Label: PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT- bnt162b2 original and omicron ba.4/ba.5 injection, suspension

  • NDC Code(s): 59267-0304-1, 59267-0304-2, 59267-1404-1, 59267-1404-2
  • Packager: Pfizer Manufacturing Belgium NV
  • Category: VACCINE LABEL
  • DEA Schedule: None

Drug Label Information

Updated September 2, 2022

If you are a consumer or patient please visit this version.

  • SPL UNCLASSIFIED SECTION

    FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE (VACCINATION PROVIDERS)

    EMERGENCY USE AUTHORIZATION (EUA)

    PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT
    (ORIGINAL AND OMICRON BA.4/BA.5)
    BOOSTER DOSE FOR 12 YEARS OF AGE AND OLDER
    DO NOT DILUTE

    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, Bivalent (Original and Omicron BA.4/BA.5) for active immunization to prevent COVID-19 in individuals 12 years of age and older.

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) is hereafter referred to as Pfizer-BioNTech COVID-19 Vaccine, Bivalent. It is supplied in single dose and multiple dose vials with gray caps and labels with gray borders.

    DO NOT DILUTE PRIOR TO USE.

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent is authorized for use in individuals 12 years of age and older as a single booster dose administered at least 2 months after either:

    • completion of primary vaccination with any authorized or approved monovalent1 COVID-19 vaccine, or
    • receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine.

    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, Bivalent. See "MANDATORY REQUIREMENTS FOR PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION" for reporting requirements.

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

    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, Bivalent 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, Bivalent supplied in:

    • single dose vials with gray caps and labels with gray borders, and
    • multiple dose vials with gray caps and labels with gray borders.

    DO NOT DILUTE PRIOR TO USE.

    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, Bivalent 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 single dose vials may take up to 2 hours to thaw at this temperature. A carton of 10 multiple dose vials may take up to 6 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, Bivalent 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.

    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, Bivalent may be stored at room temperature [8°C to 25°C (46°F to 77°F)] for a total of 12 hours prior to the first puncture. After first puncture, the multiple dose vial should be held between 2°C to 25°C (35°F to 77°F). Multiple dose vials should be discarded 12 hours after first puncture.

    Transportation of Vials

    If local redistribution is needed, 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

    A single booster dose (0.3 mL) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent may be administered at least 2 months after completion of primary vaccination or receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine.

    Dose Preparation

    • Pfizer-BioNTech COVID-19 Vaccine, Bivalent vials contain a frozen suspension without preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
    • Vials may be thawed in the refrigerator [2°C to 8°C (35°F to 46°F)] or at room temperature [up to 25°C (77°F)].
    • Refer to thawing and preparation instructions in the panels below.
    Preparation Instructions
    Pfizer-BioNTech COVID-19 Vaccine, Bivalent Vial with Gray Cap and Label with Gray Border –
    VIAL VERIFICATION
    Figure
    Gray cap and label with gray border.
    • Verify that the vial of Pfizer-BioNTech COVID-19 Vaccine, Bivalent:
      • has a gray cap and a label with a gray border
      • states Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5).
    THAWING PRIOR TO USE
    Figure
    Store in the refrigerator for up to 10 weeks prior to use.
    • Thaw vial(s) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent before use either by:
      • Allowing vial(s) to thaw in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)].
        • A carton of 10 single dose vials may take up to 2 hours to thaw.
        • A carton of 10 multiple dose vials may take up to 6 hours to thaw.
      • Allowing vial(s) to sit at room temperature [up to 25ºC (77ºF)] for 30 minutes.
    • Thawed vials can be stored in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] for up to 10 weeks prior to use.
    • Thawed vials may be stored at room temperature [up to 25ºC (77ºF)] for up to 12 hours prior to use.
    Figure
    Gently × 10
    • Before use, mix by inverting vaccine vial gently 10 times.
    • Do not shake.
    • Prior to mixing, the thawed vaccine may contain white to off-white opaque amorphous particles.
    • After mixing, the vaccine should appear as a white to off-white suspension with no visible particles.
    • Do not use if liquid is discolored or if particles are observed after mixing.
    PREPARATION OF INDIVIDUAL 0.3 mL DOSES
    Figure
    Withdraw 0.3 mL dose of vaccine.
    Single Dose Vial
    • Withdraw a single 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
    • Administer immediately.
    • Discard vial and any excess volume.
    Multiple Dose Vial
    • Multiple dose vials contain 6 doses of 0.3 mL each.
    • Withdraw 0.3 mL of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent preferentially using low dead-volume syringes and/or needles. If standard syringes and needles are used, there may not be sufficient volume to extract 6 doses from a single vial.
    • Administer immediately.
    • If the amount of vaccine remaining in a multiple dose vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
    Multiple Dose Vial – Record Date and Time of First Puncture
    Figure
    Record the date and time of first puncture.
    Use within 12 hours after first puncture.
    • Record the date and time of first vial puncture on the Pfizer-BioNTech COVID-19 Vaccine, Bivalent multiple dose vial label.
    • Store between 2°C to 25°C (35°F to 77°F).
    • Discard any unused vaccine 12 hours after first puncture.

    Administration

    Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The vaccine will be a white to off-white suspension. Do not administer if vaccine is discolored or contains particulate matter.

    After withdrawing a single 0.3 mL dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent, administer immediately.

    Contraindications

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

    Monitor Pfizer-BioNTech COVID-19 Vaccine, Bivalent 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 safety data with Pfizer-BioNTech COVID-19 Vaccine are relevant to Pfizer-BioNTech COVID-19 Vaccine, Bivalent because these vaccines are manufactured using the same process.

    Postmarketing data with authorized or approved monovalent mRNA COVID-19 vaccines demonstrate increased risks of myocarditis and pericarditis, particularly within the first week following receipt of the second primary series dose or first booster dose, with most booster doses likely administered at least 5 months after completing primary vaccination. For the Pfizer-BioNTech COVID-19 Vaccine, the observed risk is higher among adolescent males and adult males under 40 years of age than among females and older males, and 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, Bivalent.

    Limitation of Effectiveness

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

    Adverse Reactions

    The safety of a booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent is based on:

    • safety data from a clinical study which evaluated a booster dose of Pfizer-BioNTech's bivalent COVID-19 vaccine (Original and Omicron BA.1), not authorized or approved, hereafter referred to as bivalent vaccine (Original and Omicron BA.1),
    • safety data from clinical trials which evaluated primary and booster vaccination with Pfizer-BioNTech COVID-19 Vaccine, and
    • post marketing safety data with Pfizer-BioNTech COVID-19 Vaccine.

    The safety data accrued with the bivalent vaccine (Original and Omicron BA.1) and with Pfizer-BioNTech COVID-19 Vaccine are relevant to Pfizer-BioNTech COVID-19 Vaccine, Bivalent because these vaccines are manufactured using the same process. The bivalent vaccine (Original and Omicron BA.1) contained 15 mcg of nucleoside-modified messenger RNA (modRNA) encoding the S-glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 15 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Omicron variant lineage BA.1, for a total of 30 mcg modRNA per dose. This is the same total quantity of modRNA per dose as a dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent and as a dose of Pfizer-BioNTech COVID-19 Vaccine authorized for primary vaccination in individuals 12 years of age and older (and previously authorized for booster vaccination in individuals 12 years of age and older).

    Adverse Reactions in Clinical Trials

    Adverse reactions following administration of a booster dose of the Pfizer-BioNTech COVID-19 Vaccine or the bivalent vaccine (Original and Omicron BA.1) that have been reported in clinical trials include injection site pain, fatigue, headache, muscle pain, chills, joint pain, injection site swelling, fever, injection site redness, lymphadenopathy, nausea, malaise, pain in extremity, rash, and decreased appetite (see Full EUA Prescribing Information).

    Adverse Reactions Identified 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), and syncope 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 post-authorization use of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

    Use with Other Vaccines

    There is no information on the co-administration of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent 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 "Vaccine Information Fact Sheet for Recipients and Caregivers" (and provide a copy or direct the individual to the website www.cvdvaccine.com to obtain the Vaccine Information Fact Sheet for Recipients and Caregivers) prior to the individual receiving each dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent including:

    • FDA has authorized the emergency use of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent which is not an FDA-approved vaccine.
    • The recipient or their caregiver has the option to accept or refuse Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
    • The significant known and potential risks and benefits of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, and the extent to which such risks and benefits are unknown.
    • Information about available alternative vaccines and the risks and benefits of those alternatives.

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

    Provide a vaccination card to the recipient or their caregiver.

    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 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, BIVALENT ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION2

    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, Bivalent the following items are required. Use of unapproved Pfizer-BioNTech COVID-19 Vaccine, Bivalent 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, Bivalent is authorized for use in individuals 12 years of age and older.
    2. The vaccination provider must communicate to the individual receiving the Pfizer-BioNTech COVID-19 Vaccine, Bivalent or their caregiver, information consistent with the "Vaccine Information Fact Sheet for Recipients and Caregivers" prior to the individual receiving Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
    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, Bivalent 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, Bivalent to recipients.

    * Serious adverse events are defined as:

    • Death;
    • A life-threatening adverse event;
    • Inpatient hospitalization or prolongation of existing hospitalization;
    • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
    • A congenital anomaly/birth defect;
    • An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent 1 of the outcomes listed above.

    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, Bivalent 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 for use as a booster dose, including bivalent vaccines that contain or encode the spike protein of the Omicron variant of SARS-CoV-2.

    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, Bivalent 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, Bivalent 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, Bivalent 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-1537-1.0

    Revised: 31 August 2022

    END SHORT VERSION FACT SHEET

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


    1
    Monovalent refers to any authorized or approved COVID-19 vaccine that contains or encodes the spike protein of only the Original SARS-CoV-2.
    2
    Vaccination providers administering COMIRNATY (COVID-19 Vaccine, mRNA) and Pfizer-BioNTech COVID-19 Vaccine must adhere to the same reporting requirements.
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    FULL EMERGENCY USE AUTHORIZATION (EUA) PRESCRIBING INFORMATION
    PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT (ORIGINAL AND OMICRON BA.4/BA.5)
    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
     
    11.1 Pregnancy
     
    11.2 Lactation
     
    11.3 Pediatric Use
     
    11.4 Geriatric Use
    13
    DESCRIPTION
    14
    CLINICAL PHARMACOLOGY
     
    14.1 Mechanism of Action
    18
    CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA
     
    18.1 Efficacy of Primary Series of Pfizer-BioNTech COVID-19 Vaccine in Participants 16 Years of Age and Older
     
    18.2 Efficacy of Primary Series of Pfizer-BioNTech COVID-19 Vaccine in Adolescents 12 Through 15 Years of Age
     
    18.3 Immunogenicity of Primary Series of Pfizer-BioNTech COVID-19 Vaccine in Adolescents 12 Through 15 Years of Age
     
    18.4 Immunogenicity of the Bivalent Vaccine (Original and Omicron BA.1) Administered as a Second Booster Dose
     
    18.5 Immunogenicity of a First Booster Dose With a Pfizer-BioNTech COVID-19 Vaccine Primary Series in Participants 18 Through 55 Years of Age
     
    18.6 Immunogenicity of a First Booster Dose Following Primary Vaccination with Another Authorized or Approved COVID-19 Vaccine
    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.
  • SPL UNCLASSIFIED SECTION

    FULL EMERGENCY USE AUTHORIZATION (EUA) PRESCRIBING INFORMATION

  • 1 AUTHORIZED USE

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) 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 12 years of age and older.

    This EUA Prescribing Information pertains only to Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5), hereafter referred to as Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

  • 2 DOSAGE AND ADMINISTRATION

    The storage, preparation, and administration information in this Prescribing Information apply to the Pfizer-BioNTech COVID-19 Vaccine, Bivalent supplied in:

    • single dose vials with gray caps and labels with gray borders, and
    • multiple dose vials with gray caps and labels with gray borders.

    DO NOT DILUTE PRIOR TO USE.

    2.1 Preparation for Administration

    • Pfizer-BioNTech COVID-19 Vaccine, Bivalent vials contain a frozen suspension without preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
    • Vials may be thawed in the refrigerator [2°C to 8°C (35°F to 46°F)] or at room temperature [up to 25°C (77°F)] [see How Supplied/Storage and Handling (19)].
    • Refer to thawing and preparation instructions in the panels below.
    Preparation Instructions
    Pfizer-BioNTech COVID-19 Vaccine, Bivalent Vial with Gray Cap and Label with Gray Border –
    VIAL VERIFICATION
    Figure
    Gray cap and label with gray border.
    • Verify that the vial of Pfizer-BioNTech COVID-19 Vaccine, Bivalent:
      • has a gray cap and a label with a gray border
      • states Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5).
    THAWING PRIOR TO USE
    Figure
    Store in the refrigerator for up to 10 weeks prior to use.
    • Thaw vial(s) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent before use either by:
      • Allowing vial(s) to thaw in the refrigerator [2°C to 8°C (35°F to 46°F)].
        • A carton of 10 single dose vials may take up to 2 hours to thaw.
        • A carton of 10 multiple dose vials may take up to 6 hours to thaw.
      • Allowing vial(s) to sit at room temperature [up to 25°C (77°F)] for 30 minutes.
    • Thawed vials can be stored in the refrigerator [2°C to 8°C (35°F to 46°F)] for up to 10 weeks prior to use.
    • Thawed vials may be stored at room temperature [up to 25°C (77°F)] for up to 12 hours prior to use.
    Figure
    Gently × 10
    • Before use, mix by inverting vaccine vial gently 10 times.
    • Do not shake.
    • Prior to mixing, the thawed vaccine may contain white to off-white opaque amorphous particles.
    • After mixing, the vaccine should appear as a white to off-white suspension with no visible particles.
    • Do not use if liquid is discolored or if particles are observed after mixing.
    PREPARATION OF INDIVIDUAL 0.3 mL DOSES
    Figure
    Withdraw 0.3 mL dose of vaccine.
    Single Dose Vial
    • Withdraw a single 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
    • Administer immediately.
    • Discard vial and any excess volume.
    Multiple Dose Vial
    • Multiple dose vials contain 6 doses of 0.3 mL each.
    • Withdraw 0.3 mL of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent preferentially using low dead-volume syringes and/or needles. If standard syringes and needles are used, there may not be sufficient volume to extract 6 doses from a single vial.
    • Administer immediately.
    • If the amount of vaccine remaining in a multiple dose vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
    Multiple Dose Vial – Record Date and Time of First Puncture
    Figure
    Record the date and time of first puncture.
    Use within 12 hours after first puncture.
    • Record the date and time of first vial puncture on the Pfizer-BioNTech COVID-19 Vaccine, Bivalent multiple dose vial label.
    • Store between 2°C to 25°C (35°F to 77°F).
    • Discard any unused vaccine 12 hours after first puncture.

    2.2 Administration Information

    Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The vaccine will be a white to off-white suspension. Do not administer if vaccine is discolored or contains particulate matter.

    After withdrawing a single 0.3 mL dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent, administer immediately.

    2.3 Vaccination Schedule

    A single booster dose (0.3 mL) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent may be administered at least 2 months after completion of primary vaccination or receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine.

  • 3 DOSAGE FORMS AND STRENGTHS

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

    Each dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent is 0.3 mL [see Dosage and Administration (2.1)].

  • 4 CONTRAINDICATIONS

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

    Monitor Pfizer-BioNTech COVID-19 Vaccine, Bivalent 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 safety data with Pfizer-BioNTech COVID-19 Vaccine are relevant to Pfizer-BioNTech COVID-19 Vaccine, Bivalent because these vaccines are manufactured using the same process.

    Postmarketing data with authorized or approved monovalent mRNA COVID-19 vaccines demonstrate increased risks of myocarditis and pericarditis, particularly within the first week following receipt of the second primary series dose or first booster dose, with most booster doses likely administered at least 5 months after completing primary vaccination. For the Pfizer-BioNTech COVID-19 Vaccine, the observed risk is higher among adolescent males and adult males under 40 years of age than among females and older males, and 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, Bivalent.

    5.5 Limitation of Effectiveness

    The Pfizer-BioNTech COVID-19 Vaccine, Bivalent 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, Bivalent.3 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.

    The safety of a booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent is based on:

    • safety data from a clinical study which evaluated a booster dose of Pfizer-BioNTech's bivalent COVID-19 vaccine (Original and Omicron BA.1), not authorized or approved, hereafter referred to as bivalent vaccine (Original and Omicron BA.1),
    • safety data from clinical trials which evaluated primary and booster vaccination with Pfizer-BioNTech COVID-19 Vaccine, and
    • post marketing safety data with Pfizer-BioNTech COVID-19 Vaccine.

    The safety data accrued with the bivalent vaccine (Original and Omicron BA.1) and with Pfizer-BioNTech COVID-19 Vaccine are relevant to Pfizer-BioNTech COVID-19 Vaccine, Bivalent because these vaccines are manufactured using the same process. The bivalent vaccine (Original and Omicron BA.1) contained 15 mcg of nucleoside-modified messenger RNA (modRNA) encoding the S-glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 15 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Omicron variant lineage BA.1, for a total of 30 mcg modRNA per dose. This is the same total quantity of modRNA per dose as a dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent and as a dose of Pfizer-BioNTech COVID-19 Vaccine authorized for primary vaccination in individuals 12 years of age and older (and previously authorized for booster vaccination in individuals 12 years of age and older).

    The clinical study that evaluated a booster dose of the bivalent vaccine (Original and Omicron BA.1) included participants 55 years of age and older. Adverse reactions following administration of the bivalent vaccine (Original and Omicron BA.1) as a second booster dose included pain at the injection site (58.1%), fatigue (49.2%), headache (33.6%), muscle pain (22.3%), chills (13.0%), joint pain (11.3%), injection site redness (7.0%), injection site swelling (6.6%), fever (5.0%), lymphadenopathy (0.3%), nausea (0.3%), and malaise (0.3%).

    In a clinical study of participants 18 through 55 years of age, adverse reactions following administration of a first booster dose of Pfizer-BioNTech COVID-19 Vaccine were pain at the injection site (83.0%), fatigue (63.7%), headache (48.4%), muscle pain (39.1%), chills (29.1%), joint pain (25.3%), lymphadenopathy (5.2%), nausea (0.7%), decreased appetite (0.3%), rash (0.3%), and pain in extremity (0.3%). Severe allergic reactions (including anaphylaxis), myocarditis and pericarditis have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.


    3
    Vaccination providers administering COMIRNATY (COVID-19 Vaccine, mRNA) and Pfizer-BioNTech COVID-19 Vaccine must adhere to the same reporting requirements.

    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.

    Overall 3,013 participants 6 months through 4 years of age and 3,109 participants 5 through 11 years of age in Study 3 (NCT04816643) and 22,851 participants 12 years of age and older in Study 1 (NCT04380701) and Study 2 (NCT04368728) have received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine during the Phase 2/3 blinded placebo-controlled follow-up period. In a subset of Study 4 (NCT04955626), 305 participants greater than 55 years of age received a second booster dose with the bivalent vaccine (Original and Omicron BA.1).

    Bivalent Vaccine (Original and Omicron BA.1) Administered as a Second Booster Dose

    In Study 4, a total of 610 participants greater than 55 years of age previously vaccinated with a 2-dose primary series and 1 booster dose of Pfizer-BioNTech COVID-19 Vaccine went on to receive a second booster dose with either Pfizer-BioNTech COVID-19 Vaccine or the bivalent vaccine (Original and Omicron BA.1).

    The 305 participants greater than 55 years who received a second booster dose with Pfizer-BioNTech COVID-19 received it 5.3 to 13.1 months after receiving the first booster dose and had a median follow-up time of 1.8 months up to a data cut-off date of May 16, 2022. Their median age was 66 years (range 56 through 87 years of age), 47.5% were male and 52.5% were female, 87.9% were White, 18.7% were Hispanic/Latino, 4.3% were Asian, and 6.2% were Black or African American.

    The 305 participants greater than 55 years who received a second booster dose with the bivalent vaccine (Original and Omicron BA.1) received it 4.7 to 11.5 months after receiving the first booster dose and had a median follow-up time of 1.7 months up to a data cut-off date of May 16, 2022. Their median age was 67 years (range 56 through 85 years of age), 53.1% were male and 46.9% were female, 89.8% were White, 14.8% were Hispanic/Latino, 5.2% were Asian, and 4.3% were Black or African American.

    Solicited Local and Systemic Adverse Reactions

    Table 1 and Table 2 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a second booster dose of Pfizer-BioNTech COVID-19 Vaccine or bivalent vaccine (Original and Omicron BA.1).

    In participants who received the bivalent vaccine (Original and Omicron BA.1), the mean duration of injection site pain, redness, and swelling was 2.2 days (range 1 to 12 days), 2.9 days (range 1 to 10 days), and 1.9 days (range 1 to 4 days), respectively.

    Table 1: Local Adverse Reactions, by Maximum Severity, Within 7 Days After a Second Booster Dose – Adults Greater Than 55 Years of Age – Safety Population
    Pfizer-BioNTech COVID-19 Vaccine
    N*=298
    n (%)
    Bivalent Vaccine (Original and Omicron BA.1)
    N*=301
    n (%)
    Note: Adverse Reactions were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination.
    *
    N = Number of participants reporting at least 1 yes or no response for the specified reaction after the study vaccination.
    n = Number of participants with the specified adverse reaction.
    Mild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.
    §
    Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
    Redness
      Any (>2 cm)19 (6.4)21 (7.0)
      Mild12 (4.0)13 (4.3)
      Moderate6 (2.0)8 (2.7)
      Severe1 (0.3)0
    Swelling
      Any (>2 cm)18 (6.0)20 (6.6)
      Mild10 (3.4)14 (4.7)
      Moderate8 (2.7)6 (2.0)
      Severe00
    Pain at the injection site§
      Any179 (60.1)175 (58.1)
      Mild154 (51.7)159 (52.8)
      Moderate24 (8.1)15 (5.0)
      Severe1 (0.3)1 (0.3)
    Table 2: Systemic Adverse Reactions, by Maximum Severity, Within 7 Days After the Second Booster Dose – Adults Greater Than 55 Years of Age – Safety Population
    Pfizer-BioNTech COVID-19 Vaccine
    N*=298
    n (%)
    Bivalent Vaccine (Original and Omicron BA.1)
    N*=301
    n (%)
    Note: Adverse reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination.
    *
    N = Number of participants reporting at least 1 yes or no response for the specified adverse reaction after the study vaccination.
    n = Number of participants with the specified adverse 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.
    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.
    #
    Severity was not collected for use of antipyretic or pain medication.
    Fever
      ≥38.0°C11 (3.7)15 (5.0)
      ≥38.0°C to 38.4°C6 (2.0)11 (3.7)
      >38.4°C to 38.9°C5 (1.7)0
      >38.9°C to 40.0°C04 (1.3)
      >40.0°C00
    Fatigue
      Any135 (45.3)148 (49.2)
      Mild70 (23.5)88 (29.2)
      Moderate64 (21.5)55 (18.3)
      Severe1 (0.3)5 (1.7)
    Headache
      Any79 (26.5)101 (33.6)
      Mild47 (15.8)71 (23.6)
      Moderate31 (10.4)29 (9.6)
      Severe1 (0.3)1 (0.3)
    Chills
      Any49 (16.4)39 (13.0)
      Mild32 (10.7)25 (8.3)
      Moderate17 (5.7)14 (4.7)
      Severe00
    Vomiting§
      Any4 (1.3)5 (1.7)
      Mild2 (0.7)5 (1.7)
      Moderate2 (0.7)0
      Severe00
    Diarrhea
      Any13 (4.4)27 (9.0)
      Mild10 (3.4)18 (6.0)
      Moderate3 (1.0)5 (1.7)
      Severe04 (1.3)
    New or worsened muscle pain
      Any59 (19.8)67 (22.3)
      Mild35 (11.7)40 (13.3)
      Moderate24 (8.1)27 (9.0)
      Severe00
    New or worsened joint pain
      Any27 (9.1)34 (11.3)
      Mild16 (5.4)23 (7.6)
      Moderate11 (3.7)11 (3.7)
      Severe00
    Use of antipyretic or pain medication#80 (26.8)88 (29.2)

    Unsolicited Adverse Events

    Overall, the participants who received a second booster dose with the bivalent vaccine (Original and Omicron BA.1) had a median follow-up time of 1.7 months (range 1.0 to 2.0 months) to the cut-off date (May 16, 2022).

    In an analysis of all unsolicited adverse events reported following the second booster dose, through 1 month after the booster dose, those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (n = 1, 0.3%) for the Pfizer-BioNTech COVID-19 Vaccine and (n = 1, 0.3%) for the bivalent vaccine (Original and Omicron BA.1), nausea (n = 1, 0.3%) for the Pfizer-BioNTech COVID-19 Vaccine and (n = 1, 0.3%) for the bivalent vaccine (Original and Omicron BA.1), and malaise (n = 0) for the Pfizer-BioNTech COVID-19 Vaccine and (n = 1, 0.3%) for the bivalent vaccine (Original and Omicron BA.1).

    Serious Adverse Events

    Serious adverse events up to 1 month after the second booster dose in ongoing follow up were reported by no Pfizer-BioNTech COVID-19 Vaccine recipients and by 1 bivalent vaccine (Original and Omicron BA.1) recipient (1 serious adverse event considered unrelated to the vaccine).

    Pfizer-BioNTech COVID-19 Vaccine

    Primary Series

    The safety of the primary series Pfizer-BioNTech COVID-19 Vaccine was evaluated in participants 12 years of age and older in 2 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; 21,728 placebo] in Phase 2/3 are 16 years of age or older (including 138 and 145 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 adolescents are 12 through 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively).

    In Study 2, Participants are being monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month (all unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination].

    Participants 16 Years of Age and Older

    At the time of the analysis of Study 2 for the EUA, 37,586 [18,801 Pfizer-BioNTech COVID-19 Vaccine 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 of age 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 7960 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.

    Adolescents 12 Through 15 Years of Age

    In an analysis of Study 2, based on data up to the cutoff date of March 13, 2021, 2,260 adolescents (1,131 Pfizer-BioNTech COVID-19 Vaccine; 1,129 placebo) were 12 through 15 years of age. Of these, 1,308 (660 Pfizer-BioNTech COVID-19 Vaccine and 648 placebo) adolescents 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 adolescents who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Overall, among the adolescents 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 adolescents 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 5 Through 11 Years of Age

    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; 750 placebo] were 5 through 11 years of age. Of these, 2,158 (95.1%) [1,444 Pfizer-BioNTech COVID-19 Vaccine 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 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 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 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 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 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 to 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 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 group vs. 1 (0.1%) in the placebo group. In the expansion cohort from Dose 1 through the cutoff date, lymphadenopathy was reported in 6 (0.4%) participants in the Pfizer-BioNTech COVID-19 Vaccine 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 2 Through 4 Years of Age

    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; 280 placebo] were 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.

    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 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 6 Through 23 Months of Age

    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; 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.

    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.

    First Booster Dose Following a Primary Series of Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA) in Participants 18 through 55 Years of Age

    A subset of Study 2 Phase 2/3 participants of 306 adults 18 through 55 years of age received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine approximately 6 months (range of 4.8 to 8.0 months) after completing the primary series. Additionally, a total of 23 Study 2 (Phase 1) participants (11 participants 18 through 55 years of age and 12 participants 65 through 85 years of age) received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine approximately 8 months (range 7.9 to 8.8 months) after completing the primary series. Participants 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 through 1 month after vaccination and for serious adverse events for 6 months after the last vaccination.

    Among the 306 Phase 2/3 participants, the median age was 42 years (range 19 through 55 years of age), 45.8% were male and 54.2% were female, 81.4% were White, 27.8% were Hispanic/Latino, 9.2% were Black or African American, 5.2% were Asian, and 0.7% were American Indian/Alaska Native. Among the 12 Phase 1 participants 65 through 85 years of age, the median age was 69 years (range 65 through 75 years of age), 6 were male and all were White and Not Hispanic/Latino. Following the booster dose, the median follow-up time was 2.6 months (range 2.1 to 2.9 months) for Phase 1 participants and 2.6 months (range 1.1 to 2.8 months) for Phase 2/3 participants.

    Solicited Local and Systemic Adverse Reactions

    Table 3 and Table 4 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of a first booster dose with Pfizer-BioNTech COVID-19 Vaccine for Phase 2/3 participants 18 through 55 years of age.

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

    Table 3: Study 2 – Frequency and Percentages of Participants With Solicited Local Adverse Reactions, By Maximum Severity, Within 7 Days After a First Booster Dose of Pfizer-BioNTech COVID-19 Vaccine – Participants 18 through 55 Years of Age*
    Solicited Local Adverse ReactionPfizer-BioNTech COVID-19 Vaccine
    First Booster Dose
    N = 289
    n§ (%)
    Note: Adverse Reactions were collected in the electronic diary (e-diary) from day of vaccination (Day 1) to Day 7 after the booster dose.
    Note: No Grade 4 solicited local adverse reactions were reported.
    *
    A subset of Phase 2/3 participants 18 through 55 years of age who received a booster dose of COMIRNATY (COVID-19 Vaccine, mRNA) approximately 6 months after completing the primary series.
    Pfizer-BioNTech COVID-19 Vaccine .
    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: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.
    #
    Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
    Redness
      Any (>2 cm)17 (5.9)
        Mild10 (3.5)
        Moderate7 (2.4)
        Severe0
    Swelling
      Any (>2 cm)23 (8.0)
        Mild13 (4.5)
        Moderate9 (3.1)
        Severe1 (0.3)
    Pain at the injection site#
      Any240 (83.0)
        Mild174 (60.2)
        Moderate65 (22.5)
        Severe1 (0.3)
    Table 4: Study 2 – Frequency and Percentages of Participants With Solicited Systemic Adverse Reactions, by Maximum Severity, Within 7 Days After a First Booster Dose with Pfizer-BioNTech COVID-19 Vaccine – Participants 18 through 55 Years of Age*
    Solicited Systemic Adverse ReactionPfizer-BioNTech COVID-19 Vaccine
    First Booster Dose
    N = 289
    n§ (%)
    Note: Adverse reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from day of vaccination (Day 1) to Day 7 after the booster dose.
    Note: No Grade 4 solicited systemic adverse reactions were reported.
    *
    A subset of Phase 2/3 participants 18 through 55 years of age who received a booster dose of COMIRNATY (COVID-19 Vaccine, mRNA) approximately 6 months after completing the primary series.
    Pfizer-BioNTech COVID-19 Vaccine .
    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°C25 (8.7)
      ≥38.0°C to 38.4°C12 (4.2)
      >38.4°C to 38.9°C12 (4.2)
      >38.9°C to 40.0°C1 (0.3)
      >40.0°C0
    Fatigue
      Any184 (63.7)
        Mild68 (23.5)
        Moderate103 (35.6)
        Severe13 (4.5)
    Headache
      Any140 (48.4)
        Mild83 (28.7)
        Moderate54 (18.7)
        Severe3 (1.0)
    Chills
      Any84 (29.1)
        Mild37 (12.8)
        Moderate44 (15.2)
        Severe3 (1.0)
    Vomiting#
      Any5 (1.7)
        Mild5 (1.7)
        Moderate0
        Severe0
    DiarrheaÞ
      Any25 (8.7)
        Mild21 (7.3)
        Moderate4 (1.4)
        Severe0
    New or worsened muscle pain
      Any113 (39.1)
        Mild52 (18.0)
        Moderate57 (19.7)
        Severe4 (1.4)
    New or worsened joint pain
      Any73 (25.3)
        Mild36 (12.5)
        Moderate36 (12.5)
        Severe1 (0.3)
    Use of antipyretic or pain medicationß135 (46.7)

    In Phase 1 participants ≥65 years of age (n = 12), local reaction pain at the injection site (n = 8, 66.7%) and systemic reactions fatigue (n = 5, 41.7%), headache (n = 5, 41.7%), chills (n = 2, 16.7%), muscle pain (n = 4, 33.3%), and joint pain (n = 2, 16.7%) were reported after the booster dose. No participant in this age group reported a severe systemic event or fever after the booster dose.

    Unsolicited Adverse Events

    Overall, the 306 participants who received a first booster dose, had a median follow-up time of 2.6 months after the booster dose to the cut-off date (June 17, 2021).

    In an analysis of all unsolicited adverse events reported following the first booster dose, through 1 month after the booster dose, in participants 18 through 55 years of age (N = 306), those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (n = 16, 5.2%), nausea (n = 2, 0.7%), decreased appetite (n = 1, 0.3%), rash (n = 1, 0.3%), and pain in extremity (n = 1, 0.3%).

    Serious Adverse Events

    Of the 306 participants who received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine, there were no serious adverse events reported from the booster dose through 30 days after the booster dose. One participant reported a serious adverse event 61 days after the booster dose that was assessed as unrelated to vaccination.

    First Booster Dose Following a Primary Series of Pfizer-BioNTech COVID-19 in Participants 5 Through 11 Years of Age

    A subset of Phase 2/3 participants 5 through 11 years of age received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine at least 5 months after completing the primary series (range 5 to 9 months, 86.8% of participants received a booster dose at least 8 months after Dose 2). Those participants vaccinated prior to February 22, 2022 provided the safety database (n=401), and had a median safety follow-up of 1.3 months from vaccination through the data cut-off date of March 22, 2022.

    The median age of these 401 participants was 8.0 years (range 5 through 11 years of age), 52.4% were male and 47.6% were female, 70.1% were White, 7.2% were Black or African American, 22.9% were Hispanic/Latino, 7.7% were Asian, and 2.0% were American Indian/Alaska Native.

    Unsolicited Adverse Events

    Overall, the 401 participants who received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine had a median follow-up time of 1.3 months after the booster dose through the cutoff date.

    In an analysis of all unsolicited adverse events reported in participants 5 through 11 years of age (N = 401) through up to 1 month after a first booster dose, lymphadenopathy (n = 10, 2.5%) was an adverse reaction not already captured by solicited local and systemic reactions.

    Serious Adverse Events

    No serious adverse events were reported after the first booster dose through the cutoff date.

    First Booster Dose Following Primary Vaccination with Another Authorized or Approved COVID-19 Vaccine

    The safety of a Pfizer-BioNTech COVID-19 Vaccine booster dose in individuals who completed primary vaccination with another authorized or approved COVID-19 Vaccine (heterologous booster dose) is inferred from the safety of a Pfizer-BioNTech COVID-19 Vaccine booster dose administered following completion of Pfizer-BioNTech COVID-19 Vaccine primary series (homologous booster dose) and from data from an independent National Institutes of Health (NIH) study Phase 1/2 open-label clinical trial (NCT04889209) conducted in the United States that evaluated a heterologous booster dose of the Pfizer-BioNTech COVID-19 Vaccine. In this study, adults who had completed primary vaccination with a Moderna COVID-19 Vaccine 2-dose series (N=151), a Janssen COVID-19 Vaccine single dose (N=156), or a Pfizer-BioNTech COVID-19 Vaccine 2-dose series (N=151) at least 12 weeks prior to enrollment and who reported no history of SARS-CoV-2 infection were randomized 1:1:1 to receive a booster dose of 1 of 3 vaccines: Moderna COVID-19 Vaccine, Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine. Adverse events were assessed through 28 days after the booster dose. An overall review of adverse reactions reported in the study following the Pfizer-BioNTech COVID-19 Vaccine heterologous booster dose did not identify any new safety concerns, as compared with adverse reactions reported following a Pfizer-BioNTech COVID-19 Vaccine primary series doses or homologous booster dose.

    Second Booster Dose Following Primary Series and First Booster Vaccination

    Safety surveillance data from the Ministry of Health of Israel on the administration of approximately 700,000 fourth doses of the Pfizer-BioNTech COVID-19 Vaccine given at least 4 months after the third dose in adults 18 years of age and older (approximately 600,000 of whom were 60 years of age and older) revealed no new safety concerns.

    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

  • 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 administration of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent 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 children and adults
    • Cases of COVID-19 that result in hospitalization or death

    *Serious adverse events are defined as:

    • Death
    • A life-threatening adverse event
    • Inpatient hospitalization or prolongation of existing hospitalization
    • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
    • A congenital anomaly/birth defect
    • An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent 1 of the outcomes listed above

    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, Bivalent
    • 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, Bivalent 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, Bivalent 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, Bivalent with other vaccines.

  • 11 USE IN SPECIFIC POPULATIONS

    11.1 Pregnancy

    Risk Summary

    No data are available regarding the use of Pfizer-BioNTech COVID-19 Vaccine, Bivalent during pregnancy.

    All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on Pfizer-BioNTech COVID-19 Vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

    In a reproductive and developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (modRNA) (30 mcg) and other ingredients included in a single human dose of Pfizer-BioNTech COVID-19 Vaccine was administered to female rats by the intramuscular route on 4 occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.

    11.2 Lactation

    Risk Summary

    Data are not available to assess the effects of Pfizer-BioNTech COVID-19 Vaccine or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent on the breastfed infant or on milk production/excretion.

    11.3 Pediatric Use

    Emergency Use Authorization of Pfizer-BioNTech COVID-19 Vaccine, Bivalent in adolescents 12 through 17 years of age is based on the safety and effectiveness of Pfizer-BioNTech COVID-19 Vaccine in individuals 6 months of age and older and safety and immunogenicity data with the bivalent vaccine (Original and Omicron BA.1) in adults 55 years of age and older.

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent is not authorized for use in individuals younger than 12 years of age.

    11.4 Geriatric Use

    Clinical studies of Pfizer-BioNTech COVID-19 Vaccine include participants 65 years of age and older who received the primary series and their data contributes to the overall assessment of safety and effectiveness of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent [see Overall Safety Summary (6.1) and Clinical Trial Results and Supporting Data for EUA (18.1)]. Of the total number of Pfizer-BioNTech COVID-19 Vaccine recipients in Study 2 (N=20,033), 21.4% (n=4,294) were 65 years of age and older and 4.3% (n=860) were 75 years of age and older.

    A clinical study with the bivalent vaccine (Original and Omicron BA.1) included 197 individuals 65 years of age and older and their data contribute to the overall assessment of safety and effectiveness of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

  • 13 DESCRIPTION

    The Pfizer-BioNTech COVID-19 Vaccine, Bivalent is supplied as a sterile, frozen suspension in single dose and multiple dose vials with gray caps and labels with gray borders.

    Each 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent is formulated to contain 15 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 15 mcg of modRNA encoding the S glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5). The S-proteins of the SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 are identical. Each dose contains 30 mcg modRNA.

    Each 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent supplied in single dose and multiple dose vials also includes the following ingredients: lipids (0.43 mg ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.19 mg cholesterol), 0.06 mg tromethamine, 0.4 mg tromethamine hydrochloride, and 31 mg sucrose.

    The Pfizer-BioNTech COVID-19 Vaccine, Bivalent 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, Bivalent 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

    The effectiveness of a booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) is based on effectiveness of primary and booster vaccination with Pfizer-BioNTech COVID-19 Vaccine and immunogenicity of a second booster dose with the bivalent vaccine (Original and Omicron BA.1).

    18.1 Efficacy of Primary Series of Pfizer-BioNTech COVID-19 Vaccine 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 adolescents 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 subjectsÞ8
    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 subjectsÞ9
    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 Efficacy of Primary Series of Pfizer-BioNTech COVID-19 Vaccine in Adolescents 12 Through 15 Years of Age

    A descriptive efficacy analysis of Study 2 has been performed in approximately 2,200 adolescents 12 through 15 years of age evaluating confirmed COVID-19 cases accrued up to a data cutoff date of March 13, 2021.

    The efficacy information in adolescents 12 through 15 years of age is presented in Table 7.

    Table 7: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2: Without Evidence of Infection and With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Blinded Placebo-Controlled Follow-up Period, Adolescents 12 Through 15 Years of Age 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
    Confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted for surveillance time.
    First COVID-19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age without evidence of prior SARS-CoV-2 infection*
    Pfizer-BioNTech COVID-19 Vaccine
    N=1005
    Cases
    n1§
    Surveillance Time (n2#)
    Placebo
    N=978
    Cases
    n1§
    Surveillance Time (n2#)
    Vaccine Efficacy %
    (95% CIÞ)
    Adolescents 12 through 15 years of age0
    0.154 (1001)
    16
    0.147 (972)
    100.0
    (75.3, 100.0)
    First COVID-19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age with or without evidence of prior SARS-CoV-2 infection
    Pfizer-BioNTech COVID-19 Vaccine
    N=1119
    Cases
    n1§
    Surveillance Time (n2#)
    Placebo

    N=1110
    Cases
    n1§
    Surveillance Time (n2#)
    Vaccine Efficacy %
    (95% CIÞ)
    Adolescents 12 through 15 years of age0
    0.170 (1109)
    18
    0.163 (1094)
    100.0
    (78.1, 100.0)

    18.3 Immunogenicity of Primary Series of Pfizer-BioNTech COVID-19 Vaccine in Adolescents 12 Through 15 Years of Age

    In Study 2, an analysis of SARS-CoV-2 50% neutralizing titers (NT50) 1 month after Dose 2 in a randomly selected subset of participants demonstrated non-inferior immune responses (within 1.5-fold) comparing adolescents 12 through 15 years of age to participants 16 through 25 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to 1 month after Dose 2 (Table 8).

    Table 8: Summary of Geometric Mean Ratio for 50% Neutralizing Titer – Comparison of Adolescents 12 Through 15 Years of Age to Participants 16 Through 25 Years of Age (Immunogenicity Subset) –Participants Without Evidence of Infection up to 1 Month After Dose 2 – Dose 2 Evaluable Immunogenicity Population
    Pfizer-BioNTech COVID-19 Vaccine*
    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 receipt of the last dose) 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 up to 1 month after Dose 2 were included in the analysis.
    *
    Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
    n = Number of participants with valid and determinate assay results for the specified assay at the given dose/sampling time point.
    Protocol-specified timing for blood sample collection.
    §
    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.
    GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers (12 through 15 years of age minus 16 through 25 years of age) and the corresponding CI (based on the Student t distribution).
    #
    Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67.
    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.
    12 Through 15 Years
    n=190
    16 Through 25 Years
    n=170
    12 Through 15 Years/ 16 Through 25 Years
    AssayTime PointGMT§
    (95% CI§)
    GMT§
    (95% CI§)
    GMR
    (95% CI)
    Met Noninferiority Objective#
    (Y/N)
    SARS-CoV-2 neutralization assay - NT50 (titer)Þ1 month after Dose 21239.5
    (1095.5, 1402.5)
    705.1
    (621.4, 800.2)
    1.76
    (1.47, 2.10)
    Y

    18.4 Immunogenicity of the Bivalent Vaccine (Original and Omicron BA.1) Administered as a Second Booster Dose

    In an analysis of a subset from Study 4, a total of 610 adults greater than 55 years of age who had previously received a 2-dose primary series and 1 booster dose with Pfizer-BioNTech COVID-19 Vaccine received 1 of the following as a second booster dose: Pfizer-BioNTech COVID-19 Vaccine or bivalent vaccine (Original and Omicron BA.1). GMRs and seroresponse rates were evaluated at 1 month after vaccination with the bivalent vaccine (Original and Omicron BA.1). The bivalent vaccine (Original and Omicron BA.1) booster dose was administered 4.7 to 11.5 months (median 6.3 months) after the first booster dose. The Pfizer-BioNTech COVID-19 Vaccine booster dose was administered 5.3 to 13.1 months (median 6.3 months) after the first booster dose.

    The primary objective of the study was to assess superiority with respect to level of 50% neutralizing titer (NT50) and noninferiority with respect to seroresponse rate of the anti-Omicron BA.1 immune response induced by a dose of the bivalent vaccine (Original and Omicron BA.1) relative to the response elicited by a dose of Pfizer-BioNTech COVID-19 Vaccine given as a second booster dose in participants greater than 55 years of age.

    A secondary objective of the study was to assess noninferiority with respect to level of NT50 to the Original SARS-COV-2 strain induced by a dose of the bivalent vaccine (Original and Omicron BA.1) relative to the response elicited by a dose of Pfizer-BioNTech COVID-19 Vaccine given as a second booster dose. A comparison of seroresponse rates to the Original strain was descriptive.

    Superiority of the anti-Omicron BA.1 NT50 for the bivalent vaccine (Original and Omicron BA.1) relative to Pfizer-BioNTech COVID-19 Vaccine was met, as the lower bound of the 2-sided 95% CI for GMR was >1. Noninferiority of the anti-Original NT50 for the bivalent vaccine (Original and Omicron BA.1) relative to Pfizer-BioNTech COVID-19 Vaccine was met, as the lower bound of the 2-sided 95% CI for GMR was >0.67 and the point estimate of the GMR was ≥0.8 (Table 9).

    Non-inferiority of the seroresponse rate to the Omicron BA.1 variant for the bivalent vaccine (Original and Omicron BA.1) relative to Pfizer-BioNTech COVID-19 Vaccine was met as the lower limit of the 2-sided 95% CI for the difference in percentages of participants with seroresponse is >-5% (Table 10). A descriptive summary of seroresponse to the Original strain is also included in Table 10.

    Table 9: Study 4 - Geometric Mean Ratios – Participants Without Evidence of Infection Up to 1 Month After the Second Booster Dose – Immunogenicity Subset – Participants Greater Than 55 Years of Age – Evaluable Immunogenicity Population
    AssayVaccine Group
    (as randomized)
    Sampling Time Point*NGMT
    (95% CI)
    GMR
    (95% CI§)
    Abbreviations: GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of quantitation; N-binding = SARS-CoV-2 nucleoprotein–binding; NAAT = nucleic acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
    Note: Immunogenicity subset = a random sample of 230 participants in each vaccine group.
    Note: Participants who had no serological or virological evidence (prior to the 1-month post–study vaccination blood sample collection) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] result negative at the study vaccination and the 1-month post–study vaccination visits, negative NAAT [nasal swab] result at the study vaccination visit, and any unscheduled visit prior to the 1-month post–study vaccination blood sample collection) and had no medical history of COVID-19 were included in the analysis.
    *
    Protocol-specified timing for blood sample collection.
    n = number of participants with valid and determinate assay results for the specified assay at the given 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.
    §
    GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers (vaccine group in the corresponding row - Pfizer-BioNTech COVID-19 Vaccine) and the corresponding CI (based on the Student t distribution). Superiority for anti-Omicron BA.1 immune response is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 1 after satisfying multiplicity adjustment. Noninferiority for anti-Original strain is declared if the lower limit of the 2-sided 95% CI for the GMR is greater than 0.67 (1.5-fold criterion) and the point estimate of the GMR is ≥0.8, after satisfying multiplicity adjustment.
    SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain [USA-WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.1).
    SARS-CoV-2 neutralization assay - Omicron BA.1 - NT50 (titer)Pfizer-BioNTech COVID-19 Vaccine1 month163455.8
    (365.9, 567.6)
    Bivalent Vaccine (Original and Omicron BA.1)1 month178711.0
    (588.3, 859.2)
    1.56
    (1.17, 2.08)
    SARS-CoV-2 neutralization assay - Original strain - NT50 (titer)Pfizer-BioNTech COVID-19 Vaccine1 month1825998.1
    (5223.6, 6887.4)
    Bivalent Vaccine (Original and Omicron BA.1)1 month1865933.2
    (5188.2, 6785.2)
    0.99
    (0.82, 1.20)
    Table 10: Study 4 - Number (%) of Participants Achieving Seroresponse – Participants Without Evidence of Infection Up to 1 Month After the Second Booster Dose – Immunogenicity Subset – Participants Greater Than 55 Years of Age – Evaluable Immunogenicity Population
    AssayVaccine Group
    (as randomized)
    Sampling Time Point*Nn (%)
    (95% CI§)
    Difference %
    (95% CI#)
    Abbreviations: LLOQ = lower limit of quantitation; N-binding = SARS-CoV-2 nucleoprotein–binding; NAAT = nucleic acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
    Note: Immunogenicity subset = a random sample of 230 participants in each vaccine group.
    Note: Seroresponse is defined as achieving ≥ 4-fold rise from baseline (before the second booster dose). If the baseline measurement is below the LLOQ, the postvaccination measure of ≥ 4 × LLOQ is considered a seroresponse.
    Note: Participants who had no serological or virological evidence (prior to the 1-month post–study vaccination blood sample collection) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] result negative at the study vaccination and the 1-month post–study vaccination visits, negative NAAT [nasal swab] result at the study vaccination visit, and any unscheduled visit prior to the 1-month post–study vaccination blood sample collection) and had no medical history of COVID-19 were included in the analysis.
    *
    Protocol-specified timing for blood sample collection.
    N = Number of participants with valid and determinate assay results for the specified assay at both the pre-vaccination time point and the given sampling time point. This value is the denominator for the percentage calculation.
    n = Number of participants with seroresponse at 1 month after vaccination for the given assay.
    §
    Exact 2-sided CI based on the Clopper and Pearson method.
    Difference in proportions, expressed as a percentage (vaccine group in the corresponding row - Pfizer-BioNTech COVID-19 Vaccine.
    #
    2-sided CI based on the Miettinen and Nurminen method for the difference in proportions, expressed as a percentage. Noninferiority for anti-Omicron BA.1 seroresponse is declared if the lower bound of the 2-sided 95% CI for the difference is greater than -5% after satisfying multiplicity adjustment.
    Þ
    SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain [USA-WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.1).
    SARS-CoV-2 neutralization assay - Omicron BA.1 - NT50 (titer)ÞPfizer-BioNTech COVID-19 Vaccine1 month14985 (57.0)
    (48.7, 65.1)
    Bivalent Vaccine (Original and Omicron BA.1)1 month169121 (71.6)
    (64.2, 78.3)
    14.6
    (4.0, 24.9)
    SARS-CoV-2 neutralization assay - Original strain - NT50 (titer)ÞPfizer-BioNTech COVID-19 Vaccine1 month17988 (49.2)
    (41.6, 56.7)
    Bivalent Vaccine (Original and Omicron BA.1)1 month18693 (50.0)
    (42.6, 57.4)

    18.5 Immunogenicity of a First Booster Dose With a Pfizer-BioNTech COVID-19 Vaccine Primary Series in Participants 18 Through 55 Years of Age

    Effectiveness of a booster dose of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) was based on an assessment of 50% neutralizing antibody titers (NT50) against SARS-CoV-2 (USA_WA1/2020). In Study 2, analyses of NT50 1 month after the booster dose compared to 1 month after the primary series in individuals 18 through 55 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to 1 month after the booster vaccination demonstrated noninferiority for both geometric mean ratio (GMR) and difference in seroresponse rates. Seroresponse for a participant was defined as achieving a ≥4-fold rise in NT50 from baseline (before primary series). These analyses are summarized in Table 11 and Table 12.

    Table 11: Geometric Mean 50% Neutralizing Titer (SARS-CoV-2 USA_WA1/2020) – Comparison of 1 Month After Booster Dose to 1 Month After Primary Series – Participants 18 Through 55 Years of Age Without Evidence of Infection up to 1 Month After Booster Dose* – Booster Dose Evaluable Immunogenicity Population
    Assayn1 Month After Booster Dose
    GMT§
    (95% CI§)
    1 Month After Primary Series
    GMT§
    (95% CI§)
    1 Month After Booster Dose/ 1 Month After Primary Series
    GMR
    (97.5% CI)
    Met Noninferiority Objective#
    (Y/N)
    Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of quantitation; N-binding = SARS-CoV-2 nucleoprotein-binding; NAAT = nucleic acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; Y/N = yes/no.
    Note: Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
    *
    Participants who had no serological or virological evidence (up to 1 month after receipt of a booster dose of Pfizer-BioNTech COVID-19 Vaccine) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative and SARS-CoV-2 not detected by NAAT [nasal swab]) and had a negative NAAT (nasal swab) at any unscheduled visit up to 1 month after the booster dose were included in the analysis.
    All eligible participants who had received 2 doses of Pfizer-BioNTech COVID-19 Vaccine as initially randomized, with Dose 2 received within the predefined window (within 19 to 42 days after Dose 1), received a booster dose of Pfizer-BioNTech COVID-19 Vaccine, had at least 1 valid and determinate immunogenicity result after booster dose from a blood collection within an appropriate window (within 28 to 42 days after the booster dose), and had no other important protocol deviations as determined by the clinician.
    n = Number of participants with valid and determinate assay results at both sampling time points within specified window.
    §
    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.
    GMRs and 2-sided 97.5% CIs were calculated by exponentiating the mean differences in the logarithms of the assay and the corresponding CIs (based on the Student t distribution).
    #
    Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the GMR is >0.67 and the point estimate of the GMR is ≥0.80.
    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)Þ2122466.0
    (2202.6, 2760.8)

    750.6
    (656.2, 858.6)
    3.29
    (2.77, 3.90)
    Y
    Table 12: Seroresponse Rate for 50% Neutralizing Titer (SARS-CoV-2 USA_WA1/2020) – Comparison of 1 Month After Booster Dose to 1 Month After Primary Series – Participants 18 Through 55 Years of Age Without Evidence of Infection up to 1 Month After Booster Dose* – Booster Dose Evaluable Immunogenicity Population
    AssayN1 Month After Booster Dose
    n§
    % (95% CI)
    1 Month After Primary Series
    n§
    % (95% CI)
    Difference
    (1 Month After Booster Dose - 1 Month After Primary Series)
    %#
    (97.5% CIÞ)
    Met Noninferiority Objectiveß
    (Y/N)
    Abbreviations: CI = confidence interval; LLOQ = lower limit of quantitation; N-binding = SARS-CoV-2 nucleoprotein-binding; NAAT = nucleic acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; Y/N = yes/no.
    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: Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
    *
    Participants who had no serological or virological evidence (up to 1 month after receipt of booster vaccination) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative and SARS-CoV-2 not detected by NAAT [nasal swab]) and had a negative NAAT (nasal swab) at any unscheduled visit up to 1 month after booster vaccination were included in the analysis.
    All eligible participants who had received 2 doses of Pfizer-BioNTech COVID-19 Vaccine as initially randomized, with Dose 2 received within the predefined window (within 19 to 42 days after Dose 1), received a booster dose of Pfizer-BioNTech COVID-19 Vaccine, had at least 1 valid and determinate immunogenicity result after booster dose from a blood collection within an appropriate window (within 28 to 42 days after the booster dose), and had no other important protocol deviations as determined by the clinician.
    N = number of participants with valid and determinate assay results for the specified assay at baseline, 1 month after Dose 2 and 1 month after the booster dose within specified window. 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.
    #
    Difference in proportions, expressed as a percentage (1 month after booster dose – 1 month after Dose 2).
    Þ
    Adjusted Wald 2-sided CI for the difference in proportions, expressed as a percentage.
    ß
    Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the percentage difference is > -10%.
    à
    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)à200199
    99.5 (97.2, 100.0)
    196
    98.0 (95.0, 99.5)
    1.5
    (-0.7, 3.7)
    Y

    18.6 Immunogenicity of a First Booster Dose Following Primary Vaccination with Another Authorized or Approved COVID-19 Vaccine

    Effectiveness of a Pfizer-BioNTech COVID-19 Vaccine booster dose (30 mcg modRNA) in individuals who completed primary vaccination with another authorized or approved COVID-19 Vaccine (heterologous booster dose) is inferred from immunogenicity data supporting effectiveness of a Pfizer-BioNTech COVID-19 Vaccine booster dose administered following completion of Pfizer-BioNTech COVID-19 Vaccine primary series and from immunogenicity data from an independent NIH study Phase 1/2 open-label clinical trial (NCT04889209) conducted in the United States that evaluated a heterologous booster dose of the Pfizer-BioNTech COVID-19 Vaccine. In this study, adults who had completed primary vaccination with a Moderna COVID-19 Vaccine 2-dose series (N=151), a Janssen COVID-19 Vaccine single dose (N=156), or a Pfizer-BioNTech COVID-19 Vaccine 2-dose series (N=151) at least 12 weeks prior to enrollment and who reported no history of SARS-CoV-2 infection were randomized 1:1:1 to receive a booster dose of 1 of 3 vaccines: Moderna COVID-19 Vaccine, Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA). Neutralizing antibody titers, as measured by a pseudovirus neutralization assay using a lentivirus expressing the SARS-CoV-2 Spike protein with D614G mutation, were assessed on Day 1 prior to administration of the booster dose and on Day 15 after the booster dose. A booster response to the Pfizer-BioNTech COVID-19 Vaccine was demonstrated regardless of the vaccine used for primary vaccination.

  • 19 HOW SUPPLIED/STORAGE AND HANDLING

    Single Dose Vials: Pfizer-BioNTech COVID-19 Vaccine, Bivalent is a suspension for intramuscular injection. Single dose vials with gray caps and labels with gray borders are supplied in a carton containing 10 single dose vials. One vial contains 1 dose of 0.3 mL.

    • Carton of 10 single dose vials: NDC 59267-1404-2
    • Single dose vial: NDC 59267-1404-1

    Multiple Dose Vials: Pfizer-BioNTech COVID-19 Vaccine, Bivalent is a suspension for intramuscular injection. Multiple dose vials with gray caps and labels with gray borders are supplied in a carton containing 10 multiple dose vials. One vial contains 6 doses of 0.3 mL.

    • Carton of 10 multiple dose vials: NDC 59267-0304-2
    • Multiple dose vial: NDC 59267-0304-1

    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, Bivalent 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 single dose vials may take up to 2 hours to thaw at this temperature. A carton of 10 multiple dose vials may take up to 6 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, Bivalent 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.

    Vial Storage During Use

    If not previously thawed at 2°C to 8°C (35°F to 46°F), allow Pfizer-BioNTech COVID-19 Vaccine, Bivalent single dose vials or multiple dose vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent may be stored at room temperature [8°C to 25°C (46°F to 77°F)] for a total of 12 hours prior to the first puncture. After first puncture, the multiple dose vials should be held between 2°C to 25°C (35°F to 77°F). Multiple dose vials should be discarded 12 hours after first puncture.

    Transportation of Vials

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

  • 20 PATIENT COUNSELING INFORMATION

    Advise the recipient or caregiver to read the Vaccine Information 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.

  • SPL UNCLASSIFIED SECTION

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

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

    LAB-1536-1.0

    Revised: 31 August 2022

  • VACCINE INFORMATION FACT SHEET FOR RECIPIENTS AND CAREGIVERS ABOUT COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, AND THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT (ORIGINAL AND OMICRON BA.4/BA.5) TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19) FOR USE IN INDIVIDUALS 12 YEARS OF AGE AND OLDER

    FOR 12 YEARS OF AGE AND OLDER

    You are being offered either COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5), hereafter referred to as the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, to prevent Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2.

    This Vaccine Information Fact Sheet for Recipients and Caregivers comprises the Fact Sheet for the authorized Pfizer-BioNTech COVID-19 Vaccine and the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, and also includes information about the U.S. Food and Drug Administration (FDA)-licensed vaccine, COMIRNATY (COVID-19 Vaccine, mRNA) for use in individuals 12 years of age and older4.

    The FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine authorized under Emergency Use Authorization (EUA) for individuals 12 years of age and older, when prepared according to their respective instructions for use, can be used interchangeably.5

    COMIRNATY (COVID-19 Vaccine, mRNA) is an FDA-approved COVID-19 vaccine made by Pfizer for BioNTech. It is approved as a 2-dose series for prevention of COVID-19 in individuals 12 years of age and older. It is also authorized under EUA to provide:

    • a third primary series dose to individuals 12 years of age and older with certain kinds of immunocompromise.

    The Pfizer-BioNTech COVID-19 Vaccine has received EUA from FDA to provide:

    • a 2-dose primary series to individuals 12 years of age and older; and
    • a third primary series dose to individuals 12 years of age and older with certain kinds of immunocompromise.

    The Pfizer-BioNTech COVID-19 Vaccine, Bivalent has received EUA from FDA to provide either:

    • a single booster dose to individuals 12 years of age and older at least 2 months after completion of primary vaccination with any authorized or approved monovalent6 COVID-19 vaccine; or
    • a single booster dose to individuals 12 years of age and older at least 2 months after receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine.

    This Vaccine Information Fact Sheet contains information to help you understand the risks and benefits of COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, and the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, which you may receive because there is currently a pandemic of COVID-19. Talk to your 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 YOU GET ANY OF THESE VACCINES

    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.

    HOW ARE COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, AND THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT RELATED?

    COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine, when prepared according to their respective instructions for use, can be used interchangeably. The Pfizer-BioNTech COVID-19 Vaccine, Bivalent is made in the same way as COMIRNATY and Pfizer-BioNTech COVID-19 Vaccine but it also contains an Omicron component to help prevent COVID-19 caused by the Omicron variant of SARS-CoV-2.

    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 VACCINATION PROVIDER BEFORE YOU GET ANY OF THESE VACCINES?

    Tell the vaccination provider about all of your medical conditions, including if you:

    • have any allergies
    • have had myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining outside the heart)
    • have a fever
    • have a bleeding disorder or are on a blood thinner
    • are immunocompromised or are on a medicine that affects your immune system
    • are pregnant or plan to become pregnant
    • are breastfeeding
    • have received another COVID-19 vaccine
    • have ever fainted in association with an injection

    HOW ARE THESE VACCINES GIVEN?

    The Pfizer-BioNTech COVID-19 Vaccine, the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, or COMIRNATY (COVID-19 Vaccine, mRNA) will be given to you as an injection into the muscle.

    Primary Series: The Pfizer-BioNTech COVID-19 Vaccine and COMIRNATY (COVID-19 Vaccine, mRNA) are given for the primary series. The vaccine is administered as a 2-dose series, 3 weeks apart. A third primary series dose may be administered at least 4 weeks after the second dose to individuals with certain kinds of immunocompromise.

    Booster Dose: Pfizer-BioNTech COVID-19 Vaccine, Bivalent is administered as a single booster dose at least 2 months after:

    • completion of primary vaccination with any authorized or approved monovalent COVID-19 vaccine; or
    • receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine

    The vaccine may not protect everyone.

    WHO SHOULD NOT GET COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT?

    You should not get any of these vaccines if you:

    • had a severe allergic reaction after a previous dose of COMIRNATY (COVID-19 Vaccine, mRNA) or the Pfizer-BioNTech COVID-19 Vaccine
    • had a severe allergic reaction to any ingredient in these vaccines.

    WHAT ARE THE INGREDIENTS IN THESE VACCINES?

    COMIRNATY (COVID-19 Vaccine, mRNA), Pfizer-BioNTech COVID-19 Vaccine, and Pfizer-BioNTech COVID-19 Vaccine, Bivalent include the following ingredients:

    • mRNA and 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).

    Pfizer-BioNTech COVID-19 Vaccine for individuals 12 years of age and older contains 1 of the following sets of additional ingredients; ask the vaccination provider which version is being administered:

    • potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose

    OR

    • tromethamine, tromethamine hydrochloride, and sucrose

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent for individuals 12 years of age and older contains the following additional ingredients:

    • tromethamine, tromethamine hydrochloride, and sucrose

    COMIRNATY (COVID-19 Vaccine, mRNA) contains 1 of the following sets of additional ingredients; ask the vaccination provider which version is being administered:

    • potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose

    OR

    • tromethamine, tromethamine hydrochloride, and sucrose

    HAVE THESE VACCINES BEEN USED BEFORE?

    In clinical trials, approximately 23,000 individuals 12 years of age and older have received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine. Millions of individuals have received the Pfizer-BioNTech COVID-19 Vaccine under EUA since December 11, 2020.

    In a clinical trial, approximately 300 individuals greater than 55 years of age received one dose of a bivalent vaccine that differs from the Pfizer-BioNTech COVID-19 Vaccine, Bivalent in that it contains a different Omicron component.

    WHAT ARE THE BENEFITS OF THESE VACCINES?

    COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine have been shown to prevent COVID-19. FDA has authorized Pfizer-BioNTech COVID-19 Vaccine, Bivalent to provide better protection against COVID-19 caused by the Omicron variant of SARS-CoV-2.

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

    WHAT ARE THE RISKS OF THESE VACCINES?

    There is a remote chance that these vaccines could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to 1 hour after getting a dose. For this reason, your vaccination provider may ask you to stay at the place where you received your vaccine for monitoring after vaccination. Signs of a severe allergic reaction can include:

    • Difficulty breathing
    • Swelling of your face and throat
    • A fast heartbeat
    • A bad rash all over your body
    • Dizziness and weakness

    Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received COMIRNATY (COVID-19 Vaccine, mRNA) or Pfizer-BioNTech COVID-19 Vaccine, more commonly in adolescent males and adult males under 40 years of age than among females and older males. 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 you have any of the following symptoms after receiving the vaccine:

    • Chest pain
    • Shortness of breath
    • Feelings of having a fast-beating, fluttering, or pounding heart

    Side effects that have been reported with these vaccines include:

    • Severe allergic reactions
    • Non-severe allergic reactions such as rash, itching, hives, or swelling of the face
    • Myocarditis (inflammation of the heart muscle)
    • Pericarditis (inflammation of the lining outside the heart)
    • Injection site pain
    • Tiredness
    • Headache
    • Muscle pain
    • Chills
    • Joint pain
    • Fever
    • Injection site swelling
    • Injection site redness
    • Nausea
    • Feeling unwell
    • Swollen lymph nodes (lymphadenopathy)
    • Decreased appetite
    • Diarrhea
    • Vomiting
    • Arm pain
    • Fainting in association with injection of the vaccine

    These may not be all the possible side effects of these vaccines. Serious and unexpected side effects may occur. The possible side effects of these vaccines are still being studied.

    WHAT SHOULD I DO ABOUT SIDE EFFECTS?

    If you experience a severe allergic reaction, call 9-1-1, or go to the nearest hospital.

    Call the vaccination provider or your healthcare provider if you have any side effects that bother you 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 either "COMIRNATY (COVID-19 Vaccine, mRNA)", "Pfizer-BioNTech COVID-19 Vaccine EUA", or "Pfizer-BioNTech COVID-19 Vaccine, Bivalent EUA" as appropriate, 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 GET COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT?

    Under the EUA, it is your choice to receive or not receive any of these vaccines. Should you decide not to receive any of these vaccines, it will not change your standard medical care.

    ARE OTHER CHOICES AVAILABLE FOR PREVENTING COVID-19 BESIDES COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT?

    For primary vaccination, another choice for preventing COVID-19 is SPIKEVAX (COVID-19 Vaccine, mRNA), an FDA-approved COVID-19 vaccine. Other vaccines to prevent COVID-19 may be available under EUA, including bivalent vaccines that contain an Omicron component of SARS-CoV-2.

    CAN I RECEIVE COMIRNATY (COVID-19 VACCINE, mRNA), PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT AT THE SAME TIME AS OTHER VACCINES?

    Data have not yet been submitted to FDA on administration of COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent at the same time with other vaccines. If you are considering receiving COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent with other vaccines, discuss your options with your healthcare provider.

    WHAT IF I AM IMMUNOCOMPROMISED?

    If you are immunocompromised, you may receive a third primary series dose of Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA). Individuals 12 years of age and older may receive a booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent. Vaccinations may not provide full immunity to COVID-19 in people who are immunocompromised, and you should continue to maintain physical precautions to help prevent COVID-19. Your close contacts should be vaccinated as appropriate.

    WHAT IF I AM PREGNANT OR BREASTFEEDING?

    If you are pregnant or breastfeeding, discuss your options with your healthcare provider.

    WILL THESE VACCINES GIVE ME COVID-19?

    No. These vaccines do not contain SARS-CoV-2 and cannot give you COVID-19.

    KEEP YOUR VACCINATION CARD

    When you get your first COVID-19 vaccine, you will get a vaccination card. Remember to bring your card when you return.

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

    HOW CAN I LEARN MORE?

    • Ask the vaccination provider.
    • Visit CDC at https://www.cdc.gov/coronavirus/2019-ncov/index.html.
    • Visit FDA at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.
    • Contact your local or state public health department.

    WHERE WILL MY VACCINATION INFORMATION BE RECORDED?

    The vaccination provider may include your vaccination information in your state/local jurisdiction's Immunization Information System (IIS) or other designated system. This will ensure that you receive the same vaccine when you return for the second dose of the primary series. 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 THESE COVID-19 VACCINES?

    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 these vaccines. 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

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

    LAB-1451-22.0

    Revised: 31 August 2022

    ImageScan to capture that this Fact Sheet was provided to vaccine recipient for the electronic medical records/immunization information systems.
    GDTI: 0886983000332

    4
    You may receive this Vaccine Information Fact Sheet even if your child is 11 years old. Children who will turn from 11 years to 12 years of age between doses in the primary regimen may receive, for any dose in the primary regimen, either: (1) the Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 5 through 11 years of age; or (2) COMIRNATY (COVID-19 Vaccine, mRNA) or the Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 12 years of age and older.
    5
    When prepared according to their respective instructions for use, the FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the EUA-authorized Pfizer-BioNTech COVID-19 Vaccine for individuals 12 years of age and older can be used interchangeably without presenting any safety or effectiveness concerns.
    6
    Monovalent refers to any authorized or approved COVID-19 vaccine that contains or encodes the spike protein of only the Original SARS-CoV-2.
  • PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Label - 0304

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent
    Original and Omicron BA.4/BA.5

    DO NOT DILUTE
    Age 12y & older

    Vial contains 6 doses of 0.3 mL

    For intramuscular use. Contains no preservative.
    For use under Emergency Use Authorization.
    After first use store at 2 to 25°C (35 to 77°F)
    and discard after 12 hours.
    First use date and time:

    NDC 59267-0304-1

    PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Label - 0304
  • PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Carton - 0304

    NDC 59267-0304-2

    Pfizer-BioNTech
    COVID-19 Vaccine, Bivalent

    Original and Omicron BA.4/BA.5

    Suspension for Intramuscular Injection

    DO NOT DILUTE

    10 Multiple Dose Vials

    Each vial contains 6 doses of 0.3 mL

    For 12 years of age and older
    For use under Emergency Use Authorization.

    BIONTECH
    Pfizer

    Rx only

    PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Carton - 0304
  • PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Label - 1404

    Pfizer-BioNTech COVID-19 Vaccine, Bivalent
    Original and Omicron BA.4/BA.5

    DO NOT DILUTE
    Age 12y & older

    Vial contains 1 dose of 0.3 mL

    For intramuscular use.
    Contains no preservative.
    For use under Emergency Use Authorization.
    Discard after single use.

    NDC 59267-1404-1

    PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Label - 1404
  • PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Carton - 1404

    NDC 59267-1404-2

    Pfizer-BioNTech
    COVID-19 Vaccine, Bivalent

    Original and Omicron BA.4/BA.5

    Suspension for Intramuscular Injection

    DO NOT DILUTE

    10 Single Dose Vials

    Each vial contains 1 dose of 0.3 mL

    For 12 years of age and older
    For use under Emergency Use Authorization.

    BIONTECH
    Pfizer

    Rx only

    PRINCIPAL DISPLAY PANEL - 0.3 mL Vial Carton - 1404
  • INGREDIENTS AND APPEARANCE
    PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT 
    bnt162b2 original and omicron ba.4/ba.5 injection, suspension
    Product Information
    Product TypeVACCINEItem Code (Source)NDC:59267-0304
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TOZINAMERAN (UNII: 5085ZFP6SJ) (TOZINAMERAN - UNII:5085ZFP6SJ) TOZINAMERAN0.1125 mg  in 2.25 mL
    BNT162B2 OMICRON (BA.4/BA.5) (UNII: JSV288Q5CV) (BNT162B2 OMICRON (BA.4/BA.5) - UNII:JSV288Q5CV) BNT162B2 OMICRON (BA.4/BA.5)0.1125 mg  in 2.25 mL
    Inactive Ingredients
    Ingredient NameStrength
    2-(MPEG 2000)-N,N-DITETRADECYLACETAMIDE (UNII: PJH39UMU6H) 0.41 mg  in 2.25 mL
    ((4-HYDROXYBUTYL)AZANEDIYL)BIS(HEXANE-6,1-DIYL)BIS(2-HEXYLDECANOATE) (UNII: AVX8DX713V) 3.22 mg  in 2.25 mL
    TROMETHAMINE (UNII: 023C2WHX2V) 0.45 mg  in 2.25 mL
    TROMETHAMINE HYDROCHLORIDE (UNII: 383V75M34E) 2.97 mg  in 2.25 mL
    SUCROSE (UNII: C151H8M554) 231.8 mg  in 2.25 mL
    1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE (UNII: 043IPI2M0K) 0.7 mg  in 2.25 mL
    CHOLESTEROL (UNII: 97C5T2UQ7J) 1.4 mg  in 2.25 mL
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:59267-0304-210 in 1 CARTON
    1NDC:59267-0304-12.25 mL in 1 VIAL, GLASS; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    EMERGENCY USE AUTHORIZATION09/01/2022
    PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT 
    bnt162b2 original and omicron ba.4/ba.5 injection, suspension
    Product Information
    Product TypeVACCINEItem Code (Source)NDC:59267-1404
    Route of AdministrationINTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TOZINAMERAN (UNII: 5085ZFP6SJ) (TOZINAMERAN - UNII:5085ZFP6SJ) TOZINAMERAN0.024 mg  in 0.48 mL
    BNT162B2 OMICRON (BA.4/BA.5) (UNII: JSV288Q5CV) (BNT162B2 OMICRON (BA.4/BA.5) - UNII:JSV288Q5CV) BNT162B2 OMICRON (BA.4/BA.5)0.024 mg  in 0.48 mL
    Inactive Ingredients
    Ingredient NameStrength
    2-(MPEG 2000)-N,N-DITETRADECYLACETAMIDE (UNII: PJH39UMU6H) 0.09 mg  in 0.48 mL
    ((4-HYDROXYBUTYL)AZANEDIYL)BIS(HEXANE-6,1-DIYL)BIS(2-HEXYLDECANOATE) (UNII: AVX8DX713V) 0.69 mg  in 0.48 mL
    TROMETHAMINE (UNII: 023C2WHX2V) 0.1 mg  in 0.48 mL
    TROMETHAMINE HYDROCHLORIDE (UNII: 383V75M34E) 0.63 mg  in 0.48 mL
    SUCROSE (UNII: C151H8M554) 49.44 mg  in 0.48 mL
    1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE (UNII: 043IPI2M0K) 0.15 mg  in 0.48 mL
    CHOLESTEROL (UNII: 97C5T2UQ7J) 0.3 mg  in 0.48 mL
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:59267-1404-210 in 1 CARTON
    1NDC:59267-1404-10.48 mL in 1 VIAL, GLASS; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    EMERGENCY USE AUTHORIZATION09/01/2022
    Labeler - Pfizer Manufacturing Belgium NV (370156507)
    Registrant - Pfizer Inc (113480771)
    Establishment
    NameAddressID/FEIBusiness Operations
    Pfizer Manufacturing Belgium NV370156507ANALYSIS(59267-0304, 59267-1404) , MANUFACTURE(59267-0304, 59267-1404) , PACK(59267-0304, 59267-1404) , LABEL(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    Pharmacia & Upjohn Company LLC618054084ANALYSIS(59267-0304, 59267-1404) , MANUFACTURE(59267-0304, 59267-1404) , PACK(59267-0304, 59267-1404) , LABEL(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    BioNTech Innovative Manufacturing Services GmbH537365801ANALYSIS(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    BioNTech Manufacturing GmbH314382536ANALYSIS(59267-0304, 59267-1404) , API MANUFACTURE(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    BioNTech Manufacturing Marburg GmbH313270335ANALYSIS(59267-0304, 59267-1404) , API MANUFACTURE(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    Hospira, Inc.030606222ANALYSIS(59267-0304, 59267-1404) , MANUFACTURE(59267-0304, 59267-1404) , PACK(59267-0304, 59267-1404) , LABEL(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    Wyeth BioPharma Division of Wyeth Pharmaceuticals LLC174350868ANALYSIS(59267-0304, 59267-1404) , API MANUFACTURE(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    Pfizer Inc004954111ANALYSIS(59267-0304, 59267-1404)
    Establishment
    NameAddressID/FEIBusiness Operations
    Pfizer Ireland Pharmaceuticals985586408ANALYSIS(59267-0304, 59267-1404)