Assessment of the application for renewal of authorisation of Yea‐Sacc^® (Saccharomyces cerevisiae) for horses

Abstract

Yea‐Sacc^® is an additive based on a live preparation of a strain of Saccharomyces cerevisiae intended for use as a zootechnical additive (digestibility enhancer). The current assessment is performed in the context of the renewal of the authorisation of the feed additive; however, the applicant proposed also to lower (6.5 × 10⁸ colony forming unit (CFU)/kg of complete feedingstuff) the minimum dose of the additive when used in feed for horses. The additive is produced in a powder (Yea‐Sacc^®) and in a prills (Yea‐Sacc^®_TS) forms. The Panel considered that the additive currently on the market complies with the existing conditions of authorisation. Saccharomyces cerevisiae is considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment. As the identity of the production strain has been confirmed, safety for the target species, consumer and the environment were presumed. Both formulations are non‐irritant to skin, Yea‐Sacc^®_TS is non‐irritant to the eye while Yea‐Sacc^® is a moderate irritant. Both formulations should be considered skin sensitisers and because of their high proteinaceous nature, they should be considered as potential respiratory sensitisers. The applicant submitted two efficacy studies: the FEEDAP Panel concluded that in the first study inconsistent results were observed for the two lower doses which are considered microbiologically equivalent. The second study demonstrated that Yea‐Sacc^® at the level of 7.5 × 10⁸ resulted in a better digestion of organic matter which may be explained by increases in digestibility of the fibre. Based on the data provided, the FEEDAP Panel cannot conclude on the efficacy of Yea‐sacc^® when used as a feed additive in horses at the proposed level (6.5 × 10⁸ CFU/kg complete feed).

1. Introduction

1.1. Background and Terms of Reference as provided by the requestor

Regulation (EC) No 1831/20031 establishes the rules governing the Community authorisation of additives for use in animal nutrition. In particular, Article 14(1) of that Regulation lays down that an application for renewal shall be sent to the Commission at the latest one year before the expiry date of the authorisation.

The European Commission received a request from Alltech Ireland2 for renewal of the authorisation of the product Yea‐Sacc^® (Saccharomyces cerevisiae CBS 493.94), when used as a feed additive for horses (category: zootechnical additive; functional group: digestibility enhancer).

According to Article 7(1) of Regulation (EC) No 1831/2003, the Commission forwarded the application to the European Food Safety Authority (EFSA) as an application under Article 14(1) (renewal of the authorisation). The particulars and documents in support of the application were considered valid by EFSA as of 19 December 2018.

According to Article 8 of Regulation (EC) No 1831/2003, EFSA, after verifying the particulars and documents submitted by the applicant, shall undertake an assessment in order to determine whether the feed additive complies with the conditions laid down in Article 5. EFSA shall deliver an opinion on the safety for the target animals, consumer, user and the environment and on the efficacy of the product Yea‐Sacc^® (Saccharomyces cerevisiae CBS 493.94) when used under the proposed conditions of use (see Section 3.1.3).

1.2. Additional information

Yea‐Sacc^® is the trade name of an additive based on a preparation of a strain of yeast (Saccharomyces cerevisiae CBS 493.94).

The product is currently authorised for use in horses,3 dairy cows and minor dairy ruminant species, cattle for fattening and minor ruminant species for fattening.4

EFSA published three opinions on the product Yea‐Sacc^®: one on the safety for leisure horses (EFSA, 2003), one on the safety and efficacy of the same product for horses (EFSA, 2009) and another one on the safety and efficacy of Yea‐Sacc^® when used in cattle for fattening, goats for fattening, dairy cows, dairy sheep, dairy goats and buffaloes (EFSA FEEDAP Panel, 2014).

2. Data and methodologies

2.1. Data

The present assessment is based on data submitted by the applicant in the form of a technical dossier5 in support of the authorisation request for the use of Yea‐Sacc^® (Saccharomyces cerevisiae CBS 493.94) as a feed additive.

The FEEDAP Panel used the data provided by the applicant together with data from other sources, such as previous risk assessments by EFSA.

The European Union Reference Laboratory (EURL) considered that the conclusions and recommendations reached in the previous assessment are valid and applicable for the current application.6

2.2. Methodologies

The approach followed by the FEEDAP Panel to assess the safety and the efficacy of Yea‐Sacc^® (Saccharomyces cerevisiae CBS 493.94) is in line with the principles laid down in Regulation (EC) No 429/20087 and the relevant guidance documents: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2013), Guidance on the characterisation of microorganisms used as feed additives or as production organisms (EFSA FEEDAP Panel, 2018a) and Guidance on the assessment of the efficacy of feed additives (EFSA FEEDAP Panel, 2018b).

3. Assessment

The additive Yea‐Sacc^® is a preparation of a strain of yeast (Saccharomyces cerevisiae CBS 493.94), intended for use as a zootechnical additive (functional group: digestibility enhancer) in feed for horses. The current assessment is performed in the context of the renewal of the authorisation of the feed additive. The applicant is also proposing to lower the minimum dose of the additive when used in feed for horses.

3.1. Characterisation

3.1.1. Characterisation of the active agent

The active agent is a S. cerevisiae strain which is deposited both in the National Collection of Yeast Cultures (UK) with a designation NCYC 1026 and the Centralbureau voor Schimmelcultures (NL) with the accession number CBS 493.94.8

The whole genome of S. cerevisiae CBS 493.94 was sequenced and its taxonomic identification was confirmed by comparison of the D2 region of the LSU rRNA gene sequence with sequences from the validated MicroSEQ library.9 The sequence showed 100% similarity with S. cerevisiae. Moreover, the whole genome sequence (WGS) of the active agent was interrogated for the presence of antimicrobial resistance (AMR) genes and virulence factors. The presence of AMR genes was investigated comparing the sequence to the Comprehensive Antibiotic Resistance Database (CARD) and the presence of virulence factors was investigated by comparing the sequence to the Virulence Factors of Pathogenic Bacteria (VFDB) database. No known genes coding for antimicrobial resistance or virulence factors were found in the genome of the active agent.

3.1.2. Characterisation of the additive

The feed additive is marketed in two forms: dry powder (Yea‐Sacc^®) and prills (Yea‐Sacc^®_TS).

No changes in the manufacturing process or in the composition of the additive were proposed by the applicant. This was confirmed by the analysis of five batches of the additive in prills form produced in 2017–2018, and from the analysis of five batches of the additive in powder form produced in 2018–2019, which showed compliance with the current specifications for the additive (solid form minimum of 1 × 109 colony forming unit (CFU)/g additive).

Microbiological purity was also confirmed by the analysis of five batches of Yea‐Sacc^®_TS in prills produced in 2017–2018. Measurements for Yea‐Sacc^®_TS in prills included Escherichia coli (< 10 CFU/g), Sulfite‐Reducing Anaerobes (< 10 CFU/g), Salmonella (absent), coagulase‐positive staphylococci (< 1,000 CFU/g), Listeria monocytogenes (absent/25 g), Clostridium perfringens (< 10 CFU/g), moulds (< 10 CFU/g), coliforms (< 10 CFU/g). In addition, the applicant provided analytical results on the possible presence of mycotoxins (aflatoxin B1, zearalenone, ochratoxin A, fumonisin (B1 + B2), deoxynivalenol, T2 toxin and HT‐2 toxin) and heavy metals: lead (0.014 mg/kg), cadmium (0.016 mg/kg), mercury (0.007 mg/kg). Results on concentration of arsenic (0.257 mg/kg) were also provided by the applicant. All the results were below the limits established by relevant EU Directive (2002/32 EC). The amount of the impurities in the product does not raise a safety concern.

3.1.3. Stability and homogeneity

3.1.3.1. Shelf‐life of the additive

A new study on four batches of Yea‐Sacc^®_TS stored at 25°C (relative humidity (RH) 60%), for 12 months has been provided by the applicant. The data demonstrated that no significant losses of the content of Saccharomyces cerevisiae CBS 493.9 were observed.10

3.1.3.2. Homogeneity

The applicant provided homogeneity distribution data on Yea‐Sacc^®_TS in an equine feed.

The base mixture was made of barley, wheat, wheat bran, soybean meal and alfalfa pellets. The target yeast inclusion level was 1.39 × 10⁷ CFU/g. This premixture was then added to the base mixture in the twin shaft mixer and mixed for 2 minutes. From this mixture, ten 200 g samples were taken to determine the homogenous distribution of the yeast preparation. The coefficient of variation (CV) was 80.94%. The analysis showed wide variation (6.0 × 10⁵–3 × 10⁷ CFU/g).11

3.1.4. Conditions of use

The feed additive is currently authorised for feed for horses at a minimum content of 1.6 × 10⁹ CFU/kg complete feed. The applicant is now asking to reduce the minimum content to 6.5 × 10⁸ CFU/kg of complete feed.

3.2. Safety

Saccharomyces cerevisiae was considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment. As the identity of the production strain was established and as the additive essentially consists only of the active agent, safety for the target species, consumer and the environment were presumed (EFSA FEEDAP Panel, 2014).

In the present application, the applicant has provided up to date confirmation of the taxonomical identification of the strain as S. cerevisiae. Consequently, the additive can be presumed as safe for the target species, the consumer and the environment.

The safety for the user was evaluated by EFSA FEEDAP Panel in previous assessment (EFSA FEEDAP Panel, 2014). The FEEDAP Panel concluded that both formulations are non‐irritant to skin, Yea‐Sacc^®_TS is non‐irritant to the eye while Yea‐Sacc^® is a moderate irritant. Due to lack of data, both formulations should be considered skin sensitisers and because of their high proteinaceous nature, they should be considered as potential respiratory sensitisers. Yea‐Sacc^®_TS is designed to reduce dustiness and no significant exposure of users is to be expected for this form. In the absence of data on the dusting potential of Yea‐Sacc^®, it would be prudent to treat it as a respiratory sensitiser.

3.3. Efficacy

The applicant is asking to lower the minimum dose of the feed additive from 1.6 × 10⁹ to 6.5 × 10⁸ CFU/kg feed. In support of this modification, the applicant submitted two efficacy studies conducted on horses.

3.3.1. Efficacy for horses

Trial I

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Results are presented in Table 1.

Table 1.

Effects of Yea‐sacc^® on the faecal apparent digestibility in horses (trial I)

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Trial II

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Results are presented in Table 2.

Table 2.

Effects of Yea‐sacc^® on the faecal apparent digestibility in horses (trial II)

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3.3.2. Conclusions on efficacy

The FEEDAP Panel concluded that in the first study inconsistent results were observed for the two lower doses which are considered microbiologically equivalent. Moreover, a significant effect was reported only for hemicellulose which was not considered sufficient by the Panel.

The second study demonstrated that Yea‐Sacc at the level of 7.5 × 10⁸ resulted in a better digestion of organic matter which may be explained by increases in digestibility of the fibre.

Based on the data provided, the FEEDAP Panel cannot conclude on the efficacy of Yea‐sacc^® when used as a feed additive in horses at the proposed level (6.5 × 10⁸ CFU/kg complete feed).

3.4. Post‐market monitoring

The FEEDAP Panel considers that there is no need for specific requirements for a post‐market monitoring plan other than those established in the Feed Hygiene Regulation14 and Good Manufacturing Practice.

4. Conclusions

The additive currently on the market complies with the existing conditions of authorisation. The FEEDAP Panel concludes that Yea‐sacc^® remains safe for horses, consumers of products from animals fed the additive and the environment under the approved conditions of authorisation. Both formulations are non‐irritant to skin, Yea‐Sacc^®_TS is non‐irritant to the eye while Yea‐Sacc^® is a moderate irritant. Both formulations should be considered skin sensitisers and because of their high proteinaceous nature, they should be considered as potential respiratory sensitisers. The FEEDAP Panel cannot conclude on the efficacy of Yea‐sacc^® when used as a feed additive in horses at the proposed use level.

5. Documentation as provided to EFSA/Chronology

Date	Event
16/10/2018	Dossier received by EFSA. Yea‐Sacc® ‐ Saccharomyces cerevisiae CBS 493.94. Submitted by Alltech Ireland
07/11/2018	Reception mandate from the European Commission
19/12/2018	Application validated by EFSA – Start of the scientific assessment
21/12/2018	Request of supplementary information to the applicant in line with Article 8(1)(2) of Regulation (EC) No 1831/2003 – Scientific assessment suspended. Issues: efficacy
30/04/2019	Reception of supplementary information from the applicant ‐ Scientific assessment re‐started
19/03/2019	Comments received from Member States
12/11/2019	Opinion adopted by the FEEDAP Panel. End of the Scientific assessment

Abbreviations

ADF

acid detergent fibre

AMR

antimicrobial resistance

bw

body weight

CARD

Antibiotic Resistance Database

CF

crude fibre

CFU

colony forming unit

CV

coefficient of variation

DM

dry matter

EURL

European Union Reference Laboratory

NDF

neutral detergent fibre

OM

organic matter

PCR

polymerase Chain Reaction

RH

relative humidity

VFDB

Virulence Factors of Pathogenic Bacteria database

WGS

whole genome sequence

Suggested citation: EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) , Bampidis V, Azimonti G, Bastos ML, Christensen H, Dusemund B, Kouba M, Kos Durjava M, López‐Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Sanz Y, Villa RE, Woutersen R, Anguita M, Galobart J, Holczknecht O, Manini P, Tarrés‐Call J, Pettenati E and Pizzo F, 2019. Scientific Opinion on the assessment of the application for renewal of authorisation of Yea‐Sacc^® (Saccharomyces cerevisiae) for horses. EFSA Journal 2019;17(12):5918, 9 pp. 10.2903/j.efsa.2019.5918