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European Community comments on the

Proposed Draft Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance (CX/AMR 09/3/4)

At Step 3

The European Community and its Member States (ECMS) would like to express their congratulations to the USA on the comprehensive job of integrating the three previous parts to a single document and in particular for diligent efforts to streamline the document and to reconcile all different comments received. The ECMS would also like to thank all the members of the electronic working group for the very constructive discussions.

GENERAL COMMENTS

The ECMS noted that there are numerous changes to the text as compared to what was agreed by the Task Force on Antimicrobial Resistance (TF AMR). Generally, the ECMS accept these changes as we find the new document much easier to read without important content getting lost. The ECMS would like to propose in the comments provided below some amendments in order to further increase clarity and readability.

The ECMS are pleased to provide the following SPECIFIC COMMENTS to the questions posed by the Chair and also on the Proposed Draft Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance.

Introduction and Scope

The ECMS agree on the proposal to have a single introduction for the consolidated document as well as that the text provided for the "scope" in each section is maintained as proposed.

General principles

Paragraph 8

The ECMS would like to re-iterate its previous comments in relation to the inclusion of a General Principle to address animal health and welfare aspects. This question was agreed at the last session of the TF AMR. The ECMS would therefore like to suggest that the following principle is added:

"Principle 8: Evaluation of pre-harvest AMR risk management options should include, whenever appropriate, aspects related to animal health and welfare."

Organisation of Risk Management Activities

Paragraph 9

As explained by the US chair the structure of the document differs from the one agreed at the second session of the TF AMR (ALINORM 09/32/42, para. 15). In principle, the ECMS would favour the step-by-step approach as proposed by the USA, as the current proposed draft

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provides substantial improvement in readability. Working on the basis of the current structure would allow sufficient time for in-depth consideration of the proposed draft and ample scope for improving its wording while ensuring successful completion of the work in the schedule set for the Task Force by the Codex Alimentarius Commission.

Long Document

The ECMS fully share the views that the Guidelines would be further improved by focusing on AMR-specific issues. Detailed comments in this respect are provided below.

Placing of supplemental RMOs

The ECMS strongly support that the supplemental RMOs are maintained in the main body of the text and are not inserted in an annex. The ECMS consider that the use of a table places this list in its right context avoiding misinterpretations of its purpose. Specific comments are provided below.

Monitoring of RMOs vs. surveillance of AMR

The ECMS support the separate section on monitoring and surveillance as proposed by US.

ANNEX I

INTRODUCTION

Paragraph 1:

The ECMS would like to propose re-wording of the second sentence in order to improve its clarity. The sentence would read as follows:

1. “Problems related to AMR is are inherently related to antimicrobial use in any environment, including human and non-human uses.”

Paragraph 2:

In order to make the language clearer the ECMS would like to suggest replacing the word "concurred" by "agreed". It is also suggested to insert the word "foodborne" in the final sentence last use of AMR in last line:

2. “…….A series of FAO/OIE/WHO expert consultations have concurred agreed that…………… specific to foodborne AMR risk analysis"

Paragraph 5:

The ECMS note that the chapter numbers and titles of the OIE Terrestrial Animal Health Code may change over time. Therefore, the ECMS would like to suggest that the chapter numbers quoted in the draft Guidelines are deleted. The last part of the last sentence would read as follows:

5. "….and the chapters 6.5 to 6.8 related to the control of AMR for the Terrestrial Animal Health Code (OIE)"

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If accepted, this comment also applies to all the paragraphs in the text where reference is made to the Terrestrial Animal Health Code.

SCOPE

Paragraph 6:

In view of the fact that the entire document is titled “Proposed Draft Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance, the ECMS believe that “foodborne antimicrobial resistance” should be included in the first sentence in this paragraph. Therefore the ECMS would like to suggest an amendment to this paragraph as follows:

6. "The scope of this guideline is to provide science-based guidelines on methodology and processes for risk analysis and its application to non-human use of antimicrobials and foodborne antimicrobial resistance. The intent of the guideline…"

In addition, the ECMS suggest re-wording the second sentence as follows:

6. "“…develop advice on appropriate risk management advice based on that assessment to reduce such risk.”

Paragraph 7:

Many of the areas referred to are not areas of use. The ECMS suggest to revise the beginning of the paragraph to:

7. “As there are existing Codex or internationally recognized guidelines, the following areas related to uses of antimicrobials are outside the scope of the guideline: …”:

DEFINITIONS

Paragraph 8

The ECMS would like to suggest to amend the last sentence of this paragraph as there are definitions cited from other existing texts than the FAO/OIE/WHO, e.g. WTO/SPS Agreement. Therefore, it is proposed to delete the reference to the FAO/OIE/WHO:

6. "…Definitions cited from existing FAO/OIE/WHO documents are referenced as appropriate."

DALYs

The ECMS would like to propose to insert a definition of DALYs as this term is used in paragraphs 45 and 47. The proposed definition has been adapted from the WHO definition (http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/index.html)

DALYs: a measurement of the gap between current health status and an ideal situation where the entire population lives to an advanced age, free of disease and disability

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Extra- and Off-label use

The ECMS consider that as human antimicrobials can also be used off-label it seems appropriate to delete “non-human”.

Extra- and Off-label use: the non-human use of an antimicrobial that is not in accordance with the approved product labelling.

Intrinsic resistance and National treatment guidelines

The need for these definitions seems questionable as the expressions were not found in the text. Therefore the ECMS would like to propose its deletion.

Prevention and prophylactic use:

In the current Proposed Draft, the term ‘prevention/prophylaxis’ is used only once, in Table 1 page 19 (“avoid or limit use of antimicrobial agents or a specific agent for disease prevention/prophylaxis in healthy animal not considered to be at risk of infection”). The ECMS consider that this sentence seems to use the terms ‘prevention/prophylaxis’ in a different way: it implies that ‘prevention/prophylaxis’ may also cover situations where animals are not considered to be at risk. This is in contradiction with the definition adopted by Codex/OIE that can be found in the glossary of terms of the Code of Practice to Minimise and Contain AMR (CAC/RCP/61-2005), which makes clear that ‘prevention/prophylaxis’ deals only with situations where “healthy animals are considered at risk or prior to the onset of clinical infectious disease”. Therefore, the ECMS would like to propose that the text in Table 1 page 19, is amended to read:

Table 1, Food animal production, fourth bullet

“Ensure that antimicrobial agents are not used in healthy animals that are not considered at risk.”

As there is no longer any mention of ‘prevention/prophylaxis’ in the new text, then the definition of prevention and prophylactic use can be deleted.

Responsible Use Guidelines

The ECMS observe that the text in the definition provides a list of synonyms of what these guidelines may be called in other documents rather than a true definition of the expression itself.. If this definition is kept in the text the ECMS would like to suggest that a reference to the relevant Codex text is inserted.

Guidance on Responsible Use can be found e.g. in the Code of Practice to Minimize and Contain Antimicrobial Resistance (CAC/RCP 61-2005).

Risk Manager:

The ECMS note that ‘risk manager’ is defined in CAC/GL 63 -2007 and if the definition is maintained, it should be in italics and not be limited to those managing risks with AMR as there is no limitation in the term defined. Therefore, the ECMS would like to suggest a change to:

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Risk Manager – A national or international governmental organization with responsibility for AMR risk management activities.

Risk Management Option (RMO):

The ECMS understand that the options are the menu of identified actions that could potentially be taken, and not limited to the one(s) selected for implementation. Consequently, the ECMS suggest a modification as follows:

Risk Management Option (RMO) – A specific action that could be implemented taken to mitigate risk at various control points throughout the food production to consumption continuum.

GENERAL PRINCIPLES FOR AMR-RISK ANALYSIS

The ECMS would like to suggest that the term "foodborne" is introduced in the title

GENERAL PRINCIPLES FOR FOODBORNE AMR-RISK ANALYSIS

Principle 4:

The ECMS do not find this text sufficiently clear. For instance the expression “resistant microorganism” is repeated twice in the list. Further development of Principle 4 to increase readably would be appreciated.

Principle 5:

It is the understanding of the ECMS that the intention in Principle 5 is that AMR risk analyses should consider microbiological risk analyses that may have been conducted. Therefore the ECMS propose to delete the word guidelines.

"Principle 5: AMR-risk analysis, should build on existing microbiological risk analysis guidelines and, in addition, needs to consider factors relating to antimicrobial susceptibility of the microorganism(s) in question and related consequences to human disease."

Principle 6:

The ECMS note that different ways of expressing what a combination is have been used in this document. The wording of principle 6 is not consistent with the wording used in paragraphs 17 (2nd bullet), 38 and 70. The ECMS therefore propose that a harmonised approach is used throughout the document. The ECMS would like to express their preference for the combination proposed below:

Principle 6: AMR-risk analysis should focus on clearly defined combinations of the food commodity + antimicrobial resistance+ microorganism/genetic resistance determinant with consideration of co-resistance in certain situations.

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FRAMEWORK FOR AMR RISK ANALYSIS

Figure 1:

The ECMS appreciate Fig 1 and would like to provide some comments to further clarify the framework.

The figure gives the impression that following risk profile, only very urgent or provisional decisions can be taken. This is not in line with CAC/GL 63 -2007 Section 5.2 on Microbiological risk profile: ‘ …National governments may also base their decisions on Codex standards, recommendations and guidance where available. In some cases, the risk profile can give enough information for identification and selection of MRM options….’ The ECMS find those lines fully applicable to the AMR risk analysis, especially relevant in case of general measures like information campaigns and implementation of prudent use recommendations where it would be superfluous to commit a full risk assessment.

The ECMS suggest the following changes to the Figure:

• Deletion of the box “Immediate public health concern”.

• The text in the box Immediate and/or [provisional] decision] should be changed for clarity to “immediate decision, provisional in cases when data are insufficient”.

• The grey colour in the centre of the figure should be deleted.

• The box with “No action” should be moved further down to fit within the section “risk management” rather than with the section “risk assessment”.

• The text in the box "Ranking of the hazard for RA/RM priority" should be amended to read: "Ranking of the food safety issue hazard for RA/RM priority"

• The text in the box “Commissioning a risk assessment” should be amended to “Conducting a risk assessment” to fit with the structure. .

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Proposal for Figure 1: Framework for AMR-Risk Analysis

Paragraph 11:

The ECMS would suggest to delete this paragraph. The language used in the first sentence of this paragraph is too prescriptive and the second sentence is not consistent with paragraph 20. A decision to take RMOs prior to the establishment of a risk assessment could be undertaken provisionally at any occasion when there is evidence that a risk to human health exists, it is not necessary that the risk is immediate. Furthermore, the ECMS believe that the expression “clear evidence” is more restrictive than the corresponding texts in CAC/GL 63-2007 (section 5.1) and the SPS agreement Art 5.7.

Identification of an AMR food safety issue

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Establishment of a Risk Profile

Ranking of the food safety issue for RA/RM priority

Conducting Risk Assessment

Consideration of the results of the risk assessemnt No Action

Identification, evaluation and

selection of RM option

Implementation of RM options Monitoring and review of RM options

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Establishment of risk assessment policy for the conduct of the risk assessment Pr

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Paragraph 12:

The ECMS would suggest to delete this paragraph as its content is mainly a duplicate of information in paragraph 21 and 22 (see below).

PRELIMINARY AMR-RISK MANAGEMENT ACTIVITIES

Paragraph 14:

The ECMS believe that the last sentence in this paragraph is not needed, given what has already been said in the introduction and scope and therefore the ECMS suggest its deletion:

14. A potential food safety issue may arise when antimicrobial resistant microorganisms or resistance determinants are present or transmitted in food and/or animal feed, including aquaculture. Foodborne exposures to resistant microorganisms or resistance determinants may adversely impact human health. The risk manager initiates the risk management process, beginning with the preliminary risk management activities, to evaluate the scope and magnitude of the food safety issue and, where necessary, to commence activities to manage the identified risk. In the course of implementing these preliminary risk management activities, the risk managers should consider the different areas of use of antimicrobials, such as in food animals (including aquatic species) and in plants.

Identification of an AMR food safety issue

Paragraph 15:

The ECMS find this paragrapgh is too detailed and note that there are lists containing information to be provided to describe the extent of AMR at different stages of the process (risk profile, risk assessment, monitoring) three times in the document (here, in paragraph 34 and in Appendix 3). This results in substantial overlaps in their content. Therefore, in order to simplify the text the ECMS would like to suggest to insert a reference to the information contained in paragraph 34 and delete the rest: ..:

15. AMR food safety issues may be identified on the basis of information arising from a variety of sources as described in paragraph 34. such as AMR surveillance in animals and in foods of animal origin, food safety monitoring, antimicrobial usage surveys, animal and human surveillance data (including post-marketing surveillance data on approved antimicrobials), epidemiological or clinical studies, laboratory studies, research on resistance transfer, scientific, technological or medical advances, environmental monitoring, recommendations of experts and interested parties, etc. Information on AMR microorganisms and resistance determinants related to plant production and food processing should be included. Additional potential sources of information are provided in the Code of Practice to Minimize and Contain Antimicrobial Resistance (CAC/RCP 61-2005).

Development of an AMR risk profile

Paragraph 17

The ECMS support the new shorter text without the reference to an “abbreviated risk profile”. However, the text as proposed could be further improved especially considering that risk

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profiles could cover also post-harvest aspects. The ECMS would like to suggest to use the same wording as proposed for Principle 6 in the second bullet point. In addition, the ECMS would also suggest that references to specific international meetings are avoided as this document will be long lasting and new meetings will be held, and new groups may be formed.

The following amendments are proposed:

17. The depth and breadth of the AMR risk profile may vary depending on the needs of the risk managers and the complexity and urgency of the food safety issue. The fundamental elements that comprise an AMR risk profile include:

• Description of the hazard and public health problem (the AMR food safety issue);

• Identification and characterization of the combination of the food commodity + antimicrobial resistance+ microorganism/genetic resistance determinant with consideration of co-resistance in certain situations antimicrobial resistant microorganisms + antimicrobial use combination;

• Consideration of the importance of use in animals and humans of antimicrobials of relevance for the hazard e.g. by consulting critically important antimicrobial lists developed by national and international groups organisations (e.g., WHO and OIE Expert Meeting on Critically Important Antimicrobials, Rome 2008)

• Description of usage (extent and nature) of antimicrobials in food production, when available (such as veterinary applications, aquaculture, plant protection or food processing); including consideration of the possible links between animal or plant use of antimicrobials and exposure to the hazard;

• Identification of pre- and post-harvest risk mitigation measures that could be taken; and

• Identification of major knowledge gaps.

Paragraph 19:

The ECMS would like to propose the following change (please see comment on Fig 1 above):

Consideration of the information given in the risk profile may result in options leading to a range of initial decisions, such as determining that no further action is needed, commissioning an AMR risk assessment, establishing additional information gathering pathways, or implementing immediate risk mitigation measures for those food safety issues that require an immediate action by the risk manager without further scientific consideration (e.g., requiring withdrawal/recall of contaminated products).

Ranking of food safety issues and setting priorities for risk assessment and management

Paragraphs 21 and 22

The ECMS note that in order to prioritize at least two different items are necessary and therefore would like to suggest the following amendments in paragraphs 21 and 22. In addition, a couple of typographical errors were noted in paragraph 22

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21- Given the potentially high resource costs associated with conducting risk assessment and/or implementing RMOs, the AMR risk profiles provides the principal resource that should…..

22- Beyond the description of the AMR food safety issues provided by the risk profiles, other criteria may be used for ranking or prioritization; these are generally determined by the risk managers in conjunction...Other criteria that could be used to rank this ARM AMR food safety….

Establishment of broad risk management goals

Paragraphs 23-26:

The ECMS are of the opinion that these paragraphs are redundant and could be deleted from the text. In essence the message is the same as that given above in the paragraph 17-20 (with proposed amendments) on development of a risk profile and paragraph 21-22 on risk ranking. What is new is the involvement of interested parties in the process and this is addressed in the section on risk communication and does not need to be repeated here. In addition, the text is not specific for AMR-related risks but reference could be given to other Codex documents if deemed appropriate.

Commission the AMR-risk assessment

Paragraph 28:

The content of this paragraph duplicates paragraph 27 and other existing Codex texts (e.g. Principles and Guidelines for the Conduct of Microbiological Risk Management CAC/GL 63-2007). The ECMS therefore suggest to delete para 28 and introduce the relevant references , so that para 29 follows immediately after para 27.

Paragraph 29:

The ECMS suggest to amend the last bullet point to read:

• " Timelines for milestones and completion of the risk assessment and review

Paragraphs 30-31:

The ECMS find these two paragraphs out of place in this location with the ‘step-by-step’ structure used. Should this structure be maintained after discussions in next TFAMR, we suggest to move para 30-31 to the end of the Risk assessment section (i.e. para 30-31 to form para 50 bis and 50 ters). The heading does not need to be maintained, as it does not reflect the content of these paragraphs.

Paragraph 34:

The ECMS consider that there is a need to clearly state that sources of information should not be restricted to national sources but should, wherever possible, be expanded to include international sources as well. Therefore, the ECMS would like to propose to amend this paragraph as follows:

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34." Possible Both national and international sources of information should be sought, including: ….."

In addition, the ECMS would like to propose a slight amendment of the first bullet point to align the terminology with what is currently used:

• Monitoring and surveillance programs [...] or plants taking into consideration epidemiological and (microbiological) breakpoints cut off values.

Process of AMR- risk assessment

Figure 2

The ECMS would like to suggest that the figure within the “Exposure Assessment” box in figure 2 would be more appropriately placed under the same heading in the text, just before paragraph 39. This would mean that the figure within the box would have to be numbered separately. The ECMS believe this would make figure 2 more “harmonious” and in our opinion, will improve readability. In addition, given that both "Hazard Characterisation" and "Exposure Assessment" are of equal importance, the dimensions of the Hazard Characterisation box should be increased to equal that of the Exposure Assessment.

Exposure Assessment

Paragraph 41:

To reflect the mobility of plasmids/transposons/gene cassettes the ECMS suggest the following minor change:

41. “When the hazard of interest is the resistance determinant alone, including those in commensal microorganisms, then an exposure assessment should consider whether these resistance determinants can be transferred to human pathogens that subsequently become resistant……..”.

Hazard characterisation

Figure 3:

The ECMS consider that Fig 3 does not reflect the likely importance of commensal microorganisms as hosts for mobile genetic elements and so the ECMS suggest the following amendments to the exposure assessment arrows on the left hand side of the diagram:

Arrow 2: Antimicrobial use selecting resistance determinants in pathogens transferred to other pathogens or commensals.

Arrow 3: Antimicrobial use selecting resistance determinants in non-pathogens commensals transferred to other pathogens or other commensals.

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Risk Characterization

Paragraph 48:

48. Bullet 6: “…. number of microbial microorganisms species …. data are is available ……”

RISK MANAGEMENT

The ECMS would suggest to add the word "options" in the title

RISK MANAGEMENT OPTIONS

Paragraph 51:

The ECMS consider this paragraph (the scope of the former RM document) redundant in this consolidated document and propose it to be deleted.

Paragraph 52:

The ECMS are of the opinion that also this paragraph could be deleted to allow the risk management section to start with paragraph 53.

Paragraph 53:

The ECMS would like to propose that the words "as fully as possible" are deleted. In addition to this comment, the current phrasing of this paragraph gives the impression that the RCPs are collections of risk management options. To align the text with the Codex Procedural Manual, the ECMS would like to suggest the following modification:

53. When considering RMOs to address an AMR food safety issue, risk managers should ensure that Codex Codes of Practices that cover the production to consumption continuum are being implemented as fully as possible. The Codes of Practice contain RMOs that impact control points at which foodborne microbiological hazards exist, provide advice to governments on the application of food hygiene provisions, including those measures that potentially contribute influence to the selection and dissemination of AMR microorganisms. These would include:

Paragraph 55 and Table 1:

The ECMS are of the opinion that the information on supplemental options given in Table 1 should be under the subheading “Identification of AMR-RMOs” (see below). If this suggestion is accepted then the text in this paragraph should be deleted and included later in the text. In addition, in order to further clarify the text the ECMS would like to propose replacing the wording "supplemental options" in para. 55 by "options not mentioned in paragraphs 53 and 54"

Paragraph 56:

The ECMS do not fully understand the meaning of the expression “relevant food chain partners” in this context and would appreciate it if a clarification could be provided.

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Identification of AMR- RMOs

Paragraphs 58-59:

The ECMS believe that much of the text in this section is non-specific or duplicates text given elsewhere. We also think that the Table with supplemental risk management options should be introduced and given in this section and not in the introduction of “Risk management”.

In addition, the ECMS would like to replace the term "evaluation" by "review" in order to avoid problems in the Spanish and French versions of the document. Therefore, we suggest an amendment of the text as follows:

58. Risk managers will generally identify a range of RMOs with the capacity to resolve the food safety issue at hand. In general. To the extent practicable, it is valuable to consider initially a relatively broad range of possible options and then to select the most promising alternatives for more detailed evaluation review.

59. The approach to the identification of options specific to AMR should keep in mind two aspects: 1) the range of points along the food chain where options may be implemented, and 2) the food chain partners who have responsibility and act in various areas of food production. The first aspect seeks to identify areas of the production to consumption continuum that may be amenable to certain measures to reduce risk, such as animal/crop production or the processing of harvested food. Targeted interventions at various stages of these production areas should be considered by risk managers. The second aspect seeks to identify measures that can be developed and/or implemented by various food chain partners.

Paragraphs 60-63:

The ECMS believe that paragraphs 60 and 61 should be deleted as their added value is unclear and it seems to be a repetition of other paragraphs. In addition, the first sentence of para 62 should be deleted. In addition, as previously mentioned, paragraph 55 should be added directly after paragraph 63 (63 bis)

62. In addition, risk assessors, scientists, food policy analysts, economists, and other stakeholders also play important roles in identifying options based on their expertise and knowledge. Specific RMOs may be identified or developed during the process of constructing a risk profile and/or risk assessment. The potential to combine one or more RMOs or integrate them into a comprehensive food safety approach, based on a generic system such as HACCP, should be considered.

63 bis –RMOs described in Table 1 are intended to be examples of RMOs not mentioned in paragraphs 53 and 54 specific for AMR that may be implemented, at the discretion of national/regional authorities and in a manner that is proportional to the level of risk.

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Table 1 – move to this location. Please see comments on the text in the table below:

PRE-HARVEST OPTIONS Animal feed production

Monitor feed and feed ingredients for resistant microorganisms and resistance determinants:

• Consider antimicrobial resistance when assessing the microbiological safety of feed ingredients.

• Set specific maximum limits on resistant microorganisms for feed and feed ingredients.

Implement programs to minimize the presence and transmission of in feed and feed ingredients of antimicrobial resistant microorganisms and resistance determinants of microorganisms in feed and feed ingredients and the transmission of these through feed.

Monitor feed and feed ingredients for resistant microorganisms and resistance determinants:

• Consider antimicrobial resistance when assessing the microbiological safety of feed ingredients.

• Set maximum limits on resistant microorganisms for feed and feed ingredients.

Prohibit or restrict the addition of ingredients with impact on AMR in animal feed.

Food animal production

Regulatory controls on conditions of use: • marketing status limitation, • extra-/off-label prohibition, • extent of use limitation, • avoid or limit use of antimicrobial agents or a specific agent for

disease prevention/prophylaxis in healthy animal not considered to be at risk of infection, Ensure that antimicrobial agents are not used in healthy animals that are not considered at risk

• major label restriction, • withdrawal of authorization.

Development Develop and implementation implement treatment guidelines targeting a specific AMR problem supported nationally or regionally on a voluntary basis prior to regulatory control. Development Develop and regular update of species-specific responsible use guidelines by professional bodies.

Improve accuracy of microbiological diagnosis by national authorities inthe development, dissemination, and use of international standards for

• culture and susceptibility testing • breakpoints and interpretive criteria.

Implement biosecurity and animal health and infection control programs to minimize the presence and transmission of foodborne microorganisms and resistance determinants between animals, to/from animals to humans and

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between flocks/herds: • Active control programs to reduce zoonotic infections without

using antimicrobials. • Changes in production systems to minimize commingling mixing

of naïve animals with other animals and ensuring of appropriate stocking density of animals.

• Improved animal husbandry including eg hygiene and sanitary, measures, housing/ventilation systems and waste management systems, to prevent respiratory infections.

• Improved waste management systems to minimize exposure of animals to manure.

• Implement quality assurance programs as part of good production practice.

• Improved hygiene, sanitary measures (disinfection between “growouts”, rodent controls, use of disinfectants, etc.

• Vaccination when appropriate to prevent disease. • Training of personnel in the improvement of specific husbandry

practices.

Food crop production

Regulatory controls on conditions of use: • marketing status limitation, • extra-/off-label prohibition, • extent of use limitation, • discourage or limit prophylactic preventive use on healthy crops, • limit use to conditions when crops are known to be at risk of

developing disease, • withdrawal of authorization.

Implement use of alternative strategies for specific diseases: • Substitution of antimicrobial use with non-antimicrobial treatments

(chemical and non-chemical) and if not feasible, use antimicrobials in combination with alternative treatments.

• Treating only specific developmental stages where the treatment is likely to be most effective, rather than treating at all developmental stages.

Development Develop and implementation implement crop-specific responsible use guidelines targeting a specific AMR problem supported nationally and regionally on a voluntary basis prior to regulatory control.

Improve accuracy of microbiological diagnosis by national authorities in the development, dissemination, and use of international standards for

• culture and susceptibility testing • breakpoints and interpretive criteria.

Implement biosecurity and infection control programs to prevent minimize the presence and transmission of foodborne resistant AMR microorganisms and resistance determinants between crops and from crops to humans.

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Waste management

Control the spread of AMR microorganisms through other possible sources of contamination:

• Avoid direct use in agriculture of human and animal waste (biosolids, manure)

• Use proper treatment procedures that are designed to reduce or eliminate pathogens in biosolids, manure, and other natural fertilizers.

Implement control measures to limit the spread of antimicrobial resistant microorganisms and resistance determinants of microorganisms through other possible sources of contamination, such as direct use in agriculture of human and animal waste (biosolids, manure):

• Handling and storage systems where biosolids, manure or other natural fertilizers are used on crops or pastures, • Proper treatment procedures designed to reduce or eliminate pathogens in biosolids, manure, or other natural fertilizers, • Appropriate time between applying biosolids, manure, or other natural fertilizers and grazing or forage harvesting (silage and hay making) to allow the applied material to decompose and to minimize contamination, • Proper use and application of biosolids, manure, compost, or other natural fertilizers and plant nutrients, • Monitor biosolids, manure, or other natural fertilizers used in feed production for resistant microorganisms and resistance determinants and • Prohibit the use of biosolids, manure, or other natural fertilizers in food and feed production that exceeds limits on resistant microorganism.

POST-HARVEST OPTIONS Prevent food containing AMR microorganisms and AMR determinants that

constitute a risk for human health, from reaching the consumer. If already placed in the market, withdraw such food from the market for reprocessing or destruction.

Develop and check compliance with microbiological criteria, which define the acceptability of a product or a food lot in accordance with Principles for the Establishment and Application of Microbiological Criteria for Foods (CAC/GL 21-1997) and regulate action to be taken in cases of non-compliance at the level of:

• Sorting • Reprocessing • Rejection • Further investigation.

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Evaluation of AMR-risk management options

Paragraph 65:

The ECMS would like to suggest a new bullet point to be included after the current bullet point 3 (Technical information……) as it considers that this question is relevant and it is not mentioned in the document

Tools and resources to verify the correct implementation of the RMOs

Paragraph 67:

The first sentence of this paragraph is expressed in the Principle 8 (as proposed by the ECMS) Therefore, the ECMS suggest to delete the first sentence here.

67. Because antimicrobials play a major role in animal health, animal health should be considered when evaluating RMOs, but this must be considered secondary to human health protection. Consideration of animal health and welfare could be factors in evaluating RMOs in circumstances where the options are “equally effective” in protecting the health of the consumer.

Paragraph 70:

If the ECMS proposal to follow a harmonised approach throughout the document as proposed for principle 6 is accepted then the wording of this para should be amended accordingly.

Selection of AMR-risk management options

Paragraph 72:

The ECMS in general support the wording of paragraph 72 which indicates that risk managers should weigh the effectiveness of RMOs in relation to the goal against other factors. However, the factors exemplified in the document are mostly negative. Therefore the ECMS would like to suggest rephrasing the last part of this paragraph in order to reflect that also positive effects other than risk mitigation itself may be a factor in decision making:

72. In addition to establishing the ALOP or public health goal and evaluating the effectiveness of RMOs, risk managers must weigh those impacts against other factors that influence decision-making, including the feasibility and practicality of potential measures, cost-benefit considerations, stakeholder concerns, ethical considerations, availability of alternatives (therapeutic agents or husbandry practices), and positive or negative effects on public health or animal health and welfare. creation of countervailing risks such as decreases in the availability or nutritional quality of foods.

In addition, the ECMS noted that the text on ALOP in paragraphs 71 and 72 deals with matters that could be relevant to the prioritization of human health safety issues. This are discussed earlier in the document and in particular, in paragraphs 21 and 22. Therefore, further consideration should be given in relation to the place for these paragraphs.

Paragraph 73:

The ECMS would like to propose the following amendment to paragraph 73:

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73. An important means of reducing human exposure to antimicrobial resistant microorganisms through the food chain is to ensure decrease overall exposure as far as possible by implementing that good hygienic practice and HACCP are being followed….

Paragraph 74:

The ECMS suggest a minor drafting change on the final line to read:

74. “………….cross-resistance, and co-resistance……..”.

Paragraph 75:

To avoid a too high level of detail and to be consistent with risk analysis principles the ECMS would like to propose that the text on what to do in case of high level risk is made more general. In addition, the ECMS would like to add post harvest options as well. The ECMS therefore propose to replace current paragraph 75 with the following paragraph:

75. Where a high specific risk has been identified, measures such as withdrawal of contaminated food or other rapidly applied post-harvest measures might be found most appropriate. Where no urgency has been identified, but where there is clear evidence of a link to usage of a certain antimicrobial in animals and where the risk is high, restrictions of use of this antimicrobial (do not use at all, restrict their use in some species or routes of administration or specific production processes) might be considered. In cases where the level of risk is lower, measures such as information campaigns and prudent use recommendations, including improved farm management, might be found more proportionate to the level of risk.

Implementation of RMO

Paragraphs 76-78:

This text seems redundant as it is not specific to AMR-related risks. It is proposed either to delete the paragraphs (including the title) or if kept for completeness of the document the following deletion is proposed:

76. Risk managers should develop an implementation plan that describes how the options will be implemented, by whom, and when. Risk management decisions are implemented by a variety of parties, including government officials, the food chain partners, and consumers. How to implement AMR-RMOs varies according to the food safety issue and its risk characterization, the specific circumstances, and the parties involved. 77. National/regional authorities should ensure an appropriate regulatory framework and infrastructure. Monitoring and surveillance should be supported by regulation and the enforcement of control measures. 78. To effectively execute control measures, food producers and processors generally implement complete food control systems using comprehensive approaches such as Good Manufacturing Practices (GMP), Good Hygiene Practices (GHP), and HACCP systems. These approaches provide a platform to implement specific food safety RMOs as identified and selected by risk managers.

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Monitoring and review of AMR-RMOs

The ECMS suggest to condense this section to avoid repetitions and to merge with some information given or repeated in the following chapter on Monitoring and Surveillance. More information is available in CAC/GL 62-2007. The ECMS propose the following revision:

79. National/regional authorities should define a process to monitor and evaluate whether the RMOs have been properly implemented and whether or not an outcome has been successful. or food chain partners should evaluate and effectiveness of RMOs regularly, at a predetermined moment in time, and/or following the emergence of significant new evidence that has the potential to alter the approach to address the AMR food safety issue. This should also include the monitoring and review of the provisional decisions. The effectiveness of the RMOs should be assessed against the specific food safety metrics, or ALOP, or public health goals. Appendix 3 contains suggested endpoints that may be monitored.

New 80 (partly from 85). Information from standardized programs designed to monitor the presence of AMR microorganisms and the use of antimicrobials can help establish a baseline against which the effectiveness of RMOs can be measured.

New 81. When considering the results of the monitoring of a specific RMO, the effectiveness and appropriateness of the action taken should be reviewed. The risk management measures should also be reviewed when new relevant information becomes available.

80. Monitoring/control points related to specifically implemented RMOs should be measured to assess the effectiveness and need for potential adjustment. Additional monitoring/control points may be measured to identify new information on the specific food safety issue (e.g., emerging hazard, virulence of a pathogen, change in AMR patterns, prevalence and microbial load in foods, sensitivity of sub-populations, or changes in dietary intake patterns).

81. Governments should define an evaluation process to assess whether the RMOs have been properly implemented and an assessment whether or not an outcome has been successful.

MONITORING AND SURVEILLANCE OF ANTIMICROBIAL USE AND ANTIMICROBIAL RESISTANT MICROORGANISMS AND DETERMINANTS

A clear distinction should be made between the monitoring and review of implemented risk management options and more general programmes. The ECMS suggest to condense this section to avoid repetitions and to move some lines to the section above. The ECMS would like to propose the following revision:

New Paragraph 82 (adapted from parts of 82).

82. Programmes to monitoring of the use of antimicrobials and prevalence of antimicrobial resistance provide information that is useful for all parts of the risk analysis process. Data can be used to explore any relationships between antimicrobial use and the prevalence of AMR microorganisms in food and feed, as input for risk profiling and risk assessment, to measure the effect of interventions

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aimed at reducing antimicrobial use, and to identify trends. The level of detail of data collection could be implemented according to the resources available, or as needed to assess the effectiveness of specific RMOs.

New Paragraph 83 (partly from 83 & 84).

83. Monitoring schemes programmes should be harmonized (CAC/RCP 61-2005 & GL 63) between countries, to the extent possible. Standardized and validated testing methods are also essential to the ability to use information from such programs.

New Paragraph 84 (adapted from 82 & 86).

84. Monitoring of use of antimicrobials should, to the extent possible, include all antimicrobials used in food animal and crop production. Ideally, such monitoring should provide data per animal species or crop. National/regional authorities may use established guidelines such as those described in the OIE Terrestrial Animal Health Code, (Chapter 6.6.), “Monitoring of the quantities of antimicrobials used in animal husbandry” to collect data on antimicrobial usage in animals, and to the extent relevant also in plant production.

(text deleted from 82 and 86: is essential to try to establish the link between the use of an antimicrobial and the prevalence of resistant microorganisms and determinants. For making harmonization in results from assessing the efficacy and comparing the effectiveness of new antimicrobials, referring to a set of standard methods is recommended, or at least it should be stated in the paragraph that standard and valid methods have to be used.

of antimicrobial usage in animals should be compatible with existing monitoring programs taking into account relevant aspects of the drug/microorganisms/animal species/food relationship, approved label indications and if appropriate include data collection at the species level and/or category of animal within species. The level of detail of data collection could be implemented in a stepwise fashion proportionate to the risk, as needed to obtain a consumer protection or food safety goal, or as needed to assess the effectiveness of specific RMOs.

• Authorities should preferably plan the collection and analysis of data on the dissemination of AMR and on antimicrobial usage.

• AMR data should be analyzed with AM usage data together with other relevant data to assess possible relationships.)

85. Monitoring of antimicrobial resistance in bacteria microorganisms originating from animals, plants and food should ideally be integrated with programs that monitor resistance in humans. National/regional authorities may use established guidelines such as those published in the OIE Terrestrial Animal Health Code, Chapter 6.5., “Harmonisation of national AMR surveillance and monitoring programmes” to describe key elements of programs to monitor the prevalence of AMR microorganisms in animals and to the extent relevant also and plant production and food.. Standardized and validated testing methods are also essential to the ability to use information from programs designed to monitor the presence of AMR microorganisms. Information from

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these programs can help establish a baseline against which the effectiveness of RMOs can be measured. Appendix 3 contains suggested endpoints that may be monitored for RMOs. The effectiveness of the RMOs should be assessed against the specific food safety metrics and the ALOP or public health goals.

83. A minimum level of monitoring should be established in order to measure usage and risk management effects

86. Understanding the linkage between antimicrobial use and the prevalence of AMR microorganisms in food and feed will allow risk managers the opportunity to further refine or develop new RMOs. National/regional authorities may use established guidelines such as those described in the OIE Terrestrial Animal Health Code, Chapter 6.6., “Monitoring of the quantities of antimicrobials used in animal husbandry” to collect data on antimicrobial usage. Monitoring antimicrobial use is important in exploring any relationships between antimicrobial use and the prevalence of AMR microorganisms in food and feed, measuring the effect of interventions aimed at reducing antimicrobial use, and identifying trends.

RISK COMMUNICATION

The section needs to be condensed, removing unnecessary overlaps with other Codex texts while maintaining the general idea and those points that are specific for antimicrobial resistance.

Paragraph 87:

The ECMS suggest to delete the first phrase of the paragraph to simplify the text.

87. To better define the food safety issue, the risk manager may need to pursue information from sources that have specific knowledge pertaining to the issue. An open process, in which the food safety issue is clearly identified and communicated by the risk managers to risk assessors, as well as affected consumers and industry, is essential to promote both an accurate definition and a well-understood and common perception of the issue.

Paragraph 88:

To simplify delete the last phrase as this is a reiteration of the previous phrase.

88. Risk communication decision-makers can obtain vital information, provide information, and solicit feedback from interested parties. Communication with all interested parties promotes better understanding of risks and greater understanding on risk management approaches. The great value that communication adds to any risk analysis justifies expanded efforts to ensure that it is an effective part of the process.

Paragraph 90:

90. “Mechanisms may be established for engaging interested parties routinely in food safety decision-making at the national/regional level in a general way.

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Paragraph 91;

The ECMS consider that this paragraph could be simplified as the end is already reflected above under “General considerations" and in the second phrase of the paragraph.

91. Risk communication at this stage should consider the key elements of the preliminary risk management activities by the risk managers through the effective interaction with the interested parties. The scope and the extent of the specific AMR food safety issues including the impact on public health should be clearly determined with open communication among all the parties. It is important to obtain the information from multiple sources regarding the specific AMR risk issues including the known and unknown as well as the perception. Communication is also critical among the risk mangers, risk assessors, and the interested parties for activities on development of a risk profile and/or commissioning of a risk assessment in order to provide evidence-based preliminary RMOs, which are also to be communicated timely to the interested and affected parties.

Paragraph 96:

The ECMS propose a minor drafting change:

96. “……..public awareness on the nature and magnitude of the risk, …………risks…………..risks.”.

Paragraph 97:

The text under paragraph 97 does not seem to belong to “risk communication” but to “risk management”; therefore the ECMS suggest its deletion.

Paragraph 99:

The ECMS suggest adding in “The….” at the beginning of the first sentence.

99. "The Ffood Industry is responsible……"

Paragraph 100:

The ECMS would like to propose re-wording this paragraph to read:

100. Industry (pharmaceutical, food producer, food processor, etc.) associations may find it beneficial should be encouraged to develop and provide guideline documents, training programs, technical bulletins and other information that assists industry to decrease AMR.

Paragraph 102:

The ECMS would like to suggest a minor change in the first sentence as follows:

102. “Consumers can enhance both responsible for adhering to, keeping aware of and following……….”

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REFERENCES:

Editorial: it gives the impression that there is a duplication as the document "FAO/ WHO 2006a, Food safety risk analysis: a guide for national safety authorities" seems to be identical to the document "WHO/FAO 2006, Food safety risk analysis. A guide for national safety authorities" seems to be identical to the document.

APPENDIX 1: SUGGESTED ELEMENTS FOR CONSIDERATION IN AMR-RISK ASSESSEMNT:

In addition in order to explain that the lists are not exhaustive the ECMS propose to add at the end of the first sentence the following:

"….the level of details of the data may vary on a case-to-case basis. This list is provided for illustration and is not intended to be exhaustive and not all elements may be applicable in all situations"

APPENDIX 3: SUGGESTED ENDPOINTS FOR MONITORING THE EFFECTIVENESS OF AMR RISK MANAGEMENT MEASURES

There seems to be confusion between elements from monitoring useful to evaluate the need for risk management measures (e.g. within the frame of the development of a risk profile or risk assessment) and elements/endpoints for monitoring the effectiveness of AMR management measures (already taken). Only a few endpoints seem relevant for the later purpose e.g. bullet points 1 to 3, 9 and 13. It therefore seems useful to reduce the list.