SCIENTIFIC OPINION Scientific Opinion on the modification to the formulation of GalliPro and compatibility with formic acid 1 EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) 2,3 SUMMARY European Food Safety Authority (EFSA), Parma, Italy The additive GalliPro is a microbial feed additive based on Bacillus subtilis. The additive is currently authorised for use in feeds for chickens for fattening at the minimum dose of 8 x 10 8 and a maximum of 1.6 x 10 9 CFU/kg of complete feedingstuffs. The applicant is now seeking the modification of the existing authorisation to include a more concentrated formulation, guaranteeing a minimum concentration of Bacillus subtilis of 1.6 x 10 10 CFU/g additive. This would be used to deliver the same dose as presently authorised. The applicant is also seeking the authorisation for the simultaneous use of the product with formic acid. B. subtilis is considered by the European Food Safety Authority (EFSA) to be suitable for the Qualified Presumption of Safety (QPS) approach to safety assessment. In the course of previous assessments the strain was considered to satisfy the qualifications specified for the species, and so can be treated as meeting the requirements of the QPS approach. Consequently, no further assessment of safety for the target species, the consumer and the environment is required. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that the modification to the formulation of GalliPro proposed (minimum concentration of 1.6 x 10 10 CFU /g of additive) is considered unlikely to introduce hazards not already considered as part of the first assessment. The compatibility of the active agent with formic acid up to 2600 mg/kg was demonstrated when the product strain B. subtilis was used in combination with a strain of B. licheniformis in an in vivo experiment with chickens for fattening. Since the dose of B. subtilis tested was equivalent to the minimum authorised dose, and as differential counts for the two Bacillus strains were provided, the compatibility with formic acid demonstrated in this experiment can be extrapolated to GalliPro. KEY WORDS Zootechnical additives, micro-organisms, GalliPro, Bacillus subtilis, formic acid, compatibility 1 On request from the European Commission, Question No EFSA-Q-2010-01151, adopted on 15 March 2011. 2 Panel members: Gabriele Aquilina, Georges Bories, Andrew Chesson, Pier Sandro Cocconcelli, Joop de Knecht, Noël Albert Dierick, Mikolaj Antoni Gralak, Jürgen Gropp, Ingrid Halle, Reinhard Kroker, Lubomir Leng, Anne-Katrine Lundebye Haldorsen, Alberto Mantovani, Miklós Mézes, Derek Renshaw and Maria Saarela. Correspondence: FEEDAP@efsa.europa.eu 3 Acknowledgement: The Panel wishes to thank the members of the Working Group on Micro-organisms, including Guido Rychen, for the preparatory work on this scientific opinion. Suggested citation: EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); Scientific Opinion on the modification to the formulation of GalliPro and compatibility with formic acid. EFSA Journal 2011;9(3):2112. [7 pp.] doi:10.2903/j.efsa.2011.2112. Available online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2011
TABLE OF CONTENTS Table of contents... 2 Background... 3 Terms of reference... 3 Assessment... 5 1. Introduction... 5 2. Characterisation of the product... 5 2.1. Evaluation of the analytical methods by the European Union Reference Laboratory (EURL)5 3. Compatibility with formic acid... 5 Documentation provided to EFSA... 6 References... 6 2
BACKGROUND Regulation (EC) No 1831/2003 4 establishes the rules governing the Community authorisation of additives for use in animal nutrition. In particular, Article 13(3) of that Regulation lays down that if the holder of an authorisation proposes changing the terms of the authorisation by submitting an application to the Commission, accompanied by the relevant data supporting the request for the change, the Authority shall transmit its opinion on the proposal to the Commission and the Member States. The European Commission received a request from the company Chr. Hansen A/S 5 for authorisation/ of GalliPro 6, Bacillus subtilis, when used as a feed additive for target species (category: zootechnical additive; functional group: gut flora stabiliser) under the conditions mentioned 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 13(3) (modification of the authorisation of a feed additive). EFSA received directly from the applicant the technical dossier in support of this application. 7 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 6 December 2010. The additive 035 is a microbial feed additive based on Bacillus subtilis (DSM 17299). This product is permanently authorised for use in chickens for fattening (4b1821). EFSA has issued one opinion on the safety and efficacy of 035 for chickens for fattening (EFSA, 2006) and several other opinions on the compatibility of 035 with coccidiostats (EFSA, 2007, 2008, 2009 and 2010a). 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 safety for the target animal(s), consumer, user and the environment and the efficacy of the product GalliPro, Bacillus subtilis, when used under the conditions described in Table 1. 4 5 OJ L 268, 18.10.2003, p. 29. Chr. Hansen A/S, 10-12 Boege Allé, DK 2970, Hoersholm, Denmark. 6 The Applicant markets the product also under the tradename 035 7 EFSA Dossier reference: FAD-2010-0101. 3
Table 1: Description and conditions of use of the additive as proposed by the applicant Additive Bacillus subtilis DSM 17299 Registration number/ec No/No Category of additive Functional group of additive 4b1821 Zooetchnical additive Gut flora stabilisers Description Composition, description A preparation of B. subtilis, DSM 17299 Chemical formula 1.6 x 10 10 CFU/g Purity criteria Complies with EU law on undesirable substances Method of analysis Validated microbiological methods Trade name GalliPro (other names may also be used, e.g. "035") Name of the holder of authorisation Chr. Hansen A/S Conditions of use Species or category of animal Maximum Age Minimum content Maximum content Withdrawal period CFU/kg of complete feedingstuffs Chickens for fattening - 0.8 x 10 9 - - Other provisions and additional requirements for the labelling Specific conditions or restrictions for use Specific conditions or restrictions for handling Post-market monitoring Specific conditions for use in complementary feedingstuffs Store at ambient temperatures (20-25ºC) in original, closed packaging. Can be used in feed containing the approved coccidiostats decoquinate, diclazuril, halofuginone, lasalocid sodium, monensin sodium, maduramicin ammonium, narasin, narasin/nicarbazin, robenidine, salinomysin sodium, semduramicin sodium, and organic acids such as formic acid For user safety: recommended to use a facemask, gloves and goggles to reduce contact with dust. Chr. Hansen A/S will conduct post-marketing monitoring in compliance with EU law on feed hygiene, namely by use of HACCP and traceability systems, and formal monitoring of customer feedback through product or service complaints Content of Bacillus spores in final feeds should be min.0.8 x 10 9 CFU/kg Marker residue Maximum Residue Limit (MRL) Species or category of animal Target tissue(s) or food products Maximum content in tissues Not relevant Not relevant Not relevant Not relevant 4
ASSESSMENT 1. Introduction The additive GalliPro 8 is a microbial feed additive based on Bacillus subtilis (DSM 17299 9 ). The additive is currently authorised for use in feeds for chickens for fattening at the minimum dose of 8 x 10 8 and a maximum of 1.6 x 10 9 CFU/kg of complete feedingstuffs (see background). The applicant is now seeking: (i) the modification of the existing authorisation to include a more concentrated formulation, guaranteeing a minimum concentration of Bacillus subtilis (DSM 17299) of 1.6 x 10 10 CFU/g additive. This would be used to deliver the same dose as presently authorised; (ii) authorisation for the simultaneous use with formic acid. B. subtilis is considered by the European Food Safety Authority (EFSA) to be suitable for the Qualified Presumption of Safety (QPS) approach to safety assessment (EFSA, 2010). In the course of previous assessments the strain was considered to satisfy the qualifications specified for the species, and so can be treated as meeting the requirements of the QPS approach. Consequently, no further assessment of safety for the target species, the consumer and the environment is required. In the present opinion the FEEDAP Panel has considered only on the data specific to the compatibility of GalliPro with formic acid and the consequences of changing the formulation. 2. Characterisation of the product The new formulation of GalliPro differs from the authorised product only in the concentration of spores which substitutes for the carrier (whey permeate/lactose or calcium carbonate). Data on six production batches of the new formulation showed that the minimum specification of 1.6 x 10 10 CFU/g of additive was exceeded in all cases. 10 The new formulation of the additive follows the same monitoring procedure for microbial and chemical contamination as previously. Data from six batches of the new formulation confirmed compliance. 10 The increased concentration of the active agent in the product, from 1.6 x 10 9 CFU/g to 1.6 x 10 10 CFU/g, is considered unlikely to modify the conclusion on stability, homogeneity, dusting potential and particle size of the first assessment (EFSA, 2006). The modification of the formulation requested is also considered unlikely to introduce hazards for users of the product not already considered as part of the first assessment (EFSA, 2006). 2.1. Evaluation of the analytical methods by the European Union Reference Laboratory (EURL) The EURL considered that the conclusions and recommendations reached in the previous assessment are valid and applicable for the current application. 3. Compatibility with formic acid The compatibility of the active agent with formic acid up to 2600 mg/kg was demonstrated when the product strain B. subtilis DSM 17299 was used in combination with B. licheniformis DSM 5749 in the 8 The Applicant markets the product also under the tradename 035 9 This strain has been also deposited as DSM 5750 10 Technical dossier/section II/Annex 6 CoAs GalliPro 5
feed additive BioPlus 2B in an in vivo experiment with chickens for fattening (EFSA, 2011). Since the dose of B. subtilis tested was equivalent to the minimum authorised dose, and as differential counts for the two Bacillus strains were provided, the compatibility with formic acid found for BioPlus 2B can be extrapolated to GalliPro. CONCLUSIONS The FEEDAP Panel concludes that the modification to the formulation of GalliPro proposed (minimum concentration of 1.6 x 10 10 CFU/g of additive) is considered unlikely to introduce hazards not already considered as part of the first assessment. The new formulation of GalliPro is compatible with formic acid up to 2600 mg/kg. DOCUMENTATION PROVIDED TO EFSA 1. GalliPro (Bacillus subtilis DSM 17299). Zootechnical feed additive for chickens for fattening. Supplementary application for modification of authorisation. September 2010. Submitted by Chr. Hansen A/S. REFERENCES EFSA (European Food Safety Authority), 2006. Opinion of the Scientific Panel on Additives and Products or Substance used in Animal Feed on the microbiological product "035", a preparation of Bacillus subtilis DSM 17299 as a feed additive for chickens for fattening in accordance with Regulation (EC) 1831/2003. EFSA Journal (2006) 406, 1-11 http://www.efsa.europa.eu/en/scdocs/scdoc/406.htm EFSA (European Food Safety Authority), 2007. Scientific Opinion of the Panel on additives and products or substances used in animal feed (FEEDAP) on the compatibility of the microbial product 035, a preparation of Bacillus subtilis, with lasalocid sodium, maduramycin ammonium, monensin sodium, narasin, salinomycin sodium and semduramycin sodium. EFSA Journal (2007) 575, 1-7 http://www.efsa.europa.eu/en/scdocs/scdoc/575.htm EFSA (European Food Safety Authority), 2008. Scientific Opinion of the Panel on additives and products or substances used in animal feed (FEEDAP) on the compatibility of the microbial product 035 (Bacillus subtilis) with decoquinate and narasin/nicarbazin. EFSA Journal (2008) 840, 1-7 http://www.efsa.europa.eu/en/scdocs/scdoc/840.htm 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 compatibility of the microbial products 035 (Bacillus subtilis) with lasalocid sodium, maduramycin ammomium, monensin sodium, narasin, salinomycin sodium and semduramycin sodium. RFSA Journal (2009) 1096, 1-7 http://www.efsa.europa.eu/en/scdocs/scdoc/1096.htm EFSA (European Food Safety Authority), 2010a. EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); Scientific Opinion on the compatibility of the microbial product 035 (Bacillus subtilis) with lasalocid sodium, maduramycin ammonium, monensin sodium, narasin, salinomycin sodium and semduramycin sodium. EFSA Journal 2010; 8(3):1552. [7 pp.]. doi:10.2903/j.efsa.2010.1552. http://www.efsa.europa.eu/en/scdocs/scdoc/1552.htm EFSA (European Food Safety Authority), 2010b. EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the maintenance of the list of QPS biological agents intentionally added to 6
food and feed (2010 update. EFSA Journal 2010;8(12):1944. [56 pp.] doi:10.2903/j.efsa.2010.1944. http://www.efsa.europa.eu/en/efsajournal/pub/1944.htm EFSA (European Food Safety Authority), 2011. EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); Scientific Opinion on the compatibility of BioPlus 2B (Bacillus licheniformis and Bacillus subtilis) with semduramycin and formic acid in turkeys for fattening. EFSA Journal 2011;9(1):1953. [7 pp.]. doi:10.2903/j.efsa.2011.1953. http://www.efsa.europa.eu/en/efsajournal/pub/1953.htm 7