2.1 Preparation for Administration

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Pfizer-BioNTech COVID-19 Vaccine, Bivalent multiple dose vials and single dose vials contain a frozen suspension that does not contain a preservative and must be thawed prior to administration.

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There are 4 presentations of Pfizer-BioNTech COVID-19 Vaccine, Bivalent [see Dosage and Administration (2.3)]:

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Multiple dose vials with maroon caps and labels with maroon borders. This presentation is authorized to provide doses for individuals 6 months through 4 years of age. Must be diluted.

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Multiple dose vials with orange caps and labels with orange borders. This presentation is authorized to provide doses for individuals 5 through 11 years of age. Must be diluted.

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Single dose vials with gray caps and labels with gray borders. This presentation is authorized to provide doses for individuals 12 years of age and older. Do not dilute

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Multiple dose vials with gray caps and labels with gray borders. This presentation is authorized to provide doses for individuals 12 years of age and older. Do not dilute

Thawing Instructions

Thaw each vial before use following the instructions below:

Alternatively, thaw vials at room temperature [up to 25°C (77°F)] for 30 minutes.

Storage of Thawed Vials:

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Thawed vials may be stored at room temperature [up to 25°C (77°F)] for up to 12 hours prior to use.

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Thawed vials can be stored in the refrigerator between 2°C to 8°C (35°F to 46°F) for up to 10 weeks prior to use.

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Do not refreeze.

Preparation Instructions for Multiple Dose Vials with Maroon Caps or Orange Caps that MUST BE DILUTED BEFORE USE:

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Before dilution, invert vaccine vial gently 10 times. Do not shake.

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Inspect the liquid in the vial prior to dilution. The liquid is a white to off-white suspension and may contain opaque amorphous particles.

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Do not use if liquid is discolored or if other particles are observed.

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Obtain sterile 0.9% Sodium Chloride Injection, USP. Use only this as the diluent.

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Add the appropriate amount of sterile 0.9% Sodium Chloride Injection, USP into the vaccine vial as follows:

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Before removing the needle from the vial, equalize vial pressure by withdrawing air into the empty diluent syringe.

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Gently invert the vial containing the Pfizer-BioNTech COVID-19 Vaccine, Bivalent 10 times to mix.

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Do not shake.

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Inspect the vaccine in the vial.

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The vaccine will be a white to off-white suspension. Do not use if vaccine is discolored or contains particulate matter.

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Record the date and time of dilution on the vial label.

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After dilution, multiple dose vials contain 10 doses of 0.2 mL each.

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Withdraw 0.2 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 10 doses from a single vial.

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After dilution, the vial should be held between 2ºC to 25°C (35°F to 77°F). Vials should be discarded 12 hours after dilution.

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

Preparation Instructions for Single Dose Vials and Multiple Dose Vials with Gray Caps and Labels with Gray Borders that MUST NOT BE DILUTED

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Prior to mixing, the thawed vaccine may contain white to off-white opaque amorphous particles.

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Before use, mix by inverting vaccine vial gently 10 times.

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Do not shake.

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After mixing, the vaccine should appear as a white to off-white suspension with no visible particles.

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Do not use if liquid is discolored or if particles are observed after mixing.

Single Dose Vials with Gray Caps and Labels with Gray Borders

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Withdraw a single 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

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Administer immediately.

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Discard vial and any excess volume.

Multiple Dose Vials with Gray Caps and Labels with Gray Borders

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Multiple dose vials contain 6 doses of 0.3 mL each.

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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.

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Record the date and time of first vial puncture on the vial label.

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Store between 2°C to 25°C (35°F to 77°F).

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Discard any unused vaccine 12 hours after first puncture.

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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. Do not pool excess vaccine from multiple vials.

2.2 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.

Administer Pfizer-BioNTech COVID-19 Vaccine, Bivalent intramuscularly.

2.3 Dose and Schedule

Individuals 6 months of age and older not previously vaccinated with a COVID-19 vaccine

Individuals 6 months through 4 years of age previously vaccinated with the monovalent Pfizer-BioNTech COVID-19 Vaccine3

Individuals 5 years of age and older previously vaccinated with 1 or more doses of a monovalent COVID-19 vaccine4

Individuals with Certain Kinds of Immunocompromise5

For individuals with certain kinds of immunocompromise 6 months through 4 years of age who have received three 0.2 mL doses (Pfizer-BioNTech COVID-19 Vaccine or Pfizer-BioNTech COVID-19 Vaccine, Bivalent), a fourth dose (0.2 mL) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent may be administered at least 1 month following the most recent dose; additional doses of Pfizer-BioNTech COVID-19 Vaccine, Bivalent may be administered at the discretion of the healthcare provider, taking into consideration the individual’s clinical circumstances.

For individuals with certain kinds of immunocompromise 5 years of age and older, a single additional age-appropriate dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent may be administered at least 2 months following the initial dose of a bivalent COVID-19 vaccine; additional age-appropriate doses of Pfizer-BioNTech COVID-19 Vaccine, Bivalent may be administered at the discretion of the healthcare provider, taking into consideration the individual’s clinical circumstances.

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The monovalent Pfizer-BioNTech COVID-19 Vaccine is no longer authorized for use in the United States.

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Monovalent refers to a COVID-19 vaccine that contains or encodes the spike protein of only the Original SARS-CoV-2.

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Certain kinds of immunocompromise refers to individuals who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.

5.1 Management of Acute Allergic Reactions

Appropriate medical treatment 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 vaccination. For the Pfizer-BioNTech COVID-19 Vaccine, 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. Procedures should be in place to avoid injury from fainting.

5.4 Altered Immunocompetence

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

5.5 Limitations of Vaccine Effectiveness

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

6.1 Clinical Trials Experience

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

Pfizer-BioNTech COVID-19 Vaccine

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

Study BNT162-01 (Study 1) was a Phase 1/2, 2-part, dose-escalation trial that enrolled 60 participants, 18 through 55 years of age. Study C4591001 (Study 2) is a Phase 1/2/3, multicenter, multinational, randomized, saline placebo-controlled, observer-blind, dose finding, vaccine candidate-selection (Phase 1) and efficacy (Phase 2/3) study that has enrolled approximately 46,000 participants, 12 years of age and older. Of these, approximately 43,448 participants [21,720 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA); 21,728 placebo] in Phase 2/3 are 16 years of age or older (including 138 and 145 participants 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 participants are 12 through 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively). Study C4591007 (Study 3) is a Phase 1/2/3 multicenter, randomized, dose finding, open label (Phase 1) and multinational, saline placebo-controlled, observer-blind, immunogenicity and efficacy (Phase 2/3) study that has enrolled 4,695 participants 5 through 11 years of age, of whom 3,109 participants received Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 1,538 participants received placebo in Phase 2/3. Study 3 also enrolled 1,776 participants 6 through 23 months of age, of whom 1,178 participants were in the Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) group and 598 participants in the placebo group; and also enrolled 2,750 participants 2 through 4 years of age, of whom 1,835 participants were in the Pfizer-BioNTech COVID-19 Vaccine group and 915 participants in the placebo group in Phase 2/3.

In Study 2 and Study 3, all participants 6 months through 4 years of age, 5 through 11 years of age, 12 through 15 years of age, and a subset of participants 16 years of age and older, were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination in an electronic diary. Participants are being monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month after the last vaccination (all unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination].

Pfizer-BioNTech COVID-19 Vaccine Administered as a Primary Series

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

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

The safety evaluation in Study 2 is ongoing. The safety population includes participants 16 years 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.

Solicited Local and Systemic Adverse Reactions

Across both age groups, 18 through 55 years of age and 56 years of age and older, the mean duration of pain at the injection site after Dose 2 was 2.5 days (range 1 to 36 days), for redness 2.6 days (range 1 to 34 days), and for swelling 2.3 days (range 1 to 34 days) for participants in the Pfizer-BioNTech COVID-19 Vaccine group.

Solicited reactogenicity data in 16 and 17 year-old participants are limited.

Unsolicited Adverse Events

Serious Adverse Events

In Study 2, among participants 16 through 55 years of age who had received at least 1 dose of vaccine or placebo (Pfizer-BioNTech COVID-19 Vaccine = 10,841; placebo = 10,851), serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.3% of placebo recipients. In a similar analysis, in participants 56 years of age and older (Pfizer-BioNTech COVID-19 Vaccine = 7,960, placebo = 7,934), serious adverse events were reported by 0.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.6% of placebo recipients who received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine or placebo, respectively. In these analyses, 91.6% of study participants had at least 30 days of follow-up after Dose 2.

Appendicitis was reported as a serious adverse event for 12 participants, and numerically higher in the vaccine group, 8 vaccine participants and 4 placebo participants. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Non-Serious Adverse Events

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

The higher frequency of reported unsolicited non-serious adverse events among Pfizer-BioNTech COVID-19 Vaccine recipients compared to placebo recipients was primarily attributed to local and systemic adverse events reported during the first 7 days following vaccination that are consistent with adverse reactions solicited among participants in the reactogenicity subset and presented in Tables 3 and 4. 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.

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

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

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

Solicited Local and Systemic Adverse Reactions

The mean duration of pain at the injection site after Dose 1 was 2.4 days (range 1 to 10 days), for redness 2.4 days (range 1 to 16 days), and for swelling 1.9 days (range 1 to 5 days) for participants in the Pfizer-BioNTech COVID-19 Vaccine group.

Unsolicited Adverse Events

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

Serious Adverse Events

Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.1% of placebo recipients. There were no notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Non-Serious Adverse Events

Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 5.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 5.8% of placebo recipients. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy plausibly related to the study intervention were imbalanced, with notably more cases in the Pfizer-BioNTech COVID-19 Vaccine group (7) vs. the placebo group (1). There were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

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

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

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

Solicited Local and Systemic Adverse Reactions

The mean duration of pain at the injection site after Dose 2 was 2.3 days (range 1 to 11 days), for redness 2.2 days (range 1 to 10 days), and for swelling 2.2 days (range 1 to 10 days) for children in the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) group up to the cutoff date of September 06, 2021.

Unsolicited Adverse Events

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

Serious Adverse Events

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

Non-Serious Adverse Events

In 1 group of participants (initial enrollment cohort), non-serious adverse events from Dose 1 through up to 30 days after Dose 2 up to the cutoff date of September 06, 2021, in ongoing follow-up were reported by 10.9% of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) recipients and by 9.1% of placebo recipients. In this group of participants, >99% had follow-up 30 days post Dose 2. In a second group of participants (expansion cohort) for which the median follow-up was 2.4 weeks (range 0 to 3.7 weeks), non-serious adverse events from Dose 1 through the cutoff date of October 08, 2021, were reported by 7.1% of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) recipients and by 6.3% of placebo recipients.

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

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

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

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

Solicited Local and Systemic Adverse Reactions

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

Unsolicited Adverse Events

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

Serious Adverse Events

Serious adverse events from Dose 1 through 1 month after Dose 3, with an overall median of 1.4 months follow-up after Dose 3 were reported by 0.7% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.9% of placebo recipients. One serious adverse event of fever (maximum temperature 40.3°C) on Day 3 after Dose 2 in a 4-year-old was considered possibly related to vaccination.

Non-Serious Adverse Events

Non-serious adverse events from Dose 1 through up to 30 days after Dose 3, in ongoing follow-up were reported by 18.5% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 18.5% of placebo recipients.

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

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

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

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

Solicited Local and Systemic Adverse Reactions

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

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.

Third Primary Series Dose in Individuals with Certain Kinds of Immunocompromise

From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med), in 99 individuals who had undergone various solid organ transplant procedures (heart, kidney, liver, lung, pancreas) 97±8 months previously who received a third vaccine dose, the adverse event profile was similar to that after the second dose and no grade 3 or grade 4 events were reported in recipients who were followed for 1 month following post Dose 3.

Pfizer-BioNTech COVID-19 Vaccine Administered as a 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 participants 18 through 55 years of age received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) 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 13 and Table 14 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).

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 cutoff 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 (10 mcg modRNA) 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 cutoff 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.

Solicited Local and Systemic Adverse Reactions

Table 15 and Table 16 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of a booster dose of Pfizer-BioNTech COVID-19 Vaccine for Phase 2/3 participants 5 through 11 years of age.

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

Unsolicited Adverse Events

Overall, the 401 participants who received a 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.

Pfizer-BioNTech COVID-19 Vaccine Administered as a First Booster Dose Following 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 (30 mcg modRNA) 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, participants 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.

Pfizer-BioNTech COVID-19 Vaccine Administered as a Second Booster Dose Following Primary and Booster Vaccination with Another Authorized or Approved COVID-19 Vaccine

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 (30 mcg modRNA) given at least 4 months after the third dose in participants 18 years of age and older (approximately 600,000 of whom were 60 years of age and older) revealed no new safety concerns.

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

Study 5 (NCT05472038) enrolled participants 12 years of age and older to receive a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent (30 mcg modRNA). In Study 5, all participants 12 years of age and older are being monitored for safety throughout the study [through 6 months after the booster (fourth dose)].

Study 6 (NCT05543616) enrolled participants 6 months through 11 years of age to receive a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

In Study 6, all participants 6 months through 4 years of age were monitored for solicited local and systemic reactions and use of antipyretic medication after the vaccination in an electronic diary. Participants are being monitored for safety throughout the study [through 6 months after the booster (fourth dose)]. Tables 17 through 20 present the frequency and severity of solicited local and systemic reactions, within 7 days following a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent in participants 6 through 23 months of age and 2 through 4 years of age who were previously vaccinated with a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine.

Participants 12 Years of Age and Older Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)

A subset of Study 5 Phase 2/3 participants 12 through 17 years of age (n=107), 18 through 55 years of age (n=103) and 56 years of age and older (n=106) previously vaccinated with a 2-dose primary series and 1 booster dose of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA), received a second booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (30 mcg modRNA).

The participants received the second booster dose a median of 9.9 months (range 5.5 to 14.3 months) after receiving the first booster dose and had a median follow-up time of 1.6 months up to a data cutoff date of October 12, 2022. The median age was 40.0 years, 53.2% were male, 46.8% were female, 81.3% were White, 9.2% were Hispanic/Latino, 5.1% were Asian, and 10.8% were Black or African American.

Unsolicited Adverse Events

In the following analysis of Study 5, 316 participants 12 years of age and older who received a second booster of Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.6 months (range 1.3 to 1.8 months) to the cutoff date October 12, 2022.

Serious Adverse Events

Serious adverse events were reported in the 1 participant (considered unrelated to the vaccine) from the study vaccination through 1 month post vaccination.

Non-Serious Adverse Events

Lymphadenopathy 2 days post-vaccination, considered related to vaccination, was reported in 1 (0.3%) participant 12 years of age and older.

Participants 5 Through 11 Years of Age Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)

In Study 6, 113 participants 5 through 11 years of age previously vaccinated with a 2-dose primary series and 1 booster dose of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) received a booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (10 mcg modRNA).

Participants received a booster (fourth dose) with Pfizer-BioNTech COVID-19, Bivalent 2.6 to 8.5 months after receiving their third dose with Pfizer-BioNTech COVID-19 Vaccine and had a median follow-up time of 1.6 months (range 1.1 to 2.3 months) up to a data cutoff date of November 25, 2022. Their median age was 9 years (range 5 through 11 years of age), 50.4% were male and 49.6% were female, 58.4% were White, 20.4% were Hispanic/Latino, 19.5% were multi-racial, 11.5% were Asian, and 8.0% were Black or African American.

Unsolicited Adverse Events

In the following analysis of Study 6, 113 participants 5 through 11 years of age who received a booster (fourth dose) with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.6 months (range 1.1 to 2.3 months) to the cutoff date (November 25, 2022).

Serious Adverse Events

No serious adverse events were reported in the 113 participants 5 through 11 years of age from the study vaccination through 1 month post vaccination.

Non-Serious Adverse Events

Lymphadenopathy 2 days post-vaccination, considered related to vaccination, was reported in 1 (0.9%) participant 5 through 11 years of age.

Participants 2 Through 4 Years of Age Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)

In a subset of Study 6, 36 participants 2 through 4 years of age previously vaccinated with a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) received a booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (3 mcg modRNA).

Participants received a booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent 2.2 to 8.5 months after receiving their third dose with Pfizer-BioNTech COVID-19 Vaccine and had a median follow-up time of 1.9 months (range 1.6 to 2.3 months) up to a data cutoff date of November 25, 2022. Their median age was 2 years (range 2 through 4 years of age), 55.6% were male and 44.4% were female, 61.1% were White, 30.6% were Hispanic/Latino, 22.2% were multi-racial, 11.1% were Asian, and 5.6% were Black or African American.

Solicited Local and Systemic Adverse Reactions

Table 17 and Table 18 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

The mean duration of pain at the injection site was 1.1 days (range 1 to 2 days), for redness 1.3 days (range 1 to 2 days), and for swelling 3 days for participants 2 through 4 years of age.

Table 17: Local Adverse Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 2 through 4 Years of Age – Safety Population

Table 18: Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 2 Through 4 Years of Age – Safety Population

Unsolicited Adverse Events

Participants 2 through 4 years of age who received a booster (fourth dose) with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.9 months (range 1.6 to 2.3 months) to the cutoff date (November 25, 2022).

Serious Adverse Events

No serious adverse events were reported in the 36 participants 2 through 4 years of age from the study vaccination through 1 month post vaccination.

Participants 6 Through 23 Months of Age Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)

In a subset of Study 6, 24 participants 6 through 23 months previously vaccinated with a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) received a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (3 mcg modRNA).

Participants received a booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent 2.1 to 8.6 months after receiving their third dose with Pfizer-BioNTech COVID-19 and had a median follow-up time of 1.6 months (range 1.5 to 2.3 months) up to a data cutoff date of November 25, 2022. Their median age was 19 months (range 12 through 23 months), 58.3% were female and 41.7% were male, 54.2% were White, 20.8% were Asian, 20.8% were multi-racial, 16.7% were Hispanic/Latino, and 4.2% were Black or African American.

Solicited Local and Systemic Adverse Reactions

Table 19 and Table 20 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

The duration of injection site tenderness, swelling and redness for all events observed was 1 day.

Table 19: Local Adverse Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 6 Through 23 Months of Age – Safety Population

Table 20: Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 6 Through 23 Months of Age – Safety Population

Unsolicited Adverse Events

Participants 6 through 23 months of age who received a booster (fourth dose) with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.6 months (range 1.5 to 2.3 months) to the cutoff date (November 25, 2022). In an analysis of all unsolicited adverse events reported following the booster dose through 1 month after the booster dose, the adverse reaction not already captured by solicited local and systemic reactions was injection site pain (n=1; 4.2%).

Serious Adverse Events

No serious adverse events were reported in the 24 participants 6 through 23 months of age from the study vaccination through 1 month post vaccination.

Non-Serious Adverse Events

Non-serious adverse events in participants 6 through 23 months of age from the study vaccination through 1 month post vaccination were reported in 3 (12.5%) Pfizer-BioNTech COVID-19 Vaccine, Bivalent recipients. Non-serious adverse events considered related to vaccination by the study investigator were fatigue (n=1; 4.2%) and injection site pain (n=1; 4.2%).

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 cutoff 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 cutoff 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

Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving bivalent vaccine (Original and Omicron BA.1) and participants receiving Pfizer-BioNTech COVID-19 Vaccine. Events that persisted for more than 7 days were followed until resolution.

Table 21 and Table 22 present the frequency and severity of reported solicited local and systemic adverse reactions within 7 days following a second booster dose with Pfizer-BioNTech, Bivalent vaccine (Original and Omicron BA.1) booster dose compared to Pfizer-BioNTech COVID-19 Vaccine in participants greater than 55 years of age.

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.

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 cutoff 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).

6.2 Postmarketing Experience

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

Cardiac Disorders: myocarditis, pericarditis

Gastrointestinal Disorders: diarrhea, vomiting

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

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

Nervous System Disorders: syncope, dizziness

6.3 Required Reporting for Adverse Events and Vaccine Administration Errors

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for the 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 adults and children

•

Cases of COVID-19 that results 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 one 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 one 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 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 one month prior.

2.

In Box 18, description of the event:

a.

Write “Pfizer-BioNTech COVID-19 Vaccine, Bivalent EUA” as the first line

b.

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:

c.

In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.

d.

In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.

e.

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.

8.1 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 U.S. 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.

8.2 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.

8.4 Pediatric Use

Pfizer-BioNTech COVID-19 Vaccine, Bivalent is authorized for use in individuals 6 months through 17 years of age. This authorization is based on safety and effectiveness data with Pfizer-BioNTech COVID-19 Vaccine, Pfizer-BioNTech COVID-19 Vaccine, Bivalent, and the bivalent vaccine (Original and Omicron BA.1).

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

8.5 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 Adverse Reactions (6.1), Clinical Studies (14)]. 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 [see Adverse Reactions (6.1), Clinical Studies (14)].

8.6 Use in Immunocompromised Individuals

From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med), safety and effectiveness of a third dose of the Pfizer-BioNTech COVID-19 vaccine have been evaluated in persons that received solid organ transplants. The administration of a third dose of vaccine appears to be only moderately effective in increasing potentially protective antibody titers. Patients should still be counselled to maintain physical precautions to help prevent COVID-19. In addition, close contacts of immunocompromised persons should be vaccinated as appropriate for their health status.