of products is to increase absorption into the body and boost their biological impacts.

“Nanotechnology has the potential to blur the boundary between cosmetics and drugs,” said Andrew Maynard of the Project on Emerging Nanotechnologies.

How can FDA reasonably protect public health in this interim period before researchers completely understand the science of nanotechnology?

In the food arena, one way would be for the agency to just agree up front that it will reject applications seeking to declare nanoingredients as “Generally Recognized as Safe,” or GRAS—the classification granted to some foods and food additives that have a long history of safe use. Specifically, while the macro form of an ingredient may indeed be GRAS, nano versions should not be presumed to have the same safety profile and instead should be declared as being subject to the same kind of oversight as other novel foods or food additives.

In the drug arena, the billion-dollar question is going to be whether drugs that are formulated with nanomaterials deserve to be treated as entirely new chemical entities or simply as innocuously modified versions of already approved drugs. That’s going to be a tough call, and will probably need to be decided on a case-by-case basis. But it may be that the default should be “new chemical entity,” unless the manufacturer can present compelling evidence that the safety and efficacy profile of the new product is not significantly more worrisome than the old.

“If you’re going to hype it as ‘all new,’ then you ought to be testing it as ‘all new,’” said Jaydee Hanson of the Washington-based International Center for Technology Assessment.

In the arena of dietary supplements, the FDA has very little flexibility and authority, but it does have at least one legal means of keeping a grip on the growing use of nanotechnology: declare that all nanomaterials in dietary supplements will be categorized by the agency as “new dietary ingredients,” or “NDI.” By doing so, said William B. Schultz, an attorney and former FDA deputy commissioner for policy, supplement makers would be required to notify the agency at least 75 days before starting to market a product with nanomaterials in it. It would also require that these companies show the FDA the safety data they have relied on, as marketers, to ensure that the nanoproducts they are about to sell are safe. That would at least give the FDA a fighting chance of looking into the product’s potential risks before the product hits the market.

The beauty and utility of the NDI designation, Schultz noted, is that FDA does not have to prove that the product is unsafe if it wants to keep the product off the market. It must simply declare that the company did not supply adequate information to convince the agency that it is safe. Of course, that can only happen if the agency has the staff it would take to review these applications before the 75-day period passes. And given current staffing and funding, which have left the agency unable to keep up even with more pressing reports of people becoming sick from supplements, there is not much chance of it getting sufficiently ahead of the curve to review applications before products get marketed.

Today, Schultz said, the dietary supplements office of the FDA is “barely alive.”

Hopefully the FDA will figure out a way to get a handle on nano before the same can be said for those of us eating the stuff, or getting it in our medicines.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

Tags: nanotechnology

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