A negative opinion from EFSA on the product, published in October 2012, concluded it posed a risk for the spread of resistance to two antibiotics used in human and veterinary medicine, and the Commission subsequently moved to suspend existing authorizations for Toyocerin, under Regulation No (EU) 288/2013.
The feed additive had originally been authorized in the EU in 1994 for use in the diets of sows, piglets and pigs.
Rubinum, which filed the application in April 2013, is hoping the EU Court of Justice will suspend operation of Regulation No (EU) 288/2013.
The ruling is due next week – on 21 May.
“We can’t market our product in the EU as a result of this regulatory action. These restrictions are damaging our business and we have been forced to let employees go as a result,” Guillermo Jimenez, technical manager at Rubinum, told this publication yesterday.
He stressed the future of the company could be in jeopardy if it cannot revive sales of Toyocerin, which is based on the strain Bacillus toyonensis, within the EU.
Individuals, companies or organizations can bring cases before the EU Court of Justice Court, which is based in Luxembourg, if they feel their rights have been infringed by an EU institution.
In its 2013 case filing to that Court, the Spanish firm said it had proved that the feed additive did not have an adverse effect on human or animal health or on the environment. “Furthermore, evidence to the contrary was not forthcoming either from the Commission or the EFSA,” stated the application.
The feed additive producer also said the contested Regulation was “based only on assumptions” and that, in fact, neither the transfer of antibiotic resistance nor the production of toxins “could actually be established”.
Supplementary studies
Regulation No (EU) 288/2013, under which the Commission put EU authorization for Toyocerin on ice, did allow Rubinum the possibility of submitting additional supporting documentation to give EFSA’s FEEDAP Panel more scope to reconsider its assessment of the gut flora stabilizer.
In December 2013, the firm said it provided EFSA's FEEDAP panel with supplementary data including new peer reviewed (1) studies supporting:
(i) a new taxonomical classification of the micro-organism as a new Bacillus species: Bacillus toyonensis; (ii) the non-transferability of the antibiotic resistance genes and (iii) the non-functionality of the enterotoxin genes present in the genome of the strain.
The company said it also sent in studies carried out by international recognized experts in the fields of genetic toxicology, antibiotic resistance, molecular microbiology, genomic research and DNA sequencing and bacterial taxonomy, corroborating the new scientific evidence regarding the non-transferability of the resistance genes and the non-functionality of the toxin genes present in the genome of Bacillus toyonensis.
Clarification meeting with EFSA
Dag Andersen, Rubinum’s general manager, told us last year that in a bid to shore up that new evidence, the company met representatives of the EU Commission and EFSA in May 2014 where “it was agreed that some misunderstandings in regards to the data submitted could have arisen and, therefore, EFSA proposed to have a scientific meeting in June in order to clarify them.”
However, he said, that June meeting "did not allow room for any real debate, in spite of the presence of four independent scientists supporting our dossier, or clarification of any point to enable the generation of a common scientific conclusion on Toyocerin."
A spokesperson for EFSA told this publication last July: "Technical hearings are not an opportunity for the applicant to hear the views of the Panel or Working Group on their application during an ongoing risk assessment."
And, in July 2014, the Parma based risk assessor again did not find in favour of the product, saying the new evidence submitted by the manufacturer did not demonstrate the safety of Toyocerin. “On the basis of the data provided by the applicant, including the latest submissions, the FEEDAP Panel concludes that B. toyonensis has the capacity to elaborate functional toxins and thus, to pose a risk to humans exposed to the organism."
Petition submitted to Commission
Jimenez said in August last year, in accordance with Article 19 of Regulation (EC) 1831/2003, Rubinum submitted an official petition for administrative review of the EFSA opinion of July 2014 to DG Sante - the Commission's Health and Consumers DG.
“To date we have not received any official reply to our petition,” he added.
He said the Commission can either order a review of EFSA’s opinion, as per Article 19 of Reg (EC) 1831/2003 or it can deviate from EFSA’s findings as per Article 9 of that regulation.
He said the EU reassessment process for its feed additive has been “costly, time consuming and frustrating with no concrete outcome.”
"We believe we gave text book answers and still fail to understand why our submissions, supported by independent expert reports, have been found wanting by the FEEDAP Panel," said Jimenez.
He called on EFSA to set up a pre submission meeting with applicants that would be “similar in style to those run by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) in both their product risk assessment processes.”
When we put that to the Parma based risk assessor this morning, a spokesperson said: “EFSA is not considering pre-submission meetings with individual applicants. However in future, there might be the possibility of pre-submission meetings with groups of applicants, as part of the Open EFSA initiative. But nothing is decided yet.”
List of studies submitted by Rubinum (1)
Description of Bacillus toyonensis sp. nov., a novel species of the Bacillus cereus group, and pair wise genome comparisons of the species of the group by means of ANI calculations. G. Jimenez et al, Sytematic and Applied Microbiology 36 (2013) 383-391.
Complete genome sequence of the type strain of Bacillus toyonensis BCT-7112T, the active ingredient of the feed additive preparation Toyocerin. Genome announcements, November/December 2013, Vol 1, Issue 6, e01080-13.
Comparison of procedures for the extraction of supernatants and cytotoxicity tests in Vero cells, applied to assess the toxigenic potential of Bacillus spp. and Lactobacillus spp., intended for use as probiotic strains. A.R. Blanch et al, Journal of Microbiological Methods, 103 (2014) 64–69.
Validation List no. 155 by the International Committee on Systematics of Prokaryotes (ICSP), which is a body that oversees the nomenclature of prokaryotes, determines the rules by which prokaryotes are named and whose judicial commission issues opinions concerning taxonomic matters, and bacteriological code revisions.
International Journal of Systematic and Evolutionary Microbiology (2014), 64, 1–5 DOI 10.1099/ijs.0.060285-0
The use of a porcine intestinal cell model system for evaluating the food safety risk of Bacillus cereus probiotics and the implications for assessing enterotoxigenicity - M. Trapecar et al. (2011) APMIS 119:877-884.
Literature review on the safety of Toyocerin, a non-toxigenic and non-pathogenic Bacillus cereus var. toyoi preparation - L.D. Williams et al, Regulatory Toxicology and Pharmacology, 55 (2009) 236–246.