Surge in Applications: Overview of FDA GRAS Approvals in the US from 2021 to 2023

In recent years, an increasing number of domestic and international companies have sought FDA GRAS certification for new substances added to food. The U.S. Food and Drug Administration (FDA) regularly updates the list of "Generally Recognized as Safe (GRAS)" substances on its official website, with the most recent update as of October 31, 2023.

CIRS Group has made a detailed analysis and summarized the substances submitted for GRAS certification from 2021 to 2023 to provide businesses with valuable insights.

Summary of FDA GRAS applications and approvals from 2021-2023

Over the past three years, 231 products have been submitted for FDA GRAS certification. Among them, 117 were approved, while 31 ceased evaluation as requested (based on cessation dates: 13 in 2021, 14 in 2022, and 4 in 2023). The remaining 83 are still pending after submission.

Figure 1. Overview of GRAS applications from 2021 to 2023

Substances approved from 2021 to 2023 (based on approval dates): a total of 117 substances

The number of substances obtaining GRAS approval is declining from 2021 to 2023, possibly due to the increasing necessity for extensive and comprehensive data to support the GRAS conclusion for a growing number of new substances. Moreover, the surge in submission quantities has also led to delays in the review process.

It's noteworthy that Chinese enterprises successfully secured approval for 8 substances during this period, including:

• 3 types of steviol glycosides,
• 2 types of DHA algae oils,
• 1 functional substance D-psicose, 1 protein, and
• 1 enzyme preparation.

Figure 2. Number of approved FDA GRAS substances both domestically and globally from 2021-2023

Table 1. FDA GRAS substances obtained by Chinese enterprises from 2021-2023

No.	GRN No.	Substance	Approval date	Enterprise
1	1029	D-psicose	2023/8/4	L&P Foods Technology Co., Ltd.
2	1021	Transglutaminase enzyme preparation produced by Streptomyces mobaraensis strain M2020197	2022/11/3	Dongsheng Technology Co., Ltd.
3	1008	Algal oil (≥45% docosahexaenoic acid) from Aurantiochytrium limacinum TKD-1	2022/2/25	Anhui ATK Biotech Co., Ltd.
4	999	Enzyme-modified steviol glycosides	2021/12/3	Zhucheng Howtian Co., Ltd.
5	983	Purified steviol glycosides from the leaves of Stevia rebaudiana (Bertoni)	2021/6/28	Zhucheng Howtian Co., Ltd.
6	970	Enzyme-modified steviol glycosides	2021/4/9	Shandong SYX Stevia Biotech Co., Ltd.
7	948	Enzyme-treated pea protein	2021/9/9	Yantai Oriental Protein Technology Co., Ltd.
8	934	Algal oil (≥35% docosahexanoic acid (DHA)) derived from Schizochytrium sp. strain CABIO-A-2	2021/7/20	Cabio Biotech (Wuhan) Co., Ltd.

Substances in pending status (based on submission dates) from 2021 to 2023: a total of 83 substances

As illustrated in Figure 3, 2022 witnessed the most significant number of pending substances, totaling a substantial 51 substances. It's worth noticing that the FDA has extended the time for archiving new submissions (granting GRN No.) due to the surge in submissions. Consequently, many products submitted in 2023 are either yet to be archived or updated on the official website.

Regarding Chinese enterprises, among the 7 pending substances, there are 2 functional ingredients (GPC and PQQ), 2 unsaturated fatty acid supplements (fungal oil and algae oil), 1 probiotic, 1 anti-bacterial agent, and 1 antioxidant.

Figure 3. Substances in pending status both domestically and globally from 2021-2023

Table 2. Substances in pending status submitted by Chinese enterprises (published) from 2021-2023

No.	GRN No.	Substance	Enterprise
1	1141	L-α-glycerylphosphorylcholine (GPC)	Shenyang Gold Jyouki Technology Co.,Ltd.
2	1138	Hydroxytyrosol	Hangzhou Viablife BoitechCo.,Ltd.
3	1134	Bacteriophage preparation specific to Salmonella Enteritidis	Qingdao PhagepharmBoitech Co.,Ltd.
4	1130	Lactobacillus rhamnosus CGMCC21225	FenghuaBoitech Co.,Ltd
5	1128	Algal oil (≥35% docosahexaenoic acid) from Schizochytrium sp.	Jiangsu Grand Xianle Pharmaceutical Co.Ltd.
6	1118	Pyrroloquinoline quinone disodium（PQQ）salt	Zhejiang Medicine Co., Ltd.
7	1115	Fungal oil (≥40% arachidonic acid (ARA)) from Mortierella alpina strain AF	Hubei Fuxing BoitechCo.,Ltd.

Popular GRAS substances from 2021 to 2023

Over the past three years, popular GRAS substances can be categorized into several categories, including:

• 24 HMOs,
• 8 steviol glycosides,
• 54 strains, and
• 29 enzyme preparations.

HMOs and steviol glycosides have seen a substantial number of applications and approvals, aligning with the rapid advancement in synthetic biotechnology in recent years. Additionally, there is a wide variety of enzyme preparations, including amylases, proteases, invertase, and complex enzymes.

Other GRAS products serve various functions, including processing aids (emulsifiers and anti-bacterial agents), nutritional raw materials (protein, milk powder, algae oil, plant extracts, and oligosaccharides), and functional ingredients (D-psicose, dihydroquercetin and L-carnitine), etc.

Figure 4. Overview of hot substances applications from 2021-2023

Table 3. Details of hot substances from 2021-2023

Category	Substance	Number of approval	Number of pending substances	Total
HMOs	2'-FL	5	3	8
	3-FL	3	1	4
	3'-SL	3	0	3
	6'-SL	4	0	4
	LNT	3	0	3
	LNnT	2	0	2
	Total	20	4	24
Steviol glycosides	Rebaudioside B	1	0	1
	Rebaudioside I	2	0	2
	Rebaudioside M	1	0	1
	Mixed monomers	3	1	4
	Total	7	1	8
Strains	Brewer’s yeast	4	1	5
	Bifidobacterium	8	7	15
	Lactobacillus	4	10	14
	Bacillus subtilis	6	3	9
	Others	2	9	11
	Total	24	30	54

*Data Source: The inventory of GRAS notices and the latest released accepted GRAS dossiers (updated as of 2023/10/31).

*Note:

1. As the FDA doesn’t disclose dossier acceptance dates, the statistics for substances in pending status are primarily based on the submission dates recorded in the released dossiers.

2. The statistics are based on the published dossiers with GRN No. and are for reference only.

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