A Comprehensive Overview of FDA GRAS Updates in the First Half of 2025

GRAS (Generally Recognized As Safe) means that a substance is generally recognized as safe. If a substance is recognized as safe under its intended use, it is classified as GRAS and can be exempted from pre-market approval procedures required by U.S. law. As a key basis for recognizing new food ingredients in the United States, FDA GRAS notifications remain active. After nearly three months without updates, the FDA recently made a significant update to the FDA GRAS list, with the most recent update being on June 10, 2025.

CIRS Group has conducted a detailed statistical analysis and summary of the FDA GRAS substances from January to June 2025, providing insights and references for companies.

Summary of the submission and approval of FDA GRAS Notices in the first half of 2025

On the FDA website, GRAS dossier statuses are categorized into three types: FDA has no questions; Pending; and At the notifier's request, FDA ceased to evaluate this notice.

In the January 2025-June 2025 update, a total of 59 substances were updated in status. Among them, 34 substances passed the certification and updated the “FDA has no questions” status, 15 new substances were in pending, and another 10 substances were ceased to be evaluated.

Figure 1. GRAS Notice Submitted to FDA in the First Half of 2025

Substances notified and updated on the FDA website in the first half of 2025 (based on publication date): a total of 34 substances

In the first and second quarters of 2025, 34 substances were updated on the FDA website as having received “FDA has no questions” status. Among them: 13 were microbial-derived substances, 12 were other types of substances, 5 were sugar substitute ingredients, 3 were dairy-based products and 1 was a human milk oligosaccharide (HMO). These GRAS notifications were submitted by companies from a variety of countries, including the United States, China, South Korea, Japan, Canada, the Netherlands, Ireland, India, Estonia, and Chile. Notably, U.S. and Chinese companies were the most active contributors.

Note: Although these 34 substances were only recently updated on the FDA website, many of them had actually received their “FDA has no questions” letters much earlier. The approval dates range widely from February 5, 2024, to March 14, 2025. A significant portion of the dossiers were approved between June and December 2024, while a few were approved in Q1 2025. The delayed publication on the FDA website accounts for the recent appearance of these approvals in the public database.

Table 1. Substances updated with “FDA has no questions” status in Q2 2025

S.N	GRN NO.	Name	Product Type	Company	Date
1	1069	Corn protein	others	Cargill, Inc. (US)	2024.02.05
2	1109	β-agarase enzyme preparation produced by Streptomyces coelicolor	microbial-derived substances	Dyne Bio Inc. (Korea)	2024.04.15
3	1117	Mycelial biomass from Neurospora crassa	microbial-derived substances	The Better Meat Co. (US)	2024.07.09
4	1120	α-Galactosidase enzyme preparation produced by Aspergillus niger	microbial-derived substances	Novozymes North America (US)	2024.06.05
5	1122	Canola concentrate	others	NapiFeryn BioTech Sp. z o. o. (Poland)	2024.07.25
6	1126	Calcium acetate	others	Niacet Corporation (US)	2024.06.07
7	1129	Heat-killed Clostridium tyrobutyricum strain ASM#19	microbial-derived substances	Superbrewed Food, Inc. (US)	2024.02.22
8	1133	Resistant dextrin from corn	others	Anderson Global Group (US)	2024.01.22
9	1139	Transglutaminase enzyme preparation produced by Bacillus licheniformis carrying a gene encoding transglutaminase from Streptomyces mobaraensis	microbial-derived substances	Novozymes North America (US)	2024.07.02
10	1147	Copper(II) ion	others	Copperprotek SPA (Chile)	2024.07.05
11	1148	D-psicose	sugar substitute ingredients	Daesang Corporation (Korea)	2024.09.30
12	1151	Fava bean protein	others	Cooperative Koninklijke Cosun U.A. (Netherlands)	2024.06.12
13	1154	Triacylglycerol lipase enzyme preparation produced by Komagataella phaffii expressing the gene encoding lipase from Fusarium oxysporum	microbial-derived substances	Lallemand Inc. (Canada)	2024.08.15
14	1157	2'-fucosyllactose	HMO	Synaura Biotechnology (Shanghai) Co., Ltd.(China)	2024.08.07
15	1159	Heyndrickxia coagulans strain MTCC 25460 spore preparation	microbial-derived substances	Pellucid Lifesciences Pvt., Limited (India)	2024.05.06
16	1161	Triacylglycerol lipase enzyme preparation produced by Candida cylindracea	microbial-derived substances	Meito Sangyo Co., Ltd. (Japan)	2024.09.24
17	1164	A chemically synthesized analog of pediocin PA-1 specific to Listeria monocytogenes	others	Innodal and Quality Systems Solutions (Canada)	2024.08.07
18	1166	Fava bean (Vicia faba L.) protein hydrolysate	others	Nuritas (Ireland)	2024.11.13
19	1167	Brazzein produced by Komagataella phaffii expressing a gene encoding for brazzein from Pentadiplandra brazzeana	sugar substitute ingredients	Perfect Day, Inc. (US)	2024.10.08
20	1170	Resistant dextrin from tapioca in powder or syrup form	others	Icon Foods, Inc. (US)	2024.10.22
21	1171	Collagen polypeptide produced by Escherichia coli K-12 S9188	others	Geltor, Inc. (US)	2024.10.22
22	1174	Dry whole goat milk	dairy products	The LittleOak Company (US)	2024.12.06
23	1175	Lactiplantibacillus plantarum DSM 23881	microbial-derived substances	Nordwise BioCC OÜ (Estonia)	2024.10.22
24	1183	Monellin preparation produced by Komagataella phaffii P-MON-040 expressing a gene encoding for a modified monellin	microbial-derived substances	Oobli, Inc. (US)	2024.11.22
25	1184	Rebaudioside M from a modified strain of Escherichia coli BL21(DE3)	sugar substitute ingredients	Sichuan Ingia Biosynthetic Co., Ltd. (China)	2024.10.23
26	1187	Polygalacturonase enzyme preparation produced by Trichoderma reesei expressing a gene encoding polygalacturonase from Aspergillus luchuensis mut kawachii	microbial-derived substances	AB Enzymes Inc. (US)	2025.02.28
27	1188	D-psicose	sugar substitute ingredients	Shandong Starlight So True Biological Technology Co., Ltd (China)	2024.11.19
28	1190	Saccharomyces cerevisiae strain OYR-481 expressing a gene encoding acetolactate decarboxylase from Brevibacillus brevis	microbial-derived substances	Omega Yeast Labs, LLC (US)	2024.09.27
29	1191	Ergothioneine produced by Escherichia coli BL-21 (DE3) expressing ergothioneine synthases from Schizosaccharomyces pombe	others	Shanghai EGT Synbio Group Co., LTD (China)	2025.01.30
30	1197	Fructanase enzyme preparation produced by Trichoderma reesei AR-577 expressing the gene encoding fructanase from Lactobacillus crispatus	microbial-derived substances	AB Enzymes Inc. (US)	2025.03.14
31	1198	Inositol	others	Sichuan Bohaoda Biological Technology Co., Ltd. (China)	2025.02.03
32	1206	Rebaudioside M produced by enzymatic treatment of rebaudioside A purified from the leaves of Stevia rebaudiana (Bertoni) Bertoni	sugar substitute ingredients	Adorvia Biotechnology Co., Ltd. (China)	2025.02.28
33	1211	Reduced minerals goat whey	dairy products	Crossway Foods Limited (Ireland)	2025.02.04
34	1212	Liquid whole goat milk	dairy products	Crossway Foods Limited (Ireland)	2025.02.07

Note: GRN 1187 is a resubmission of GRN 1110, and GRN 1197 is a resubmission of GRN 1121.

Substances ceased to be evaluated in the first half of 2025 and their reasons

As of June 10, 2025, a total of 10 GRAS notifications were marked as “At the notifier’s request, FDA ceased to evaluate this notice” in the FDA database during the first half of the year. Due to delays in the FDA’s website updates, most of these dossiers were actually withdrawn in 2024, but their status was not publicly updated until 2025. Details are summarized in Table 1 below.

Table 2. GRAS notifications marked as ceased to be evaluated in the first half of 2025

GRN NO.	Name	Product Type	Company	Date	Reasons
1141	L-α-glycerophosphorylcholine	others	Shenyang Gold Jyouki Technology Co., Ltd (China)	2024.04.29	Insufficient EDI data and safety data.
1152	Phoenix oyster mushroom (Pleurotus pulmonarius) mycelia biomass	others	Mushlabs GmbH (Germany)	2024.03.21	The lack of data on potential gene expression differences between the fruiting body and the mycelium raises concerns regarding differential safety profiles for human consumption.
1153	Pongamia bean oil	others	Terviva, Inc. (US)	2024.05.23	The substance exhibits pharmacological activity.
1160	Lemna leaf protein	others	Plantible Foods (US)	2024.05.06	Key safety data are not publicly available.
1163	A preparation containing two bacteriophages (phage) specific to Salmonella enterica	microbial-derived substances	Cytophage Technologies inc. (Canada)	2024.05.28	Change in manufacturing process.
1168	Tigernuts flour	others	Tigernut Traders, SL (Spain)	2024.08.06	There are concerns regarding the reliability of the safety data. The extrapolation factor from animal studies lacks justification, and the toxicological study was conducted solely in female rats.
1169		HMO	GeneChem, Inc. (Korea)	2024.10.07	There is inadequate information on the removal of impurities such as lithium during production. The compositional data are not clearly presented, and the exposure assessment based on intended use lacks transparency and scientific rigor.
1176	Lacto-N-tetraose	HMO	FrieslandCampina Ingredients B.V.(Netherlands)	2024.09.24	Deficiencies were identified in the compositional analysis of LNT, including the absence of impurity profiles and the use of cobalt in fermentation, which may pose risks if not properly controlled.
1180	Cellobiose	sugar substitute ingredients	SAVANNA Ingredients GmbH (Germany)	2024.09.09	The submission lacks sufficient detail on the manufacturing process, raises questions concerning the intended use and the accuracy of dietary exposure estimates, and does not provide adequate data on the safety and tolerability of cellobiose in infants.
1194	Partially hydrolyzed eggshell membrane powder derived from chicken eggs	others	ESM Technologies, LLC (US)	2025.02.04	The current safety data package is inadequate, with key gaps in information such as protein characterization, allergenicity assessment, accurate estimation of dietary exposure, and evaluation of long-term effects. Additionally, the intended use of the substance requires clarification, and potential arsenic content should be carefully addressed.

GRAS notice by Chinese companies in the first half of 2025

In this update cycle, a total of nine GRAS notices submitted by Chinese companies had their statuses updated on the FDA website. Among them: 6 substances received “FDA has no questions” letters, 2 substances were new submissions currently in pending and 1 substance was ceased to be evaluated. The substances involved include HMOs, sugar substitutes, microbial-derived substances, and other nutritional supplements.

Table 3. GRAS notifications submitted by Chinese companies that updated in the first half of 2025

SN	GRN NO.	Name	Product Type	Company	Status	Date
1	1141	L-α-glycerophosphorylcholine	others	Shenyang Gold Jyouki Technology Co., Ltd	At the notifier's request, FDA ceased to evaluate this notice	2024.04.29
2	1157	2'-fucosyllactose	HMO	Synaura Biotechnology (Shanghai) Co., Ltd.	FDA has no questions	2024.08.07
3	1184	Rebaudioside M from a modified strain of Escherichia coli BL21(DE3)	sugar substitute ingredients	Sichuan Ingia Biosynthetic Co., Ltd.	FDA has no questions	2024.10.23
4	1188	D-psicose	sugar substitute ingredients	Shandong Starlight So True Biological Technology Co., Ltd	FDA has no questions	2024.11.19
5	1191	Ergothioneine produced by Escherichia coli BL-21 (DE3) expressing ergothioneine synthases from Schizosaccharomyces pombe	others	Shanghai EGT Synbio Group Co., LTD	FDA has no questions	2025.01.30
6	1198	Inositol	others	Sichuan Bohaoda Biological Technology Co., Ltd.	FDA has no questions	2025.02.03
7	1206	Rebaudioside M produced by enzymatic treatment of rebaudioside A purified from the leaves of Stevia rebaudiana (Bertoni) Bertoni	sugar substitute ingredients	Adorvia Biotechnology Co., Ltd.	FDA has no questions	2025.02.28
8	1230	Vanillin	others	Sichuan Ingia Biosynthetic Co., Ltd.	pending	/
9	1232	Lacticaseibacillus paracasei DSMZ 28047	microbial-derived substances	SunWay Biotech Co., Ltd.	pending	/

Summary

In the first half of 2025, the FDA’s GRAS database updates primarily reflected the backlog of submissions from 2024, leading to a significant increase in the number of notified substances. Chinese companies remained highly active in GRAS notices, continuing to show strong performance in the sugar substitute category, while also expanding into areas such as HMOs, microbial-derived ingredients, and functional raw materials.

To improve the pass rate of GRAS notice, CIRS Group recommends that companies should provide comprehensive safety assessment data, establish clear and reliable specifications, and calculate reasonable dietary exposure levels to ensure the safety of the substance. CIRS will continue to provide full-service support to help companies successfully navigate the GRAS notice process.

Data Source: FDA GRAS Inventory and most recently published GRAS notices (last updated on June 10, 2025).

Notes:

Since the FDA does not disclose dossier notified dates, the data on substances in pending are based primarily on the submission dates disclosed in the notices.

All data in this report are based on publicly available GRAS notices with assigned GRAS numbers and are for reference only.

If you need any assistance or have any questions, please get in touch with us via service@cirs-group.com.

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