GRAS – One of FDA’s Most Widely Misunderstood Acronyms (Part 2)

By Carrie Rabe

Another of the widely held misconceptions about GRAS status is that it means that an ingredient is considered safe by the FDA, irrespective of how much is used and for what purpose. This interpretation is, however, quite different than what is stated in Section 201(s) of the Federal Food Drug & Cosmetic Act wherein GRAS refers to a conclusion regarding safety of a food substance “under the intended conditions of use.” Thus, GRAS is a conditional designation rather than a broad acknowledgment of safety. The intended conditions of use under which a substance is considered to be GRAS are noted in the CFR in Sections 182, 184, and 186. These sections pertain to direct addition to foods in order to achieve a physical, nutritional, or other technical effect in the food (Sections 182 and 184 of the CFR) or indirect incorporation in foods as result of use of the substance in food manufacturing, processing, or packaging (Sections 182 and 186 of the CFR). In some cases, GRAS substances are broadly characterized by the type of intended effect and in other cases very specific limits on the type of use considered to be GRAS are specified. Irrespective of whether the use description is broad or narrow, it is a stipulation of the GRAS designation that when a substance is directly added to food for an intended purpose, the amount used is not greater than what is needed to achieve the intended effect. In most cases the CFR does not specify what use levels are acceptable for a specific use, leaving the discretion about how much to use to the food manufacturers. However, many substances are determined to be GRAS only when used at levels below a certain maximum. If a manufacturer uses a GRAS-designated substance for purposes other than those described in the CFR or in amounts much greater than what is reasonably needed to achieve the specified effect described in the CFR, the substance may no longer be considered GRAS. Even substances designated as GRAS for multiple purposes were given GRAS status taking into consideration the total potential exposures based on known uses in foods at the time that the designation was made. New uses or amounts of use that deviate significantly from those envisioned at the time that the GRAS determination was made may not necessarily be considered GRAS; even for those substances with a multipurpose GRAS designation. Limitations on exposure are often found for GRAS substances that have the potential to migrate into foods during manufacturing, processing, or packaging. Consistent with the concept of not using more of a GRAS substance than is needed for an intended effect when that substance is intentionally added to foods, the FDA stipulates that the amounts of GRAS substances that indirectly migrate into foods should be minimized. Thus, even though maximum use levels are not stipulated in most cases in Sections 182, 184, and 186 of the CFR, potential exposure is a principal determinant of whether a substance is considered to be GRAS. Potential exposure should also be considered when citing a substance’s GRAS status as evidence of safety of a substance for a non-food use. Any conclusion regarding the safety of a substance that relies on GRAS status should consider the route and extent of exposure for the non-food to assure that it does not deviate in significant ways from the GRAS food use cited in the CFR.

Carrie Rabe, Ph.D. is a Senior Consultant at The Weinberg Group, the world’s leading food and drug consulting firm. If you have any questions or thoughts on this blog post or others, please contact us.