Recommendations to CCRVDF on risk management
A) Substances, whose residues are generally recognised as highly toxic and which should not be used as veterinary drugs have to be addressed by the Codex Alimentarius:
CCRVDF should identify these substances and develop a policy that aims to ensure that they are not used in food animal production.
There is also a need for an agreement on parameters for the analytical methods that are used to determine the residues of unsafe drugs. Specifically the requirements for the detection capability and performance of such methods should be discussed and harmonized, if possible.
CCRVDF should establish harmonized criteria and rules for the evaluation of food consignments containing residues of these substances.
All of the above should not condone the illegal use of these substances.
For veterinary drugs which, because of health concerns, JECFA cannot allocate an ADI and recommend an MRL, CCRVDF should request that JECFA perform and report, if possible, an estimate of the risks associated with the anticipated exposure of consumers to the residues of the veterinary drug. Such risk estimates would be useful for management of risks associated with the residues.
The Codex Alimentarius Commission should include consideration of cost-benefit and risk comparisons in its risk analysis policies.
The recommended performance level (RPL) for regulatory analytical methods should be established by the risk manager to reflect the toxicological risk of the veterinary drug residue and/or the control strategy chosen by the competent authority.
B) For substances which have been evaluated by national governments and are legally used in many countries but which have no Codex MRL, CCRVDF should develop a more comprehensive approach which would allow completion of the work on MRLs within the coming ten years.
Such an approach should aim to elaborate a comprehensive list of MRLs that cover all substances used in veterinary drugs. It is recognized that efforts are already being made to address this and that several options exist.
One option would be to ask JECFA to perform risk assessments for all these substances. However, the considerable number of substances, the resources required for their evaluation, and the lack of sponsors make this option less attractive.
Another option would, with the assistance of JECFA, be the creation of an initial list of temporary/operative MRLs which is based on national/regional MRLs and their accompanying assessment reports which have been adopted using a procedure that applies risk assessment principles. This initial list should be valid for a certain time period (to be determined by Codex) and the MRL should subsequently be made permanent if (a) no comments have been received that put the original risk assessment into question, or (b) JECFA was enabled to establish an ADI based on review of the underlying data and to propose an MRL. Substances which do not fulfil either of these conditions should be moved to a list of compounds not to be used in food animals.
In this context, CCRVDF should monitor the progress of the CCPR/JMPR pilot "Work sharing" project and consider the development of a policy and mechanisms (including cooperation of drug sponsors and national/regional veterinary drug approval authorities) for the use of national and regional risk assessments by JECFA in order to expedite review and avoid unnecessary duplications of effort. The JECFA would be a peer review forum with particular focus on the international considerations.
C) Drugs which are seen as important in developing countries should be assessed by a consultative process that may involve JECFA and subsequently be added into the temporary list of the abovementioned second option. It is noted that this approach still requires significant work and support from developing countries since the conditions of use (species, dosage regime, waiting periods) of these drugs are not known outside of the country. In order to facilitate this work, FAO and WHO should explore the development of more detailed procedures to develop MRLs for species where data do not exist by extrapolating from existing data. It is urgently required that the Joint FAO/WHO Project to Update the Principles and Methods for the Risk Assessment of Chemicals in Food develops guidance to JECFA that would allow extrapolation of the data from species to species. In parallel, CCVRDF should develop a corresponding risk assessment policy.
CCRVDF should amend its procedures in its ad hoc working group on priorities for selection of veterinary drugs for JECFA evaluation to facilitate development of MRLs for veterinary drugs routinely used by developing countries in their food animal production programmes and take other measures as appropriate to meet this critical need.
FAO and WHO should convene an expert workshop to consider the needs for veterinary drugs for aquaculture.
D) CCRVDF should expedite completion of its revised guidance for science-based residue (regulatory) control programmes and analytical method validation for residue control programmes.
E) CCRVDF should complete development of its risk management policy to provide assistance to governments, with particular attention to developing countries, for improving their science-based regulatory framework for control of residues of veterinary drugs in food, including those veterinary drugs without an ADI or MRLs.
Recommendations related to risk assessment and JECFA
F) Mathematical tools such as the Benchmark Dose approach, low dose extrapolation and others can make better use of dose-response information so that it is possible for the risk manager to use the estimate of the risk to the human consumer at different exposure levels to manage the risk. It is recommended that the CCRVDF request that the JECFA develop approaches for the use of tools such as these to provide risk estimates when there is no ADI or MRL.
For compounds with extensive human use, clinical, non-clinical, and epidemiological data may be used to provide information on the dose-response characteristics of the drug. These data may be evaluated using mathematical extrapolation techniques such as the Benchmark Dose approach to estimate the concentration of veterinary drug with no appreciable risk in food or to estimate the risk of a given concentration of the drug in food.
G) CCRVDF and the JECFA meetings evaluating residues of veterinary drugs should work with the Joint FAO/WHO Project to Update the Principles and Methods for the Assessment Chemicals in Food to evaluate additional tools to assess the risk of veterinary drug residues, particularly in those instances where an ADI may not be established. Closer interaction between risk managers and risk assessors should result in the development of different approaches to the risk analysis of low level residues.
H) The JECFA meetings evaluating food additives and contaminants, and some national/regional authorities (FDAs Center for Food Safety and Applied Nutrition, European Commission) have validated the approach of a threshold of toxicological concern for low level exposure to certain classes of compounds (examples include flavouring agents and food contact materials as indirect food additives). It is recommended that Codex work in conjunction with JECFA to consider the margin of exposure and threshold of toxicological concern approaches being considered by Australia and Japan, respectively, as discussed in the working papers of this workshop. Approaches being considered by international activities (link with other ongoing activities) such as the Joint FAO/WHO Project to Update the Principles and Methods for the Assessment Chemicals in Food should also be addressed.
Recommendations to governments
I) Governments should develop and implement food safety regulatory frameworks with the participation of all stakeholders to ensure sustainability of safer food animal products.
J) Governments should focus on preventive measures for residue control to ensure compliance with science-based national food safety standards (e.g., MRLs) through good veterinary practice in accordance with Codex Guidelines on the Establishment of a Regulatory Programme for Control of Veterinary Drug Residues in Foods (CAC/GL 16-1993).
K) Analytical laboratories should develop adequate sample preparation procedures in cases of analysis of processed foods to ensure appropriate analysis of matrices of animal origin.
Recommendations to FAO, WHO and other international organisations
L) To facilitate transparency and the sharing of scientific analytical methods for the control of residues, it is recommended that FAO, in cooperation with other international agencies, develop an international network among official residue control laboratories.
Recommendations on capacity building
M) When Codex documents are updated or developed, this should be done in a way that the texts are easily understandable and readily implementable.
N) Some developing countries require specific advice and technical assistance on:
Legislation pertaining to the responsible use of veterinary medicines and on the control of production, importation, registration and distribution of veterinary medicines. Individual countries should make a formal request to OIE and FAO for assistance.
Risk analysis of drugs without ADI/MRL. Individual countries must specify their exact needs to FAO and WHO.
Organization of forums and formulation of training modules to promote the responsible use of veterinary medicines at farm level, explaining the possible economic & public health consequences of misuse/abuse of veterinary medicines. This should be addressed by FAO.
The theory and practice concerning the application of appropriate analytical methods. This may be directed towards screening technologies and/or towards more sophisticated confirmatory technologies, as dictated by the needs of the individual country. This should be addressed, to the Joint FAO/IAEA Division at IAEA.
Best practice on analytical method validation and assessment of Measurement Uncertainty according to international guidelines. This may be addressed by seeking technical assistance from international funding agencies.
O) International bodies and governments that fund international research projects should give preference to those project applications that incorporate developing countries as end-users of the developed technologies and processes. This would enhance the funding body's capacity building efforts and would ensure that developing countries have an opportunity to be associated with state-of-the-art international research.
P) International agencies should work more closely together to ensure the efficient use of the funds available for capacity building at a global level. This may be facilitated by interaction with the Standards and Trade Development Facility (STDF). This facility is managed by FAO, WHO, World Bank, WTO and OIE.
