Cannabis adverse reaction reporting for licence holders: Reporting procedures

On this page

• Personnel and training
• Overview of steps
• Record keeping requirements

Reporting procedures are the collection, evaluation and monitoring of adverse reactions (serious and non-serious) associated with the use of a cannabis product. This includes a set of methods and tools that allows for the surveillance and evaluation of the risks of cannabis products. These methods and tools should also contribute to real world data and evidence-based decision-making process and knowledge translation. This may also be referred to as post-market surveillance, cannabis vigilance or pharmacovigilance.

Personnel and training

Licence holders should have qualified personnel who are responsible for screening and assessing adverse reactions submitted to the licence holder. The qualified personnel should have:

• necessary qualifications
• experience and training relevant to the responsibilities of adverse reaction reporting, for example:
  • background in medical or health-related fields
  • experience in interpretation of medical information in adverse reaction reports
  • knowledge of the Cannabis Regulations (the Regulations)

A qualified health professional should exercise clinical judgement in:

• deciding whether an adverse reaction report is serious
• determining if an adverse reaction is medically important, as well as
• determining if it is related to the product itself or due to other factors (causality assessment)

Qualified personnel should also be involved in determining:

• the completeness of the case report
• whether follow-up is required
• if there is significant new information from follow-up that requires reporting within 15 days based on clinical judgement

The qualified personnel are responsible for establishing and maintaining a system whereby adverse reaction data is collected, monitored, followed up, and properly assessed. All personnel involved in collecting reports of complaints or adverse reactions (for example, customer care service) should have their responsibilities outlined in writing.

Licence holders should give adequate and ongoing training to personnel as necessary. Third party companies with contractual agreements for adverse reaction reporting for a licence holder should also have the necessary qualifications, training and experience to conduct the reporting activities.

Overview of steps

Licence holders should have written standard operating procedures outlining the following steps for all adverse reactions.

• Collecting
  • keeping an eye on different sources
  • monitoring and handling of adverse reactions from reporters received spontaneously (unsolicited reports) or collected in studies or other organized data collection sources (solicited reports)
  • determining if a complaint includes an adverse reaction
  • assigning a unique identifier to each case for tracking and follow-up purposes
• verifying their complaint records to ensure that all serious adverse reactions are identified
• Following up
  • appropriate follow up procedures
  • following up with reporters to get as much information as possible, including products, patient medical history and outcomes
• Evaluating
  • investigating to provide opinion on causality and possible causes (for example, root cause analysis)
• Reporting
  • submitting adverse reaction reports to Health Canada
• Record keeping
  • keeping all adverse reaction reports and documentation of investigations (for example, causality, root cause analysis, certificates of analysis)

In general, each step should define:

• key responsibilities
• responsible personnel
• investigating adverse reactions
• reporting adverse reactions
• record keeping activities

Reports should be accurate, legible and as complete as possible.

Collecting

Surveillance of adverse reaction reports

Licence holders are expected to monitor and analyze adverse reactions, which may originate from various sources, including:

• submitted to licence holders spontaneously by consumers or patients, health care practitioners, retailers, as unsolicited reports
• submitted directly to Health Canada and appearing on the Canada Vigilance adverse reaction online database
• reported on social media platforms that licence holders are responsible for
• published in the scientific literature
• collected from an epidemiological study, research study involving humans (outside of the scope of a clinical trial, like non-therapeutic research on cannabis [NTRC]), or other organized data collection systems as solicited reports

Types of reports

Adverse reaction reports fall into 2 categories, spontaneous (unsolicited) and study (solicited) reports.

Spontaneous reports are those received on an unsolicited basis from consumers, patients, health care practitioners or other reporters (for example, retailers). They describe an adverse reaction in a consumer or patient with one or more cannabis products. They do not originate from a study or any organized data collection system (for example, patient registries or monitoring programs).

If a reporter submits a spontaneous report to a licence holder, even if the relationship is unknown or unstated, it is considered a reportable adverse reaction. This is based on the suspicion of the initial reporter that there is a suspected relationship between a cannabis product and the adverse reaction.

Spontaneous reports may be stimulated by certain factors, for example, advisories, recalls or other information that communicates about reporting of adverse reactions.

Study reports are adverse reaction reports that come from:

• epidemiological studies or
• other types of organized data collection systems where data is actively collected or solicited (such as registries, patient utilization or monitoring programs)
• research studies in humans involving cannabis that do not meet the definition of a clinical trial (for example, sensory testing)

Study reports are also called "solicited reports."

Licence holders must submit a report on serious adverse reactions from a study if there is a reasonable possibility that cannabis product caused the adverse reaction (that is, the relationship cannot be ruled out).

Reports submitted directly to Health Canada

Licence holders should monitor the Canada Vigilance adverse reaction online database to identify any reports with their cannabis products submitted directly to Health Canada. This is to ensure that adverse reaction report records held by licence holders are complete.

Licence holders should verify the Canada Vigilance adverse reaction online database to identify adverse reaction reports with their cannabis products, by licence holder name or brand name of cannabis product.

Licence holders should not resubmit reports originating from the database unless they have more information to add. In that case, the licence holder should submit a follow-up report citing the original adverse reaction number.

Scientific literature reports

Licence holders should screen medical and scientific literature for case reports with their cannabis products. If a licence holder becomes aware of a published case report or a study reporting a serious adverse reaction with their cannabis product, they must report this adverse reaction to Health Canada. This includes if it is explicitly reported in the publication or implicitly known by the licence holder. This only applies in cases where the publication's authors have identified at least a possible causal link with the cannabis products, irrespective if the published case report happened inside or outside of Canada.

Licence holders should create a unique report for each patient identified in the publication, and they should include all relevant case details (including citation of the publication). The publication authors would be the initial reporter, and the full literature citation should be provided.

Social media or media reports

If a licence holder becomes aware of a serious adverse reaction in the media or social media with one of their cannabis products, it is a reportable case if it meets the 4 minimum criteria. Given the limited nature of these sources, licence should make efforts to obtain as much detail as possible. In the reporting form, they should be identified as being from the media or social media.

Study reports from licence holders

Licence holders who are conducting studies with cannabis products should monitor adverse reactions to meet serious adverse reaction reporting obligations under section 248 of the Regulations, including both domestic and foreign adverse reactions. Study protocols should include a safety monitoring plan and procedures that describe how adverse events will be monitored, recorded and assessed and the proposed strategy to mitigate the risks of adverse events, and how serious adverse reactions will be reported per section 248.2 of the Regulations. For more information on conducting research with cannabis, refer to Cannabis licensing application: Research licence - Canada.ca.

When reporting serious adverse reactions from studies, the following information should be included, if known:

• study ID and title
• study type (for example, cohort study, case-control, survey, other)
• location of study
• status of study (ongoing or completed, with dates)

If an adverse reaction is reported outside of the parameters of an epidemiological study or organized data collection scheme (such as, after the study has been completed), it should be considered a spontaneous report.

Study reports from other stakeholders

Licence holders could receive reports of serious adverse reactions with one or more of their cannabis products derived from studies conducted by other stakeholders, for example:

• academic center
• private investigator
• other licence holder
• market authorization holder

In such cases, licence holders should try to get follow-up information from the other stakeholder, and the report treated like any other adverse reaction report. A licence holder should not alter the causality provided by the initial reporter and should identify their own causality in the report.

Non-therapeutic research on cannabis (NTRC)

Non-therapeutic research on cannabis studies are interventional, non-therapeutic studies with cannabis regulated under the Act and its Regulations.

The purpose of NTRC is to:

• increase the knowledge on cannabis and its non-therapeutic effects
• gain knowledge to inform public health and public safety measures, public education, and policy
• further research and development of cannabis products

An example of an NTRC study is assessing participants in a driving simulation test to find out how long they're impaired for after researchers have administered cannabis.

Licences allowing for this specific and limited type of human research include several terms and conditions, including the requirement to submit all serious adverse reactions for all cannabis that is administered or distributed to human research subjects. These obligations are outlined under section 248.2 of the Regulations. For more information on adverse reaction reporting obligations in NTRC studies, refer to Report a side effect to cannabis: Licence holders. For more information on post-licence obligations more generally, refer to Cannabis research licence: Additional information to conduct non-therapeutic research on cannabis.

In all cases, the detailed report submitted to Health Canada must contain all information in the possession of the licence holder that is associated with the use of the cannabis or cannabis accessory by the individual who experienced the serious adverse reaction. The report should have a cover page providing key details to identify the study, for example:

• licence number
• name of the research licence holder
• study category
• name of the principal investigator
• individual responsible for assessing the adverse reaction
• study location if multi-site

The report should include:

• the intended use of the cannabis (for example, oral, inhalation, topical, etc.) or cannabis accessory,
• an assessment of the cause of the serious adverse reaction and
• a statement of what further actions, if any, that need to be taken by the research licence holder

Handling and coding of reports

Licence holders should have a system, database or program to collect and analyze adverse reaction data. This may include an electronic system (for example, Argus Safety Case Management system) to collect information in a standardized manner. The use of international standardized medical terminology (such as MedDRA) is recommended as a tool to code adverse reaction data for cannabis adverse reactions to classify, search and retrieve adverse reaction reports. It is also helpful for reporting purposes (for example, for individual case reports and for the preparation of annual summary reports). If standardized medical terminology is used, the report should still include the initial reporter verbatim details to ensure that all details are captured.

Narrative information

Narrative information in case reports is important for describing the clinical course of the adverse reaction. Include as much narrative information as possible, including:

• diagnosis (including investigations)
• additional details of past medical history
• outcome (including sequelae or no sequelae)
• clinical course of the adverse reaction (including time to onset)
• history of use of suspect products (including cannabis products)
• any other information that may support or rule out a causal association, such as positive de-challenge and re-challenge information

Licence holders should also include their assessment of causality and root cause analysis of the adverse reaction, including whether product quality or other factors are suspected of being involved.

Follow-up

If a licence holder does not obtain sufficient information through the initial report, then they should be conducting follow-up to obtain as much detail as possible. This additional information should be submitted to Health Canada in a follow-up report citing the original adverse reaction number regardless of how much time has elapsed since the initial report was submitted to Health Canada. Follow-up information may include additional information submitted by the original reporter (for example, notes, medical history, discharge records, product details) or additional information from the licence holder themselves (for example, certificate of analysis of the lot involved in the adverse reaction report, information pertaining to root cause analysis).

It is expected that licence holders exercise due diligence in obtaining as much detail about an adverse reaction from a reporter for assessment. Follow-up should be attempted for each case report, especially for serious adverse reactions that must be submitted to Health Canada. If efforts to follow-up with a reporter are met with no response or refusal to share information, then this should be stated within the case report submitted by the licence holder to Health Canada. In addition, the reporter should also be informed by the licence holder that they can share any additional information directly with Health Canada by voluntarily submitting an adverse reaction report. This may help to minimize requests for information from Health Canada when evaluating the cases.

Evaluating

All adverse reaction reports received by licence holders should be reviewed by a qualified person, including:

• screening of complaint records to ensure that all adverse reactions are documented and reported in accordance with section 248.1 of the Regulations
• reviewing the adverse reaction report to ensure quality and completeness of the information
• conducting follow-up, particularly on serious or medically important cases
• determining seriousness for expedited reporting purposes
• investigating the adverse reaction, including evaluating the likelihood that the suspect product caused the adverse reaction (causality analysis) and possible underlying cause (root cause). If causality has already been attributed by the original reporter, this should not be changed, but the licence holder can identify in the report their own opinion of causality in addition to that reported by the original reporter
• determining whether product quality is involved or not
• if corrective or preventive actions have been taken for a particular issue involving an adverse reaction according to an investigation of quality (subsections 19(2) and 88(1) of the Regulations), these details should be included as follow-up to the adverse reaction report

For further information on the World Health Organization's criteria for causality, refer to Appendix 6 of the Reporting adverse reactions to marketed health products guidance.

Further information on root cause analysis may be found in the Good production practices guide for cannabis.

Reporting

It is recommended that licence holders report adverse reactions to Health Canada using the Mandatory adverse reaction reporting form for industry. Licence holders may also choose to report adverse reactions using the Council for International Organizations of Medical Sciences (CIOMS) form.

How to submit the form

Complete the applicable form and send to the Canada Vigilance Program:

• Send by fax at: 613-957-0335
• Mail to:
  Canada Vigilance Program
  Marketed Health Products Directorate
  Health Canada
  Postal Locator 1908C
  Ottawa, Ontario K1A 0K9

Certain licence holders may already be enrolled with Canada Vigilance as trading partners to submit adverse reaction reports electronically. If this method of transmission is used, it is important to follow best practices for electronic transmission of adverse reaction reports (ICH E2B guidance). For further information, see Appendix 4 of Reporting adverse reactions to marketed health products.

Minimum information for a report

The minimum information for reporting an adverse reaction to Health Canada are:

• an identifiable reporter (source)
• an identifiable patient or consumer
• a suspect cannabis product
• a description of the adverse reaction

If the licence holder has these 4 pieces of information, a case is considered reportable to Health Canada, even if details are minimal.

To be considered identifiable, the licence holder should be able to verify the existence of the reporter and the patient or consumer. Any of the following qualify a patient as being identifiable:

• age or age category
• sex
• unique identifier or reference to a patient

In the context of a suspect cannabis product, this refers to a cannabis product that an individual consumed (intentional or unintentional) and that is suspected of having caused the adverse reaction.

It is expected that licence holders collect as much information as possible so that reports submitted to Health Canada capture clinically relevant and complete information for evaluation. Required content is outlined below to assist licence holders in submitting detailed adverse reaction reports.

Key information in the reporting form

The following key data elements are also useful to include in adverse reaction reports submitted to Health Canada from other sources, including health care practitioners, consumers/patients, retailers or others. This information follows the format of the Mandatory adverse reaction reporting form for industry.

Reporter information

• Report source (origin of information): Spontaneous, study, not available or unknown, other
  • spontaneous sources may include community members, consumers, family members, health professionals, retailers
• Reporter qualification (initial reporter): Physician, pharmacist, other health professional, lawyer, consumer, other
• If the reporter also sent a report to the Canada Vigilance Program: Yes, no, unknown
• Contact office: Name of responsible person and address of licence holder (or company submitting report on behalf of licence holder, with name of licence holder for which the report is being submitted)
• Report number: Identification number assigned by the licence holder to a report for record-keeping purposes.
  • for a follow-up report on the same case, the report number should be the same as the number assigned to the initial report
• Type of report: Initial, follow-up
• Date of most recent information
  • this date is when the licence holder received the information for this report
• Date the report is being sent to Health Canada

Patient/Consumer information

• Unique identifier: Patient identifier to readily locate the case for follow-up purposes. For privacy purposes, do not use the patient's name or initials
• Age at the time of the reaction, or
  • date of birth
  • patient age group according to available information
• Sex
• Height and weight

Adverse reaction information

• Country in which the adverse reaction occurred
• Date that the adverse reaction occurred
• Serious report: Yes, No
• Criteria for report seriousness (indicate all that apply)
  • death (date of death if available)
  • caused or prolonged hospitalization
  • congenital anomaly, birth defect
  • other medically important condition (specify)
  • life-threatening
  • disabling, incapacitation

  Note: Hospitalization refers to formal admittance to the hospital and excludes out-patient treatment at emergency departments or clinics. Out-patient treatment at emergency departments or clinics should not be considered a hospitalization; this should be classified as a medically important condition.

• Outcome
  • recovered
  • not recovered
  • recovering
  • fatal
  • recovered with sequelae
• Full description of the adverse reaction as provided by the initial reporter (that is, verbatim), including:
  • body site and severity
  • duration of the reaction
  • any relevant clinical information (reported signs and symptoms, clinical course, specific diagnosis)
• Relevant diagnostic tests and laboratory data
  • if the patient sought medical care, list any diagnostic tests and laboratory data that were conducted or provided to assess the patient (including any with negative results)
  • for a fatal outcome, stated cause of death and provide any relevant post-mortem findings.
• Other relevant medical history (personal or familial), including:
  • pre-existing medical conditions
  • cannabis use history and if known, provide relevant information such as dates, product names, dosage forms, route of administrations, and frequency of use
  • any known hypersensitivities or allergies to cannabis or other substances, foods or health products, including the nature of the allergies or hypersensitivities
  • Medication history, including the use of pharmaceutical drugs (prescription and non-prescription), biologic drugs and natural health products, including the duration and frequency of use, if known

Health products

More than one cannabis product may be involved in a case. Include all details of the cannabis product(s) suspected in the adverse reaction, including:

• Suspected product name
  • brand name assigned by the licence holder under which it is sold, including any name extensions or modifiers
  • product class
    • dried or fresh cannabis
    • cannabis extract
    • cannabis topical
    • edible cannabis
    • cannabis accessory that contains any of these
  • product form
    • pre-rolled, milled, whole flower
    • oil, capsule, oral spray, vaping liquid, vaping cartridge
    • beverage, confectionary, baked good
    • cream, lotion, gel, transdermal
  • quantity or concentration of:
    • THC
    • THCA
    • CBD
    • CBDA
  • list of other constituents (terpenes) or ingredients (carrier oil, food ingredients)
  • device or accessory used include details such as brand name and model number
  • place of purchase
• Dose, frequency and route used
  • daily dose, frequency of use, specify dose and regimen (for example, once a day or as needed)
  • route of administration:
    • oral (ingested, buccal, sublingual)
    • inhaled (vaped or smoked)
    • intranasal
    • topical
• Therapy dates (if unknown, give duration)
• Indication for use of suspected product
  • specify if the cannabis product was being used for medical or non-medical purposes
  • if used for medical purposes, describe the reason for use (for example, pain) and specify if there is a medical authorization document
• Reaction abated (dechallenged) after discontinuation or dose reduced: Yes, no, does not apply
• Reaction reappeared (re-challenged) after reintroduction: Yes, no, does not apply
• Lot number: batch number, unique product identifier such as universal product code (UPC), stock-keeping unit (SKU), global trade item number (GTIN) (as applicable)
• Concomitant health products (exclude treatment of action): other health products that were used at the same time as the adverse reaction
  • describe if any drugs or health products are also suspected in the reported adverse reactions (such as, co-suspected in the adverse reaction with the cannabis product)
  • these may include prescription or non-prescription drugs, natural health products, drugs, alcohol, tobacco
• Treatment of adverse reaction
  • describe the treatment of the adverse reaction, including any health products or therapies that were used

Duplicate or linked reports

If a duplicate or follow-up report is received after the initial report has been submitted, a licence holder should report these to Health Canada using the Mandatory Adverse Reaction Reporting Form for Industry selecting "Follow-up" (under section A6) and citing the original adverse reaction number. It is important to indicate whether the report is a follow-up (same reporter) or duplicate (different reporter) to the initial report. The proper identification of duplicate reports will also help licence holders to reflect the accurate number of unique cases, particularly for serious adverse reactions, for signal detection purposes and to avoid issues related to multiple counting of a single case when developing the annual summary report. Licence holders should have in place a system or method for identification and management of duplicate and linked reports.

Record keeping

Good documentation is an important part of a quality assurance system for adverse reaction reporting. Under subsection 248.1 (2) of the Regulations, licence holders must maintain the adverse reaction reports for at least 25 years after the day on which they are prepared, including both individual adverse reaction reports and annual summary reports.

As such, licence holders should ensure that adverse reaction reports are stored appropriately in order to protect personal information.

If adverse reaction reports are transmitted between stakeholders with contractual agreements or between licence holders, this should be done while ensuring privacy and data security of personal information.

A qualified person should verify adverse reaction data for appropriateness, completeness, follow-up and determination of seriousness, especially if customer care representatives are initially receiving adverse reactions among other types of incidents or complaints (for example, collected within a broader complaint system or process).

If case reports are coded, verbatim from the reporter should always be maintained in the narrative and reflect as much detail as possible about the reaction.

For purposes of verifying record keeping requirements, information should be readily available to Health Canada. This includes written procedures for handling reports, conducting follow-up and analysis of adverse reaction reports, record keeping of individual case reports as well as annual summary reports. These records should be easily accessible to permit submission upon request to Health Canada and for auditing purposes during an inspection.