Animal Food GRAS Conclusions

Introduction

“GRAS” is an acronym for Generally Recognized As Safe, which stands as an important food regulatory category in the United States. Simply speaking, if a substance is GRAS under the conditions of its intended use among qualified experts, it is excluded from the definition of a food additive and is not subject to the premarket approval requirements of the Federal Food, Drug, and Cosmetic Act.

This means that a substance that has been concluded GRAS may be marketed for its intended use in human food or animal food without FDA review or approval. It is, however, important to note that it is the use of a substance, rather than the substance itself, that is eligible for GRAS status.

Boasting widespread recognition internationally, GRAS has become a gateway for enterprises to access global markets.

The general underlying principles and legal and regulatory framework are the same regardless of whether a GRAS substance is intended for use in human food or animal food. A general discussion regarding GRAS is can be found here US FDA GRAS Notice. This article discusses those aspects of independent conclusions of GRAS status and GRAS notices that are unique to animal food GRAS conclusions (i.e., the differences between human food GRAS conclusions and animal food GRAS conclusions).

Aspects of GRAS conclusions unique to animal food dossiers:

• Definitions appearing in the Official and Tentative Definitions of Feed Ingredient section of the annual Official Publication of the Association of American Feed Control Officials (AAFCO), are generally regarded as common or usual names of substances used in animal food.
• Animal species for which the foods containing the substance are intended (i.e., target animals) must be identified, and when appropriate, any “subpopulation” (e.g., life state of an animal) must be described.
• The necessity to provide data and information that bear on the safety of the physical or other technical effect of the substance is determined on a case-by-case basis but may be required more frequently for an animal food GRAS conclusion relative to a human food GRAS conclusion.
  • Animal food is often formulated to supply all the animal’s nutritional needs for a specific life stage and fed to the animal as the sole diet for long periods of time. Thus, a GRAS substance intended for use for a nutritive effect may need to demonstrate its ability to meet that need (i.e., demonstration that is use does not result in poor growth, excessive weight loss, organ system failures, or death) if such data is not already generally available. In such cases, it may be necessary to conduct and publish animal feeding studies using doses providing the proposed use level as well as levels above and below the proposed level. Such studies should be conducted according to AAFCO guidelines and published.
  • Additionally, some physical or technical functional effects of the GRAS substance that are not nutritive effects may also bear on safety and, therefore, require demonstration of their effectiveness (e.g., enzymes or binders and fillers that affect bioavailable of nutrients in the feed). Such substances may require both animal feeding studies as well as stability studies when such information is not already generally available.
• When the target animals of a GRAS conclusion are food-producing animals, the general recognition of safety requires both exposure estimates and safety evaluations for both the target animals and humans consuming food derived from the target animals.
• If safety studies are conducted in animals other than the target animals, the GRAS conclusion must address how such data and information can be extrapolated to the target animals. Interspecies extrapolation requires consideration of differences and similarities in digestive systems, physiology and metabolism, and normal diets.
• When studies are necessary in target animals, they should be conducted in animals of the life stage for which the substance is intended. These studies should be published.
  • In general, toxicological studies in target animals should be conducted in groups of animals of both sexes using a negative control group, the maximum proposed use level, 3 times the proposed use level, and 5 time the proposed use level for a minimum of 90 consecutive days. These studies should evaluate the following examinations: detailed physical examinations and daily clinical observations (e.g., general health, behavior, appearance, and eating patterns), mortality, weight gain, feed intake, clinical pathology (e.g., hematology, blood chemistry, urinalysis), necropsy findings (e.g., organ weights and gross pathology), and histopathology. Appropriate guidelines and good laboratory practice should be followed.
  • Other studies (e.g., pharmacokinetics, reproductive and developmental toxicity) should be considered on a case-by-case basis.
• When a candidate GRAS substance is intended for use at multiple life stages and/or in multiple species, safety studies should be conducted in the most sensitive life stage and/or species when extrapolation of data is determined to be justified.

FDA GRAS Notice

The general discussion regarding FDA GRAS notices at US FDA GRAS Notice is applicable to animal food GRAS notices. Upon conclusion of their evaluation of an animal food GRAS notice, FDA will post the GRAS notice and their response letter to the Current Animal Food GRAS Notices Inventory on their website.

Estimated timeframe

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