The U.S. Food and Drug Administration in April 2012 issued two draft guidance documents relating to the use of nanotechnology in food and food packaging and cosmetics.
"[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," covers the use of nanotechnology in the manufacture of food ingredients, including color additives, and food contact substances, e.g., packaging.
“[Draft] Guidance for Industry: Safety of Nanomaterials in Cosmetic Products,” covers the use of nanotechnology in cosmetics.
These draft guidance documents are the subject of a summary article by attorney Lynn Tyler (Barnes & Thornburg LLP), published in Product Liability Law360, on May 29, 2012, "Tightening FDA Nanotech Regs on Food, Cosmetics."
According to Tyler: "The message of the two guidance documents is similar: Manufacturers in these industries who incorporate nanoscale ingredients into their products should be prepared to prove that the resulting products are safe and that appropriate tests were used to validate their safety."
Excerpts of the article are provided below.
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Draft Guidance for Industry on Food
The food guidance includes a review of the statutory and regulatory provisions governing food, food additives and food contact substances. The food guidance then describes the FDA’s process for assessing the safety of a food substance.
In connection with the manufacturing process, the draft guidance notes that the manufacturing process can affect the identity of the food, the conditions of its use, and the level of impurities it contains. The food guidance then states:
As with any other manufacturing technologies applied to food, nanotechnology and other emerging technologies may introduce issues that warrant additional or different evaluation during a safety assessment of a food substance. For example, so-called nano-engineered food substances can have significantly altered bioavailability and may, therefore, raise new safety issues that have not been seen in their traditionally manufactured counterparts. . . . When a food substance is manufactured to include a particle size distribution shifted more fully into the nanometer range, safety assessments should be based on data relevant to the nanometer version of the food substance. Where nano-engineered food substances have new properties, additional or different testing methods may be necessary to determine the safety of the food substance. . . . Thus, as with any studies to support the safety of food substances, studies to establish the safety of food substances manufactured using nanotechnology should have been appropriately validated for these materials.
For (1) food or color additives that have been approved by regulation, (2) foods that have been identified as generally recognized as safe (GRAS) or (3) food contact substances that have been approved via a food contact notification to the FDA, when there is a significant change to the manufacturing process, including the incorporation of nanoscale ingredients, the food guidance recommends that the manufacturer take several steps:
• Determine what changes have been made to the food substance, including its physicochemical structure and properties, purity and impurities;
• Conduct a safety assessment for the food substance, including the factors set forth above, bioavailability and toxicity;
• Consider whether the substance is within a relevant regulation, GRAS determination or food contact notification;
• Consult with FDA about your conclusions; and
• Make a regulatory submission if warranted.
The food guidance states it is unlikely that nanotechnology applications in food substances will qualify as GRAS, so formal premarket review and approval will be necessary. This should conjure up images of calendars and dollar signs. Although food, food additive and food packaging manufacturers are used to more regulation, those who plan to incorporate nanoscale materials into their products will have to consider conducting safety testing of their products, according to tests that are validated for use with nanoscale materials, and obtain the FDA’s approval prior to marketing the products, or risk FDA enforcement action.
Draft Guidance for Industry on Cosmetics
Somewhat ominously, the cosmetics guidance states near the beginning that “[nano]materials can have chemical, physical and biological properties that differ from those of their larger counterparts. Importantly, properties of a material might change in ways that could affect the performance, quality, safety and/or effectiveness, if applicable, of a product that incorporates that specific nanomaterial.”
In light of that introduction, it is not surprising that the cosmetics guidance recommends extensive safety testing of cosmetics that incorporate nanomaterials before those products are put on the market, even though only color additives are subject to FDA’s premarket approval.
The cosmetics guidance divides the safety assessment into two broad categories: (1) nanomaterial characterization and (2) toxicology considerations. Under nanomaterial characterization, the draft guidance states that the characterization should include the nanomaterial name, the Chemical Abstracts Service (CAS) number, the structural formula and the elemental composition, including the degree of purity and any known impurities or additives.
For physicochemical properties, the characterization should further include: measurement of particle size and distribution; aggregation and agglomeration characteristics; surface chemistry, including zeta potential/surface charge, surface coating, functionalization and catalytic activity; morphology, including shape, surface area, surface topology and crystallinity; solubility; density; stability and porosity.
As to toxicology, the cosmetics guidance states that safety testing should consider “each ingredient’s chemical structure and physicochemical properties, purity/impurities, agglomeration and size distribution, stability, conditions of exposure, uptake and absorption, bioavailability, toxicity and any other qualities that may affect the safety of the product according to its intended use.” Further, the cosmetics guidance asserts that both short-term and long-term toxicity of nanomaterials must be considered.
Other factors addressed in connection with toxicology include routes of exposure, uptake and absorption, and testing methods. The cosmetics guidance notes that while most cosmetics are applied to the skin, some are applied in areas where there is a risk of exposure through the mouth or nose, so safety must be assessed in that context.
With respect to uptake and absorption, the cosmetics guidance states that the reduced particle size of nanomaterials may result in increased absorption, which must thus be considered, and that tests should be conducted on both intact and damaged skin.
Because of the different routes of exposure and potential for increased absorption, the cosmetics guidance recommends that safety assessments include the issues of toxicokinetics and toxicodynamics. The cosmetics guidance discusses several testing methods that will have to be considered depending on the type of product and other factors.
Like the food guidance, the cosmetics guidance states that because of the different properties of nanomaterials, it may be necessary to develop and validate new test methods to ensure safety of the products. The FDA recommends that manufacturers request meetings “to discuss the test methods and data needed to substantiate the product’s safety, including short-term toxicity and other long-term toxicity data as appropriate.”
If this is starting to sound like a lot of work, time, and expense, you are getting the message. Manufacturers of cosmetics considering the addition of nanomaterials to their products should consider increasing their research and development and regulatory budgets to account for the validation of safety tests and extensive safety assessments that the FDA will apparently recommend, or to evaluate whether the addition of the nanomaterials to their products will provide sufficient incremental benefit to their products and sales to justify the costs of the safety assessments.
Source: Law360 (www.law360.com), Lynn Tyler (Lynn.Tyler@btlaw.com). Mr. Tyler is a partner in Barnes & Thornburg's Indianapolis office, where he chairs the firm’s Food, Drug and Device Law Practice Group.