COMIRNATY is contraindicated in individuals who are hypersensitive to the active substance or to any ingredient in the formulation. For a complete listing see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

4.1 Dosing Considerations

The storage, preparation and administration information differ depending on which presentation of the vaccine is considered. Careful attention should be paid to the vial cap and label border colour and the appropriate corresponding instructions must be followed under the subsections below.

For 12 Years of Age and Older 
COMIRNATY is a suspension for intramuscular injection. There are two formulations of COMIRNATY authorized for use in individuals 12 years of age and older. 

• DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)
• DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)

After preparation, a single dose is 0.3 mL.

For Age 5 Years to <12 Years
COMIRNATY is a suspension for intramuscular injection which must be diluted prior to administration. 

• DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)

After preparation, a single dose is 0.2 mL.

For Age 6 Months to <5 Years

COMIRNATY is a suspension for intramuscular injection which must be diluted prior to administration. 

• DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border)

After preparation, a single dose is 0.2 mL. 

4.2 Recommended Dose and Dosage Adjustment

4.2.1 Vaccination Schedule for Individuals 12 Years of Age and Older

• COMIRNATY is administered intramuscularly as a primary series of two doses (0.3 mL each) 3 weeks apart in individuals 12 years of age and older.
• A booster dose of COMIRNATY (0.3 mL) may be administered intramuscularly at least 6 months after completion of the primary series in individuals 16 years of age or older. 

There are currently no data available from Pfizer and BioNTech clinical trials on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the primary vaccination series or for a booster dose. 

When prepared according to their respective instructions, COMIRNATY for 12 years of age and older (DILUTE BEFORE USE: purple cap and purple label border) and COMIRNATY for 12 years of age and older (DO NOT DILUTE: gray cap and gray label border) can be used interchangeably to provide the COVID-19 vaccination series.

COMIRNATY and the Interim Order authorized Pfizer-BioNTech COVID-19 Vaccine, for use in individuals 12 years of age and older, have the same formulation and can be used interchangeably to provide the COVID-19 vaccination series.

Vials of COMIRNATY intended for individuals 12 years of age and older (purple cap/purple label border or gray cap/gray label border) cannot be used to prepare doses for individuals aged 6 months to <12 years.

4.2.2 Vaccination Schedule for Individuals Aged 5 Years to <12 Years

• COMIRNATY is administered intramuscularly as a primary series of two doses (0.2 mL each) 3 weeks apart.
• A booster dose of COMIRNATY (0.2 mL) may be administered intramuscularly at least 6 months after completion of the primary series in individuals 5 years through ˂12 years of age. 

There are no data available on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the primary vaccination series or for a booster dose. Individuals who have received one dose of COMIRNATY should receive a second dose of COMIRNATY to complete the primary vaccination series and for any additional doses.

Vials of COMIRNATY intended for individuals aged 5 years to <12 years (orange cap/orange label border) cannot be used to prepare doses for individuals 6 months to <5 years or 12 years of age and older.

4.2.3 Vaccination Schedule for Individuals Aged 6 Months to <5 Years

COMIRNATY is administered intramuscularly as a primary series of three doses (0.2 mL each). The initial 2 doses are administered 3 weeks apart followed by a third dose administered at least 8 weeks after the second dose.

Children who will turn from 4 to 5 years of age between their doses in the vaccination series should receive their age-appropriate dose at the time of the vaccination and the interval between doses is determined by the child’s age at the start of the vaccination series.

There are no data available on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose of COMIRNATY should continue to receive COMIRNATY to complete the vaccination series.

Vials of COMIRNATY intended for individuals aged 6 months to <5 years (maroon cap/maroon label border) cannot be used to prepare doses for individuals 5 years of age and older.

4.3 Reconstitution

4.3.1 For 12 Years of Age and Older

Two formulations of COMIRNATY are available for individuals 12 years of age and older.

4.3.1.1 For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)

Preparation for Administration

Prior to Dilution:

• The COMIRNATY multiple dose vial with a purple cap and purple label border contains a volume of 0.45 mL. It is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed and diluted prior to administration.
• Vials may be thawed in the refrigerator (2°C to 8°C [35°F to 46°F])or at room temperature (up to 25°C [77°F]) (see  11 STORAGE, STABILITY AND DISPOSAL).
• Prior to dilution, the thawed suspension may contain white to off-white opaque amorphous particles.
• Refer to thawing instructions in the panels below.

Dilution:

• Dilute the vial contents using 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP to form COMIRNATY. Do not add more than 1.8 mL of diluent.
• ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
• After dilution, one vial contains 6^† doses of 0.3 mL.
• After dilution, the vaccine will be an off-white suspension. Inspect vials to confirm there are no particulates and no discolouration is observed. 
• Strict adherence to aseptic techniques must be followed.
• Refer to dilution and dose preparation instructions in the panels below.

†

Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6^th dose from a single vial.

For 12 Years of Age and Older: DILUTE BEFORE USE  (Vials with Purple Cap and Purple Label Border) VIAL AND DOSE VERIFICATION
	Verify that the vial has a purple plastic cap and purple label border.  If the vial has a gray plastic cap and gray label border, refer to the preparation instructions for 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border).  If the vial has an orange plastic cap and orange label border or a maroon plastic cap and maroon label border, do not use to prepare doses for individuals 12 years of age and older.
For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) THAWING PRIOR TO DILUTION
	Thaw vial(s) of COMIRNATY before use either by:  Allowing vial(s) to thaw in the refrigerator (2°C to 8°C [35°F to 46°F]). A carton of vials may take up to 3 hours to thaw, and thawed vials can be stored in the refrigerator for up to 1 month. Allowing vial(s) to sit at room temperature (up to 25°C [77°F]) for 30 minutes. Using either thawing method, vials must reach room temperature before dilution and must be diluted within 2 hours of exposure to room temperature.
	Before dilution, invert vaccine vial gently 10 times. Do not shake. Inspect the liquid in the vial prior to dilution. The liquid is a white to off-white suspension and may contain white to off-white opaque amorphous particles. Do not use if liquid is discoloured or if other particles are observed.
For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) DILUTION
	Obtain sterile 0.9% Sodium Chloride Injection, USP. Use only this as the diluent. Using aseptic technique, withdraw 1.8 mL of 0.9% Sodium Chloride Injection, USP into a transfer syringe (using 21-gauge or narrower needle). Cleanse the vaccine vial stopper with a single-use antiseptic swab. Add 1.8 mL of 0.9% Sodium Chloride Injection, USP into the vaccine vial.
	Equalize vial pressure before removing the needle from the vial by withdrawing 1.8 mL air into the empty diluent syringe.
	Gently invert the vial containing COMIRNATY 10 times to mix.  Do not shake. Inspect the vaccine in the vial. The vaccine will be an off-white suspension. Do not use if vaccine is discoloured or contains particulate matter.
	Record the date and time of first vial puncture (dilution) on the COMIRNATY vial label.  Store between 2°C to 25°C (35°F to 77°F).  Do not freeze or shake the diluted vaccine. If refrigerated, allow the diluted vaccine to come to room temperature prior to use.

For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border) PREPARATION OF INDIVIDUAL 0.3 mL DOSES

Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab, and withdraw 0.3 mL of COMIRNATY, preferentially using low dead-volume syringes and/or needles. Each dose must contain 0.3 mL of vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume. Administer immediately, and no later than 6 hours after dilution. Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. In order to ensure consistent withdrawal of 6 doses of 0.3 mL, it is important to adhere to minimizing volume loss during dose extraction.

4.3.1.2 For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)

The COMIRNATY multiple dose vial with a gray cap and gray label border MUST NOT BE DILUTED prior to administration. Instructions on the handling and dose preparation of the vaccine prior to administration are provided below.

Preparation for Administration
DO NOT DILUTE

• The COMIRNATY multiple dose vial with a gray cap and a gray label border contains a volume of 2.25 mL, and is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
• Vials may be thawed in the refrigerator (2°C to 8°C [35°F to 46°F]) or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
• The thawed suspension may contain white to off-white opaque amorphous particles. 
• One vial contains  6^† doses of 0.3 mL.
• Refer to thawing and dose preparation instructions in the panels below.

†

Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6^th dose from a single vial.

For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) VIAL AND DOSE VERIFICATION
	Verify that the vial has a gray plastic cap and gray label border. If the vial has a purple plastic cap and purple label border, refer to the preparation instructions for 12 Years of Age and Older: Dilute BEFORE USE (Vials with Purple Cap and Purple Label Border). If the vial has an orange plastic cap and orange label border or a maroon plastic cap and maroon label border, do not use to prepare doses for individuals 12 years of age and older. The date printed on the vial and carton reflects the date of manufacture. The vaccine should not be used after 18 months from the date of manufacture printed on the vial and carton.
For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) THAWING PRIOR TO USE
	Thaw vial(s) of COMIRNATY before use either by:  Allowing vial(s) to thaw in the refrigerator [2°C to 8°C (35°F to 46°F)]. A carton of 10 vials may take up to 6 hours to thaw, and thawed vials can be stored in the refrigerator for up to 10 weeks. Allowing vial(s) to sit at room temperature [up to 25°C (77°F)] for 30 minutes. Vials may be stored at room temperature [up to 25°C (77°F)] for up to 12 hours prior to use.
	Before use, mix by inverting vaccine vial gently 10 times.  Do not shake. Prior to mixing, the thawed vaccine may contain white to off-white opaque amorphous particles. After mixing, the vaccine should appear as a white to off-white suspension with no visible particles. Do not use if liquid is discoloured or if particles are observed after mixing.
For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border) PREPARATION OF INDIVIDUAL 0.3 mL DOSES
	Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab, and withdraw 0.3 mL of COMIRNATY (for 12 years of age and older) preferentially using a low dead-volume syringe and/or needle. Each dose must contain 0.3 mL of vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume. Administer immediately and no later than 12 hours after first puncture. Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. In order to ensure consistent withdrawal of 6 doses of 0.3 mL, it is important to adhere to minimizing volume loss during dose extraction.
	Record the date and time of first vial puncture on the vial label.  Store between 2°C to 25°C (35°F to 77°F).  Discard any unused vaccine 121 hours after first puncture.

1

Vial labels and cartons may state that a vial should be discarded 6 hours after first use. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.

4.3.2 For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)

Preparation for Administration

Prior to Dilution:

• The COMIRNATY multiple dose vial (for ages 5 years to <12 years) has an orange cap and an orange label border and contains a volume of 1.3 mL. It is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed and diluted prior to administration.
• Vials of COMIRNATY intended for 12 years of age or older with a purple cap/purple label border or gray cap/gray label border and vials of COMIRNATY intended for individuals aged 6 months to <5 years with a maroon cap/maroon label border cannot be used to prepare doses for individuals aged 5 years to <12 years. 
• Vials may be thawed in the refrigerator at 2°C to 8°C [35°F to 46°F] or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
• Prior to dilution, the thawed suspension may contain opaque amorphous particles.
• Refer to thawing instructions in the panels below.

Dilution:

• Dilute the vial contents using 1.3 mL of sterile 0.9% Sodium Chloride Injection, USP to form COMIRNATY. Do not add more than 1.3 mL of diluent.
• ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
• After dilution, one vial contains 10^* doses of 0.2 mL.
• After dilution, the vaccine will be a white to off-white suspension. Inspect vials to confirm there are no particulates and no discolouration is observed.
• Strict adherence to aseptic techniques must be followed.
• Refer to dilution and dose preparation instructions in the panels below.

*

Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.

For Age 5 Years to <12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border) VIAL AND DOSE VERIFICATION

Verify that the vial has an orange plastic cap and an orange label border. Do not use COMIRNATY vials with a  maroon plastic cap and maroon label border, purple plastic cap/purple label border or gray plastic cap/gray label border to prepare doses for individuals aged 5 years to <12 years.  The date printed on the vial and carton reflects the date of manufacture. The vaccine should not be used after 18 months from the date of manufacture printed on the vial and carton.

THAWING PRIOR TO DILUTION
	Thaw vial(s) of COMIRNATY before use either by: Allowing vial(s) to thaw in the refrigerator [2°C to 8°C (35°F to 46°F)]. A carton of 10 vials may take up to 4 hours to thaw, and thawed vials can be stored in the refrigerator for up to 10 weeks. Allowing vial(s) to sit at room temperature [up to 25°C (77°F)] for 30 minutes. Vials may be stored at room temperature [up to 25°C (77°F)] for up to 12 hours prior to dilution.
	Before dilution, allow the thawed vial to come to room temperature. When at room temperature, mix by inverting vaccine vial gently 10 times.  Do not shake. Inspect the liquid in the vial prior to dilution. The liquid is a white to off-white suspension and may contain white to off-white opaque amorphous particles. Do not use if liquid is discoloured or if other particles are observed.
DILUTION
	Obtain sterile 0.9% Sodium Chloride Injection, USP. Use only this as the diluent. Using aseptic technique, withdraw 1.3 mL of diluent into a transfer syringe (using 21‑gauge or narrower needle). Cleanse the vaccine vial stopper with a single‑use antiseptic swab. Add 1.3 mL of 0.9% Sodium Chloride Injection, USP into the vaccine vial.
	Equalize vial pressure before removing the needle from the vial by withdrawing 1.3 mL air into the empty diluent syringe.
	Gently invert the vial containing COMIRNATY 10 times to mix. Do not shake. Inspect the vaccine in the vial. The vaccine will be a white to off-white suspension. Do not use if vaccine is discoloured or contains particulate matter.
	Record the date and time of first vial puncture (dilution) on the COMIRNATY (for age 5 years to <12 years) vial label. Store between 2°C to 25°C (35°F to 77°F). Do not freeze or shake the diluted vaccine. If refrigerated, allow the diluted vaccine to come to room temperature prior to use. Discard any unused vaccine 121 hours after dilution.
PREPARATION OF INDIVIDUAL 0.2 mL DOSES
	Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab, and withdraw 2 mL of COMIRNATY (for age 5 years to <12 years) preferentially using a low dead-volume syringe and/or needle. Each dose must contain 0.2 mL of vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume. Administer immediately, and no later than 121 hours after dilution. Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. In order to ensure consistent withdrawal of 10 doses of 0.2 mL, it is important to adhere to minimizing volume loss during dose extraction.

4.3.3 For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border)

Preparation for Administration

Prior to Dilution:

• The COMIRNATY multiple dose vial (for age 6 months to <5 years) has a maroon cap and a maroon label border and contains a volume of 0.4 mL. It is supplied as a frozen suspension that does not contain preservative. Each vial must be thawed and diluted prior to administration.
• Vials of COMIRNATY intended for individuals 12 years of age or older with a purple cap/purple label border or gray cap/gray label border and vials of COMIRNATY intended for individuals aged 5 years to <12 years with an orange cap/orange label border cannot be used to prepare doses for individuals aged 6 months to <5 years. 
• Vials may be thawed in the refrigerator at 2°C to 8°C [35°F to 46°F] or at room temperature (up to 25°C [77°F]) (see 11 STORAGE, STABILITY AND DISPOSAL).
• Prior to dilution, the thawed suspension may contain opaque amorphous particles. 
• Refer to thawing instructions in the panels below.

Dilution:

• Dilute the vial contents using 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP to form COMIRNATY. Do not add more than 2.2 mL of diluent.
• ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent.
• After dilution, one vial contains 10* doses of 0.2 mL. 
• After dilution, the vaccine will be a white to off-white suspension. Inspect vials to confirm there are no particulates and no discolouration is observed. 
• Strict adherence to aseptic techniques must be followed. 
• Refer to dilution and dose preparation instructions in the panels below.

1

Vial labels and cartons may state that a vial should be discarded 6 hours after dilution. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.

 

 

*

Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.

 

 

 

For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) VIAL AND DOSE VERIFICATION
	Verify that the vial has a maroon plastic cap and a maroon label border. Do not use COMIRNATY vials with an orange plastic cap/orange label border, purple plastic cap/purple label border or gray plastic cap/gray label border to prepare doses for individuals aged 6 months to <5 years.  The date printed on the vial and carton reflects the date of manufacture. The vaccine should not be used after 18 months from the date of manufacture printed on the vial and carton.
For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) THAWING PRIOR TO DILUTION
	Thaw vial(s) of COMIRNATY before use either by: Allowing vial(s) to thaw in the refrigerator [2°C to 8°C (35°F to 46°F)]. A carton of 10 vials may take up to 2 hours to thaw, and thawed vials can be stored in the refrigerator for up to 10 weeks.  Allowing vial(s) to sit at room temperature [up to 25°C (77°F)] for 30 minutes. Vials may be stored at room temperature [up to 25°C (77°F)] for up to 12 hours prior to dilution.
	Before dilution, allow the thawed vial to come to room temperature. When at room temperature, mix by inverting vaccine vial gently 10 times.  Do not shake. Inspect the liquid in the vial prior to dilution. The liquid is a white to off-white suspension and may contain white to off-white opaque amorphous particles. Do not use if liquid is discoloured or if other particles are observed.
For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) DILUTION
	Obtain sterile 0.9% Sodium Chloride Injection, USP. Use only this as the diluent. Using aseptic technique, withdraw 2.2 mL of diluent into a transfer syringe (using 21 gauge or narrower needle). Cleanse the vaccine vial stopper with a single use antiseptic swab.  Add 2.2 mL of 0.9% Sodium Chloride Injection, USP into the vaccine vial.
	Equalize vial pressure before removing the needle from the vial by withdrawing 2.2 mL air into the empty diluent syringe.
	Gently invert the vial containing COMIRNATY 10 times to mix.  Do not shake. Inspect the vaccine in the vial. The vaccine will be a white to off-white suspension. Do not use if vaccine is discoloured or contains particulate matter.
	Record the date and time of first vial puncture (dilution) on the COMIRNATY (for age 6 months to <5 years) vial label.  Store between 2°C to 25°C (35°F to 77°F).  Do not freeze or shake the diluted vaccine. If refrigerated, allow the diluted vaccine to come to room temperature prior to use. Discard any unused vaccine 121 hours after dilution.

For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border) PREPARATION OF INDIVIDUAL 0.2 mL DOSES

Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab, and withdraw 0.2 mL of COMIRNATY (for age 6 months to  <5 years) preferentially using a low dead-volume syringe and/or needle. Each dose must contain 0.2 mL of vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume. Administer immediately, and no later than 121 hours after dilution. Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. In order to ensure consistent withdrawal of 10 doses of 0.2 mL, it is important to adhere to minimizing volume loss during dose extraction.

1

Vial labels and cartons may state that a vial should be discarded 6 hours after dilution. The information in this Product Monograph supersedes the number of hours printed on vial labels and cartons.

4.4 Administration

4.4.1 For 12 Years of Age and Older

Administer a single 0.3 mL dose of COMIRNATY intramuscularly, preferably in the deltoid muscle.

Do not inject the vaccine intravascularly, subcutaneously or intradermally.

Two formulations of COMIRNATY are available for individuals 12 years of age and older.

• DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)
  After dilution, vials of COMIRNATY (with purple cap and purple label border) contain 6 doses of 0.3 mL of vaccine. 
• DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)
  Vials of COMIRNATY with gray caps and gray label borders contain 6 doses of 0.3 mL of vaccine.

Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off white suspension. During the visual inspection:

• Verify the final dosing volume of 0.3 mL.
• Confirm there are no particulates and that no discolouration is observed. 
• Do not administer if vaccine is discoloured or contains particulate matter.

Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. In order to ensure consistent withdrawal of 6 doses of 0.3 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract a 6^th dose from a single vial. Irrespective of the type of syringe and needle:

• Each dose must contain 0.3 mL of vaccine.
• If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume. 
• Do not pool excess vaccine from multiple vials.

4.4.2 For Age 5 Years to <12 Years 

Administer a single 0.2 mL dose of COMIRNATY intramuscularly, preferably in the deltoid muscle.

Do not inject the vaccine intravascularly, subcutaneously or intradermally. 

DILUTE PRIOR TO USE (Vial with Orange Cap and Orange Label Border).

Visually inspect each dose in the dosing syringe prior to administration. The diluted vaccine will be a white to off white suspension. During the visual inspection:

• Verify the final dosing volume of 0.2 mL.
• Confirm there are no particulates and that no discolouration is observed. 
• Do not administer if vaccine is discoloured or contains particulate matter.

After dilution, vials of COMIRNATY (for age 5 years to <12 years) contain 10 doses of 0.2 mL of vaccine. Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. In order to ensure consistent withdrawal of 10 doses of 0.2 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial. Irrespective of the type of syringe and needle:

• Each dose must contain 0.2 mL of vaccine.
• If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume. 
• Do not pool excess vaccine from multiple vials.

4.4.3 For Age 6 Months to <5 Years 

Administer a single 0.2 mL dose of COMIRNATY intramuscularly. In individuals from 6 to less than 12 months of age, the recommended injection site is the anterolateral aspect of the thigh. In individuals 1 year of age and older, the recommended injection site is the anterolateral aspect of the thigh or the deltoid muscle.

Do not inject the vaccine intravascularly, subcutaneously or intradermally. 

DILUTE PRIOR TO USE (Vial with Maroon Cap and Maroon Label Border).

Visually inspect each dose in the dosing syringe prior to administration. The diluted vaccine will be a white to off white suspension. During the visual inspection:

• Verify the final dosing volume of 0.2 mL.
• Confirm there are no particulates and that no discolouration is observed. 
• Do not administer if vaccine is discoloured or contains particulate matter.

 
After dilution, vials of COMIRNATY (for age 6 months to <5 years) contain 10 doses of 0.2 mL of vaccine. Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. In order to ensure consistent withdrawal of 10 doses of 0.2 mL, it is important to adhere to minimizing volume loss during dose extraction. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial. Irrespective of the type of syringe and needle:

• Each dose must contain 0.2 mL of vaccine.
• If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume. 
• Do not pool excess vaccine from multiple vials.

To help ensure the traceability of vaccines for patient immunization record-keeping as well as safety monitoring, health professionals should record the time and date of administration, quantity of administered dose (if applicable), anatomical site and route of administration, brand name and generic name of the vaccine, the product lot number and expiry date (or manufacture date).

For 12 Years of Age and Older: DILUTE BEFORE USE (Vials with Purple Cap and Purple Label Border)

COMIRNATY is supplied as a frozen suspension in multiple dose vials. Each vial must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine, and contains 6^† doses of 0.3 mL after dilution. Each 0.3 mL dose of COMIRNATY contains 30 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 1. 

COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex. 

COMIRNATY multiple dose vials (with purple cap and purple label border) are supplied in a carton containing 25 multiple dose vials or 195 multiple dose vials. Not all pack sizes may be available.

For 12 Years of Age and Older: DO NOT DILUTE (Vials with Gray Cap and Gray Label Border)

COMIRNATY is supplied as a frozen suspension in multiple dose vials. Do not dilute. Each vial contains 6^† doses of 0.3 mL. Each 0.3 mL dose of COMIRNATY contains 30 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 1. 

COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex. 

COMIRNATY multiple dose vials (with gray cap and gray label border) are supplied in a carton containing 10 multiple dose vials or 195 multiple dose vials. Not all pack sizes may be available.

†

Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a 6th dose from a single vial.

For Age 5 Years to < 12 Years: DILUTE PRIOR TO USE (Vials with Orange Cap and Orange Label Border)

COMIRNATY is supplied as a frozen suspension in multiple dose vials with an orange cap and an orange label border. Each vial must be diluted with 1.3 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine, and contains 10^* doses of 0.2 mL after dilution. Each 0.2 mL dose of COMIRNATY contains 10 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 2. COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex. 

COMIRNATY multiple dose vials (with orange cap and orange label border) are supplied in a carton containing 10 multiple dose vials or 195 multiple dose vials. Not all pack sizes may be available.

*

Low dead-volume syringes and/or needles can be used to extract 10 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 10 doses from a single vial.

For Age 6 Months to <5 Years: DILUTE PRIOR TO USE (Vials with Maroon Cap and Maroon Label Border)

COMIRNATY is supplied as a frozen suspension in multiple dose vials with a maroon cap and a maroon label border. Each vial must be diluted with 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine, and contains 10* doses of 0.2 mL after dilution. Each 0.2 mL dose of COMIRNATY contains 3 mcg of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 (original strain) and the non-medicinal ingredients listed in Table 2.  COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex. 

COMIRNATY multiple dose vials (with maroon cap and maroon label border) are supplied in a carton containing 10 multiple dose vials.

8.1 Adverse Reaction Overview

The safety of the primary series of COMIRNATY was evaluated in participants 6 months of age and older in three clinical studies conducted in the United States, Europe, Turkey, South Africa, and South America.

Study BNT162‑01 (Study 1) was a Phase 1/2, two-part dose-escalation trial that enrolled 60 participants 18 through 55 years of age and 36 participants 56 through 85 years of age.

Study C4591001 (Study 2) is a Phase 1/2/3, multicenter, multinational, randomized, saline placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection (Phase 1) and efficacy (Phase 2/3) study that has enrolled approximately 46,000 participants, 12 years of age or older. Of these, approximately 44,047 participants (22,026 COMIRNATY; 22,021 placebo) in Phase 2/3 are 16 years of age or older (including 378 and 376 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 adolescents are 12 to 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively). Of the total number of COMIRNATY recipients in the study, 20.7 % were 65 years of age and older. Study 2 also included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. HIV-positive participants are included in safety population disposition but are summarized separately in safety analyses.

Study C4591007 (Study 3) is a Phase 1/2/3 study comprised of an open-label vaccine dose finding portion (Phase 1) and a multicenter, multinational, randomized, saline placebo-controlled, observer-blind immunogenicity and efficacy portion (Phase 2/3) that has enrolled approximately 4,600 participants 5 years through <12 years of age. Of these, approximately 3,100 participants received COMIRNATY 10 mcg and approximately 1,500 participants received placebo in the Phase 2/3 part of the study.  Study 3 also enrolled 1,776 participants 6 months through <2 years of age (1,178 COMIRNATY 3 mcg; 598 placebo), and 2,750 participants 2 through <5 years of age (1,835 COMIRNATY 3 mcg; 915 placebo) in Phase 2/3.

Additionally, 306 existing Phase 3 participants 18 through 55 years of age received a booster dose of COMIRNATY approximately 6 months (range of 4.8 to 8.0 months) after completing the second dose in the non‑placebo‑controlled booster dose portion of Study 2. The overall safety profile for the booster dose was similar to that seen after 2 doses.

In a subset of Study 3 Phase 2/3 participants, 401 participants 5 years through <12 years of age received a booster dose of COMIRNATY at least 5 months (range 5 to 9 months) after completing the primary series. The overall safety profile for the booster dose was similar to that seen after the primary series. The analysis of the Study 3 Phase 2/3 subset is based on data up to the cut-off date of March 22, 2022 (median follow-up time of 1.3 months). 

In Study C4591031 (Study 4), a placebo-controlled booster study, 5,081 participants 16 years of age and older were recruited from Study 2 to receive a booster dose of COMIRNATY at least 6 months after the second dose. The overall safety profile for the booster dose was similar to that seen after 2 doses.

The safety evaluation of participants in Study 2, Study 3 and Study 4 is ongoing. In Study 2 and Study 3, all participants 6 months through <5 years of age, 5 through <12 years of age, 12 to 15 years of age and 16 years of age and older in the reactogenicity subset, and a subset of 306 participants 18 through 55 years of age who received a booster dose in Study 2, were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination with an electronic diary during the 7 days following any dose of vaccination. Participants, including those who received a booster in Study 4, continue to be monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 to 1 month after the last dose (all unsolicited adverse events) and 6 months (serious adverse events) after the last vaccination].

Participants 12 Years of Age and Older

At the time of the analysis of Study 2 (data accrued through March 13, 2021), a total of 25,651 (58.2%) participants (13,031 in vaccine group and 12,620 in placebo group) 16 years of age and older had been followed up for at least 4 months, with 3,082 (7.0%) participants (1,778 in vaccine group and 1,304 in placebo group) followed up for at least 6 months after the second dose during the blinded placebo-controlled follow-up period. A total of 12,006 (54.5%) participants originally randomized to the vaccine group in Study 2 had been followed up for at least 6 months after the second dose including the blinded and open-label periods.

In an analysis of Study 2, based on data up to the cut-off date of March 13, 2021, a total of 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 to 15 years of age. Of these, 1,559 (786 COMIRNATY and 773 placebo) adolescents have been followed for ≥4 months after the second dose of COMIRNATY.

In clinical studies with a data cut-off of March 13, 2021, and where 2 doses were administered 3 weeks apart, the most common adverse reactions in the reactogenicity subset (n=4,924) of participants 16 years of age and older after any dose included injection site pain (84.3%), fatigue (64.7%), headache (57.1%), muscle pain (40.2%), chills (34.7%), joint pain (25.0%), fever (15.2%), injection site swelling (11.1%), and injection site redness (9.9%). Additional adverse events reported in the safety population (n=21,926) of participants 16 years of age and older from dose 1 to 1 month after dose 2 included nausea (1.2%), malaise (0.6%), lymphadenopathy (0.4%), asthenia (0.3%), decreased appetite (0.2%), hyperhidrosis (0.1%), lethargy (0.1%), and night sweats (0.1%).  Adverse reactions were usually mild or moderate in intensity and resolved within a few days after vaccination.

The safety profile in 545 participants receiving COMIRNATY that were seropositive for SARS-CoV-2 at baseline was similar to that seen in the general population.

In a clinical study with a data cut-off date of 02 September 2021, the most commonly reported (≥8%) adverse reactions in adolescents 12 through 15 years of age following any dose were pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), and injection site redness (8.6%).

In a clinical study of participants 18 through 55 years of age (N=306), 289 participants (94%) completed the e-diary recording adverse reactions. The most commonly reported adverse reactions (≥10%) following administration of a booster dose were pain at the injection site (83.0%), fatigue (63.7%), headache (48.4%), muscle pain (39.1%), chills (29.1%), and joint pain (25.3%).

In a clinical study of approximately 10,000 participants 16 years of age and older, unsolicited adverse reactions following administration of a booster dose included headache (5%), fever (4.8%), lymphadenopathy (2.8%), pain in extremity (1.1%), nausea (0.9%), malaise (0.7%), and decreased appetite (0.2%).

Participants 5 Years Through ˂12 Years of Age

In an analysis of Study 3 Phase 2/3, based on data up to the cut-off date of October 8, 2021, 2,268  participants (initial enrolment group: 1,518 COMIRNATY 10 mcg and 750 placebo) were 5 years through ˂12 years of age. Of these, 2,171 (95.7%) (1,456 COMIRNATY 10 mcg and 715 placebo) participants have been followed for at least 3 months after Dose 2.  An analysis of Study 3 Phase 2/3 adverse event data also included another 2,379 participants (safety expansion group: 1,591 COMIRNATY 10 mcg and 788 placebo), of whom 71.2% had a follow-up period for at least 2 weeks after Dose 2. The safety evaluation in Study 3 is ongoing.

Adverse reactions following administration of any dose in the initial enrolment safety population (n = 1,518) of children 5 years through ˂12 years of age included pain at the injection site (84.3%), fatigue (51.7%), headache (38.2%), injection site redness (26.4%), injection site swelling (20.4%), muscle pain (17.5%), chills (12.4%), fever (8.3%), joint pain (7.6%), lymphadenopathy (0.9%), rash (0.5%), nausea (0.4%), malaise (0.1%), and decreased appetite (0.1%).

The most frequent adverse reactions in participants 5 years through <12 years of age following the booster dose (data cut-off date of March 22, 2022; median follow-up time of 1.3 months) were injection site pain (73.9%), fatigue (45.6%), headache (34.0%), myalgia (18.3%), chills (10.5%), injection site redness (15.6%), and swelling (16.4%). The most frequently reported unsolicited adverse event was lymphadenopathy (2.5%).

Participants 2 Through <5 Years of Age

Study 3 (Phase 2/3) enrolled 2,750 participants 2 through <5 years of age (1,835 COMIRNATY 3 mcg; 915 placebo). Of these, 2,726 participants (1,819 COMIRNATY 3 mcg; 907 placebo) received 2 doses and 1,369 (50.2%; 910 COMIRNATY 3 mcg and 459 placebo) participants have been followed for at least 4 months after the second dose; 886 participants received a 3-dose primary series (606 COMIRNATY 3 mcg; 280 placebo) and have been followed for a median of 1.4 months after the third dose, based on data in the blinded, placebo-controlled follow-up period up to the cut-off date of April 29, 2022. Adverse reactions following administration of any dose included pain at the injection site (47.0%), fatigue (44.8%), injection site redness (18.9%), fever (10.5%), headache (8.7%), injection site swelling (8.4%), chills (5.7%), muscle pain (5.0%), joint pain (2.4%), and lymphadenopathy (0.1%).

Participants 6 Months Through <2 Years of Age

Study 3 (Phase 2/3) also enrolled 1,776 participants 6 months through <2 years of age (1,178 COMIRNATY 3 mcg; 598 placebo). Of these, 1,762 participants (1,166 COMIRNATY 3 mcg; 596 placebo) received 2 doses and 1,207 (68.5%; 801 COMIRNATY 3 mcg and 406 placebo) participants have been followed for at least 4 months after the second dose; 570 participants received a 3-dose primary series (386 COMIRNATY 3 mcg; 184 placebo) and have been followed for a median of 1.3 months after the third dose, based on data in the blinded, placebo-controlled follow-up period up to the cut-off date of April 29, 2022. Adverse reactions following administration of any dose included irritability (68.4%), decreased appetite (38.6%), tenderness at the injection site (26.4%), injection site redness (17.8%), fever (14.4%), injection site swelling (7.3%), and lymphadenopathy (0.2%).

8.2 Clinical Trial Adverse Reactions

Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

Participants 16 Years of Age and Older – Primary Series (Two Doses)

Solicited Adverse Reactions

Tables 3 through 6 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in the subset of participants 16 years of age and older (n=9,839) in the safety population who were monitored for reactogenicity with an electronic diary.

Study 2 also included 200 participants with confirmed stable human immunodeficiency virus
(HIV) infection. The safety profile of the participants with stable HIV infection receiving COMIRNATY (n = 100) was similar to that seen in the general population.

Unsolicited Adverse Events

The participants were unblinded to offer placebo participants COMIRNATY when they became locally eligible under regulatory approval in December 2020. A total of 25,651 (58.2%) participants (13,031 in vaccine group and 12,620 in placebo group) 16 years of age and older had been followed up for at least 4 months, with 3,082 (7.0%) participants (1,778 in vaccine group and 1,304 in placebo group) followed up for at least 6 months after the second dose during the blinded placebo-controlled follow-up period in Study 2. Adverse events detailed below for participants 16 years of age and older are for the placebo-controlled blinded follow-up period up to the participants’ unblinding dates.

No deaths related to the vaccine were reported in the study.

Among participants 16 through 55 years of age who received at least one dose of study vaccine, 12,995 of whom received COMIRNATY and 13,026 of whom received placebo, unsolicited adverse events were reported by 4,396 (33.8%) participants in the COMIRNATY group and 2,136 (16.4%) participants in the placebo group. In a similar analysis in participants 56 years of age and older that included 8,931 COMIRNATY recipients and 8,895 placebo recipients, unsolicited adverse events were reported by 2,551 (28.6%) participants in the COMIRNATY group and 1,432 (16.1%) participants in the placebo group.  Among participants with confirmed stable HIV infection that included 100 COMIRNATY recipients and 100 placebo recipients, unsolicited adverse events were reported by 29 (29%) participants in the COMIRNATY group and 15 (15%) participants in the placebo group.

Lymphadenopathy was reported in 87 (0.4%) participants in the vaccine group compared to 8 (<0.1%) participants in the placebo group, which is plausibly related to vaccination. Bell’s palsy (facial paralysis and facial paresis) was reported by four participants in the vaccine group and two in the placebo group. In the four vaccinated participants, events began from 3 to 48 days after their last dose, were mild to moderate in severity, and duration ranged from 3 to 68 days. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. Cumulative safety follow-up to at least 6 months after Dose 2 for approximately 12,000 participants who received COMIRNATY showed no other safety signals arising from longer-term follow-up of the study.

Serious Adverse Events
In Study 2, among participants 16 through 55 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY =12,995; placebo = 13,026), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (COMIRNATY = 8,931; placebo = 8,895), serious adverse events were reported by 165 (1.8%) COMIRNATY recipients and 151 (1.7%) placebo recipients who received at least 1 dose of COMIRNATY or placebo, respectively. Among participants with confirmed stable HIV infection serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 2 (2%) COMIRNATY recipients and 2 (2%) placebo recipients.

Pericarditis was reported for one participant in the vaccine group, and no case was reported in the placebo group. Appendicitis was reported as a serious adverse event for 27 participants, 15 vaccine participants and 12 placebo participants. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, thrombotic events, myocarditis or anaphylactic reaction to the vaccine) reported during the blinded placebo-controlled follow-up period of the study.

Participants 16 Years of Age and Older – After Booster Dose

A subset from Study C4591001 (Study 2) Phase 2/3 participants, of 306 adults 18 through 55 years of age who completed the original COMIRNATY 2-dose series, received a booster dose of COMIRNATY approximately 6 months (range of 4.8 to 8.0 months) after receiving Dose 2.

In Study C4591031 (Study 4), a placebo-controlled booster study, participants 16 years of age and older recruited from Study C4591001 (Study 2) received a booster dose of COMIRNATY (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of COMIRNATY. Overall, participants who received a booster dose, had a median follow-up time of 2.5 months after the booster dose to the cut-off date (5 October 2021). Among the participants, the median age was 53.0 years (range 16 through 87 years of age), including 1,175 booster dose recipients (23.1%) who were ≥65 years of age, 49.1% were male and 50.9% were female, 79.0% were White, 14.9% were Hispanic/Latino, 9.2% were Black or African American, 5.5% were Asian, and 1.7% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

Overall, among participants who received a booster dose in a subset from Study C4591001 (Study 2), the median age was 42 years (range 19 through 55 years of age), 45.8% were male and 54.2% were female, 81.4% were White, 27.8% were Hispanic/Latino, 9.2% were Black or African American, 5.2% were Asian, and 0.7% were American Indian/Alaska Native.

In participants who received a booster dose the mean duration of pain at the injection site after the booster dose was 2.6 days (range 1 to 8 days), for redness 2.2 days (range 1 to 15 days), and for swelling 2.2 days (range 1 to 8 days).

Unsolicited Adverse Events

Overall, participants who received a booster dose in Study C4591031 (Study 4), had a median follow-up time of 2.5 months after the booster dose to the cut-off date (October 5, 2021).

In an analysis of all unsolicited adverse events reported following the booster dose of COMIRNATY, through 1 month after the booster dose, in participants 16 through 87 years of age (N = 5,055), adverse reactions included headache (5%), fever (4.8%), lymphadenopathy (2.8%), decreased appetite (0.2%), malaise (0.7%), nausea (0.9%), and pain in extremity (1.1%).

Serious Adverse Events

Of the participants who received a booster dose of COMIRNATY or placebo (COMIRNATY = 5,055; placebo = 5,020) to the cut-off date (October 5, 2021), serious adverse events were reported by 0.3% of COMIRNATY recipients and 0.5% by placebo recipients. There were no notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY. A 17-year-old male in Study 2 was diagnosed with myocarditis three days after receiving the booster dose (Dose 3). The participant was treated and recovered.

Adolescents 12 to 15 Years of Age– Primary Series (Two Doses)

Solicited Adverse Reactions

Table 9 and Table 10 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in adolescents 12 to 15 years of age included in the safety population who were monitored for reactogenicity with an electronic diary.

Unsolicited Adverse Events

In the analysis of Study 2 of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in adolescents 12 to 15 years of age (N=2260; 1,131 COMIRNATY group vs. 1,129 placebo group), those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (9 (0.8%) vs. 2 (0.2%)), and nausea (5 (0.4%) vs. 1 (0.1%)). 

In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date, 69.0% of study participants 12 through 15 years of age had at least 4 months of follow-up after Dose 2. Among participants 12 through 15 years of age who received at least one dose of study vaccine, 1,131 of whom received COMIRNATY and 1,129 of whom received placebo, unsolicited adverse events were reported by 95 (8.4%) participants in the COMIRNATY group and 113 (10.0%) participants in the placebo group.

Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow up were reported by 5.8% of COMIRNATY recipients and by 5.8% of placebo recipients. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy plausibly related to the study intervention were imbalanced, with notably more cases in the COMIRNATY group (7) vs. the placebo group (1). In the analysis of blinded, placebo controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY. 

Serious Adverse Events

In Study 2, among participants 12 through 15 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY = 1,131; placebo = 1,129), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 10 (0.9%) COMIRNATY recipients and 2 (0.2%) placebo recipients. In these analyses, 69.0% (786 COMIRNATY and 773 placebo) of study participants had at least 4 months of follow-up after Dose 2. In the analysis of blinded, placebo-controlled follow-up, there were no notable patterns between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY. In study 2, a 16-year-old male was diagnosed with myopericarditis 3 days after his 2nd dose. The participant was treated and recovered.

Children 5 Years Through ˂12 Years of Age – Primary Series (Two Doses)

Solicited Adverse Reactions

Table 11 and Table 12 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in children 5 years through ˂12 years of age included in the initial enrolment safety population who were monitored for reactogenicity with an electronic diary.

Unsolicited Adverse Events

In the analyses of Study 3 in children 5 years through ˂12 years of age (initial enrolment group: 1,518 COMIRNATY 10 mcg and 750 placebo), 99.5% of participants had at least 30 days and 95.7% of participants had at least 3 months follow-up after Dose 2.

Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow‑up in the initial enrolment group were reported by 1 participant (0.1%) in each group after receiving the vaccine or placebo through the data cut-off date. No serious adverse events were reported that were considered related to vaccination.

Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow‑up in the initial enrolment group were reported by 10.9% of COMIRNATY 10 mcg recipients and by 9.1% of placebo recipients. Lymphadenopathy was reported in 13 (0.9%) participants in the COMIRNATY 10 mcg group vs. 1 (0.1%) in the placebo group. All cases were considered to be mild, with a median onset of 3 days after Dose 1, and 2 days after Dose 2 in the vaccine group. The median duration was 3.5 days (ranged from 1 to 14 days) in the vaccine group. Skin and subcutaneous tissue disorders (including skin rash, dermatitis, eczema and urticaria) were reported in 17 (1.1%) participants in the vaccine group and 5 (0.7%) participants in the placebo group. Most of the events began from 3-11 days after the second dose and were characterized as mild and self-limited. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY. There were no reports of myocarditis/pericarditis or anaphylaxis by the study cut-off date.

Children 5 Years Through ˂12 Years of Age – After Booster Dose

A subset of Phase 2/3 participants 5 years through ˂12 years of age received a booster dose of COMIRNATY at least 5 months after completing the primary series (range 5 to 9 months, 86.8% of participants received the booster dose at least 8 months after Dose 2). Those participants vaccinated prior to February 22, 2022 provided the safety database (n=401), and had a median safety follow-up of 1.3 months from vaccination through the data cut-off date of March 22, 2022. 

The median age of these 401 participants was 8.0 years (range 5 years through ˂12 years of age), 52.4% were male and 47.6% were female, 70.1% were White, 7.2% were Black or African American, 22.9% were Hispanic/Latino, 7.7% were Asian, and 2.0% were American Indian/Alaska Native. 

Solicited Local and Systemic Adverse Reactions

Table 13 and Table 14 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of a booster dose of COMIRNATY for Phase 2/3 participants 5 years through ˂12 years of age.

In participants who received a booster dose, the mean duration of pain at the injection site after the booster dose was 2.4 days (range 1 to 35 days), for redness 2.3 days (range 1 to 12 days), and for swelling 2.3 days (range 1 to 9 days).

Unsolicited Adverse Events

Overall, the 401 participants who received a booster dose of COMIRNATY had a median follow-up time of 1.3 months after the booster dose through the cut-off date. 

In an analysis of all unsolicited adverse events reported in participants 5 years through ˂12 years of age (N = 401) through up to 1 month after the booster dose, lymphadenopathy (n = 10, 2.5%) was an adverse reaction not already captured by solicited local and systemic reactions.

Serious Adverse Events

No serious adverse events were reported after the booster dose through the cut-off date.

Children 2 Through <5 Years of Age – Primary Series (Three Doses)

Solicited Adverse Reactions

Table 15 and Table 16 present the frequency of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in children 2 through <5 years of age who were monitored for reactogenicity with an electronic diary. 

Unsolicited Adverse Events

In the analyses of Study 3 in participants 2 through <5 years of age (606 COMIRNATY; 280 placebo), 76.6% of participants had at least 30 days of follow-up after Dose 3.

Serious adverse events from Dose 1 through 1 month after Dose 3, with an overall median of 1.4 months follow-up after Dose 3, were reported by 0.7% of COMIRNATY recipients and by 0.9% of placebo recipients. One serious adverse event of fever (maximum temperature 40.3°C) on Day 3 after Dose 2 in a 4-year-old was considered possibly related to vaccination.

Non-serious adverse events from Dose 1 through up to 30 days after Dose 3, in ongoing follow up were reported by 18.5% of COMIRNATY recipients and by 18.5% of placebo recipients.

From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 1 (0.1%) of COMIRNATY recipients vs. 0 (0.0%) of placebo recipients. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.

Children 6 Months Through <2 Years of Age – Primary Series (Three Doses)

Solicited Adverse Reactions

Table 17 and Table 18 present the frequency of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in children 6 months through <2 years of age who were monitored for reactogenicity with an electronic diary.

Unsolicited Adverse Events

In the analyses of Study 3 in participants 6 months through 2 years of age (386 COMIRNATY; 184 placebo), 83.7% of participants had at least 30 days of follow-up after Dose 3.

Serious adverse events from Dose 1 through 1 month after Dose 3, with an overall median of 1.3 months follow up after Dose 3, were reported by 1.4% of COMIRNATY recipients and by 2.3% of placebo recipients. No serious adverse events were reported that were considered related to vaccination.

Non-serious adverse events from Dose 1 through up to 1 month after Dose 3, in ongoing follow up were reported by 29.1% of COMIRNATY recipients and by 26.3% of placebo recipients. 

From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 2 (0.2%) of COMIRNATY recipients vs. 0 (0%) of placebo recipients. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.
 

8.5 Post-Market Adverse Reactions

The following adverse reactions have been identified during post authorization use of COMIRNATY.

Cardiac disorders: myocarditis and/or pericarditis (see WARNING AND PRECAUTIONS section)

Immune System Disorders: severe allergic reactions, including anaphylaxis

Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)

Nervous System Disorders: Facial paralysis / Bell’s Palsy, hypoesthesia, paresthesia, dizziness

Skin and subcutaneous tissue disorders and other hypersensitivity reactions: skin rash, pruritus, urticaria, angioedema, erythema multiforme

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. They are included because: a) they represent reactions that are known to occur following immunizations generally; b) they are potentially serious; or c) on the basis of their frequency of reporting.

10.1 Mechanism of Action

The nucleoside-modified messenger RNA in COMIRNATY is formulated in lipid nanoparticles, which enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits both neutralizing antibody and cellular immune responses to the spike (S) antigen, which may contribute to protection against COVID-19 disease.