Introduction
Background and Terms of Reference as provided by the requestor
Regulation (EC) No 1831/2003 establishes rules governing the Community authorisation of additives for animal nutrition and, in particular, Article 9 defines the terms of the authorisation by the Commission.
The applicant, DSM Nutritional Products Ltd, is seeking a Community authorisation of Enterococcus faecium NCIMB 10415 to be used as a zootechnical additive for pigs for fattening, piglets (suckling and weaned piglets) and sows, in order to have benefit in piglets. (Table 1 )
Table 1
Description of the substance
| Category of additive | Zootechnical additive |
| Functional group of additive | Gut flora stabiliser |
| Description | Enterococcus faecium NCIMB 10415 |
| Target animal category | pigs for fattening, piglets (suckling and weaned piglets) and sows, in order to have benefit in piglets |
| Applicant | DSM Nutritional Products Ltd |
| Type of request | New opinion |
On 17 June 2015, the Panel on Additives and Products or Substances used in Animal Feed of the European Food Safety Authority (“Authority”), in its opinion on the safety and efficacy of the product, considered that insufficient data were provided to support the efficacy of Cylactin ® when used in pigs for fattening.
The Commission gave the possibility to the applicant to submit complementary information in order to complete the assessment and to allow a revision of Authority's opinion. The new data have been sent to the Commission and EFSA on 22 March 2017.
In view of the above, the Commission asks the Authority to deliver a new opinion of Enterococcus faecium NCIMB 10415 to be used as a zootechnical additive for pigs for fattening, piglets (suckling and weaned piglets) and sows, in order to have benefit in piglets.
Interpretation of the ToR
The safety of Cylactin ® for pigs for fattening, piglets, sows, consumers, users, and the environment, and its efficacy for sows and weaned piglets were established in a previous opinion (EFSA FEEDAP Panel, 2015 ). Since no conclusion could be drawn on the efficacy for pigs for fattening, this opinion will focus only on the efficacy of Cylactin ® to improve performance of this target species.
Data and methodologies
Data
The present assessment is based on data submitted by the applicant in the form of additional information 1 to a previous application on the same product. 2
Methodologies
The approach followed by the FEEDAP Panel to assess the efficacy of Cylactin ® is in line with the principles laid down in Regulation (EC) No 429/2008 and the relevant guidance documents: Guidance on zootechnical additives (EFSA FEEDAP Panel, 2012 ) and the Technical guidance: tolerance and efficacy studies in target animals (EFSA FEEDAP Panel, 2011 ).
Assessment
Cylactin ® is a feed additive based on dehydrated cells of Enterococcus faecium NCIMB 10415. It is marketed in three forms: Cylactin ® LBC ME10 and Cylactin ® LBC ME20 Plus (coated forms) which contain the microencapsulated bacterium in concentrations of 1 × 10 10 CFU/g and 2 × 10 10 CFU/g, respectively, and Cylactin ® LBC G35, a granulated non‐coated form with a guaranteed content of 3.5 × 10 10 CFU/g. The additive was fully characterised in the previous opinion (EFSA FEEDAP Panel, 2015 ).
Cylactin ® is intended for use in feeds for pigs for fattening at the minimum concentration of 3.5 × 10 8 CFU/kg complete feed and the maximum of 1 × 10 9 CFU/kg complete feed.
The scope of this opinion is to assess the efficacy of Cylactin ® when used as a zootechnical additive (gut flora stabiliser) in feed for pigs for fattening at the minimum concentration of 3.5 × 10 8 CFU/kg complete feed.
Efficacy for pigs for fattening
The dossier submitted in 2012 included six efficacy studies with pigs for fattening aiming to demonstrate the potential of Cylactin ® to improve zootechnical performance of animals (EFSA FEEDAP Panel, 2015 ). However, four of them were rejected due to limitations in the design or reporting and only two could be considered. In these two studies, feed to gain ratio was significantly improved in Cylactin ® treated‐animals, in one case when the additive was used at the minimum recommended dose and the other at the maximum recommended dose (studies 4 3 and 5, 4 respectively).
The applicant has submitted three new studies conducted in two Member States, in two different locations aiming to investigate the effects of the additive on the growth of pigs for fattening. The design of the studies is presented in Table 2 . The new studies are identified as 1 5 , 2 6 and 3, 7 while the two studies already presented in the previous opinion (EFSA FEEDAP Panel, 2015 ) are studies 4 3 and 5. 4 The results are presented in Table 3 .
In the three new studies animals were individually housed and allocated, based on body weights and gender, to two experimental groups: a control group receiving the basal diets and a second group receiving the basal diets supplemented with Cylactin ® LBC ME20 Plus in order to provide 3.5 × 10 8 CFU/kg feed. Intended cell counts were confirmed by analysis of feed. The FEEDAP Panel considers that the three available formulations are equivalent when used to deliver the same dose. The diets were offered to the animals ad libitum . Health status was monitored throughout the experimental periods. Individual feed intake and body weight of the animals were measured and the average daily gain (ADG) and feed to gain ratio were calculated. Morbidity and mortality of animals were also monitored. In these three studies, data were analysed using an analysis of variance (ANOVA) and considering the animal as the experimental unit. Significance was established at p < 0.05.
No significant differences in any of the studied parameters were observed in the new studies submitted (Table 3 ).
Table 2
Details on the study design for the studies performed in pigs for fattening
a 112 in the control group and 104 in the treated group, 7/8 animals per replicate. b 119 females and 121 barrows. c In this case the administration of the additive started with the sows.
| Study | Total animals Replicates/treatment | Breed (sex) | Duration of the study (days) | Basal diets (main ingredients) Form |
| 1 | 200 100 | Line 990 (♀, castrated ♂) | 111 | (triticale/wheat/rapeseed meal/soybean meal) Pelleted |
| 2 | 184 92 | Pietrain × Danbreed (♀, ♂) | 117 | (wheat/barley/rye/triticale/soybean meal) mash and pelleted |
| 3 | 240 120 | Pietrain × Topigs (♀, castrated ♂) b | 101 | (wheat/rye/triticale/barley/soybean meal) Pelleted |
| 4 | 60 30 | cross‐bred (♀, ♂) | 121–126 (until slaughter) | (Wheat/barley/cassava/rapeseed/soybean meal) Pelleted |
| 5 | 216 a 14 | Large White × Landrace (♀, ♂) | 84–112 (until slaughter at 105–110 kg) | (commercial diet c ) pelleted |
Table 3
Overview of results of efficacy studies with Cylactin ® in pigs for fattening
CFU: colony forming unit. * Six out of 10 animals were removed from the study due to tail biting. a,b Means in a column within a given trial with different superscript letters are significantly different p < 0.05.
| Study | Cylactin ® (CFU/kg feed) | Initial weight (kg) | Final weight (kg) | Average daily feed intake (kg) | Average daily gain (g/day) | Feed to gain ratio | Mortality and removal (n/total) |
| 1 | 0 3.5 × 10 8 | 27.5 27.3 | 114.7 115.9 | 2.66 2.58 | 869 886 | 2.77 2.73 | 2/100 2/100 |
| 2 | 0 3.5 × 10 8 | 27.7 27.7 | 122.0 122.2 | 2.41 2.41 | 989 1,000 | 2.45 2.41 | 1/92 1/92 |
| 3 | 0 3.5 × 10 8 | 29.7 29.6 | 116.2 116.4 | 2.21 2.22 | 852 859 | 2.60 2.59 | 10/120 * 3/120 |
| 4 | 0 3.5 × 10 8 | 24.6 24.7 | 111.6 112.2 | 2.19 2.21 | 861 867 | 2.55 2.55 | 2/30 1/30 |
| 5 | 0 3.5 × 10 8 | 21.3 22.8 | 107.3 108.8 | 2.28 2.27 | 858 882 | 2.69 a 2.60 b | 0/112 1/104 |
The data on ADG and feed to gain ratio of the five studies were pooled. 8 The studies included in the analysis were homogeneous with regards to weight range and study duration, genders involved (1:1 sex ratio), inclusion level of the additive and control diets. The only identifiable source of heterogeneity is related to the different study design of study 5. In this case, piglets entered the study at birth and the administration of the additive started with the sows; however, the data included in the analysis considered only the fattening period. The estimated effects in each study were combined using an inverse‐variance‐weighting approach. The (random effects) analysis estimate of the true underlying effect of Cylactin ® vs the control group on ADG was 11.6 g/day (p < 0.05) and on feed to gain ratio it was −0.03 (p < 0.05).
Conclusions
Based on the results of the pooled analysis of five efficacy studies, but not supported by four out of the five individual studies, the FEEDAP Panel concludes that Cylactin ® has some potential to improve performance of pigs for fattening at 3.5 × 10 8 CFU/kg feed.
Documentation provided to EFSA
Additional data on use of Cylactin ® for pigs for fattening. Technical dossier‐ Efficacy according to Regulation (EC) No 1831/2003 for authorisation. March 2017. Submitted by DSM Nutritional Products Ltd.
Abbreviations
ADG average daily gain ANOVA analysis of variance CFU colony forming unit FEEDAP EFSA Panel on Additives and Products or Substances used in Animal Feed
Notes
FEED dossier reference: FAD‐2017‐0020.
FEED dossier reference: FAD‐2010‐0269.
Technical dossier/Annex 5.
Technical dossier/Annex 6.
Technical dossier/Annex 2.
Technical dossier/Annex 3.
Technical dossier/Annex 4.
Technical dossier/Annex 7.
References
EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2011 . Technical guidance: tolerance and efficacy studies in target animals . EFSA Journal 2011; 9 ( 5 ): 2175 , 15 pp. 10.2903/j.efsa.2011.2175 PMC13177317 42148398
EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2012 . Guidance for the preparation of dossiers for zootechnical additives . EFSA Journal 2012; 10 ( 1 ): 2536 , 19 pp. 10.2903/j.efsa.2012.2536
EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2015 . Scientific Opinion on the safety and efficacy of Cylactin ® ( Enterococcus faecium NCIMB 10415) as a feed additive for pigs for fattening, piglets and sows . EFSA Journal 2015; 13 ( 7 ): 4158 , 18 pp. 10.2903/j.efsa.2015.4158 PMC13151605 42109800