Modern science for better quality control of medicinal products “Towards global harmonization of 3Rs in biologicals”: The report of an EPAA Workshop

This article summarizes the outcome of an international workshop organized by the European Partnership for Alternative Approaches to Animal Testing (EPAA) on Modern science for better quality control of medicinal products: Towards global harmonization of 3Rs in biologicals. As regards the safety testing of biologicals, the workshop participants agreed to actively encourage the deletion of abnormal toxicity tests and target animal batch safety tests from all relevant legal requirements and guidance documents (country-specific guidelines, pharmacopoeia monographs, WHO recommendations). To facilitate the global regulatory acceptance of non-animal methods for the potency testing of, e.g., human diphtheria and tetanus vaccines and veterinary swine erysipelas vaccines, international convergence on the scientific principles of the use of appropriately validated in vitro assays for replacing in vivo methods was recognized as a further means to unify regulatory approaches in different jurisdictions. It was recommended to include key regulators and manufacturers early in the corresponding discussions. Manufacturers and responsible expert groups, e.g. at the European Directorate for the Quality of Medicines and Health Care of the Council of Europe or the European Medicines Agency, were invited to consider leadership for international collaboration.JRC.F.3-Chemicals Safety and Alternative Method

European-wide antimicrobial resistance monitoring in commensal Escherichia coli isolated from healthy food animals between 2004 and 2018

International audienceMethods: Intestinal contents from cattle, pigs and broilers were randomly sampled (5-6 countries/host; ≥4 abattoirs/country; one sample/animal/farm) for isolation of Escherichia coli; antimicrobial susceptibilities were centrally determined by CLSI agar dilution. Clinical breakpoints (CLSI) and epidemiological cutoff values (EUCAST) were applied for data interpretation. Results: In total, 10 613 E. coli strains were recovered. In broilers, resistance percentages were the lowest (P ≤ 0.01) in the latest time period. A significant decrease in MDR over time was also observed for broilers and a tendency for a decrease for pigs. Resistance to meropenem and tigecycline was absent, and resistance to azithromycin was 0.2%-2.0%. Also, low resistance to third-generation cephalosporins (1.1%-7.4%) was detected in broilers. Resistance to colistin varied between 0.1%-4.8%. E. coli from broilers showed high resistance to ciprofloxacin (7.3%-23.3%), whereas for cattle and pigs this was 0.2%-2.5%. Low/moderate resistance to chloramphenicol (9.3%-21.3%) and gentamicin (0.9%-7.0%) was observed in pigs and broilers. The highest resistance was noted for ampicillin (32.7%-65.3%), tetracycline (41.3%-67.5%), trimethoprim (32.0%-35.7%) and trimethoprim/sulfamethoxazole (27.5%-49.7%) from pigs and broilers, with marked country differences. MDR peaked in pigs and broilers with 24 and 26 phenotypes, with 21.9%-26.2% and 18.7%-34.1% resistance, respectively. Conclusions: In this pan-EU survey antibiotic susceptibility of commensal E. coli varied largely between antibiotics, animal species and countries. Resistance to critically important antibiotics for human medicine was absent or low, except for ciprofloxacin in broilers and ampicillin in pigs and broilers