New report on maximum levels of cross-contamination for antimicrobials in non-target feed

After the establishment of the new Medicated Feed Regulation (Regulation 2019/4 of the European Parliament and Council), the European Commission asked EFSA to conduct research and report on the maximum levels of cross-contamination in feed which is not intended to contain any specific active substance (so-called non-target feed).

UAC director, Dan Andersson, has been part of this work, together with the EFSA Panel on Biological Hazards (BIOHAZ) and over 30 other scientists. The team worked to assess, for 24 antimicrobial actives sustances, the following:

• the specific concentrations of antimicrobials resulting from cross-contamination in non-target feed for food-producing animals, below which there would not be an effect on the emergence of and/or selection for resistance in microbial agents relevant for human and animal health
• the levels of the antimicrobials which have a growth promotion/increase yield effect.

To estimate the antimicrobial levels that would not result in emergence of, and/or selection for resistance, they developed the "Feed Antimicrobial Resistance Selection Concentration" (FARSC) model based on:

• the minimal selective concentration, either measured or predicted
• the fraction of antimicrobial dose available for exposure to microorganisms in the large intestine or rumen (considering pharmacokinetic parameters)
• the daily faecal output or rumen volume
• the daily feed intake

The methodology, detailed results per antimicrobial class, conclusions and recommendations can be read in 13 separate scientific opinion pieces published in the EFSA Journal.

The work done in this report has brought foward a series of recommendations that are needed to determine the FARSC of the substances in the European Commission mandate:

• Generation of MIC data using low levels of antimicrobials (below ECOFFs) for a wider range of bacteria and strains.
• Studies to determine the MSCs for all the antimicrobials under assessment for a range of bacteria, including the most susceptible species, using experiments with both pure cultures and complex bacterial communities.
• Studies to determine the lowest antimicrobial levels that promote emergence of resistance (e.g. via the promotion of horizontal resistance gene transfer and/or mutations) using pure cultures and complex bacterial communities.
• Studies to supply missing data and fully evaluate the diversity of parameters for different animal species/breeds/ages/diets, including the total and active concentrations of antimicrobials or their active metabolites in the different segments of the digestive tract after oral administration, taking into account standard pharmacokinetic factors, such as absorption, distribution, metabolism and excretion.
• Studies to determine the antibacterial activity of antimicrobial metabolites occurring in the intestinal tract.
• Development of sensitive, fit for purpose, standardised and robust methods to determine the lowest antimicrobial concentrations that could select for antimicrobial resistance in the target animal species.

References

EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards), Koutsoumanis K, Allende A, Alvarez-Ordoñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, L opez Puente S, L opez-Alonso M, Nielsen SS, Pechov a A, Petkova M, Girault S, Broglia A, Guerra B, Innocenti ML, Li ebana E, L opez-G alvez G, Manini P, Stella P and Peixe L, 2021. Scientific Opinion on the maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 1: Methodology, general data gaps and uncertainties. EFSA Journal 2021;19(10):6852, 57 pp https://doi.org/10.2903/j.efsa.2021.6852

/Eva Garmendia