Introduction to GRAS & NDI
An ingredient can get into the diet by being a food, food additive, drug, dietary supplement, or GRAS ingredient. The way that ingredient is used and what the finished product marketer says about it determines which category it goes into. Depending on product use and marketing claims, one ingredient could go into many buckets.
GRAS Ingredients & GRAS Determination:
GRAS ingredients are intended to become a component of food. They must have general recognition of safety based only on the views of experts qualified by scientific training and experience to evaluate the safety of substances directly or indirectly added to food. GRAS ingredients are supported by either scientific procedures or everyday use in food before January 1, 1958. GRAS is a summary of all available evidence, positive or negative.
GRAS requires the same safety standard as food additives, i.e., reasonable certainty of no harm. However, unlike a food additive, the Information must be publicly available. For GRAS determination, a history of consumer exposure is required, and the product labeling can’t limit intake by amount or population. A GRAS determination must also outline the intended effect or practical use.
GRAS Status:
GRAS status was a carve-out of the food additives group created in the Food Additives Amendment of 1958. In 1997, legislation allowed GRAS status to be self-determined, taking it out of the premarket-approval process. Before this, a company needed to petition FDA; however, this process caused GRAS petitions to backlog in FDA offices. Companies would sometimes have to wait years to get approval. Post-1997, companies can still petition FDA, but it is not an approval process. Once a company self-affirms an ingredient as GRAS, it can send it to FDA for review. FDA can then issue a “no-objection or an objection” to the GRAS status of an ingredient.
Food Additives & Dietary Ingredients:
Food Additives also become a food component, but they require premarket approval. The research on food additives doesn’t have to be publicly available or acceptable. Like GRAS, food additives cannot exclude sub-populations or limit intake.
Dietary Ingredients supplemented the diet and were legally created with the Dietary Supplement and Health Education Act of 1994 (DSHEA). Dietary supplements are not subject to premarket approval but require premarket notification with a 75-day review period. Dietary ingredients can limit intake by amount and population on the label. The safety data on nutritional ingredients don’t need to be publicly available or accepted. Still, DSHEA said the safety needs to be reasonably expected to be safe under the conditions used in the labeling.
FDA Draft Guidance GRAS or NDIN Clarification:
According to the Draft Guidance, the categories can seem straightforward, but some ingredients, such as probiotics, that industry considered dietary ingredients that may fall into the food additive category. Regarding probiotics, it’s up to product manufacturers to prove they were in man’s diet before they were isolated as an ingredient and used in a dietary supplement or as a GRAS ingredient. If not, they are considered food additives.
Novel strains will typically require regulatory approval to lawfully enter the U.S. market, even if some strains within the species have regulatory approval or have a history of use. The most common pathways to achieve regulatory compliance are through Generally Recognized as Safe (GRAS) or a New Dietary Ingredient Notification (NDIN). Determining the best way is specific to the individual probiotic and product goals. This installment of our probiotic series will walk through some primary considerations to help you decide the best path to regulatory compliance for a novel probiotic ingredient. To help determine the best path, we can start by answering the following questions:
What is the intended use (GRAS vs NDI)?
If the goal is to add the ingredient to conventional foods, the GRAS pathway is best. Once you have the ingredient GRAS for use in conventional foods, the ingredient is placed in the food supply. The ingredient (must be the same as what was GRAS and in the food supply) can be used as a new dietary ingredient (NDI) in dietary supplements as well, and in this case, the NDIN to FDA is not required. Suppose the goal is to add the ingredient into dietary supplements only. In that case, either the GRAS or NDIN pathway may be available, and the best path could depend on the answers to the additional questions below.
Does the ingredient qualify as a dietary ingredient under DSHEA?
To utilize the NDIN pathway, the substance must meet the definition of “dietary ingredient.” DSHEA defines a “dietary ingredient” as a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any of the above dietary ingredients.
Is there a population that should be excluded from using the ingredient?
The NDI pathway provides more freedom to exclude specific populations or age groups. For example, if the ingredient does not have any clinical studies in pregnant or nursing women or children under 2, these groups could be excluded from an NDIN.
Is the GRAS or NDI safety information publicly available?
All information that is pivotal to showing the safety of an ingredient in the GRAS process must be publicly available. This is not the case for the NDIN pathway. In an NDIN, safety studies do not have to be published, and more information in the notification is permitted to be redacted compared to the GRAS pathway. Because of this, the NDIN pathway allows for more proprietary data.
Does the client need to notify the FDA for GRAS notification?
For the NDI pathway, notification to FDA is mandatory, whereas notification to FDA on a GRAS conclusion is voluntary (some exceptions apply).
Conclusion:
The NDI pathway is a possible pathway for a probiotic ingredient found in the food supply. The NDI pathway is only applicable to dietary supplement usage and does not extend to regulatory compliance for use in conventional food products. The NDI pathway allows for more protection of proprietary information.
The GRAS pathway is a possible pathway for a probiotic ingredient found in the food supply and one derived from non-food sources. The GRAS pathway requires pivotal safety data to be publicly available. A conclusion of GRAS may or may not be notified to FDA. Suppose a probiotic is GRAS and placed into the food supply. In that case, the probiotic may be used in a dietary supplement as a new dietary ingredient without the required NDI notification, provided the dietary supplement does not contain significantly higher levels of the NDI than is used in already established conventional foods or does not exceed the levels established as safe in a GRAS conclusion.
Determining the best pathway to regulatory compliance can seem overwhelming but considering the above factors can direct you to the most appropriate path for your specific novel probiotic. RNI is also available to help you determine the best path forward based on your ingredient needs and goals and can support the development of your GRAS and NDIN dossiers for regulatory compliance. Learn more about self-affirmed GRAS here:
We hope this post helped you understand food additives and preservatives a little better. There are many different kinds, and they can have a big impact on your health.
Please contact our team for more information on food classification, ingredient feasibility questions, ingredient submissions, and food labeling projects. Our specialists are here to help with the following services: Novel Food Notifications, SFCR License application, HACCP & PCP program, TMA License for Supplemented Foods, Nutrition Facts Table (NFT) Creation and label compliance!
