On April 25, 2012, the U.S. Food & Drug Administration (FDA) published a draft guidance document with the somewhat unwieldy title “Draft Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food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.” Without reading further, you might never know that this document is primarily aimed at nanotechnology and its use in food and food-contact materials.
This document is one of the guidances that FDA has been urged by industry and others to produce to help clarify the regulatory picture regarding “nanosizing” of previously authorized food ingredients and food-contact substances.
FDA’s draft guidance urges caution upon the industry when making determinations of compliance with existing authorizations. For those substances and uses where FDA has an existing authorizing regulation (food additives, color additives, and affirmed GRAS ingredients), the agency has advised manufacturers to look beyond the plain language of the authorizing regulation to determine whether the new nanoscale substance is truly the same substance in terms of identity and intended technical effect.
FDA has traditionally taken the position that if a substance was manufactured in a manner such that it was chemically identical to the substance in an existing regulation and met the specifications and limitations of the existing regulation then the substance was permitted for the regulated use. FDA’s assertion that the administrative record should be considered as well as the regulation raises questions regarding how a manufacturer can confidently interpret regulations without reviewing the entire record of FDA’s action; a cumbersome prospect at best.
FDA’s position regarding the record of the safety determination has more merit with regard to GRAS self-determinations and those food-contact substances authorized under the agency’s Food Contact Notification program. For GRAS self-determinations, it is clear that significant changes in manufacturing processes may change the facts of the safety assessment and thus may invalidate a previous assessment and make a new assessment necessary. For notified food-contact substances, the FD&C Act makes the authorization manufacturer specific (See 21 U.S.C. 348(h)(2)(C). Consequently, FDA has always advised that the entire record of the notification is relevant to the authorization, including the manufacturing process. Thus, if a significant change has been made to the manufacturing process, a food-contact substance will generally need to be renotified.
The draft guidance also emphasizes the current level of uncertainty regarding the safety assessment of nanomaterials and advises manufacturers incorporating nanoscale versions of authorized food ingredients and food-contact substances to perform a safety assessment of such materials as a first step in determining compliance. FDA cites reviews of the existing uncertainty in the testing and safety assessment of nanomaterials and reminds manufacturers that they are responsible for marketing a safe product no matter whether it appears to comply with an existing authorization or not. With regard to GRAS self-determinations, FDA’s guidance points to the uncertainty regarding toxicity testing and assessment of nanomaterials as evidence that the safety of nanoscale materials may not be directly inferred from data on their traditionally manufactured counterparts. Perhaps more significantly, FDA’s guidance points to the current uncertainties in the applicability of standard toxicity testing to nanomaterials as a significant if not impossible hurdle for reaching general recognition of safety. Essentially, FDA is asserting that there is significant scientific disagreement regarding the safety of nanomaterials generally, creating a potential bar to GRAS determinations across the board. It is important to note that, although FDA has all but pre-cluded GRAS determinations, it has not and cannot eliminate the possibility of GRAS determinations for nanomaterials without at least conducting rulemaking.
All the policy and scientific intricacies aside, FDA’s guidance document includes some very good advice. Manufacturers need to carefully consider the use of nanotechnology to produce food ingredients and food-contact substances to ensure that they have thoughtfully addressed all potential safety and regulatory issues. Without this consideration, manufacturers run the risk of finding their products the target of a highly publicized FDA enforcement action. As bad as that would be for the manufacturer or brand owner involved, it would be equally bad for what promises to be a valuable technology for the food industry and for advancing public health.
Mitchell Cheeseman, Ph.D., an IFT member, is Managing Director of Environmental and Life Sciences at Steptoe and Johnson LLP, Washington, DC 20036 ([email protected]).