Draft guidance on preparing and submitting summary reports for marketed drugs and natural health products: Preparing annual summary reports under the NHPR

On this page

• About NHP annual summary report preparation requirements
• Preparing NHP annual summary reports
• Content of NHP annual summary report
• Acceptable document format for NHP summary reports
• Notification of significant change - NHPs
• Discontinued NHPs

About NHP annual summary report preparation requirements

Licence holders must prepare and maintain a summary report on an annual basis. This is in accordance with section 24(2) of the Natural Health Products Regulations (NHPR).

The annual summary report (ASR) contains a concise and critical analysis of all domestic adverse reactions and foreign serious unexpected adverse reactions to a natural health product (NHP) reported over the previous 12 months.

The requirement to prepare an ASR begins on the date that the product is licensed for sale in Canada and continues throughout the product’s life cycle.

Preparing NHP annual summary reports

You must meet all regulatory requirements of the NHPR. This includes preparing annually and maintaining the ASR.

Preparing the report consists of collecting, analyzing and organizing the relevant data about adverse reactions and serious adverse reactions, including contextual information, that enables you to determine whether there has been a significant change. The preparation of the report is an ongoing activity linked to signal management processes and monitoring activities.

Continuous and periodic signal management processes and monitoring activities, such as environmental scanning, are both important parts of routine pharmacovigilance and signal detection for the preparation of an ASR.

It’s essential that manufacturers and regulatory authorities have the most up-to-date information on an NHP. Your concise, critical analysis must be able to detect significant changes in the risk-benefit profile. The timing, frequency and nature of monitoring activities for signal detection depend on a number of factors, such as:

• the product’s risk profile
• known or specific emerging issues
• scheduled timing or preparation of the summary report

Identified and potential safety issues, as well as knowledge gaps (for example, toxicity in vulnerable sub-populations, interactions with other products, emergent use patterns) may require more active monitoring.

In addition to reviewing your internal databases and information, you are advised to review the Canada Vigilance Adverse Reaction online database for information relevant to the preparation of your ASR. However, you should avoid duplication of adverse reaction reporting, as discussed in the notice from Health Canada:

• Clarification of section 4.3 of the Reporting adverse reactions to marketed health products – Guidance document for industry

For information on reporting adverse reactions to Health Canada, consult:

• Reporting adverse reactions to marketed health products - Guidance document for industry

You are encouraged to use terminology from the Medical Dictionary for Regulatory Activities (MedDRA) to analyze and present data.

You may choose the 12-month period for which the ASR is prepared. We prefer that ASRs be prepared as a cumulative summary from the date of first licensing or sale in Canada. The ASR should be prepared within 70 days of the end of the most recent 12-month period.

Relevant unique Canadian identifiers (NPN, DIN-HM) should be included in an ASR report. This makes it easier for Health Canada to link the report to other information about the marketed product.

Visit Definitions for an explanation of “significant change” and “vulnerable sub-populations”.

Content of NHP annual summary report

The information you include in the ASR will vary depending on the adverse reaction data received or known to you. If you cannot complete a section (for example because you have not become aware of any adverse reactions within a reporting period), note this and provide an explanation.

Adverse reaction reports as well as other sources of information that might be necessary for the analysis should be considered. Other data sources may include:

• foreign regulatory websites
• consumer complaints of side effects
• medication errors (including incidents without clinical consequences)
• public information, such as social media or media reports of side effects
• international or Canadian poison centre data (where available and accessible)

You should include in your concise critical analysis information on emerging safety issues related to your product or its ingredients. Collecting this information is part of your ongoing monitoring activities for signal detection.

An ASR should add to what is known about the product’s safety from real-world use. Available reference safety information (such as product and ingredient monographs, approved product labelling or terms of market authorization) should be part of the assessment.

Safety issues may arise even for products with well-established safety profiles. The depth of analysis needed for an ASR depends on the nature and amount of the information collected. ASRs summarize and integrate new safety knowledge gained from experience during the reporting period.

At minimum, your concise critical analysis should discuss the following:

• action taken for safety reasons during the reporting interval by the licence holder or foreign competent authorities
• changes to reference safety information during the reporting interval
  • include copy of current reference safety information (such as company core safety information)
• global and Canadian exposure (interval/cumulative)
• summary of significant safety findings during the reporting interval
• summary of medication errors, misuse or overuse, and off-label use during the reporting interval
• summary of reports of lack of effectiveness during the reporting interval
• opened, ongoing and closed safety signals during the reporting interval
• summary of new safety information identified during the reporting interval
• conclusions on whether there has been a significant change in what is known about the risks and benefits during the reporting interval

Interval summary tabulations from various sources do not need to be included in the ASR however, they should be provided if requested.

Refer to the section on cumulative and interval summary tabulations.

Canadian-specific information should be included in the ASR or in a Canadian-specific section or addendum, including:

• product label
• product packaging
• Canadian exposure
• regulatory contact information in Canada
• date of first marketing and current marketing status in Canada

Conclusions about a significant change

In preparing your ASR, you should include your conclusions on whether there has been a significant change in what is known about the risks and benefits of the NHP during the period covered by the report. As such, you should determine whether there has been a change in the balance of the benefits and risks that would warrant urgent action. These conclusions are based on your concise critical analysis.

Not all changes to risks and benefits are considered significant. You should note changes and assess if they meet the threshold of significant change.

Examples of significant change could include urgent action needed to:

• modify labelling to include warnings or contraindications
• change in packaging to include child safety features
• communicate risks to public or health professionals

Changes to reference safety information resulting from your signal assessment processes could also lead to the conclusion of a significant change.

Visit Definitions for an explanation of “significant change”.

Acceptable document format for NHP summary reports

You may prepare an ASR using one of the following standardized document formats:

• Periodic benefit-risk evaluation report (PBRER) format
  • preferred international format for drug summary safety reporting
  • follow the standards defined in the ICH E2C (R2) guidance (PDF)
• Periodic safety update report (PSUR) format
  • EU format acceptable and comparable to the PBRER format

You may also prepare an ASR using a non-standardized format, as long as it respects the expected content outlined in this guidance.

Although the PBRER document format is preferred, the format you choose will depend on the nature of the product and your preference.

Although standardized periodic summary reports such as PBRERs and PSURs are used globally, regional differences may exist. You should consider the need for a Canadian-specific section or addendum when preparing an ASR in these formats. If using a global PBRER or PSUR prepared for a period greater than one year, the Canadian-specific information must be annualized to meet the requirements.

Notification of significant change – NHPs

You are encouraged to inform us immediately if there’s a significant change in what is known about the risks and benefits of the NHP.

To avoid overburdening the system, do not submit a notification of significant change unless it meets the threshold outlined in the definition of significant change.

Issues related to the quality of the product or good manufacturing practices (GMP) are not in scope of this requirement, and should not be notified in this manner.

If you have questions about what constitutes a significant change, contact us for advice.

Visit Definitions for an explanation of “significant change”.

How to notify

When informing us of a significant change, the information should be clear and explicit and should contain a description of:

• the significant change
• how the significant change was identified
• the impacted sections within the ASR, if applicable

You are also encouraged to include in your notification the following:

• clinical impacts of the issue on patient or public health, or impact on the product’s benefit-risk profile
• any significant impact on product, including in other jurisdictions, for example:
  • recommended use
  • formulation
  • risk information
• what further assessments may be needed in the Canadian context
• follow-up actions needed in Canada with proposed timelines, if applicable, including:
  • changes to packaging, labelling, terms of market authorization, product design or product accessibility
  • risk communication

Note: You are expected to take the actions outlined in your notification.

To notify us of a significant change, complete the form:

• Draft - Notifying Health Canada of a significant change in what is known about the risks and benefits of a product

For information on how to submit the form via Canada Post’s secure email service, ePost Connect, refer to:

• Management of post-market vigilance submissions guidance document

Discontinued NHPs

After an NHP licence is cancelled, you should continue to prepare an ASR until the expiry date of the last lot sold. You are also encouraged to inform us immediately if there’s a significant change.

Some adverse reactions (ARs) and associated safety signals may appear soon after use of the product starts, while others may take longer to appear. For example:

• Late reactions occur rarely or not at all at the beginning of use, but whose incidence increases with continued or repeated exposure.
• Delayed reactions become apparent some time after a product is used, even if it’s withdrawn before the reaction appears.
• Interactions may occur with health products that have not previously been taken or combined.