Latest Compliance Advances of Human Milk Oligosaccharides (HMOs) in China

Human Milk Oligosaccharides (HMOs) stand as a vital category of naturally occurring nutrients found in breast milk. Currently, there are over 200 known structures of HMOs, with six types being extensively researched, of which the nutritional necessity and safety have gained broad international recognition.

Notably, in China, there’s widespread attention on four compliant HMOs:

• 2’-fucosyllactose (2’-FL);
• lacto-N-neotetraose (LNnT);
• 6’-sialyllactose sodium salt (6’-SL); and
• 3’-sialyllactose sodium salt (3’-SL).

To clarify the compliance advances of HMOs in China, CIRS Group has summarized detailed application and approval status as follows.

Approved HMOs: one type of LNnT and three types of 2’-FL

As of now, one type of lacto-N-neotetraose (LNnT) and three types of 2'-fucosyllactose (2’-FL) have obtained approval. Specifically, the approved 2’-FL are all prepared through fermentation sources, with the same standard requirements but differing production strains. Details are shown in the table below:

Name	Approval date	Source	Donor
2’-FL	2023.10.7 NHC Notice No. 8, 2023	E.coli K-12 DH1 MDO	Helicobacter spp. a
		E.coli K-12 MG1655	Helicobacter spp. a
		E.coli BL21(DE3)	Neisseria spp. a
LNnT	2023.10.7 NHC Notice No. 8, 2023	E. coli K-12 DH1 MDO	Neisseria spp. a and Helicobacter spp. b
a is the donor of α-1, 2-fucosyltransferase b is the donor of β-1,4-galactosyltransferase

Two types of 2’-FL issued for public comments but not yet approved

It can be seen from the table below that the synthetically derived 2’-FL has faced another extension since January 2022, with no further public review progress after supplementing dossiers. On a different note, a fermentation-based 2’-FL was just open for public comments on August 23, this year. If all progresses smoothly, it’s highly likely to be one of the next batch of approved HMOs.

Name	Acceptance number	Acceptance date	Latest updates
2’-FL (Synthesis)	卫食添新申字(2021) No. 0028	2021.7.2	2021.10.21 Issued for public comments 2022.1.18 NHC issued a notice on delaying the review
2’-FL Source: ATCC 13032； Donor: Pseudopedobacter saltans a	卫食添新申字(2023) No. 0045	2023.7.14	2023.8.23 Issued for public comments
a is the donor of α-1, 2-fucosyltransferase

8 HMOs that have been accepted and are in the process of technical review

According to the information released on the Administrative Service Platform of the National Health Commission (NHC), in addition to the HMOs already approved and issued for public comments, there are eight HMOs currently undergoing technical review, which include four types of 2’-FL, two types of 6’-SL, and two types of 3’-SL. Details are shown in the table below:

Name	Acceptance number	Acceptance Date	Latest public review status
2’-FL	卫食添新申字(2022) No. 0085	2022.11.15	2023.1.19 NHC issued a notice on delaying the review
2’-FL	卫食添新申字(2023) No. 0058	2023.9.19	/
2’-FL	卫食添新申字(2023) No. 0059	2023.9.20	/
2’-FL	卫食添新申字(2023) No. 0061	2023.9.20	/
6’-SL	卫食添新申字(2023) No. 0033	2023.5.4	2023.6.6 NHC issued a notice on delaying the review
6’-SL	卫食添新申字(2023) No. 0046	2023.7.17	2023.8.4 Delivering a notification of review opinion
3’-SL	卫食添新申字(2023) No. 0047	2023.7.17	2023.8.4 NHC issued a notice on delaying the review
3’-SL	卫食添新申字(2023) No. 0062	2023.9.21	/

Warm Reminder

Since the inception of HMO compliance in China, major dairy enterprises have been gearing up for action. With the recent introduction of 2’-FL and LNnT, numerous leading brands have promptly launched new products. It’s worth mentioning that the current offerings are HMOs-enriched children's milk powder. The introduction of infant formula with added HMOs will require formula adjustments or registration, requiring a certain time period. With the anticipated approval of more HMO substances, the infant formula industry is likely to witness a significant upgrade in formulas.

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