FDA Withdraws NDI Approval – Is NMN still Available for Food? Is GRAS Declaration Affected?

In recent years, NMN (β-Nicotinamide mononucleotide) products are quite popular among businesses and consumers for its “anti-aging” function. In May 2022, SyncoZymes (Shanghai) Co., Ltd. received the first US FDA New Dietary Ingredient (NDI) approval for its NMN ingredient. Recently, however, the FDA has changed its position and stated that NMN cannot be marketed as a dietary supplement because it has been authorized for investigation as a new drug.

01. Conflict of restrictive provisions should be blamed for the withdrawal of NDI

In the past two years, a number of companies have submitted applications to the FDA for the approval of using NMN as a new dietary ingredient. However, they were generally rejected for a lack of “safety basis”.

In May this year, the NMN ingredient (NDI 1247) of SyncoZymes was finally approved officially, making it possible to use NMN in dietary supplement products in the US.

However, on October 11, the FDA, in response to an NDI notification submitted by Inner Mongolia Kingdomway Pharmaceutical Limited (Kingdomway), the FDA stated that NMN does not fall within the definition of a dietary supplement and cannot be marketed as a dietary supplement as well.

According to the FDA, NMN is excluded from the dietary supplements definition under the Federal Food, Drug and Cosmetic Act (the FD&C Act). Under the act, if an article has been authorized for investigation as a new drug for which substantial clinical investigation has been instituted and for which the existence of such investigation has been made public, the article may not be marketed as or in a dietary supplement unless the article was marketed as a dietary supplement or as a food before being authorized for investigation as a new drug. Ultimately, after being reviewed by the FDA, it was determined that NMN could not be marketed as a dietary supplement.

(Source: Food and Drug Administration)

Based on the above-mentioned terms, SyncoZymes (Shanghai) Co., Ltd., on November 4, received the notification on the withdrawal of NDI from the FDA. On November 20, SyncoZymes released an announcement that since the date of receiving the withdrawal notification, SyncoZymes has been in contact with relevant experts, partners, legal teams, trade associations, and other parties to further communicate and negotiate with the FDA via reasonable means, with the hopes that the FDA will withdraw its decision and restore the legality of selling NMN ingredients in the US market as dietary supplements.

As can be seen, the withdrawal has nothing to do with the safety of NMN. It is due to the exclusion term against dietary supplements, or in other words, the protective policy for new drug development. However, research on a new drug can be hard to know even by the Center for Food Safety and Applied Nutrition (CFSAN), because in many cases such research is confidential. The approval of NMN as a new dietary ingredient by the FDA may involve the interests of the drug companies.

02. NDI is prohibited, can GRAS still be declared?

The generally recognized as safe (GRAS) assessment of NMN applies to the food additive/food ingredient, thus NMN does meet the definition of “food additive” in Section 201(s) of the FFD&C Act. There are two significant factors indicating that the GRAS declaration of NMN will not be affected:

Although the definition of “food additive” under Section 201(s) of the FFD&C Act has an “exclusion” category, unlike the dietary supplement, “new drug approval” does not appear in the exclusion category for food additives.

The ingredient can be considered a food ingredient when it has one or more of the physical or technical functional effects listed in 21 CFR 170.3(o). NMN is qualified for its nutritional supplementation effects listed in 170.3(o)(20) because of its niacin (vitamin B3 ) activity.

In summary, although NMN is currently excluded from dietary supplements in the US, it does not affect the GRAS application for common foods.

03. Conclusion

There is no doubt that the prohibition on the use of NMN in dietary supplement products in the US is a heavy blow to the industry. Currently, manufacturers of NMN dietary supplements and related associations are actively communicating with FDA and seeking solutions, trying to get themselves out of the situation. CIRS Group will keep a close eye on the latest developments in this matter.

What should be highlighted is that the prohibition is valid only for NMN dietary supplement products manufactured and marketed within the US. It will not affect the manufacture and sale of NMN in other countries, nor shall it affect the GRAS declaration for NMN in common food.

China also issued several announcements on the compliance of NMN. For the moment, NMN has not been licensed in China and cannot be produced and marketed as food. In response to the No. 1067 proposal of the fourth session of the 13th National People's Congress, the SAMR stated that due to the uncertainty of positioning and safety as well as the lack of food safety national standards, it is suggested to carry out a safety evaluation for NMN as a novel food or establish the food safety national standard for this ingredient.

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