Safety and efficacy of the feed additive consisting of Clostridium butyricum FERM BP‐2789 (Miya‐Gold® S) for chickens for fattening, chickens reared for laying, turkeys for fattening, turkeys reared for breeding, minor avian species (excluding laying birds), piglets (suckling and weaned) and minor porcine species (Miyarisan Pharmaceutical Co. Ltd.)
2021; Wiley; Volume: 19; Issue: 3 Linguagem: Inglês
10.2903/j.efsa.2021.6450
ISSN1831-4732
AutoresVasileios Bampidis, Giovanna Azimonti, Maria de Lourdes Bastos, Henrik Christensen, Birgit Dusemund, Maryline Kouba, Mojca Fašmon Durjava, Marta López‐Alonso, Secundino López Puente, Francesca Marcon, Baltasar Mayo, Alena Pechová, Mariana Petkova, Fernando Ramos, Yolanda Sanz, Roberto Edoardo Villa, Ruud Woutersen, Pier Sandro Cocconcelli, Boet Glandorf, Lieve Herman, Miguel Prieto Maradona, Maria Saarela, Montserrat Anguita, Jaume Galobart, Orsolya Holczknecht, Paola Manini, Fabiola Pizzo, Jordi Tarrés‐Call, Elisa Pettenati,
Tópico(s)Pharmaceutical Economics and Policy
ResumoEFSA JournalVolume 19, Issue 3 e06450 Scientific OpinionOpen Access Safety and efficacy of the feed additive consisting of Clostridium butyricum FERM BP-2789 (Miya-Gold® S) for chickens for fattening, chickens reared for laying, turkeys for fattening, turkeys reared for breeding, minor avian species (excluding laying birds), piglets (suckling and weaned) and minor porcine species (Miyarisan Pharmaceutical Co. Ltd.) EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Corresponding Author EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) feedap@efsa.europa.eu Correspondence:feedap@efsa.europa.euSearch for more papers by this authorVasileios Bampidis, Vasileios BampidisSearch for more papers by this authorGiovanna Azimonti, Giovanna AzimontiSearch for more papers by this authorMaria de Lourdes Bastos, Maria de Lourdes BastosSearch for more papers by this authorHenrik Christensen, Henrik ChristensenSearch for more papers by this authorBirgit Dusemund, Birgit DusemundSearch for more papers by this authorMaryline Kouba, Maryline KoubaSearch for more papers by this authorMojca Kos Durjava, Mojca Kos DurjavaSearch for more papers by this authorMarta López-Alonso, Marta López-AlonsoSearch for more papers by this authorSecundino López Puente, Secundino López PuenteSearch for more papers by this authorFrancesca Marcon, Francesca MarconSearch for more papers by this authorBaltasar Mayo, Baltasar MayoSearch for more papers by this authorAlena Pechová, Alena PechováSearch for more papers by this authorMariana Petkova, Mariana PetkovaSearch for more papers by this authorFernando Ramos, Fernando RamosSearch for more papers by this authorYolanda Sanz, Yolanda SanzSearch for more papers by this authorRoberto Edoardo Villa, Roberto Edoardo VillaSearch for more papers by this authorRuud Woutersen, Ruud WoutersenSearch for more papers by this authorPier Sandro Cocconcelli, Pier Sandro CocconcelliSearch for more papers by this authorBoet Glandorf, Boet GlandorfSearch for more papers by this authorLieve Herman, Lieve HermanSearch for more papers by this authorMiguel Prieto Maradona, Miguel Prieto MaradonaSearch for more papers by this authorMaria Saarela, Maria SaarelaSearch for more papers by this authorMontserrat Anguita, Montserrat AnguitaSearch for more papers by this authorJaume Galobart, Jaume GalobartSearch for more papers by this authorOrsolya Holczknecht, Orsolya HolczknechtSearch for more papers by this authorPaola Manini, Paola ManiniSearch for more papers by this authorFabiola Pizzo, Fabiola PizzoSearch for more papers by this authorJordi Tarrés-Call, Jordi Tarrés-CallSearch for more papers by this authorElisa Pettenati, Elisa PettenatiSearch for more papers by this author EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Corresponding Author EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) feedap@efsa.europa.eu Correspondence:feedap@efsa.europa.euSearch for more papers by this authorVasileios Bampidis, Vasileios BampidisSearch for more papers by this authorGiovanna Azimonti, Giovanna AzimontiSearch for more papers by this authorMaria de Lourdes Bastos, Maria de Lourdes BastosSearch for more papers by this authorHenrik Christensen, Henrik ChristensenSearch for more papers by this authorBirgit Dusemund, Birgit DusemundSearch for more papers by this authorMaryline Kouba, Maryline KoubaSearch for more papers by this authorMojca Kos Durjava, Mojca Kos DurjavaSearch for more papers by this authorMarta López-Alonso, Marta López-AlonsoSearch for more papers by this authorSecundino López Puente, Secundino López PuenteSearch for more papers by this authorFrancesca Marcon, Francesca MarconSearch for more papers by this authorBaltasar Mayo, Baltasar MayoSearch for more papers by this authorAlena Pechová, Alena PechováSearch for more papers by this authorMariana Petkova, Mariana PetkovaSearch for more papers by this authorFernando Ramos, Fernando RamosSearch for more papers by this authorYolanda Sanz, Yolanda SanzSearch for more papers by this authorRoberto Edoardo Villa, Roberto Edoardo VillaSearch for more papers by this authorRuud Woutersen, Ruud WoutersenSearch for more papers by this authorPier Sandro Cocconcelli, Pier Sandro CocconcelliSearch for more papers by this authorBoet Glandorf, Boet GlandorfSearch for more papers by this authorLieve Herman, Lieve HermanSearch for more papers by this authorMiguel Prieto Maradona, Miguel Prieto MaradonaSearch for more papers by this authorMaria Saarela, Maria SaarelaSearch for more papers by this authorMontserrat Anguita, Montserrat AnguitaSearch for more papers by this authorJaume Galobart, Jaume GalobartSearch for more papers by this authorOrsolya Holczknecht, Orsolya HolczknechtSearch for more papers by this authorPaola Manini, Paola ManiniSearch for more papers by this authorFabiola Pizzo, Fabiola PizzoSearch for more papers by this authorJordi Tarrés-Call, Jordi Tarrés-CallSearch for more papers by this authorElisa Pettenati, Elisa PettenatiSearch for more papers by this author First published: 08 March 2021 https://doi.org/10.2903/j.efsa.2021.6450Citations: 1 Requestor: European Commission Question number: EFSA-Q-2019-00802 Panel members: Giovanna Azimonti, Vasileios Bampidis, Maria de Lourdes Bastos, Henrik Christensen, Birgit Dusemund, Mojca Fašmon Durjava, Maryline Kouba, Marta López-Alonso, Secundino López Puente, Francesca Marcon, Baltasar Mayo, Alena Pechová, Mariana Petkova, Fernando Ramos, Yolanda Sanz, Roberto Edoardo Villa and Ruud Woutersen. Legal notice: Relevant information or parts of this scientific output have been blackened in accordance with the confidentiality requests formulated by the applicant pending a decision thereon by the European Commission. The full output has been shared with the European Commission, EU Member States and the applicant. The blackening will be subject to review once the decision on the confidentiality requests is adopted by the European Commission. Declarations of interest: The declarations of interest of all scientific experts active in EFSA's work are available at https://ess.efsa.europa.eu/doi/doiweb/doisearch. Acknowledgments: The Panel wishes to acknowledge the contribution of Rosella Brozzi and Maria Vittoria Vettori to this opinion. Adopted: 27 January 2021 AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The feed additive under assessment (trade name: Miya-Gold® S) is based on viable spores of Clostridium butyricum FERM BP-2789. It is authorised for use in minor avian species (excluding laying birds), weaned piglets and minor weaned porcine species, chickens reared for laying, turkeys for fattening and turkeys reared for breeding. This opinion concerns the request for renewal of the authorisation of Miya-Gold® S for the species/categories for which an authorisation exists, the use in chickens for fattening, for which the previous authorisation had expired, and the extension of use to suckling piglets and suckling minor porcine species. The applicant provided evidence that the additive currently in the market complies with the conditions of authorisation. There is no new evidence that would lead the Panel to reconsider previous conclusions that Miya-Gold® S remains safe for the animal species/categories, the consumer and the environment under the current and previously authorised conditions of use. This conclusion applies also to the new target species for which a request of use is made. Regarding the safety for the user, the Panel concluded that the additive is not irritant to skin and eyes and that sensitisation via respiratory route cannot be excluded. There is no need for assessing the efficacy of Miya-Gold® S in the context of the renewal of the authorisation in chickens reared for laying, turkeys for fattening and reared for breeding, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species. The additive has the potential to be efficacious in chickens for fattening, suckling piglets and suckling minor porcine species at the level of 2.5 × 108 CFU/kg complete feedingstuff. Miya-Gold® S is compatible with decoquinate, diclazuril, lasalocid, maduramicin ammonium, narasin, narasin/nicarbazin, monensin sodium, robenidine, salinomycin sodium and semduramicin. 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 4(1) of that Regulation lays down that any person seeking authorisation for a feed additive or for a new use of a feed additive shall submit an application in accordance with Article 7. In addition, 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 Huvepharma N.V. on behalf of Miyarisan Pharmaceutical Co. Ltd.2 for authorisation of the feed additive consisting of Clostridium butyricum FERM BP-2789 (Miya-Gold® S), when used as a feed additive for chickens for fattening, suckling piglets and suckling minor porcine species and renewal of the authorisation of the product for chickens reared for laying, turkeys for fattening, turkey reared for breeding, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species (category: zootechnical additives; functional group: gut flora stabilisers). 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) and under Article 14(1) (renewal of the authorisation). The particulars and documents in support of the application were considered valid by EFSA as of 4 February 2020. 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 feed additive consisting of C. butyricum FERM BP-2789 (Miya-Gold® S), when used under the proposed conditions of use (see Section 3.1.3). 1.2 Additional information The additive is based on viable spores of C. butyricum FERM BP-2789. EFSA has issued four opinions on the safety and efficacy of the additive based on C. butyricum FERM BP-2789 for chickens for fattening (EFSA, 2009), for weaned piglets, weaned minor porcine species and minor avian species (EFSA FEEDAP Panel, 2011), for chickens for fattening, chickens reared for laying and minor avian species (EFSA FEEDAP Panel, 2013a) and for turkeys for fattening and turkeys reared for breeding (EFSA FEEDAP Panel, 2014). The additive (4b1830) is authorised for use in feed for minor avian species (excluding laying birds), weaned piglets and minor weaned porcine species,3 chickens reared for laying,4 turkeys for fattening and turkeys reared for breeding.5 The additive was also authorised (until 19 October 2019) as a feed additive for chickens for fattening.6 However, as an application for renewal of the authorisation was not sent one year before its expiry date, the authorisation expired and the applicant submitted a new application for authorisation of the additive for this target species. The additive is authorised as a novel food ingredient to be used in food supplements with a maximum dose of 1.35 × 108 colony forming units (CFU) per day.7 The applicant has requested the renewal of the authorisation for the product consisting of C. butyricum FERM BP-2789 (Miya-Gold® S) for the species/categories for which there is an authorisation. Moreover, the applicant has requested the authorisation for use of the additive in feed for chickens for fattening and the extension of use of the additive to suckling piglets and suckling minor porcine species. 2 Data and methodologies 2.1 Data The present assessment is based on data submitted by the applicant in the form of a technical dossier8 in support of the authorisation request for the use of the product consisting of C. butyricum FERM BP-2789 (Miya-Gold® S) 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 to deliver the present output. The European Union Reference Laboratory (EURL) considered that the conclusions and recommendations reached in the previous assessments are valid and applicable for the current application.9 2.2 Methodologies The approach followed by the FEEDAP Panel to assess the safety and the efficacy of the product consisting of C. butyricum FERM BP-2789 (Miya-Gold® S) is in line with the principles laid down in Regulation (EC) No 429/200810 and the relevant guidance documents: Guidance on the renewal of the authorisation of feed additives (EFSA FEEDAP Panel, 2013b), Guidance on the characterisation of microorganisms used as feed additives or as production organisms (EFSA FEEDAP Panel, 2018a), Guidance on the assessment of the safety of feed additives for the target species (EFSA FEEDAP Panel, 2017) and Guidance on the assessment of the efficacy of feed additives (EFSA FEEDAP Panel, 2018b). 3 Assessment This assessment regards the renewal of the authorisation of the feed additive consisting of C. butyricum FERM BP-2789 (Miya-Gold® S) when used as a zootechnical additive (functional group: gut flora stabilisers) for chickens reared for laying, turkeys for fattening, turkeys reared for breeding, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species. It also regards the request for authorisation for use in feed for chickens for fattening, for which the previous authorisation had expired, and the request for an extension of use to suckling piglets and suckling minor porcine species. It will be hereafter referred to as Miya-Gold® S. 3.1 Characterisation 3.1.1 Characterisation of the additive Miya-Gold® S is a greyish-white granular powder based on viable spores of C. butyricum FERM BP-2789. In previous applications, two formulations were described: Miya-Gold® S, guaranteeing a minimum concentration of C. butyricum FERM BP-2789 of 5.0 × 108 CFU/g additive, and a more concentrated formulation, Miya-Gold® EU, guaranteeing a minimum concentration of C. butyricum FERM BP-2789 of 1 × 1010 CFU/g additive. The applicant states that the product is present on the market only in the form of Miya-Gold® S. The applicant stated that no changes in the manufacturing process have been introduced since the original authorisation was granted. The spores of C. butyricum FERM BP-2789 are harvested by centrifugation, washed, diluted in corn starch (60%), calcium carbonate (25%) and lactose (9%), and spray-dried. The spore powder is diluted with Brewers' yeast (20%), glucose, corn starch and zeolite as anti-caking agent. The additive contains about 2% of spent growth medium. The additive currently authorised contains viable spores of C. butyricum FERM BP-2789 at the minimum concentration of 5 × 108 CFU/g additive. Compliance with this specification was demonstrated in three recent batches of Miya-Gold® S (5.0 × 108 CFU/g in all three batches).11 Three recent batches of Miya-Gold® S were analysed for chemical and microbiological contamination.12 The analysis of chemical contamination included cadmium (< limit of quantification (LOQ)), lead (range 1.5–2.2 mg/kg), mercury (< LOQ), arsenic (< LOQ except for 0.5 mg/kg in one batch), aflatoxins B1, B2, G1, G2 (< LOQ), ochratoxin A (< LOQ), deoxynivalenol (< LOQ), zearalenone (< LOQ except for 15.8 μg/kg in one batch), fumonisins B1, B2 (< LOQ), T-2 toxin (< LOQ), and HT-2 toxin (< LOQ).13 Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and dioxin-like polychlorinated biphenyls (PCBs) were below the corresponding LOQs in three batches of the additive. The levels of dioxins and the sum of dioxins and dioxin-like-PCBs (upper bond) were calculated to be 0.16 ng WHO-PCDD/F-TEQ/kg and 0.30 ng WHO-PCDD/F-PCB-TEQ/kg, respectively. The same three batches were analysed for microbial contamination and the analysis included Salmonella spp. (not detected in 25 g), Enterobacteriaceae (< 40 CFU/g), yeasts (< 40 CFU/g except for 1.5 × 102 CFU/g in one batch) and filamentous fungi (from < 40 to 91 CFU/g).14 The above-mentioned impurities/contaminants do not represent a safety concern. 3.1.2 Characterisation of the active agent Miya-Gold® S is based on viable spores of a C. butyricum strain isolated from soil. The strain is deposited at the National Institute of Technology and Evaluation, International Patent Organism Depositary, Japan, with the accession number FERM BP-2789.15 The taxonomic identification of the strain FERM BP-2789 as C. butyricum was established ■■■■■16■■■■■. The susceptibility of the strain to the antibiotics recommended by the FEEDAP Guidance (EFSA FEEDAP Panel, 2018a), ■■■■■16■■■■■ (EFSA FEEDAP Panel, 2018a). ■■■■■ ■■■■■.16 The WGS of the active agent, ■■■■■, was interrogated for the presence of antimicrobial resistance (AMR) genes ■■■■■ ■■■■■ The WGS of the active agent, ■■■■■, was interrogated for the presence of toxin and virulence factors genes ■■■■■16■■■■■.17 No antimicrobial activity was detected in the supernatant of C. butyricum FERM BP-2789 analysed ■■■■■16■■■■■ 3.1.3 Conditions of use The additive Miya-Gold® S is currently authorised for use in feed for chickens reared for laying, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species at a minimum recommended inclusion level of 2.5 × 108 CFU/kg complete feed and in turkeys for fattening and turkeys reared for breeding at a minimum recommended inclusion level of 1.25 × 108 CFU/kg complete feed. The applicant has not asked to modify these conditions of use. The use of the additive is authorised in feed containing the authorised cocciodiostats as follows: in chickens reared for laying: monensin sodium, diclazuril, salinomycin sodium or lasalocid sodium; in minor avian species (excluding laying birds): monensin sodium, diclazuril, maduramycin ammonium, robenidine, narasin, narasin/nicarbazin, semduramicin, decoquinate, salinomycin sodium or lasalocid sodium; in turkeys for fattening and turkeys reared for breeding: monensin sodium, robenidine, maduramicin ammonium, lasalocid sodium or diclazuril. In the other provisions of the authorisation it is specified that: 'For safety: breathing protection and safety glasses shall be used during handling'. In addition, the applicant proposed the use of the product at the minimum recommended inclusion level of 2.5 × 108 CFU/kg feed for chickens for fattening, as it was previously authorised, and proposed the extension of use of the additive to suckling piglets and suckling minor porcine species at a minimum recommended inclusion level of 2.5 × 108 CFU/kg complete feed. The applicant also requested the authorisation for the simultaneous use of the additive with the coccidiostats: decoquinate, diclazuril, halofuginone, lasalocid, maduramicin ammonium, narasin, narasin/nicarbazin, monensin sodium, robenidine, salinomycin sodium and semduramicin. 3.2 Safety Safety aspects regarding the use of Miya-Gold® S in feed including the safety for the target animals, consumers, users and the environment have been evaluated in previous opinions (EFSA, 2009; EFSA FEEDAP Panel, 2011, 2013a, 2014). The Panel concluded that the additive is safe for the target species evaluated and the use of the product as a feed additive would be of no concern for the consumers of products derived from animals fed with the additive, or for the environment. Regarding the safety for the user, the Panel concluded that the additive is not irritant to skin and eyes. As the particle size data indicate that a significant proportion of the product is potentially respirable, sensitisation via respiratory route cannot be excluded. The data newly provided allow to confirm the identification of the active agent as C. butyricum. Based on the WGS data provided, the active agent is not expected to produce any toxic compound and does not harbour acquired AMR genes. The FEEDAP Panel notes that the additive was previously assessed for its use in chickens for fattening (EFSA, 2009; EFSA FEEDAP Panel, 2013a) and authorised for this use for ten years. Consequently, the Panel considers that the approach used for the renewal of the authorisation can be applied also in the case of the assessment of this new use in chickens for fattening. In line with the requirements established in the EFSA guidance on the renewal (EFSA FEEDAP Panel, 2013b), the applicant performed a literature search in order to provide evidence that in the light of the current knowledge the additive remains safe under the approved conditions for target species, consumers, users and the environment. The applicant searched in a total of three relevant databases (CAB Abstracts, PubMed and Veterinary Science Database).18 The search covered the period 2009–2019 and the search terms and search strategy were provided. The main search terms regarded the safety for the target animals (pigs and poultry), safety for the consumers, workers and the environment, interactions/incompatibilities and safety of the microorganism. The literature search did not identify hits other than previous EFSA opinions. The applicant stated that no adverse events have been detected under its post-marketing monitoring plan.19 Therefore, the FEEDAP Panel concludes that there is no new evidence that would lead the Panel to reconsider its previous conclusions on the safety of the product for target species evaluated, consumers and the environment under the current and previously authorised conditions of use. The applicant has requested for an extension of use of the additive to suckling piglets and suckling minor porcine species. The FEEDAP Panel evaluated in the past tolerance trials which showed that the additive is safe for weaned piglets (EFSA FEEDAP Panel, 2011). Therefore, the Panel considers that the conclusions reached in weaned piglets can be extended to suckling piglets and extrapolated to suckling minor porcine species. Consequently, the additive is considered safe for suckling piglets and suckling minor porcine species at the minimum recommended inclusion level of 2.5 × 108 CFU/kg complete feed. 3.2.1 Conclusions on safety Based on the above and the fact that the manufacturing process, the composition of the additive and the conditions of use for the species/categories for which the additive is or had been authorised have not been modified, the FEEDAP Panel considers that there is no evidence to reconsider the conclusions reached in previous assessments. The Panel concludes that the additive Miya-Gold® S remains safe for chickens for fattening, chickens reared for laying, turkeys for fattening, turkeys reared for breeding, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species, the consumer and the environment under the current and previously authorised conditions of use. Regarding the safety for the user, the Panel concludes that the additive is not irritant to skin and eyes and that sensitisation via respiratory route cannot be excluded. Miya-Gold® S is considered safe for suckling piglets and suckling minor porcine species at the minimum recommended inclusion level of 2.5 × 108 CFU/kg complete feed. 3.3 Efficacy 3.3.1 Efficacy for weaned piglets, weaned minor porcine species, chickens reared for laying, minor avian species (excluding laying birds), turkeys for fattening and turkeys reared for breeding The efficacy of Miya-Gold® S was previously established in weaned piglets and weaned minor porcine species at a minimum recommended inclusion level of 2.5 × 108 CFU/kg complete feed (EFSA FEEDAP Panel 2011), chickens reared for laying and minor avian species (excluding laying birds) at a minimum recommended inclusion level of 2.5 × 108 CFU/kg complete feed (EFSA FEEDAP Panel, 2013a) and in turkeys for fattening and turkeys reared for breeding at a minimum recommended level of 1.25 × 108 CFU/kg complete feed (EFSA FEEDAP Panel, 2014). The conditions of use for these target species have not been modified and, therefore, no further assessment is needed for the renewal of the authorisation in these species. 3.3.2 Efficacy for suckling piglets and suckling minor porcine species The applicant asked for the extension of use to suckling piglets and suckling minor porcine species at the level of 2.5 × 108 CFU/kg complete feed. Considering that efficacy has been demonstrated in weaned piglets at the level of 2.5 × 108 CFU/kg complete feed and the fact that the mode of action of the additive can be reasonably assumed to be the same, the conclusions from the efficacy studies in weaned piglets can be extended/extrapolated to suckling piglets and suckling minor porcine species for the period in which solid feed is given (EFSA FEEDAP Panel, 2018b). Therefore, the FEEDAP Panel considers that the additive has the potential to be efficacious in these species at the proposed conditions of use. 3.3.3 Efficacy for chickens for fattening The efficacy of the additive when used in chickens for fattening at 2.5 × 108 CFU/kg complete feed was already assessed in the previous opinions of the FEEDAP Panel (EFSA 2009; EFSA FEEDAP Panel, 2013a). The Panel concluded that the additive had some potential to improve the performance of chickens for fattening at 2.5 × 108 CFU/kg complete feed (EFSA FEEDAP Panel, 2013a). Subsequently, the authorisation was modified to include this minimum recommended inclusion level. The applicant has submitted the same studies already evaluated in the previous opinions with some new statistical analyses of the data and pooling of studies.20 The Panel has assessed these data and considers that there is no new information which would lead the Panel to modify its previous conclusions. Therefore, the FEEDAP Panel concludes that the additive has the potential to be efficacious in chickens for fattening at 2.5 × 108 CFU/kg complete feed. 3.3.4 Compatibility with coccidiostats The compatibility of Miya-Gold® S with the coccidiostats decoquinate, diclazuril, halofuginone, lasalocid, maduramicin ammonium, narasin, narasin/nicarbazin, monensin sodium, robenidine, salinomycin sodium and semduramicin at the maximum authorised concentrations for chickens for fattening was assessed in previous opinions (EFSA, 2009; EFSA FEEDAP Panel, 2011). The Panel concluded that compatibility was demonstrated with decoquinate, diclazuril, lasalocid, maduramicin ammonium, narasin, narasin/nicarbazin, monensin sodium, robenidine, salinomycin sodium and semduramicin at the maximum authorised concentrations for chickens for fattening. The Panel also concluded that halofuginone was supplied in a form not authorised in Europe and at a dose which was difficult to relate to the authorised level. In previous opinions (EFSA FEEDAP Panel, 2011, 2014), the Panel considered that since compatibility had been demonstrated in chickens for fattening, the same conclusion would apply to its use in minor avian species and turkeys for fattening and reared for breeding. No new data have been made available that would lead the Panel to reconsider the conclusions reached previously. Therefore, the FEEDAP Panel considers that Miya-Gold® S is compatible with decoquinate, diclazuril, lasalocid, maduramicin ammonium, narasin, narasin/nicarbazin, monensin sodium, robenidine, salinomycin sodium and semduramicin. 3.3.5 Conclusions on efficacy The present application for renewal of the authorisation does not include a proposal for amending or supplementing the conditions of use for those species/categories for which there is an authorisation. Therefore, there is no need for assessing the efficacy of Miya-Gold® S in the context of the renewal of the authorisation in chickens reared for laying, turkeys for fattening, turkey reared for breeding, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species. The current application includes the request for an extension of use to suckling piglets and suckling minor porcine species and the request for authorisation for use in feed for chickens for fattening, for which the previous authorisation had expired. The efficacy data from weaned piglets can be extended/extrapolated to suckling piglets and suckling minor porcine species. Therefore, the Panel concludes that the additive has the potential to be efficacious in suckling piglets and suckling minor porcine species at the inclusion level of 2.5 × 108 CFU/kg complete feed. There is no new information which would lead the Panel to modify its previous conclusions that the additive has the potential to be efficacious in chickens for fattening at 2.5 × 108 CFU/kg complete feed. Miya-Gold® S is compatible with decoquinate, diclazuril, lasalocid, maduramicin ammonium, narasin, narasin/nicarbazin, monensin sodium, robenidine, salinomycin sodium and semduramicin. 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 Regulation21 and Good Manufacturing Practice. 4 Conclusions The additive currently in the market complies with the conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions that Miya-Gold® S is safe for chickens for fattening, chickens reared for laying, turkeys for fattening, turkey reared for breeding, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species, the consumer and the environment under the current or previously authorised conditions of use. This conclusion applies also to the new target species for which a request for an extension of use is made. Regarding the safety for the user, the Panel concludes that the additive is not irritant to skin and eyes and that sensitisation via respiratory route cannot be excluded. There is no need for assessing the efficacy of Miya-Gold® S in the context of the renewal of the authorisation in chickens reared for laying, turkeys for fattening, turkey reared for breeding, minor avian species (excluding laying birds), weaned piglets and weaned minor porcine species. The FEEDAP Panel concludes that the additive has the potential to be efficacious in chickens for fattening, suckling piglets and suckling minor porcine species at the inclusion level of 2.5 × 108 CFU/kg complete feed. Miya-Gold® S is compatible with decoquinate, diclazuril, lasalocid, maduramicin ammonium, narasin, narasin/nicarbazin, monensin sodium, robenidine, salinomycin sodium and semduramicin. 5 Documentation as provided to EFSA/Chronology Date Event 23/08/2019 Dossier received by EFSA. Clostridium butyricum FERM BP-2789 for Chickens for fattening, Chickens reared for laying, Turkeys for fattening, Turkeys reared for breeding, Minor poultry species (excluding laying birds), Piglets (suckling and weaned piglets), Minor porcine species. Submitted by Huvepharma N.V. on behalf of Miyarisan Pharmaceutical Co. Ltd. 12/12/2019 Reception mandate from the European Commission 04/02/2020 Application validated by EFSA – Start of the scientific assessment 03/03/2020 Request of supplementary information to the applicant in line with Article 8(1)(2) of Regulation (EC) No 1831/2003 – Scientific assessment suspended. Issues: characterisation, safety for the target species, efficacy 04/05/2020 Comments received from Member States 30/07/2020 Reception of supplementary information from the applicant - Scientific assessment re-started 27/01/2021 Opinion adopted by the FEEDAP Panel. End of the Scientific assessment Notes 1 Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition. OJ L 268, 18.10.2003, p. 29. 2 Miyarisan Pharmaceutical Co. Ltd. represented in the EU by Huvepharma NV Belgium, Uitbreidingstraat 80, B-2600 Berchem, Belgium. 3 Commission Implementing Regulation (EU) No 373/2011 of 15 April 2011 concerning the authorisation of the preparation of Clostridium butyricum FERM-BP 2789 as a feed additive for minor avian species except laying birds, weaned piglets and minor porcine species (weaned) and amending Regulation (EC) No 903/2009 (holder of authorisation Miyarisan Pharmaceutical Co. Ltd, represented by Miyarisan Pharmaceutical Europe S.L.U.) OJ L 102, 16.04.2011, p. 10, amended by Commission Implementing Regulation (EU) No 357/2013. 4 Commission Implementing Regulation (EU) No 374/2013 of 23 April 2013 concerning the authorisation of a preparation of Clostridium butyricum (FERM BP-2789) as a feed additive for chickens reared for laying (holder of authorisation Miyarisan Pharmaceutical Europe S.L.U.) OJ L 112, 24.4.2013, p. 13 and amendment. 5 Commission Implementing Regulation (EU) No 1108/2014 of 20 October 2014 concerning the authorisation of a preparation of Clostridium butyricum (FERM BP-2789) as a feed additive for turkeys for fattening and turkeys reared for breeding (holder of authorisation Miyarisan Pharmaceutical Co. Ltd represented by Miyarisan Pharmaceutical Europe S.L.U.) OJ L 301, 21.10.2014, p. 16 and amendment. 6 Commission Regulation (EC) No 903/2009 of 28 September 2009 concerning the authorisation of a preparation of Clostridium butyricum MIYAIRI 588 (FERM P-1467) as a feed additive for chickens for fattening (holder of authorisation Miyarisan Pharmaceutical Co. Ltd, represented by Mitsui & Co. Deutschland GmbH) OJ L 256, 29.9.2009, p. 111–112, amended by Commission Implementing Regulation (EU) No 357/2013. 7 Commission Implementing Decision of 11 December 2014 authorising the placing on the market of Clostridium butyricum CBM 588 as a novel food ingredient under Regulation (EC) No 258/97 of the European Parliament and of the Council. OJ L 359, 16.12.2014, p. 153–154. 8 FEED dossier reference: FAD-2019-0058. 9 The full report is available on the EURL website: https://ec.europa.eu/jrc/sites/jrcsh/files/FinRep-FAD-2008-0012.pdf and https://ec.europa.eu/jrc/sites/jrcsh/files/FinRep-FAD-2010-0005.pdf 10 Commission Regulation (EC) No 429/2008 of 25 April 2008 on detailed rules for the implementation of Regulation (EC) No 1831/2003 of the European Parliament and of the Council as regards the preparation and the presentation of applications and the assessment and the authorisation of feed additives. OJ L 133, 22.5.2008, p. 1. 11 Technical dossier/Section II/Annex Sect. II/Annex II_1_3_2. 12 Technical dossier/Section II/Annex Sect. II/Annex II_1_4_2. 13 LOQ: 1.0 µg/kg for aflatoxin B1, B2, G1, G2; 0.5 µg/kg for ochratoxin A; 0.05 µg/kg for deoxynivalenol; 5 µg/kg for zearalenone; 20 µg/kg for fumonisin B1, B2; 10 µg/kg for T-2 toxin; 10 µg/kg for HT-2 toxin. LOQ and LOD were, respectively: 0.10 mg/kg and 20 µg/kg for cadmium; 0.30 mg/kg and 50 µg/kg for lead; 0.10 mg/kg and 20 µg/kg for mercury; 0.30 mg/kg and 50 µg/kg for arsenic. 14 Limit of detection (LOD): 10 CFU/25 g for Salmonella spp.; 10 CFU/g for Enterobacteriaceae, yeasts and filamentous fungi. 15 Technical dossier/Section II/Annex Sect. II/Annex II_2_1_2_181 and Supplementary information July 2020/annexes/Annex II.2.1.2.184. 16 Technical dossier/Supplementary information July 2020/annexes/Annex II_2_2_2_9. 17 Technical dossier/Section II/Annex Sect. II/Annex II_2_1_2_14. 18 Technical dossier/Section III/Bibliography Sect. III/RCVS_2019. 19 Technical dossier/Section III/Annexes Sect. III/Annex_III_1. 20 Technical dossier/Supplementary information July 2020/annexes/Annex IV_3_1_1, Annex IV_3_2_1, Annex IV_3_3_1, Annex IV_3_4_1, Annex IV_3_5_1, Annex IV_3_6 and Annex IV_3_7. 21 Regulation (EC) No 183/2005 of the European Parliament and of the Council of 12 January 2005 laying down requirements for feed hygiene. OJ L 35, 8.2.2005, p. 1. References Collins MD, Lawson PA, Willems A, Cordoba JJ, Fernandez-Garayzabal J, Garcia P, Cai J, Hippe H and Farrow JA, 1994. The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations. International Journal of Systematic Bacteriology, 44, 812– 826. EFSA (European Food Safety Authority), 2009. Scientific Opinion of the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) on a request from the European Commission on the safety and efficacy of the product Miya-Gold®S (Clostridium butyricum) as a feed additive for chickens for fattening. EFSA Journal 2009;1039, 1–16. https://doi.org/10.2903/j.efsa.2009.1039 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2011. Scientific Opinion on Miya-Gold® (Clostridium butyricum) as a feed additive for weaned piglets, minor weaned porcine species and minor avian species. EFSA Journal 2011;9(1):1951, 15 pp. https://doi.org/10.2903/j.efsa.2011.1951 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2013a. Scientific Opinion on the safety and efficacy of Miya-Gold (Clostridium butyricum) for chickens for fattening, chickens reared for laying and minor avian species. EFSA Journal 2013;11(1):3040, 9 pp. https://doi.org/10.2903/j.efsa.2013.3040 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2013b. Guidance on the renewal of the authorisation of feed additives. EFSA Journal 2013;11(10):3431, 8 pp. https://doi.org/10.2903/j.efsa.2013.3431 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2014. Scientific Opinion on the safety and efficacy of Miya-Gold® (Clostridium butyricum) for turkeys for fattening and turkeys reared for breeding. EFSA Journal 2014;12(3):3603, 10 pp. https://doi.org/10.2903/j.efsa.2014.3603 Available online: www.efsa.europa.eu/efsajournal EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López-Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Villa RE, Wallace RJ, Wester P, Anguita M, Galobart J, Innocenti ML and Martino L, 2017. Guidance on the assessment of the safety of feed additives for the target species. EFSA Journal 2017;15(10):5021, 19 pp. https://doi.org/10.2903/j.efsa.2017.5021 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López-Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Villa RE, Wallace RJ, Wester P, Glandorf B, Herman L, Kärenlampi S, Aguilera J, Anguita M, Brozzi R and Galobart J, 2018a. Guidance on the characterisation of microorganisms used as feed additives or as production organisms. EFSA Journal 2018;16(3):5206, 24 pp. https://doi.org/10.2903/j.efsa.2018.5206 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López-Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Villa RE, Wallace RJ, Wester P, Anguita M, Galobart J, Innocenti ML and Martino L, 2018b. Guidance on the assessment of the efficacy of feed additives. EFSA Journal 2018;16(5):5274, 25 pp. https://doi.org/10.2903/j.efsa.2018.5274 Lawson PA and Rainey FA, 2016. Proposal to restrict the genus Clostridium prazmowski to Clostridium butyricum and related species. International Journal of Systematic and Evolutionary Microbiology, 66, 1009– 1016. Rasmussen BA, Bush K and Tally FP, 1997. Antimicrobial Resistance in Anaerobes. Clinical Infectious Diseases, 24(Suppl 1), S110–S120. Abbreviations AMR antimicrobial resistance CFU colony forming unit EURL European Union Reference Laboratory FEEDAP EFSA Panel on Additives and Products or Substances used in Animal Feed LOD limit of detection LOQ limit of quantification PCB polychlorinated biphenyl PCDD/F polychlorinated dibenzo-p-dioxin and dibenzofuran TEQ toxic equivalent WGS whole genome sequences WHO World Health Organization Citing Literature Volume19, Issue3March 2021e06450 ReferencesRelatedInformation
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