Submitting risk management plans guidance document: Canadian-specific addendum template

A Canadian-specific addendum should address:

• risks or uncertainties that are unique to the Canadian context
• measures that the manufacturer intends to take that are unique to the Canadian context

Information may vary, however, a Canadian-specific addendum should contain the following sections:

• cover page
• safety specification
• pharmacovigilance measures in Canada
• risk minimization measures and evaluation of their effectiveness in Canada
• references
• appendices

However, indicate if the sections:

• do not apply
  • indicate that the section is not applicable, along with a rationale
• do not have Canadian specific content
  • indicate that the Canadian context does not differ from that in the reference RMP, there are no risks or uncertainties unique to the Canadian context or the measures the manufacturer intends to take described in the reference RMP apply to the Canadian context

Cover page

The cover page of the Canadian-specific addendum should include:

• a title that includes the name of the product or the proposed brand name and that it is a Canadian-specific addendum to the reference RMP
• the proper name or non-proprietary name of the drug in final dosage form
• the version, date of final sign-off and data lock point for the current Canadian-specific addendum
• the version, date of final sign-off and data lock point for the reference RMP

Safety specification

In this section, provide:

• the Canadian epidemiology
• a summary of Canadian-specific safety concerns

Epidemiology of the indications and target populations relevant to Canada

Note: This section may have reduced content for certain products, such as generics or biosimilars, or certain well-characterized non-prescription drugs.

Indication

Provide the current or proposed indications according to the Canadian product monograph.

Epidemiology in Canada

Provide a brief summary of the Canadian epidemiology of the product's indication (incidence and prevalence in Canada), including main existing treatments available in Canada. Specify any notable differences from the reference RMP, including:

• the epidemiology of the medical condition
• risk factors for the authorized indication in Canada
  • for example, in cases where it is different from the authorized indication in other major jurisdictions, such as Europe and the US
• when the drug is meant to be used by a small group of patients in Canada

Details of target population

Provide any relevant information such as demographics of the target population and the setting for use of the product in Canada, including:

• available information about population characteristics, such as:
  • age or age categories such as pediatric or geriatric
  • sex or gender
  • underrepresented or underserved populations (when relevant for assessment of safety and risk management), such as:
    • racialized or ethnic minorities
    • pregnant or lactating people
    • patients with psychiatric disorders
    • patients with relevant comorbidities
• the intended prescriber for the drug and any considerations related to the medication use process, from prescribing to dispensing to administering and monitoring the drug
• the setting in which the drug should be used, such as:
  • hospitals
  • outpatient clinics
  • at home
• potential challenges to risk management
  • for example, remote locations and rural communities may present challenges for monitoring or follow-ups
• particular risk management considerations for specified groups or populations, such as Indigenous populations
• potential for medication errors
• misuse or illegal use
• potential challenges related to availability of technologies, devices or supplies in Canada required for risk management or use of the product

Post-authorization experience

Include cumulative patient exposure in Canada since product launch, if applicable (the global cumulative patient exposure should be included in the reference RMP).

The cumulative patient exposure in Canada must be presented separately from the global information. If the Canadian-specific data has been included separately in the reference RMP, this should be specified.

If needed, Health Canada may request an annual summary report under C.01.018 of the Food and Drugs Regulations (FDR).

Canadian-specific safety concerns

Indicate whether the safety concerns listed in the reference RMP are applicable to Canada. If not, explain why.

If there are Canadian-specific safety concerns that are not listed in the reference RMP, provide a detailed description of the safety concerns.

Provide a clear justification, including scientific evidence, if there are safety concerns that:

• have been changed or amended
• were included in the previous version and have now been removed
• were included in the reference RMP that are not considered relevant in Canada

It's not enough to cite acceptance of such a change by another regulator without providing a rationale.

If additional safety concerns need to be considered or a risk is reclassified or removed, describe the concerns and provide the underlying scientific rationale for any changes.

Examples of safety concerns specific to the Canadian context may include:

• genetic, external or other factors that are unique to the population, such as:
  • age
  • sex
  • gender
  • race
  • ethnicity
• the proposed or approved indications
• the expected use of the product, including the:
  • potential for off-label use
  • potential for medication errors
  • potential harm from an overdose
  • potential for transmission of infectious agents
  • risks in pregnant and lactating people or in children
  • risks associated with other members of the pharmacological class

If applicable, include information on clinical trial exposure in Canada.

Sample summary table of safety concerns in Canada

Summary of sponsor's safety concerns

Safety concern	Reference RMP	Canadian-specific addendum
Important identified risks
-	-	-
-	-	-
Important potential risks
-	-	-
-	-	-
Missing information
-	-	-
-	-	-

Pharmacovigilance measures in Canada

In this section, provide:

• the routine pharmacovigilance measures in Canada
• the additional pharmacovigilance measures in Canada
• a summary table of pharmacovigilance measures in Canada

Also, in this section, confirm whether all pharmacovigilance measures, including routine measures and additional measures, listed in the reference RMP apply to Canada. Provide an explanation if the pharmacovigilance measures are not relevant.

Routine pharmacovigilance measures in Canada

Provide information on the routine pharmacovigilance measures in the Canadian context, including:

• details of pharmacovigilance practices since product launch
• Canada-specific monitoring of adverse events, including search strategy, and reconciliation with the Canada Vigilance Database

Provide an explanation if these routine pharmacovigilance measures in Canada differ from the reference RMP.

Describe the routine pharmacovigilance measures that have been or will be implemented to address these safety concerns if there are Canada-specific safety concerns.

Refer to the sections in the reference RMP, if applicable.

Additional pharmacovigilance measures in Canada

Provide information on the additional pharmacovigilance measures in the Canadian context, such as:

• synopsis of studies
• copies of the study protocols for studies requested in Canada or with Canadian sites
  • or with potential Canadian sites if the study has not yet been approved elsewhere or has not yet started

For each additional pharmacovigilance measure listed in the reference RMP, state how it is relevant to the Canadian context at the time of submission. Include how:

• findings from the activity will inform the risk characterization and RMP updates in Canada
• milestones and timelines for reporting, including any deliverables, will be provided to Health Canada
• the pharmacovigilance measure is conducted in Canada, for example:
  • study has Canadian sites
  • registry can enroll Canadian patients

Provide a description and a detailed reason for these differences if:

• additional pharmacovigilance measures only apply to Canada or
• international pharmacovigilance measures differ from those proposed for Canada

Refer to the sections in the reference RMP, if applicable.

If there are Canadian-specific additional pharmacovigilance measures that are not listed in the reference RMP, provide a detailed description of these measures using the same format as in the reference RMP.

Sample summary table of pharmacovigilance measures in Canada

Study and status	Summary of objectives	Safety concerns addressed	Milestones (Canadian context)	Due dates and deliverables
Important identified risks
-	-	-	-	-
-	-	-	-	-
Important potential risks
-	-	-	-	-
-	-	-	-	-
Missing information
-	-	-	-	-
-	-	-	-	-

Risk minimization measures in Canada and evaluation of their effectiveness

In this section, provide details of:

• the routine risk minimization measures in Canada
• the additional risk minimization measures in Canada, including the plans to evaluate the effectiveness of risk minimization measures in Canada
• a summary table of risk minimization measures in Canada

Also, in this section, confirm whether all risk minimization measures, including routine measures and additional measures listed in the reference RMP apply to Canada. Provide an explanation if they do not apply to Canada.

Routine risk minimization measures in Canada

Provide detailed information on the routine risk minimization measures in Canada for the safety concerns that apply to Canada at the time of submission. Provide an explanation if these measures differ from the reference RMP.

When discussing routine risk minimization measures in Canada, refer to the most recent version of the Canadian product monograph, product packaging and product labels. Indicate in the RMP note to reviewer if the Canadian product monograph, product packaging or product labels are currently under review with Health Canada.

Additional risk minimization measures in Canada

Provide information on the additional risk minimization measures in the Canadian context. This could include a history of those additional measures that may have been discontinued.

For these measures:

• describe the risk minimization tool (RMT) that is intended to be used
• include the objective and rationale
• describe their implementation including the target audience, how and when the tools or material will be disseminated
  • if applicable, compare additional risk minimization measures proposed in Canada with those in other jurisdictions and provide a reason for using a different approach
• describe methods to evaluate their effectiveness and include timelines for reporting
  • if applicable, compare the manner used to evaluate the effectiveness of the risk minimization measures in Canada with the manner used in other jurisdictions and, if they differ, explain the reason for these differences

Include in the appendix copies of any RMTs used in risk minimization measures.

Provide a rationale if an RMT is not available at the time of submission, as well as a timeline for completing the preparation of the tool and its submission to Health Canada for review.

If an RMT is not available at the time of submission, Health Canada may request a draft or mock-up of the tool during the review, as needed.

Sample summary table of additional risk minimization measures in Canada

Safety concern	Routine risk minimization measures (for example, product labelling and packaging)	Additional risk minimization measures (for example, controlled access or distribution program, educational materials)	Evaluation of the effectiveness of additional risk minimization measures (for example, evaluation plan and criteria for success)
Important identified risks
-	-	-	-
-	-	-	-
Important potential risks
-	-	-	-
-	-	-	-
Missing information
-	-	-	-
-	-	-	-

References and appendices

You may use references and appendices in the Canadian-specific addendum to provide further information.

References

In this section, provide any references used in the Canadian-specific addendum.

Appendices

Include as an appendix any materials referred to within the Canadian-specific addendum. Examples include:

• study protocols for planned Canadian pharmacovigilance studies
• pharmacovigilance materials such as adverse event and medication error follow-up questionnaires implemented or to be implemented in Canada
• risk minimization tools used in Canada