Navigating 2’-FL Regulations: A Global Perspective

 


In recent years, there has been an increasing interest in Human milk oligosaccharides (HMOs). 2’-fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk. As a typical representative ingredient of HMOs, it has been approved for use in food in many countries and regions, such as the EU, the US and Australia and New Zealand.


Now, it also has good news in China: on February 10, 2022, the Chinese National Health Commission (NHC) started another public comment on 2'-FL. It is proposed to use 2'-FL produced by E. coli BL21(DE3) ((Neisseria spp.) as a transferase donor) as a nutritional fortification (NHC Application For New Food Additive Varieties (2023) No. 0003).


I.Status of regulations for 2'-FL in China

In China, 2'-FL has not been officially approved for use as a general food ingredient. However, as early as August 10, 2016, an attempt was made to make an application for this substance (NHC Application For New Food Additive Varieties (2016) No. 0040).

Of all applications, one chemically synthesized source, and three microbial fermentation sources of 2'-FL are in the comment stage.

Application status of different 2'-FL

(NHC Application For New Food Additive Varieties)

Application Info: 

Source

Transferase donors

Application Progress Update

Microbial fermentation sources

(2023) No. 0003

E. coli BL21(DE3)#1540

Not publicly available

2016.08.15:The first public consultation, intended for infant formula, formula for older infants and toddlers. Proposed usage amount: 1-17g/kg.

No follow-up updates.

(2021) No.0048

E. coli DH1 MDO

Helicobacter spp.

2022.10.28:The second public consultation, intended to be used for prepared milk powder (for children only), infant formula, formula for older infants and toddlers, formula for infants for special medical purposes. Proposed usage amount: 0.7-2.4 g/L.a) b)

2023.01.19:Posting of extension notice information

(2021) No.0050

E. coli K-12 MG 1655

Helicobacter spp.

(2022) No.0085

Not publicly available

Not publicly available

2023.01.19:Posting of extension notice information

(2023) No.0003

E. coli BL21(DE3)

Neisseria spp.

2023.02.10:The first public consultation, intended to be used for prepared milk powder (for children only), infant formula, formula for older infants and toddlers, formula for infants for special medical purposes. Proposed usage amount: 0.7-2.4 g/L.a) b)

Chemical synthesis source

(2021) No.0028

Chemical synthesis

None

2021.10.21:The first public consultation, intended to be used for prepared milk powder (for children only). Proposed usage amount: 0.7-2.4 g/L. a)

2022.01.18:Posting of extension notice information

Notes:

a) The amount used is in ready-to-eat condition. For powdered products, increase the amount of use by the dilution of the brew.

b) When mixed with lactose-N-neotetrasaccharide, oligogalactose, oligofructose, polyfructose and Raffinose, the total amount of such substances shall not exceed 64.5g/kg


II.Status of regulations for 2'-FL in other countries and regions

Globally, 2'-FL has been approved for use in food in several countries and regions. ZMUni summarizes the status of regulations in major countries and regions such as the United States and the European Union.

Countries and regions

Current Status

Based on

USA

A number of 2'-FL (single or mixed ingredient products) have been notified as "Generally Recognized as Safe" (GRAS) by the U.S. Food and Drug Administration (FDA).

GRN No.

Name

Date

1034

2'-fucosyllactose

2022/10/21

1014

2’-fucosyllactose

2022/7/15

951

3-fucosyllactose

2021/8/12

932

2'-fucosyllactose

2021/2/18

929

2'-fucosyllactose

2021/2/26

897

2'-O-fucosyllactose

2020/6/12

852

2'-fucosyllactose

2019/11/15

749

2'-O-fucosyllactose

2018/4/23

735

2'-Fucosyllactose

2018/4/6

650

2'-O-fucosyllactose

2016/11/23

571

2'-Fucosyllactose

2015/11/6

546

2'-O-fucosyllactose

2015/9/16


The scope of use includes Infant and toddler formula, as well as baked goods, dairy products, beverages and other food categories.

The amount of use varies depending on the application unit and the scope of use requirements.

Generally Recognized as Safe (GRAS) database

EU

2'-FL is included in the (EU) 2015/2283 list of novel foods, consisting of:

        1. 2'-FL of chemically synthesized source,
        2. 2'-FL of transgenic E. coli BL21 source,
        3. 2'-FL of transgenic E. coli K-12 source。


The range of use includes infant formula, dietary supplements, fermented dairy products, coffee, tea, etc.

The amount of use specified in different food categories varies, with the maximum individual amount in infant and older infant formula being 1.2 g/L (based on ready-to-eat products). When mixed with lactose-N-neotetrasaccharide, the maximum amount of 2'-FL is 0.6 g/L, and the ratio of 2:1 should be met in the final product.

(EU)2015/2283

Australia and New Zealand

The following approved 2'-FLs are included in the ANZ Food Standards Code.:

        1. 2'-FL of Transgenic E. coli K-12 source(containing the gene for alpha-1,2-fucosyltransferase from Helicobacter pylori)
        2. 2'-FL of Transgenic E. coli BL21 source(containing the gene for alpha-1,2-fucosyltransferase from Escherichia coli O126)
        3. 2'-FL of Transgenic E. coli K-12 source(containing the gene for alpha-1,2-fucosyltransferase from Bacteroides vulgatus)


All three of the above can only be used in Infant and toddler formula products.

When used alone, the maximum amount is 96mg/100kJ. When mixed with lactose-N-neotetrasaccharide (LNnT), the maximum use of 2'-FL and LNnT should be 96mg/100kJ in total, and the content of LNnT should not exceed 24mg/100kJ.

Australia New Zealand Food Standards Code

-Schedule 26 Food produced using gene technology

Canada

Canada has approved the following three 2'-FL as novel foods:

        1. 2'-FL of transgenic E. coli K12 MG1655 source (can be used in infant and toddler formulas, as well as other foods for consumers of all ages)
        2. 2'-FL of E. coli BL21 (DE3) #1242 source (can be used in infant and toddler formulas)
        3. 2'-FL of E. coli BL21 (DE3) #1540 source (can be used in infant formulas)


The above three sources of 2'-FL in their respective permitted food categories are added to the maximum use level of 1.2g/L.

Novel foods including genetically modified (GM) foods database


Brazil

Brazil approved the following five 2'-FLs as novel foods:

  1. 2'-FL of E. coli BL21 (DE3) #1540 source,
  2. 2'-FL of E. coli K-12 MG1655 INB000846 source,
  3. 2'-FL of E. coli K-12 SCR6 source,
  4. 2'-FL of E. coli K-12 (DH1) MAP1001d source,
  5. 2'-FL of E. coli K-12 SCR6 or K-12 (DH1) MAP1001d source.


The scope of use includes Infant and toddler formula, pasteurized and ultra-high temperature sterilized milk, fermented milk, milk beverages and other food categories.

The amount used varies depending on the declared unit and the range of use.

ANVISA-Approved New Foods, New Ingredients, Probiotics and Enzymes

Taiwan, China

The following sources of 2'-FL are allowed in Taiwan, China:

  1. Transgenic E. coli K-12 (DH1) MDO MAP1001d
  2. Transgenic E. coli BL21(DE3)#1540


Use is limited to infant and older infant formulae and milk powder or similar products intended for children under 7 years of age.

The use limit is 1.2 g/L, calculated as ready-to-eat or in the state in which it is prepared for consumption according to label directions.

Announcement No. 1091303448 on December 16, 109 of the Republic of China;

Announcement No. 1101301211 on June 16, 110 of the Republic of China;

Amendment No. 1111303588 on February 7, 112 of the Republic of China

Singapore

The maximum use level in infant formula is 1.2g/L.

Singapore Food Regulations Special Part Purpose Foods 252 Infant formula


ZMUni can provide related services for companies:

* Application for GRAS in the USA

* Application for EU Novel food

* Application for Brazil Novel food

* Application for New food ingredient in China

* Other Customised compliance consultation


Information source:

1.China National Center for Food Safety Risk Assessment(CFSA)

2.U.S. Food and Drug Administration(FDA)

3.European Commission(EC)

4.Food Standards Australia New Zealand(FSANZ)

5.Novel foods including genetically modified (GM) foods database

6.Brazilian Health Regulatory Agency (ANVISA)

7.Taiwan Food and Drug Administration (TFDA)

8Singapore Food Regulations

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