Under the Food and Drugs Act (1985) and Regulations, pharmaceutical companies are legally required to report serious adverse reactions related to a vaccine. The Canada Vigilance Program offers oversight after vaccines have been licensed, with systemic safeguards to ensure that vaccines have continued monitoring. The program includes safety reports, surveillance systems, risk management plans, and product risk/benefit assessments.
Safety Reports
According to the Food and Drugs Act (1985), pharmaceutical companies are required to prepare an annual report that comprehensively analyzes all adverse drug reactions occurring anywhere in the world. Drug companies are also responsible for notifying Health Canada if they become aware of any significant issues that could affect the benefit-risk profile.
Canadian Adverse Events Following Immunization Surveillance System (CAEFISS)
All health professionals must report adverse events following immunization (AEFI) to local authorities, who report to provincial authorities, who in turn report to federal authorities. CAEFISS is responsible for using this information for ongoing safety monitoring and AEFI investigations in Canada. An AEFI may or may not have a causal relationship to the use of the vaccine.
Evaluation of Vaccines Post-License
The safety profile of a vaccine is heavily scrutinized before licensure. Rigorous monitoring and evaluation continues once the vaccine is available to the general population to identify potential rare side effects and frequency of adverse events following immunization. This period is often referred to as the post-marketing period because the vaccine continues to be monitored after it is licensed. Table 4.2 outlines the various stages of post-license evaluations.
Table 4.2: Post-License Evaluation Stages
| Life Cycle Phase | Regulatory Requirements | Description |
|
Lot release program
|
Food and Drugs Act and Regulations
|
Ensures that each marketed lot of vaccine does not differ from vaccine lots shown to be safe and effective in clinical trials.
|
|
Establishment inspections
|
Food and Drugs Act and Regulations, including GMP
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Ensures that the facilities in which the product (the active pharmaceutical ingredient) is manufactured are appropriate to the specifications that apply to that product. Generally, inspections occur every two to three years; however, inspections can be more or less frequent depending on the activity and product.
|
|
Post-marketing studies
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Not required by regulation, but suggested by Health Canada. Researchers may conduct large studies to test causal relationship between a vaccine and adverse events.
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Phase IV (≥ 100 thousand subjects). Expand data on vaccine safety profile in target population to identify rare adverse events not detected during pre-marketing phase. Assess safety profile in special populations not studied as part of pre-authorization trials (e.g., immunocompromised, diabetics, etc.). Study possible interactions with other vaccines.
|
|
Adverse Events Following Immunization (AEFI) surveillance systems
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Food and Drugs Act and Regulations by market authorization holders. CAEFISS activities are undertaken voluntarily, although some jurisdictions require AEFI reporting as part of public health legislation.
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Detect new vaccine safety signals which could be:
Conduct special investigations to determine root cause of vaccine safety signals.
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|
Studies designed to test hypotheses related to vaccine adverse event association
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May be requested by regulators in response to new safety signals.
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Test hypothesis that a vaccine can cause an AEFI, including very rare events.
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AEFIs should be reported:
- When the event has a temporal association with a vaccine. A causal relationship does not need to be proven before reporting.
- When the event is serious or unexpected (e.g., life threatening or results in death, requires hospitalization or prolongation of an existing hospitalization, results in residual disability, or causes congenital malformation).
- If there is any doubt as to whether or not an event should be reported, health professionals should always choose to report the event.
Table 4.3 is an example of a protocol for reporting adverse events. Each province and territory has their own reporting system outlining local and provincial/territorial activities. It is important that health professionals know what and how to report in their jurisdiction. The Public Health Agency of Canada has a national reporting form that is available. Completed forms are sent to the local public health unit. All reports are eventually reported up to CAEFISS at a national level.
Table 4.3: Adverse Event Type Requiring Reporting
| Adverse Event Type | TEMPORAL CRITERIA
for Non-live vaccines |
TEMPORAL CRITERIA
for Live vaccines |
|
Injection Site Reactions
|
||
|
Pain, redness, or swelling lasting 4 days or more OR extending beyond the nearest joint
|
0 to 48 hours
|
0 to 48 hours
|
|
Infected abscess
|
0 to 7 days
|
0 to 7 days
|
|
Sterile abscess
|
0 to 7 days
|
0 to 7 days
|
|
Nodule
|
0 to 7 days
|
0 to 7 days
|
|
Cellulitis
|
0 to 7 days
|
0 to 7 days
|
|
Systemic Reactions
|
||
|
Rash
|
0 to 7 days
|
5 to 42 days
|
|
Adenopathy/lymphadenopathy
|
0 to 7 days
|
5 to 42 days
|
|
Severe vomiting/diarrhea
|
0 to 72 hours
|
0 to 42 days
|
|
Parotitis
|
N/A
|
5 to 30 days
|
|
Hypotonic-hyporesponsive episode (HHE); under 2 years of age only
|
0 to 48 hours
|
0 to 48 hours
|
|
Persistent crying/screaming; under 2 years of age only
|
0 to 72 hours
|
0 to 72 hours
|
|
Allergic reactions
|
||
|
Event managed as anaphylaxis (i.e., epinephrine administered)
|
0 to 24 hours
|
0 to 24 hours
|
|
Oculorespiratory Syndrome (ORS)
|
0 to 24 hours
|
0 to 24 hours
|
|
Allergic skin reaction (e.g., hives)
|
0 to 48 hours
|
0 to 48 hours
|
|
Neurologic events
|
||
|
Convulsions/seizure
|
0 to 72 hours
|
5 to 42 days
|
|
Encephalopathy/encephalitis
|
0 to 15 days
|
5 to 42 days
|
|
Meningitis
|
0 to 15 days
|
5 to 42 days
|
|
Anaesthesia/paraesthesia
|
0 to 15 days
|
0 to 42 days
|
|
Paralysis
|
0 to 15 days
|
5 to 42 days
|
|
Myelitis/acute disseminated encephalomyelitis
|
0 to 15 days
|
5 to 42 days
|
|
Guillian Barré Syndrome (GBS)
|
1 to 8 weeks
|
1 to 8 weeks
|
|
Bell’s palsy
|
0 to 3 months
|
0 to 3 months
|
|
Other events of interest
|
||
|
Arthritis/arthralgia
|
0 to 15 days
|
1 to 3 weeks
|
|
Intussusception
|
N/A
|
0 to 42 days
|
|
Thrombocytopenia
|
0 to 30 days
|
0 to 30 days
|
|
Syncope (fainting) with injury
|
0 to 30 minutes
|
0 to 30 minutes
|
|
Other severe/unusual events
|
Reportable regardless of timeline
|
Reportable regardless of timeline
|
As a health professional, it is important to monitor adverse events and follow the steps below:
Step 1
- Advise clients to contact you or your team if they experience an adverse event after vaccination.
Step 2
- Complete either the local form or the Public Health Agency of Canada form for reporting an AEFI. A user guide is available.
- Submit the completed form to the local public health unit or consult them if you have any questions.
Attribution Statement
Table 4.3 was adapted with editorial changes from “Adverse Event Following Immunization Reporting for Health Care Providers in Ontario” by Public Health Ontario. Contact the copyright holder for appropriate permission.
Information that indicates a potential link between a vaccine and an event previously unknown or incompletely documented, that could affect health