Comirnaty Injection, Suspension
FDA Label NDC 0069-2501

COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

COMIRNATY is approved for use in individuals who are:

• 65 years of age and older, or
• 5 years through 64 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19.

For intramuscular use.

COMIRNATY Single-Dose Prefilled Syringes for Individuals 65 Years of Age and Older and Individuals 12 Years Through 64 Years of Age with at Least One Underlying Condition that Puts Them at High Risk for Severe Outcomes from COVID-19:

• Verify that the label on the prefilled syringe states 2026-2027 Formula.
• If prefilled syringe has been frozen, discard.
• Do not shake.
• Remove tip cap by slowly turning the cap counterclockwise while holding the Luer lock and attach a sterile needle. Use immediately. If COMIRNATY cannot be used immediately, it must be used within 4 hours.

COMIRNATY Single-Dose Vials for Individuals 5 Years Through 11 Years of Age with at Least One Underlying Condition that Puts Them at High Risk for Severe Outcomes from COVID-19:

• Verify that the label on the vial states 2026-2027 Formula.
• If vial is frozen, thaw vial in the refrigerator [2°C to 8°C (35°F to 46°F) for up to 2 hours] or at room temperature [up to 25°C (77°F) for 30 minutes] [see How Supplied/Storage and Handling (16)].
• Prior to use, mix by inverting vial gently 10 times. Do not shake.
• Withdraw a single 0.3 mL dose using a sterile needle and syringe.
• Discard vial and any excess volume.

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

Administer the 0.3 mL dose intramuscularly immediately after preparation. For the prefilled syringe, administer the entire volume to deliver a single 0.3 mL dose.

COMIRNATY is administered as a single dose for individuals 5 years of age and older.

For individuals previously vaccinated with any COVID-19 vaccine, administer the dose of COMIRNATY at least 2 months after the last dose of COVID-19 vaccine.

COMIRNATY is an injectable suspension.

• For individuals 5 years through 11 years of age: a single dose is 0.3 mL supplied in vials with blue caps and labeled with blue borders.
• For individuals 12 years of age and older: a single dose is 0.3 mL supplied in prefilled syringes labeled with gray borders.

Do not administer COMIRNATY to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of COMIRNATY [see Description (11)] or to individuals who had a severe allergic reaction (e.g., anaphylaxis) following a previous dose of a Pfizer-BioNTech COVID-19 vaccine.

Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of COMIRNATY.

Analyses of postmarketing data from use of authorized or approved mRNA COVID-19 vaccines, including COMIRNATY, have demonstrated increased risks of myocarditis and pericarditis, with onset of symptoms typically in the first week following vaccination. The observed risk has been highest in males 12 years through 24 years of age.

Based on analyses of commercial health insurance claims data from inpatient and outpatient settings, the estimated unadjusted incidence of myocarditis and/or pericarditis during the period 1 through 7 days following administration of the 2023-2024 Formula of mRNA COVID-19 vaccines was approximately 8 cases per million doses in individuals 6 months through 64 years of age and approximately 27 cases per million doses in males 12 through 24 years of age.

Although some individuals with myocarditis and/or pericarditis following administration of mRNA COVID-19 vaccines have required intensive care support, available data suggest that individuals typically have resolution of symptoms within a few days with conservative management.

Follow-up information on cardiovascular outcomes in hospitalized patients who had been diagnosed with COVID-19 vaccine-associated myocarditis is available from a longitudinal retrospective observational study. Most of these patients had received a two-dose primary series of an mRNA COVID-19 vaccine prior to their diagnosis. In this study, at a median follow-up of approximately 5 months postvaccination, persistence of abnormal cardiac magnetic resonance imaging (CMR) findings that are a marker for myocardial injury was common. The clinical and prognostic significance of these CMR findings is not known¹ [see Adverse Reactions (6.2)].

Information is not yet available about potential long-term sequelae of myocarditis or pericarditis following administration of mRNA COVID-19 vaccines.

The Centers for Disease Control and Prevention (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 (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY. Procedures should be in place to avoid injury from fainting.

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to COMIRNATY [see Use in Specific Populations (8.6)].

COMIRNATY may not protect all vaccine recipients.

An overview of clinical studies contributing to the safety assessment of COMIRNATY is provided in Table 1 and Table 2. Participants in these clinical studies received a single dose or a 2-dose series administered 3 weeks apart (referred to as a primary series) and subsequent doses referred to as booster doses.

Participants 12 years of age and older: The most commonly reported adverse reactions (≥10%) after a dose of COMIRNATY were pain at the injection site (up to 90.5%), fatigue (up to 77.5%), headache (up to 75.5%), chills (up to 49.2%), muscle pain (up to 45.5%), joint pain (up to 27.5%), fever (up to 24.3%), injection site swelling (up to 11.8%), and injection site redness (up to 10.4%).

Participants 5 years through 11 years of age: The most commonly reported adverse reactions (≥5%) following any dose were pain at the injection site (up to 83.8%), fatigue (up to 51.9%), headache (up to 38.4%), injection site redness (up to 25.9%), injection site swelling (up to 20.0%), muscle pain (up to 18.1%), chills (up to 13.3%), fever (up to 7.8%), and joint pain (up to 7.6%).

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

Adults and Adolescents 12 Years of Age and Older

Two-Dose Series (Original Monovalent) in Vaccine-Naïve Individuals 16 Years of Age and Older

The safety of a 2-dose primary series of COMIRNATY was evaluated in participants 12 years of age and older in 2 clinical studies conducted in Germany (Study 1), United States, Argentina, Brazil, Turkey, South Africa, and Germany (Study 2). 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 and 36 participants, 56 through 85 years of age. Study 2 was a Phase 1/2/3 multicenter, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study that enrolled approximately 44,000 participants 16 years of age or older (22,026 COMIRNATY; 22,021 placebo).

Study 2 included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. Confirmed stable HIV infection was defined as documented viral load <50 copies/mL and CD4 count >200 cells/mm³ within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 months. HIV-positive participants are included in the safety population but are summarized separately in the safety analyses.

In Study 2, participants 16 years and older in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Tables 3 through 6 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.

At the time of the analysis of Study 2 with a data cutoff of March 13, 2021, there were 25,651 (58.2%) participants (13,031 COMIRNATY; 12,620 placebo) 16 years of age and older followed for ≥4 months after the second dose.

Demographic characteristics in Study 2 were generally similar with regard to age, sex, race, and ethnicity among participants who received COMIRNATY and those who received placebo. Overall, among the total participants who received either COMIRNATY or placebo, 50.9% were male, 49.1% were female, 79.3% were 16 through 64 years of age, 20.7% were 65 years of age and older, 82.0% were White, 9.6% were Black or African American, 25.9% were Hispanic/Latino, 4.3% were Asian, and 1.0% were American Indian or Alaska Native.

Local and Systemic Solicited Adverse Reactions

In participants 16 through 55 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 70 days), for redness 2.2 days (range 1 to 9 days), and for swelling 2.1 days (range 1 to 8 days) for participants in the COMIRNATY group.

In participants 56 years of age and older after receiving Dose 2, the mean duration of pain at the injection site was 2.4 days (range 1 to 36 days), for redness 3.0 days (range 1 to 34 days), and for swelling 2.6 days (range 1 to 34 days) for participants in the COMIRNATY group.

In participants with chronic, stable HIV infection the frequencies of solicited local and systemic adverse reactions were similar to or lower than those observed for all participants 16 years of age and older.

Unsolicited Adverse Events

Overall, 11,253 (51.1%) participants 16 years of age and older in the COMIRNATY group and 11,316 (51.4%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 1,778 (8.1%) and 1,304 (5.9%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.

A total of 12,006 (54.5%) participants originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2.

In an analysis of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in participants 16 years of age and older (N = 43,847; 21,926 COMIRNATY group vs. 21,921 placebo group), those assessed as adverse reactions not already captured by solicited local and systemic reactions were nausea (274 vs. 87), malaise (130 vs. 22), lymphadenopathy (83 vs. 7), asthenia (76 vs. 25), decreased appetite (39 vs. 9), hyperhidrosis (31 vs. 9), lethargy (25 vs. 6), and night sweats (17 vs. 3).

In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants 16 through 55 years of age who received at least 1 dose of study vaccine, 12,995 of whom received COMIRNATY and 13,026 of whom received placebo, unsolicited adverse events were reported by 4,396 (33.8%) participants in the COMIRNATY group and 2,136 (16.4%) participants in the placebo group. In a similar analysis in participants 56 years of age and older that included 8,931 COMIRNATY recipients and 8,895 placebo recipients, unsolicited adverse events were reported by 2,551 (28.6%) participants in the COMIRNATY group and 1,432 (16.1%) participants in the placebo group. Among participants with confirmed stable HIV infection that included 100 COMIRNATY recipients and 100 placebo recipients, unsolicited adverse events were reported by 29 (29%) participants in the COMIRNATY group and 15 (15%) participants in the placebo group. The higher frequency of reported unsolicited adverse events among COMIRNATY recipients compared with placebo recipients was primarily attributed to events that are consistent with adverse reactions solicited among participants in the reactogenicity subset (Table 5 and Table 6).

Throughout the placebo-controlled safety follow-up period, Bell’s palsy (facial paralysis) was reported by 4 participants in the COMIRNATY group and 2 participants in the placebo 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. In the placebo group the onset of facial paralysis was Day 32 and Day 102. Currently available information is insufficient to determine a causal relationship with the vaccine. In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.

Serious Adverse Events

Participants 16 through 55 years of age in Study 2 who had received at least 1 dose of vaccine or placebo (COMIRNATY = 12,995; placebo = 13,026), reported serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up as follows: 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (8,931 COMIRNATY group and 8,895 placebo group), serious adverse events were reported by 165 (1.8%) COMIRNATY recipients and 151 (1.7%) placebo recipients who received at least 1 dose of COMIRNATY or placebo, respectively. In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants with confirmed stable HIV infection serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 2 (2%) COMIRNATY recipients and 2 (2%) placebo recipients.

In the analysis of blinded, placebo-controlled follow-up, there were no notable patterns between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY.

Two-Dose Series (Original Monovalent) in Vaccine-Naïve Adolescents 12 Through 15 Years of Age

Study 2 was a Phase 1/2/3 multicenter, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study. In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. At the time of the analysis of the ongoing Study 2 with a data cutoff of September 2, 2021, there were 1,559 (69.0%) adolescents (786 COMIRNATY and 773 placebo) 12 through 15 years of age followed for ≥4 months after the second dose.

Demographic characteristics in Study 2 were generally similar with regard to age, sex, race, and ethnicity among adolescents who received COMIRNATY and those who received placebo. Overall, among the adolescents who received COMIRNATY, 50.1% were male and 49.9% were female, 85.8% 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.

In Study 2, participants 12 through 15 years of age in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Table 7 and Table 8 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.

Local and Systemic Solicited Adverse Reactions

In adolescents 12 through 15 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 11 days), for redness 1.8 days (range 1 to 5 days), and for swelling 1.6 days (range 1 to 5 days) in the COMIRNATY group.

Unsolicited Adverse Events

In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. Of these, 634 (56.1%) participants in the COMIRNATY group and 629 (55.7%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 152 (13.4%) and 144 (12.8%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.

A total of 1,113 (98.4%) participants 12 through 15 years of age originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2. An analysis of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date was conducted. Among participants 12 through 15 years of age who received at least 1 dose of study vaccine, unsolicited adverse events were reported by 95 (8.4%) participants in the COMIRNATY group and 113 (10.0%) participants in the placebo group.

In an analysis of all unsolicited adverse events reported during blinded follow-up from Dose 1 through 1 month after Dose 2, in adolescents 12 to 15 years of age, those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (9 vs. 2), and nausea (5 vs. 2).

In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of unsolicited adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.

Serious Adverse Events

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

Single Dose (Original Monovalent) in Vaccine-Experienced Individuals 12 Years of Age and Older

16 Years of Age and Older

In Study 4, a double-blind placebo-controlled booster study, 5,081 participants 16 years of age and older recruited from Study 2 received a booster dose of COMIRNATY 10.8 months (median time, range of 5.0 to 12.6 months) after completing the primary series of COMIRNATY series and had a median follow-up time of 2.9 months based on data up to the cutoff date of February 8, 2022. The median age of participants who received COMIRNATY or placebo was 53.0 years (range 16 through 87 years of age), 49.1% were male and 50.9% were female, 79.0% were White, 14.9% were Hispanic/Latino, 9.2% were Black or African American, 5.5% were Asian, and 1.7% were American Indian/Alaska Native.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 141 (2.8%) participants who received a booster dose of COMIRNATY and in 83 (0.4%) participants who received COMIRNATY as a primary series.

18 Years Through 55 Years of Age

A subset of 306 Study 2 Phase 2/3 participants 18 through 55 years of age received a booster dose of COMIRNATY 6.8 months (median time, range 4.8 to 8.0 months) after completing the primary series. These participants had a median follow-up time of 8.3 months up to a data cutoff date of November 22, 2021. Among the 306 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.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 16 (5.2%) of participants who received a booster dose of COMIRNATY and 83 (0.4%) in participants who received COMIRNATY as a primary series.

12 Years Through 17 Years of Age

A subset of 65 Study 4 participants 12 through 17 years of age received a booster dose of COMIRNATY 13.3 months (median time, range 6.5 to 16.9 months) after completing the primary series and had a median follow-up time of 5.6 months up to a data cutoff date of July 14, 2022. The median age of participants was 14 years (range 12 through 17 years of age), 49.2% were male and 50.8% were female, 76.9% were White, 16.9% were Hispanic/Latino, 13.8% were Black or African American, 7.7% were Asian, and 1.5% were American Indian/Alaska Native.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. There were no cases of lymphadenopathy reported in participants who received a booster dose of COMIRNATY.

12 Years Through 15 Years of Age

A subset of 825 Study 2 Phase 2/3 participants 12 through 15 years of age received a booster dose of COMIRNATY 11.2 months (median time, range 6.3 to 20.1 months) after completing the primary series and had a median follow-up time of 9.5 months up to a data cutoff date of November 3, 2022. The median age of participants was 14.0 years (range 13 through 15 years of age), 49.3% were male and 50.7% were female, 83.5% were White, 10.8% were Hispanic/Latino, 4.6% were Black or African American, 7.5% were Asian, and 0.4% were American Indian/Alaska Native.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 8 (1.0%) participants who received a booster dose of COMIRNATY and in 9 (0.8%) participants who received COMIRNATY as a primary series.

Single Dose (Bivalent Original and BA.4/BA.5) in Vaccine-Experienced Individuals 12 Years of Age and Older

A subset of 107 Study 5 Phase 2/3 participants 12 through 17 years of age, 313 participants 18 through 55 years of age and 306 participants 56 years of age and older previously vaccinated with a 2-dose primary series and 1 booster dose of COMIRNATY, went on to receive a second booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

Participants received a second booster dose 11.1 months (median time; range 5.4 to 16.9 months) after receiving the first booster dose and had a median follow-up time of 1.5 months up to a data cutoff date of October 31, 2022. The median age was 48.0 years, 42.7% were male, 57.3% were female, 80.6% were White, 11.4% were Hispanic/Latino, 5.9% were Asian, and 11.4% were Black or African American.

Local and Systemic Solicited Adverse Reactions

Table 9 and Table 10 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, Bivalent.

In participants 12 years of age and older who received a second booster dose, the mean duration of injection site pain was 2.1 to 2.4 days (range 1 to 11 days), injection site redness was 1.5 to 2.5 days (range 1 to 4 days), and injection site swelling was 1.3 to 1.9 days (range 1 to 4 days), respectively.

Unsolicited Adverse Events

Among participants 12 years of age and older, unsolicited adverse events were reported by 48 (6.6%) participants who received a second booster dose through 1 month after the booster dose. Lymphadenopathy occurred in 7 (1.0%) participants.

Concomitant Administration of COMIRNATY (Original Monovalent) With Influenza Vaccine in Adults 18 Years Through 64 Years of Age

In Study 8, a Phase 3 study, participants 18 through 64 years of age who received COMIRNATY concomitantly administered with Influenza Vaccine (Afluria Quadrivalent) followed 1 month later by saline placebo (n = 564) were compared with participants who received influenza vaccine with saline placebo followed 1 month later by COMIRNATY (n = 564).

Demographic characteristics in Study 8 among the participants in the concomitant administration and separate administration groups were similar with regard to age, sex, race, and ethnicity. Among the 564 participants in the concomitant administration group, the median age was 39.0 years (range 18 through 64 years of age), 36.9% were male and 63.1% were female, 79.1% were White, 12.9% were Asian, and 0.9% were Hispanic/Latino.

Solicited local and systemic adverse reactions were reported more frequently by participants who received COMIRNATY concomitantly with influenza vaccine, compared with participants who received COMIRNATY alone. The most common adverse reactions reported in the concomitant administration group and after COMIRNATY alone were injection site pain (COMIRNATY injection site) (86.2% and 84.4%, respectively), fatigue (64.0% and 50.8%, respectively), and headache (47.2% and 37.8%, respectively).

Children 5 Years Through 11 Years of Age

Two-Dose Series (Original Monovalent) in Vaccine-Naïve Children 5 Years Through 11 Years of Age

Study 3 is a Phase 1/2/3 multicenter, randomized, dose-finding, open label (Phase 1) and multinational, placebo controlled (saline placebo), observer-blind, immunogenicity and efficacy (Phase 2/3) study that has evaluated 4,695 participants 5 through 11 years of age, of whom 3,109 participants received COMIRNATY and 1,538 participants received placebo in Phase 2/3.

Demographic characteristics were generally similar with regard to age, sex, race, and ethnicity among participants who received COMIRNATY and those who received placebo. Overall, among the 4,647 participants who received at least 1 dose of COMIRNATY or placebo, 51.4% were male and 48.6% were female, 77.5% were White, 6.0% were Black or African American, 17.0% were Hispanic/Latino, 8.1% were Asian, and 0.4% were American Indian/Alaska Native.

In an analysis of Study 3 (Phase 2/3), 4,632 participants 5 through 11 years of age who received a 2-dose primary series [3,100 COMIRNATY; 1,532 placebo] have been followed a median of 1.9 months (range 0.1 to 7.5 months) after the second dose in the blinded placebo-controlled follow-up period up to the cutoff date of May 20, 2022.

In Study 3, participants 5 years through 11 years of age in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic adverse reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Table 11 and Table 12 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.

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 37 days), for redness 2.0 days (range 1 to 10 days), and for swelling 2.2 days (range 1 to 16 days) for children in the COMIRNATY group in the blinded placebo-controlled follow-up period up to the cutoff date of May 20, 2022.

Unsolicited Adverse Events

In the following analyses of Study 3 in participants 5 through 11 years of age, 3,109 participants received COMIRNATY and 1,538 participants received placebo. Among those who received 2 doses of COMIRNATY or placebo, 1,185 participants in the COMIRNATY group and 575 participants in the placebo group had follow-up time ≥4 to <6 months and 296 participants in the COMIRNATY group and 150 participants in the placebo group had follow-up time of >6 months in the blinded placebo-controlled follow-up period.

Among participants who received at least 1 dose of study vaccine, unsolicited adverse events were reported by 333 (10.7%) participants in the COMIRNATY group and 150 (9.8%) participants in the placebo group.

In an analysis of all unsolicited adverse events reported following administration of Dose 1 to one month after administration of Dose 2, the adverse reactions (excluding reactions reported as solicited adverse reactions) in participants who received COMIRNATY compared with participants who received placebo were lymphadenopathy (n=23; 0.7% vs. n=4; 0.3%), nausea (n=7; 0.2% vs. n=3; 0.2%), decreased appetite (n=3; 0.1% vs. n=2; 0.1%), malaise (n=2; 0.1% vs. n=0), and night sweats (n=1; 0.0% vs. n=0).

Serious Adverse Events

Serious adverse events, from administration of Dose 1 to the participant unblinding date, were reported in 8 (0.3%) COMIRNATY recipients and in 2 (0.1%) placebo recipients. No serious adverse events were considered related to vaccination.

Single Dose (Original Monovalent) in Vaccine-Experienced Children 5 Years Through 11 Years of Age

In Phase 2/3 of Study 3, 2,408 participants 5 years through 11 years of age received a first booster dose of COMIRNATY at a median of 7.9 months (range 5.3 to 19.4 months) after completing the primary series. These participants had a median safety follow-up of 6.4 months from vaccination through the data cutoff date of February 28, 2023. The median age was 8.0 years (range 5 through 11 years of age), 50.5% were male and 49.5% were female, 76.3% were White, 5.9% were Black or African American, 16.9% were Hispanic/Latino, 8.2% were Asian, and 0.5% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

The frequency of solicited adverse reactions reported in participants receiving a booster dose of COMIRNATY were generally consistent with those reported in pediatric participants receiving COMIRNATY as part of the two-dose series.

Unsolicited Adverse Events

Lymphadenopathy occurred in 46 (1.9%) participants who received a booster dose of COMIRNATY and in 23 (0.7%) participants who received COMIRNATY as a primary series.

Serious Adverse Events

Serious adverse events from study vaccination through 6 months after study vaccination were reported by 10 (0.4%) COMIRNATY recipients. No serious adverse events were considered related to vaccination.

Single Dose (Bivalent Original and BA.4/BA.5) in Vaccine-Experienced Children 5 Years Through 11 Years of Age

In Study 6, 113 participants 5 years through 11 years of age previously vaccinated with a 2-dose primary series and 1 booster dose of COMIRNATY received a second booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5). Participants received a second booster with Pfizer-BioNTech COVID-19, Bivalent 2.6 to 8.5 months after receiving their third dose with COMIRNATY and had a median follow-up time of 6.3 months (range 1.1 to 6.8 months) up to a data cutoff date of April 20, 2023. The median age of participants 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 multiracial, 11.5% were Asian, and 8.0% were Black or African American.

Solicited Local and Systemic Adverse Reactions

The frequency of solicited adverse reactions reported in participants receiving a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and BA.4/BA.5) were generally consistent with those reported in pediatric participants receiving COMIRNATY.

Unsolicited Adverse Events

Lymphadenopathy was reported in 1 (0.9%) participant who received Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and BA.4/BA.5).

Serious Adverse Events

No serious adverse events were reported.

Single Dose (Monovalent XBB.1.5) in Vaccine-Naïve Children 5 Years Through 11 Years of Age

In a subset of Study 6, the safety of a single dose of COMIRNATY (encoding the viral spike (S) glycoprotein of SARS-CoV-2 Omicron XBB.1.5) was evaluated in 310 COVID-19 vaccine-naïve participants 5 through 11 years of age. Participants had a median follow-up time of 6.4 months (range 1.7 to 6.9 months). The median age of participants was 7.0 years (range 5 through 11 years of age), 47.1% were male and 52.9% were female, 41.3% were White, 52.9% were Black or African American, 52.3% were Hispanic or Latino, 1.9% were Asian, and 0.3% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

The frequency of solicited adverse reactions reported in participants who received a single dose of COMIRNATY, monovalent (XBB.1.5) were generally consistent with those previously reported by participants receiving COMIRNATY.

Unsolicited Adverse Events

In an analysis of all unsolicited adverse events through 1 month after study vaccination, unsolicited adverse events were reported by 11 (3.5%) COMIRNATY recipients. The adverse reaction not already captured by solicited local and systemic reactions was decreased appetite (n=1; 0.3%).

Serious Adverse Events

Serious adverse events from study vaccination through 6 months after study vaccination were reported by 3 (1.0%) COMIRNATY recipients. No serious adverse events were considered related to vaccination.

Efficacy Against COVID-19

The population for the analysis of the protocol pre-specified primary efficacy endpoint included 36,621 participants 12 years of age and older (18,242 in the COMIRNATY 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. The population in the protocol pre-specified 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.

For participants without evidence of SARS-CoV-2 infection prior to 7 days after Dose 2, vaccine efficacy against confirmed COVID-19 occurring at least 7 days after Dose 2 was 95.0% (95% credible interval: 90.3, 97.6), which met the pre-specified success criterion. The case split was 8 COVID-19 cases in the COMIRNATY group compared to 162 COVID-19 cases in the placebo group.

The population for the updated vaccine efficacy analysis included participants 16 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 during blinded placebo-controlled follow-up through March 13, 2021, representing up to 6 months of follow-up after Dose 2. There were 12,796 (60.8%) participants in the COMIRNATY group and 12,449 (58.7%) in the placebo group followed for ≥4 months after Dose 2 in the blinded placebo-controlled follow-up period.

SARS-CoV-2 variants of concern identified from COVID-19 cases for this age group from this data cutoff include B.1.1.7 (Alpha) and B.1.351 (Beta). Representation of identified variants among cases in vaccine versus placebo recipients did not suggest decreased vaccine effectiveness against these variants.

The updated vaccine efficacy information is presented in Table 14.

Subgroup analyses of vaccine efficacy (although limited by small numbers of cases in some subgroups) did not suggest meaningful differences in efficacy across sex, ethnic groups, geographies, or for participants with obesity or medical comorbidities associated with high risk of severe COVID-19.

Efficacy Against Severe COVID-19

Efficacy analyses of secondary efficacy endpoints supported the benefit of COMIRNATY in preventing severe COVID-19. Vaccine efficacy against severe COVID-19 is presented only for participants with or without prior SARS-CoV-2 infection (Table 15) as the COVID-19 case counts in participants without prior SARS-CoV-2 infection were the same as those in participants with or without prior SARS-CoV-2 infection in both the COMIRNATY and placebo groups.

Efficacy and Immunogenicity of Two-Dose Series (Original Monovalent) in Vaccine-Naïve Adolescents 12 Through 15 Years of Age

A descriptive efficacy analysis of Study 2 has been performed in 2,260 adolescents 12 through 15 years of age evaluating confirmed COVID-19 cases accrued up to a data cutoff date of September 2, 2021.

The vaccine efficacy information in adolescents 12 through 15 years of age is presented in Table 16.

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 noninferior 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 17).

Immunogenicity of Single Dose (Original Monovalent) in Vaccine-Experienced Adults 18 Years Through 55 Years of Age

Effectiveness of a booster dose of COMIRNATY was based on an assessment of 50% neutralizing antibody titers (NT50) against SARS-CoV-2 reference strain (USA_WA1/2020) in Study 2 participants 18 through 55 years of age (n = 200 – 212) who had no serological or virological evidence of past SARS‑CoV‑2 infection up to 1 month after the booster vaccination. Analyses of NT50 1 month after the booster dose compared with 1 month after the primary series demonstrated noninferiority for both geometric mean ratio (GMR) [3.26 (97.5% CI: 2.76, 3.86)] and difference in seroresponse rates (percentage) [4.5% (97.5% CI: 1.0, 7.9)]. Seroresponse for a participant was defined as achieving a ≥4-fold rise in NT50 from baseline (before primary series).

Immunogenicity of a Single Dose (Bivalent Original and BA.4/BA.5) in Vaccine-Experienced Individuals 12 Years of Age and Older

In an analysis of a subset from Study 5, 105 participants 12 through 17 years of age, 297 participants 18 through 55 years of age, and 286 participants 56 years of age and older who had previously received a 2-dose primary series and 1 booster dose with COMIRNATY received a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent. In participants 12 through 17 years of age, 18 through 55 years of age, and 56 years of age and older, 75.2%, 71.7% and 61.5% were positive for SARS-CoV-2 at baseline, respectively.

Analyses of NT50 against Omicron BA.4/BA.5 and against reference strain among participants 56 years of age and older who received a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent in Study 5 compared with a subset of participants from Study 4 who received a second booster dose of COMIRNATY demonstrated superiority of Pfizer-BioNTech COVID-19 Vaccine, Bivalent to COMIRNATY based on GMR and noninferiority based on difference in seroresponse rates with respect to anti-Omicron BA.4/BA.5 response, and noninferiority of anti-reference strain immune response based on GMR (Table 18 and Table 19).

Analyses of NT50 against Omicron BA.4/BA.5 among participants 18 through 55 years of age compared with participants 56 years of age and older who received a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent in Study 5 demonstrated noninferiority of anti-Omicron BA.4/BA.5 response among participants 18 through 55 years of age to participants 56 years of age and older for both GMR and difference in seroresponse rates (Table 18 and Table 19).

The study also assessed the level of NT50 against the anti-Omicron BA.4/BA.5 and original SARS-CoV-2 strains pre-vaccination and 1 month after vaccination in participants who received a second booster dose (Table 20).

Immunogenicity of a Single Dose (Bivalent Alpha and Delta) in Seropositive, Vaccine-Naïve Adults 18 Years of Age and Older

In a post-hoc analysis in a subset of participants 18 through 85 years of age enrolled in Study 7 (NCT05004181), immunogenicity of a single dose of a Pfizer-BioNTech bivalent COVID-19 vaccine containing equal quantities of modRNA (30 mcg total) encoding the viral spike (S) glycoprotein for the Alpha and Delta SARS-CoV-2 variants [not authorized or approved in the U.S., hereafter referred to as bivalent vaccine (Alpha and Delta)] was assessed in COVID-19 vaccine-naïve participants with evidence of prior SARS-CoV-2 infection (n = 262) compared with participants without prior SARS-CoV-2 infection who received 2 doses of COMIRNATY in Study 2 (n = 275). Among Study 7 participants, 253 were from study sites in South Africa and 9 were from study sites in the U.S. The immunogenicity of the bivalent Alpha and Delta vaccine is relevant to COMIRNATY because these vaccines are manufactured using the same process with differences only in the encoded spike proteins.

Table 21 presents demographic characteristics for participants in the immunogenicity analysis set.

The objective of this analysis was to assess noninferiority with respect to level of 50% neutralizing titer (NT50) and to the seroresponse rate to the reference strain induced by a single dose of the bivalent Alpha and Delta vaccine in COVID-19 vaccine-naïve participants with evidence of prior infection relative to participants without evidence of SARS-CoV-2 infection who received 2 doses of COMIRNATY.

Noninferiority of the reference strain immune response with respect to level of NT50 was met, as the lower bound of the 2-sided 95% CI for the geometric mean ratio (GMR) was >0.67 (Table 22). Noninferiority of the seroresponse rate to the reference strain was not met, as the lower bound of the 2-sided 95% CIs for the difference in seroresponse rate of reference strain was -10.04%, below the noninferiority margin of -10% (Table 23).

Concomitant Administration of COMIRNATY (Original Monovalent) With Influenza Vaccine in Adults 18 Years Through 64 Years of Age

In Study 8, a Phase 3 multicenter, randomized, observer-blind study, 1,134 participants 18 through 64 years of age who had received 3 doses of COMIRNATY at least 3 months prior were randomized in a 1:1 ratio to receive either COMIRNATY concomitantly administered with Influenza Vaccine (Afluria Quadrivalent) followed 1 month later by placebo (Group 1, n = 568) or influenza vaccine with placebo followed 1 month later with COMIRNATY (Group 2, n = 566).

Full-length spike (S)-binding IgG responses to COMIRNATY and influenza strain-specific hemagglutination inhibition (HAI) titers were assessed 1-month postvaccination in each group.

The non-inferiority criteria (lower bound of the 2-sided 95% CI >0.67) for the comparison of concomitant administration versus separate administration were met. The GMC ratio of full-length S-binding IgG levels of SARS-CoV-2 Wuhan-Hu-1 strain (Original) (Group 1/Group 2) was 0.83 [95% CI: 0.77, 0.89]. The GMT ratio (Group 1/Group 2) for the 4 strain-specific influenza HAI titers were H1N1 A/Victoria: 0.95 [95% CI: 0.83, 1.09]; H3N2 A/Darwin: 0.96 [95% CI: 0.85, 1.09]; B/Austria: 0.89 [95% CI: 0.77, 1.04]; B/Phuket: 1.00 [95% CI: 0.89, 1.13].

SARS-CoV-2 Wuhan-Hu-1 strain (Original) neutralizing GMTs were descriptively assessed in a subset of participants, 100 participants from Group 1 and 100 participants from Group 2.

The SARS-CoV-2 neutralization assay (NT50 titer) GMTs increased from baseline to 1 month after vaccination with COMIRNATY from 2,755.9 to 6,773.9 in Group 1 and from 2,421.2 to 7,886.6 in Group 2.

Logo (Comirnaty 01)

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

Logo (Comirnaty 02)

Manufactured by
Pfizer Inc., New York, NY 10001

LAB-1490-17.0

US Govt. License No. 2229

The following adverse reactions have been identified during postmarketing use of COMIRNATY, Pfizer-BioNTech COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, Bivalent. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to 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, febrile seizures (in children 5 through 11 years of age)

Cardiovascular Outcomes in Patients Diagnosed With mRNA COVID-19 Vaccine-associated Myocarditis

In a longitudinal retrospective observational cohort study across 38 hospitals in the U.S., information on cardiovascular outcomes was collected on 333 patients 5 through 29 years of age who had been diagnosed with COVID-19 vaccine-associated myocarditis. Among these patients, 322 were confirmed to have received an mRNA COVID-19 vaccine encoding the S glycoprotein of the Original SARS-CoV-2. Of 331 patients, 278 had onset of symptoms following the second dose of a primary series, 33 following the first dose of a primary series, and 20 following a first booster dose¹.

Among 307 patients who had been diagnosed with COVID-19 vaccine-associated myocarditis for whom follow-up information was available, 89 reported cardiac symptoms at a median follow-up of 91 days (interquartile range 25-186 days) postvaccination¹.

Initial gadolinium-enhanced cardiac magnetic resonance imaging (CMR) was performed on 216 patients, of whom 177 had late gadolinium enhancement (LGE), a marker of myocardial injury. Among 161 patients who had LGE on initial CMR and who had a follow-up gadolinium-enhanced CMR at a median follow-up of 159 days (interquartile range 78-253 days), 98 had persistence of LGE. Overall, the severity of LGE decreased during follow-up. The clinical and prognostic significance of these CMR findings is not known¹.

Limitations of this study include potential selection bias towards patients with more severe myocarditis who are more likely to be hospitalized and have CMR, variability in diagnostic testing, and variability in follow-up¹.

Risk Summary

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, miscarriage and pre-eclampsia in clinically recognized pregnancies is 2% to 4%, 15% to 20%, and 5% to 7%, respectively. There are no available data with COMIRNATY use in pregnant women before 24 weeks gestation to inform about risks for major birth defects and miscarriage.

A developmental toxicity study has been performed in female rats administered the equivalent of a single human dose of COMIRNATY [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)] on 4 occasions, twice prior to mating and twice during gestation. These studies revealed no evidence of harm to the fetus due to the vaccine (see Data).

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnant individuals infected with SARS-CoV-2 are at increased risk of severe COVID-19 compared with non-pregnant individuals.

Data

Human Data

In Study 9, a randomized, placebo-controlled trial (NCT04754594), COVID-19 vaccine naïve, pregnant women 18 years of age and older received 2 doses of COMIRNATY (Original Monovalent) (n=173 received at least 1 dose) or placebo (n=173 received at least 1 dose), approximately 21 days apart, with the first dose administered at 24 to 34 weeks gestation (i.e., late second trimester and early third trimester of pregnancy). The trial was conducted in Brazil, South Africa, Spain, United Kingdom, and the US. The trial failed to reach target accrual (originally designed to be 4,000 participants), as it was terminated prematurely, resulting in uncertainty regarding differences in outcomes.

In an analysis which excluded participants with HIV infection, a numerical imbalance in pre-eclampsia in COMIRNATY recipients (6 of 161, 3.7%) compared with placebo recipients (2 of 163, 1.2%) was observed in this study. These data are insufficient to establish or exclude a causal relationship between COMIRNATY and pre-eclampsia.

Major or minor congenital anomalies or chromosomal abnormalities were reported in 10 of 156 (6.4%) infants born to women in the COMIRNATY group and 7 of 159 (4.4%) infants born to women in the placebo group (see Table 13). Some infants had more than one event listed in the table. The available trial data are insufficient to establish or exclude vaccine-associated risk of congenital anomalies because COMIRNATY was not administered in the first trimester (the period when the risk of major congenital anomalies is highest). In addition, predisposing factors including genetic risk factors and potential maternal risk factors were reported in some cases in the COMIRNATY group.

Descriptive immunogenicity analyses of geometric mean [neutralizing] titers (GMT) in pregnant participants compared with GMTs from non-pregnant participants enrolled in another study (Study 2) were inconclusive due to study limitations including a small sample size.

Animal Data

In a developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (30 mcg of modRNA) and other ingredients included in a single human dose of COMIRNATY [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)] 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.

Risk Summary

It is not known whether COMIRNATY is excreted in human milk. Data are not available to assess the effects of COMIRNATY on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for COMIRNATY and any potential adverse effects on the breastfed child from COMIRNATY or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

Safety and effectiveness of COMIRNATY in individuals 5 years through 17 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19 is based on safety and effectiveness data in this age group and in adults [see Adverse Reactions (6) and Clinical Studies (14)].

The safety and effectiveness of COMIRNATY in individuals younger than 5 years of age have not been established. Evidence from clinical studies in individuals 6 months through 4 years of age strongly suggests that a single dose of COMIRNATY would be ineffective in individuals younger than 6 months of age.

Of the total number of COMIRNATY recipients in Study 2 as of March 13, 2021 (N = 22,026), 20.7% (n = 4,552) were 65 years of age and older and 4.2% (n = 925) were 75 years of age and older [see Clinical Studies (14.1)]. In Study 4, of 5,081 recipients who received COMIRNATY as the first booster dose, 23.1% (n = 1,175) were 65 years of age and older and 5.2% (n = 265) were 75 years of age and older. In Study 5, of 726 recipients who received Pfizer-BioNTech COVID-19 Vaccine, Bivalent as the second booster dose, 21.9% (n = 159) were 65 years of age and older and 4.8% (n = 35) were 75 years of age and older [see Clinical Studies (14.1)]. No overall differences in safety or effectiveness were observed between these recipients and younger recipients.

In an open-label descriptive study (NCT04895982, Study 10), 87 immunocompromised participants 5 years of age and older received up to 4 age-appropriate doses of COMIRNATY (Original Monovalent) in a 4-dose regimen (an unapproved dosing regimen), with the first 2 doses separated by approximately 21 days, a third dose approximately 28 days after Dose 2, and a fourth dose administered approximately 3 to 6 months after Dose 3. The study evaluated safety and immunogenicity in participants 5 years through 11 years of age (n=65), 12 years through 17 years (n=15), and 18 years of age and older (n=7) with the following immunocompromising conditions: autoimmune inflammatory disorders on immunomodulatory therapy (n=31), solid organ transplant (n=25), stem cell transplant (n=29), non-small cell lung cancer (n=1), or hemodialysis (n=1). Study completion rates were 83.1% (54/65), 53.3% (8/15), and 57.1% (4/7) for the respective age groups. The trial was stopped early due to challenges with study enrollment.

Overall, 58.6% were male, 82.8% were White, 20.7% were Hispanic/Latino, 6.9% were Black or African American, 2.3% were Asian, 1.1% were American Indian or Alaska Native, 2.3% were Multiracial, and race and ethnicity was not reported by 4.6% of participants. The median age of participants in age groups 5 years through 11 years, 12 through 17 years, and 18 years of age and older was 9.0, 12.0, and 40.0 years, respectively.

The safety profile in immunocompromised participants 5 years of age and older who received COMIRNATY (Original Monovalent) was similar to that in immunocompetent participants in other clinical studies [see Adverse Reactions (6.1)]. There were no deaths in the study and no serious adverse events were assessed as related to vaccination.

Seroresponse rates (defined as achieving a ≥4-fold rise in neutralizing titers from baseline) were evaluated in all participants with at least one valid immunogenicity result after vaccination, regardless of prior SARS-CoV-2 infection status.

Among participants 5 years through 11 years of age: At 1 month after Dose 3, seroresponse rate was 81.7% [95% confidence interval (CI): 69.6%, 90.5%] (n=60). At 1 month after Dose 4, seroresponse rate was 96.0% (95% CI: 86.3%, 99.5%) (n=50). At 6 months after Dose 4, seroresponse rate was 87.8% (95% CI: 75.2%, 95.4%) (n=49).

Among participants 12 years through 17 years of age: At 1 month after Dose 3, seroresponse rate was 92.9% (95% CI: 66.1%, 99.8%) (n=14). At 1 month after Dose 4, seroresponse rate was 100.0% (95% CI: 66.4%, 100.0%) (n=9). At 6 months after Dose 4, seroresponse rate was 100.0% (95% CI: 63.1%, 100.0%) (n=8).

Among participants 18 years of age and older: At 1 month after Dose 3, seroresponse rate was 50.0% (95% CI: 11.8%, 88.2%) (n=6). At 1 month after Dose 4, seroresponse rate was 75.0% (95% CI: 19.4%, 99.4%) (n=4). At 6 months after Dose 4, seroresponse rate was 33.3% (95% CI: 0.8%, 90.6%) (n=3).

The limitations of the study data include small sample sizes, particularly in the 12 through 17 years and ≥18 years age groups, and early study termination due to enrollment challenges. The data from this study do not establish the effectiveness of COMIRNATY in immunocompromised individuals.

The Centers for Disease Control and Prevention has published considerations related to COVID-19 vaccination guidance for people who are immunocompromised.

COMIRNATY (COVID-19 Vaccine, mRNA) is a sterile injectable suspension for intramuscular use.

Single-Dose Prefilled Syringe for Individuals 65 Years of Age and Older and Individuals 12 Years Through 64 Years of Age with at Least One Underlying Condition that Puts Them at High Risk for Severe Outcomes from COVID-19:

Each 0.3 mL dose of COMIRNATY (2026-2027 Formula) is formulated to contain 30 mcg nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2 JN.1-descendent variant XFG.

Each 0.3 mL dose of COMIRNATY 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.

Single-Dose Vial for Individuals 5 Years Through 11 Years of Age with at Least One Underlying Condition that Puts Them at High Risk for Severe Outcomes from COVID-19:

Each 0.3 mL dose of COMIRNATY (2026-2027 Formula) is formulated to contain 10 mcg nucleoside-modified RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2 JN.1-descendent variant XFG.

Each 0.3 mL dose of COMIRNATY also includes the following ingredients: lipids (0.14 mg ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.02 mg 2-(polyethylene glycol 2000)-N,N-ditetradecylacetamide, 0.03 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.06 mg cholesterol), 0.06 mg tromethamine, 0.4 mg tromethamine hydrochloride, and 31 mg sucrose.

COMIRNATY does not contain preservatives.

The vial stoppers are not made with natural rubber latex.

The prefilled syringe tip cap and plunger stopper are not made with natural rubber latex.

The nucleoside-modified mRNA in COMIRNATY is formulated in lipid particles, which enable delivery of the mRNA 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.

COMIRNATY has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility. In a developmental toxicity study in rats with COMIRNATY [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)] there were no vaccine-related effects on female fertility [see Use in Specific Populations (8.1)].

Efficacy of Two-Dose Series (Original Monovalent) in Vaccine-Naïve Individuals 16 Years of Age and Older

Study 2 is an ongoing, multicenter, multinational, 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 HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).

In Study 2, based on data accrued through March 13, 2021, approximately 44,000 participants 12 years of age and older were randomized equally and received 2 doses of COMIRNATY or placebo. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.

Overall, among the total participants who received COMIRNATY or placebo, 51.4% and 50.3% were male and 48.6% and 49.7% were female, 79.1% and 79.2% were 16 through 64 years of age, 20.9% and 20.8% were 65 years of age and older, 81.9% and 82.1% were White, 9.5% and 9.6% were Black or African American, 1.0% and 0.9% were American Indian or Alaska Native, 4.4% and 4.3% were Asian, 0.3% and 0.2% Native Hawaiian or other Pacific Islander, 25.6% and 25.4% were Hispanic/Latino, 73.9% and 74.1% were non-Hispanic/Latino, 0.5% and 0.5% did not report ethnicity, 46.0% and 45.7% had comorbidities [participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease: defined as subjects who had at least 1 of the Charlson comorbidity index category or body mass index (BMI) ≥30 kg/m²], respectively. The mean age at vaccination was 49.8 and 49.7 years and median age was 51.0 and 51.0 in participants who received COMIRNATY or placebo, respectively.

Efficacy and Immunogenicity of Two-Dose Series (Original Monovalent) in Vaccine-Naïve Children 5 Years Through 11 Years of Age

An efficacy analysis of Study 3 has been performed in 4,051 participants 5 years through 11 years of age without evidence of infection prior to 7 days after Dose 2. This analysis evaluated confirmed symptomatic COVID-19 cases in the placebo-controlled blinded follow-up period accrued up to a data cutoff date of 20 May 2022.

In Study 3, participants 5 years through 11 years of age were enrolled in the United States, Spain, Finland, and Poland. Among participants 5 years through 11 years of age without evidence of prior infection with SARS-CoV-2 through 7 days after Dose 2, who received COMIRNATY (n=2,703) or placebo (n=1,348) in the evaluable efficacy population, 51.2% and 51.0% were male, 48.8% and 49.0% were female, 76.3% and 77.2% were White, 5.5% and 6.0% were Black or African American, 0.5% and 0.3% were American Indian or Alaska Native, 8.9% and 8.5% were Asian, 0.3% and 0% were Native Hawaiian or other Pacific Islander, 8.5% and 7.9% were multiracial or not reported, 15.1% and 15.7% were Hispanic/Latino, 84.8% and 84.3% were non-Hispanic/Latino, and 0.1% and 0% did not report ethnicity, respectively. In the evaluable efficacy population, 25.7% and 25.9% of participants had 1 or more comorbidities that increase the risk of severe COVID-19 disease: defined as participants who had at least 1 of the pre-specified comorbidities based on MMWR 69(32);1081-1088 and/or obesity (BMI ≥95^th percentile), respectively. The median age of participants at vaccination was 8.0 years with a range of 5 through 11 years of age in both the COMIRNATY and placebo groups.

The overall vaccine efficacy results and subgroup analysis in participants 5 years through 11 years of age without evidence of prior SARS-CoV-2 infection are presented in Table 24. None of the cases met criteria for severe COVID-19 or multisystem inflammatory syndrome in children (MIS-C).

SARS-CoV-2 50% neutralizing antibody titers (NT50) 1 month after the two-dose series were compared between randomly selected subsets of participants 5 years through 11 years of age from Study 3 (Phase 2/3) and participants 16 years through 25 years of age from efficacy Study 2 (Phase 2/3), using a microneutralization assay against the reference strain (USA_WA1/2020). The primary immunobridging analyses compared the geometric mean titers (using a geometric mean ratio [GMR]) and the seroresponse (defined as achieving at least 4-fold rise in SARS-CoV-2 NT50 from before Dose 1) rate percentages in the evaluable immunogenicity population of participants without evidence of prior SARS-CoV-2 infection up to 1 month after Dose 2 in each group. The pre-specified noninferiority criteria were met for both the GMR and the seroresponse difference (Table 25 and Table 26).

Immunogenicity of a Single Dose (Original Monovalent) in Vaccine-Experienced Children 5 Years Through 11 Years of Age

In Study 3, immunogenicity of a first booster dose of COMIRNATY administered after the second dose of the two-dose series with COMIRNATY was evaluated in 67 study participants 5 through 11 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to 1 month after the booster dose. Using a microneutralization assay against the reference strain of SARS-CoV-2 (USA_WA1/2020), the NT50 GMT at 1 month after the booster dose (2,720.9 [95% CI: 2,280.1, 3,247.0]) was increased compared with before the booster dose (271.0 [95% CI: 229.1, 320.6]).

Immunogenicity of a Single Dose (Monovalent XBB.1.5) in Vaccine-Naïve Children 5 Years Through 11 Years of Age

In an analysis of a subset of Study 6, immunogenicity of a single dose of COMIRNATY (encoding the viral spike (S) glycoprotein of SARS-CoV-2 Omicron XBB.1.5) in COVID-19 vaccine-naïve participants 5 through 11 years of age (n=285) was compared with participants 12 years of age and older who had received at least 3 prior U.S.-authorized mRNA COVID-19 vaccine doses and then received a single dose of COMIRNATY (encoding the viral spike (S) glycoprotein of SARS-CoV-2 Omicron XBB.1.5, 30 mcg of modRNA) in a subset of study C4591054 (Study 13; NCT 05997290) (n=302). Study 13 evaluated safety and immunogenicity of a single dose of COMIRNATY administered to COVID-19 vaccine-experienced participants 12 years of age and older. In Study 6 and Study 13, 98.9% and 99.3% of participants had evidence of prior SARS-CoV-2 infection at baseline, respectively.

Study 6 was conducted in Brazil, Puerto Rico, South Africa and United States. Among the COVID-19 vaccine−naïve participants 5 through 11 years of age in Study 6 (n=285) and COVID-19 vaccine-experienced participants 12 years of age and older in Study 13 (n=302) who received a single dose of COMIRNATY in the evaluable immunogenicity population, 46.3% and 41.7% were male, 53.7% and 58.3% were female, 41.1% and 79.1% were White, 53.0% and 12.9% were Black or African American, 0.4% and 0% were American Indian or Alaska Native, 2.1% and 5.0% were Asian, 0% and 0.3% were Native Hawaiian or other Pacific Islander, 3.5% and 2.6% were multiracial, not reported, or unknown, 53.3% and 19.2% were Hispanic/Latino, and 46.7% and 80.1% were non-Hispanic/Latino, respectively. At study vaccination, the median age of participants in Study 6 was 7.0 years (range 5 through 11 years of age) and the median age of participants in Study 13 was 53.5 years (range 12 through 82 years).

The primary immunobridging analyses compared the geometric mean titers (using a geometric mean ratio [GMR]) and the seroresponse (defined as achieving at least 4-fold rise from baseline) rates in the COVID-19 vaccine-naïve participants 5 through 11 years of age to COVID-19 vaccine-experienced participants 12 years of age and older. The noninferiority criteria were met for both the GMR and the seroresponse rate percentages (Table 27 and Table 28).

• 1.Jain SS, Anderson SA, Steele JM, et al. Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study. Lancet. 2024;76:1-13. https://doi.org/10.1016/j.eclinm.2024.102809

COMIRNATY is supplied as follows:

• COMIRNATY Single-Dose Prefilled Syringes for Individuals 65 Years of Age and Older and Individuals 12 Years Through 64 Years of Age with at Least One Underlying Condition that Puts Them at High Risk for Severe Outcomes from COVID-19:
  
  • oCarton of 10 single-dose prefilled syringes: NDC 0069-2631-10
  • oSingle-dose prefilled syringe: NDC 0069-2631-01
  • oSupplied in prefilled syringes labeled with gray borders
  • COMIRNATY Single-Dose Vials for Individuals 5 Through 11 Years of Age with at Least One Underlying Condition that Puts Them at High Risk for Severe Outcomes from COVID-19:
    
    • oCarton of 10 single-dose vials: NDC 0069-2609-10
    • oSingle-dose vial: NDC 0069-2609-01
    • oSupplied in vials with blue caps and labeled with blue borders

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

Do not use the vaccine after the expiration date printed on the vials, prefilled syringes, and cartons.

Storage Prior to Use

Prefilled Syringes

Store COMIRNATY prefilled syringes refrigerated at 2°C to 8°C (35°F to 46°F). DO NOT FREEZE.

The total time out of refrigeration (at temperatures between 8°C and 25°C (46°F and 77°F) must not exceed 12 hours.

Single-Dose Vials

COMIRNATY single-dose vials may arrive frozen at ultra-cold conditions in thermal containers with dry ice. Once received, frozen vials may be immediately transferred to the refrigerator at 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. Cartons of 10 single-dose vials may take up to 2 hours to thaw at this temperature. Once thawed, they should not be refrozen.

Alternatively, single-dose vials may be stored in an ultra-low temperature freezer at -90°C to -60°C (-130°F to -76°F). Do not store vials at -25°C to -15°C (-13°F to 5°F).

Cartons of COMIRNATY single-dose vials may be received at 2°C to 8°C (35°F to 46°F), and they should be stored at 2°C to 8°C (35°F to 46°F). Check that the carton has been previously updated to reflect the 10-week refrigerated expiry date.

The total time out of refrigeration (at temperatures between 8°C and 25°C (46°F and 77°F)) must not exceed 12 hours.

Advise the vaccine recipient or caregiver to read the FDA-approved patient labeling.

Inform the vaccine recipient or caregiver of the potential benefits and risks of vaccination with COMIRNATY.

Advise the vaccine recipient or caregiver to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822-7967 and www.vaers.hhs.gov.

This product’s labeling may have been updated. For the most recent prescribing information, please visit https://dailymed.nlm.nih.gov/dailymed/.

NDC 0069-2528-01
Rx only

COVID-19 Vaccine, mRNA
COMIRNATY^®

2025 – 2026 Formula

DO NOT FREEZE

1 dose of 0.3 mL

For intramuscular use.
US License No. 2229
BioNTech Manufacturing
GmbH & Pfizer Inc.

Principal Display Panel (Glass Prefilled Syringe Label 2025-2026 Formula)

NDC 0069-2528-10

COVID-19 Vaccine, mRNA
COMIRNATY^®

2025 – 2026 Formula

Injectable Suspension, for Intramuscular Use

10 Single-Dose Prefilled Syringes

Each prefilled syringe contains 1 dose of 0.3 mL

For 12 years through 64 years of age at
high-risk for severe COVID-19
For 65 years of age and older

DO NOT FREEZE

BIONTECH
Pfizer
Rx only

Principal Display Panel (Glass Prefilled Syringe Carton 2025-2026 Formula)

COVID-19 Vaccine, mRNA
COMIRNATY^®
Rx only

2025 – 2026 Formula

DO NOT DILUTE

Vial contains 1 dose of 0.3 mL

For intramuscular use.
US License No. 2229
BioNTech Manufacturing GmbH & Pfizer Inc.

NDC 0069-2501-01

Principal Display Panel (Glass Single-Dose Vial Label 2025-2026 Formula)

NDC 0069-2501-10

COVID-19 Vaccine, mRNA
COMIRNATY^®

2025 – 2026 Formula

Injectable Suspension, for Intramuscular Use

DO NOT DILUTE

10 Single-Dose Vials

Each vial contains 1 dose of 0.3 mL

For 5 years through 11 years of age at high-risk for severe COVID-19

BIONTECH
Pfizer
Rx only

Principal Display Panel (Glass Single-Dose Vial Carton 2025-2026 Formula)

NDC 0069-2631-01
Rx only

COVID-19 Vaccine, mRNA
COMIRNATY^®

2026 – 2027 Formula

DO NOT FREEZE

1 dose of 0.3 mL

For intramuscular use.
US License No. 2229
BioNTech Manufacturing
GmbH & Pfizer Inc.

Principal Display Panel (Glass Prefilled Syringe Label 2026-2027 Formula)

NDC 0069-2631-10

COVID-19 Vaccine, mRNA
COMIRNATY^®

2026 – 2027 Formula

Injectable Suspension, for Intramuscular Use

10 Single-Dose Prefilled Syringes

Each prefilled syringe contains 1 dose of 0.3 mL

For 12 years through 64 years of age at
high-risk for severe COVID-19
For 65 years of age and older

DO NOT FREEZE

BIONTECH
Pfizer
Rx only

Principal Display Panel (Glass Prefilled Syringe Carton 2026-2027 Formula)

COVID-19 Vaccine, mRNA
COMIRNATY^®
Rx only

2026 – 2027 Formula

DO NOT DILUTE

Vial contains 1 dose of 0.3 mL

For intramuscular use.
US License No. 2229
BioNTech Manufacturing GmbH & Pfizer Inc.

NDC 0069-2609-01

Principal Display Panel (Glass Single-Dose Vial Label 2026-2027 Formula)

NDC 0069-2609-10

COVID-19 Vaccine, mRNA
COMIRNATY^®

2026 – 2027 Formula

Injectable Suspension, for Intramuscular Use

DO NOT DILUTE

10 Single-Dose Vials

Each vial contains 1 dose of 0.3 mL

For 5 years through 11 years of age at high-risk for severe COVID-19

BIONTECH
Pfizer
Rx only

Principal Display Panel (Glass Single-Dose Vial Carton 2026-2027 Formula)