2.1 Preparation for Administration

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:

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Verify that the label on the prefilled syringe states 2025-2026 Formula.

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If prefilled syringe has been frozen, discard.

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Do not shake.

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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:

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Verify that the label on the vial states 2025-2026 Formula.

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If vial is frozen, thaw vial in the refrigerator [2ºC to 8ºC (35ºF to 46ºF) for up to 2 hours] or at room temperature [up to 25ºC (77ºF) for 30 minutes] [see How Supplied/Storage and Handling (16)].

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Prior to use, mix by inverting vial gently 10 times. Do not shake.

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Withdraw a single 0.3 mL dose using a sterile needle and syringe.

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Discard vial and any excess volume.

2.2 Administration Information

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.

2.3 Vaccination Schedule

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.

5.1 Management of Acute Allergic Reactions

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

5.2 Myocarditis and Pericarditis

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 post-vaccination, 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).

5.3 Syncope

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

5.4 Altered Immunocompetence

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

5.5 Limitation of Effectiveness

COMIRNATY 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 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 and 6 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.

6.2 Postmarketing Experience

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) post-vaccination1.

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.

8.1 Pregnancy

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 and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on COMIRNATY administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

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 Animal 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

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.

8.2 Lactation

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.

8.4 Pediatric Use

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.

8.5 Geriatric Use

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.

8.6 Immunocompromised Individuals

The Centers for Disease Control and Prevention has published considerations related to COVID-19 vaccination for individuals who are moderately to severely immunocompromised (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html).

12.1 Mechanism of Action

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.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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)].

14.1 Adults and Adolescents 12 Years of Age and Older

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 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 13.

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 14) 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 15.

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 16).

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 to 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 to 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 17 and Table 18).

Analyses of NT50 against Omicron BA.4/BA.5 among participants 18 through 55 years of age compared to 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 17 and Table 18).

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 19).

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 to 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 20 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 21). 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 22).

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 post-vaccination in each group.

The noninferiority 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.

14.2 Children 5 Years Through 11 Years of Age

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 ≥95th 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 23. 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 24 and Table 25).

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 to 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 to 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 26 and Table 27).

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 2ºC to 8ºC (35ºF to 46ºF), 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 -90ºC to -60ºC (-130ºF to -76ºF). 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 (35ºF to 46ºF), and they should be stored at 2°C to 8°C (35ºF to 46ºF). 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.