Rosella Brozzi

EMA and EFSA Joint Scientific Opinion on measures to reduce the need to use antimicrobial agents in animal husbandry in the European Union, and the resulting impacts on food safety (RONAFA)

Abstract EFSA and EMA have jointly reviewed measures taken in the EU to reduce the need for and use of antimicrobials in food‐producing animals, and the resultant impacts on antimicrobial resistance (AMR). Reduction strategies have been implemented successfully in some Member States. Such strategies include national reduction targets, benchmarking of antimicrobial use, controls on prescribing and restrictions on use of specific critically important antimicrobials, together with improvements to animal husbandry and disease prevention and control measures. Due to the multiplicity of factors contributing to AMR, the impact of any single measure is difficult to quantify, although there is evidence of an association between reduction in antimicrobial use and reduced AMR. To minimise antimicrobial use, a multifaceted integrated approach should be implemented, adapted to local circumstances. Recommended options (non‐prioritised) include: development of national strategies; harmonised systems for monitoring antimicrobial use and AMR development; establishing national targets for antimicrobial use reduction; use of on‐farm health plans; increasing the responsibility of veterinarians for antimicrobial prescribing; training, education and raising public awareness; increasing the availability of rapid and reliable diagnostics; improving husbandry and management procedures for disease prevention and control; rethinking livestock production systems to reduce inherent disease risk. A limited number of studies provide robust evidence of alternatives to antimicrobials that positively influence health parameters. Possible alternatives include probiotics and prebiotics, competitive exclusion, bacteriophages, immunomodulators, organic acids and teat sealants. Development of a legislative framework that permits the use of specific products as alternatives should be considered. Further research to evaluate the potential of alternative farming systems on reducing AMR is also recommended. Animals suffering from bacterial infections should only be treated with antimicrobials based on veterinary diagnosis and prescription. Options should be reviewed to phase out most preventive use of antimicrobials and to reduce and refine metaphylaxis by applying recognised alternative measures.

Guidance on the characterisation of microorganisms used as feed additives or as production organisms

Draft Endorsed by the FEEDAP Panel * 18 May 2017 Submitted for public consultation 15 June 2017 End of public consultation 15 September 2017 Adopted by the FEEDAP Panel 21 February 2018 Implementation date 1 September 2018 * Sections 3.1 and 3.2 were also endorsed by the EFSA Panel on Genetically Modified Organisms (GMO), EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) and EFSA Panel on Food Additives and Nutrient Sources Added to Food (ANS) on 18 May (GMO) and 7 June (CEF and ANS) 2017. Abstract This guidance document is intended to assist the applicant in the preparation and the presentation of an application, as foreseen in Article 7.6 of Regulation (EC) No 1831/2003, for the authorisation of additives for use in animal nutrition. It specifically covers the characterisation of microorganisms used as feed additives or as production organisms.

Safety and efficacy of Bacillus subtilis PB6 (Bacillus subtilis ATCC PTA‐6737) as a feed additive for sows

Abstract Bacillus subtilis PB6 is a feed additive based on viable spores of a strain of Bacillus subtilis. EFSA has already issued several opinions on the safety and efficacy of the additive when used in the feed for a number of avian and porcine species/categories. The applicant is now seeking authorisation for use in sows in order to have benefits in piglets. In the course of previous assessments, no evidence of a toxigenic potential or resistance to relevant antibiotics was found. Consequently, the strain of B. subtilis in the additive, following the qualified presumption of safety approach to safety assessment, is presumed safe for target animals including sows and their offspring, consumers and the environment. In a previous assessment, it was also concluded that the additive is not a skin/eye irritant or a skin sensitiser and that there were no concerns on respiratory sensitisation. The use of the additive with feed for sows is considered unlikely to introduce hazards for users of the product not already considered. Five studies are described in which groups of sows given the additive for a minimum period from the last 3 weeks of pregnancy, throughout farrowing and lactation, until weaning of piglets were compared with a control group. In only two of five studies, there was a significant beneficial effect seen in terms of piglet performance. However, when data from the four similar were pooled and analysed, significant increases in weaned weight and average daily gain were indicated for piglets from sows given the additive. Consequently, the FEEDAP Panel concludes that Bacillus subtilis PB6 when added to diets of sows from 3 weeks before parturition until weaning of piglets at a dose of 1 × 108 CFU/kg complete feed has the potential to improve the growth of piglets from birth to weaning.

Assessment of the application for renewal of authorisation of Levucell® SC (Saccharomyces cerevisiae CNCM I‐1077) as a feed additive for dairy ewes and dairy goats

Abstract Levucell® SC is the trade name for a feed additive based on viable cells of a strain Saccharomyces cerevisiae. The product is currently authorised for use in feed for horses, lambs, dairy sheep, dairy goats, dairy cows and cattle for fattening. This opinion concerns the renewal of the authorisation of Levucell® SC as a zootechnical additive for dairy ewes and dairy goats. S. cerevisiae is considered by EFSA to be suitable for the Qualified Presumption of Safety (QPS) approach to establishing safety for the target species, consumers and the environment. The identity of the strain present in the additive was established. Accordingly, this strain is presumed safe for the target species, consumers of products from animals fed the additive and the environment. Since no concerns are expected from other components of the additive, Levucell® SC is considered safe for the target species, consumers of products from animals fed the additive and the environment. The applicant has provided data demonstrating that the additive currently in the market complies with the conditions of authorisation. Furthermore, according to the information provided in the technical dossier, no new evidence has been identified that would make the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) reconsider the previous conclusions on the safety of the product for target species, consumers and the environment under the authorised conditions of use.

Safety and efficacy of Pediococcus pentosaceus DSM 32291 as a silage additive for all animal species

Abstract Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed was asked to deliver a scientific opinion on the safety and efficacy of a strain of Pediococcus pentosaceus when used as a technological additive intended to improve ensiling at a proposed application rate of 5 × 107 CFU kg/fresh matter. The species P. pentosaceus is considered by EFSA to be suitable for the qualified presumption of safety approach to safety assessment and not to require specific demonstration of safety other than the absence of resistance to antibiotics of human and veterinary significance. As the identity of the strain was clearly established and as no antibiotic resistance was detected, the use of the strain in the production of silage is presumed safe for livestock species, consumers of products from animals fed treated silage and the environment. In the absence of data, no conclusion can be drawn on the skin and eye irritancy of the additive. The additive should be considered a potential respiratory sensitiser. Pediococcus pentosaceus DSM 32291 at a minimum dose of 5 × 107 CFU/kg has the potential to improve the production of silage from easy and moderately difficult to ensile materials by decreasing dry matter loss and protein degradation during ensiling.

Safety and efficacy of Lactobacillus acidophilus D2/CSL (Lactobacillus acidophilus CECT 4529) as a feed additive for cats and dogs

Abstract Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Lactobacillus acidophilus D2/CSL when used in feed for cats and dogs at a minimum dose of 5 × 109 colony forming units (CFU)/kg complete feedingstuffs. The additive is a preparation of viable cells of Lactobacillus acidophilus CECT 4529. This species is considered by the European Food Safety Authority to be suitable for the qualified presumption of safety (QPS) approach to establishing safety for the target species and the environment. The safety of L. acidophilus CECT 4529 was assessed by EFSA in 2014. Following the QPS approach to safety assessment, L. acidophilus CECT 4529 is assumed to be safe for the target species and the environment without the need for further studies. No concerns are expected from other excipients present in the product, so Lactobacillus acidophilus D2/CSL is also considered safe for target animals, including cats and dogs, and the environment. The safety of the additive for the user was also considered in that opinion. The FEEDAP Panel is unaware of any new data that would lead it to revise its conclusions that the additive should be considered to be an eye/skin irritant and a skin/respiratory sensitiser. Lactobacillus acidophilus D2/CSL has some potential to reduce the moisture of stools from dogs and cats receiving the additive at 5 x 109 CFU/kg feed. However, the biological relevance of the magnitude of the effect detected is questionable.

Assessment of the application for renewal of authorisation of Actisaf® Sc47 (Saccharomyces cerevisiae CNCM I‐4407) for lambs for fattening, minor dairy ruminants, horses and pigs for fattening

Abstract Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the renewal of the authorisation of Actisaf Sc47 as a zootechnical additive for lambs for fattening, minor dairy ruminants, horses and pigs for fattening. In 2006, 2007 and 2008, the FEEDAP Panel adopted opinions on the safety and efficacy of Actisaf Sc47 when used in lambs for fattening, minor dairy ruminants, horses and pigs for fattening. Actisaf Sc47 is the trade name for a feed additive based on viable cells of Saccharomyces cerevisiae CNCM I‐4407 with no carrier. It is currently authorised for use in sows, piglets, pigs for fattening, cattle for fattening, calves for rearing, dairy cows, dairy buffaloes, lambs for fattening, dairy sheep, dairy goats, horses, rabbits for fattening and non‐food producing rabbits. Actisaf Sc47 is marketed in three forms: standard, powder and HR. All of them are authorised with a declared minimal concentration of viable yeast cells in the additive of 5 × 109 CFU/g. The applicant has provided data demonstrating that the additive currently in the market complies with the conditions of authorisation. In previous opinions, Actisaf Sc47 was presumed safe for the target species, consumers of products from animals fed the additive and the environment. Additionally, it was not found to be a skin or eye irritant. No new evidence has been identified that would make the FEEDAP Panel reconsider the previous conclusions on the safety of Actisaf Sc47. Therefore, the Panel considers that the additive Actisaf SC47 remains safe under the approved conditions for lambs for fattening, minor dairy ruminants, horses and pigs for fattening, the consumer, user and the environment.

Safety and efficacy of Calsporin® (Bacillus subtilis DSM 15544) as a feed additive for pigs for fattening

Abstract Following a request from the European Commission, the European Food Safety Authority (EFSA) Panel on Additives and Products or Substances used in Animal Feed was asked to deliver a scientific opinion on the safety and efficacy of Calsporin® when used in feed for pigs for fattening. The additive contains viable spores of a single strain of Bacillus subtilis. This species is considered by EFSA to be suitable for the Qualified Presumption of Safety (QPS) approach to safety assessment. This approach requires the identity of the strain to be conclusively established, evidence that the strain is not toxigenic and that it does not show resistance to antibiotics of human and veterinary importance. The strain was found to meet the criteria for the QPS approach in the context of previous opinions and since concerns are not expected from other components of the additive, Calsporin® is presumed safe for all target species, including pigs, consumers of products derived from animals treated and for the environment. In a previous opinion, the Panel also concluded that the additive is not a dermal/eye irritant or a skin sensitiser but should be considered a potential respiratory sensitiser. The use of the additive in pigs for fattening is considered unlikely to introduce hazards for users of the product not already considered as part of the first assessment. Therefore, the conclusions reached apply to the current application. Based on the results of the pooled analysis of four studies, the Panel on additives and products or substances used in animal feed (FEEDAP) concludes that Calsporin® has the potential to improve performance of pigs for fattening at 1.5 × 108 CFU/kg feed.

Safety and efficacy of Alterion NE® (Bacillus subtilis DSM 29784) as a feed additive for minor poultry species for fattening and reared for laying

Abstract Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed was asked to deliver a scientific opinion on the safety and efficacy of Alterion NE ® when used in feed for chickens for fattening and chickens reared for laying. Alterion NE ® is a preparation containing viable spores of Bacillus subtilis DSM 29784 intended for use in feed for the target species at the recommended dose of 1 × 108 CFU/kg complete feedingstuffs. B. subtilis is a species considered by EFSA to be suitable for the qualified presumption of safety (QPS) approach to safety assessment, which requires the identity of the strain to be conclusively established, evidence that the strain is not toxigenic and that it does not show resistance to antibiotics of human and veterinary importance. The strain was found to meet the criteria for the QPS approach in the context of a previous opinion and since concerns are not expected from other components of the additive, the additive is presumed safe for all target species, consumers and the environment. In the same opinion, the FEEDAP Panel concluded that Alterion NE ® is not a dermal irritant but is irritant to eyes and should be considered a potential respiratory sensitiser. In the absence of data, no conclusion could be drawn on the dermal sensitisation of the additive. Alterion NE ® at the recommended dose 1 × 108 CFU/kg feed has the potential to be efficacious in minor poultry species for fattening and reared for laying. B. subtilis DSM 29784 is compatible with the coccidiostats monensin sodium, narasin/nicarbazin, salinomycin sodium, lasalocid sodium, diclazuril, narasin, maduramicin ammonium, robenidine hydrochloride and decoquinate at the respective authorised levels.

Safety and efficacy of ZM16 10 (Bacillus amyloliquefaciens DSM 25840) as a feed additive for weaned piglets and minor porcine species

Abstract Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of ZM16 10 for weaned piglets and minor porcine species. The additive is a preparation containing viable spores of a strain of Bacillus amyloliquefaciens intended for use in feed at the proposed dose of 5 × 108 CFU/kg complete feedingstuffs and in water for drinking at 1.7 × 108 CFU/L. The additive exists in two forms, ZM16 and ZM16 10, which contain the bacterium in concentrations of 1.25 × 109 CFU/g additive and 1.25 × 1010 CFU/g additive, respectively. The two formulations are considered equivalent when used to deliver the same dose. B. amyloliquefaciens is considered by EFSA to be suitable for the qualified presumption of safety (QPS) approach to establishing safety. The active agent fulfils the requirements of the QPS approach to the assessment of safety. Consequently, the additive can be presumed safe for the target animals, consumers of products from treated animals and the environment. Given the proteinaceous nature of the active agent, the additive should be considered a potential respiratory sensitiser. In the absence of data, the FEEDAP Panel cannot conclude on the irritancy of the additive to skin and eyes or its dermal sensitisation. Insufficient evidence was provided to conclude on the efficacy of the additive in weaned piglets or minor weaned porcine species.