PFIZER-BIONTECH COVID-19 VACCINE- bnt162b2 injection, suspension 
Pfizer Manufacturing Belgium NV

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PFIZER-BIONTECH COVID-19 VACCINE

FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE (VACCINATION PROVIDERS)

EMERGENCY USE AUTHORIZATION (EUA) OF THE PFIZER-BIONTECH COVID-19 VACCINE TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19)

FOR 6 MONTHS THROUGH 4 YEARS OF AGE
DILUTE BEFORE USE

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved product, Pfizer-BioNTech COVID-19 Vaccine, for active immunization to prevent COVID-19 in individuals 6 months of age and older.

This Fact Sheet pertains only to Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a maroon cap and a label with a maroon border, which MUST BE DILUTED PRIOR TO USE.

The vial labels may state "Age 2y to < 5y" or "Age 6m to < 5y" and carton labels may state "For age 2 years to < 5 years" or "For age 6 months to < 5 years". Vials with either printed age range can be used for individuals 6 months through 4 years of age.

Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a maroon cap and a label with a maroon border is authorized for use to provide a 3-dose primary series to individuals 6 months through 4 years of age.

Pfizer-BioNTech COVID-19 Vaccine, which is supplied in a multiple dose vial with a maroon cap and a label with a maroon border, should not be used in individuals 5 years of age and older because of the potential for vaccine administration errors, including dosing errors.1

SUMMARY OF INSTRUCTIONS FOR COVID-19 VACCINATION PROVIDERS

Vaccination providers enrolled in the federal COVID-19 Vaccination Program must report all vaccine administration errors, all serious adverse events, cases of myocarditis, cases of pericarditis, cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and cases of COVID-19 that result in hospitalization or death following administration of Pfizer-BioNTech COVID-19 Vaccine. See "MANDATORY REQUIREMENTS FOR PFIZER-BIONTECH COVID-19 VACCINE ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION" for reporting requirements.

The Pfizer-BioNTech COVID-19 Vaccine is a suspension for intramuscular injection.

The Pfizer-BioNTech COVID-19 Vaccine for individuals 6 months through 4 years of age is supplied in a multiple dose vial with a maroon cap and a label with a maroon border. The Pfizer-BioNTech COVID-19 Vaccine is administered, after dilution, as a primary series of 3 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 in individuals 6 months through 4 years of age.

Individuals who will turn from 4 years to 5 years of age between any doses in the primary series may receive:

See this Fact Sheet for instructions for preparation and administration. This Fact Sheet may have been updated. For the most recent Fact Sheet, please see www.cvdvaccine.com.

For information on clinical trials that are testing the use of the Pfizer-BioNTech COVID-19 Vaccine for active immunization to prevent COVID-19, please see www.clinicaltrials.gov.

DESCRIPTION OF COVID-19

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus, SARS-CoV-2, that appeared in late 2019. It is predominantly a respiratory illness that can affect other organs. People with COVID-19 have reported a wide range of symptoms, ranging from mild symptoms to severe illness. Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may include: fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhea.

DOSAGE AND ADMINISTRATION

The storage, preparation, and administration information in this Fact Sheet apply to the Pfizer-BioNTech COVID-19 Vaccine which is supplied in a multiple dose vial with a maroon cap and a label with a maroon border and MUST BE DILUTED before use.

Pfizer-BioNTech COVID-19 Vaccine, Multiple Dose Vial with Maroon Cap and a Label with a Maroon Border
Age RangeDilution InformationDoses Per Vial After DilutionDose Volume
*
The vial labels may state "Age 2y to < 5y" or "Age 6m to < 5y" and carton labels may state "For age 2 years to < 5 years" or "For age 6 months to < 5 years". Vials with either printed age range can be used for individuals 6 months through 4 years of age.
6 months through 4 years*Dilute with 2.2 mL sterile 0.9% Sodium Chloride Injection, USP prior to use100.2 mL

Storage and Handling

During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.

Do not refreeze thawed vials.

Vial Storage Prior to Use

Cartons of Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with maroon caps and labels with maroon borders may arrive frozen at ultra-cold conditions in thermal containers with dry ice.

Once received, frozen vials may be immediately transferred to the refrigerator [2°C to 8°C (35°F to 46°F)], thawed and stored for up to 10 weeks. The 10-week refrigerated expiry date should be recorded on the carton at the time of transfer. A carton of 10 vials may take up to 2 hours to thaw at this temperature.

Alternatively, frozen vials may be stored in an ultra-low temperature freezer at -90°C to -60°C (-130°F to -76°F) for up to 12 months from the date of manufacture. Do not store vials at -25°C to -15°C (-13°F to 5°F). Once vials are thawed, they should not be refrozen.

If cartons of Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with maroon caps and labels with maroon borders are received at 2°C to 8°C (35°F to 46°F), they should be stored at 2°C to 8°C (35°F to 46°F). Check that the carton has been updated to reflect the 10 week refrigerated expiry date.

Regardless of storage condition, the vaccine should not be used after 12 months from the date of manufacture printed on the vial and cartons. Expiry dates based on 12 months from the date of the manufacture are shown below.

Printed Manufacturing Date12-Month Expiry Date
01/2022 31-Dec-2022
02/2022 31-Jan-2023
03/2022 28-Feb-2023
04/2022 31-Mar-2023
05/2022 30-Apr-2023
06/2022 31-May-2023

Vial Storage During Use

If not previously thawed at 2°C to 8°C (35°F to 46°F), allow vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.

Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with maroon caps and labels with maroon borders may be stored at room temperature [8°C to 25°C (46°F to 77°F)] for a total of 12 hours prior to dilution.

After dilution, the vial should be held between 2ºC to 25°C (35°F to 77°F). Vials should be discarded 12 hours after dilution, even though some vial and carton labels may state that a vial should be discarded 6 hours after dilution. The information in this Fact Sheet supersedes the information printed on vial labels and cartons.

Transportation of Vials

If local redistribution is needed, undiluted vials may be transported at -90°C to -60°C (-130°F to -76°F) or at 2°C to 8°C (35°F to 46°F).

Dosing and Schedule

The Pfizer-BioNTech COVID-19 Vaccine for individuals 6 months through 4 years of age is supplied in multiple dose vials with maroon caps and labels with maroon borders. The Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly as a primary series of 3 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 in individuals 6 months through 4 years of age.

Individuals who will turn from 4 years to 5 years of age between any doses in the primary series may receive:

Dose Preparation

Each vial MUST BE DILUTED before administering the vaccine.

Prior to Dilution

Dilution

Dilute the vial contents using 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP (not provided) to form the Pfizer-BioNTech COVID-19 Vaccine.

ONLY use sterile 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. Do not add more than 2.2 mL of diluent.

After dilution, 1 vial contains 10 doses of 0.2 mL.

Dilution and Preparation Instructions
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border –
VIAL VERIFICATION
Figure
Maroon plastic cap and label with maroon border.
  • Verify that the vial of Pfizer-BioNTech COVID-19 Vaccine has a maroon plastic cap and a label with a maroon border.
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border –
THAWING PRIOR TO DILUTION
Figure
Store in the refrigerator for up to 10 weeks prior to use.
  • Thaw vial(s) of Pfizer-BioNTech COVID-19 Vaccine before use either by:
    • Allowing vial(s) to thaw in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)]. 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 25ºC (77ºF)] for 30 minutes.
  • Vials may be stored at room temperature [up to 25ºC (77ºF)] for up to 12 hours prior to use.
Figure
Gently × 10
  • Before dilution, 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 opaque amorphous particles.
  • Do not use if liquid is discolored or if other particles are observed.
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border – DILUTION
Figure
Add 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP.
  • 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 (21-gauge or narrower needle).
  • Cleanse the vaccine vial stopper with a single-use antiseptic swab.
  • Add 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP into the vaccine vial.
Figure
Pull back plunger to 2.2 mL to remove air from vial.
  • Equalize vial pressure before removing the needle from the vial by withdrawing 2.2 mL air into the empty diluent syringe.
Figure
Gently × 10
  • Gently invert the vial containing the Pfizer-BioNTech COVID-19 Vaccine 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 discolored or contains particulate matter.
Figure
Record the date and time of dilution.
Use within 12 hours after dilution.
  • Record the date and time of dilution on the vial label.
  • Store between 2°C to 25°C (35°F to 77°F).
  • Discard any unused vaccine 12 hours after dilution.
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border -
WITHRAWAL OF INDIVIDUAL 0.2 mL DOSES
Figure
Withdraw 0.2 mL dose of vaccine.
  • Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab, and withdraw 0.2 mL of the Pfizer-BioNTech COVID-19 Vaccine 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.

Administration

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

Administer the Pfizer-BioNTech COVID-19 Vaccine intramuscularly.

After dilution, vials of Pfizer-BioNTech COVID-19 Vaccine with maroon caps and labels with maroon borders 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. 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:

Contraindications

Do not administer Pfizer-BioNTech COVID-19 Vaccine to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 Vaccine (see Full EUA Prescribing Information).

Warnings

Management of Acute Allergic Reactions

Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of Pfizer-BioNTech COVID-19 Vaccine.

Monitor Pfizer-BioNTech COVID-19 Vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention (CDC) guidelines (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html).

Myocarditis and Pericarditis

Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is highest in males 12 through 17 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae. The CDC has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html).

Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines, in particular in adolescents. Procedures should be in place to avoid injury from fainting.

Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer-BioNTech COVID-19 Vaccine.

Limitation of Effectiveness

Pfizer-BioNTech COVID-19 Vaccine may not protect all vaccine recipients.

Adverse Reactions

Adverse Reactions in Clinical Trials

Adverse reactions in participants 6 through 23 months of age following administration of the Pfizer-BioNTech COVID-19 Vaccine included irritability, decreased appetite, tenderness at the injection site, injection site redness, fever, injection site swelling, and lymphadenopathy (see Full EUA Prescribing Information).

Adverse reactions in participants 2 through 4 years of age following administration of the Pfizer-BioNTech COVID-19 Vaccine included pain at the injection site, fatigue, injection site redness, fever, headache, injection site swelling, chills, muscle pain, joint pain, and lymphadenopathy (see Full EUA Prescribing Information).

Adverse Reactions in Post Authorization Experience

Severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema), diarrhea, vomiting, pain in extremity (arm), syncope, and dizziness have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.

Myocarditis and pericarditis have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.

Additional adverse reactions, some of which may be serious, may become apparent with more widespread use of the Pfizer-BioNTech COVID-19 Vaccine.

Use with Other Vaccines

There is no information on the co-administration of the Pfizer-BioNTech COVID-19 Vaccine with other vaccines.

INFORMATION TO PROVIDE TO VACCINE RECIPIENTS/CAREGIVERS

As the vaccination provider, you must communicate to the recipient or their caregiver, information consistent with the "Fact Sheet for Recipients and Caregivers" (and provide a copy or direct the individual to the website www.cvdvaccine.com to obtain the Fact Sheet for Recipients and Caregivers) prior to the individual receiving each dose of Pfizer-BioNTech COVID-19 Vaccine, including:

For information on clinical trials that are testing the use of the Pfizer-BioNTech COVID-19 Vaccine to prevent COVID-19, please see www.clinicaltrials.gov.

Provide a vaccination card to the recipient or their caregiver with the date when the recipient needs to return for the second dose of Pfizer-BioNTech COVID-19 Vaccine.

Provide the v-safe information sheet to vaccine recipients/caregivers and encourage vaccine recipients to participate in v-safe. V-safe is a new voluntary smartphone-based tool that uses text messaging and web surveys to check in with people who have been vaccinated to identify potential side effects after COVID-19 vaccination. V-safe asks questions that help CDC monitor the safety of COVID-19 vaccines. V-safe also provides second-dose reminders if needed and live telephone follow-up by CDC if participants report a significant health impact following COVID-19 vaccination. For more information, visit: www.cdc.gov/vsafe.

MANDATORY REQUIREMENTS FOR PFIZER-BIONTECH COVID-19 VACCINE ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION

In order to mitigate the risks of using this unapproved product under EUA and to optimize the potential benefit of Pfizer-BioNTech COVID-19 Vaccine, the following items are required. Use of unapproved Pfizer-BioNTech COVID-19 Vaccine for active immunization to prevent COVID-19 under this EUA is limited to the following (all requirements must be met):

  1. Pfizer-BioNTech COVID-19 Vaccine is authorized for use in individuals 6 months of age and older.
  2. The vaccination provider must communicate to the individual receiving the Pfizer-BioNTech COVID-19 Vaccine or their caregiver, information consistent with the "Fact Sheet for Recipients and Caregivers" prior to the individual receiving Pfizer-BioNTech COVID-19 Vaccine.
  3. The vaccination provider must include vaccination information in the state/local jurisdiction's Immunization Information System (IIS) or other designated system.
  4. The vaccination provider is responsible for mandatory reporting of the following to the Vaccine Adverse Event Reporting System (VAERS):
    • vaccine administration errors whether or not associated with an adverse event,
    • serious adverse events* (irrespective of attribution to vaccination),
    • cases of myocarditis,
    • cases of pericarditis,
    • cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and
    • cases of COVID-19 that result in hospitalization or death.
    Complete and submit reports to VAERS online at https://vaers.hhs.gov/reportevent.html. For further assistance with reporting to VAERS call 1-800-822-7967. The reports should include the words "Pfizer-BioNTech COVID-19 Vaccine EUA" in the description section of the report.
  5. The vaccination provider is responsible for responding to FDA requests for information about vaccine administration errors, adverse events, cases of myocarditis, cases of pericarditis, cases of MIS in adults and children, and cases of COVID-19 that result in hospitalization or death following administration of Pfizer-BioNTech COVID-19 Vaccine to recipients.

* Serious adverse events are defined as:

OTHER ADVERSE EVENT REPORTING TO VAERS AND PFIZER INC.

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.

To the extent feasible, report adverse events to Pfizer Inc. using the contact information below or by providing a copy of the VAERS form to Pfizer Inc.

WebsiteFax numberTelephone number
www.pfizersafetyreporting.com1-866-635-83371-800-438-1985

ADDITIONAL INFORMATION

For general questions, visit the website or call the telephone number provided below.

To access the most recent Pfizer-BioNTech COVID-19 Vaccine Fact Sheets, please scan the QR code provided below.

Global websiteTelephone number
www.cvdvaccine.com
Image
1-877-829-2619
(1-877-VAX-CO19)

AVAILABLE ALTERNATIVES

There may be clinical trials or availability under EUA of other COVID-19 vaccines.

FEDERAL COVID-19 VACCINATION PROGRAM

This vaccine is being made available for emergency use exclusively through the CDC COVID-19 Vaccination Program (the Vaccination Program). Healthcare providers must enroll as providers in the Vaccination Program and comply with the provider requirements. Vaccination providers may not charge any fee for the vaccine and may not charge the vaccine recipient any out-of-pocket charge for administration. However, vaccination providers may seek appropriate reimbursement from a program or plan that covers COVID-19 vaccine administration fees for the vaccine recipient (private insurance, Medicare, Medicaid, Health Resources & Services Administration [HRSA] COVID-19 Uninsured Program for non-insured recipients). For information regarding provider requirements and enrollment in the CDC COVID-19 Vaccination Program, see https://www.cdc.gov/vaccines/covid-19/provider-enrollment.html.

Individuals becoming aware of any potential violations of the CDC COVID-19 Vaccination Program requirements are encouraged to report them to the Office of the Inspector General, U.S. Department of Health and Human Services, at 1-800-HHS-TIPS or https://TIPS.HHS.GOV.

AUTHORITY FOR ISSUANCE OF THE EUA

The Secretary of Health and Human Services (HHS) has declared a public health emergency that justifies the emergency use of drugs and biological products during the COVID-19 pandemic. In response, FDA has issued an EUA for the unapproved product, Pfizer-BioNTech COVID-19 Vaccine for active immunization to prevent COVID-19.

FDA issued this EUA, based on Pfizer-BioNTech's request and submitted data.

For the authorized uses, although limited scientific information is available, based on the totality of the scientific evidence available to date, it is reasonable to believe that the Pfizer-BioNTech COVID-19 Vaccine may be effective for the prevention of COVID-19 in individuals as specified in the Full EUA Prescribing Information.

This EUA for the Pfizer-BioNTech COVID-19 Vaccine will end when the Secretary of HHS determines that the circumstances justifying the EUA no longer exist or when there is a change in the approval status of the product such that an EUA is no longer needed.

For additional information about Emergency Use Authorization visit FDA at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.

The Countermeasures Injury Compensation Program

The Countermeasures Injury Compensation Program (CICP) is a federal program that has been created to help pay for related costs of medical care and other specific expenses to compensate people injured after use of certain medical countermeasures. Medical countermeasures are specific vaccines, medications, devices, or other items used to prevent, diagnose, or treat the public during a public health emergency or a security threat. For more information about CICP regarding the Pfizer-BioNTech COVID-19 Vaccine used to prevent COVID-19, visit www.hrsa.gov/cicp, email cicp@hrsa.gov, or call: 1-855-266-2427.

Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany

Logo
Manufactured by
Pfizer Inc., New York, NY 10017

LAB-1516-3.0

Revised: 22 November 2022

END SHORT VERSION FACT SHEET

Long Version (Full EUA Prescribing Information) Begins On Next Page


1
For vaccination of individuals 5 through 11 years of age and 12 years of age and older, refer to the respective Pfizer-BioNTech COVID-19 Vaccine Fact Sheet for Healthcare Providers Administering Vaccine.

FULL EMERGENCY USE AUTHORIZATION (EUA) PRESCRIBING INFORMATION
PFIZER-BIONTECH COVID-19 VACCINE
FULL EMERGENCY USE AUTHORIZATION PRESCRIBING INFORMATION: CONTENTS*
1
AUTHORIZED USE
2
DOSAGE AND ADMINISTRATION
 
2.1 Preparation for Administration
 
2.2 Administration Information
 
2.3 Vaccination Schedule
3
DOSAGE FORMS AND STRENGTHS
4
CONTRAINDICATIONS
5
WARNINGS AND PRECAUTIONS
 
5.1 Management of Acute Allergic Reactions
 
5.2 Myocarditis and Pericarditis
 
5.3 Syncope
 
5.4 Altered Immunocompetence
 
5.5 Limitation of Effectiveness
6
OVERALL SAFETY SUMMARY
 
6.1 Clinical Trials Experience
 
6.2 Post Authorization Experience
8
REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS
10
DRUG INTERACTIONS
11
USE IN SPECIFIC POPULATIONS
 
 
11.3 Pediatric Use
13
DESCRIPTION
14
CLINICAL PHARMACOLOGY
 
14.1 Mechanism of Action
18
CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA
 
18.1 Efficacy of a 2-Dose Primary Series in Participants 16 Years of Age and Older
 
18.2 Effectiveness of a 3-Dose Primary Series in Participants 6 Months Through 4 Years of Age
19
HOW SUPPLIED/STORAGE AND HANDLING
20
PATIENT COUNSELING INFORMATION
21
CONTACT INFORMATION
* Sections or subsections omitted from the full emergency use authorization prescribing information are not listed.

FULL EMERGENCY USE AUTHORIZATION (EUA) PRESCRIBING INFORMATION

1 AUTHORIZED USE

Pfizer-BioNTech COVID-19 Vaccine is authorized for use under an Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months of age and older.

This EUA Prescribing Information pertains only to Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a maroon cap and a label with a maroon border, which is authorized for use in individuals 6 months through 4 years of age.

2 DOSAGE AND ADMINISTRATION

For intramuscular injection only.

The storage, preparation, and administration information in this Prescribing Information apply to the Pfizer-BioNTech COVID-19 Vaccine, which is supplied in a multiple dose vial with a maroon cap and a label with a maroon border.

Pfizer-BioNTech COVID-19 Vaccine, Multiple Dose Vial with Maroon Cap and a Label with a Maroon Border
Age RangeDilution InformationDoses Per Vial After DilutionDose Volume
*
The vial labels may state "Age 2y to < 5y" or "Age 6m to < 5y" and carton labels may state "For age 2 years to < 5 years" or "For age 6 months to < 5 years". Vials with either printed age range can be used for individuals 6 months through 4 years of age.
6 months through 4 years*Dilute with 2.2 mL sterile 0.9% Sodium Chloride Injection, USP prior to use100.2 mL

2.1 Preparation for Administration

Each vial MUST BE DILUTED before administering the vaccine.

Prior to Dilution

  • The Pfizer-BioNTech COVID-19 Vaccine multiple dose vial with a maroon cap and a label with a maroon border contains a volume of 0.4 mL, and is supplied as a frozen suspension that does not contain preservative.
  • Each vial must be thawed before dilution.
    • Vials may be thawed in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room temperature [up to 25ºC (77ºF)].
    • 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 (not provided) to form the Pfizer-BioNTech COVID-19 Vaccine.
  • ONLY use sterile 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. Do not add more than 2.2 mL of diluent.
  • After dilution, 1 vial contains 10 doses of 0.2 mL.
Dilution and Preparation Instructions
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border –
VIAL VERIFICATION
Figure
Maroon plastic cap and label with maroon border.
  • Verify that the vial of Pfizer-BioNTech COVID-19 Vaccine has a maroon plastic cap and a label with a maroon border.
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border –
THAWING PRIOR TO DILUTION
Figure
Store in the refrigerator for up to 10 weeks prior to use.
  • Thaw vial(s) of Pfizer-BioNTech COVID-19 Vaccine before use either by:
    • Allowing vial(s) to thaw in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)]. 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 25ºC (77ºF)] for 30 minutes.
  • Vials may be stored at room temperature [up to 25ºC (77ºF)] for up to 12 hours prior to use.
Figure
Gently × 10
  • Before dilution, 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 opaque amorphous particles.
  • Do not use if liquid is discolored or if other particles are observed.
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border –
DILUTION
Figure
Add 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP.
  • 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 (21-gauge or narrower needle).
  • Cleanse the vaccine vial stopper with a single-use antiseptic swab.
  • Add 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP into the vaccine vial.
Figure
Pull back plunger to 2.2 mL to remove air from vial.
  • Equalize vial pressure before removing the needle from the vial by withdrawing 2.2 mL air into the empty diluent syringe.
Figure
Gently × 10
  • Gently invert the vial containing the Pfizer-BioNTech COVID-19 Vaccine 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 discolored or contains particulate matter.
Figure
Record the date and time of dilution.
Use within 12 hours after dilution.
  • Record the date and time of dilution on the vial label.
  • Store between 2°C to 25°C (35°F to 77°F).
  • Discard any unused vaccine 12 hours after dilution.
Pfizer-BioNTech COVID-19 Vaccine Vial with Maroon Cap and Label with Maroon Border -
WITHRAWAL OF INDIVIDUAL 0.2 mL DOSES
Figure
Withdraw 0.2 mL dose of vaccine.
  • Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab, and withdraw 0.2 mL of the Pfizer-BioNTech COVID-19 Vaccine 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.

2.2 Administration Information

Visually inspect each dose in the dosing syringe prior to administration. The 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 discoloration is observed.
  • do not administer if vaccine is discolored or contains particulate matter.

Administer the Pfizer-BioNTech COVID-19 Vaccine intramuscularly.

After dilution, vials of Pfizer-BioNTech COVID-19 Vaccine with maroon caps and labels with maroon borders 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. 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 content.
  • Do not pool excess vaccine from multiple vials.

2.3 Vaccination Schedule

The Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly as a primary series of 3 doses (0.2 mL each) in individuals 6 months through 4 years of age. The initial 2 doses are administered 3 weeks apart followed by a third dose administered at least 8 weeks after the second dose.

Individuals who will turn from 4 years to 5 years of age between any doses in the primary series may receive:

  • a 2-dose primary series with the Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 5 through 11 years of age (each 0.2 mL dose containing 10 mcg modRNA, supplied in multiple dose vials with orange caps and labels with orange borders).
    OR
  • a 3-dose primary series initiated with the Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 6 months through 4 years of age (each 0.2 mL dose containing 3 mcg modRNA, supplied in multiple dose vials with maroon caps). Each of Doses 2 and 3 may be with:
    • Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 6 months through 4 years of age (supplied in multiple dose vials with maroon caps), or
    • Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 5 years through 11 years of age (supplied in multiple dose vials with orange caps and labels with orange borders).

3 DOSAGE FORMS AND STRENGTHS

Pfizer-BioNTech COVID-19 Vaccine is a suspension for injection.

After preparation, each dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with maroon caps and labels with maroon borders is 0.2 mL for individuals 6 months through 4 years of age [see Dosage and Administration (2.1)].

4 CONTRAINDICATIONS

Do not administer Pfizer-BioNTech COVID-19 Vaccine to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 Vaccine [see Description (13)].

5 WARNINGS AND PRECAUTIONS

5.1 Management of Acute Allergic Reactions

Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of Pfizer-BioNTech COVID-19 Vaccine.

Monitor Pfizer-BioNTech COVID-19 Vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention (CDC) guidelines (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html).

5.2 Myocarditis and Pericarditis

Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is highest in males 12 through 17 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae. The CDC has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html).

5.3 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines, in particular in adolescents. Procedures should be in place to avoid injury from fainting.

5.4 Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer-BioNTech COVID-19 Vaccine.

5.5 Limitation of Effectiveness

The Pfizer-BioNTech COVID-19 Vaccine may not protect all vaccine recipients.

6 OVERALL SAFETY SUMMARY

It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of myocarditis, cases of pericarditis, cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and hospitalized or fatal cases of COVID-19 following vaccination with the Pfizer-BioNTech COVID-19 Vaccine. To the extent feasible, provide a copy of the VAERS form to Pfizer Inc. Please see the REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS section for details on reporting to VAERS and Pfizer Inc.

In a clinical study (Study 3) in participants 6 through 23 months of age who received Pfizer-BioNTech COVID-19 Vaccine containing 3 mcg of a nucleoside-modified messenger RNA encoding the viral spike (S) glycoprotein of SARS-CoV-2 (3 mcg modRNA), 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%).

In a clinical study (Study 3) in participants 2 through 4 years of age who received Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA), 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%).

Post Authorization Experience

Severe allergic reactions, including anaphylaxis, have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.

Myocarditis and pericarditis have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of the primary series Pfizer-BioNTech COVID-19 Vaccine was evaluated in participants 6 months of age and older in 3 clinical studies conducted in the United States, Europe, Turkey, South Africa, and South America.

Study BNT162-01 (Study 1) was a Phase 1/2, 2-part, dose-escalation trial that enrolled 60 participants, 18 through 55 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 43,448 participants [21,720 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA); 21,728 placebo] in Phase 2/3 are 16 years of age or older (including 138 and 145 participants 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 participants are 12 through 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively). Study C4591007 (Study 3) is a Phase 1/2/3 multicenter, randomized, dose-finding, open-label (Phase 1) and multinational, saline placebo-controlled, observer-blind, immunogenicity and efficacy (Phase 2/3) study that has enrolled 4,695 participants 5 through 11 years of age, of whom 3,109 participants received Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 1,538 participants received placebo in Phase 2/3. Study 3 also enrolled 1,776 participants 6 through 23 months of age, of whom 1,178 participants were in the Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) group and 598 participants in the placebo group; and also enrolled 2,750 participants 2 through 4 years of age, of whom 1,835 participants were in the Pfizer-BioNTech COVID-19 Vaccine group and 915 participants in the placebo group in Phase 2/3.

In Study 2 and Study 3, all participants 6 months through 4 years of age, 5 through 11 years of age, 12 through 15 years of age, and a subset of participants 16 years of age and older, were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination in an electronic diary. Participants are being monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month after the last vaccination (all unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination]. Tables 1 through 4 present the frequency and severity of solicited local and systemic reactions, within 7 days following each dose of Pfizer-BioNTech COVID 19 Vaccine and placebo in participants 6 months through 4 years of age.

Participants 6 Through 23 Months of Age (3-Dose Primary Series)

In an analysis of Study 3 (Phase 2/3), based on data in the blinded placebo-controlled follow-up period up to the cutoff date of April 29, 2022, 570 participants 6 through 23 months of age who received a 3-dose primary series [386 Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA); 184 placebo] have been followed for a median of 1.3 months after the third dose.

Demographic characteristics in Study 3 were generally similar with regard to age, gender, race, and ethnicity among participants 6 through 23 months of age who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Among the 1,178 participants 6 through 23 months of age who received at least 1 dose of the Pfizer-BioNTech COVID-19 Vaccine, 50.0% were male and 50.0% were female, 78.3% were White, 9.9% were multi-racial, 13.7% were Hispanic/Latino, 7.7% were Asian, 3.6% were Black or African American, and 0.3% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

The mean duration of tenderness at the injection site after Dose 3 was 1.5 days (range 1 to 9 days), for redness 1.5 days (range 1 to 5 days), and for swelling 1.8 days (range 1 to 3 days) for participants 6 through 23 months of age in the Pfizer-BioNTech COVID-19 Vaccine group in the blinded placebo-controlled follow-up period (cutoff date of April 29, 2022).

Table 1: Study 3 – Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 6 Through 23 Months of Age – Safety Population*
Pfizer-BioNTech COVID-19 Vaccine
Dose 1
N=1159 to 1173
n§ (%)
Placebo
Dose 1
N=591 to 595
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 2
N=1137 to 1147
n§ (%)
Placebo
Dose 2
N=590 to 591
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 3
N=362 to 365
n§ (%)
Placebo
Dose 3
N=170
n§ (%)
Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
*
Randomized participants who received at least 1 dose of the study intervention.
Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA).
N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.
§
n = Number of participants with the specified reaction.
Mild: ≥0.5 to ≤2.0 cm; Moderate: >2.0 to ≤7.0 cm; Severe: >7.0 cm.
#
Mild: hurts if gently touched; Moderate: hurts if gently touched with crying; Severe: causes limitation of limb movement.
Redness
  Any
(≥0.5 cm)
124 (10.6)44 (7.4)107 (9.3)39 (6.6)26 (7.1)9 (5.3)
    Mild114 (9.7)41 (6.9)97 (8.5)36 (6.1)17 (4.7)8 (4.7)
    Moderate10 (0.9)3 (0.5)10 (0.9)3 (0.5)8 (2.2)1 (0.6)
    Severe00001 (0.3)0
Swelling
  Any
(≥0.5 cm)
46 (3.9)15 (2.5)45 (3.9)9 (1.5)10 (2.7)3 (1.8)
    Mild40 (3.4)13 (2.2)39 (3.4)8 (1.4)7 (1.9)3 (1.8)
    Moderate6 (0.5)2 (0.3)6 (0.5)1 (0.2)3 (0.8)0
    Severe000000
Tenderness at the injection site#
  Any192 (16.6)66 (11.2)171 (15.0)50 (8.5)58 (16.0)20 (11.8)
    Mild181 (15.6)61 (10.3)154 (13.5)42 (7.1)51 (14.1)17 (10.0)
    Moderate11 (0.9)5 (0.8)16 (1.4)8 (1.4)7 (1.9)3 (1.8)
    Severe001 (0.1)000
Table 2: Study 3 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 6 Through 23 Months of Age – Safety Population*
Pfizer-BioNTech COVID-19 Vaccine
Dose 1
N=1159 to 1173
n§ (%)
Placebo
Dose 1
N=591 to 595
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 2
N=1137 to 1147
n§ (%)
Placebo
Dose 2
N=590 to 591
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 3
N=362 to 365
n§ (%)
Placebo
Dose 3
N=170
n§ (%)
Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose.
*
Randomized participants who received at least 1 dose of the study intervention.
Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA).
N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose.
§
n = Number of participants with the specified reaction.
Mild: decreased interest in eating; Moderate: decreased oral intake; Severe: refusal to feed.
#
Mild: increased or prolonged sleeping bouts; Moderate: slightly subdued interfering with daily activity; Severe: disabling; not interested in usual daily activity.
Þ
Mild: easily consolable; Moderate: requiring increased attention; Severe: inconsolable; crying cannot be comforted.
ß
Severity was not collected for use of antipyretic or pain medication.
Fever
    ≥38.0℃85 (7.2)43 (7.2)85 (7.4)36 (6.1)25 (6.8)10 (5.9)
    ≥38.0℃ to 38.4℃42 (3.6)22 (3.7)41 (3.6)18 (3.0)14 (3.8)7 (4.1)
    >38.4℃ to 38.9℃23 (2.0)14 (2.4)20 (1.7)11 (1.9)5 (1.4)2 (1.2)
    >38.9℃ to 40.0℃19 (1.6)6 (1.0)23 (2.0)7 (1.2)5 (1.4)1 (0.6)
    >40.0℃1 (0.1)1 (0.2)1 (0.1)01 (0.3)0
Decreased appetite
  Any257 (22.2)125 (21.2)252 (22.2)106 (18.0)73 (20.2)23 (13.5)
    Mild138 (11.9)73 (12.4)157 (13.8)63 (10.7)42 (11.6)13 (7.6)
    Moderate116 (10.0)51 (8.6)91 (8.0)42 (7.1)27 (7.5)10 (5.9)
    Severe3 (0.3)1 (0.2)4 (0.4)1 (0.2)4 (1.1)0
Drowsiness#
  Any313 (27.0)173 (29.3)271 (23.8)125 (21.2)72 (19.9)22 (12.9)
    Mild251 (21.7)130 (22.0)201 (17.7)98 (16.6)50 (13.8)15 (8.8)
    Moderate60 (5.2)41 (6.9)66 (5.8)26 (4.4)21 (5.8)6 (3.5)
    Severe2 (0.2)2 (0.3)4 (0.4)1 (0.2)1 (0.3)1 (0.6)
IrritabilityÞ
  Any593 (51.2)279 (47.2)539 (47.4)240 (40.7)158 (43.6)64 (37.6)
    Mild245 (21.1)106 (17.9)213 (18.7)89 (15.1)56 (15.5)27 (15.9)
    Moderate341 (29.4)173 (29.3)319 (28.1)146 (24.7)101 (27.9)37 (21.8)
    Severe7 (0.6)07 (0.6)5 (0.8)1 (0.3)0
Use of antipyretic or pain medicationß281 (24.0)117 (19.7)243 (21.2)111 (18.8)70 (19.2)28 (16.5)

Unsolicited Adverse Events

In the following analyses of Study 3 in participants 6 through 23 months of age (386 of whom received Pfizer-BioNTech COVID-19 Vaccine and 184 of whom received placebo), 83.7% of participants had at least 30 days of follow-up after Dose 3.

Serious Adverse Events

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 Pfizer-BioNTech COVID-19 Vaccine recipients and by 2.3% of placebo recipients. No serious adverse events were reported that were considered related to vaccination.

Non-Serious Adverse Events

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 Pfizer-BioNTech COVID-19 Vaccine recipients and by 26.3% of placebo recipients.

From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 2 (0.2%) participants in the Pfizer-BioNTech COVID-19 Vaccine group vs. 0 (0%) in the placebo group. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Participants 2 Through 4 Years of Age (3-Dose Primary Series)

In an analysis of Study 3 (Phase 2/3), based on data in the blinded placebo-controlled follow-up period up to the cutoff date of April 29, 2022, 886 participants 2 through 4 years of age who received a 3-dose primary series [606 Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA); 280 placebo] have been followed a median of 1.4 months after the third dose.

Demographic characteristics in Study 3 were generally similar with regard to age, gender, race, and ethnicity among participants 2 through 4 years of age who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Among the 1,835 participants 2 through 4 years of age who received at least 1 dose of the Pfizer-BioNTech COVID-19 Vaccine, 49.1% were male and 50.9% were female, 80.1% were White, 14.4% were Hispanic/Latino, 7.1% were multi-racial, 6.9% were Asian, 5.1% were Black or African American, and 0.2% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

The mean duration of pain at the injection site after Dose 3 was 1.7 days (range 1 to 14 days), for redness 1.5 days (range 1 to 3 days), and for swelling 1.8 days (range 1 to 4 days) for participants 2 through 4 years of age in the Pfizer-BioNTech COVID-19 Vaccine group in the blinded placebo-controlled follow-up period (cutoff date of April 29, 2022).

Table 3: Study 3 – Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 2 Through 4 Years of Age – Safety Population*
Pfizer-BioNTech COVID-19 Vaccine
Dose 1
N=1814 to 1825
n§ (%)
Placebo
Dose 1
N=905 to 909
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 2
N=1772 to 1779
n§ (%)
Placebo
Dose 2
N=877 to 878
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 3
N=547 to 552
n§ (%)
Placebo
Dose 3
N=262
n§ (%)
Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
*
Randomized participants who received at least 1 dose of the study intervention.
Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA).
N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.
§
n = Number of participants with the specified reaction.
Mild: ≥0.5 to ≤2.0 cm; Moderate: >2.0 to ≤7.0 cm; Severe: >7.0 cm.
#
Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Redness
  Any (≥0.5 cm)160 (8.8)77 (8.5)202 (11.4)50 (5.7)60 (10.9)9 (3.4)
    Mild137 (7.5)67 (7.4)170 (9.6)43 (4.9)53 (9.6)7 (2.7)
    Moderate22 (1.2)9 (1.0)31 (1.7)7 (0.8)7 (1.3)2 (0.8)
    Severe1 (0.1)1 (0.1)1 (0.1)000
Swelling
  Any (≥0.5 cm)67 (3.7)26 (2.9)102 (5.7)18 (2.1)17 (3.1)3 (1.1)
    Mild59 (3.2)21 (2.3)81 (4.6)16 (1.8)16 (2.9)3 (1.1)
    Moderate8 (0.4)5 (0.6)21 (1.2)2 (0.2)1 (0.2)0
    Severe000000
Pain at the injection site#
  Any559 (30.8)186 (20.6)550 (31.0)178 (20.3)146 (26.7)35 (13.4)
    Mild522 (28.8)178 (19.7)514 (29.0)169 (19.3)130 (23.8)33 (12.6)
    Moderate37 (2.0)7 (0.8)36 (2.0)8 (0.9)16 (2.9)2 (0.8)
    Severe01 (0.1)01 (0.1)00
Table 4: Study 3 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 2 Through 4 Years of Age – Safety Population*
Pfizer-BioNTech COVID-19 Vaccine
Dose 1
N=1813 to 1824
n§ (%)
Placebo
Dose 1
N=905 to 909
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 2
N=1772 to 1779
n§ (%)
Placebo
Dose 2
N=877 to 878
n§ (%)
Pfizer-BioNTech COVID-19 Vaccine
Dose 3
N=547 to 552
n§ (%)
Placebo
Dose 3
N=262
n§ (%)
Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose.
*
Randomized participants who received at least 1 dose of the study intervention.
Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA).
N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose.
§
n = Number of participants with the specified reaction.
Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.
#
Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.
Þ
Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
ß
Severity was not collected for use of antipyretic or pain medication.
Fever
    ≥38.0℃95 (5.2)48 (5.3)88 (4.9)46 (5.2)28 (5.1)11 (4.2)
    ≥38.0℃ to 38.4℃57 (3.1)24 (2.6)41 (2.3)17 (1.9)16 (2.9)4 (1.5)
    >38.4℃ to 38.9℃24 (1.3)16 (1.8)26 (1.5)21 (2.4)8 (1.4)4 (1.5)
    >38.9℃ to 40.0℃13 (0.7)8 (0.9)19 (1.1)8 (0.9)4 (0.7)3 (1.1)
    >40.0℃1 (0.1)02 (0.1)000
Fatigue
  Any539 (29.7)277 (30.6)456 (25.7)201 (22.9)134 (24.5)57 (21.8)
    Mild335 (18.5)176 (19.4)267 (15.1)120 (13.7)87 (15.9)35 (13.4)
    Moderate198 (10.9)96 (10.6)181 (10.2)78 (8.9)45 (8.2)22 (8.4)
    Severe6 (0.3)5 (0.6)8 (0.5)3 (0.3)2 (0.4)0
Headache
  Any81 (4.5)44 (4.9)81 (4.6)36 (4.1)27 (4.9)11 (4.2)
    Mild63 (3.5)35 (3.9)63 (3.6)23 (2.6)19 (3.5)10 (3.8)
    Moderate18 (1.0)8 (0.9)18 (1.0)12 (1.4)8 (1.5)1 (0.4)
    Severe01 (0.1)01 (0.1)00
Chills
  Any41 (2.3)22 (2.4)53 (3.0)23 (2.6)18 (3.3)7 (2.7)
    Mild28 (1.5)16 (1.8)35 (2.0)17 (1.9)14 (2.6)7 (2.7)
    Moderate10 (0.6)6 (0.7)18 (1.0)6 (0.7)3 (0.5)0
    Severe3 (0.2)0001 (0.2)0
Vomiting#
  Any54 (3.0)24 (2.7)61 (3.4)29 (3.3)9 (1.6)10 (3.8)
    Mild44 (2.4)14 (1.5)55 (3.1)26 (3.0)7 (1.3)9 (3.4)
    Moderate10 (0.6)10 (1.1)6 (0.3)3 (0.3)2 (0.4)1 (0.4)
    Severe000000
DiarrheaÞ
  Any139 (7.7)72 (8.0)118 (6.7)64 (7.3)28 (5.1)13 (5.0)
    Mild130 (7.2)64 (7.1)105 (5.9)57 (6.5)21 (3.8)10 (3.8)
    Moderate9 (0.5)8 (0.9)12 (0.7)7 (0.8)7 (1.3)3 (1.1)
    Severe001 (0.1)000
New or worsened muscle pain
  Any43 (2.4)15 (1.7)46 (2.6)21 (2.4)11 (2.0)4 (1.5)
    Mild33 (1.8)13 (1.4)33 (1.9)17 (1.9)8 (1.5)4 (1.5)
    Moderate9 (0.5)2 (0.2)13 (0.7)4 (0.5)3 (0.5)0
    Severe1 (0.1)00000
New or worsened joint pain
  Any14 (0.8)18 (2.0)24 (1.4)9 (1.0)7 (1.3)2 (0.8)
    Mild12 (0.7)13 (1.4)18 (1.0)6 (0.7)5 (0.9)2 (0.8)
    Moderate2 (0.1)5 (0.6)6 (0.3)3 (0.3)1 (0.2)0
    Severe00001 (0.2)0
Use of antipyretic or pain medicationß197 (10.8)83 (9.1)177 (9.9)74 (8.4)47 (8.5)18 (6.9)

Unsolicited Adverse Events

In the following analyses of Study 3 in participants 2 through 4 years of age (606 of whom received Pfizer-BioNTech COVID-19 Vaccine and 280 of whom received placebo), 76.6% of participants had at least 30 days of follow-up after Dose 3.

Serious Adverse Events

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 Pfizer-BioNTech COVID-19 Vaccine 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

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 Pfizer-BioNTech COVID-19 Vaccine recipients and by 18.5% of placebo recipients.

From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 1 (0.1%) participant in the Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) group vs. 0 (0.0%) in the placebo group. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Participants 5 Through 11 Years of Age (2-Dose Primary Series)

In an analysis of Study 3 (Phase 2/3), based on data up to the cutoff date of September 06, 2021, 2,268 participants [1,518 Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA); 750 placebo] were 5 through 11 years of age. Of these, 2,158 (95.1%) [1,444 Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 714 placebo] participants have been followed for at least 2 months after the second dose. An analysis of Study 3 Phase 2/3 adverse event data also included another 2,379 participants [1,591 Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 788 placebo], of whom 71.2% had a follow-up period for at least 2 weeks after Dose 2 up to the cutoff date of October 8, 2021. The safety evaluation in Study 3 is ongoing.

Demographic characteristics in Study 3 were generally similar with regard to age, gender, race, and ethnicity among participants 5 through 11 years of age who received Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and those who received placebo. Among the 4,647 participants 5 through 11 years of age who received at least 1 dose of the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) or placebo, 51.8% were male and 48.2% were female, 77.3% were White, 5.8% were Black or African American, 16.9% were Hispanic/Latino, 8.3% were Asian, and 0.4% were American Indian/Alaska Native.

Unsolicited Adverse Events

In the following analyses of Study 3 in participants 5 through 11 years of age (1,518 of whom received Pfizer-BioNTech COVID-19 Vaccine [10 mcg modRNA] and 750 of whom received placebo), 99.5% of participants had at least 30 days of follow-up after Dose 2.

Serious Adverse Events

In 1 group of participants (initial enrollment cohort) with a median of 2.3 months follow-up post Dose 2, no serious adverse events were reported that were considered related to vaccination. In a second group of participants (expansion cohort) with a median of 2.4 weeks follow-up post Dose 2, no serious adverse events were reported that were considered related to vaccination.

Non-Serious Adverse Events

In 1 group of participants (initial enrollment cohort), non-serious adverse events from Dose 1 through up to 30 days after Dose 2 up to the cutoff date of September 06, 2021, in ongoing follow-up were reported by 10.9% of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) recipients and by 9.1% of placebo recipients. In this group of participants, >99% had follow-up 30 days post Dose 2. In a second group of participants (expansion cohort) for which the median follow-up was 2.4 weeks (range 0 – 3.7 weeks), non-serious adverse events from Dose 1 through the cutoff date of October 8, 2021, were reported by 7.1% of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) recipients and by 6.3% of placebo recipients.

In the initial enrollment cohort, from Dose 1 through 30 days after Dose 2, lymphadenopathy was reported in 13 (0.9%) participants in the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) group vs. 1 (0.1%) in the placebo group. In the expansion cohort from Dose 1 through the cut-off date, lymphadenopathy was reported in 6 (0.4%) participants in the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) group vs. 3 (0.4%) in the placebo group. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Participants 12 Through 15 Years of Age (2-Dose Primary Series)

In an analysis of Study 2, based on data up to the cutoff date of March 13, 2021, 2,260 participants [1,131 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA); 1,129 placebo] were 12 through 15 years of age. Of these, 1,308 (660 Pfizer-BioNTech COVID-19 Vaccine and 648 placebo) participants have been followed for at least 2 months after the second dose. The safety evaluation in Study 2 is ongoing.

Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Overall, among the participants who received the Pfizer-BioNTech COVID-19 Vaccine, 50.1% were male and 49.9% were female, 85.9% were White, 4.6% were Black or African American, 11.7% were Hispanic/Latino, 6.4% were Asian, and 0.4% were American Indian/Alaska Native.

Unsolicited Adverse Events

In the following analyses of Study 2 in participants 12 through 15 years of age (1,131 of whom received Pfizer-BioNTech COVID-19 Vaccine and 1,129 of whom received placebo), 98.3% of study participants had at least 30 days of follow-up after Dose 2.

Serious Adverse Events

Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.1% of 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 Pfizer-BioNTech COVID-19 Vaccine.

Non-Serious Adverse Events

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 Pfizer-BioNTech COVID-19 Vaccine 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 Pfizer-BioNTech COVID-19 Vaccine group (7) vs. the placebo group (1). There were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Participants 16 Years of Age and Older (2-Dose Primary Series)

At the time of the analysis of Study 2 for the EUA, 37,586 [18,801 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) and 18,785 placebo] participants 16 years of age or older had been followed for a median of 2 months after the second dose.

The safety evaluation in Study 2 is ongoing. The safety population includes participants 16 years and older enrolled by October 9, 2020, and includes safety data accrued through November 14, 2020.

Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Overall, among the total participants who received either the Pfizer-BioNTech COVID-19 Vaccine or placebo, 50.6% were male and 49.4% were female, 83.1% were White, 9.1% were Black or African American, 28.0% were Hispanic/Latino, 4.3% were Asian, and 0.5% were American Indian/Alaska Native.

Unsolicited Adverse Events

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 (Pfizer-BioNTech COVID-19 Vaccine = 10,841; placebo = 10,851), serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.3% of placebo recipients. In a similar analysis, in participants 56 years of age and older (Pfizer-BioNTech COVID-19 Vaccine = 7,960, placebo = 7,934), serious adverse events were reported by 0.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.6% of placebo recipients who received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine or placebo, respectively. In these analyses, 91.6% of study participants had at least 30 days of follow-up after Dose 2.

Appendicitis was reported as a serious adverse event for 12 participants, and numerically higher in the vaccine group, 8 vaccine participants and 4 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, and thrombotic events) that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Non-Serious Adverse Events

In Study 2 in which 10,841 participants 16 through 55 years of age received Pfizer-BioNTech COVID-19 Vaccine and 10,851 participants received placebo, non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported in 29.3% of participants who received Pfizer-BioNTech COVID-19 Vaccine and 13.2% of participants in the placebo group, for participants who received at least 1 dose. Overall in a similar analysis in which 7,960 participants 56 years of age and older received Pfizer-BioNTech COVID-19 Vaccine, non-serious adverse events within 30 days were reported in 23.8% of participants who received Pfizer-BioNTech COVID-19 Vaccine and 11.7% of participants in the placebo group, for participants who received at least 1 dose. In these analyses, 91.6% of study participants had at least 30 days of follow-up after Dose 2.

The higher frequency of reported unsolicited non-serious adverse events among Pfizer-BioNTech COVID-19 Vaccine recipients compared to placebo recipients was primarily attributed to local and systemic adverse events reported during the first 7 days following vaccination that are consistent with adverse reactions solicited among participants in the reactogenicity subset. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy were imbalanced with notably more cases in the Pfizer-BioNTech COVID-19 Vaccine group (64) vs. the placebo group (6), which is plausibly related to vaccination. Throughout the safety follow-up period to date, Bell's palsy (facial paralysis) was reported by 4 participants in the Pfizer-BioNTech COVID-19 Vaccine group. Onset of facial paralysis was Day 37 after Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of Bell's palsy were reported in the placebo group. 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 Pfizer-BioNTech COVID-19 Vaccine.

6.2 Post Authorization Experience

The following adverse reactions have been identified during post authorization use of Pfizer-BioNTech COVID-19 Vaccine. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.

Cardiac Disorders: myocarditis, pericarditis

Gastrointestinal Disorders: diarrhea, vomiting

Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema)

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

Nervous System Disorders: syncope, dizziness

8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS

See Overall Safety Summary (Section 6) for additional information.

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for MANDATORY reporting of the listed events following Pfizer-BioNTech COVID-19 Vaccine to the Vaccine Adverse Event Reporting System (VAERS):

*Serious adverse events are defined as:

Instructions for Reporting to VAERS

The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a VAERS form to FDA using 1 of the following methods:

  • Complete and submit the report online: https://vaers.hhs.gov/reportevent.html, or
  • If you are unable to submit this form electronically, you may fax it to VAERS at 1-877-721-0366. If you need additional help submitting a report you may call the VAERS toll-free information line at 1-800-822-7967 or send an email to info@vaers.org.

IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

  • Patient demographics (e.g., patient name, date of birth)
  • Pertinent medical history
  • Pertinent details regarding admission and course of illness
  • Concomitant medications
  • Timing of adverse event(s) in relationship to administration of the Pfizer-BioNTech COVID-19 Vaccine
  • Pertinent laboratory and virology information
  • Outcome of the event and any additional follow-up information if it is available at the time of the VAERS report. Subsequent reporting of follow-up information should be completed if additional details become available.

The following steps are highlighted to provide the necessary information for safety tracking:

  1. In Box 17, provide information on Pfizer-BioNTech COVID-19 Vaccine and any other vaccines administered on the same day; and in Box 22, provide information on any other vaccines received within 1 month prior.
  2. In Box 18, description of the event:
    1. Write "Pfizer-BioNTech COVID-19 Vaccine EUA" as the first line.
    2. Provide a detailed report of vaccine administration error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved vaccine. Please see information to include listed above.
  3. Contact information:
    1. In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
    2. In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.
    3. In Box 15, provide the address of the facility where vaccine was given (NOT the healthcare provider's office address).

Other Reporting Instructions

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.

To the extent feasible, report adverse events to Pfizer Inc. using the contact information below or by providing a copy of the VAERS form to Pfizer Inc.

WebsiteFax numberTelephone number
www.pfizersafetyreporting.com1-866-635-83371-800-438-1985

10 DRUG INTERACTIONS

There are no data to assess the concomitant administration of the Pfizer-BioNTech COVID-19 Vaccine with other vaccines.

11 USE IN SPECIFIC POPULATIONS

11.3 Pediatric Use

Pfizer-BioNTech COVID-19 Vaccine is authorized for use in individuals 6 months through 17 years of age. This authorization is based on safety and effectiveness data in this age group and adults.

Pfizer-BioNTech COVID-19 Vaccine is not authorized for use in individuals younger than 6 months of age.

13 DESCRIPTION

The Pfizer-BioNTech COVID-19 Vaccine in multiple dose vials with maroon caps and labels with maroon borders is supplied as a frozen suspension; each vial must be diluted with 2.2 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine. Each 0.2 mL dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with maroon caps and labels with maroon borders contains 3 mcg of modRNA encoding the viral spike (S) glycoprotein of the SARS-CoV-2 Wuhan-Hu-1 strain.

Each 0.2 mL dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with maroon caps and labels with maroon borders also includes the following ingredients: lipids (0.04 mg ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.005 mg 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 0.01 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.02 mg cholesterol), 3.2 mg sucrose, 0.006 mg tromethamine, and 0.04 mg tromethamine hydrochloride. The diluent (sterile 0.9% Sodium Chloride Injection, USP) contributes 1.52 mg sodium chloride per dose.

The Pfizer-BioNTech COVID-19 Vaccine does not contain preservative. The vial stoppers are not made with natural rubber latex.

14 CLINICAL PHARMACOLOGY

14.1 Mechanism of Action

The modRNA in the Pfizer-BioNTech COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.

18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

18.1 Efficacy of a 2-Dose Primary Series in Participants 16 Years of Age and Older

Study 2 is a multicenter, multinational, Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in participants 12 years of age and older. Randomization was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19. Participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, were included as were participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).

In the Phase 2/3 portion of Study 2, based on data accrued through November 14, 2020, approximately 44,000 participants 12 years of age and older were randomized equally and received 2 doses of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) or placebo separated by 21 days. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.

The population for the analysis of the primary efficacy endpoint included 36,621 participants 12 years of age and older (18,242 in the Pfizer-BioNTech COVID-19 Vaccine group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. Table 5 presents the specific demographic characteristics in the studied population.

Table 5: Demographics (population for the primary efficacy endpoint)*
Pfizer-BioNTech
COVID-19 Vaccine
(N=18,242)
n (%)
Placebo
(N=18,379)
n (%)
*
All eligible randomized participants who receive all vaccination(s) as randomized within the predefined window, have no other important protocol deviations as determined by the clinician, and have no evidence of SARS-CoV-2 infection prior to 7 days after Dose 2.
Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
100 participants 12 through 15 years of age with limited follow-up in the randomized population received at least 1 dose (49 in the vaccine group and 51 in the placebo group). Some of these participants were included in the efficacy evaluation depending on the population analyzed. They contributed to exposure information but with no confirmed COVID-19 cases, and did not affect efficacy conclusions.
§
Includes multiracial and not reported.
Number of participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease
  • Chronic lung disease (e.g., emphysema and chronic bronchitis, idiopathic pulmonary fibrosis, and cystic fibrosis) or moderate to severe asthma
  • Significant cardiac disease (e.g., heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and pulmonary hypertension)
  • Obesity (body mass index ≥30 kg/m2)
  • Diabetes (Type 1, Type 2 or gestational)
  • Liver disease
  • Human Immunodeficiency Virus (HIV) infection (not included in the efficacy evaluation)
Sex
  Male9318 (51.1)9225 (50.2)
  Female8924 (48.9)9154 (49.8)
Age (years)
  Mean (SD)50.6 (15.70)50.4 (15.81)
  Median52.052.0
  Min, max(12, 89)(12, 91)
Age group
  ≥12 through 15 years46 (0.3)42 (0.2)
  ≥16 through 17 years66 (0.4)68 (0.4)
  ≥16 through 64 years14,216 (77.9)14,299 (77.8)
  ≥65 through 74 years3176 (17.4)3226 (17.6)
  ≥75 years804 (4.4)812 (4.4)
Race
  White15,110 (82.8)15,301 (83.3)
  Black or African American1617 (8.9)1617 (8.8)
  American Indian or Alaska Native118 (0.6)106 (0.6)
  Asian815 (4.5)810 (4.4)
  Native Hawaiian or other Pacific Islander48 (0.3)29 (0.2)
  Other§534 (2.9)516 (2.8)
Ethnicity
  Hispanic or Latino4886 (26.8)4857 (26.4)
  Not Hispanic or Latino13,253 (72.7)13,412 (73.0)
  Not reported103 (0.6)110 (0.6)
Comorbidities
  Yes8432 (46.2)8450 (46.0)
  No9810 (53.8)9929 (54.0)

The population in the primary efficacy analysis included all participants 12 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 through November 14, 2020. Participants 18 through 55 years of age and 56 years of age and older began enrollment from July 27, 2020, 16 through 17 years of age began enrollment from September 16, 2020, and 12 through 15 years of age began enrollment from October 15, 2020.

The vaccine efficacy information is presented in Table 6.

Table 6: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Age Subgroup – Participants Without Evidence of Infection and Participants With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population
Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
*
Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.
Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
N = Number of participants in the specified group.
§
n1 = Number of participants meeting the endpoint definition.
Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
#
n2 = Number of participants at risk for the endpoint.
Þ
No confirmed cases were identified in participants 12 through 15 years of age.
ß
Credible interval for vaccine efficacy (VE) was calculated using a beta-binomial model with a beta (0.700102, 1) prior for θ=r(1-VE)/(1+r(1-VE)), where r is the ratio of surveillance time in the active vaccine group over that in the placebo group.
à
Confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the surveillance time.
First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior SARS-CoV-2 infection*
SubgroupPfizer-BioNTech COVID-19 Vaccine
N=18,198
Cases
n1§
Surveillance Time (n2#)
Placebo
N=18,325
Cases
n1§
Surveillance Time (n2#)
Vaccine Efficacy %
(95% CI)
All participantsÞ8
2.214 (17,411)
162
2.222 (17,511)
95.0
(90.3, 97.6)ß
  16 through 64 years7
1.706 (13,549)
143
1.710 (13,618)
95.1
(89.6, 98.1)à
  65 years and older1
0.508 (3848)
19
0.511 (3880)
94.7
(66.7, 99.9)à
First COVID-19 occurrence from 7 days after Dose 2 in participants with or without evidence of prior SARS-CoV-2 infection
SubgroupPfizer-BioNTech COVID-19 Vaccine
N=19,965
Cases
n1§
Surveillance Time (n2#)
Placebo
N=20,172
Cases
n1§
Surveillance Time (n2#)
Vaccine Efficacy %
(95% CI)
All participantsÞ9
2.332 (18,559)
169
2.345 (18,708)
94.6
(89.9, 97.3)ß
  16 through 64 years8
1.802 (14,501)
150
1.814 (14,627)
94.6
(89.1, 97.7)à
  65 years and older1
0.530 (4044)
19
0.532 (4067)
94.7
(66.8, 99.9)à

18.2 Effectiveness of a 3-Dose Primary Series in Participants 6 Months Through 4 Years of Age

Study 3 is an ongoing Phase 1/2/3 multicenter, randomized, dose finding, open label (Phase 1) and multinational, saline placebo-controlled, observer-blind, immunogenicity and efficacy (Phase 2/3) study to evaluate the safety and effectiveness of Pfizer-BioNTech COVID-19 Vaccine in individuals 6 months through 11 years of age. Randomization was stratified by age: 6 through 23 months of age, 2 through 4 years of age, or 5 through 11 years of age. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19. Results from participants 6 months through 4 years of age are presented in this subsection. In Phase 2/3, a total of 1,776 participants 6 through 23 months of age and 2,750 participants 2 through 4 years of age were randomized 2:1 and received 3 doses of the Pfizer-BioNTech COVID-19 Vaccine or saline placebo.

Effectiveness in individuals 6 months through 4 years of age is based on a comparison of immune responses in this age group to individuals 16 through 25 years of age.

Immunogenicity in Participants 2 Through 4 Years of Age After a 3-Dose Primary Series

Immunogenicity analyses have been performed in the immunobridging subset of 143 Study 3 participants 2 through 4 years of age without evidence of infection up to 1 month after Dose 3 based on a data cutoff date of April 29, 2022.

The evaluable immunogenicity population without prior evidence of SARS-CoV-2 infection up to 1 month after Dose 3 of Pfizer-BioNTech COVID-19 Vaccine was comprised of 143 participants 2 through 4 years of age. Most participants in this analysis population were White (69.2%), with 5.6% Black or African American participants, 11.2% Asian participants, and 11.9% multiracial participants. There were 11.2% Hispanic/Latino participants. The median age was 3.0 years and 44.1% of participants were male. There were 6.3% of participants reported as obese. In the evaluable immunogenicity population (regardless of evidence of prior infection), 11/204 participants (5.4%) were baseline positive for prior SARS-CoV-2 infection.

SARS-CoV-2 50% neutralizing antibody titers (NT50) were compared between an immunogenicity subset of Phase 2/3 participants 2 through 4 years of age from Study 3 at 1 month after the 3-dose primary series and a randomly selected subset from Study 2 Phase 2/3 participants 16 through 25 years of age at 1 month after the 2-dose primary series, using a microneutralization assay against the reference strain (USA_WA1/2020). The primary immunobridging analyses compared the geometric mean titers (using a geometric mean ratio [GMR]) and the seroresponse (defined as achieving at least 4-fold rise in SARS-CoV-2 NT50 from before Dose 1) rates in the evaluable immunogenicity population of participants without evidence of prior SARS-CoV-2 infection up to 1 month after Dose 3 in participants 2 through 4 years of age and up to 1 month after Dose 2 in participants 16 through 25 years of age. The prespecified immunobridging criteria were met for both the GMR and the seroresponse difference (Table 7 and Table 8, respectively).

Table 7: SARS-CoV-2 GMTs (NT50) at 1 Month After Vaccination Series – Immunobridging Subset - Participants 2 Through 4 Years of Age (Study 3) 1 Month After Dose 3 and Participants 16 Through 25 Years of Age (Study 2) 1 Month After Dose 2 – Without Evidence of SARS-CoV-2 Infection – Evaluable Immunogenicity Population
Pfizer-BioNTech COVID-19 Vaccine GMR (95%CI)
(2 Through 4 Years of Age/16 Through 25 Years of Age)*,
3 mcg/Dose
2 Through 4 Years of Age
(1 Month After Dose 3)
n=143
30 mcg/Dose
16 Through 25 Years of Age
(1 Month After Dose 2)
n=170
AssayGMT§
(95% CI§)
GMT§
(95% CI§)
Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of quantitation; NAAT = nucleic-acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Note: Participants who had no serological or virological evidence [(up to 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3) blood sample collection)] of past SARS-CoV-2 infection [(i.e., N-binding antibody [serum] negative at Dose 1, Dose 3 (Study 3) and 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3), SARS-CoV-2 not detected by NAAT [nasal swab] at Dose 1, Dose 2, and Dose 3 (Study 3) study visits, and negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3) blood collection)] and had no medical history of COVID-19 were included in the analysis.
b. Protocol-specified timing for blood sample collection.
*
GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers ([2 through 4 years of age] – [16 through 25 years of age]) and the corresponding CI (based on the Student t distribution).
Immunobridging is declared if the lower bound of the 2-sided 95% CI for the GMR ratio is greater than 0.67 and the point estimate of the GMR is ≥0.8.
n = Number of participants with valid and determinate assay results for the specified assay at the given dose/sampling time point.
§
GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.
SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.
SARS-CoV-2 neutralization assay - NT50 (titer)1535.2
(1388.2, 1697.8)
1180.0
(1066.6, 1305.4)
1.30
(1.13, 1.50)
Table 8: Difference in Percentages of Participants with Seroresponse at 1 Month After Vaccination Series – Immunobridging Subset –Participants 2 Through 4 Years of Age (Study 3) 1 Month after Dose 3 and Participants 16 Through 25 Years of Age (Study 2) 1 Month after Dose 2 Without Evidence of Infection – Evaluable Immunogenicity Population
Pfizer-BioNTech COVID-19 VaccineDifference in Seroresponse Rates %*
(95% CI)
(2 Through 4 Years of Age minus 16 Through 25 Years of Age)
3 mcg/Dose
2 Through 4 Years of Age
(1 Month After Dose 3)
N§=141
30 mcg/Dose
16 Through 25 Years of Age
(1 Month After Dose 2)
N§=170
Assayn (%)
(95% CI#)
n (%)
(95% CI#)
Abbreviations: LLOQ = lower limit of quantitation; NAAT = nucleic acid amplification test; N-binding = SARS-CoV-2 nucleoprotein–binding; NT50 = 50% neutralizing titer 50; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Note: Seroresponse is defined as achieving a ≥4-fold rise from baseline (before Dose 1). If the baseline measurement is below the LLOQ, a postvaccination assay result ≥4 × LLOQ is considered a seroresponse.
Note: Participants who had no serological or virological evidence (up to 1 month after Dose 2 [(Study 2) or 1 month after Dose 3 (Study 3) blood sample collection)[ of past SARS-CoV-2 infection [(i.e., N-binding antibody [serum] negative at pre-Dose 1, pre-Dose 3 (Study 3) and 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3), SARS-CoV-2 not detected by NAAT [nasal swab] at pre-Dose 1, pre-Dose 2, and pre-Dose 3 (Study 3) study visits, and negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3) blood collection)] and had no medical history of COVID-19 were included in the analysis.
b. Protocol-specified timing for blood sample collection.
*
Difference in proportions, expressed as a percentage ([2 through 4 years of age] – [16 through 25 years of age]).
2-sided CI, based on the Miettinen and Nurminen method for the difference in proportions, expressed as a percentage.
Immunobridging is declared if the lower bound of the 2-sided 95% CI for the difference in proportions is greater than -10.0% provided that the immunobridging criteria based on GMR were met.
§
N = number of participants with valid and determinate assay results both before vaccination and at 1 month after Dose 2. These values are the denominators for the percentage calculations.
n = Number of participants with seroresponse for the given assay at the given dose/sampling time point.
#
Exact 2-sided CI based on the Clopper and Pearson method.
Þ
SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.
SARS-CoV-2 neutralization assay - NT50 (titer)Þ141 (100.0)
(97.4, 100.0)
168 (98.8)
(95.8, 99.9)
1.2
(-1.5, 4.2)

Using a non-validated fluorescence focus reduction neutralization test assay against the Omicron variant of SARS-CoV-2 (BA.1), the NT50 GMT at 1 month after Dose 3 among a subset of 34 study participants without evidence of prior SARS-CoV-2 infection (82.5 [95% CI: 55.4, 122.9]) was increased compared to the NT50 GMT before Dose 3 (14.0 [95% CI: 10.6, 18.5]).

Immunogenicity in Participants 6 Through 23 Months of Age After a 3-Dose Primary Series

Immunogenicity analyses have been performed in the immunobridging subset of 82 Study 3 participants 6 through 23 months of age without evidence of infection up to 1 month after Dose 3 based on a data cutoff date of April 29, 2022.

The evaluable immunogenicity population without prior evidence of SARS-CoV-2 infection up to 1 month after Dose 3 of Pfizer-BioNTech COVID-19 Vaccine was comprised of 82 participants 6 through 23 months of age. Most participants in this analysis population were White (72.0%), with 1.2% Black or African American participants, 13.4% Asian participants, and 12.2% multiracial participants. There were 15.9% Hispanic/Latino participants. The median age was 16.0 months and 62.2% of participants were male. In the evaluable immunogenicity population (regardless of evidence of prior infection), 6/132 participants (4.5%) were baseline positive for prior SARS-CoV-2 infection.

SARS-CoV-2 50% neutralizing antibody titers (NT50) 1 month after the vaccination series were compared between an immunogenicity subset of Phase 2/3 participants 6 through 23 months of age from Study 3 and a randomly selected subset from Study 2 Phase 2/3 participants 16 through 25 years of age, using a microneutralization assay against the reference strain (USA_WA1/2020). The primary immunobridging analyses compared the geometric mean titers (using a GMR) and the seroresponse (defined as achieving at least 4-fold rise in SARS-CoV-2 NT50 from before Dose 1) rates in the evaluable immunogenicity population of participants without evidence of prior SARS-CoV-2 infection up to 1 month after Dose 3 in participants 6 through 23 months of age and up to 1 month after Dose 2 in participants 16 through 25 years of age. The prespecified immunobridging criteria were met for both the GMR and the seroresponse difference (Table 9 and Table 10, respectively).

Table 9: SARS-CoV-2 GMTs (NT50) at 1 Month After Vaccination Series – Immunobridging Subset - Participants 6 Through 23 Months of Age (Study 3) 1 Month After Dose 3 and Participants 16 Through 25 Years of Age (Study 2) 1 Month After Dose 2 – Without Evidence of SARS-CoV-2– Evaluable Immunogenicity Population
Pfizer-BioNTech COVID-19 Vaccine GMR (95%CI)
(6 Through 23 months of Age/16 Through 25 Years of Age)*,
3 mcg/Dose
6 Through 23 months of Age
(1 Month After Dose 3)
n=82
30 mcg/Dose
16 Through 25 Years of Age
(1 Month After Dose 2)
n=170
AssayGMT§
(95% CI§)
GMT§
(95% CI§)
Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of quantitation; NAAT = nucleic-acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Note: Participants who had no serological or virological evidence [(up to 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3) blood sample collection)] of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Dose 1, Dose 3 (Study 3) and 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3), SARS-CoV-2 not detected by NAAT [nasal swab] at Dose 1, Dose 2, and Dose 3 (Study 3) study visits, and negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3) blood collection)] and had no medical history of COVID-19 were included in the analysis.
b. Protocol-specified timing for blood sample collection.
*
GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers ([6 through 23 months of age] – [16 through 25 years of age]) and the corresponding CI (based on the Student t distribution).
Immunobridging is declared if the lower bound of the 2-sided 95% CI for the GMR ratio is greater than 0.67 and the point estimate of the GMR is ≥0.8.
n = Number of participants with valid and determinate assay results for the specified assay at the given dose/sampling time point.
§
GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.
SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.
SARS-CoV-2 neutralization assay - NT50 (titer)1406.5
(1211.3, 1633.1)
1180.0
(1066.6, 1305.4)
1.19
(1.00, 1.42)
Table 10: Difference in Percentages of Participants with Seroresponse at 1 Month After Vaccination Series – Immunobridging Subset – Participants 6 Through 23 months of Age (Study 3) 1 Month After Dose 3 and Participants 16 Through 25 Years of Age (Study 2) to 1 Month After Dose 2 Without Evidence of Infection – Evaluable Immunogenicity Population
Pfizer-BioNTech COVID-19 VaccineDifference in Seroresponse Rates %*
(95% CI)
(6 Through 23 months of Age minus 16 Through 25 Years of Age)
3 mcg/Dose 6 Through 23 months of Age
(1 Month After Dose 3)
N§=80
30 mcg/Dose
16 Through 25 Years of Age
(1 Month After Dose 2)
N§=170
Assayn (%)
(95% CI#)
n (%)
(95% CI#)
Abbreviations: LLOQ = lower limit of quantitation; NAAT = nucleic acid amplification test; N-binding = SARS-CoV-2 nucleoprotein–binding; NT50 = 50% neutralizing titer 50; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Note: Seroresponse is defined as achieving a ≥4-fold rise from baseline (before Dose 1). If the baseline measurement is below the LLOQ, a postvaccination assay result ≥4 × LLOQ is considered a seroresponse.
Note: Participants who had no serological or virological evidence [(up to 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3) blood sample collection) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at pre-Dose 1, Dose 3 (Study 3) and 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3), SARS-CoV-2 not detected by NAAT [nasal swab] at pre-Dose 1, pre-Dose 2, and pre-Dose 3 (Study 3) study visits, and negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 (Study 2) or 1 month after Dose 3 (Study 3) blood collection)] and had no medical history of COVID-19 were included in the analysis.
b. Protocol-specified timing for blood sample collection.
*
Difference in proportions, expressed as a percentage ([6 through 23 months of age] – [16 through 25 years of age]).
2-sided CI, based on the Miettinen and Nurminen method for the difference in proportions, expressed as a percentage.
Immunobridging is declared if the lower bound of the 2-sided 95% CI for the difference in proportions is greater than -10.0% provided that the immunobridging criteria based on GMR were met.
§
N = number of participants with valid and determinate assay results both before vaccination and at 1 month after Dose 2. These values are the denominators for the percentage calculations.
n = Number of participants with seroresponse for the given assay at the given dose/sampling time point.
#
Exact 2-sided CI based on the Clopper and Pearson method.
Þ
SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.
SARS-CoV-2 neutralization assay - NT50 (titer)Þ80 (100.0)
(95.5, 100.0)
168 (98.8)
(95.8, 99.9)
1.2
(-3.4, 4.2,)

Using a non-validated fluorescence focus reduction neutralization test assay against the Omicron variant of SARS-CoV-2 (BA.1), the NT50 GMT at 1 month after Dose 3 among a subset of 32 study participants without evidence of prior SARS-CoV-2 infection (127.5 [95% CI: 90.2, 180.1]) was increased compared to the NT50 GMT before Dose 3 (16.3 [95% CI: 12.8, 20.8]).

Efficacy in Participants 6 Months Through 4 Years of Age After a 3-Dose Primary Series

A descriptive efficacy analysis of Study 3 was performed across the combined population of participants 6 months through 4 years of age based on PCR-confirmed COVID-19 cases among 873 participants in the Pfizer-BioNTech COVID-19 Vaccine group and 381 participants in the placebo group (2:1 randomization) who received 3 doses of study intervention during the blinded follow-up period when the Omicron variant of SARS-CoV-2 (BA.2) was the predominant variant in circulation (data cutoff date of June 17, 2022).

The evaluable efficacy population without prior evidence of SARS-CoV-2 infection up to 7 days after Dose 3 of Pfizer-BioNTech COVID-19 Vaccine was comprised of 873 vaccine recipients and 381 placebo recipients 6 months through 4 years of age. Most vaccine recipients in this analysis population were White (76.3%), with 3.4% Black or African American participants, 10.0% Asian participants, and 10.1% who identified as multiracial, other or not reported. There were 11.2% Hispanic/Latino vaccine recipients. Among the vaccine recipients, 51.1% were female. The median age was 16.0 months in vaccine recipients 6 through 23 months of age and the median age was 3.0 years in vaccine recipients 2 through 4 years of age. In the evaluable efficacy population, 8.7% of vaccine recipients had one or more comorbidities that increase the risk of severe COVID-19 as described in the Morbidity and Mortality Weekly Report (MMWR) 69(32);1081–8 and/or obesity (BMI ≥95th percentile) for participants 2 through 4 years of age. Between participants who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo, there were no notable differences in demographics.

The median dose interval between Dose 2 and Dose 3 was 13.4 weeks (range 8 to 33 weeks) among participants 6 through 23 months of age and 10 weeks (range 8 to 34 weeks) among participants 2 through 4 years of age who received Pfizer-BioNTech COVID-19 Vaccine. The median length of blinded follow-up for efficacy after Dose 3 was 1.7 months for participants 6 through 23 months of age and 2.1 months for participants 2 through 4 years of age in the Dose 3 Evaluable Efficacy Population who received Pfizer-BioNTech COVID-19 Vaccine or placebo.

The vaccine efficacy results after Dose 3 in participants 6 months through 4 years of age are presented in Table 11.

Table 11: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 3 – Blinded Follow-Up Period – Participants Without Evidence of Infection and Participants With or Without Evidence of Infection Prior to 7 Days After Dose 3 – Phase 2/3 – 6 Months to <5 Years of Age – Evaluable Efficacy (3-Dose) Population
Abbreviations: NAAT = nucleic acid amplification test; N-binding = SARS-CoV-2 nucleoprotein–binding; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; VE = vaccine efficacy.
Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting; inability to eat/poor feeding).
*
Participants who had no serological or virological evidence (prior to 7 days after receipt of Dose 3) of past SARS-CoV-2 infection (i.e., negative N-binding antibody [serum] result at Dose 1, 1 month post-Dose 2 (if available), Dose 3 (if available) visits, SARS-CoV-2 not detected by NAAT [nasal swab] at Dose 1, Dose 2, and Dose 3 study visits, and a negative NAAT [nasal swab] result at any unscheduled visit prior to 7 days after receipt of Dose 3) and had no medical history of COVID-19 were included in the analysis.
N = number of participants in the specified group.
n1 = Number of participants meeting the endpoint definition.
§
Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 3 to the end of the surveillance period.
n2 = Number of participants at risk for the endpoint.
#
Two-sided 95% confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
First COVID-19 occurrence from 7 days after Dose 3 in participants without evidence of prior SARS-CoV-2 infection*
SubgroupPfizer-BioNTech COVID-19 Vaccine
3 mcg/Dose
N=873
Cases
n1
Surveillance Time§ (n2)
Placebo
N=381
Cases
n1
Surveillance Time§ (n2)
Vaccine Efficacy %
(95% CI#)
6 months through 4 years#13
0.124 (794)
21
0.054 (351)
73.2
(43.8, 87.6)
  2 through 4 years9
0.081 (498)
13
0.033 (204)
71.8
(28.6, 89.4)
  6 through 23 months4
0.042 (296)
8
0.020 (147)
75.8
(9.7, 94.7)
First COVID-19 occurrence from 7 days after Dose 3 in participants with or without evidence of prior SARS-CoV-2 infection
SubgroupPfizer-BioNTech COVID-19 Vaccine
3 mcg/Dose
N=1294
Cases
n1
Surveillance Time§
(n2)
Placebo
N=612
Cases
n1
Surveillance Time§
(n2)
Vaccine Efficacy %
(95% CI#)
6 months through 4 years#14
0.149 (981)
23
0.067 (459)
72.5
(44.3, 86.9)
  2 through 4 years10
0.100 (639)
15
0.044 (286)
70.7
(30.3, 88.2)
  6 through 23 months4
0.048 (342)
8
0.023 (173)
76.2
(11.1, 94.8)

Among participants 6 months through 4 years of age, severe COVID-19 case criteria were fulfilled after Dose 3 in 1 placebo recipient in the 6 through 23-month age group. This case occurred 44 days after Dose 3, based on a single criterion (increased heart rate) and did not require hospitalization. There were no cases of multisystem inflammatory syndrome in children reported through the June 17, 2022 data cutoff date.

19 HOW SUPPLIED/STORAGE AND HANDLING

The information in this section applies to the Pfizer-BioNTech COVID-19 Vaccine that is supplied in multiple dose vials with maroon caps and labels with maroon borders. These multiple dose vials are supplied in a carton containing 10 multiple dose vials (NDC 59267-0078-4). After dilution, 1 vial contains 10 doses of 0.2 mL.

During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.

Do not refreeze thawed vials.

Vial Storage Prior to Use

Cartons of Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with maroon caps and labels with maroon borders may arrive frozen at ultra-cold conditions in thermal containers with dry ice.

Once received, frozen vials may be immediately transferred to the refrigerator [2°C to 8°C (35°F to 46°F)], thawed and stored for up to 10 weeks. The 10-week refrigerated expiry date should be recorded on the carton at the time of transfer. A carton of 10 vials may take up to 2 hours to thaw at this temperature.

Alternatively, frozen vials may be stored in an ultra-low temperature freezer at -90°C to -60°C (-130°F to -76°F) for up to 12 months from the date of manufacture. Do not store vials at -25°C to -15°C (-13°F to 5°F). Once vials are thawed, they should not be refrozen.

If cartons of Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with maroon caps and labels with maroon borders are received at 2°C to 8°C (35°F to 46°F), they should be stored at 2°C to 8°C (35°F to 46°F). Check that the carton has been updated to reflect the 10-week refrigerated expiry date.

Regardless of storage condition, the vaccine should not be used after 12 months from the date of manufacture printed on the vial and cartons. Expiry dates based on 12 months from the date of the manufacture are shown below.

Printed Manufacturing Date12-Month Expiry Date
01/202231-Dec-2022
02/202231-Jan-2023
03/202228-Feb-2023
04/202231-Mar-2023
05/202230-Apr-2023
06/202231-May-2023

Vial Storage During Use

If not previously thawed at 2°C to 8°C (35°F to 46°F), allow vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.

Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with maroon caps and labels with maroon borders may be stored at room temperature [8°C to 25°C (46°F to 77°F)] for a total of 12 hours prior to dilution.

After dilution, the vial should be held between 2°C to 25°C (35°F to 77°F). Vials should be discarded 12 hours after dilution, even though some vial and carton labels may state that a vial should be discarded 6 hours after dilution. The information in this Full EUA Prescribing Information supersedes the information printed on vial labels and cartons.

Transportation of Vials

If local redistribution is needed, undiluted vials may be transported at -90°C to -60°C (-130°F to -76°F) or at 2°C to 8°C (35°F to 46°F).

20 PATIENT COUNSELING INFORMATION

Advise the caregiver to read the Fact Sheet for Recipients and Caregivers.

The vaccination provider must include vaccination information in the state/local jurisdiction's Immunization Information System (IIS) or other designated system. Advise recipient or caregiver that more information about IISs can be found at: https://www.cdc.gov/vaccines/programs/iis/about.html.

21 CONTACT INFORMATION

For general questions, visit the website or call the telephone number provided below.

WebsiteTelephone number
www.cvdvaccine.com

Image
1-877-829-2619
(1-877-VAX-CO19)

This Full EUA Prescribing Information may have been updated. For the most recent Full EUA Prescribing Information, please see www.cvdvaccine.com.

Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany

Logo
Manufactured by
Pfizer Inc., New York, NY 10017

LAB-1515-3.0

Revised: 22 November 2022

FACT SHEET FOR RECIPIENTS AND CAREGIVERS ABOUT THE PFIZER-BIONTECH COVID-19 VACCINE TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19) FOR USE IN INDIVIDUALS 6 MONTHS THROUGH 4 YEARS OF AGE

FOR 6 MONTHS THROUGH 4 YEARS OF AGE

Your child is being offered the Pfizer-BioNTech COVID-19 Vaccine to prevent Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2.

The Pfizer-BioNTech COVID-19 Vaccine has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) to provide a 3-dose primary series to individuals 6 months through 4 years of age.2

This Fact Sheet contains information to help you understand the risks and benefits of the Pfizer-BioNTech COVID-19 Vaccine, which your child may receive because there is currently a pandemic of COVID-19. Talk to your child's vaccination provider if you have questions.

This Fact Sheet may have been updated. For the most recent Fact Sheet, please see www.cvdvaccine.com.

WHAT YOU NEED TO KNOW BEFORE YOUR CHILD GETS THIS VACCINE

WHAT IS COVID-19?

COVID-19 disease is caused by a coronavirus called SARS-CoV-2. You can get COVID-19 through contact with another person who has the virus. It is predominantly a respiratory illness that can affect other organs. People with COVID-19 have had a wide range of symptoms reported, ranging from mild symptoms to severe illness leading to death. Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may include: fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhea.

For more information on EUA, see the "What is an Emergency Use Authorization (EUA)?" section at the end of this Fact Sheet.

WHAT SHOULD YOU MENTION TO YOUR CHILD'S VACCINATION PROVIDER BEFORE YOUR CHILD GETS THE VACCINE?

Tell the vaccination provider about all of your child's medical conditions, including if your child:

HOW IS THE VACCINE GIVEN?

The Pfizer-BioNTech COVID-19 Vaccine will be given to your child as an injection into the muscle.

The vaccine is administered as a 3-dose series. The initial 2 doses are administered 3 weeks apart followed by a third dose administered at least 8 weeks after the second dose.

The vaccine may not protect everyone.

WHO SHOULD NOT GET THE VACCINE?

Your child should not get the vaccine if your child:

WHAT ARE THE INGREDIENTS IN THE VACCINE?

The vaccine includes the following ingredients: mRNA, lipids (((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-Distearoyl-sn-glycero-3-phosphocholine, and cholesterol), tromethamine, tromethamine hydrochloride, sucrose, and sodium chloride.

HAS THE VACCINE BEEN USED BEFORE?

Millions of individuals 5 years of age and older have received the Pfizer-BioNTech COVID-19 Vaccine under EUA since December 11, 2020. In a clinical trial, approximately 1,200 individuals 6 months through 23 months of age, approximately 1,800 individuals 2 through 4 years of age, and approximately 3,100 individuals 5 through 11 years of age have received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine. In another clinical trial, approximately 23,000 individuals 12 years of age and older have received at least 1 dose of the Pfizer-BioNTech COVID-19 Vaccine.

The vaccine that is authorized for use in children 6 months through 4 years of age includes the same mRNA and lipids but different inactive ingredients compared to the vaccine that has been studied in clinical trials. The use of the different inactive ingredients helps stabilize the vaccine under refrigerated temperatures.

WHAT ARE THE BENEFITS OF THE VACCINE?

The vaccine has been shown to prevent COVID-19.

The duration of protection against COVID-19 is currently unknown.

WHAT ARE THE RISKS OF THE VACCINE?

There is a remote chance that the vaccine could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to one hour after getting a dose of the vaccine. For this reason, your child's vaccination provider may ask your child to stay at the place where your child received the vaccine for monitoring after vaccination. Signs of a severe allergic reaction can include:

Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received the vaccine. In most of these people, symptoms began within a few days following receipt of the second dose of vaccine. The chance of having this occur is very low. You should seek medical attention right away if your child has any of the following symptoms after receiving the vaccine, particularly during the 2 weeks after your child receives a dose of the vaccine:

Side effects that have been reported with the vaccine include:

These may not be all the possible side effects of the vaccine. Serious and unexpected side effects may occur. The possible side effects of the vaccine are still being studied in clinical trials.

WHAT SHOULD I DO ABOUT SIDE EFFECTS?

If your child experiences a severe allergic reaction, call 9-1-1, or go to the nearest hospital.

Call the vaccination provider or your child's healthcare provider if your child has any side effects that bother your child or do not go away.

Report vaccine side effects to FDA/CDC Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967 or report online to https://vaers.hhs.gov/reportevent.html. Please include "Pfizer-BioNTech COVID-19 Vaccine EUA" in the first line of box #18 of the report form.

In addition, you can report side effects to Pfizer Inc. at the contact information provided below.

WebsiteFax numberTelephone number
www.pfizersafetyreporting.com1-866-635-83371-800-438-1985

You may also be given an option to enroll in v-safe. V-safe is a voluntary smartphone-based tool that uses text messaging and web surveys to check in with people who have been vaccinated to identify potential side effects after COVID-19 vaccination. V-safe asks questions that help CDC monitor the safety of COVID-19 vaccines. V-safe also provides second-dose reminders if needed and live telephone follow-up by CDC if participants report a significant health impact following COVID-19 vaccination. For more information on how to sign up, visit: www.cdc.gov/vsafe.

WHAT IF I DECIDE NOT TO HAVE MY CHILD GET THE PFIZER-BIONTECH COVID-19 VACCINE?

Under the EUA, there is an option to accept or refuse receiving the vaccine. Should you decide for your child not to receive it, it will not change your child's standard medical care.

ARE OTHER CHOICES AVAILABLE FOR PREVENTING COVID-19 BESIDES PFIZER-BIONTECH COVID-19 VACCINE?

Other vaccines to prevent COVID-19 may be available under Emergency Use Authorization.

CAN MY CHILD RECEIVE THE PFIZER-BIONTECH COVID-19 VACCINE AT THE SAME TIME AS OTHER VACCINES?

Data have not yet been submitted to FDA on administration of the Pfizer-BioNTech COVID-19 Vaccine at the same time with other vaccines. If you are considering to have your child receive the Pfizer-BioNTech COVID-19 Vaccine with other vaccines, discuss the options with your child's healthcare provider.

WILL THE VACCINE GIVE MY CHILD COVID-19?

No. The vaccine does not contain SARS-CoV-2 and cannot give your child COVID-19.

KEEP YOUR CHILD'S VACCINATION CARD

When your child gets the first dose, you will get a vaccination card to show when to return for your child's next dose of the vaccine. Remember to bring the card when your child returns.

ADDITIONAL INFORMATION

If you have questions, visit the website or call the telephone number provided below.

To access the most recent Fact Sheets, please scan the QR code provided below.

Global websiteTelephone number
www.cvdvaccine.com
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1-877-829-2619
(1-877-VAX-CO19)

HOW CAN I LEARN MORE?

WHERE WILL MY CHILD'S VACCINATION INFORMATION BE RECORDED?

The vaccination provider may include your child's vaccination information in your state/local jurisdiction's Immunization Information System (IIS) or other designated system. This will ensure that your child receives the same vaccine when your child returns for the second dose. For more information about IISs visit: https://www.cdc.gov/vaccines/programs/iis/about.html.

CAN I BE CHARGED AN ADMINISTRATION FEE FOR RECEIPT OF THE COVID-19 VACCINE?

No. At this time, the provider cannot charge you for a vaccine dose and you cannot be charged an out-of-pocket vaccine administration fee or any other fee if only receiving a COVID-19 vaccination. However, vaccination providers may seek appropriate reimbursement from a program or plan that covers COVID-19 vaccine administration fees for the vaccine recipient (private insurance, Medicare, Medicaid, Health Resources & Services Administration [HRSA] COVID-19 Uninsured Program for non-insured recipients).

WHERE CAN I REPORT CASES OF SUSPECTED FRAUD?

Individuals becoming aware of any potential violations of the CDC COVID-19 Vaccination Program requirements are encouraged to report them to the Office of the Inspector General, U.S. Department of Health and Human Services, at 1-800-HHS-TIPS or https://TIPS.HHS.GOV.

WHAT IS THE COUNTERMEASURES INJURY COMPENSATION PROGRAM?

The Countermeasures Injury Compensation Program (CICP) is a federal program that may help pay for costs of medical care and other specific expenses of certain people who have been seriously injured by certain medicines or vaccines, including this vaccine. Generally, a claim must be submitted to the CICP within one (1) year from the date of receiving the vaccine. To learn more about this program, visit www.hrsa.gov/cicp/ or call 1-855-266-2427.

WHAT IS AN EMERGENCY USE AUTHORIZATION (EUA)?

An EUA is a mechanism to facilitate the availability and use of medical products, including vaccines, during public health emergencies, such as the current COVID-19 pandemic. An EUA is supported by a Secretary of Health and Human Services (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic. A product authorized for emergency use has not undergone the same type of review by FDA as an FDA-approved product.

FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, and available alternatives. In addition, the FDA decision is based on the totality of the scientific evidence available showing that the product may be effective to prevent COVID-19 during the COVID-19 pandemic and that the known and potential benefits of the product outweigh the known and potential risks of the product. All of these criteria must be met to allow for the product to be used during the COVID-19 pandemic.

An EUA is in effect for the duration of the COVID-19 EUA declaration justifying emergency use of this product, unless terminated or revoked (after which the product may no longer be used).

Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany

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Manufactured by
Pfizer Inc., New York, NY 10017

LAB-1517-3.0

Revised: 22 November 2022

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Scan to capture that this Fact Sheet was provided to vaccine recipient for the electronic medical records/immunization information systems.
GDTI: 0886983000486

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You may receive this Fact Sheet even if your child is 5 years old. Children who will turn from 4 years to 5 years of age between any doses in the primary series, and who received a first dose with the Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 6 months through 4 years of age, may also receive this vaccine for doses 2 and/or 3 of the primary series.

Revised: 11/2022
Document Id: 31c84ad4-0e4e-42e0-a506-3a43b29368ec
Set id: 196608f2-21c1-4236-b3e1-06637f7be060
Version: 7
Effective Time: 20221129
 
Pfizer Manufacturing Belgium NV