Archived 1: Recommendations on the use of COVID-19 vaccine(s) [2020-12-12]

Notice to reader

This is an archived version. Please refer to current COVID-19 vaccine pages:

Publication date: December 12, 2020

Preamble

The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.

In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence-based recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels.

The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI Statements will require in-depth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidence-informed tools to identify distinct issues that could impact decision-making for recommendation development, only distinct issues identified as being specific to the vaccine or vaccine-preventable disease will be included.

This statement contains NACI's independent advice and recommendations, which are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

Summary

The following highlights key, current information for immunization providers on COVID-19 vaccine. The evidence on COVID-19 disease and vaccines is evolving. Evidence from clinical trial data is limited due to limitations in the size and duration of follow-up of trial populations; however, studies are ongoing. NACI will continue to monitor the data and update its recommendations as needed. Please refer to the remainder of the Statement for details.

What

Disease

Novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Anyone can be infected with SARS-CoV-2. However, some populations are at increased risk of exposure to the virus (e.g., due to living or work settings), and some populations are at increased risk of severe disease and death due to biological (e.g., advanced age, pre-existing medical conditions) and social (e.g., low socioeconomic status, belonging to a racialized population) factors that may intersect. Risk factors for exposure and severe disease may overlap, further increasing risk. Any combination of these factors, as well as varying access to health care services, has the potential for disproportionate consequences for specific populations.

Currently authorized vaccine: Pfizer BioNTech COVID-19

This vaccine is authorized for use in Canada for individuals 16 years of age and older.
In clinical trials, the vaccine is efficacious in the short-term against symptomatic, confirmed COVID-19 disease; trials are ongoing.
Protection offered by the first dose is lower than the efficacy achieved after the second dose. Peak humoral and specific cellular immune responses occur after the second dose.
There is currently insufficient evidence on the duration of protection and on the efficacy of this vaccine in preventing death, hospitalization, infection and reducing transmission of SARS-CoV-2, although studies are ongoing.
No serious safety concerns have been identified to date in clinical trials; however, studies are ongoing. Some adverse events are very common and were reported to affect more than 10% of people who receive the vaccine. However, they are mild or moderate and transient, resolving within a few days. These include: pain at the injection site, fatigue, headache, muscle pain, chills, joint pain, and fever. Some adverse events, including fever, are more frequent after the second dose.
There is currently minimal evidence to inform on differences in vaccine efficacy or safety between those with and those without prior evidence of SARS-CoV-2 infection at the time of vaccination.

Who

NACI makes the following recommendations:

A complete vaccine series of currently authorized COVID-19 vaccine should be offered to:

Individuals in the authorized age group without contraindications to the vaccine. In the context of limited vaccine supply, initial doses of COVID-19 vaccine(s) should be prioritized for the key populations outlined in NACI's Guidance on the Prioritization of Initial Doses of COVID-19 Vaccine(s).

A complete vaccine series of COVID-19 vaccine may be offered to:

Individuals in the authorized age group without contraindications to the vaccine who have had previously PCR-confirmed SARS-CoV-2 infection. In the context of limited vaccine supply, initial doses may be prioritized for those who have not had previously PCR-confirmed SARS-CoV-2 infection. Testing for previous SARS-CoV-2 infection is not needed prior to COVID-19 vaccination.

COVID-19 vaccine should not be offered to the following populations excluded from clinical trials until further evidence is available. However, if a risk assessment deems that the benefits of vaccine outweigh the potential risks for the individual (e.g. where the risk of severe outcomes of COVID-19 and risk of exposure to SARS-CoV-2 is high) or for the fetus/infant (in the case of pregnancy/breastfeeding) and if informed consent includes discussion about the insufficient evidence in this population, then a complete series of authorized COVID-19 vaccine may be offered to individuals in the following populations:

Immunosuppressed due to disease or treatment or suffering from autoimmune disorder
Pregnant or breastfeeding
Adolescents 12 to 15 years of age

NACI also recommends that:

All individuals should continue to practice recommended public health measures for prevention and control of SARS-CoV-2 infection and transmission regardless of vaccination with COVID-19 vaccine, at this time, due to insufficient evidence on the duration of protection and effectiveness of COVID-19 vaccines in preventing asymptomatic infection and reducing transmission of SARS-CoV-2.
Routine immunization programs and immunization with other vaccines recommended by NACI should continue during the COVID-19 pandemic with mitigation of risks of COVID-19 transmission during the immunization process as outlined in the Interim guidance on continuity of immunization programs during the COVID-19 pandemic.
Clinical trials assessing COVID-19 vaccines should continue to be encouraged to include individuals with potential vulnerabilities to disease related to biological (e.g., pre-existing medical conditions, frailty, pregnancy and breastfeeding, immunocompromised), and social (e.g., residence in long term care facilities or crowded/remote locations, belonging to a racialized population, occupation) factors to ensure that vaccine options are informed by robust safety, immunogenicity, and efficacy data as outlined in NACI's guidance on Research Priorities for COVID-19 Vaccines to Support Public Health Decisions.
In addition to ongoing vaccine pharmacovigilance activities in Canada with Phase 4 clinical trials and post-marketing studies, additional research and surveillance of COVID-19 vaccination, particularly in populations not currently included in clinical trials (e.g., pregnant, breastfeeding, immunocompromised, seniors living in congregate care settings, children and adolescents) is recommended. Furthermore, NACI recommends the continuation of clinical trials and ongoing follow-up of participants for as long as it is ethically feasible to determine the level of immunity needed to prevent disease, duration of protection, efficacy in different sub-populations, and medium- and long-term safety.

NACI continues to recommend the following elements to guide ethical decision-making, as outlined in NACI's guidance on Key Populations for Early COVID-19 Immunization:

Efforts should be made to increase access to immunization services to reduce health inequities without further stigmatization or discrimination, and to engage systemically marginalized populations and racialized populations in immunization program planning.
Jurisdictions should ensure close and rapid monitoring of safety, coverage and effectiveness of the vaccine(s) in different key populations, as well as effective and efficient immunization of populations in remote and isolated communities.
Efforts should be made to improve knowledge about the benefits of vaccines in general and of COVID-19 vaccine(s) specifically once available, address misinformation, and communicate transparently about COVID-19 vaccine allocation decisions.

How

Currently authorized COVID-19 vaccine is administered intramuscularly in a two-dose schedule with the second dose administered according to the schedule in Table 2.
Attempts should be made to complete the vaccine series with the same vaccine product.
Serologic testing is not needed before or after receipt of a COVID-19 vaccine to assess susceptibility to SARS-CoV-2 or immune response to the vaccine.
COVID-19 vaccines should not be given simultaneously with other live or inactivated vaccines at this time, unless other vaccines are required for post-exposure prophylaxis.
COVID-19 vaccines should not be given simultaneously with monoclonal antibodies or convalescent plasma.

Why

The COVID-19 pandemic has caused significant morbidity and mortality, as well as social and economic disruption in Canada and worldwide.
The authorized COVID-19 vaccine that is recommended for use by NACI in this Statement has demonstrated safety and efficacy against symptomatic laboratory-confirmed COVID-19 disease.

Introduction

The goal of Canada's pandemic response is to minimize serious illness and death while minimizing societal disruption as a result of the COVID-19 pandemic. Safe and effective COVID-19 vaccines could help achieve this goal. Clinical trials of numerous candidate COVID-19 vaccines are currently underway.

This guidance document will provide recommendations on the use of authorized COVID-19 vaccine(s) as they are approved for use in Canada.

COVID-19 vaccines currently authorized for use in Canada:

The Pfizer-BioNTech COVID-19 vaccine (Pfizer-BioNTech) was authorized for use in Canada on December 9, 2020.

The evidence on COVID-19 and COVID-19 vaccines has been rapidly evolving. To date, NACI has published the following evidence-informed guidance:

Research priorities for COVID-19 vaccines to support public health decisions to inform clinical trials of candidate COVID-19 vaccines to protect against infection, serious illness, and deaths caused by SARS-CoV-2.
Preliminary guidance on key populations for early COVID-19 immunization to plan for the efficient, effective, and equitable allocation of an eventual COVID-19 vaccine when limited initial vaccine supply will necessitate the immunization of some populations earlier than others.
Guidance on the prioritization of initial doses of COVID-19 vaccine(s) for the efficient and equitable prioritization of initial doses of COVID-19 vaccines to assist with the planning for allocation of the first COVID-19 immunization programs.

Guidance objective

The objective of this advisory committee statement is to provide guidance on the effective and equitable use of COVID-19 vaccines authorized for use in Canada in the context of staggered authorization of these vaccines. This evergreen document will be updated as COVID-19 vaccines are authorized for use in Canada, and as evidence on these vaccines evolves. In this guidance document, the evidence and rationale for recommendations as well as current knowledge gaps (e.g. due to the size and short-term follow up in ongoing clinical trials) will be summarized. Clinical trial details on vaccine characteristics for specific COVID-19 vaccines will be included in appendices.

Methods

Details of NACI's recommendation development process can be found elsewhere.^{Footnote 1}^{Footnote 2}

In brief, the broad stages in the preparation of this NACI advisory committee statement included:

Knowledge synthesis
Synthesis of the body of evidence of benefits and harms, considering the quality of the synthesized evidence and magnitude and certainty of effects observed across the studies
Translation of evidence into recommendations

In order to develop comprehensive, appropriate immunization program recommendations, NACI considers a number of factors. In addition to critically appraising evidence on burden of disease and vaccine characteristics such as safety, efficacy, immunogenicity and effectiveness, NACI uses a published, peer-reviewed framework and evidence-informed tools to ensure that issues related to ethics, equity, feasibility, and acceptability (EEFA) are systematically assessed and integrated into its guidance^{Footnote 2}. The NACI Secretariat applied this framework with accompanying evidence-informed tools (Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, Acceptability Matrix) to systematically consider these programmatic factors for the development of clear, comprehensive, appropriate recommendations for timely, transparent decision-making. For details on the development and application of NACI's EEFA Framework and evidence-informed tools (including the Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, and Acceptability Matrix), please see A framework for the systematic consideration of ethics, equity, feasibility, and acceptability in vaccine program recommendations.

For this advisory committee statement, NACI used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to develop population-focused recommendations. Further information on this framework can be found in the GRADE handbook.

NACI reviewed and approved the key policy questions used to guide recommendation development on November 25, 2020 and rated the outcomes for their importance for decision-making. The Canadian Immunization Committee (CIC) provided feedback on the key policy questions to ensure alignment with program needs. Important ethical considerations relating to the key policy questions were presented on November 26, 2020 to the PHAC Public Health Ethics Consultative Group, who provided an assessment of ethical considerations that are relevant to the development of recommendations. Knowledge synthesis and quality appraisal were performed by the NACI Secretariat for unpublished clinical trial evidence and were informed by NACI's rating of the outcomes. Unpublished data from Phase 1 and 2/3 clinical trials were presented to the High Consequence Infectious Disease Working Group and NACI on December 4, 2020 for discussion. Proposed recommendations were then presented and approved on December 7, 2020 at an emergency NACI meeting. The description of relevant considerations, rationale for specific decisions, and knowledge gaps are described in the text.

Epidemiology

Information on COVID-19 is continually evolving. The following section will describe the current basis of knowledge, with an emphasis on the best available Canadian data where possible. To access the most recent updates to specific elements, please refer to the links below.

Disease description

Infectious agent

COVID-19 is caused by the SARS-CoV-2, which was first recognized in Wuhan, China in December 2019.

Transmission

Current evidence suggests that COVID-19 is spread through respiratory droplets and aerosols created when an infected person coughs, sneezes, sings, shouts, or talks. A person may be infectious for up to three days before showing symptoms. More information on the transmission of COVID-19 can be found on the PHAC webpages for COVID-19: Main modes of transmission and COVID-19 signs, symptoms and severity of disease: A clinician guide.

Risk factors

Anyone can be infected with SARS-CoV-2. However, some populations are at increased risk of exposure to the virus (e.g., due to living or work settings), and some populations are at increased risk of severe disease and outcomes (e.g., hospitalization and death) due to various biological (e.g. advanced age, pre-existing medical conditions) and social (e.g., socioeconomic status, belonging to a racialized population) factors that may intersect. Exposure and risk of severe disease factors may overlap, further increasing risk. Any combination of these factors, as well as varying access to health care services, has the potential for disproportionate consequences for specific populations characterized by increased rates of infection and disease, severe illness, hospitalizations, and/or deaths.

Please see NACI's Advisory Committee Statement on Key Populations for Early COVID-19 Immunization and the Equity Matrix^{Footnote 3} for a summary of inequities associated with COVID-19, potential reasons for and intersections between these inequities, and suggested interventions to reduce inequities and improve access to vaccine(s).

More information on the risk factors associated with COVID-19 can be found on PHAC webpages for People who are at high risk for severe illness from COVID-19 and Vulnerable populations and COVID-19.

Spectrum of clinical illness

The median incubation period for COVID-19 has been estimated to be 5 to 6 days from exposure to symptom onset, with most individuals (97.5%) developing symptoms within 11.5 days of exposure.

Clinical presentation and symptoms of COVID-19 vary in frequency and severity. To date, there is no list of symptoms that has been validated to have high specificity or sensitivity for COVID-19.

More information on the spectrum of clinical illness is available on the PHAC webpage for COVID-19 signs, symptoms and severity of disease: A clinician guide.

Disease incidence

Global

Updated international data on COVID-19 cases and deaths is available at: Interactive data visualizations of COVID-19.

Weekly epidemiological updates highlighting key global, regional and country-level data on COVID-19 cases and deaths are available from the World Health Organization (WHO) at: Coronavirus disease (COVID-19) Weekly Epidemiological Update and Weekly Operational Update.

National

Updated national, provincial and territorial-level data on COVID-19 cases and deaths in Canada over time is available from the PHAC webpage on Coronavirus disease (COVID-19): Outbreak update.

Vaccine(s)

The following section summarizes information about COVID-19 vaccines authorized for use in Canada. More detailed vaccine-specific information is included in the appendices. The current landscape of all candidate COVID-19 vaccines in clinical evaluation can be found on the WHO webpage Draft landscape of COVID-19 candidate vaccines. Under the Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19, Health Canada can make regulatory decisions for COVID-19 vaccines that have completed Phase 3 clinical trials for authorized use in Canada.

Most vaccine candidates in development that may become authorized for use in Canada use various technologies to deliver SARS-CoV-2 spike protein to vaccine recipients. This protein is expressed on the surface of the SARS-CoV-2 virus and is a major target for binding and neutralizing antibodies as well as cell-mediated immune responses.

mRNA vaccines

COVID-19 vaccines that use messenger RNA (mRNA) platforms contain modified nucleotides that code for the SARS-CoV-2 spike protein. A lipid nanoparticle formulation delivers the mRNA into the recipient's cells. Once inside a cell, the mRNA provides the instructions that allows the cell to manufacture the spike protein. Once manufactured, the spike protein exits the cell, and becomes anchored onto the cell's surface. The immune system is activated to recognize the spike protein as foreign and initiates an immune response. The mRNA and spike protein are then cleared by the immune system.

mRNA vaccines are not live vaccines and cannot cause infection in the host. mRNA vaccines also cannot alter a person's DNA.

Preparation(s) of COVID-19 vaccines authorized for use in Canada

Table 1: COVID-19 vaccine(s) authorized for use in Canada
Product brand name (Manufacturer)	Pfizer-BioNTech COVID-19 vaccine (Pfizer-BioNTech)
Type of vaccine	COVID-19 mRNA
Date of authorization in Canada	December 9, 2020
Authorized ages for use	16 years of age and older
Dose	30 mcg of mRNA per 0.3 mL (after dilution - see product monograph for choice of diluent and dilution instructions)
Schedule	2 Doses, a minimum of 19 days apart (recommended interval 21-28 days apart)
Route of administration	IM
Nature of the antigen	Prefusion spike protein
Adjuvant (if present)	None
Primary storage requirements	-80°C to -60°C and protected from light
Formats available	Multi-dose vial (5 doses), preservative-free
Usage limit post-dilution	6 Hours from the time of dilution at 2°C to 25°C.
Abbreviations: IM: intramuscular mRNA: messenger ribonucleic acid

Efficacy and effectiveness

Due to the availability of only short-term clinical trial data, the duration of COVID-19 vaccine efficacy, and vaccine effectiveness, are currently unknown. However, studies are ongoing.

The following section highlights key efficacy data for the authorized COVID-19 vaccine (Pfizer-BioNTech COVID-19 vaccine) only. For additional details regarding trial design, including study population, length of follow-up, and efficacy for the Pfizer-BioNTech COVID-19 vaccine, refer to the evidence summary in Appendix A.

Efficacy against symptomatic COVID-19 disease

The currently authorized COVID-19 vaccine has been shown to be highly efficacious in the short term against confirmed symptomatic COVID-19 disease (presence of one or more symptoms plus laboratory confirmation of SARS-CoV-2 infection) from one week after receiving the full two-dose series. This authorized vaccine is similarly efficacious in adults with one or more comorbidities, as well as in younger adults and older adults. However, evidence in adults of a much more advanced age (e.g., 85 years and older) and in long-term care facilities is limited.

The clinical trial data demonstrates that the authorized vaccine is efficacious over the short term in individuals with or without evidence of prior SARS-CoV-2 infection. However, participants with laboratory-confirmed SARS-CoV-2 infection prior to trial start were excluded from the trial and the number of trial participants with evidence of previous infection (as defined by trial protocol) who had confirmed symptomatic COVID-19 disease during the trial was small; therefore, the efficacy in this population and how it compares to those without evidence of previous infection is unknown at this time.

The first dose of the authorized vaccine has been shown to offer at least short-term protection against confirmed COVID-19 disease. The highest efficacy is seen after the second dose is administered. There is currently no available evidence on medium- and long-term efficacy of the authorized COVID-19 vaccine, however trials are ongoing and this Statement will be updated as evidence emerges.

Efficacy against severe disease

There are no data yet to be able to assess the efficacy of the authorized COVID-19 vaccine against hospitalizations or deaths specifically.

The authorized COVID-19 vaccine may be efficacious against severe COVID-19 outcomes (refer to Appendix A for definition of outcomes used in clinical trials), but the number of severe cases that have been observed in clinical trials to date are insufficient to draw firm conclusions at this time.

Efficacy against asymptomatic infection and transmission

There is currently no reported evidence on the efficacy of the authorized COVID-19 vaccine to prevent asymptomatic infection, to reduce viral shedding, or to prevent transmission. However, studies are ongoing.

Immunogenicity

No immunological correlate of protection has been determined for SARS-COV-2; therefore, all immunological evidence in support of vaccine efficacy is indirect and cannot directly be used to estimate efficacy.

There are several key knowledge gaps that affect the understanding of immune responses to COVID-19 vaccine:

Which type of immune responses are important for protection from infection, severe disease, or transmission
The durability of immune responses and how they may change over time
How immune responses to natural infection compare to responses elicited from a vaccine
How immune responses differ across populations (e.g., in immunocompromised, children) or by SARS-CoV-2 serostatus (i.e., past COVID-19 infection)
How immune responses differ based on previous infection with non-SARS-CoV-2 coronaviruses

Due to limitations in the number of participants and duration of follow up from COVID-19 clinical trial data, medium and long-term evidence on immunogenicity is unknown. However, studies are ongoing.

The following section highlights key immunogenicity data for the authorized COVID-19 vaccine (Pfizer-BioNTech COVID-19 vaccine) only. For additional details regarding trial design, including study population and length of follow-up, and immunogenicity for the Pfizer-BioNTech COVID-19 vaccine, refer to the evidence summary in Appendix A.

Humoral immune responses

The peak humoral immune response to the Pfizer-BioNTech COVID-19 vaccine occurred one week after administration of the second dose, based on a small number of participants. After four weeks, the antibody response persisted, but evidence beyond four weeks after the second dose with this vaccine is not available at this time. The immune response (neutralizing antibodies) elicited by one dose accounted for up to 20% of the maximum response seen after the second dose, with evidence of boosting after the second dose. In general, immune responses in older adults were lower than immune responses in younger adults; however, age-related differences reduced over time

Cellular immune responses

The Pfizer-BioNTech COVID-19 vaccine produces a cellular immune response by one week after administration of the second dose. Increases in this response were seen in both younger and older adults.

Vaccine administration

For additional vaccine product-specific information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database. Refer to Vaccine Administration Practices in the Canadian Immunization Guide (CIG), Part 1 - Key Immunization Information for additional general information.

Dose, route of administration, and schedule

Dose

Pfizer-BioNTech COVID-19 vaccine

Each dose is 0.3 mL after dilution, containing 30 mcg of SARS-CoV-2 spike protein mRNA.

The dose for the Pfizer-BioNTech COVID-19 vaccine (0.3 mL) is unique compared to that of most routine vaccinations. Special precaution should be taken to ensure the correct dose is taken from the multi-dose vial.

Route of administration

COVID-19 vaccine is given as an intramuscular (IM) injection into the deltoid muscle. Please refer to the product monograph for details on a specific COVID-19 vaccine prior to administration.

Refer to Vaccine Administration Practices in Part 1 of the CIG for more information on general vaccine administration practices.

Schedule

Refer to Table 2 for a summary of immunization schedules for authorized COVID-19 vaccines.

Table 2: Recommended immunization schedule, by COVID-19 vaccine
Vaccine product (manufacturer)	Immunization schedule	Minimum interval	Authorized interval	Alternate interval
Pfizer-BioNTech COVID-19 (Pfizer-BioNTech)	2-dose schedule	19 days	21 days	28 days

The Pfizer-BioNTech COVID-19 vaccine is efficacious against symptomatic laboratory-confirmed COVID-19 disease when provided as a two-dose schedule 21 days apart. The majority of participants in the clinical trial received the second dose 21 to 27 days apart; however, some received vaccine with a shortened interval. The per-protocol design was 19 to 23 days. An alternate interval of 28 days may be more feasible to implement. This interval is consistent with the minimum interval required for other routine immunizations (e.g., measles-mumps-rubella vaccine) and other COVID-19 vaccines under review by Health Canada. A harmonized approach to the scheduling of COVID-19 vaccines could prevent erroneous administration of other vaccines at less than the recommended minimal interval, should they be authorized.

If administration of the second dose of a COVID-19 vaccine is delayed, the second dose should be provided as soon as possible. Currently, no data on a maximum interval between doses or on medium- or long-term efficacy of COVID-19 vaccines are available. Therefore, every effort should be made to vaccinate with the second dose according to the recommended schedule.

In general, regardless of the time between doses, interruption of a vaccine series does not require restarting the series as delays between doses do not result in a reduction in final antibody concentrations for most multi-dose products. However, the follow-up time in COVID-19 vaccine clinical trials is short and maximum protection may not be attained until the complete vaccine series has been administered.

Refer to Timing of Vaccine Administration in the CIG, Part 1 - Key Immunization Information for more information on general principles for timing of vaccine administration.

Booster doses and re-immunization

There is currently no evidence on the need for booster doses of COVID-19 vaccine after the vaccine series is complete.

Interchangeability

NACI recommends that the vaccine series be completed with the same COVID-19 vaccine product.

Currently, no data exist on the interchangeability of COVID-19 vaccines.

Refer to Principles of Vaccine Interchangeability in the CIG, Part 1 - Key Immunization Information for information on the interchangeability of vaccines in general.

Post-vaccination counseling

NACI recommends that prophylactic oral analgesics or antipyretics (e.g., acetaminophen or ibuprofen) should not be routinely used before or at the time of vaccination, but their use is not a contraindication to vaccination. Oral analgesics or antipyretics may be considered for the management of adverse events (e.g., pain or fever, respectively), if they occur after vaccination.

Analgesics and antipyretics were used in clinical trials of COVID-19 vaccine for the management of pain and/or fever after vaccination. There is currently no evidence on the benefit from administration of oral analgesics for the prevention of immunization injection pain or systemic reactions.

Refer to Vaccine Administration Practices in the CIG, Part 1 - Key Immunization Information for more information on pre- and post-vaccination counseling.

Serological testing

Serologic testing is not needed before or after immunization with COVID-19 vaccine.

Storage requirements

Pfizer-BioNTech COVID-19 vaccine

Frozen vials prior to use

The Pfizer-BioNTech COVID-19 vaccine must be stored at ultra-low temperatures of -80°C to -60°C and protected from light, in the original packaging, until ready to use.

Refer to the re-icing guidelines packaged with the vaccine for instructions regarding the use of the manufacturer's original thermal container for temporary storage.

Vials prior to dilution

The Pfizer-BioNTech COVID-19 vaccine may be thawed and stored at +2°C to +8°C for up to 120 hours (5 days) or at room temperature (up to +25°C) for no more than 2 hours. During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. Thawed vials can be handled in room light conditions.

Do not refreeze thawed vials.

Vials after dilution

The Pfizer-BioNTech COVID-19 vaccine must be stored between +2°C to +25°C and used within 6 hours from the time of dilution. During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. After dilution, the vaccine vials can be handled in room light conditions.

For more information, consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database. Refer to Storage and Handling of Immunizing Agents in the CIG, Part 1 - Key Immunization Information for additional general information.

Simultaneous administration with other vaccines

NACI recommends that COVID-19 vaccines should not be given simultaneously with other live or inactivated vaccines.

Currently, no data exist on the simultaneous administration of COVID-19 vaccine with other vaccines. In the absence of evidence, attempts should be made to avoid simultaneous administration to maximize benefits of COVID-19 vaccination while minimizing any risks of harm, including the potential for immune interference or the erroneous attribution of an adverse event following immunization (AEFI) to a particular vaccine. However, if a COVID-19 vaccine is inadvertently administered at the same time as another vaccine, neither dose should be repeated.

In the absence of evidence, it would be prudent to wait for a period of at least 28 days after the administration of the complete two-dose vaccine series of an mRNA COVID-19 vaccine before the administration of another vaccine (except in the case where another vaccine is required for post-exposure prophylaxis) due to the elicitation of an inflammatory cytokine response. It would be prudent to wait for a period of at least 14 days after the administration of another vaccine before administrating a COVID-19 vaccine.

Refer to Timing of Vaccine Administration in the CIG, Part 1 - Key Immunization Information for more information on simultaneous administration of other vaccines in general.

Vaccine safety and adverse events following immunization (AEFI)

Due to limitations in the number of participants and duration of follow-up from COVID-19 clinical trials, medium- and long-term evidence on vaccine safety is limited. However, studies are ongoing.

The following section highlights key safety and AEFI data for the authorized COVID-19 vaccine (Pfizer-BioNTech COVID-19 vaccine) only. For additional details regarding trial design, including study population and length of follow-up, and safety for the Pfizer-BioNTech COVID-19 vaccine, refer to the evidence summary in Appendix A.

Refer to Part 2 - Vaccine Safety in the CIG for definitions of AEFIs and additional general information on vaccine safety.

Very common and common adverse events

Common adverse events are defined as those that occur in 1% to less than 10% of vaccinees; very common adverse events occur in 10% or more of vaccinees.

Pfizer-BioNTech COVID-19 vaccine

Local

Pain at the injection site is very common after administration of the currently authorized COVID-19 vaccine. More than 80% of recipients experienced injection site pain. Redness and swelling are common after administration. Local adverse events are usually mild or moderate and resolve within a few days of vaccination. Pain at the injection site was slightly more frequent in adults less than 56 years of age.

Systemic

Fatigue, headache, muscle pain, chills, joint pain and fever are all very common after the administration of the currently authorized COVID-19 vaccine. More than half of vaccine recipients experienced headache and/or fatigue. Systemic adverse events are usually mild or moderate intensity and resolve within a few days of vaccination. Systemic reactions are more frequent after the second vaccine dose and among individuals less than 56 years of age.

Uncommon, rare, and very rare adverse events

Uncommon adverse events occur in 0.1% to less than 1% of vaccinees. Rare and very rare adverse events occur in 0.01% to less than 0.1% and less than 0.01% of vaccines, respectively. The probability of detection of very rare adverse events in clinical trials is low given clinical trial population sizes and the duration of follow-up, therefore ongoing pharmacovigilance is essential.

Pfizer-BioNTech COVID-19 vaccine

To date, the available data does not indicate that vaccination of SARS-CoV-2 naïve individuals with authorized COVID-19 vaccines will elicit enhanced or altered disease upon subsequent infection by SARS-CoV-2 (e.g., vaccine-enhanced disease); however, further study is needed.

Lymphadenopathy is an uncommon adverse event that can occur after administration of the currently authorized COVID-19 vaccine.

No other uncommon, rare, or very rare adverse events were reported among vaccinated participants in the clinical trials at this time.

Guidance on reporting adverse events following immunization (AEFI)

Vaccine providers are asked to report AEFIs through local public health departments and to follow AEFI reporting requirements that are specific to their province or territory. In general, any serious (defined as resulting in hospitalization, permanent disability or death) or unexpected adverse event that is temporally related to vaccination should be reported.

In addition to provincial or territorial reporting requirements, the Brighton Collaboration has developed a list of Adverse Events of Special Interest (AESI) that are of particular interest and should be reported, refer to Brighton Collaboration: COVID-19 for the list with definitions.

There may be additional very rare AEFIs that have not been detected through clinical trials to date.

Refer to Adverse Events Following Immunization (AEFI) in the CIG for more information on definitions, reporting, investigating and managing, and causality assessments for AEFIs.

Refer to Reporting Adverse Events Following Immunization (AEFI) in Canada for more information on the completion and submission of AEFI reports.

Contraindications and precautions

Contraindications

The authorized COVID-19 vaccine is contraindicated in individuals with a history of anaphylaxis after previous administration of the vaccine. Vaccine is also contraindicated in persons with proven immediate or anaphylactic hypersensitivity to any component of the vaccine or its container. Clinical trials of the authorized COVID-19 vaccines excluded individuals with a history of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine. Individuals with a history of severe allergic reaction to a component of the COVID-19 vaccine should not receive the COVID-19 vaccine.

For a comprehensive list of components in the vaccine and its container, please consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database.

Potential non-medicinal ingredients in the vaccines known to cause type 1 hypersensitivity reactions ranging from mild cutaneous reactions to anaphylaxis are summarized in Table 3.

Table 3: Potential allergens known to cause type 1 hypersensitivity reactions
Vaccine product (manufacturer)	Potential allergen included in the vaccine or its container^{Footnote 1}	Other products where the allergen may be found^{Footnote 1}
Pfizer-BioNTech COVID-19 (Pfizer-BioNTech)	polyethylene glycol (PEG)	Bowel preparation products for colonoscopy, laxatives, cough syrup, cosmetics, skin care products, and some food and drinks
Footnote 1 N.B. This may not be a complete list. Return to footnote 1 referrer

Refer to Anaphylaxis and other Acute Reactions Following Vaccination in the CIG for information on the management of anaphylaxis post-vaccination in a community setting.

In situations of suspected hypersensitivity or non-anaphylactic allergy to COVID-19 vaccine components, investigation is indicated which may lead to immunization in a controlled setting. Consultation with an allergist is advised. Most instances of anaphylaxis to a vaccine begin within 30 minutes after administration of vaccine. Therefore, if there is a specific concern about a possible allergy to a component of the COVID-19 vaccine being administered, an extended period of observation post-vaccination of 30 minutes may be warranted. Recommendations for the post-vaccination observation period for other vaccines during the pandemic, such as for influenza vaccine, should continue to be followed.

Refer to Anaphylaxis and other Acute Reactions Following Vaccination in the CIG for definition of AEFIs and additional general information.

Precautions

In individuals with bleeding disorders, the condition should be optimally managed prior to immunization to minimize the risk of bleeding. Individuals receiving long-term anticoagulation are not considered to be at higher risk of bleeding complications following immunization and may be safely immunized without discontinuation of their anticoagulation therapy.

Vaccination of individuals who may be currently infected with SARS-CoV-2 is not known to have a detrimental effect on the illness. However, vaccination should be deferred in symptomatic individuals with confirmed or suspected SARS-CoV-2 infection, or those with respiratory symptoms, in order to avoid attributing any complications resulting from infection with SARS-CoV-2 to vaccine-related AEFI and to minimize the risk of COVID-19 transmission at an immunization clinic/venue. If any persons are identified with symptoms on arrival at the venue, they should be instructed to follow current local public health measures.

As a precautionary measure and in light of the need to be able to monitor for COVID-19 vaccine adverse events without potential confounding from symptoms of COVID-19 or other co-existing illnesses, it would be prudent to wait until all symptoms of an acute illness are completely resolved before vaccinating with an authorized COVID-19 vaccine.

Refer to Contraindications and Precautions in the CIG, Part 2 - Vaccine Safety for additional general information.

Drug interactions

There have been no drug interactions studies performed to date.

For more information about potential interactions with products containing anti-SARS-CoV-2 antibodies, refer to section Blood products, human immunoglobulin and timing of immunization, in this Statement.

Blood products, human immunoglobulin and timing of immunization

To date, there is insufficient evidence on the receipt of both a COVID-19 vaccine and anti-SARS-CoV-2 monoclonal antibodies or convalescent plasma for treatment or prevention. Therefore, timing of administration and potential interference between these two products are currently unknown. Administration of these products close together may result in decreased effectiveness of a COVID-19 vaccine and/or anti-SARS-CoV-2 monoclonal antibodies because the monoclonal antibodies have high affinity for the spike protein expressed by the vaccines.

In the post-exposure setting, expert clinical opinion should be sought on a case-by-case basis when deciding whether anti-SARS-CoV-2 monoclonal antibodies would be appropriate to administer after receipt of COVID-19 vaccine, taking into consideration the risk of exposure and the risk of severe COVID-19 disease in the individual.

To date, there is also insufficient evidence on the receipt of both a COVID-19 vaccine and any monoclonal antibodies or convalescent plasma for treatment or prevention of non-COVID-19 disease. Therefore, timing of administration and potential interference between these two products are currently unknown and expert clinical opinion should be sought on a case-by-case basis.

Recommendations

Following the thorough review of available evidence summarized above, as well as the systematic assessment of ethics, equity, feasibility and acceptability considerations with the EEFA Framework^{Footnote 2} as summarized in NACI's Guidance on Key Populations for Early COVID-19 Immunization, NACI makes the following recommendations for public health program level decision-making for the effective and equitable use of COVID-19 vaccines authorized for use in Canada.

NACI will continue to carefully monitor the scientific developments related to COVID-19 and COVID-19 vaccines, as well as ongoing vaccine pharmacovigilance, and will update recommendations as evidence evolves.

Please note:

A strong recommendation applies to most populations/individuals and should be followed unless a clear and compelling rationale for an alternative approach is present.
A discretionary recommendation may be offered for some populations/individuals in some circumstances. Alternative approaches may be reasonable.

Please see Table 4 for a more detailed explanation of the strength of NACI recommendations.

Recommendations on authorized COVID-19 vaccine(s) for public health program level decision-making

(i.e., Provinces/Territories making decisions for publicly funded immunization programs)

These recommendations apply only to COVID-19 vaccine(s) currently authorized in Canada (Pfizer-BioNTech). In considering these recommendations and for the purposes of publicly funded program implementation, provinces and territories may consider local programmatic factors (e.g., logistical and operational contexts, resources).

1. NACI recommends that a complete vaccine series of COVID-19 vaccine should be offered to individuals in the authorized age group without contraindications to the vaccine. In the context of limited vaccine supply, initial doses of COVID-19 vaccine should be prioritized for the key populations outlined in NACI's Guidance on the Prioritization of Initial Doses of COVID-19 Vaccine(s). (Strong NACI Recommendation)