the codex view on veterinary drug residues 4 th international symposium on food safety sao paulo, sp...
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The Codex View on Veterinary Drug Residues
4th International Symposium on Food Safety
Sao Paulo, SPJune 13-14, 2005
Richard Ellis, Ph.D. FDA-CVM
A view of Codex, CCRVDF and Food Safety
• Codex principles and objectives• Codex Committee on Residues of
Veterinary Drugs in Food (CCRVDF)– Terms of reference and working principles
• CCRVDF Risk Analysis - CCRVDF and JECFA roles
• Current areas of interest in CCRVDF – Substances without ADI and MRLs
Codex Alimentarius Commission (CAC)
•The Joint FAO/WHO Food Standards Program
•Three objectives
•Consumer protection
•Fair practices in food trade
•Co-ordination of all food standards work
•172 Member Governments (>98% world population)
•Meets annually
•Adopts draft Codex standards
•Reviews the Program of Work
•Reviews the budget
FOOD & AGRICULTURE ORGANIZATION
OF THE UNITED NATIONS
ECONOMIC & SOCIAL DEPARTMENT
FOOD & NUTRITION DIVISION
FOOD QUALITY & STANDARDS SERVICE
FOOD STANDARDS
GROUP (CODEX)
FOOD QUALITY LIAISON GROUP (JECFA)
Codex General Subject Committees
• General Principle (France)• Import/Export Inspection and Certification
Systems (Australia)• Food Labeling (Canada)• Methods of Analysis & Sampling (Hungary)• Food Hygiene (USA)• Residues of Veterinary Drugs in Food (USA)• Pesticide Residues (Netherlands)• Food Additives & Contaminants
(Netherlands)
Active Commodity Committees
• Nutrition and Foods for Special Dietary Uses (Germany)
• Fats and Oils (UK)• Fish and Fishery Products (Norway)• Milk and Milk Products (New Zealand)• Fresh Fruits and Vegetables (Mexico)• Cocoa Products & Chocolate (Switzerland)• Meat Hygiene (New Zealand)• Processed Fruits and Vegetables (USA)
Codex Committees & Task Forces
• Ad hoc Inter-governmental Task forces– Fruit and Vegetable
Juices (Brasil)– Food Derived from
Biotechnology (Japan)– Animal Feeding
(Denmark)
• Regional Coordinating Committees– Asia (Korea)– Africa (Morocco)– Europe (Slovak
Republic)– Latin America and
Caribbean (Dominican Republic)
– Near East (Jordan)– North America &
Southwest Pacific (Samoa)
Codex Standard Development Process
• Always initiated by CAC
• Normal Procedure:– Eight (8) Steps– 2 rounds of written
comments– 1 round of comments
can be omitted (by vote)
• Accelerated Procedure:– Five (5) Steps– 1 round of written
comments
• 1. Decision of CAC• 2. Proposed draft
standard• 3. Request for written
comments• 4. Amendments/Session• 5. Adoption of draft
standard• 6. Request for written
comments• 7. Amendments/Session• 8. Adoption as a Codex
standard
Major Codex (CAC) Accomplishments
• Food standards for commodities: 237• Codes of hygienic/technology practice: 41• Food Additives evaluated: 1005• Guidelines for contaminants: 25• Pesticides evaluated: 185• Pesticide MRLs: 3274• Veterinary drugs evaluated (1986-date): 80 • Veterinary drug MRLs: (39 to 28th CAC) 393• Veterinary drugs without ADI: 29
GATT, WTO and Codex
• 1994 General Agreement on Tariffs and Trade attached significant importance to food safety agreements– Referenced specific steps to protect the
sanitary status of member countries and reduce barriers to trade
– Elaborated food safety agreements for the Sanitary and Phytosanitary (SPS) and Technical Barriers to Trade (TBT) measures
– Established the World Trade Organization
Implications of WTO Agreements
• SPS Measures:– Discourage the use of SPS measures as barriers to
international trade– Recognizes Codex as a reference on food safety– Codex may be used to settle trade disputes– Calls for harmonization based on Codex (standards)
• TBT Measures:– Prevents the use of technical requirements as
barriers to trade– Covers all consumer protections not covered by SPS– Places emphasis on international standards for foods
Food Safety Provisions Recognized by SPS
• Maximum residue limits for pesticides and veterinary drugs
• Maximum level of use of food additives
• Maximum levels of contaminants
• Food hygiene requirements of Codex standards
Codex Provisions Recognized by TBT
• Food labeling
• Quality provisions
• Nutritional requirements
• Methods of analysis and sampling
National Regulations and Codex
• National regulations that are consistent with Codex standards meet the requirements of the SPS and TBT measures
Codex Committee Residues of Veterinary Drugs in Food
• CCRVDF established 1986, 15 sessions to date
• CCRVDF has four responsibilities– Priorities for veterinary drug residues in food– Recommend maximum residue levels – Consider methods of analysis and sampling– Develop codes of practice
• CCRVDF has three ad hoc working groups – Priorities, methods of analysis and sampling
and drugs without ADI and MRLs
• Role of Science and scientific principles
Role of Science in Codex-Statements of Principle
• Food standards based on scientific analysis and evidence to assure quality and safety of foods
• Regard other legitimate factors relevant to health protection of consumers
• Food labeling is important for protection of consumers and promoting fair food trade practices
• When members agree on level of protection but differ on other concerns, they may abstain from but not prevent decisions by Codex
Statement of Codex Principle onRole of Food Safety Risk Analysis
• CCRVDF endorses the statements of principle in standards development (MRLs and codes of practice):– Health and safety aspects of Codex decisions and
recommendations should be based on a risk analysis appropriate to the circumstances
– The risk analysis should be soundly based on science and incorporate the four steps of the risk assessment process and documented in a transparent manner
– There should be a functional separation of risk assessment and risk management recognizing pragmatic interactions
Major & New CCRVDF Accomplishments
• Codex Alimentarius Volume 3: Residues of Veterinary Drugs in Food (parts being revised)– List of MRLs (1995)– Code of practice for control of use of veterinary drugs– Guidelines for establishing a regulatory program for control
of veterinary drug residues (methods and sampling guidelines)
– Glossary of terms and definitions
• Code of practice to minimize antimicrobial resistance (at step 8)
• New initiative on substances without an ADI or MRLs (new working group established)
• New risk management policy under development• Revision on analytical methods sections in Volume
3• Revision of guidelines for residue control programs
CCRVDF Risk Assessment & Risk Management
• Risk assessment expert advice provided by JECFA – Joint FAO/WHO Expert Committee on Food Additives
CCRVDF proposes vet drug for MRLs
CAC approves new work
JECFA receives request for evaluation
JECFA Secretariats invite experts
Determination of ADI and MRLs
CCRVDF reviews and decides on MRLs
JECFA - The Risk Assessors
• Members are invited by WHO and FAO as experts in their independent, personal capacity
• Meetings are ad hoc, meeting only when needed• For reasons of confidentiality and prevention of
external influences, meetings are closed sessions– Results are made public immediately thereafter
• Provide scientific advice on specific issues for:– FAO and WHO member countries– FAO and WHO governing bodies– Codex Alimentarius Commission and subsidiary Codex
Committees (e.g., CCRVDF)
First Things First – The ADI
• Adverse systemic effects• Reproduction and developmental effects• Mutagenic effects• Carcinogenic effects• Effects on human intestinal flora• Immunologic effects• Pharmacological properties• Endocrine effects
Specific Considerations -ADI
• The extent of data needed depends on dietary exposure
• Determine if residues are normally present in edible tissues
• If drug is also used in humans, data from human case reports and epidemiological studies
• Special studies to investigate specific effects of mechanisms of toxicity
• An effect and no-effect dose level should be determined from these studies and tests
Studies for Recommending MRLs
• Chemical identity and properties• Uses and recommended doses in food animals• Pharmacokinetic, metabolism and
pharmacodynamic data• Total residue (radiolabel) studies• Residue depletion studies in food animals• Available routine method of analysis including
method performance• Special studies on residue effects as
necessary
From an ADI to MRLsADI
MRLT
If MRLU < MRLT
If MRLM > MRLU
and MRLM < MRLT
use MRLM
If MRLM ≤ MRLU
Use MRLU
If MRLU > MRLT
No MRL recommend
ed
If MRLT ≥ MRLM
use MRLT
If MRLT < MRLM
No MRL recommended
CCRVDF Recommendation Process
• CCRVDF receives JECFA recommendation at Step 3 and proceeds through Step 8 with a recommendation to Codex Alimentarius 1. Decision of CAC
2. Proposed draft standard3. Request for written comments 4. Amendments/Session5. Adoption of draft standard6. Request for written comments7. Amendments/Session8. Adoption as a Codex standard
Codex Alimentarius Commission Options
• Adopt CCRVDF recommendation as a standard
• Hold the recommendation pending additional information from CCRVDF or JECFA
• Request CCRVDF reconsideration based on CAC comments on matters of concern (e.g., new scientific studies)
• Reject CCRVDF recommendation (e.g., due to a lack of consensus)
Current Matters of CCRVDF Interest
• Report of 15th Session Alinorm 05/28/31 http://www.codexalimentarius.net/web/reports.jsp?lang=en
•MRLs from JECFA recommendations
•Code of Practice to Minimize and Contain Antimicrobial Resistance
•Revised guidelines for establishing a regulatory program for control of veterinary drug residues in food
•Revised General considerations on analytical methods
•Rounding of ADIs for veterinary drugs
•Veterinary drugs without ADI/MRL
MRLs Recommended for 28th CAC
• Step 8– Cyhalothrin: cattle, pigs, sheep –muscle, liver,
kidney, fat and cattle milk– Flumequine: cattle, pig, chicken, sheep –
muscle, liver, kidney, fat and trout muscle– Neomycin: cattle – liver, kidney and milk– Dicyclanil: sheep – muscle, liver, kidney and fat
• Step 5/8– Imidocarb: cattle – muscle, liver, kidney, fat and
milk (recommended MRLs in sheep withdrawn)
CCRVDF – Antimicrobial Resistance
• Responsibilities of regulatory authorities– Assessment of efficacy and safety, surveillance,
distribution, advertising, training, research, etc.
• Responsibilities of veterinary pharmaceutical industry– Marketing authorization, export, advertising, etc.
• Responsibilities of wholesale/retail distributors
• Responsibilities of veterinarians– Off-label use, records, training
• Responsibilities of producers
CCRVDF Revised GuidelinesRegulatory Program
• Revision of current Codex Volume 3 regulatory control guidelines (published 1995) needed
• Current document precedes Codex adoption of HACCP food safety principles
• CCRVDF scope will be a more holistic approach– Risk based approaches to regulatory programs – Residue control programs for food producing
animals and food producing animal products (e.g., milk)
Early in development (Step 2)
CCRVDF – Methods of Analysis
• Similar activity for Codex Volume 3 - review and amend Part II on General Considerations
• Coordinated by ad hoc Working Group – Methods of Analysis and Sampling
• Update following the recent Codex decisions on analytical method performance – e.g., method validation procedures
• Expand compendia of analytical methods for review by ad hoc working group
CCRVDF – Risk Management IssueRounding of JECFA ADIs
• Potential differences with ADI calculation by JECFA and member governments (e.g., very small ADI)– JECFA rounding ADI to one significant figure– Numerous examples - 11 higher, 14 lower
• Related issue with differences in MRLs • Three recommendations considered –preferences:
– JECFA: use calculated ADI, round ADI for publication of JECFA recommendation
– CCRVDF: use calculated ADI and publish the calculated ADI as the JECFA recommendation
CCRVDF will apply to future evaluations and recalculations of substances already considered by JECFA case-by-case
Veterinary Drugs Without ADI and MRLs
• Growing concern with significant consequences
National action levels based on detection limits
Significant increases in detection capabilities
Increased dependence on MS and LC-MS/MS
A technology imbalance between primarily import and export countries
Increased prevalence of residues of concern
Rejection of imported products
With no ADI/MRL:
Result: International Trade Disruption
CCRVDF and FAO/WHO Response
• Seriousness of issue raised primarily by developing countries highly dependent on export trade at CCRVDF– Thailand and Argentina highlighted issues with
emphasis on nitrofuran and chloramphenicol in food products
• CCRVDF and FAO/WHO agreed to hold a technical workshop on the issue– Held in Bangkok in September 2004
Bangkok Consultation
• Risk assessments/Analytical methodologies– Progress of analytical methods and impact on
international trade– Analysis and management of risk of low level
residues– Risk assessments by JECFA
• Regulatory framework/Capacity building– Regulatory framework at the national and
regional level– International regulatory framework provided by
Codex and WTO– Capacity building
Analytical Methods Impact on Trade
• National action levels based on detection limits
• Detection capabilities based on best science and latest technology
• “Best” (and costly) instrumentation
• Development of methods in
a regional laboratory
• National action limits based on hazard or risk estimates
• Detection capability based on hazard or risk
• Instrumentation to accomplish regulatory need
• Availability of methods across laboratories
Management of Risk - No ADI/MRLs
No ADI/MRL
Toxicological data did not support an ADI
No suitably validated analytical method
Good agricultural practice could result in exceeding possible MRL
No valid sponsor
Residue data are insufficient to support an MRL
Use conditions not
consistent with ADI
Management of Risk - Low Level Residues
• In the absence of an ADI and MRLs:– National authorities may regulate to no detectable
residues– The prevalence of residues of concern changes as
analytical method detection capability improves
• Changes in technology and improved detection capability results in previously non-detectable residues becoming reportable
• Change in reported amounts of residues is independent of toxicological risk
CCRVDF and JECFA Critical Issue of Managing Risk of Low Levels of
Residues
Considering the close relationship between the nature and extent of available data and the ability to establish an ADI and MRLs:
What data does JECFA need to establish an ADI and MRLs?
How does JECFA obtain the necessary data to establish an ADI and recommend MRLs?
•Need alternate approaches to evaluate data for an ADI
•Need alternate approaches to an ADI to evaluate risk and safety
JECFA Risk Assessments - Current Scenario
Large number of substances currently used in veterinary medicine
ADI and MRLs recommended
No ADI/MR
L
Developed
countries
Major uses
No sponsor no dataMinor uses?
Developing country needs?
Regional needs?
Substances
evaluated by JECFA
Regulatory Framework/Capacity Building
• 12 of the 23 discussion papers addressed regulatory frameworks on six continents
• Three had unique features and many others provided general nature details – the unique:– Margin of Exposure concept– Positive lists for agricultural chemicals in food– Spectrum of residue control programs and
capability within a continent
Regulatory Lessons Learned
• No ADI/MRL – “No detectable residues”
• Risk communication: Difficulties with managing perceptions of foods not being “legal”, yet of low risk to public health and safety
Public policy
Analytical technology
Public health
Regulatory Framework Discussions
Regulatory framework componen
ts
Data and information systems
Public health
objectives
Legislation, regulations and
guidance documents
Suitable analytical methods
Effective surveillance
and compliance
Risk based residue control
program
Adequate technical resources
Status quo: Framework capacity differs significantly between countries
Identified Regulatory Framework Weaknesses
• Lack of high commitment to national policies
• Low priority commitment to national food safety measures
• Inadequate resources for food safety programs
• Lack of coordination among relevant stakeholders
• Stakeholders not always involved in developing food safety programs
• Limited numbers of safe veterinary drugs with Codex MRLs for adoption by national governments
• Inadequate enforcement to ensure judicious use of veterinary drugs
Measures to Facilitate Improvement
• Improved awareness and commitment to public health protection and international trade
• Designing capacity building to meet specific national needs
• Encourage stakeholder involvement in food safety programs
• Improve coordination and communication among competent authorities for food safety programs
• Implement mentoring programs with countries having comprehensive food safety programs
• Improve good veterinary drug practices especially at the farm level
Promising Factors to Improve Food Safety Programs
• Marketing access and economic factors
• Consumer demand for safer foods
• Export market access increases demand and need for safer and higher quality food
• Ending international trade and market disruptions
• Increasing attention to substances without an ADI or MRL
• Better attention to WTO/SPS obligations
• Recognizing that developing countries are not receiving full benefit of the SPS provisions
Codex and WTO Problems and Gaps
• Codex (CCRVDF) has not fulfilled its mandate to evaluate all veterinary drugs posing a potential significant threat to health and consumer risk
• Where JECFA has evaluated but not established and ADI or MRLs, these substances are “forgotten” and disappear from adoption procedures
• WTO notification procedures seem to be inadequate, not assuring sufficient consultation and involvement of exporting countries
• Summary: No comprehensive set of standards for implementation by member governments results in a patchwork of national solutions
Capacity Building: Issues and Approaches
• Building capacity is frequently driven by growth of consumer demand for safer food
• Lack awareness of roles and responsibilities of international agencies (e.g., FAO) and organizations (e.g., Codex) that impedes capacity development
• Ability to provide needed expertise is limited by developing country resources and commitment
• Effective capacity building requires a global vision and commitment at the highest levels
• Needs to be approached in a holistic manner• Should be directed to the most appropriate sector
in recipient countries
Bangkok Recommendations
• Five blocks of recommendations– To CCRVDF on risk management– To JECFA on issues related to risk assessment– To governments– To FAO, WHO and other international
organizations– To organizations addressing capacity building
Highlight Recommendations
• CCRVDF and JECFA should develop a list of substances not to be used as veterinary drugs (and not condone their illegal use)
• Develop an approach to prepare a comprehensive list of MRLs covering all substances used as veterinary drugs within the next ten years
• CCRVDF should facilitate creation of a list of drugs that are seen as important to developing countries
• CCRVDF should complete development of its risk management policy and update its guidance documents
Highlight Recommendations (2)
• Develop approaches for using techniques providing dose-response characteristics and estimates of risk when no ADI or MRL
• Develop new approaches to the risk analysis of low level residues
• Develop a holistic approach to capacity building with international organizations
CCRVDF Establishes a New Working Group
• CCRVDF agreed to a Circular Letter to collect necessary information on– 1) all substances with no Codex MRLs used at the
national level; 2) substances that raise health concerns; 3) substances that create trade problems; 4) substances for inclusion on a negative list; 5) national or regional MRLs; and 6) information on analytical methods detection or determination
• CCRVDF defined the specific tasks– 1) establish lists to circular letter request; 2) prioritize
listed compounds for future consideration; 3) develop recommendations on how to proceed with priorities; 4) develop risk management options; and 5) develop a timetable for action