The Canadian Approach to Antimicrobial Related Regulations

Table of Contents

1. Abstract
2. Manuscript
3. Public Health Concerns
4. Canadian Approaches
5. Approval of Veterinary Drugs
6. Distribution and Use of Antimicrobials
7. Controlling Antimicrobial Resistance - An Integrated Action Plan for Canadians - May, 1997
8. Canadian Coordinating Committee for Antimicrobial Resistance (CCCAR)
9. Food Program Policy Framework
10. Antimicrobial Resistance and Use of Antimicrobials in Food Production
11. Food Directorate Antimicrobial Resistance Policy Development Advisory Committee
12. Next Steps

Abstract

In Canada, the Food Directorate (Bureau of Veterinary Drugs) and the Pest Management Regulatory Agency of Health Canada and the Animal Products Directorate of the Canadian Food Inspection Agency (CFIA) each play a role in the federal regulation of agricultural antibiotics. Health Canada, recognizing the impact of antibiotic resistance on human health, co-sponsored a conference with the Canadian Infectious Disease Society in 1997 to address this issue. The Food Directorate is taking the lead role in actioning a number of recommendations derived from this conference. In conjunction with the CFIA and other stakeholder groups, a comprehensive overarching policy aimed at identifying and managing risks associated with agricultural and aquacultural uses of antimicrobial agents will be developed in accordance to the Food Program Policy Framework and its key principles. In 1998, a consultation workshop with multiple stakeholders was held to identify relevant issues related to antimicrobial resistance and the use of antimicrobials in food production. Three key issues identified were the development of a prudent use policy, the need for a comprehensive surveillance program and the prioritizing of research activities to support policy development. A steering committee, capable of providing advice to the Food Directorate, was formed. This committee will meet regularly to identify and prioritize antimicrobial issues, to keep up to date with the latest international regulatory approaches and to provide input into the development of policies on the use of antimicrobial agents in agriculture and aquaculture.

Manuscript

The emergence of antimicrobial resistance among human and animal pathogens has prompted international public health authorities to examine and develop policies related to the responsible use of antimicrobial agents. In Canada, the federal regulation of agricultural antibiotics is the shared responsibility of the Food Directorate (Bureau of Veterinary Drugs) and the Pest Management Regulatory Agency of Health Canada and the Animal Products Directorate of the Canadian Food Inspection Agency (CFIA).

Health Canada, recognizing the impact of antibiotic resistance on human health, co-sponsored a conference entitled "Controlling Antimicrobial Resistance: An Integrated Action Plan for Canadians" with the Canadian Infectious Disease Society in 1997 . Health Canada's Food Directorate is taking the lead role in actioning a number of recommendations from this conference with the ultimate goal to develop key strategies to track usage of antimicrobials, and to control the emergence and spread of antimicrobial resistance from livestock and aquaculture sources. In conjunction with the CFIA and other stakeholder groups, the Food Directorate will develop a comprehensive overarching policy aimed at identifying and managing risks associated with agriculture and aquaculture use of antimicrobial agents. The development of this policy will follow the Health Protection Branch Food Program Policy Framework developed in 1997. This policy framework features five key principles:

All activities must contribute to the protection or improvement of the health of Canadians. Health and safety must be the basis of every stage of the process: risk analysis, science, consultation, process and impact assessment.

Foundation of food policy decision-making is risk-benefit assessment, based on scientific evidence. Recognized risk-benefit assessment and risk management frameworks will be applied

Economic, trade, social and environmental impacts should be considered after establishing the health and safety impact. These impact assessments provide a broader picture of the implications of decisions and they should be based on objective evidence.

A well-defined, transparent process based on good management practices (GMP) will sustain public policy development. GMP means effective communication, consultation, timeliness, predictability, an agreed-upon dispute resolution mechanism, establishing and adhering to a legitimate priority-setting process, commitment to decisions, appropriate resourcing, documentation, a defined process that sets out roles and responsibilities and accountabilities.
Consultation is essential throughout the process: issue identification, prioritization, evaluation and decision-making. At the outset of an issue, all stakeholders must be considered. Consultation may take different forms, and information on issues should be widely available, not just to stakeholders involved in the consultations.

Participants in the process must have credibility (participants must represent and understand the issue) and legitimacy (participant involvement impacts on a decision). It is recognized that not all participants may understand the issue at the outset and an effort must be made from all parties to work toward understanding. Participants should have an involvement in the issue, whether it is a health outcome, an economic interest, or professional expertise. Associations must act on behalf of their membership and should be prepared to disclose information concerning their association (i.e., membership, voting procedure) to other participants. Everyone involved should recognize the different viewpoints of participants.

In June, 1998, the Food Directorate held a consultation workshop with a wide range of stakeholders to identify and define relevant issues related to antimicrobial resistance and the use of antimicrobials in food production. Based on recommendations from this meeting, a steering committee comprising of representatives from stakeholders including the agriculture and aquaculture industries, the pharmaceutical industry, animal health organizations, the Canadian Veterinary Medical Association, health professionals, academia, consumer groups, provincial governments, etc., has been formed. It is the responsibility of this multi-sectoral group to meet regularly to identify and prioritize current issues related to antimicrobial resistance, to keep up to date with the latest international regulatory approaches in this area as well as to provide input into the development of Health Canada policies on the use of antimicrobial agents in agriculture and aquaculture.

Presentation

Public Health Concerns

• Increase in antimicrobial resistance in human pathogens
  • MRSA/VRSA
  • VRE
  • Multi-resistant TB
  • Streptococcus pneumoniae
• Focused attention on the medical and agricultural use of antimicrobials

Public Health Concerns - Link to Agricultural Use

Concerns with antibiotic use in agriculture leading to increasing levels of drug resistance in:

• Multi-resistant Salmonella typhiumurium DT 104
• Fluoroquinolone-resistant Campylobacter jejuni

S. typhimurium DT 104 - Human Isolations in Canada (Source: LCDC)

• 1970: first isolation of DT 104 (sensitive)
• 1989: 4 cases acquired from infected calf (ACSSuT)
• 1993-96: 221/544 (40.6%) of total S. typhimurium
• 1997: 352/766 (46.0%) of total S. typhimurium; 221/348 (63.5%) R-type (ACSSuT); 33% of R-type also resistant to kanamycin, nitrofurantoin and trimethoprim

Residue = Resistance?

Canadian Approaches

Federal Regulation of Agricultural Antibiotics

Health Canada

• Food Directorate
  • Bureau of Veterinary Drugs
• PMRA

Canadian Food Inspection Agency

• Animal Products Directorate
  • Feeds Program
  • Meat and Processed Animal Products

Approval of Veterinary Drugs

• Human safety (toxicity, residue)
• Safety in intended species
• Efficacy
• Manufacturing and Quality Control
• Labelling

Human Safety

• Lab animal toxicity
  • Acute, subacute and chronic
  • Carcinogenicity, mutagenicity and teratogenicity
  • Reproductive functions
• Pharmacology
• Residue Studies

Safety in the Intended Species

• Margin of safety studies
• Reproductive functions
• Clincial trials

Efficacy

• In vitro sensitivity
• Dose titration
• Challenge studies
• Clincial trials

Manufacturing Data

• Drug Substance
• Dosage Form

Labelling

Main Panel:

• Proper name
• Drug identification number
• "Veterinary Use Only"
• Prescription status
• Warnings

Other Panel:

• Drug substance
• Net contents
• Use directions
• Manufacturer's name and address
• Lot number and expiry date

Distribution and Use of Antimicrobials

Variable across Canada...

Not Prescription

• OTC (Provincial - Livestock Medicine Act)
• Livestock Feeds (CFIA- Feeds Act and Regualtions, CMIB)

Prescription (Schedule F)

• under authority of a practitioner licensed by provincial veterinary authorities
• label (DIN), extra-label, EDR

Criteria for Placing Veterinary Drugs on Prescription

• Veterinary drugs likely to be diverted to human medicine
• Veterinary drugs for which instructions easily understandable by a lay person is not available
• Veterinary drugs hazardous to the administrator
• New antibiotics for veterinary medicine which are useful in human medicine

Figure 1. Health Canada - Building consensus among stakeholders.

Controlling Antimicrobial Resistance - An Integrated Action Plan for Canadians - May, 1997

Conference Summary:

Visit Health Canada's Website

Outcome:

• Action plan with 27 recommendations
• Use, detection, partnerships and communication

Recommendations...

• "To establish a multidisciplinary coordinating committee to facilitate implementation of the 27 recommendations..."
• e.g. To reduce antimicrobial prescriptions by 25% within 3 years by focusing on community acquired respiratory infections

Canadian Coordinating Committee for Antimicrobial Resistance (CCCAR)

Goal

To promote development and implementation strategies to focus efforts toward the goal of more effective and efficient use of antibiotics, and to limit the development and transmission of antimicrobial resistant organisms.

• communication
• promote networks
• provide clearing house for information

From Controlling Antimicrobial Resistance - An Integrated Action Plan for Canadians - May 1997...

"To establish a national surveillance system to monitor antimicrobial resistance and use in the agri-food and aquaculture sectors..."

Food Program Policy Framework

• 1997 - Development of a new process in Food Program for any major new policy or regulatory change.
• Process was developed in full consultation with staff and stakeholders
• January 1998 stakeholder meeting - Five key principles and process stages identified.

Policy Framework Principles

• All activities must contribute to the protection or improvement of the health of Canadians
• Foundation of decision making is risk benefit assessment, based on scientific evidence
• Economic, trade, social and environmental impaces considered after health/safety impact established. Impace assessments are based on objective evidence.
• A well defined transparent process based on good management practice will sustain public policy development

Consultation is essential throughout the issue identification, prioritization, evaluation and decision making process.

• HPB Coordination
• Stakeholder Steering Committee
• International liaisons
• Closer linkage with CCCAR
• Supporting surveillance and research initiatives
• Risk assessment

Antimicrobial Resistance and Use of Antimicrobials in Food Production
Stakeholder Consultation Workshop - June 10, 1998

Food Producers: poultry, beef, dairy, pork, aquaculture
Academia: Veterinary epidemology, microbiology, CARC
Consumers: CAC, CSPI, Sierra Club
Government: Federal/Provincial Agriculture, Health
Public Health: Hospital Infection Control, Reg. Health Unit, Epidemiology
CVMA, CAHI, CCCAR

Three key areas for discussion:

• Development of prudent use policies
• Surveillance
• Research and Development

Concerns and Suggestions

• Prudent use: Implications of international policies on trade, risk-benefit, supporting science.
• Surveillance: Use data, standardization, confidentiality, cost
• Research: Alternatives, epidemiology, intervention strategies, cost
• Need to form an advisory committee

Food Directorate Antimicrobial Resistance Policy Development Advisory Committee

Membership - A small multi-sectoral group of experts representing a balanced perspective from a wide range of interested external parties.

Scope - Focus on the potential human health and safety impact(s) associated with agricultural, aquacultural and other non-human uses of antimicrobial agents.

Role and Mandate - Provide advice and assistance to the Director, Bureau of Food Policy Integration, Food Directorate, in the development of policy options related to teh use of antimicrobial agents...

• Issue identification and prioritization
• Expert advise on preparation of draf policy documents
• Analyse issues, generate options and make recommendation concerning potential solutions
• Provide feedback to stakeholder groups

Next Steps

• Official Establishment of an Expert Advisory Committee - October, 1999
• First Meeting of Expert Advisory Committee - December, 1999
• Establishment and Coordination of a National Surveillance Program

Related Links

• Controlling Antimicrobial Resistance - An Integrated Action Plan for Canadians

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