Post-market re-evaluation of medically important antimicrobials for veterinary use

On this page

• Notices
• Approach to re-evaluation
• Evidence-based factors that may prompt a re-evaluation
• Steps of the re-evaluation process
• Contact us
• Related links

Notices

• Notice to stakeholders: Post-market re-evaluation of medically important antimicrobials for veterinary use with unspecified or prolonged durations of use [2022-05 -10]

Approach to re-evaluation

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. We will use an evidence-based approach to conduct re-evaluations on MIAs previously authorized for veterinary use.

The key objective of the re-evaluation is to determine whether the availability of MIAs or specific conditions of their use in veterinary medicine may contribute to anti-microbial resistance (AMR) in humans (that is, whether it increases the risk that MIAs become ineffective in treating infections in humans).

This approach to re-evaluation:

• considers domestic and international best practices for the post-market management of AMR risks
• is one of several inter-connected initiatives aimed at taking action to address AMR and promote the responsible use of antimicrobials in animals

Our key activities include:

• using an evidence- and risk-based approach to evaluate antimicrobial products for animals
• collaborating with key stakeholders to support the responsible use of these products
• assessing data on the sale of MIAs to:
  • support the surveillance and interpretation of trends of AMR
  • monitor the effectiveness of these actions to slow the development of resistance

These initiatives are consistent with activities outlined in the Federal Action Plan on Antimicrobial Resistance and Use in Canada and Tackling Antimicrobial Resistance and Antimicrobial Use: A Pan-Canadian Framework for Action.

Scope

The evidence-based approach to the re-evaluation of antimicrobials on List A applies to:

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

We will consider using this approach for the post-market re-evaluation of other veterinary drugs, as appropriate, to protect the health of Canadians.

Evidence-based 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
  • the responsible use of MIAs is 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

Steps of the process

There are 5 key steps to our re-evaluation process. The extent and duration of a re-evaluation depends on:

• the amount of information that needs to be assessed
• the complexity of the potential issues associated with a given MIA

We will work with impacted stakeholders on timelines and processes for particular re-evaluations.

Step 1 – Preliminary analysis

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

Step 2 – Notice and preparation for re-evaluation

Before we undertake a re-evaluation, we will communicate with affected 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

Step 3 – 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

We will assess the risks of AMR using various guidances, 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

Step 4 – Re-evaluation outcomes

Our re-evaluation may result in using various risk management measures supported by authorities under the Food and Drugs Act and regulations. These measures may include:

• 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

Step 5 – Notification of re-evaluation results

When we complete the re-evaluation, we will:

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

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

• communicating with stakeholders, and other domestic and international partners
• posting updated drug labels in the Drug Product Database and the Notice of Compliance Database

Contact us

For questions, contact us by email: hc.vdd.vetdrugs-medsvet.dmv.sc@canada.ca