FDA Publishes Draft Guidance on Nanotechnology

FDA has published a draft guidance on FDA’s current thinking on whether FDA-regulated products contain nanomaterials or otherwise involve the application of nanotechnology. The guidance is intended for manufacturers, suppliers, importers, and other stakeholders.

The application of nanotechnology may result in product attributes that differ from those of conventionally-manufactured products, and thus may merit examination. However, FDA does not categorically judge all products containing nanomaterials or otherwise involving application of nanotechnology as intrinsically benign or harmful.

FDA has not to date established regulatory definitions of “nanotechnology,” “nanoscale” or related terms.  However, 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. 

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.

As a first step toward developing the framework for considering whether FDA-regulated products include nanomaterials or otherwise involve nanotechnology, the agency has developed the following points. They are intended to be broadly applicable to all FDA-regulated products, although additional guidance may be articulated for specific product areas, as appropriate in the future.

1. Engineered material or end product. This term is used to distinguish between products that have been engineered to contain nanoscale materials or involve the application of nanotechnology from those products that contain incidental or background levels of nanomaterials or those that contain materials that naturally occur in the nanoscale range.  FDA is particularly interested in the deliberate manipulation and control of particle size to produce specific properties, because the emergence of these new properties or phenomena may warrant further evaluation. This is distinct from the more familiar use of biological or chemical substances that may naturally exist at small scales, including at the nanoscale, such as microorganisms or proteins.  
2. At least one dimension in the nanoscale range (approximately 1 nm to 100 nm). A size range of approximately 1 nm to 100 nm is commonly used in various working definitions or descriptions proposed by the regulatory and scientific community. In this size range, materials can exhibit new or altered physicochemical properties which enable novel applications.
3. Exhibits properties or phenomena . . . that are attributable to its dimension(s). Properties and phenomena of materials at the nanoscale enable applications that can affect the safety, effectiveness, performance, quality, and, where applicable, public health impact of FDA-regulated products. This may be due to altered chemical, biological, or magnetic properties, altered electrical or optical activity, increased structural integrity, or other unique characteristics of nanoscale materials not normally observed in their larger counterparts. In addition, considerations such as routes of exposure, dosage, and behavior in various biological systems (including specific tissues and organs) are critical for evaluating the wide array of products under FDA’s jurisdiction.
4. Size range of up to one micrometer (1,000 nm). Materials or end products can also exhibit properties or phenomena attributable to a dimension(s) above the approximate 100 nm range.  A reduction in size can lead to properties that are clearly different from those of the conventionally-scaled material although the material or end product itself may not necessarily be within the nanoscale range.  Structures such as agglomerates and aggregates are of interest in this context as are coated, functionalized, or hierarchically assembled structures. To account for such materials, some definitions of nanomaterial have applied the 100 nm upper dimension to the internal structure. In the absence of a bright line as to where an upper limit should be set, the agency considers that an upper bound of one micrometer (i.e., 1,000 nm) would serve as a reasonable parameter for screening materials with dimensions beyond the nanoscale range for further examination to determine whether these materials exhibit properties or phenomena attributable to their dimension(s) and relevant to nanotechnology. The agency believes that the one micrometer upper limit in the second point to consider serves both to (1) exclude macro-scaled materials that may have properties attributable to their dimension(s) but are not likely relevant to nanotechnology; and (2) include those materials (such as aggregates, agglomerates, or coated, functionalized, or hierarchically assembled structures) with dimension(s) above 100 nm that may exhibit dimension-dependent properties or phenomena relevant to nanotechnology and distinct from those of macro-scaled materials.

FDA notes that there is a critical need to learn more about the potential role and importance of dimensions in the characteristics exhibited by engineered nanomaterials that may be used in producing products regulated by FDA. Premarket review, when required, offers an opportunity to better understand the properties and behavior of products that contain engineered nanomaterials or otherwise involve application of nanotechnology. Where products applying nanotechnology are not subject to premarket review, the agency urges manufacturers to consult with the agency early in the product development process.  In this way, any questions related to the regulatory status, safety, effectiveness, or public health impact of these products can be appropriately and adequately addressed. 

Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance.  Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov.  All comments should be identified with the docket number (FDA-2010-D-0530) listed in the notice of availability that publishes in the Federal Register.

More information is available at FDA.