In June 2011 the FDA issued draft guidance for industry entitled “Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology.” Building on the recommendations within that document, the agency released two new nanotechnology-related guidances in April:
- Draft Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that are Color Additives
- Draft Guidance for Industry: Safety of Nanomaterials in Cosmetic Products
The overall tone is cautionary, rather than restrictive. The FDA is using these documents to re-emphasize how nanotechnology can inherently change the behavior of materials, which can potentially affect the safety, usage, and regulatory status of products made from these materials.
For foods the FDA warns that nanotechnology can:
- Affect the identity of the food substance
- Affect the safety of the food substance
- Affect the regulatory status of the use of the food substance
- Require a regulatory submission to FDA
“Altering the manufacturing process of a notified food contact substance to either produce components in the nanometer scale or increase the proportion of nanometer-scale components,” continues the FDA, “can sometimes be a significant manufacturing change that could result in a substantive change to the specifications and/or in the identity of the food contact substance or its impurities, and/or levels of impurities.” The FDA also points out that a food substance manufactured for the purpose of creating very small particle sizes with new functional properties likely would not be covered by an existing GRAS (generally recognized as safe) determination.
For cosmetics, the FDA warns that:
- Cosmetics are not subject to premarket approval; however, they must be safe for consumers under labeled or customary conditions use and be properly labeled
- Cosmetics manufactured using nanomaterials are subject to the same legal requirements as any other cosmetics
- In general, the processes currently in use for assessing safety are appropriate for cosmetics containing nanomaterials; however, standard safety tests may need to be modified or new methods developed to evaluate new or unusual properties or functions exhibited by nanomaterials
The FDA recommends that the safety assessment for cosmetic products using nanomaterials should address a number of important factors, including:
- Physio-chemical characteristics
- Agglomeration and size distribution of nanomaterials at the toxicity testing conditions that should correspond to those of a final product
- Potential product exposure levels and the potential for agglomeration of nanoparticles in the final product
- Dosimetry for in vitro and in vivo toxicology studies
- In vitro and in vivo toxicological data on ingredients and their impurities, dermal penetration, irritation (skin and eye) and sensitization studies, and mutagenicity/ genotoxicity studies
- Clinical studies to test the ingredient, or finished product, in human volunteers under controlled conditions
“Industry remains responsible for ensuring that its products meet all applicable legal requirements, including standards for safety—regardless of the emerging nature of a technology involved in the manufacturing a product,” writes the FDA. “We encourage industry to consult early with the agency to address any questions related to the safety, effectiveness, or other attributes of products that contain nanomaterials, or about the regulatory status of such products.”
It never hurts to be reminded of the obvious, which unfortunately can be overlooked or forgotten in the rush to market, or through incomplete science or testing.
It would be prudent for manufacturers who use nanotechnology to review these guidances to see the latest in FDA thinking. The FDA is also investing in an FDA-wide nanotechnology regulatory science program to further enhance its scientific capabilities, including developing necessary data and tools to identify properties of nanomaterials and assess the impact they may have on products—so expect more guidance (and more informed scrutiny and assessment) from the FDA in the future.