Commission Implementing Regulation (EU) 2024/1047 of 9 April 2024 authorising the placing on the market of 3′-Sialyllactose sodium salt produced using a derivative strain of Escherichia coli W (ATCC 9637) as a novel food and amending Implementing Regulation (EU) 2017/2470

Official Journal EN of the European Union L series 2024/1047 10.4.2024 COMMISSION IMPLEMENTING REGULATION (EU) 2024/1047 of 9 April 2024 authorising the placing on the market of 3′-Sialyllactose sodium salt produced using a derivative strain of Escherichia coli W (ATCC 9637) as a novel food and amending Implementing Regulation

(EU) 2017/2470 (Text with EEA relevance) THE EUROPEAN COMMISSION, Having regard to the Treaty on the Functioning of the European Union, Having regard to Regulation (EU) 2015/2283 of the European Parliament and of the Council of 25 November 2015 on novel foods, amending Regulation (EU) No 1169/2011 of the European Parliament and of the Council and repealing Regulation (EC) No 258/97 of the European Parliament and of the Council and Commission Regulation (EC) No 1852/2001(1), and in particular Article 12(1) thereof,

Whereas:

(1) Regulation (EU) 2015/2283 provides that only novel foods authorised and included in the Union list of novel foods may be placed on the market within the Union.

(2) Pursuant to Article 8 of Regulation (EU) 2015/2283, Commission Implementing Regulation (EU) 2017/2470(2)has established a Union list of novel foods.

(3) On 25 March 2021, the company Kyowa Hakko Bio Co., Ltd. (‘the applicant’) submitted an application for an authorisation to the Commission in accordance with Article 10(1) of Regulation (EU) 2015/2283 to place 3′- Sialyllactose (‘3′-SL’) sodium salt, obtained by microbial fermentation using a genetically modified strain (Escherichia coli NEO3) derived from the host strain Escherichia coli (E. coli) W (ATCC 9637), on the Union market as a novel food.

The applicant requested for the so produced 3′-SL sodium salt to be used in unflavoured pasteurised and unflavoured sterilised milk products, unflavoured fermented milk-based products, flavoured fermented milk-based products including heat-treated products, beverages (flavoured drinks excluding drinks with a pH less than 5), cereal bars, infant formula and follow-on formula as defined in Regulation (EU) No 609/2013 of the European Parliament and of the Council(3), processed cereal-based food and baby food for infants and young children as defined in Regulation (EU) No 609/2013, milk-based drinks and similar products, total diet replacement foods for weight control as defined in Regulation (EU) No 609/2013, foods for special medical purposes as defined in Regulation (EU) No 609/2013, and in food supplements as defined in Directive 2002/46/EC of the European Parliament and of the Council(4) intended for the general population. With regard to conditions of use, the applicant also proposed that food supplements containing 3′-SL sodium salt produced using a derivative strain of E.

coli W (ATCC 9637) should not be consumed if other foods with added 3′-SL sodium salt are consumed on the same day. Subsequently, on 19 October 2023, the applicant modified the initial request in the application for the use of 3′-SL sodium salt produced using a derivative strain of E. coli W (ATCC 9637) in food supplements to exclude infants and children under three years of age.

(1) OJ L 327, 11.12.2015, p. 1, ELI: http://data.europa.eu/eli/reg/2015/2283/oj.

(2) Commission Implementing Regulation (EU) 2017/2470 of 20 December 2017 establishing the Union list of novel foods in accordance with Regulation (EU) 2015/2283 of the European Parliament and of the Council on novel foods (OJ L 351, 30.12.2017, p. 72, ELI:

http://data.europa.eu/eli/reg_impl/2017/2470/oj).

(3) Regulation (EU) No 609/2013 of the European Parliament and of the Council of 12 June 2013 on food intended for infants and young children, food for special medical purposes, and total diet replacement for weight control and repealing Council Directive 92/52/EEC, Commission Directives 96/8/EC, 1999/21/EC, 2006/125/EC and 2006/141/EC, Directive 2009/39/EC of the European Parliament and of the Council and Commission Regulations (EC) No 41/2009 and (EC) No 953/2009 (OJ L 181, 29.6.2013, p. 35, ELI:

http://data.europa.eu/eli/reg/2013/609/oj).

(4) Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements (OJ L 183, 12.7.2002, p. 51, ELI: http://data.europa.eu/eli/dir/2002/46/oj).

ELI: http://data.europa.eu/eli/reg_impl/2024/1047/oj 1/7EN OJ L, 10.4.2024

(4) On 26 March 2021, the applicant also made a request to the Commission for the protection of proprietary scientific studies and data, namely, a liquid chromatography-mass spectrometry (‘LC-MS/MS’) study, a nuclear magnetic resonance (‘NMR’) study, and a high-performance liquid chromatography – charged aerosol detection (‘HPLC-CAD’) study for the determination of the identity of 3′-SL(5); a description of the genetically modified 3′-SL sodium salt production strain(6); a detailed description of the production process(7); a bacterial reverse mutation test with 3′-SL sodium salt(8); an in vitro mammalian cell micronucleus test with 3′-SL sodium salt(9); an in vivo mammalian cell micronucleus test with 3′-SL sodium salt(10); an in vivo mammalian cell micronucleus test with 6′-Sialyllactose (‘6′-SL’) sodium salt(11); a bacterial reverse mutation test with 6′-SL sodium salt(12); a 90-day oral toxicity study in rats with 3′-SL sodium salt(13); a bioinformatics analysis study on the genome of the E. coli W (ATCC 9637) to detect heterologous sequences that could encode possible allergens(14); and, a 90-day oral toxicity study in rats with 6′-SL sodium salt(15), submitted in support of the application.

(5) In accordance with Article 10(3) of Regulation (EU) 2015/2283, on 7 December 2021, the Commission requested the European Food Safety Authority (‘the Authority’) to carry out an assessment of 3′-SL sodium salt obtained by microbial fermentation using a genetically modified strain of E. coli W (ATCC 9637), as a novel food.

(6) On 3 August 2023, the Authority adopted its scientific opinion on the ‘Safety of 3′-sialyllactose (‘3′-SL’) sodium salt produced by a derivative strain (Escherichia coli NEO3) of Escherichia coli W (ATCC 9637) as a novel food pursuant to Regulation (EU) 2015/2283’(16), in accordance with Article 11 of Regulation (EU) 2015/2283.

(7) In its scientific opinion, the Authority concluded that 3′-SL sodium salt is safe under the proposed conditions of use and for the proposed target populations. Therefore, that scientific opinion gives sufficient grounds to establish that 3′-SL sodium salt produced using a derivative strain of E. coli W (ATCC 9637), when used in unflavoured pasteurised and unflavoured sterilised milk products, unflavoured fermented milk-based products, flavoured fermented milk-based products including heat-treated products, beverages (flavoured drinks excluding drinks with a pH less than 5), cereal bars, infant formula and follow-on formula, processed cereal-based food and baby food for infants and young children, milk-based drinks and similar products, total diet replacement foods for weight control, foods for special medical purposes, and in food supplements, complies with the authorisation requirements laid down Article 12(1) of Regulation (EU) 2015/2283.

(8) In its scientific opinion, the Authority noted that its conclusion on the safety of the novel food was based on scientific studies and data from the LC-MS/MS, the NMR and the HPLC-CAD studies for the determination of the identity of 3′-SL; the description of the genetically modified 3′-SL sodium salt production strain; the detailed description of the production process; the bacterial reverse mutation test with 3′-SL sodium salt; the in vitro mammalian cell micronucleus test with 3′-SL sodium salt; the in vivo mammalian cell micronucleus test with 3′-SL sodium salt; the bioinformatics analysis study on the genome of the E. coli W (ATCC 9637) to detect heterologous sequences that could encode possible allergens; and the 90-day oral toxicity study in rats with 3′-SL sodium salt, contained in the applicant’s file, without which it could not have assessed the novel food and reached its conclusion.

(5) Kyowa Hakko Bio Co., Ltd, 2021, 2022, and 2023 (unpublished).

(6) Kyowa Hakko Bio Co., Ltd, 2021, 2022, and 2023 (unpublished).

(7) Kyowa Hakko Bio Co., Ltd, 2021, 2022, and 2023 (unpublished).

(8) Kyowa Hakko Bio Co., Ltd, 2020 (unpublished).

(9) Kyowa Hakko Bio Co., Ltd, 2022 (unpublished).

(10) Kyowa Hakko Bio Co., Ltd, 2020 (unpublished).

(11) Kyowa Hakko Bio Co., Ltd, 2020 (unpublished).

(12) Kyowa Hakko Bio Co., Ltd, 2020 (unpublished).

(13) Kyowa Hakko Bio Co., Ltd, 2021 (unpublished).

(14) Kyowa Hakko Bio Co., Ltd, 2021 (unpublished).

(15) Kyowa Hakko Bio Co., Ltd, 2021 (unpublished).

(16) EFSA Journal 2023;21(9):8224.

2/7 ELI: http://data.europa.eu/eli/reg_impl/2024/1047/ojEN OJ L, 10.4.2024

(9) The Commission requested the applicant to further clarify the justification provided with regard to its proprietary claim over those scientific studies and data, and to clarify its claim to an exclusive right of reference to them in accordance with Article 26(2), point (b) of Regulation (EU) 2015/2283.

(10) The applicant declared that it held proprietary and exclusive rights of reference to the scientific studies and data, namely, the LC-MS/MS, the NMR and the HPLC-CAD studies for the determination of the identity of 3′-SL; the description of the genetically modified 3′-SL sodium salt production strain; the detailed description of the production process; the bacterial reverse mutation test with 3′-SL sodium salt; the in vitro mammalian cell micronucleus test with 3′-SL sodium salt; the in vivo mammalian cell micronucleus test with 3′-SL sodium salt; a bioinformatics analysis study on the genome of the E. coli W (ATCC 9637) to detect heterologous sequences that could encode possible allergens; and the 90-day oral toxicity study in rats with 3′-SL sodium salt, under national law at the time of submission of the application and that third parties cannot lawfully access, use or refer to those data and studies.

(11) The Commission assessed all the information provided by the applicant and considered that the applicant has sufficiently substantiated the fulfilment of the requirements laid down in Article 26(2) of Regulation

(EU) 2015/2283. Therefore, the scientific studies and data submitted in support of the application, namely, the LC-MS/MS, the NMR and the HPLC-CAD studies for the determination of the identity of 3′-SL; the description of the genetically modified 3′-SL sodium salt production strain; the detailed description of the production process; the bacterial reverse mutation test with 3′-SL sodium salt; the in vitro mammalian cell micronucleus test with 3′-SL sodium salt; the in vivo mammalian cell micronucleus test with 3′-SL sodium salt; the bioinformatics analysis study on the genome of the E. coli W (ATCC 9637) to detect heterologous sequences that could encode possible allergens;

and the 90-day oral toxicity study in rats with 3′-SL sodium salt, should be protected in accordance with Article 27(1) of Regulation (EU) 2015/2283. Accordingly, only the applicant should be authorised to place 3′-SL sodium salt produced using a derivative strain of E. coli W (ATCC 9637) on the market within the Union during a period of five years from the entry into force of this Regulation.

(12) However, restricting the authorisation of 3′-SL sodium salt produced using a derivative strain of E. coli W (ATCC

9637) and the reference to the scientific studies and data contained in the applicant’s file for the sole use by them does not prevent subsequent applicants from applying for an authorisation to place on the market the same novel food provided that their application is based on legally obtained information supporting such an authorisation.

(13) In line with the conditions of use of food supplements containing 3′-SL sodium salt produced using a derivative strain of E. coli W (ATCC 9637), as proposed by the applicant, it is necessary to inform consumers by appropriate labelling that food supplements containing 3′-SL sodium salt, produced with a derivative strain of E. coli W (ATCC

9637), should not be consumed by infants and children under three years of age and should not be used if other foods with added 3′-SL sodium salt are consumed on the same day.

(14) It is appropriate that the inclusion of 3′-SL sodium salt produced using a derivative strain of E. coli W (ATCC 9637) as a novel food in the Union list of novel foods contains also the information referred to in Article 9(3) of Regulation

(EU) 2015/2283.

(15) 3′-SL sodium salt produced using a derivative strain of E. coli W (ATCC 9637) should be included in the Union list of novel foods set out in Implementing Regulation (EU) 2017/2470. The Annex to Implementing Regulation

(EU) 2017/2470 should therefore be amended accordingly.

(16) The measures provided for in this Regulation are in accordance with the opinion of the Standing Committee on Plants, Animals, Food and Feed,

ELI: http://data.europa.eu/eli/reg_impl/2024/1047/oj 3/7EN OJ L, 10.4.2024

HAS ADOPTED THIS REGULATION:

Article 1

1. 3′-Sialyllactose sodium salt produced using a derivative strain of Escherichia coli W (ATCC 9637) is authorised to be placed on the market within the Union.

3′-Sialyllactose sodium salt produced using a derivative strain of Escherichia coli W (ATCC 9637) shall be included in the Union list of novel foods set out in Implementing Regulation (EU) 2017/2470.

2. The Annex to Implementing Regulation (EU) 2017/2470 is amended in accordance with the Annex to this Regulation.

Article 2 Only the company Kyowa Hakko Bio Co., Ltd.(17) is authorised to place on the market within the Union the novel food referred to in Article 1, for a period of 5 years from 30 April 2024, unless a subsequent applicant obtains an authorisation for that novel food without reference to the scientific data protected pursuant to Article 3 or with the agreement of Kyowa Hakko Bio Co., Ltd.

Article 3 The scientific data contained in the application file and fulfilling the conditions laid down in Article 26(2) of Regulation

(EU) 2015/2283 shall not be used for the benefit of a subsequent applicant for a period of 5 years from30 April 2024, without the agreement of Kyowa Hakko Bio Co., Ltd.

Article 4 This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.

This Regulation shall be binding in its entirety and directly applicable in all Member States.

Done at Brussels, 9 April 2024.

For the Commission The President Ursula VON DER LEYEN

(17) Address: Nakano Central Park South, Nakano 4-10-2, Nakano-ku, Tokyo 164-0001 Japan.

4/7 ELI: http://data.europa.eu/eli/reg_impl/2024/1047/ojANNEX The Annex to Implementing Regulation (EU) 2017/2470 is amended as follows:

(1) in Table 1 (Authorised novel foods), the following entry is inserted in alphabetical order:

Authorised novel food Conditions under which the novel food may be used Additional specific labelling Other Data Protection requirements requirements ‘3′-Sialyllactose (3′-SL) Specified food category Maximum levels (expressed as 3′-Sialyl­ The designation of the novel food on Authorised on 30 April sodium salt lactose) the labelling of the foodstuffs con­ 2024.

(produced using a deriva­ taining it shall be “3′-Sialyllactose This inclusion is based on tive strain of E. coli W Unflavoured pasteurised and 0,25 g/L sodium salt”. proprietary scientific evi­ (ATCC 9637)) unflavoured sterilised (includ­ dence and scientific data ing UHT) milk products The labelling of food supplements protected in accordance 0,25 g/L (beverages) containing 3′-Sialyllactose (3′-SL) with Article 26 of Regula­ Unflavoured fermented milk- sodium salt shall bear a statement tion (EU) 2015/2283.

that they should not be consumed: based products 0,5 g/kg (products other than

(a) if foods containing added 3′- Applicant: Kyowa Hakko Bio beverages) Sialyllactose sodium salt are Co., Ltd, Nakano Central 0,25 g/L (beverages) consumed on the same day; Park South, Nakano 4-10-2, Flavoured fermented milk- (b) by children under 3 years of age. Nakano-ku Tokyo, based products including 164-0001 Japan. During 2,5 g/kg (products other than heat-treated products the period of data protec­ beverages) tion, the novel food 3′-sialyl­ Beverages (flavoured drinks, 0,25 g/L lactose sodium salt pro­ excluding drinks with a pH duced using a derivative less than 5) strain of E. coli W (ATCC

9637) is authorised for pla­ Cereal bars 2,5 g/kg cing on the market within the Union only by Kyowa 0,2 g/L in the final product ready Hakko Bio Co., Ltd, unless a Infant formula as defined for use, marketed as such or subsequent applicant under Regulation (EU) reconstituted as instructed by the obtains authorisation for No 609/2013 manufacturer the novel food without refer­ ence to the proprietary 0,15 g/L in the final product ready scientific evidence or scien­ Follow-on formula as defined for use, marketed as such or tific data protected in accor­ under Regulation (EU) reconstituted as instructed by the dance with Article 26 of Reg­ No 609/2013 manufacturer ulation (EU) 2015/2283 or with the agreement of 0,15 g/L (beverages) in the final Kyowa Hakko Bio Co., Ltd.

Processed cereal-based food product ready for use, marketed as and baby food for infants and such or reconstituted as instructed End date of the data protec­

young children as defined by the manufacturer tion: 30 April 2029.’ under Regulation (EU) No 609/2013 1,25 g/kg for products other than beverages

ELI:

http://data.europa.eu/eli/reg_impl/2024/1047/oj 5/7 OJ L,

10.4.2024 EN0,15 g/L (beverages) in the final Milk based drinks and similar product ready for use, marketed as products such or reconstituted as instructed by the manufacturer Total diet replacement foods 0,5 g/L (beverages) for weight control as defined 5,0 g/kg (products other than under Regulation (EU) beverages) No 609/2013 In accordance with the particular Food for special medical pur­ nutritional requirements of the poses as defined under Regu­ persons for whom the products lation (EU) No 609/2013 are intended Food supplements as defined 1,0 g/day in Directive 2002/46/EC, excluding food supplements for infants and young children

(2) in Table 2 (Specifications), the following entry is inserted in alphabetical order:

Authorised novel food Specification ‘3′-Sialyllactose (3′-SL) sodium salt Description: (produced using a derivative strain of 3′-Sialyllactose (3′-SL) sodium salt is a purified, concentrated, white to off-white powder that is produced by a microbial process. It contains E. coli W (ATCC 9637)) limited levels of Sialic acid, D-Lactose, D-Glucose, and 3′-Sialyllactulose and 6′-Sialyllactose sodium salts.

Source:

Genetically modified strain of Escherichia coli W (ATCC 9637)

Definition:

Chemical formula: C H NO Na 23 38 19

Chemical name: N-Acetyl-α-D-neuraminyl-(2→3)-β-D-galactopyranosyl-(1→4)-D-glucose, sodium salt

Molecular mass: 655,53 Da

CAS No: 128596-80-5 6/7

ELI:

http://data.europa.eu/eli/reg_impl/2024/1047/oj EN OJ L,

10.4.2024Characteristics/Composition:

3′-Sialyllactose sodium salt (% w/w of dry matter): ≥ 82,0 Sialic acid (% w/w of dry matter): ≤ 6,0 D-Lactose (% w/w of dry matter): ≤ 3,0 D-Glucose (% w/w of dry matter): ≤ 3,0 Sum of 3′- Sialyllactulose and 6′-Sialyllactose sodium salts (% w/w of dry matter): ≤ 5,0 Sum of other carbohydratesa (% w/w of dry matter): ≤ 12,0 Moisture (% w/w): ≤ 10,5 Sodium (% w/w): ≤ 5,0 pH (25 °C, 5 % solution): 4,5 -7,5 Residual protein (% w/w): ≤ 0,01

Heavy metals and contaminants:

Arsenic (mg/kg): ≤ 0,2 Lead (mg/kg): ≤ 0,2 Cadmium (mg/kg): ≤ 0,2 Mercury (mg/kg): ≤ 0,1 Aflatoxin M1: < 0,025 (μg/kg)

Microbiological criteria: Τοtal plate count: ≤ 1 000CFU/g

Enterobacteriaceae: Absence in 10 g Cronobacter spp.: Absence in 10 g Salmonella spp.: Absence in 25 g

Yeasts and moulds: ≤ 100 CFU/g

Listeria monocytogenes: Absence in 25 g

Presumptive Bacillus cereus: ≤ 50 CFU/g

Residual endotoxins: ≤ 10 EU/mg aSum of other carbohydrates = 100 % w/w of dry matter – 3′-Sialyllactose (acid, % w/w of dry matter) –quantified carbohydrates ((% w/w of dry matter), Sialic acid + D-Lactose + D-Glucose + (3′- Sialyllactulose and 6′-Sialyllactose (acids)) – sodium (w/w of dry matter); CFU: Colony Forming Units; EU: Endotoxin Units’

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http://data.europa.eu/eli/reg_impl/2024/1047/oj 7/7 OJ L,

10.4.2024 EN