Frequently Asked Questions on FDA Generally Recognized As Safe (GRAS) Certification, Vol. 2

Q1: What does GRAS mean and how is it different from NDI?

NDI is an acronym for the phrase “New Dietary Ingredient”, and GRAS is an acronym for the phrase “Generally Recognized As Safe”. Simply put, NDI pertains to ingredients intended to be added in dietary supplements (health foods), while GRAS is for common food ingredients.

In addition, an NDI must undergo the premarket review before being marketed; whereas an applicant may choose between Self-GRAS (Self-affirmed GRAS) or FDA GRAS (FDA GRAS Notification). In other words, NDI must be submitted to FDA, while the notifier’s decision to submit a GRAS notice is voluntary.

Q2: If I submit a GRAS notice, how long will it take for me to receive a response from FDA?

1. The FDA will conduct a preliminary review upon receiving the GRAS dossier, which can be regarded as the acceptance stage. Once accepted, the dossier is filed, and a GRN No. is assigned. In the past, this step didn’t take more than a few days to process. However, due to the recent surge in the number of FDA GRAS applications, the timeframe has been extended and it may now take several months.

2. The GRAS notification procedure requires that FDA respond to a GRAS notice within 180 days, with an option to extend the 180-day timeframe by 90 days on an as needed basis.

Q3: What are the types of response I may receive from FDA when applying for FDA GRAS?

Examples of the types of response FDA commonly sends include:

Response	Status	Remarks
FDA has no questions	√ Approval	FDA recognizes the safety of the substance for market use
Notice does not provide a basis for a GRAS determination	× Disapproval	FDA doesn’t recognize the safety of the substance
At the notifier’s request, FDA ceased to evaluate this notice	○Cease to evaluate the notice	An applicant may request FDA to cease to evaluate the notice and resubmit a notice for the same substance.

Q4: For food substances already in the marketplace, is GRAS application required if new manufacturing processes are adopted?

A4: Yes. It is required if there are significant manufacturing process changes.

(You may refer to the Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that Are Color Additives by FDA.)

In simple terms, when determining whether there have been significant manufacturing process changes of food ingredients already on the market, the following factors should be considered:

• Whether it alters the identity of the food substance;
• Whether it affects the safety of food consumption;
• Whether it affects the regulatory status of the food substance; and
• Whether it requires regulatory submission to FDA

For instance, for a chemically synthesized food ingredient already authorized on the market, if the applicant adopts a new process involving genetically modified microorganisms, it would be deemed as a significant manufacturing process change, requiring resubmitting GRAS notice.

Q5: After submitting a GRAS notice, is it necessary to resubmit if the production factory is changed?

GRAS aims to assess the safety of the notified substance and its manufacturing process. As mentioned above, changing the production factory/contract manufacturing facility is not considered a significant process change, thus resubmitting a GRAS notice is not required.

Moreover, although regulations do not prohibit companies from using previously approved GRAS dossiers to demonstrate the safety of their substances, due to the challenge of proving complete consistency in manufacturing processes and product specifications with submitted GRAS, GRAS maintains a certain exclusivity and is not generally applicable across industries.

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Further Information

Frequently Asked Questions about FDA Generally Recognized As Safe (GRAS) Certification, Vol. 1