Global Compliance Perspective on HMOs: Approvals and Applications in the EU

Human Milk Oligosaccharides (HMOs) are found exclusively in human milk and represent the third largest solid component after lactose and lipids. They possess a wide range of functions, including modulation of the gut microbiota, enhancement of cognitive development, and improvement of irritable bowel syndrome. There are numerous types of HMOs. To date, a total of eight HMOs have been approved in the European Union, including:

2’-FL
3-FL
LNT
LNnT
3’-SL
6’-SL
2’-FL/DFL
LNFP-I/2’-FL

CIRS Group has compiled and summarized the intended uses and use levels of HMOs approved in the EU for industry reference. Among them, chemically synthesized and microbially produced 2’-FL have identical scope of use and use levels; similarly, chemically synthesized and microbially produced LNnT share the same conditions of use. The remaining HMOs are produced via microbial sources, and their intended uses may vary depending on the production organism. Details are provided in Tables 1–7.

Table 1. Intended Uses and Maximum Use Levels of 2’-FL from Chemical and Microbial Sources

Intended Uses	Maximum Use Levels
Plain pasteurized milk and sterilized milk (including UHT milk)	1.2 g/L
Plain fermented milk	Liquid 1.2 g/L Others 19.2 g/kg
Flavored fermented milk, including heat-treated products	Liquid 1.2 g/L Others 19.2 g/kg
Dairy analogues, including coffee whiteners	Liquid 1.2 g/L Others 12 g/kg coffee whiteners 400 g/kg
Cereal bars	12 g/kg
Table-top sweeteners	200 g/kg
Infant formula as defined in Regulation (EU) No 609/2013	3 g /L (as consumed)
Follow-on formula as defined in Regulation (EU) No 609/2013	3.64 g /L (as consumed)
Processed cereal-based foods and baby foods as defined in Regulation (EU) No 609/2013	Liquid 1.2 g/L (as consumed) Others 12 g/kg
Milk-based drinks and similar products for young children	1.2 g/L (as consumed)
Foods for special medical purposes as defined in Regulation (EU) No 609/2013	According to the specific nutritional requirements of the target population
Total diet replacement for weight control as defined in Regulation (EU) No 609/2013	Liquid 4.8 g/L Bars 40 g/kg
Bread and pasta products labeled as gluten-free or very low gluten in accordance with Implementing Regulation (EU) No 828/2014	60 g/kg
Flavored beverages	1.2 g/L
Coffee, tea (excluding black tea), herbal and fruit infusions, chicory; extracts thereof; and instant or mixed products	9.6 g/L (as consumed)
Food supplements as defined in Directive 2002/46/EC (excluding infants)	General population 3 g/day Young children 1.2g/day

Table 2. Intended Uses and Maximum Use Levels of 3-FL from Different Microbial Sources

Intended Uses	Maximum Use Levels
Intended Uses	E. coli K12 MG1655	E. coli BL21 (DE3)	E. coli K-12 DH1（as 3-FL）
Pasteurized milk and sterilized milk (including UHT milk)	0.85 g/L	/	2 g/L
Plain and flavored fermented milk (including heat-treated products)	Liquid 0.5 g/L Others 5 g/kg	/	Plain: Liquid 2 g/L; Others 4 g/kg Flavored: Liquid 2 g/L; Others 12 g/kg
Dairy analogues	Liquid 0.85 g/L Others 8.5 g/kg	/	/
Flavored beverages, energy drinks, sports drinks	1 g/L	/	/
Beverages (excluding flavored drinks with pH < 5)	/	/	1.25 g/L
Cereal bars	30 g/kg	/	25 g/kg
Infant formula as defined in EU No 609/2013	0.85 g /L (as consumed)	1.75 g /L (as consumed)	1.75 g /L (as consumed)
Follow-on formula as defined in EU No 609/2013	0.85 g /L (as consumed)	1.75 g /L (as consumed)	1.75 g /L (as consumed)
Milk drinks for young children	0.85 g/L (as consumed)	1.2 g/L(as consumed)	Liquid 2 g/L (as consumed) Others 12 g/kg
Processed cereal-based foods and baby foods as defined in EU No 609/2013	Liquid 0.3 g/L (as consumed) Others 3.0 g/kg	1.2 g/L or 1.2 g/kg (as consumed)	/
Total diet replacement for weight control as defined in EU No 609/2013	Liquid 2 g/L Others 30 g/kg	/	Liquid 2 g/L Others 25 g/kg
Foods for special medical purposes as defined in EU No 609/2013	According to nutritional needs	Infants: ≤1.75 g/L; Others: per needs	Infants: ≤1.75 g/L Others: ≤4 g/L
Food supplements as defined in Directive 2002/46/EC	Not for use in food supplements for infants and young children, 5 g/day	For the general population, excluding infants and young children, 4 g/day	For the general population, excluding infants and young children, 4 g/day

Table 3. Intended Uses and Maximum Use Levels of LNT from Different Microbial Sources

Intended Uses	Maximum Use Levels
Intended Uses	E. coli K-12 DH1	E. Coli BL21(DE3) (as LNT)
Plain pasteurized milk, sterilized milk (including ultra-high-temperature milk)	1 g/L	/
Plain fermented milk	Liquid 1 g/L Others 10 g/kg	/
Flavored fermented milk, including heat-treated products	Liquid 1 g/L Others 10 g/kg	/
Beverages (flavored beverages)	1 g/L	/
Cereal bars	10 g/kg	/
Infant formula as defined in EU No 609/2013	0.8 g /L (as consumed)	1.82 g /L (as consumed)
Follow-on formula as defined in EU No 609/2013	0.6 g /L (as consumed)	1.82 g /L (as consumed)
Processed cereal-based foods and foods intended for infants and young children, as defined in Regulation (EU) No 609/2013	Liquid 0.6 g/L (as consumed) Others 5 g/kg	1.82 g /L or 1.82 g/kg (as consumed)
Milk-based drinks and similar products intended for young children	Liquid 0.6 g/L (as consumed) Others 5 g/kg	1.82 g/L (as consumed)
Total diet replacement for weight control as defined in EU No 609/2013	Liquid 2 g/L Others 20 g/kg	/
Foods for special medical purposes as defined in EU No 609/2013	According to nutritional needs	Infants: ≤1.82 g/L or 1.82 g/kg Others: per needs
Food supplements as defined in Directive 2002/46/EC	Not for use in food for infants, suitable for toddlers, children, adolescents, and adults, 2 g/day	For the general population, not for infants and young children, 4.6 g/day

Table 4. Intended Uses and Maximum Use Levels of LNnT

Intended Uses	Maximum Use Levels
Plain pasteurized milk, sterilized milk (including ultra-high-temperature milk)	0.6 g/L
Plain fermented milk	Liquid 0.6 g/L Others 9.6 g/kg
Flavored fermented milk, including heat-treated products	Liquid 0.6 g/L Others 9.6 g/kg
Dairy analogues, including coffee whiteners	Liquid 0.6 g/L Others 6 g/kg coffee whiteners 200 g/kg
Cereal bars	6 g/kg
Tabletop sweeteners	100 g/kg
Infant formula as defined in Regulation (EU) No 609/2013	0.6 g /L (as consumed)
Follow-on formula as defined in Regulation (EU) No 609/2013	0.6 g /L (as consumed)
Processed cereal-based foods and foods for infants and young children as defined in Regulation (EU) No 609/2013	Liquid 0.6 g/L (as consumed) Others 6 g/kg
Milk-based drinks and similar products for young children	0.6 g/L (as consumed)
Foods for special medical purposes as defined in Regulation (EU) No 609/2013	According to nutritional needs
Complete nutritional formula foods for weight control as defined in Regulation (EU) No 609/2013	Liquid 2.4 g/L Bars 20 g/kg
Bread and pasta products labeled as gluten-free or low-gluten under Implementing Regulation (EU) No 828/2014	30 g/kg
Flavored beverages	0.6 g/L
Coffee, tea (excluding black tea), herbal and fruit infusions, chicory; extracts of tea, herbal and fruit infusions, and chicory; products for brewing from tea, plants, fruits, and cereals, as well as mixes and instant formulations of these products	4.8 g/L (as consumed)
Food supplements, as defined in Directive 2002/46/EC, are intended for the general population, excluding infants	For general population1.5 g/day young children 0.6 g/day

Table 5. Intended Uses and Maximum Use Levels of 3’-SL

Intended Uses	Maximum Use Levels
Intended Uses	E. coli K-12 DH1(as 3’-SL)	E. coli BL21 (DE3)	E. coli W (ATCC 9637)(as 3’-SL)
Plain pasteurized milk, sterilized milk (including ultra-high-temperature [UHT] milk)	0.25 g/L	/	0.25 g/L
Plain fermented milk	Liquid 0.25 g/L Others 0.5 g/kg	/	Liquid 0.25 g/L Others 0.5 g/kg
Flavored fermented milk, including heat-treated products	Liquid 0.25 g/L Others 2.5 g/kg	/	Liquid 0.25 g/L Others 2.5 g/kg
Beverages (excluding flavored beverages with a pH below 5)	0.25 g/L	/	0.25 g/L
Cereal bars	2.5 g/kg	/	2.5 g/kg
Infant formula as defined in Regulation (EU) No 609/2013	0.2 g /L (as consumed)	0.28 g /L (as consumed)	0.2 g /L (as consumed)
Follow-on formula as defined in Regulation (EU) No 609/2013	0.15 g /L (as consumed)	0.28 g /L (as consumed)	0.15 g /L (as consumed)
Processed cereal-based foods and foods for infants and young children as defined in Regulation (EU) No 609/2013	Liquid 0.15 g/L (as consumed) Others 1.25 g/kg	0.28 g/L or 0.28 g/kg (as consumed)	Liquid 0.15 g/L (as consumed) Others 1.25 g/kg
Milk-based drinks and similar products	0.15 g/L (as consumed)	0.28 g/L (as consumed)	Liquid 0.15 g/L (as consumed)
Complete nutritional formula foods for weight control as defined in Regulation (EU) No 609/2013	Liquid 0.5 g/L Others 5 g/kg	/	Liquid 0.5 g/L Others 5 g/kg
Foods for special medical purposes as defined in Regulation (EU) No 609/2013	According to nutritional needs	Infants: ≤0.28 g/L or 0.28 g/kg Others: per needs	According to nutritional needs
Food supplements as defined in Directive 2002/46/EC	Not for use in food supplements for infants, 0.5 g/day	For general population use, excluding infants, 0.7 g/day	Not for use in food supplements for infants, 1 g/day

Table 6. Intended Uses and Maximum Use Levels of 6’-SL

Intended Uses	Maximum Use Levels
Intended Uses	E. coli K-12 DH1(as 6’-SL)	E. coli BL21 (DE3)	E. coli W (ATCC 9637) (as 6’-SL)
Plain pasteurized milk, sterilized milk (including ultra-high-temperature [UHT] milk)	0.5 g/L	/	0.5 g/L
Plain fermented milk	Liquid 0.5 g/L Others 2.5 g/kg	/	Liquid 0.5 g/L Others 2.5 g/kg
Flavored fermented milk, including heat-treated products	Liquid 0.5 g/L Others 5 g/kg	/	Liquid 0.5 g/L Others 5 g/kg
Beverages (excluding flavored beverages with a pH below 5)	0.5 g/L	/	0.5 g/L
Cereal bars	5 g/kg	/	5 g/kg
Infant formula as defined in Regulation (EU) No 609/2013	0.4 g /L (as consumed)	0.7 g /L (as consumed)	0.4 g /L (as consumed)
Follow-on formula as defined in Regulation (EU) No 609/2013	0.3 g /L (as consumed)	0.7 g /L (as consumed)	0.3 g /L (as consumed)
Processed cereal-based foods and foods for infants and young children as defined in Regulation (EU) No 609/2013	Liquid 0.3 g/L (as consumed) Others 2.5 g/kg	0.7 g/L or 0.7 g/kg (as consumed)	Liquid 0.3 g/L (as consumed) Others 2.5 g/kg
Milk-based drinks and similar products	0.3 g/L (as consumed)	0.7 g/L (as consumed)	Liquid 0.3 g/L (as consumed)
Complete nutritional formula foods for weight control as defined in Regulation (EU) No 609/2013	Liquid 1 g/L Others 10 g/kg	/	Liquid 1 g/L Others 10 g/kg
Foods for special medical purposes as defined in Regulation (EU) No 609/2013	According to nutritional needs	Infants: ≤0.7 g/L or 0.7 g/kg Others: per needs	According to nutritional needs
Food supplements as defined in Directive 2002/46/EC	Not for use in food supplements for infants, 1 g/day	For the general population use, excluding infants, 1.8 g/day	Not for use in food supplements for infants, 1 g/day

Table 7. Intended Uses and Maximum Use Levels of Mixed HMOs

Intended Uses	Maximum Use Levels
Intended Uses	*2’-FL/DFL (produced using a derivative strain of Escherichia coli* K-12 DH1)**	*LNFP I / 2’-FL (produced using a derivative strain of Escherichia coli* K-12 DH1) (as the mixture of LNFP I / 2’-FL)**
Plain pasteurized milk, sterilized milk (including ultra-high-temperature milk)	2 g/L	1.5 g/L
Plain fermented milk	Liquid 2 g/L Others 20 g/kg	Liquid 1.5 g/L Others 3 g/kg
Flavored fermented milk, including heat-treated products	Liquid 2 g/L Others 20 g/kg	Liquid 1.5 g/L Others 15.0 g/kg
Beverages (flavored beverages)	2 g/L	Not for use in beverages with a pH below 5, 1.5 g/kg
Cereal bars	20 g/kg	15 g/kg
Infant formula as defined in Regulation (EU) No 609/2013	1.6 g /L (as consumed)	2 g /L (as consumed)
Follow-on formula as defined in Regulation (EU) No 609/2013	1.2 g /L (as consumed)	2 g /L (as consumed)
Processed cereal-based foods and foods for infants and young children as defined in Regulation (EU) No 609/2013	Liquid 1.2 g/L (as consumed) Others 10 g/kg	Liquid 1.5 g/L (as consumed) Others 9.1 g/kg
Complete nutritional formula foods for weight control as defined in Regulation (EU) No 609/2013	Liquid 4 g/L Others 40 g/kg	Liquid 3 g/L Others 4.5 g/kg
Foods for special medical purposes as defined in Regulation (EU) No 609/2013	According to nutritional needs	Infants: ≤2 g/L or 2 g/kg Others: ≤4.5 g/day (as consumed)
Food supplements, as defined in Directive 2002/46/EC, are intended for the general population	Not for use in food for infants, 4 g/day	Not for use in food for infants and young children, 4.5 g/day
Milk-based drinks and similar products	1.2 g /L (as consumed)	1.5 g /L (as consumed)

HMOs are already subject to regulatory requirements in many countries. In addition to the EU, CIRS Group has compiled information on the approval and scope of use for HMOs in other countries and regions, such as the U.S., and Australia and New Zealand. Furthermore, CIRS Group has extensive experience in regulatory compliance for global submissions. If you have any HMO submission needs, please feel free to contact us or visit our office.

Note: The data in this text are sourced from Regulation (EU) 2017/2470, with statistics as of December 31, 2025, and are for reference only.

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