Nanotechnology — the use of nanometer-sized particles in consumer and other products — has been at the forefront of commercial innovation across several industries over the past decade, from personal care products to pharmaceuticals. Today, untold numbers of commercial products contain so-called nanoparticles. However, some in the nanotechnology industry have bemoaned the lack of clear guidance from the US Food & Drug Administration (FDA) and other regulatory authorities regarding the nature and scope of regulation of this unique technology.
On June 9, 2011, FDA took a step toward clarifying the regulatory framework by publishing a draft guidance that explains the factors it will use to determine whether a FDA-regulated product contains nanomaterials or otherwise involves the application of nanotechnology (Nanotechnology Guidance).1 By publishing the Nanotechnology Guidance, FDA hopes to help manufacturers identify instances when the use of nanotechnology may have implications on their products’ regulatory status, safety or effectiveness. According to the 2007 report from FDA’s Nanotechnology Task Force, the introduction of nanoscale materials or manufacturing processes into FDA-regulated products could trigger additional reporting requirements for drugs, biological products, devices and other FDA-regulated products.2
The United States Food, Drug and Cosmetic Act and FDA’s implementing regulations require drug and device manufacturers to obtain FDA authorization prior to introducing a new drug or device into the market.3 Once a drug, biological product or device is approved or cleared for marketing, the manufacturer must notify FDA about changes in the product’s manufacture or use.4 Since nanoscale materials often have chemical, physical or biological properties that are different from their larger counterparts, companies that introduce nanoscale ingredients or manufacturing processes into drugs would be required to file a supplemental notification with FDA, and, depending on the scope of the change, could require an entirely new approval.5
Similarly, for devices subject to FDA’s premarket notification regulations (510(k) notification) or premarket approval regulations (PMA), the introduction of nanoscale materials or manufacturing processes could require submission of a new 510(k) notification or PMA supplement.6
Drug and device manufacturers may find it challenging to comply with FDA’s reporting regulations because FDA has not yet established regulatory definitions of "nanotechnology" or "nanoscale." Although the Nanotechnology Guidance does not create definitions for these terms, the document reduces the uncertainty surrounding nanotechnology by explaining FDA’s current thoughts on the subject. The Agency will consider two factors in determining whether a FDA-regulated product contains nanomaterials or involves nanotechnology:
- Whether an engineered material or end product has at least one dimension in the nanoscale range (approximately 1 nm to 100 nm); or
- 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.
FDA notes that these factors are "intended to be broadly applicable to all FDA-regulated products," although they are subject to change and refinement in future product-specific guidance documents. The factors apply to new products as well as existing products that are altered in the dimensions, properties or effects of any of their components.
The Nanotechnology Guidance provides the reasons FDA decided to use these two "points to consider" to determine whether a product uses nanotechnology. FDA chose a particle size range of 1 nm to 100 nm because the scientific community commonly recognizes that materials within this range "can exhibit new or altered physiochemical properties which enable novel applications." FDA also limited its consideration to "engineered material[s] or end product[s]" to emphasize the Agency’s interest in the "deliberate manipulation and control of particle size to produce specific properties." FDA does not intend the Nanotechnology Guidance to apply to substances that naturally exist at the nanoscale level, such as microorganisms or proteins, nor to products that contain "incidental or background levels of nanomaterials."
As explained in the Guidance, the 100 nm size limitation should be a "first reference point in considering whether a FDA-regulated product contains nanomaterials." The second "point to consider" expands the particle size limitation to materials up to 1 micrometer (1,000 nm) if a material or end product "exhibits properties or phenomena … that are attributable to its dimensions." In setting this limit, FDA intends to include "agglomerates and aggregates" as well as "coated, functionalized, or hierarchically assembled structures" that may exhibit nanoscale-like properties distinct from their macro-scaled counterparts. For instance, a drug or device with a total particle size over 100 nm could be deemed a "nanomaterial" if the product contains one or more active sites that function by way of properties unique to the nanoscale configuration of the materials. FDA set an "upper limit" of 1 micrometer to exclude macro-scaled materials that may have dimension-dependent properties that are not relevant to nanotechnology.
The Nanotechnology Guidance does not establish any regulatory definitions or address the regulatory status of products that contain nanomaterials. As a draft guidance, it does not create any legally-enforceable responsibilities and should be viewed only as FDA’s recommendations. Companies should use the Guidance to evaluate whether their products — particularly products subject to FDA’s premarket authorization or notification requirements — contain nanomaterials or involve the application of nanotechnology. If the products involve nanotechnology, FDA encourages all manufacturers to consult with the Agency early in the product development process so that any questions related to the regulatory status, safety, effectiveness or public health impact of the products may be adequately addressed.
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It remains to be seen whether the Nanotechnology Guidance will gain traction and achieve its desired effect of spurring innovation and commercialization of nanotechnology products. FDA plans to release future guidance to establish broad nanotechnology rules for different products, and public input on FDA’s recommendations may guide the Agency in developing regulatory definitions. Interested parties may submit electronic or written comments to the Nanotechnology Guidance by August 15, 2011.7