Framework to guide the process for a post-market re-evaluation of medically important antimicrobials for veterinary use

About the re-evaluation framework

We review veterinary drugs (including antimicrobials) before they go on the market and monitor them once they are on the market.

As science evolves, new information may become available about antimicrobials, including medically important antimicrobials (MIAs). MIAs are those important to human medicine (Categories I, II and III as per Health Canada’s Categorization of Antimicrobial Drugs Based on Importance in Human Medicine).

The key objective of this framework is to outline the various steps Health Canada could take to assess the antimicrobial resistance (AMR) risk of MIAs due to their specific conditions of use in veterinary medicine, and what information or actions could be required to support the appropriate risk management measures should Health Canda decide to undertake a re-evaluation of a product.

This framework to re-evaluation:

considers domestic and international best practices for the post-market management of AMR risks,
supports a collaborative approach to the responsible use of antimicrobials, while still maintaining access to safe and efficacious antimicrobials on the Canadian market, and;
aligns with the key pillars of the Pan-Canadian Action Plan on Antimicrobial Resistance.

Key activities to re-evaluation include:

using an evidence and risk-based approach to assess antimicrobial products for animals,
communicating risk and risk management options to implicated stakeholders to support the responsible use of these products, and;
administering the veterinary antimicrobial sales reporting (VASR) system to inform data gaps, assess trends and surveillance and stewardship actions.

Scope

The re-evaluation framework of antimicrobials on List A applies to:

antimicrobials belonging to Categories I, II and III
first-in-class antimicrobials

Factors that may prompt a re-evaluation

The re-evaluation of an MIA or a class of MIAs may be initiated for a variety of reasons that relate to a change in an authorized product's risk-benefit profile. These factors may include:

label claims that do not align with responsible use principles
- for example, the responsible use of MIAs should be limited to treatment and prevention of diseases, and not for long, unspecified time periods in animals
findings of changes in the antimicrobial susceptibility profile, novel AMR trends, or increasing AMR trends in bacteria of public health concern
- for example, this could include evidence from AMR surveillance data that shows possible links to specific veterinary antimicrobial uses
concerns with lack of efficacy
- for example, if there is literature or surveillance data, including pharmacovigilance information, that shows a lack of efficacy in treating a specific disease in animals
emerging scientific information
- for example, the emergence of new resistance gene(s) of public health concern in bacterial isolates of animal origin
international context
- for example, if other regulatory jurisdictions identify veterinary drug-related AMR issues, such as:
  - safety reviews
  - risk mitigation measures

Re-evaluation steps

There are 5 key steps that could be triggered during the re-evaluation. The extent and duration of a re-evaluation depends on:

the amount of information that needs to be assessed, and;
the complexity of the potential issues associated with a given MIA.

The steps applied to the re-evaluation will not be linear and will vary based on the identified risk profile, specific product needs and risk management measures.

Preliminary analysis

We analyze any information to determine whether the drug's established risk-benefit profile warrants a re-evaluation.

The purpose is to:

determine the aspect(s) of concern that may require further investigation
identify what information may be required and the potential sources of information

Notice and preparation for re-evaluation

Before re-evaluation, we will communicate with implicated stakeholders.

We may seek additional information about the drug(s) from:

academics/researchers
the market authorization holder
international regulatory partners
other federal and provincial government departments and agencies

Science-based re-evaluation

The re-evaluation will focus on the:

risk-benefit profile of the MIA
potential for the transfer of resistant bacteria or resistant determinants of public health concern
conditions of use in the intended animal species and the potential to develop AMR, including cross-resistance and co-resistance to MIAs
risk management measures that can be implemented

To identify the AMR risk and assess gaps in the available information, various guidance’s are consulted such as:

Guidance for Industry Preparation of Veterinary New Drug Submissions with emphasis on microbiological safety studies, lack of efficacy or possible changes to clinical use
CODEX Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance

Re-evaluation outcomes

Our re-evaluation may result in recommending various risk management measures. For example:

labelling changes, such as:
- changes to the indication (claim) of the drug
- changes to the drug dosage regime, including the duration of use
- additions or changes to the warning statement(s)
- removal of an indication for an animal species
- removal of an animal species altogether
package size considerations
enhanced AMR and/or antimicrobial use (AMU) surveillance requirements (as part of a post-market approval monitoring program)
enhanced pharmacovigilance requirements, such as enhanced record keeping and education of end-users
stop sale action

Notification of re-evaluation results

When a re-evaluation is completed, we will:

inform the market authorization holder(s) of the findings
work with market authorization holder(s) to implement any needed risk management measures

Depending on the type of change(s), we may share this information in different ways, such as:

targeted communications with stakeholders, and other domestic and international partners, where relevant
posting updated drug labels in the Drug Product Database and the Notice of Compliance Database

Notices

Contact us

For questions, contact us by email: vdd.HSD-DIH.dmv@hc-sc.gc.ca

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2025-03-07