GRAS Status for Probiotics: Leveraging Market Potential in the U.S.

About GRAS (Generally Recognized as Safe) 

GRAS (Generally Recognized as Safe) is a food substance classification established by the U.S. Food and Drug Administration (FDA). It designates substances that are generally recognized, among qualified experts, as having been adequately shown to be safe under the conditions of their intended use.

GRAS status can be established through two pathways: FDA GRAS Notification and Self-affirmed GRAS.

• Self-affirmed GRAS: This involves a safety assessment and conclusion by a panel of qualified experts without notification to the FDA. The related documentation is generally not made public.
• FDA notified GRAS: This involves submitting a GRAS notification to the FDA for official review. Upon receiving a “Has no questions ” letter from the FDA, the substance is listed in the public GRAS Notice Inventory and can be verified on the FDA’s website.

Substances that have obtained GRAS status through either pathway can be legally marketed in the United States.

Probiotic Regulation in the U.S.

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, such as balancing gut microbiota and enhancing immune function. This has led to their widespread application in the food industry.

However, under the current U.S. regulatory framework, there is no separate regulatory category for “probiotics.” Instead, they are regulated based on the product’s intended use and claims.

When are probiotics used in conventional foods?

They must meet the safety standards for conventional foods. If the probiotic is a new ingredient, it must undergo a Food Additive Petition (FAP) or obtain GRAS status.

When are probiotics used in dietary supplements?

They must meet the definition of a dietary ingredient. New ingredients can be introduced via a New Dietary Ingredient Notification (NDIN) or through the same pathways as new ingredients in conventional foods (i.e., FAP or GRAS).

From a global industry perspective, FDA GRAS status serves as a key indicator of a probiotic’s market acceptance and safety.

To date, 76 probiotic dossiers have received an “FDA has no questions ” letter from the FDA, reflecting the vast market potential for probiotics worldwide. Based on this public data, REACH24H has conducted a comprehensive analysis of these FDA-recognized probiotics.

Accelerated Growth of FDA GRAS Notifications for Probiotics

Since the first probiotic dossier received an “FDA has no questions ” letter in 2002, the number of probiotics with FDA GRAS status has steadily increased. REACH24H has compiled statistics on the number of FDA GRAS notifications for probiotics over the years.

Number of Probiotics Certified by FDA GRAS Notifications

*Due to a lag in updates on the FDA’s official website, data for 2024 and 2025 is incomplete.

The data shows that prior to 2018, the number of annual approvals for probiotics remained in the single digits. Beginning in 2019, the market entered a period of high activity, which culminated in explosive growth in 2023 with 23 notifications approved.

The number of FDA GRAS notifications for probiotics in the last six years accounts for 70% of the total number to date. This data clearly indicates that the GRAS notification process has become an accelerated pathway, presenting a significant opportunity for companies looking to enter the U.S. market.

An Increasingly Diverse Range of Probiotic Strains

As the number of GRAS notifications grows, so does the diversity of probiotic strains. REACH24H has compiled statistics on the currently approved probiotic strains by classification. 

Analysis of the data shows:
The majority of FDA GRAS-notified probiotic strains are highly concentrated in four major genera: Bifidobacterium (26), Lactobacillus (21), Lactiplantibacillus (10), and Bacillus (8). These four genera account for 65 approved strains, representing over 83% of the total. Traditional probiotic species continue to dominate industrial applications.

However, it is noteworthy that the landscape of approved probiotics is expanding, driven by breakthroughs in microbiological research and diverse market demands. The FDA GRAS list now includes novel genera such as Streptococcus, Weissella, Clostridium, Bacteroides, and Anaerobutyricum. These novel strains often possess unique metabolic properties that can help companies create more differentiated products. This trend also signifies the sustained and growing enthusiasm in the global probiotics market.

Application Scenarios for GRAS-Notified Probiotics

In the food market, probiotics have been widely integrated into various product categories.

REACH24H has compiled statistics on the application category of products that are intended to use probiotics that have obtained FDA GRAS certification.

Statistical analysis reveals:
Probiotics have permeated a wide array of food product categories, from specialized areas like infant formula to mass-market segments like dairy and beverages; from staple foods like cereals and baked goods to recreational foods like snacks and confectionery; and finally, to dietary supplements and nutritional products.

The addition of FDA GRAS-notified probiotics can infuse products with unique health attributes, helping companies stand out in a competitive market.

How to Apply for GRAS Status for Probiotics

In theory, any organization or individual can apply for GRAS status through either of the following pathways:

1. Self-affirmed GRAS
   This involves preparing a GRAS assessment dossier and having it reviewed and signed off by a panel of qualified experts. The evaluation materials are not submitted to the FDA and the information is not made public.
2. FDA GRAS Notification
   This requires preparing a GRAS assessment dossier and submitting it to the FDA. The submission is then evaluated by FDA experts, and it requires receiving a formal “no questions letter” from the FDA. It is important to note that an FDA notified GRAS dossier often needs to include the conclusion from a self-affirmed GRAS expert panel as part of the evidence.

In summary, a self-affirmed GRAS determination is sufficient for legally marketing a probiotic in the United States. However, an FDA GRAS notification is more advantageous for marketing and promotion, despite the longer timeline. Companies can choose the most suitable pathway based on their specific market strategy.