Typically this column covers issues related to the design of a clinical trial (study), the interpretation of a recently published study, implications of legal cases related to research, how to obtain tax credits for sponsoring clinical studies (as well as how to organize your corporate divisions for tax credits) via IRS Tax Codes 41 and 174, as well as general research issues surrounding the nutrition industry.
In recent months, much attention has been paid to FDA’s New Dietary Ingredient (NDI) Guidance. Since this guidance was issued, many leading trade associations and other industry entities have held “town hall” meetings to discuss various interpretations in an effort to craft reasonable comments for FDA consideration.
One aspect not often discussed is the Generally Recognized as Safe (GRAS) designation and how it might help bring products to market amidst all the current NDI controversy in the marketplace.
Is the ‘GRAS’ Always Greener?
In 1958 Congress enacted the Food Additives Amendment to the FD&C Act. This amendment defined the term “food additive” and required premarket approval for new uses of food additives. It also established the standard for review and approval of these items. Food additives are different than GRAS substances. Congress explicitly states that a food additive includes any substance of which the intended use results in or may result in direct or indirect inclusion as a component of a food. This includes substances that when added to a food, they become part of that food. Examples of this include preservatives, coloring agents, emulsifiers, sweeteners, thickeners and so forth.
At the time, Congress also stated that “substances that are generally recognized, among experts qualified by scientific training and experience to evaluate their safety as have been adequately shown…to be safe under the conditions of intended use” are excluded from the definition of a food additive. In other words, Congress stated that substances that are GRAS under conditions of intended use are not food additives and do not require premarket approval by FDA.
To obtain GRAS status is not as straightforward as Congress might have made it sound. Essentially, FDA states that in order for an ingredient to be determined to be GRAS, the scientific data and information about the use of the substance must be widely known and there must be a consensus that the substance is safe under the conditions it is set to be used for. One example of a GRAS substance that is widely known is rice bran fiber. If you are interested in what substances and ingredients have undergone GRAS review by FDA (versus self-affirmed GRAS), the agency maintains a database known as the GRAS Notice Inventory. To date, there are 421 substances on this list.
If you apply to FDA to conduct the GRAS review, then it will occur within 30 days of receipt of the packet. In 1997, FDA issued a proposed rule stating that an independent panel (of experts meeting the Congressional guidelines) could confirm the safety of a substance and notify the agency of the “self-affirmation” of GRAS. This option might allow the opportunity for quicker and more expedient innovation in the marketplace. It is interesting to note, however, that while FDA accepts self-affirmed GRAS, the proposed rule was never finalized.
GRAS ingredients and substances typically come from these groups: carbohydrates (sugars and fibers), lipids, proteins, extracts, enzymes, as well as minerals and other substances. Once an “active” is either self-affirmed as GRAS or FDA GRAS, it can be used in foods and beverages without special labels. Use of GRAS ingredients in dietary supplements is also allowed under DSHEA, since it defined dietary supplements as foods.
In the end, achieving GRAS status is worth considering when developing a novel ingredient. Toxicology via animal studies and safety studies in animals are typically required. Further, it appears at least one human prospective safety study would add to the benefits of the GRAS filing, as it would demonstrate human safety at the dose intended. Couple this with historical use data and the file (application) should sail through any independent or FDA review process.