WHO Activities Concerning the Use of Antimicrobials in Livestock Production
Joint FAO/WHO Activities Concerning the Non-Human medical Use of Antimicrobials
CCRVDF Discussions Concerning the Use of Antimicrobials in Animal Production
Report on the Joint FAO/NACA/WHO Study Group on Food Safety Issues Associated with Products from Aquaculture
6. The Committee noted matters arising from the Codex Alimentarius Commission (CAC) and other Codex Committees concerning Amendments to the Procedural Manual of the Codex Alimentarius Commission; Draft Maximum Residue Limits for Bovine Somatotropins (BST); the adoption of Draft and Proposed Draft Maximum Residue Limits at Various Steps; Methods Validation for Food Control Purposes; Maximum Residue Limits for Honey, Low-Fat Meat and Fish; the Review of the Status and Acceptance of Codex Texts under the WTO Agreements; and the Draft Code of Practice on Good Animal Feeding. The following specific Codex activities were also noted by the Committee:
Withdrawal of Codex Maximum Residue Limits for Oxytetracycline in Fat Tissue (Cattle, Pig, Sheep, Chicken and Turkey)
7. The Committee noted that the Executive Committee at its 45th Session[3] had agreed to the decision of the 10th Session of the CCRVDF[4] to withdraw the MRLs for Oxytetracycline in fat of cattle, pig, sheep, chicken and turkey, subject to confirmation by the next session of the Commission. On the basis of this decision, these MRLs had already been deleted from the database of MRLs for veterinary drugs.
MRLs for Compounds Used Both as Veterinary Drugs and Pesticides
8. The Committee noted discussions held at the 22nd Session of the Commission, the 29th and 30th Sessions of Codex Committee on Pesticide Residues (CCPR) and the 1997 Joint FAO/WHO Meeting on Pesticide Residues (JMPR)[5] concerning differences in the way the CCRVDF and the CCPR established MRLs. These discussions emphasized the need for harmonization and consistency throughout Codex, particularly in the areas of the consideration of fat solubility of compounds; residue definitions; commodity definitions, especially the definition of "muscle" in relation to fat content; levels recommended for the same commodity/compound combinations; and dietary models used for risk assessment. The Committee further noted the recommendations of the JMPR on harmonization of recommendations from that body and JECFA for MRLs for compounds with both agricultural and veterinary uses.
9. The Committee generally recognized the need for harmonization and requested the FAO Secretaries of the JECFA and JMPR to convene an informal meeting of experts in the areas of residues of veterinary drugs and pesticides to consider these issues (also see paras. 11 and 62). The outcome of this meeting would be reported and considered by the CCRVDF and the CCPR. As a number of issues needing to be addressed depended on the outcome of this meeting, the Committee deferred discussions on this matter until its next session.
Revision of Recommended Methods of Sampling for the Determination of Pesticide Residues
10. The Committee was informed of the work of the 29th and 30th Sessions of the CCPR[6] on the revision of the Recommended Methods of Sampling for the Determination of Pesticide Residues[7]. Noting the importance of harmonization and the impracticality of having different systems of sampling for residues of pesticides and veterinary drugs, the Committee expressed concern that the views of the CCRVDF and the Codex Committee on Food Import and Export Inspection and Certification Systems had not been obtained.
11. Noting that there were still substantial differences in the way MRLs were derived, defined and analyzed between the two Committees, the Committee agreed that it should be clarified that the revised methods of sampling developed by the CCPR were applicable only to residues of pesticides used for plant protection purposes but not to veterinary uses. It also requested the JECFA and JMPR informal meeting (see para. 9) to consider the revised methods of sampling. As the text was forwarded by the 30th CCPR for final adoption by the 23rd Session of the Commission at Step 8, delegations were encouraged to comment on the text for direct consideration by the Commission.
12. Dr Stoehr, representative of WHO, reported on two meetings WHO organized recently to identify priority public health issues arising from the use of antimicrobials in livestock production. These meetings were organized against concerns that microbiological and clinical evidence was mounting that resistant bacteria or resistant determinants might be passed from animals to humans, possibly resulting in infections that were more difficult to treat.
13. Dr. Stoehr stated that the WHO focus on this subject was on human health and its activities were based on the scientific information relevant for the assessment of human health problems. Dr. Stoehr emphasized that any antimicrobial use had the potential to cause selection of resistant forms of bacteria in the ecosystem of use. This would occur with all uses, including treatment, prophylactic and growth promotion, as well as therapeutic use of such drugs in humans. The WHO representative noted that despite the uncertainty over the full magnitude of the public health impact of antimicrobial use in food animal production, there was enough evidence to cause concern and therefore, action was needed both in the veterinary and human use of antimicrobial agents to control or mitigate any problems related to the widespread application of antimicrobials.
WHO Meeting on the Medical Impact of the Use of Antimicrobial Drugs in Food Animals (Berlin, Germany; 13-17 October 1997)[8]
14. Dr. Stoehr indicated that the WHO meeting report focused on the medical consequences of resistance acquisition in bacteria of animal origin. This was highlighted by examples of resistance in foodborne Salmonella, Campylobacter, Enterococci and E. coli, which had already been identified of being of particular human health concern. Antimicrobials particularly addressed were Glycopeptides, Macrolides and Quinolones.
15. Recommendations as presented in the report of the Consultation focused on the use of antimicrobial growth promoters and alternatives to it, threshold levels for mitigation procedures, risk assessment, and antimicrobial consumption. In terms of food standards, the report recommended that national authorities should define threshold levels of resistance in bacteria and circumstances where mitigation procedures should be instigated and, if such procedures were unsuccessful, then approval should be withdrawn. The implementation of this recommendation would require standards to be developed and agreed upon at national and consequently also at international levels. The Consultation also recommended that the CAC should include issues of antimicrobial resistance among the terms of reference of the Codex Committee on Residues of Veterinary Drugs in Food.
16. Furthermore, the report of the Consultation recommended that the use of any antimicrobial agent for growth production in animals should be terminated if it was used in human therapeutics or was known to select for cross-resistance to antimicrobials used in human medicine. The report recommended that in general, WHO should promote the development of a systematic approach towards replacing growth-promoting antimicrobials with safer non-antimicrobial alternatives. This would entail establishing a list of priority compounds and a comprehensive assessment of the potential health risks posed by them.
WHO Meeting on the Use of Quinolones in Food Animals and Potential Impact on Human Health (Geneva, Switzerland; 2-5 June 1998)[9]
17. The meeting report was not printed at the time of the CCRVDF meeting. Dr. Stoehr summarized the major conclusions and recommendations of the Consultation in regard to food safety and food trade. The major objective of the meeting was to identify known and potential links between quinolone resistance in foodborne and other bacteria, and human treatment problems.
18. Recommendations as presented in the report of the Consultation concluded that the use of fluoroquinolones in food animals had lead to the emergence of fluoroquinolone resistant Campylobacter and of Salmonella with reduced susceptibility to fluoroquinolones. There had been little documented impact of this resistance on human health to date, but there was concern about the potential human health consequences if resistance were to increase and spread. The representative of WHO provided additional information on the unpublished report of an outbreak of multidrug (including quinolones) resistant Salmonellosis (S. typhimurium DT 104) from Denmark with seven invasive cases of which none responded to treatment with fluorquinolones; one patient died.
19. Furthermore, the report recommended that member countries include the evaluation of antimicrobial resistance and the monitoring of susceptibility of zoonotic and/or target animal pathogens post-approval as a critical part of the registration process.
20. Recommendations from the Consultation also covered research needs, data gathering needs and the prudent use of antimicrobials in livestock and aquaculture.
21. In the research needs section, amongst others, a critical need was identified by the Consultation to investigate methods and procedures to appropriately address resistance concerns that arise prior to licensing of quinolones. The meeting noted that this research should define the appropriate risk assessment models and data needed to allow the models to be implemented. Additionally, the most appropriate post-approval monitoring schemes should be developed which complement the pre-approval risk assessment models. The Consultation also recommended that WHO, jointly with FAO, OIE and other organizations, should develop a code of practice for prudent use of antimicrobials in food animal production which should include public health safeguards.
22. The Committee noted WHO's request for better international cooperation in the field of non-human use of antimicrobials. Antimicrobial use in livestock, aquaculture, horticulture and other areas outside the human medical area was of concern to a variety of professions, agencies and organizations. This would also encompass all aspects of food production and processing including the setting of standards on the microbiological specifications of food related to the prevention of human infections due to antimicrobial resistant pathogens.
23. The representative of the OIE informed the Committee of the interest OIE was taking in the subject of antimicrobial resistance. In this matter, it had assisted a number of international expert consultations, including those two mentioned by WHO. In regard to its terms of reference, OIE had as a first initiative prepared a report on the role of international trade in animal, products of animal origin and animal feed in the transmissibility of antimicrobial resistance and the means of controlling the spread of resistance factors of infective agents. This report, which had been based on the input of OIE European member countries, will be presented for consideration and further initiatives to the OIE Regional Commission for Europe at its 18th Conference (Prague, 22-25 September 1998).
24. The representative of WHO informed the Committee that joint WHO and FAO discussions on the above subject would include the consideration of the non-human use of antimicrobials and the consequences of this use on human health. A joint FAO/WHO body had been established, whose work would primarily focus on the health impact of non-human medical use of antibiotics, including:
25. Preliminary FAO/WHO discussions emphasized that better and more mechanisms needed to be developed to address food issues related to antimicrobial resistance including the microbiological safety of food of animal origin. The discussions also noted that an appropriate body needed to be identified for both evaluating the human health risk from the consumption of food contaminated with antimicrobial resistant pathogens and to develop standards ensuring the safety of food as well as facilitating food trade.
Proposed Joint FAO/WHO Expert Consultation on Food Microbiological Risk Assessment
26. The 22nd Session of the Codex Alimentarius Commission (June 1997) had requested FAO and WHO to convene an international expert advisory body (similar to JECFA and JMPR) on the microbiological aspects of food safety to address particularly microbiological risk assessments[10]. The 45th Session of the Executive Committee of the Codex Alimentarius Commission (June 1998) noted that discussions were underway between FAO and WHO on how such a body could be established on a permanent basis and in this regard, noted that an ad hoc body would be convened to consider the work programme and proposed terms of reference for the expert advisory body.
27. While acknowledging the occurrence of some public health problems from antimicrobial resistant foodborne commensals and pathogens, some delegations noted that the majority of the current problems were caused by the overuse of antimicrobials in human medicine. However, these delegations expressed concern about the potential human health consequences if resistance in foodborne and animal pathogens were to further increase and spread.
28. Some delegations suggested that CCRVDF should address issues relating to antimicrobial resistance and the safety of food of animal origin and in this regard, suggested that the CAC might wish to consider extending the terms of reference of the CCRVDF accordingly. Whilst supporting that the CCRVDF should address the assessment of health risks from the consumption of food contaminated with resistant bacteria, other delegates pointed out that such an extension would not be necessary as the current CCRVDF terms of reference would already cover the subject of antimicrobial resistance. It was noted that JECFA currently considered the impact of antimicrobial residues on the gut based on available information, but did not consider the transfer of antimicrobial resistance arising from the use of antimicrobials and their release into the environment, which was outside the terms of reference of JECFA.
29. In addition, the Committee noted that there might also be a lack of data on which to build consensus, and that other international organizations such as the OIE, EU and the World Veterinary Association (WVA) were also addressing the subject.
30. The representative of WHO stressed that there was sufficient evidence to cause concern. Addressing them would require a very close collaboration between human and veterinary medicine, agriculture, academia and national agencies. The aim of such collaboration would be, in view of human health, to assess the scope of the problems and to identify mitigation procedures. As food is involved, it would be inevitable that safety and trade related issues would be raised which needed to be resolved at both national and international levels.
31. The Committee agreed to further consider this issue at its next meeting, taking into account the activities of other international bodies. This information would be presented to the Committee at its next session.
32. Dr. Moy of the WHO noted that a Study Group on Food Safety issues associated with products from aquaculture was jointly organized in July 1997 in Thailand by the Programme of Food Safety and Food Aid of WHO, in collaboration with the Fisheries Department of the FAO, and the Network of Aquaculture Centres in Asia and the Pacific (NACA). The meeting was attended by experts from 15 countries.
33. The Study Group considered food safety issues associated with farmed fin fish and crustaceans, particularly those associated with biological and chemical contamination that may occur during the production of these aquatic products.
34. The principal conclusions from the meeting were that there was a need for an integrated approach to controlling hazards associated with products from aquaculture which required close collaboration between the health, agriculture and aquaculture, food safety, and education sectors. Food safety assurance measures should form an integral part of the fish "farm-to-table" food safety continuum and should be based on the Hazard Analysis and Critical Control Point (HACCP) system. The Committee noted that the Codex Committee on Fish and Fishery Products was already taking action on several issues raised in the Consultation report.
