Analysis of the Approval Status of Steviol Glycosides and Rebaudioside in China, EU and the U.S. - Regulatory News - Food & Food Contact Materials

In recent years, fueled by consumers’ growing demand for low-calorie diets, sweetness-related keywords such as “low-sugar” and “zero-sugar” remain highly popular. Sugar substitutes are widely used in the downstream food and beverage industry, due to the characteristics of high-sweet, low-calorie, and not causing a rise in blood sugar levels.

Steviol glycosides is a high-sweet, low-calorie natural sweetener extracted from stevia. Currently approved for use in food in China, the EU, the United States, Australia, New Zealand, Canada, and other countries/regions, it is hailed as the world’s third-generation natural zero-calorie healthy sugar source.

Steviol glycosides are composed of various glycosides. According to the National Food Safety Standard for Food Additives - Steviol Glycosides (GB 1886.355-2022) implemented by the China National Health Commission (NHC) in 2022, known glycosides in China include stevioside, Rebaudioside A, B, C, D, E, F, M, N, O, Dulcoside A, Rubusoside, and Steviolbioside.

Since the sweetness levels of glycosides vary, an increasing number of enterprises globally are applying for individual glycosides to meet the diverse market demands, with the application of rebaudioside being the most popular. Primarily extracted from the leaves of the stevia plant, steviol glycosides and rebaudioside A present at the highest level in stevia and have a subtle bitter and lingering taste profile despite the relatively mature production process. Rebaudioside D and rebaudioside M present at very low levels in the stevia leaf, which has a taste profile that is more reflective of sucrose due to the high sweetness and pure taste when compared to the major glycosides. However, the traditional plant extraction method used for their preparation not only incurs high costs but also struggles to meet market demand. Currently, they are mainly prepared through microbial conversion or enzymatic synthesis methods.

CIRS has summarized the approval information of steviol glycosides and rebaudioside in the EU and the United States in the following.

EU

In 2011, E 960 (steviol glycosides) was included in Regulation (EC) No 1333/2008 on food additives, and steviol glycosides were authorized to be used as a sweetener in food and beverages in the EU market.

In 2021, Commission Regulation (EU) 2021/1156 was released, authorizing the use of enzymatically produced rebaudioside as a sweetener. In the interest of clarity, the entry for “E 960 (Steviol glycosides)” is replaced by “E 960a (Steviol glycosides from Stevia)” and “E 960c (Enzymatically produced steviol glycosides)”.

In 2022, (EU) 2022/1922 was released, amending the above-mentioned regulations and inserting the following entries after the Enzymatically produced steviol glycosides (E 960c): Rebaudioside M produced via enzyme modification of Steviol glycosides from stevia (E 960c (i)), Rebaudioside M produced via enzymatic conversion of highly purified Rebaudioside A stevia leaf extracts (E 960c (ii)), Rebaudioside D produced via enzymatic conversion of highly purified Rebaudioside A stevia leaf extracts (E 960c (iii)), and Rebaudioside AM produced via enzymatic conversion of highly purified stevioside stevia leaf extracts (E 960c (iv)).

In 2023, Commission Regulation (EU) 2023/447 was released, amending the above-mentioned regulations and inserting the entry of Glucosylated steviol glycosides (E960d).

The current specifications stipulate that steviol glycosides (E 960) are to contain not less than 95 % of eleven named steviol glycosides: stevioside, rubusoside, dulcoside A, steviolbioside and rebaudiosides A, B, C, D, E, F and M.

It’s worth noticing that steviol glycosides are classified and managed as a food additive instead of a novel Food in the EU*.

* Novel Food refers to food that wasn’t widely consumed in the EU before May 15, 1997, including newly developed innovative foods, those produced using new technologies or processes, and traditional foods from a third country. If an enterprise plans to place products containing novel food on the EU market, it must undergo the novel food application process, a pre-market evaluation procedure.

U.S.

Based on the inventory of FDA GRAS notices, CIRS has made a thorough summary of the approved steviol glycosides and rebaudiosides and analyzed them from multiple perspectives (see Table 1).

Overall approval status

Since 2008, over 70 steviol glycosides and rebaudiosides have been granted GRAS approval. Approved rebaudiosides include Rebaudioside A, B, C, D, E, M, and I.

Approval,EU,US,Food,Additive,China,Registration

Number of approvals by countries

According to publicly available information, applicants for steviol glycosides and rebaudioside are from the United States, China, Canada, South Korea, Japan, Thailand, the Netherlands, and Chile. The number of applicants in China and the United States far exceeds those of other countries, as shown in Figure 2.

Approval,EU,US,Food,Additive,China,Registration

Number of approvals by year

The number of applications for steviol glycosides and rebaudioside peaked in 2011 and 2018 respectively, as indicated in Fig. 3. Around 2011, the applications focused predominantly on steviol glycosides and rebaudioside A. Between 2011 and 2018, the production process of steviol glycosides and its monomers underwent upgrades to align with the market demand, resulting in a wider range of applications. Around 2018, there was a notable shift in application focus towards steviol glycosides and rebaudioside produced through enzymatic treatment and fermentation process.

Approval,EU,US,Food,Additive,China,Registration

Trends in the production process

The production process of GRAS-approved steviol glycosides and rebaudiosides mainly falls into three categories, namely purification from the leaves of stevia, enzymatic treatment (mainly involving genetically modified microorganisms), and fermentation process (using genetically modified microorganisms). Based on the data below (see Table 1), it’s evident that with the growing differentiation in the sweetener market demands, the focus in applications is shifting towards specific glycosides. Additionally, the production processes are gradually transitioning from simple plant extraction methods towards synthetic biology technologies capable of producing specific glycosides.

Table 1: List of GRAS certification of steviol glycosides and rebaudiosides

S.N.	Substance	Production process	Acceptance No. /Date	Applicant
1	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 252 / 2008.12.17	Whole Earth Sweetener Company LLC - U.S.
2	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 253 / 2008.12.17	Cargill, Inc. - U.S.
3	Purified steviol glycosides with rebaudioside A as the principal component	Purified from the leaves of Stevia rebaudiana	GRN No. 275 / 2009.6.11	McNeil Nutritionals, LLC - U.S.
4	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 278 / 2009.7.20	Blue California - U.S.
5	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 282 / 2009.8.11	Sweet Green Fields, LLC - U.S.
6	Purified steviol glycosides with rebaudioside A and stevioside as the principal components	Purified from the leaves of Stevia rebaudiana	GRN No. 287 / 2009.8.28	Wisdom Natural Brands - U.S.
7	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 303 / 2010.3.22	Sunwin USA, LLC & WILD Flavors - U.S.
8	Purified steviol glycosides with rebaudioside A and stevioside as the principal components	Purified from the leaves of Stevia rebaudiana	GRN No. 304 / 2010.3.22	Sunwin USA, LLC & WILD Flavors - U.S.
9	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 318 / 2010.5.15	Pyure Brands, LLC - U.S.
10	Purified steviol glycosides with rebaudioside A and stevioside as the principal components	Purified from the leaves of Stevia rebaudiana	GRN No. 323 / 2010.7.9	PureCircle USA, Inc. - U.S.
11	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 329 / 2010.9.10	GLG Life Tech, Ltd. - Canada
12	Enzyme-modified steviol glycosides preparation	Enzymatic treatment	GRN No. 337 / 2011.6.17	NOW Foods - U.S.
13	Purified steviol glycosides with rebaudioside A and stevioside as the principal components	Purified from the leaves of Stevia rebaudiana	GRN No. 349 / 2011.7.14	GLG Life Tech, Ltd. - Canada
14	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 354 / 2011.7.15	Guilin Layn Natural Ingredients, Corp. - China
15	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 365 / 2011.8.18	BrazTek International Inc. - U.S.
16	Purified steviol glycosides with rebaudioside A and stevioside as the principal components	Purified from the leaves of Stevia rebaudiana	GRN No. 367 / 2011.7.8	Sinochem Health Company, Ltd. - China
17	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 369 / 2011.10.11	Zhucheng Haotian Pharm Co., Ltd. & Shanghai Freemen Americas, LLC - China
18	Enzyme-modified steviol glycosides preparation	Enzymatic treatment	GRN No. 375 / 2011.9.2	Toyo Sugar Refining Co., Ltd. & Nippon Paper Chemicals Co., Ltd. - Japan
19	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 380 / 2011.11.28	GLG Life Tech Corporation - Canada
20	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 388 / 2012.1.9	Chengdu Wagott Pharmaceutical - China
21	Steviol glycosides with stevioside as the principal component	Purified from the leaves of Stevia rebaudiana	GRN No. 389 / 2012.1.18	Chengdu Wagott Pharmaceutical - China
22	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 393 / 2012.1.23	Daepyung Co., Ltd. - Korea
23	Steviol glycosides with rebaudioside A and stevioside as the principal components	Purified from the leaves of Stevia rebaudiana	GRN No. 395 / 2012.1.24	Daepyung Co., Ltd. - Korea
24	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 418 / 2012.6.7	MiniStar International, Inc. - U.S.
25	Enzyme-modified steviol glycosides preparation	Enzymatic treatment	GRN No.448 / 2013.5.3	Daepyung Co., Ltd. - Korea
26	Enzyme-modified steviol glycosides	Enzymatic treatment (GMO: Bacillus licheniformis)	GRN No.452 / 2013.7.1	Daepyung Co., Ltd. - Korea
27	Rebaudioside D	Purified from the leaves of Stevia rebaudiana	GRN No. 456 / 2013.7.1	PureCircle USA, Inc. - U.S.
28	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 461 / 2013.8.14	Almendra Limited - Thailand
29	Rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 467 / 2013.11.25	Qufu Xiangzhou Stevia Products Co., Ltd. - China
30	Purified steviol glycosides with rebaudioside X as the principal component	Purified from the leaves of Stevia rebaudiana	GRN No. 473 / 2013.12.17	PureCircle, Ltd. - U.S.
31	High-purity steviol glycosides (minimum purity 95%)	Purified from the leaves of Stevia rebaudiana	GRN No.493 / 2014.5.30	GLG Life Tech Corporation - Canada
32	Rebaudioside M	Purified from the leaves of Stevia rebaudiana	GRN No. 512 / 2014.10.24	GLG Life Tech Corporation - U.S.
33	Rebaudioside C	Purified from the leaves of Stevia rebaudiana	GRN No. 536 / 2015.2.12	GLG Life Tech Corporation - Canada
34	Rebaudioside D	Purified from the leaves of Stevia rebaudiana	GRN No. 548 / 2015.4.22	GLG Life Tech Corporation - Canada
35	Steviol glycosides with rebaudioside A and stevioside as the principal components	Purified from the leaves of Stevia rebaudiana	GRN No. 516 / 2014.10.31	Almenda (Thailand) Limited - Thailand
36	Purified steviol glycosides with rebaudioside A as the principal component	Purified from the leaves of Stevia rebaudiana	GRN No. 555 / 2015.4.21	Procuctora Alysa SpA - Chile
37	Glucosylated steviol glycosides	Enzymatic treatment (Bacillus stearothermophilus)	GRN No.607 / 2016.10.14	PureCircle Limited - U.S.
38	Purified steviol glycosides	Purified from the leaves of Stevia rebaudiana	GRN No.619 / 2016.5.27	PureCircle Limited - U.S.
39	Steviol glycosides produced in Saccharomyces cerevisiae	Fermentation process (GMO: Saccharomyces cerevisiae)	GRN No.626 / 2016.5.27	Cargill, Inc. - U.S.
40	Rebaudioside A	Fermentation process (GMO: Yarrowia lipolytica)	GRN No. 632 / 2016.6.24	DSM Nutritional Products, LLC - U.S.
41	High-purity steviol glycosides (minimum purity 97%) consisting primarily of rebaudioside A	Purified from the leaves of Stevia rebaudiana	GRN No. 638 / 2016.7.10	Hunan Huacheng Biotech Inc. - China
42	Enzyme-modified steviol glycosides	Enzymatic treatment	GRN No.656 / 2016.9.28	GLG Life Tech Corporation - U.S.
43	Glucosylated steviol glycosides (minimum purity 95%)	Enzymatic treatment	GRN No.662 / 2016.9.29	PureCircle USA - U.S.
44	Rebaudioside M	Fermentation process (GMO: Saccharomyces)	GRN No. 667 / 2017.2.17	Blue California - U.S.
45	Purified steviol glycosides	Purified from the leaves of Stevia rebaudiana	GRN No.702 / 2017.9.28	Xinghua GL Stevia Co., Ltd. - China
46	Rebaudioside D	Fermentation process (GMO: Saccharomyces)	GRN No. 715 / 2017.10.24	Blue California - U.S.
47	Purified steviol glycosides	Purified from the leaves of Stevia rebaudiana	GRN No.733 / 2018.1.9	Shangdong Shengxiangyuan Biotechnology - China
48	Steviol glycosides consisting primarily of rebaudioside M	Fermentation process (GMO: Brewer’s yeast)	GRN No. 744 / 2018.3.23	PureCircle Limited - U.S.
49	Steviol glycosides consisting primarily of rebaudioside M	Enzymatic treatment (GMO: E. coli)	GRN No. 745 / 2018.4.20	PureCircle Limited - U.S.
50	Steviol glycosides consisting primarily of rebaudioside M	Fermentation process (GMO: Yarrowia lipolytica）	GRN No. 759 / 2018.5.25	DSM Food Specialties / DSM Nutritional Products North America - Netherlands
51	Rebaudioside D	Enzymatic treatment (GMO: Pichia pastoris)	GRN No. 764 / 2018.7.10	Sichuan Ingia Biosynthetic Co., Ltd. - China
52	Rebaudioside M	Enzymatic treatment (GMO: E. coli)	GRN No. 780 / 2018.7.31	Tate and Lyle - U.S.
53	Steviol glycosides (minimum purity 95%)	Purified from the leaves of Stevia rebaudiana	GRN No.790 / 2019.2.26	GLG Life Tech Corporation - U.S.
54	Purified steviol glycosides	Purified from the leaves of Stevia rebaudiana	GRN No.795 / 2018.9.25	Steviana Bioscience (Suzhou) Inc. - China
55	Rebaudioside M	Enzymatic treatment (GMO: Pichia pastoris)	GRN No. 799 / 2018.9.25	Sichuan Ingia Biosynthetic Co., Ltd. - China
56	Rebaudioside M	Fermentation process (GMO: Brewer’s yeast)	GRN No.812 / 2018.12.8	Amyris, Inc. - U.S.
57	Glucosylated steviol glycosides	Enzymatic treatment (non-genetically modified)	GRN No.821 / 2019.5.7	Haigen-BGG Natural Ingredients Limited - China
58	Rebaudioside E	Fermentation process (GMO: Pichia pastoris)	GRN No.823 / 2019.6.21	Blue California - U.S.
59	Purified steviol glycosides	Enzymatic treatment	GRN No.838 / 2019.7.12	Jiang Su Svetia Biotechnology Co., Ltd. - China
60	Purified steviol glycosides	Enzymatic treatment	GRN No.839 / 2019.7.8	Sinochem Health Company Ltd. - China
61	Rebaudioside M	Enzymatic treatment (GMO: E. coli)	GRN No.846 / 2019.8.23	GLG Life Tech Corporation - Canada
62	Glucosylated steviol glycosides	Enzymatic treatment	GRN No.858 / 2019.10.4	Qufu Shengren Pharmaceutical Co., Ltd - China
63	Glucosylated steviol glycosides	Enzymatic treatment (GMO: Bacillus licheniformis )	GRN No.878 / 2019.12.19	Daepyung Co., Ltd. - Korea
64	Rebaudioside M (genetically modified microorganisms synthesis)	Fermentation process (GMO: Yarrowia lipolytica）	GRN No.882 / 2020.2.2	Cargill, Inc. - U.S.
65	Rebaudioside I	Fermentation process (GMO: Pichia pastoris)	GRN No.911 / 2021.6.8	Blue California - U.S.
66	Rebaudioside B	Fermentation process (GMO: Pichia pastoris)	GRN No.968 / 2022.3.10	Blue California - U.S.
67	Enzyme-modified steviol glycosides	Enzymatic treatment (GMO: Bacillus licheniformis )	GRN No.970 / 2021.4.9	Shandong Shengxiangyuan Biotechnology Co., Ltd - China
68	Purified steviol glycosides from the leaves of Stevia rebaudiana (Bertoni)	Purified from the leaves of Stevia rebaudiana	GRN No.983 / 2021.6.28	Zhucheng Haotian Pharm Co., Ltd - China
69	Enzyme-modified steviol glycosides	Enzymatic treatment	GRN No.999 / 2021.12.3	Zhucheng Haotian Pharm Co., Ltd - China
70	Rebaudioside M	Enzymatic treatment (GMO: E. coli)	GRN No.1010/ 2022.1.26	Manus Bio, Inc. - U.S.
71	Rebaudioside I	Enzymatic treatment (GMO: E. coli)	GRN No.1106/ 2023.1.16	Manus Bio, Inc. - U.S.
/	Enzyme-modified steviol glycosides	/	GRN No.1140 / Pending	Tate & Lyle - U.S.

China

As of now, the compliance process for stevia and its various extracts has begun in China. Detailed application and approval information is shown in the Table below.

Table 2: Regulatory status of stevia and its extracts in China - approved substances

Substance	Function
Stevia rebaudiana oil	Food additive - food flavoring
Steviol glycosides	Food additive-sweetener; available excipient for health food filing products
Glucosylated steviol glycosides	Food additive - food flavoring

Table 3: Regulatory status of stevia and its extracts in China - accepted substances

Substance	Type of application	Acceptance code	Date of acceptance	Status
Rebaudioside A	New food additive	衛食添新申字 (2022)第0004號	2022.2.11	2022.8.16 Issued for a disapproval decision*
Stevia	New food additive	衛食添新申字 (2022)第0005號	2022.2.11	2022.8.16 Issued for a disapproval decision*
Stevia extract	New food additive	衛食添新申字 (2022)第0006號	2022.2.11	2022.8.1 Issued for a disapproval decision*
Rebaudioside M	New food raw material	衛食添新申字 (2023)第0030號	2023.3.6	2023.5.9 Issued for a disapproval decision *
Stevia	New food raw material	衛食新申字 (2023)第0008號	2023.7.9	/
Stevia extract	New food raw material	衛食新申字 (2023)第0015號	2023.9.7	2023.9.26 NHC issued a notice on delaying the review
Rebaudioside M	New food raw material	衛食添新申字 (2023)第0034號	2023.5.10	2023.10.26 Issued for public comments

* Disapproved ≠ not allowed to resubmit. In most cases, based on the results of the technical review, the applicant can refine the materials and then resubmit.

In light of the relevant provisions regarding the application for “Three New Foods” in China, the feasibility and difficulty of applying for one substance is, to some extent, influenced by its international application and approval status. If an enterprise intends to apply for one substance as a new food raw material or new food additive in China, obtaining FDA GRAS certification in the United States or approval as a novel food or food additive in the EU can serve as favorable grounds for the application.

The Food Division at CIRS Group boasts a highly professional team specializing in the application of “Three New Foods” in China, namely new food raw materials, new food additives, and food contact materials, as well as FDA GRAS in the United States and Novel Food in the EU. With extensive experience in these fields, our team has numerous successful cases. As of now, CIRS Group has acted as an agent for dozens of domestic and international applications for new materials and additives involving genetically modified microorganisms, positioning our project experience at the forefront of the industry. We welcome inquiries or visits for a deeper understanding of our technical capabilities.

Note: The data presented is accurate as of December 25, 2023. The information is sourced from publicly available platforms and is for reference only.

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

We have launched a LinkedIn newsletter to keep you up to date on the latest developments across the chemical industry including food and FCMs and personal and home care.