SCIENTIFIC OPINION. Safety and efficacy of Biosaf Sc47 (Saccharomyces cerevisiae) as feed additive for dairy buffaloes 1

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1 The EFSA Journal (2008) 837, 1-10 SCIENTIFIC OPINION Safety and efficacy of Biosaf Sc47 (Saccharomyces cerevisiae) as feed additive for dairy buffaloes 1 Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed (Question No EFSA-Q ) Adopted on 21 October 2008 PANEL MEMBERS Georges Bories, Paul Brantom, Joaquim Brufau de Barberà, Andrew Chesson, Pier Sandro Cocconcelli, Bogdan Debski, Noël Dierick, Jürgen Gropp, Ingrid Halle, Christer Hogstrand, Joop de Knecht, Lubomir Leng, Sven Lindgren, Anne-Katrine Lundebye Haldorsen, Alberto Mantovani, Miklós Mézes, Carlo Nebbia, Walter Rambeck, Guido Rychen, Atte von Wright and Pieter Wester SUMMARY Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the safety and efficacy of the product Biosaf Sc47 when used as a feed additive for dairy buffaloes. Biosaf Sc47 is the trade name for a feed additive based on viable cells of a strain of Saccharomyces cerevisiae. The product and its active component have already been extensively assessed as a feed additive. The product is currently authorised for use with pigs (sows, piglets and pigs for fattening), horses, rabbits for fattening, ruminants for fattening (cattle and lambs) and ruminants for milk production (dairy cows, sheep and goats). The present opinion concerns a request for an additional authorisation for the use of Biosaf Sc47 in feed for dairy buffaloes to improve the protein content in milk. The additive is recommended to be included in feed from beginning to end of the lactation at a minimum dose of 5 x 10 8 CFU and a maximum dose of 1.4 x 10 9 CFU kg -1 complete feed. Dairy buffaloes are considered to be a minor species. As the proposed dose range is similar and the mechanism of action can be presumed to be essentially the same, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) considers that efficacy for buffaloes at the minimum dose can be extrapolated from dairy cattle. This view is supported by the experimental data from two studies, one at the minimum dose and one at the maximum dose, in which significant increases in milk protein content were recorded. 1 For citation purposes: Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed on the safety and efficacy of Biosaf Sc47 (Saccharomyces cerevisiae NCYC Sc47) as feed additive for dairy buffaloes. The EFSA Journal (2008) 837, 1-10 European Food Safety Authority, 2008

2 The active component, a strain of Saccharomyces cerevisiae, is considered by EFSA to have QPS status and, as such, can be presumed as safe for the target species, the consumers and the wider environment. The additional experimental data provided in support of target animal safety does not conflict in any way with the conclusion reached on safety using the QPS approach. The use of the product Biosaf Sc47 with dairy buffaloes is not expected to introduce any additional hazards for users of the product. Key words: zootechnical additive, gut-flora stabiliser, Biosaf Sc47, Saccharomyces cerevisiae, dairy buffaloes, efficacy, safety, QPS The EFSA Journal (2008) 837, 2-10

3 TABLE OF CONTENTS Panel Members...1 Summary...1 Table of Contents...3 Background...4 Terms of reference...4 Acknowledgements...4 Assessment Introduction Identity, characterisation and conditions of use Characterisation of the active agent Stability and homogeneity Proposed conditions of use Evaluation of the analytical methods by the Community Reference Laboratory Efficacy Safety Safety for the target species Safety for the user Post-marketing monitoring...8 Conclusions...8 Documentation provided to EFSA...8 References...8 Appendix...10 The EFSA Journal (2008) 837, 3-10

4 BACKGROUND Regulation (EC) No 1831/ establishes the rules governing the Community authorisation of additives for use in animal nutrition. In particular, Article 4(1) of that Regulation lays down that any person seeking an authorisation for a feed additive or for a new use of a feed additive shall submit an application in accordance with Article 7. The European Commission received a request from the company Lesaffre Feed Additives 3 for authorisation of the product Biosaf Sc47 to be used as a feed additive for dairy buffaloes (category: zootechnical additives; functional group: gut flora stabilisers) under the conditions described in Table 1. 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 4(1) (authorisation of a feed additive or new use of a feed additive). EFSA received directly from the applicant the technical dossier in support of this application. 4 According to Article 8 of that Regulation, 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. The particulars and documents in support of the application were considered valid by EFSA as of 22 April The additive Biosaf Sc 47 is a preparation of Saccharomyces cerevisiae NCYC Sc47. This product is already permanently authorised for use in cattle for fattening, dairy cows, rabbits for fattening, sows and piglets. It has also been authorised under Regulation (EC) No 1831/2003 for lambs for fattening, 5 horses, 6 dairy goats and dairy sheep, 7 and pigs for fattening. 8 The Scientific Committee on Animal Nutrition (SCAN) issued an opinion on the safety of this product for the piglets, sows, beef and dairy cattle, including the safety for the user, the consumer and the environment (EC, 1997/2003), and another on the efficacy for cattle for fattening (EC, 2002). EFSA issued five opinions on the safety and efficacy of this product for the following species: lambs for fattening (EFSA, 2006a), dairy small ruminants (EFSA, 2006b), horses (EFSA, 2006c), calves for rearing (EFSA, 2007a) and pigs for fattening (EFSA, 2007b). TERMS OF REFERENCE According to Article 8 of Regulation (EC) No 1831/2003, EFSA shall determine whether the feed additive complies with the conditions laid down in Article 5. EFSA shall deliver an opinion on the efficacy and the safety for the target animals, the consumer, user and the environment of the product Biosaf Sc47 which is a preparation of Saccharomyces cerevisiae NCYC Sc47, when used under the conditions described in Table 1. ACKNOWLEDGEMENTS The European Food Safety Authority wishes to thank the members of the Working Group on Micro-organisms as well as Anders Franklin for the preparation of this opinion. 2 OJ L 268, , p.29 3 Lesaffre Feed Additives, 90, rue de Lille, Marquette-Lez-Lille, France. 4 Dossier reference: FAD OJ L 271, , p.28 6 OJ L 63, , p.6 7 OJ L 57, , p.3 8 OJ L 63, , p. 3 The EFSA Journal (2008) 837, 4-10

5 Table 1. Register entry as proposed by the applicant Additive Saccharomyces cerevisiae NCYC Sc47 Registration number/ec No/No Category of additive Zootechnical additives Functional group of additive Gut flora stabilisers Description Composition, description Chemical formula Purity criteria (if appropriate) Method of analysis (if appropriate) Preparation of Saccharomyces cerevisiae containing a minimum of 5 x 109 CFU/g of additive Not appropriate Not appropriate Trade name (if appropriate) Name of the holder of authorisation (if appropriate) BIOSAF Sc47 Société Industrielle Lesaffre Conditions of use Species or category of animal Maximum Age Minimum content Maximum content Withdrawal period CFU/kg of complete feedingstuffs Dairy buffaloes x x 10 9 Not appropriate Other provisions and additional requirements for the labelling Specific conditions or restrictions for use Specific conditions or restrictions for handling Post market monitoring Reserved exclusively to the manufacture of animals feeds Production/expiry dates and batch number printed on the commercial packaging Stable for pellets at dye temperatures up to 83 C Stable for milk replacer at milk temperature under 62 C and for mix preparation time under 5 minutes Store in a cool and dry place Not appropriate Specific conditions for use in complementary feedingstuffs Maximum Residue Limit (MRL) (if appropriate) Marker residue Species or category of animal Target tissue(s) or food products Not appropriate Maximum content in tissues Not appropriate Not appropriate Not appropriate Not appropriate The EFSA Journal (2008) 837, 5-10

6 ASSESSMENT 1. Introduction Biosaf Sc47 is the trade name for a feed additive based on viable cells of a strain of Saccharomyces cerevisiae, a yeast species which EFSA recognises as having QPS status. The product and its active component have already been extensively assessed as a feed additive in the European Community latterly under the category of zootechnical additives (functional group: gut flora stabilisers). The product is currently authorised for use in pigs (sows, piglets and pigs for fattening), horses, rabbits for fattening, ruminants for fattening (cattle and lambs) and, of particular relevance to this application, ruminants for milk production (dairy cows, sheep and goats). The applicant has now applied for an additional authorisation for a period of ten years for the use of Biosaf Sc47 in dairy buffaloes to improve the protein content in milk. 2. Identity, characterisation and conditions of use 2.1. Characterisation of the active agent The yeast strain used for the production of Biosaf Sc47 is deposited with the UK National Collection of Yeast Cultures (NCYC) with accession number NCYC Sc47. The identity of the deposited strain was initially established by the NCYC on the basis of morphology and biochemical characteristics. Subsequently, pulsed field electrophoresis was used to confirm identity and demonstrate genetic stability. Comparison of electrophoresis patterns between samples of the product taken between 1990 and 2000 showed no differences. PCR methods are available to distinguish the production strain from other strains of the same species Stability and homogeneity The shelf life of the product (one year under ambient conditions) and its stability when incorporated into premixtures and complete feedingstuffs have been extensively considered in the context of previous opinions. Studies made with protein concentrates and mineral premixtures for dairy cattle in which the product demonstrated stability for a minimum of three and nine months, respectively, were included. Stability was also demonstrated during pelleting provided that die temperatures did not exceed 83 o C. The FEEDAP Panel considers that, given the essential similarity between feed for dairy cattle and for dairy buffaloes, those results could be extrapolated to premixtures and concentrates intended for buffaloes. Similarly, data demonstrating that the product could be homogeneously mixed into a mineral premix and mash and pelleted concentrate for dairy cows (a coefficient of variation of ~ 5 %) can be extrapolated to the corresponding premixtures/feeds for dairy buffaloes Proposed conditions of use The additive is proposed for use in feed or feed supplements for dairy buffaloes from beginning to end of the lactation at a minimum dose of 5 x 10 8 CFU and a maximum dose of 1.4 x 10 9 CFU kg -1 complete feed. The EFSA Journal (2008) 837, 6-10

7 2.4. Evaluation of the analytical methods by the Community Reference Laboratory EFSA has verified the CRL report as it relates to the methods used for the control of the active agent in animal feed. The Executive Summary of the CRL report can be found in the Appendix. 3. Efficacy Dairy buffaloes are considered a minor species and no experimental demonstration of efficiency is required provided that efficacy has already been demonstrated in a relevant major species (dairy cows in this instance) at a similar dose and that the underlying mechanism of action is likely to be the same. Given the essential similarity of rumen function in both cattle and buffaloes, the FEEDAP Panel considers it reasonable to assume a common mechanism of action in both species. The dose authorised for dairy cattle (4 x 10 8 to 2 x 10 9 CFU kg -1 complete feed) is very similar to the range claimed as effective in buffaloes. Consequently, the FEEDAP Panel considers that efficacy at the lowest dose can be presumed from the results demonstrated in dairy cattle (and small ruminants). However, the applicant submitted a single efficacy study, 9 carried out in India with dairy buffaloes, in which Biosaf Sc47 was fed at the minimum recommended dose. A total of 40 Murah buffaloes were assigned to one of two experimental groups on the basis of milk production for the seven days preceding the start of the experiment. Both groups were given a common feed with the treatment group also given Biosaf Sc47 at 5 x 10 8 CFU kg -1 of complete feedstuffs (confirmed by analysis) via the concentrate. Milk yield and quality were recorded after 7, 14, 28, and 60 days and at the end of the experiment (90 days). No significant effects on milk yield were seen but Biosaf Sc47 addition significantly increased the concentration of milk protein (4.02 vs %, P = 0.02) and milk fat (7.48 vs. 7.64, P = 0.08). Efficacy at the maximum recommended dose has also been demonstrated as part of a tolerance study submitted in support of the assessment of safety for the target animal (see Section 4.1). 4. Safety The species Saccharomyces cerevisiae is considered by EFSA to have QPS status and not to require any specific demonstration of safety other than for the user. In the view of the FEEDAP Panel, the identity of the production strain is established and therefore no further assessment of safety is required for the active agent. However, the dossier supplied by the manufacturer was prepared and submitted to EFSA before QPS was established as an assessment tool and so contains data relevant to a safety assessment of an already authorised product for which an extension of use is sought. This has been reviewed by the FEEDAP Panel and summarised below Safety for the target species Data from a single tolerance study 10 was provided involving 36 European buffaloes for a full lactation. The animals were assigned to one of three groups, a control group given only the basal diet and two treatment groups given Biosaf Sc47 by top dressing either at the maximum recommended dose or at ten times the maximum recommended dose (1.4 x 10 9 and 1.4 x 10 10, respectively, confirmed by analysis). Animals were assigned to the groups on the basis of parity, calving date and milk yield. Health status was monitored daily and milk yields and quality recorded at monthly intervals, with the first recorded value used as covariate in the statistical analysis. 9 Technical dossier/section III 10 Technical dossier/section IV The EFSA Journal (2008) 837, 7-10

8 No treatment-related adverse effects on health were noted. There were no significant differences in milk yield or milk fat content between the three groups but both treatment groups showed a significant increase (P <0.05) in protein content compared to the control group (4.71 vs and 4.97 %) Safety for the user No additional data was provided in relation to user safety. However, the FEEDAP Panel considers this application to be an extension of use for a product already authorised for use with a wide variety of livestock. As such, it does not expect the use in buffaloes to introduce any additional hazards for users of the product. 5. Post-marketing monitoring No risks associated with the use of the product are foreseen. It is considered that there is no need for specific requirements for a post-market monitoring plan other than those established in the Feed Hygiene Regulation (Regulation (EC) No 183/2005) and Good Manufacturing Practice. CONCLUSIONS Dairy buffaloes are considered to be a minor species. As the proposed dose range is similar and the mechanism of action can be presumed to be essentially the same, the FEEDAP Panel considers that efficacy for dairy buffaloes at the minimum dose can be presumed from the authorised use in dairy cattle. Although efficacy data has not been assessed in detail by SCAN or the FEEDAP Panel, the experimental data from two studies, one at the minimum dose and one at the maximum dose, in which significant increases in milk protein content were recorded provide evidence of efficacy. The active agent has been identified as a strain of Saccharomyces cerevisiae and consequently meets the qualifications required by the QPS approach. It can thus be presumed safe for the target species, consumers and the wider environment. The additional experimental data provided in support of target animal safety does not conflict in any way with the conclusion reached on safety using the QPS approach. The FEEDAP Panel considers this application to be an extension of use for a product already authorised for use with a wide variety of livestock. As such, it does not expect the use of the product in dairy buffaloes to introduce any additional hazards for users of the product. DOCUMENTATION PROVIDED TO EFSA 1. Technical dossier for the product Biosaf Sc47 (Saccharomyces cerevisiae NCYC Sc47). December Submitted by Lesaffre Feed Additives. 2. Evaluation report of the Community Reference Laboratory feed additives authorisation on the methods(s) of analysis for Biosaf Sc47 for dairy buffaloes. 3. Comments from Member States received through thesciencenet. REFERENCES EC (European Commission), 1997, updated Scientific Committee on Animal Nutrition. Opinion on the use of certain micro-organisms as additives in feedingstuffs. < > The EFSA Journal (2008) 837, 8-10

9 EC (European Commission), Scientific Committee on Animal Nutrition. Evaluation of the efficacy of micro-organism product Biosaf Sc 47. < > EFSA (European Food Safety Authority), 2006a. Opinion of the Scientific Panel on additives and products or substances used in animal feed (FEEDAP) on the safety and efficacy of the product Biosaf Sc 47, a preparation of Saccharomyces cerevisiae (NCYC Sc 47), as a feed additive for lambs in accordance with Regulation (EC) No 1831/2003. < EFSA (European Food Safety Authority), 2006b. Opinion of the Panel on additives and products or substances used in animal feed (FEEDAP) on the safety and efficacy of the product Biosaf Sc 47, a preparation of Saccharomyces cerevisiae, as a feed additive for dairy small ruminants. < EFSA (European Food Safety Authority), 2006c. Opinion of the Panel on additives and products or substances used in animal feed (FEEDAP) on the safety and efficacy of the product Biosaf Sc 47, a preparation of Saccharomyces cerevisiae, as a feed additive for horses. < EFSA (European Food Safety Authority), 2007a. Summary of the Opinion of the Scientific Panel on additives and products or substances used in animal feed (FEEDAP) on the safety and efficacy of Biosaf Sc 47, a preparation of Saccharomyces cerevisiae, as a feed additive for calves for rearing according to Regulation (EC) No 1831/2003. < EFSA (European Food Safety Authority), 2007b. Safety and efficacy of Biosaf Sc 47 (Saccharomyces cerevisiae) as feed additive for pigs for fattening - Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed. < The EFSA Journal (2008) 837, 9-10

10 APPENDIX Executive Summary of the Evaluation Report of the Community Reference Laboratory for Feed Additives Authorisation on the Method(s) of Analysis for Biosaf Sc47 for dairy buffaloes In the current application authorisation is sought for the microbial feed additive BIOSAF Sc47 under the category 'zootechnical additives', functional group 'gut flora stabilisers' according to Annex I of Regulation (EC) No 1831/2003. Specifically, the use of BIOSAF Sc47 for dairy buffalos is requested. BIOSAF Sc47 contains a minimum of 5 x 10 9 of viable cells (c.f.u., colony-forming units) of Saccharomyces cerevisiae NCYC Sc47 (as active agent) per gram. The feed additive is intended to be mixed into complete feedingstuffs at a final concentration of 5.0 x 10 8 to 1.4 x 10 9 c.f.u./kg. For the determination of the active agent, a strain of Saccharomyces cerevisiae NCYC Sc47, in the feed additive, a pour plate method and a molecular identification method (polymerase chain reaction (PCR)) are proposed by the applicant, which are considered appropriate. For the determination of the active agent S. cerevisiae NCYC Sc47 in feedingstuffs a similar pour plate method for enumeration and the same molecular PCR method for identification of the strain are proposed by the applicant. This enumeration method was validated in a collaborative study [System. Appl. Microbiol , ]. The method s performance characteristics of the enumeration method are standard deviations for repeatability (s r ) and reproducibility (s R ) of around log 10 and log 10 calculated from the base 10 logarithms of the measured c.f.u./g in feedingstuffs, respectively. The limits of quantification (LOQ) of this method are 1000 colony forming units (c.f.u) per gram (g) feed additive or premixture and 10 6 c.f.u./kg feedingstuff. These performance characteristics are considered acceptable. This method is recommended for official controls of the active agent in the feed additive, premixtures and feedingstuffs. The PCR method for strain identification was ring trial validated and demonstrated a high level of correct identification between laboratories [System. Appl. Microbiol , ]. It is therefore considered appropriate for official controls. On the basis of the supplied documentation, no supplementary experimental work (testing or method validation) is required. The EFSA Journal (2008) 837, 10-10