iWhether formulating a new food or developing a novel ingredient, a critical first step is understanding the regulatory framework for bringing a new ingredient (or a food containing a new ingredient) to the market. This article briefly describes the most common regulatory pathways available to a new ingredient or otherwise new use.
To begin, any substance that is reasonably expected to become a component of a food is a food additive that is subject to premarket approval by FDA, unless the substance is generally recognized as safe (GRAS) among experts qualified by scientific training and experience to evaluate its safety under the conditions of its intended use, or meets one of the other exclusions from the food additive definition in Section 201(s) of the Federal Food, Drug, and Cosmetic Act (FFDCA).
We discuss the definition of food additive and briefly summarize the regulatory process for each food ingredient categories: GRAS, and Food Contact Substances notifications.
Food Additives – The Lengthiest Pathway
As defined in FFDCA § 201(s), a food additive is any substance, other than GRAS or otherwise excluded substances, whose use results (or may reasonably be expected to result) in the substance becoming a component of food, or affecting the characteristics of a food (whether directly or indirectly). This broad definition encompasses substances used not only as food ingredients, but also substances used in manufacturing, packing, processing, preparing, treating, packaging, transporting, and holding a food, as well as any source of radiation used in any stage of food production. Categories of food additives are numerous, and include acids, anticaking/antifoaming agents, antioxidants, food coloring, bulking agents (e.g., starch), preservatives, stabilizers, and sweeteners, among others.
All food additives must be submitted for approval by petitioning the FDA unless they are exempted or otherwise specifically addressed by existing FDA regulations. While the statutory period for review is 180 days, in reality, the food additive petition process can take multiple years to obtain approval. Because the GRAS process, described below, is significantly faster, an early gating issue will be whether your new ingredient can go down the GRAS pathway or whether it will be considered a food additive. More information on the food additive petition process can be found here.
GRAS – A Pathway with Two Forks in the Road
A substance that is generally recognized as safe has either been scientifically proven to be safe based upon testing by qualified experts with adequate data that is at least equivalent to what it would take to obtain FDA approval or, for older substances in use prior to 1958, through experience based on long-term common food use and general recognition of safety based on common knowledge amongst the scientific community (21 CFR 170.30).
A GRAS determination is the obligation of the ingredient manufacturer. While there are two distinct pathways to determine GRAS status (so-called “self-affirmation” and the “GRAS notification” pathway), it is up to the manufacturer to decide which pathway to pursue and to ensure it complies with FDA requirements.
In both instances the statutory requirement that must be met is the same. However, in the self-affirmation pathway, a manufacturer prepares a GRAS dossier which is then submitted to a third-party GRAS panel. (The composition of a GRAS panel can vary based on the ingredient and Foley has experience with consulting groups who assist the selection of a GRAS panel). The panel then evaluates whether the ingredient may be deemed GRAS or not. (For guidance on best practices for convening a GRAS panel, see here.) If the panel determines the ingredient is GRAS, the ingredient may be commercialized without any FDA involvement. However, although this is a legally sufficient process, for commercial reasons, a self-affirmed GRAS pathway may not be advisable. This is because many large food manufacturers will not accept (i.e., not begin formulating or purchasing) a “self-affirmation” GRAS ingredient and instead, specify manufacturers to prove GRAS by notification to FDA.
The GRAS notification pathway is not an FDA approval pathway in that FDA does not “approve” a GRAS notification. Rather, FDA will review the GRAS notification, and provide one of three responses:
- The agency does not question the basis for the notifier’s GRAS conclusion (“no objection letter”);
- The agency concludes that the notice does not provide a sufficient basis for a GRAS conclusion (e.g., because the notice does not include appropriate data and information, or because the available data and information raise questions about the safety of the notified substance); or
- The response letter states that the agency has, at the notifier’s request, ceased to evaluate the GRAS notice (“a withdrawal letter”).
The GRAS notification pathway can be a collaborative process with the FDA, and so some back-and-forth with the agency is not unusual. It is also possible, and often wise, to pursue a pre-submission meeting with FDA to increase the likelihood of receiving a “no objection” letter.
Food Contact Substance Notification – The Packaging Pathway
Under FFDCA § 409 (21 U.S.C. § 348), food contact substances are any substances intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding foods, as long as such substances are not intended to have a technical effect on the food. This includes substances used in food packaging (and its components), food processing equipment, food-contact surfaces, and cookware, as well as substances added to or applied on packaging surfaces.
The governing rules on food contact substances specify that a substance may be exempt from regulation as an additive if it satisfies four conditions: (1) the substance has not been shown to be a carcinogen, and based on the chemical structure of the substance there is no reason to suspect it of being a carcinogen, (2) the substance poses no other health and safety concerns, (3) the substance has no technical effect on the food, and (4) the substance has no significant adverse impact on the environment (21 CFR 170.39).
The FDA requires companies who wish to use a food contact substance to submit Food Contact Substance Notifications (FCNs) to FDA prior to marketing the product. The FDA has a mandated 120-day time-period to review that submission, and if the agency does not express any objections about the safety of the substance in that time-period, then the company can legally market the product. Note however, that an effective FCN applies only to the food contact substance that is the subject of the FCN and is applicable only to the manufacturer/supplier listed within the notification.
