Document text
FDA-CBER-2022-5812-0236002
FDA-CBER-2022-5812-0236003
3 Preparation Instructions
COMIRNATY Multiple Dose Vial with Gray Cap and Label with Gray Border –
Thawin g Prior to Use
• Thaw vial(s) of COMIRNAT Y before use either by:
o Allowing vial(s) to thaw in the refrigerator [2ºC to
8ºC (35ºF to 46ºF)]. A carton of 10 vials may take
up to 6 hours to thaw, and thawed vials can be
stored in the refrigerator for up to 10 weeks.
o Allowing vial(s) to sit at room temperature [up to
25ºC (77ºF)] for 30 minutes.
• Vials may be stored at room temperature [up to 25ºC
(77ºF)] for up to 12 hours prior to use.
• Before use, mix by inverting vaccine vial gently
10 times.
• Do not shake.
• Prior to mixing, the thawed vaccine may contain white
to off-white opaque amorphous particles.
• After mixing, the vaccine should appear as a white to off-white suspension with no visible particles.
• Do not use if liquid is disco lored or if particles are
observed after mixing.
Gently × 10 Store in the
refrigerator for
up to 10 weeks
prior to use.
FDA-CBER-2022-5812-0236004
FDA-CBER-2022-5812-0236005
5 2.2 Administration Information
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
administration, whenever solution and container permit. The vac cine will be a white to off-white suspension.
Do not administer if vaccine is discolored or contains particul ate matter.
Administer a single 0.3 mL dose of COMIRNATY intramuscularly.
Vials of COMIRNATY with gray cap s and labels with gray borders contain 6 doses of 0.3 mL of vaccine. Low
dead-volume syringes and/or needles can be used to extract 6 do ses from a single vial. If standard syringes and
needles are used, there may not be sufficient volume to extract 6 doses from a single vial. Irrespective of the
type of syringe and needle,
• each dose must contain 0.3 mL of vaccine.
• if the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and
any excess volume.
• do not pool excess vaccine from multiple vials.
2.3 Vaccination Schedule
COMIRNATY is administered intramuscularly as a series of 2 dose s (0.3 mL each) 3 weeks apart.
There are no data available on the interchangeability of COMIRN ATY with COVID-19 vaccines from other
manufacturers to complete the vaccination series. Individuals w ho have received 1 dose of COMIRNATY should
receive a second dose of COMIRNATY to complete the vaccination series.
3 DOSAGE FORMS AND STRENGTHS
COMIRNATY is a suspension for injection. Each dose of COMIRNATY supplied in vials with gray caps and
labels with gray borders is 0.3 mL.
4 CONTRAINDICATIONS
Do not administer COMIRNATY to individuals with known history o f a severe allergic reaction (e.g.,
anaphylaxis) to any component of the COMIRNATY [see Description (11)] .
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in
the event an acute anaphylactic reaction occurs following admin istration of COMIRNATY.
5.2 Myocarditis and Pericarditis
Postmarketing data demonstrate increased risks of myocarditis a nd pericarditis, particularly within 7 days
following the second dose. The observed risk is higher among ma les under 40 years of age than among females
and older males. The observed risk is highest in males 12 through 17 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had
resolution of symptoms with conservative management. Information is not yet available about potential long-
term sequelae. The CDC has published considerations related to myocarditis and pericarditis after vaccination,
FDA-CBER-2022-5812-0236006
6 including for vaccination of individuals with a history of myocarditis or pericarditis
(https://www.cdc.gov/vaccines/covid-19/clinical-considerations/m yocarditis.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 f ainting.
5.4 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immu nosuppressant therapy, may have a
diminished immune response to the COMIRNATY. 5.5
Limitation of Effectiveness
COMIRNATY may not protect all vaccine recipients.
6 ADVERSE REACTIONS In clinical studies, the most commonly reported (≥10%) adverse reactions in participants 16 through 55 years of
age following any dose were pain at the injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain
(45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), and injection site swelling (10.6%).
In clinical studies, the most commonly reported (≥10%) adverse reactions in participants 56 years of age and
older following any dose were pain at the injection site (78.2%), fatigue (56.9%), headache, (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection sit e swelling (11.8%), fever (11.5%), and injection
site redness (10.4%).
In a clinical study, the most commonly reported (≥8%) adverse r eactions in adolescents 12 through 15 years of
age following any dose were pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills
(49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%) , injection site swelling (9.2%), and injection
site redness (8.6%).
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying cond itions, adverse reaction rates observed in the
clinical trials of a vaccine cannot be directly compared to rat es in the clinical trials of another vaccine and may
not reflect the rates observed in practice.
The safety of COMIRNATY was evaluated in participants 16 12 years of age and older in 2 clinical studies
conducted in Germany (Study 1), United States, Argentina, Brazi l, Turkey, South Africa, and Germany
(Study 2). Study BNT162-01 (Study 1) was a Phase 1/2, 2-part, d ose-escalation trial that enrolled
60 participants, 18 through 55 years of age and 36 participants , 56 through 85 years of age. Study C4591001
(Study 2) is a Phase 1/2/3 multicenter, multinational, randomiz ed, saline placebo-controlled, double-blinded
(Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study that has enrolled approximately
44,04746,000 participants (22,026 COMIRNATY; 22,021 placebo) 1612 years of age or older . Of these,
approximately 44,047 participants (22,026 COMIRNATY; 22,021 pla cebo) in Phase 2/3 are 16 years of age or
older (including 378 and 376 participants 16 through 17 years of age in the vaccine COMIRNATY and placebo
groups, respectively) and 2,260 adolescents are 12 through 15 years of age (1,131 an d 1,129 in the
COMIRNATY and placebo groups, respectively) . Upon issuance of the Emergency Use Authorization
FDA-CBER-2022-5812-0236007
7 (December 11, 2020) for COMIRNATY, participants were unblinded to offer placebo par ticipants
COMIRNATY. Participants were unblinded in a phased manner over a period of months to offer placebo
participants COMIRNATY. Study 2 also included 200 participants with confirmed stable human
immunodeficiency virus (HIV) infection; HIV-positive participan ts are included in safety population disposition
but are summarized separately in safety analyses. 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.
At the time of the analysis of the ongoing Study 2 with a data cut-off of March 13, 2021, there were
25,651 (58.2%) participants (13,031 COMIRNATY and 12,620 placeb o) 16 years of age and older followed for
≥4 months after the second dose.
In Study 2, all participants 12 through 15 years of age, and Pa rticipants 16 years and older in the reactogenicity
subset were monitored for solicited local and systemic reactions and use of antipyretic medication after each
vaccination in an electronic diary. Participants are being moni tored for unsolicited adverse events, including
serious adverse events, throughout the study [from Dose 1 throu gh 1 month (all unsolicited adverse events) or
6 months (serious adverse events) after the last vaccination]. Tables 1 through 6 present the frequency and
severity of solicited local and systemic reactions, respectivel y, within 7 days following each dose of
COMIRNATY and placebo.
Participants 16 Years of Age and Older
At the time of the analysis of the ongoing Study 2 with a data cutoff of March 13, 2021, there were
25,651 (58.2%) participants (13,031 COMIRNATY and 12,620 placeb o) 16 years of age and older followed for
≥4 months after the second dose.
Demographic characteristics in Study 2 were generally similar w ith regard to age, gender, race, and ethnicity
among participants who received COMIRNATY and those who receive d placebo. Overall, among the total
participants who received either COMIRNATY or placebo, 50.9% we re male, 49.1% were female, 79.3% were
16 through 64 years of age, 20.7% were 65 years of age and olde r, 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 Adverse Reactions Solicited in the Study 2
Table 1 and Table 2 present the frequency and severity of repor ted solicited local and systemic reactions,
respectively, within 7 days following each dose of COMIRNATY and placebo in the subset of participants
16 through 55 years of age included in the safety population wh o were monitored for reactogenicity with an
electronic diary.
Table 3 and Table 4 present the frequency and severity of repor ted solicited local and systemic reactions,
respectively, within 7 days of each dose of COMIRNATY and place bo for participants 56 years of age and
older.
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 participant s 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.
FDA-CBER-2022-5812-0236008
8 Table 1: Study 2 – Frequency and Percentages of Participants w ith Solicited Local Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of
Age – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Rednessc
Any (>2.0 cm) 156 (5.4) 28 (1.0) 151 (5.6) 18 (0.7)
Mild 113 (3.9) 19 (0.7) 90 (3.4) 12 (0.4)
Moderate 36 (1.2) 6 (0.2) 50 (1.9) 6 (0.2)
Severe 7 (0.2) 3 (0.1) 11 (0.4) 0
Swellin gc
Any (>2.0 cm) 184 (6.3) 16 (0.6) 183 (6.8) 5 (0.2)
Mild 124 (4.3) 6 (0.2) 110 (4.1) 3 (0.1)
Moderate 54 (1.9) 8 (0.3) 66 (2.5) 2 (0.1)
Severe 6 (0.2) 2 (0.1) 7 (0.3) 0
Pain at the injection sited
Any 2426 (83.7) 414 (14.2) 2101 (78.3) 312 (11.6)
Mild 1464 (50.5) 391 (13.4) 1274 (47.5) 284(10.6)
Moderate 923 (31.8) 20 (0.7) 788(29.4) 28(1.0)
Severe 39 (1.3) 3 (0.1) 39 (1.5) 0
Notes: Reactions were collected in the electronic diary (e-diar y) from Day 1 to Day 7 after vaccination
No Grade 4 solicited local reactions were reported in participa nts 16 through 55 years of age
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention Participan ts with
chronic, stable HIV infection were excluded
a N = Number of participants reporting at least 1 yes or no r esponse for the specified reaction after the specified dose Th e N for each
reaction was the same, therefore, this information was included in the column header
b n = Number of participants with the specified reaction
c Mild: >2 0 to ≤5 0 cm; Moderate: >5 0 to ≤10 0 cm; Severe: > 10 0 cm
d Mild: does not interfere with a ctivity; Moderate: interferes with activity; Severe: prevents daily activity
Table 2: Study 2 – Frequency and Percentages of Participants w ith Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of
Age – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Fever
≥38.0℃ 119 (4.1) 25 (0.9) 440 (16.4) 11 (0.4)
≥38.0℃ to 38.4℃ 86 (3.0) 16 (0.6) 254 (9.5) 5 (0.2)
>38.4℃ to 38.9℃ 25 (0.9) 5 (0.2) 146 (5.4) 4 (0.1)
>38.9℃ to 40.0℃ 8 (0.3) 4 (0.1) 39 (1.5) 2 (0.1)
>40.0℃ 0 0 1 (0.0) 0
Fatiguec
Any 1431 (49.4) 960 (33.0) 1649 (61.5) 614(22.9)
Mild 760 (26.2) 570 (19.6) 558 (20.8) 317 (11.8)
Moderate 630 (21.7) 372 (12.8) 949 (35.4) 283 (10.5)
Severe 41 (1.4) 18 (0.6) 142 (5.3) 14 (0.5)
FDA-CBER-2022-5812-0236009
9 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Headachec
Any 1262 (43.5) 975 (33.5) 1448 (54.0) 652 (24.3)
Mild 785 (27.1) 633 (21.8) 699 (26.1) 404 (15.1)
Moderate 444 (15.3) 318 (10.9) 658 (24.5) 230 (8.6)
Severe 33 (1.1) 24 (0.8) 91 (3.4) 18 (0.7)
Chillsc
Any 479 (16.5) 199 (6.8) 1015 (37.8) 114 (4.2)
Mild 338 (11.7) 148 (5.1) 477 (17.8) 89 (3.3)
Moderate 126 (4.3) 4 9 (1.7) 469 (17.5) 23(0.9)
Severe 15 (0.5) 2 (0.1) 69 (2.6) 2 (0.1)
Vomitingd
Any 34 (1.2) 36 (1.2) 58 (2.2) 30 (1.1)
Mild 29 (1.0) 3 0 (1.0) 4 2(1.6) 20(0.7)
Moderate 5 (0.2) 5 (0.2) 12 (0.4) 10 (0.4)
Severe 0 1 (0.0) 4 (0.1) 0
Diarrheae
Any 3 09 (10.7) 323 (11.1) 269(10.0) 205(7.6)
Mild 251 (8.7) 264 (9.1) 219 (8.2) 169 (6.3)
Moderate 55 (1.9) 58 (2.0) 44 (1.6) 35 (1.3)
Severe 3 (0.1) 1 (0.0) 6 (0.2) 1 (0.0)
New or worsened muscle painc
Any 664 (22.9) 329 (11.3) 1055 (39.3) 237 (8.8)
Mild 353 (12.2) 2 3 1 (7.9) 441 (16.4) 150(5.6)
Moderate 296 (10.2) 9 6 (3.3) 552 (20.6) 84(3.1)
Severe 15 (0.5) 2 (0.1) 62 (2.3) 3 (0.1)
New or worsened joint painc
Any 342 (11.8) 168 (5.8) 638 (23.8) 147 (5.5)
Mild 200 (6.9) 112 (3.9) 291 (10.9) 82 (3.1)
Moderate 137 (4.7) 55 (1.9) 320 (11.9) 61 (2.3)
Severe 5 (0.2) 1 (0.0) 27 (1.0) 4 (0.1)
Use of antipyretic or
pain medicationf 805 (27.8) 398 (13.7) 1213 (45.2) 320 (11.9)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after
each dose
No Grade 4 solicited systemic reactions were reported in partic ipants 16 through 55 years of age
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention Participan ts with
chronic, stable HIV infection were excluded
a N = Number of participants reporting at least 1 yes or no re sponse for the specified reaction after the specified dose The N for each
reaction or use of antipyretic or pain medication was the same, therefore, this information was included in the column header
b n = Number of participants with the specified reaction c Mild: does not interfere with a ctivity; Moderate: some inter ference with activity; Severe: prevents daily activity
d Mild: 1 to 2 times i n 24 hours; Moderate: >2 times in 24 hou rs; Severe: requires intravenous hydration
e Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loos e stools in 24 hours; Severe: 6 or more loose stools in 24 hour s
f Severity was not collected for use of antipyretic or pain me dication
FDA-CBER-2022-5812-0236010
10 Table 3: Study 2 – Frequency and Percentages of Participants w ith Solicited Local Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and
Older – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Rednessc
Any (>2.0 cm) 106 (5.3) 20 (1.0) 133 (7.2) 14 (0.8)
Mild 71 (3.5) 13 (0.7) 65 (3.5) 10 (0.5)
Moderate 30 (1.5) 5 (0.3) 58 (3.1) 3 (0.2)
Severe 5 (0.2) 2 (0.1) 10 (0.5) 1 (0.1)
Swellin gc
Any (>2.0 cm) 141 (7.0) 23 (1.2) 145 (7.8) 13 (0.7)
Mild 87 (4.3) 11 (0.6) 80 (4.3) 5 (0.3)
Moderate 52 (2.6) 12 (0.6) 61 (3.3) 7 (0.4)
Severe 2 (0.1) 0 4 (0.2) 1 (0.1)
Pain at the injection sited
Any (>2.0 cm) 1408 (70.1) 185 (9.3) 1230 (66.1) 143 (7.8)
Mild 1108 (55.2) 177 (8.9) 873(46.9) 138(7.5)
Moderate 296 (14.7) 8 (0.4) 3 47(18.7) 5(0.3)
Severe 4 (0.2) 0 10 (0.5) 0
Notes: Reactions were collected in the electronic diary (e-diar y) from Day 1 to Day 7 after vaccination
No Grade 4 solicited local reactions were reported in participa nts 56 years of age and older
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention Participan ts with
chronic, stable HIV infection were excluded
a N = Number of participants reporting at least 1 yes or no re sponse for the specified reaction after the specified dose The N for each
reaction was the same, therefore, the information was included in the column header
b n = Number of participants with the specified reaction
c Mild: >2 0 to ≤5 0 cm; Moderate: >5 0 to ≤10 0 cm; Severe: > 10 0 cm
d Mild: does not interfere with activity; Moderate: interfere s with activity; Severe: prevents daily activity
Table 4: Study 2 – Frequency and Percentages of Participants wi th Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and
Older – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Fever
≥38.0℃ 26 (1.3) 8 (0.4) 219 (11.8) 4 (0.2)
≥38.0℃ to 38.4℃ 23 (1.1) 3 (0.2) 158 (8.5) 2 (0.1)
>38.4℃ to 38.9℃ 2 (0.1) 3 (0.2) 54 (2.9) 1 (0.1)
>38.9℃ to 40.0℃ 1 (0.0) 2 (0.1) 7 (0.4) 1 (0.1)
>40.0℃ 0 0 0 0
FDA-CBER-2022-5812-0236011
11 COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Fatiguec
Any 677 (33.7) 447 (22.5) 949 (51.0) 306 (16.7)
Mild 415 (20.7) 281 (14.1) 391 (21.0) 183 (10.0)
Moderate 259 (12.9) 163 (8.2) 497 (26.7) 121 (6.6)
Severe 3 (0.1) 3 (0.2) 60 (3.2) 2 (0.1)
Grade 4 0 0 1 (0.1) 0
Headachec
Any 503 (25.0) 363 (18.3) 733 (39.4) 259 (14.1)
Mild 381 (19.0) 2 6 7 (13.4) 464(24.9) 189(10.3)
Moderate 120 (6.0) 93 (4.7) 256 (13.8) 65 (3.5)
Severe 2 (0.1) 3 (0.2) 13 (0.7) 5 (0.3)
Chillsc
Any 130 (6.5) 6 9 (3.5) 435(23.4) 57(3.1)
Mild 102 (5.1) 49 (2.5) 229 (12.3) 45 (2.5)
Moderate 28 (1.4) 19 (1.0) 185 (9.9) 12 (0.7)
Severe 0 1 (0.1) 21(1.1) 0
Vomitin gd
Any 10 (0.5) 9 (0.5) 13 (0.7) 5 (0.3)
Mild 9 (0.4) 9 (0.5) 10 (0.5) 5 (0.3)
Moderate 1 (0.0) 0 1 (0.1) 0
Severe 0 0 2 (0.1) 0
Diarrheae
Any 168 (8.4) 130 (6.5) 152(8.2) 102(5.6)
Mild 137 (6.8) 109 (5.5) 125(6.7) 76(4.1)
Moderate 27 (1.3) 20 (1.0) 25 (1.3) 22 (1.2)
Severe 4 (0.2) 1 (0.1) 2 (0.1) 4 (0.2)
New or worsened muscle painc
Any 274 (13.6) 165 (8.3) 537 (28.9) 99 (5.4)
Mild 183 (9.1) 111 (5.6) 229 (12.3) 65 (3.5)
Moderate 90 (4.5) 51 (2.6) 288 (15.5) 33 (1.8)
Severe 1 (0.0) 3 (0.2) 20(1.1) 1(0.1)
New or worsened joint painc
Any 175 (8.7) 124 (6.2) 353 (19.0) 72 (3.9)
Mild 119 (5.9) 78 (3.9) 183 (9.8) 44 (2.4)
Moderate 53 (2.6) 45 (2.3) 161 (8.7) 27 (1.5)
Severe 3 (0.1) 1 (0.1) 9 (0.5) 1 (0.1)
Use of antipyretic or
pain medicationf 382 (19.0) 224 (11.3) 688 (37.0) 170 (9.3)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after
each dose
The only Grade 4 solicited syst emic reaction reported in participants 56 years of age and older was fatigue
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention Participan ts with
chronic, stable HIV infection were excluded
a N = Number of participants reporting at least 1 yes or no re sponse for the specified reaction after the specified dose N for each
reaction or use of antipyretic or pain medication was the same, therefore was included in the column header
b n = Number of participants with the specified reaction
FDA-CBER-2022-5812-0236012
12 c Mild: does not interfere with a ctivity; Moderate: some inter ference with activity; Severe: pr events daily activity; Grade 4 reactions
were defined in the clinical stu dy protocol as emergency room v isit or hospitalization for severe fatigue, severe headache, se vere
chills, severe muscle pain, or severe joint pain
d Mild: 1 to 2 times i n 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration; Grade 4 emergency v isit or
hospitalization for severe vomiting
e Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loos e stools in 24 hours; Severe: 6 or more loose stools in 24 hour s; Grade 4:
emergency room or hospitalization for severe diarrhea
f Severity was not collected for use of antipyretic or pain me dication
In participants with chronic, stable HIV infection the frequenc ies 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 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, res pectively.
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 follo wing any dose, through 1 month after Dose 2, in
participants 16 years of age and older (N=43,847; 21,926 COMIRN ATY 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 D ose 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 wer e reported by 4,396 (33.8%) participants in
the COMIRNATY group and 2,136 (16.4%) participants in the place bo group. In a similar analysis in
participants 56 years of age and older that included 8,931 COMI RNATY 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 g roup. 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 adv erse events among COMIRNATY recipients
compared to placebo recipients was primarily attributed to even ts that are consistent with adverse reactions
solicited among participants in the reactogenicity subset (Tabl e 3 and Table 4).
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. Cur rently available information is insufficient to
determine a causal relationship with the vaccine. In the analys is 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 analys is of unblinded follow-up, there were no
FDA-CBER-2022-5812-0236013
13 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 16 through 55 years of age who h ad received at least 1 dose of vaccine or
placebo (COMIRNATY =12,995; placebo = 13,026), serious adverse events from Dose 1 up to the participant
unblinding date in ongoing follow-up were reported by 103 (0.8%) COMIRNATY recipients and 117 (0.9%)
placebo recipients. In a similar analysis, in participants 56 y ears of age and older (COMIRNATY = 8,931;
placebo = 8,895), 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 (inclu ding 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 categorie s of serious adverse events that would suggest a
causal relationship to COMIRNATY.
Adolescents 12 Through 15 Years of Age
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
(70.769.0%) adolescents (786 COMIRNATY and 773 placebo) 12 through 15 years of age followed for
≥4 months after the second dose. The safety evaluation in Study 2 is ongoing.
Demographic characteristics in Study 2 were generally similar w ith regard to age, gender, 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% w ere 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.
Local and Systemic Adverse Reactions Solicited in Study 2
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.
Table 5: Study 2 – Frequency and Percentages of Adolescents Wi th Solicited Local Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Adolescents 1 2 Through 15 Years of
Age – Safety Population*
COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Rednessc
Any (>2 cm) 65 (5.8) 12 (1.1) 55 (5.0) 10 (0.9)
Mild 44 (3.9) 11 (1.0) 29 (2.6) 8 (0.7)
Moderate 20 (1.8) 1 (0.1) 26 (2.4) 2 (0.2)
FDA-CBER-2022-5812-0236014
14 COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Severe 1 (0.1) 0 (0.0) 0( 0 . 0 ) 0( 0 . 0 )
Swellingc
Any (>2 cm) 78 (6.9) 11 (1.0) 54 (4.9) 6 (0.6)
Mild 55 (4.9) 9 (0.8) 36 (3.3) 4 (0.4)
Moderate 23 (2.0) 2 (0.2) 18 (1.6) 2 (0.2)
Severe 0 (0.0) 0 (0.0) 0(0.0) 0(0.0)
Pain at the injection sited
Any 971 (86.2) 263 (23.3) 866 (78.9) 193 (17.9)
Mild 467 (41.4) 227 (20.1) 466 (42.5) 164 (15.2)
Moderate 493 (43.7) 36 (3.2) 393 (35.8) 29 (2.7)
Severe 11 (1.0) 0 (0.0) 7 (0.6) 0( 0 . 0 )
Note: Reactions were collected in the electronic diary (e-diary ) from Day 1 to Day 7 after vaccination
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention
a N = Number of participants reporting at least 1 yes or no r esponse for the specified reaction after the specified dose
b n = Number of participants with the specified reaction
c Mild: >2 0 to ≤5 0 cm Moderate: >5 0 to ≤10 0 cm Severe: > 10 0 cm
d Mild: does not interfere with a ctivity Moderate: interferes with activity Severe: prevents daily activity
Table 6: Study 2 – Frequency and Percentages of Adolescents with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Adolescents 1 2 Through 15 Years of
Age – Safety Population*
COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Fever
≥38.0℃ 114 (10.1) 12 (1.1) 215 (19.6) 7 (0.6)
≥38.0℃ to 38.4℃ 74 (6.6) 8 (0.7) 107 (9.8) 5 (0.5)
>38.4℃ to 38.9℃ 29 (2.6) 2 (0.2) 83 (7.6) 1 (0.1)
>38.9℃ to 40.0℃ 10 (0.9) 2 (0.2) 25 (2.3) 1 (0.1)
>40.0℃ 1 (0.1) 0 (0.0) 0 (0.0) 0( 0 . 0 )
Fatiguec
Any 677 (60.1) 457 (40.6) 726 (66.2) 264 (24.5)
Mild 278 (24.7) 250 (22.2) 232 (21.1) 133 (12.3)
Moderate 384 (34.1) 199 (17.7) 468 (42.7) 127 (11.8)
Severe 15 (1.3) 8 (0.7) 26 (2.4) 4 (0.4)
Headachec
Any 623 (55.3) 396 (35.1) 708 (64.5) 264 (24.5)
Mild 361 (32.0) 256 (22.7) 302 (27.5) 170 (15.8)
Moderate 251 (22.3) 131 (11.6) 384 (35.0) 93 (8.6)
Severe 11 (1.0) 9 (0.8) 22 (2.0) 1 (0.1)
Chillsc
Any 311 (27.6) 109 (9.7) 455 (41.5) 74(6.9)
Mild 195 (17.3) 82 (7.3) 221 (20.1) 53 (4.9)
Moderate 111 (9.8) 25 (2.2) 214 (19.5) 21 (1.9)
Severe 5 (0.4) 2 (0.2) 20 (1.8) 0( 0 . 0 )
FDA-CBER-2022-5812-0236015
15 COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Vomitingd
Any 31 (2.8) 10 (0.9) 29 (2.6) 12 (1.1)
Mild 30 (2.7) 8 (0.7) 25 (2.3) 11 (1.0)
Moderate 0 (0.0) 2 (0.2) 4 (0.4) 1 (0.1)
Severe 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Diarrheae
Any 90 (8.0) 82 (7.3) 65 (5.9) 44 (4.1)
Mild 77 (6.8) 72 (6.4) 59 (5.4) 39 (3.6)
Moderate 13 (1.2) 10 (0.9) 6 (0.5) 5 (0.5)
Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
New or worsened muscle painc
Any 272 (24.1) 148 (13.1) 355 (32.4) 90 (8.3)
Mild 125 (11.1) 88 (7.8) 152 (13.9) 51 (4.7)
Moderate 145 (12.9) 60 (5.3) 197 (18.0) 37 (3.4)
Severe 2 (0.2) 0 (0.0) 6 (0.5) 2 (0.2)
New or worsened joint painc
Any 109 (9.7) 77 (6.8) 173 (15.8) 51 (4.7)
Mild 66 (5.9) 50 (4.4) 91 (8.3) 30 (2.8)
Moderate 42 (3.7) 27 (2.4) 78 (7.1) 21 (1.9)
Severe 1 (0.1) 0 (0.0) 4 (0.4) 0( 0 . 0 )
Use of antipyretic or
pain medicationf 413 (36.6) 111 (9.8) 557 (50.8) 95 (8.8)
Note: Events and use of antipyretic or pain medication were col lected in the electronic diary (e -diary) from Day 1 to Day 7 after each
dose
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention
a N = Number of participants reporting at least 1 yes or no re sponse for the specified event after the specified dose
b n = Number of participants with the specified reaction
c Mild: does not interfere with a ctivity Moderate: some inter ference with activity Severe: prevents daily activity
d Mild: 1 to 2 times i n 24 hours; Moderate: >2 times in 24 hou rs; Severe: requires intravenous hydration
e Mild: 2 to 3 loose stools in 24 hours Moderate: 4 to 5 loos e stools in 24 hours Severe: 6 or more loose stools in 24 hour s
f Severity was not collected for use of antipyretic or pain me dication
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 t he 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 ag e 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 D ose 1 up to the participant unblinding date was
conducted. Among participants 12 through 15 years of age who received at least one dose of study vaccine,
unsolicited adverse events were reported by 95 (8.4%) participa nts in the COMIRNATY group and
113 (10.0%) participants in the placebo group.
FDA-CBER-2022-5812-0236016
FDA-CBER-2022-5812-0236017
17 A developmental toxicity study has been performed in female rat s administered the equivalent of a single
human dose of COMIRNATY 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) .
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) and other ingredients included in a single
human dose of COMIRNATY 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 rep orted 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 c linical 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 s usceptibility to disease prevented by the vaccine.
8.4 Pediatric Use Safety and effectiveness of COMIRNATY in individuals 126 through 17 years of age is based on safety and
effectiveness data in this age group and in adults [see Adverse Reactions (6) and Clinical Studies (14.1)] .
The safety and effectiveness of COMIRNATY in individuals younge r than 1 26 years of age have not been
established.
8.5 Geriatric Use
Of the total number of COMIRNATY recipients in Study 2 as of Ma rch 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)] . No overall differences in safety or effectiveness were observ ed between these
recipients and younger recipients.
11 DESCRIPTION
COMIRNATY (COVID-19 Vaccine, mRNA) is a sterile suspension for injection for intramuscular use.
COMIRNATY is supplied as a frozen suspension in multiple dose v ials with gray caps and labels with gray
borders. Each 0.3 mL dose of COMIRNATY supplied in multiple dos e vials with gray caps and labels with gray
borders contains 30 mcg of a nucleoside-modified messenger RNA (mRNA) encoding the viral spike (S)
glycoprotein of SARS-CoV-2.
Each 0.3 mL dose of the COMIRNATY supplied in multiple dose via ls with gray caps and labels with gray
borders also includes the following ingredients: lipids (0.43 m g
((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecan oate), 0.05 mg 2-(ω-methoxy-(Pp olyethylene
FDA-CBER-2022-5812-0236018
FDA-CBER-2022-5812-0236019
19
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 CO MIRNATY group and 18,379 in the placebo
group) who did not have evidence of prior infection with SARS-C oV-2 through 7 days after the second dose.
The population in the protocol pre-specified primary efficacy a nalysis included all participants 12 years of age
and older who had been enrolled from July 27, 2020, and followe d 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 g roup.
The population for the updated vaccine efficacy analysis includ ed participants 16 years of age and older who
had been enrolled from July 27, 2020, and followed for the deve lopment of COVID-19 during blinded
placebo-controlled follow-up through March 13, 2021, representi ng up to 6 months of follow-up after Dose 2.
There were 12,796 (60.8%) participants in the COMIRNATY group a nd 12,449 (58.7%) in the placebo group
followed for ≥4 months after Dose 2 in the blinded placebo-cont rolled follow-up period.
SARS-CoV-2 variants of concern identified from COVID-19 cases for this age group from this data cutoffin
this study 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 vac cine effectiveness against these variants.
The updated vaccine efficacy information is presented in Table 57.
Table 57: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days Afte r Dose 2, by Age
Subgroup – Participants 16 Years of Age and Older Without Evide nce of Infection and
Participants With or Without Evidence of Infection Prior to 7 D ays After Dose 2 – Evaluable
Efficacy (7 Days) Population During the Placebo-Controlled Follow-up Period
First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior
SARS-CoV-2 infection*
Subgroup COMIRNATY
Na=19,993
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=20,118
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CIe)
All partici pants 77
6.092 (19,711 ) 833
5.857 (19,741 )91.1
(88.8, 93.1 )
16 throu gh 64 years 70
4.859 (15,519 ) 709
4.654 (15,515 )90.5
(87.9, 92.7 )
65 years and older 7
1.233 (4192 ) 124
1.202 (4226 )94.5
(88.3, 97.8 )
FDA-CBER-2022-5812-0236020
20 First COVID-19 occurrence from 7 days after Dose 2 in participa nts with or without* evidence of prior
SARS-CoV-2 infection
Subgroup COMIRNATY
Na=21,047
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,210
Cases
n1b
Surveillance Timec (n2d)Vaccine Efficacy %
(95% CIe)
All participants 81
6.340 (20,533) 854
6.110 (20,595)90.9
(88.5, 92.8)
16 through 64 years 74
5.073 (16,218) 726
4.879 (16,269)90.2
(87.5, 92.4)
65 years and older 7
1.267 (4315) 128
1.232 (4326)94.7
(88.7, 97.9)
Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT- PCR) and at least 1 symptom
consistent with COVID-19 (symptom s included: fever; new or incr eased cough; new or increased sho rtness of breath; chills; new or
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting)
* Participants who had no evidence of past SARS-CoV-2 infection (i e , N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [ nasal swab] at Visits 1 and 2) , and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis
a N = Number of participants in the specified group
b n1 = Number of participants meeting the endpoint definition
c Total surveillance time in 1000 person-years for the given e ndpoint across all participants within each group at risk for t he endpoint
Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period
d n2 = Number of participants at risk for the endpoint e Two-sided confidence interval (CI) for vaccine efficacy is d erived based on the Clopper and Pearson method adjusted to the
surveillance time
Subgroup analyses of vaccine efficacy (although limited by smal l numbers of cases in some subgroups) did not
suggest meaningful differences in efficacy across genders, ethn ic groups, geographies, or for participants with
obesity or medical comorbidities associated with high risk of s evere COVID-19.
Efficacy Against Severe COVID-19
Efficacy analyses of secondary efficacy endpoints supported 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 68) as the COVID-19 case counts in participants without prior SAR S-CoV-2
infection were the same as those in participants with or withou t prior SARS-CoV-2 infection in both the
COMIRNATY and placebo groups.
FDA-CBER-2022-5812-0236021
21 Table 68: Vaccine Efficacy – First Severe COVID-19 Occurrence in Participants 16 Years of Age and
Older With or Without* Prior SARS-CoV-2 Infection Based on Prot ocol† or Centers for
Disease Control and Prevention (CDC)‡ Definition From 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population During the Placebo-Controlled Follow-up
Vaccine Efficac y – First Severe COVID-19 Occurrence
COMIRNATY
Cases
n1a
Surveillance Timeb (n2c) Placebo
Cases
n1a
Surveillance Timeb (n2c)Vaccine Efficacy %
(95% CId)
7 days after Dose 2d 1
6.353 (20,540 ) 21
6.237 (20,629 )95.3
(70.9, 99.9 )
Vaccine Efficacy – First Severe COVID-19 Occurrence Based on CD C Definition
COMIRNATY
Cases
n1a
Surveillance Timeb (n2c) Placebo
Cases
n1a
Surveillance Timeb (n2c)Vaccine Efficacy %
(95% CId)
7 days after Dose 2d 0
6.345 (20,513) 31
6.225 (20,593) 100
(87.6, 100.0)
Note: Confirmed cases were determined by Reverse Transcription- Polymerase Chain Reaction (RT- PCR) and at least 1 symptom
consistent with COVID-19 (symptom s included: fever; new or incr eased cough; new or increased sho rtness of breath; chills; new or
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting)
* Participants who had no evidence of past SARS-CoV-2 infection (i e , N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [ nasal swab] at Visits 1 and 2) , and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis
† Severe illness from COVID-19 is d efined in the protocol as con firmed COVID-19 and presence of at least 1 of the following:
• Clinical signs at rest indicative of severe systemic illness (r espiratory rate ≥30 breaths per minute, heart rate ≥125 beats p er
minute, saturation of oxygen ≤93% on room air at sea level, or ratio of arterial oxygen partial pressure to fractional inspire d
oxygen <300 mm Hg);
• Respiratory failure [defined as needing high-flow oxygen, nonin vasive ventilation, mechanical ventilation or extracorporeal
membrane oxygenation (ECMO)];
• Evidence of shock (systolic blood pressure <90 mm Hg, diastolic blood pressure <60 mm Hg, or requiring vasopressors);
• Significant acute renal, hepatic, or neurologic dysfunction;
• Admission to an Intensive Care Unit;
• Death
‡ Severe illness from COVID-19 as defined by CDC is confirmed COV ID-19 and presence of at least 1 of the following:
• Hospitalization;
• Admission to the Intensive Care Unit;
• Intubation or mechanical ventilation;
• Death
a n1 = Number of participants meeting the endpoint definition
b Total surveillance time in 1000 person-years for the given e ndpoint across all participants within each group at risk for t he endpoint
Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period
c n2 = Number of participants at risk for the endpoint
d Two-side confidence interval (CI) for vaccine efficacy is de rived based on the Clopper and Pearson method adjusted to the
surveillance time
14.2 Efficacy in Adolescents 12 Through 15 Years of Age
A descriptive efficacy analysis of Study 2 has been performed i n 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 9.
FDA-CBER-2022-5812-0236022
22
Table 9: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2: Without Evidence
of Infection and With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Blinded
Placebo-Controlled Follow-up Period, Adolescents 12 Through 15 Years of Age Evaluable
Efficacy (7 Days) Population
First COVID-19 occurrence from 7 days after Dose 2 in adolescen ts 12 through 15 years of age without
evidence of prior SARS-CoV-2 infection*
COMIRNATY
Na=1057
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=1030
Cases
n1b
Surveillance Timec (n2d)Vaccine Efficacy %
(95% CIe)
Adolescents
12 throu gh 15 years of a ge 0
0.343 (1043 ) 28
0.322 (1019 )100.0
(86.8, 100.0 )
First COVID-19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age with or
without evidence of prior SARS-CoV-2 infection
COMIRNATY
Na=1119
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=1109
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CIe)
Adolescents
12 through 15 years of age 0
0.362 (1098) 30f
0.345 (1088)100.0
(87.5, 100.0)
Note: Confirmed cases were determined by Reverse Transcription- Polymerase Chain Reaction (RT-PCR) and at least 1 symptom
consistent with COVID-19 (symptoms included: fever new or incr eased cough new or increased shortness of breath chills new or
increased muscle pain new loss of taste or smell sore throat diarrhea vomiting)
* Participants who had no evidence of past SARS-CoV-2 infection (i e , N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis
a N = Number of participants in the specified group
b n1 = Number of participants meeting the endpoint definition
c Total surveillance time in 1000 person-years for the given e ndpoint across all participants within each group at risk for t he endpoint
Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period
d n2 = Number of participants at risk for the endpoint
e Two-side confidence interval (CI) for vaccine efficacy is de rived based on the Clopper and Pearson method adjusted for
surveillance time
f T h e o n l y SARS-CoV-2 variant of concern identified from COVID-19 cases in this age group from this data cutoff was B 1 1 7
(Alpha)
14.3 Immunogenicity in Adolescents 12 Through 15 Years of Age
In Study 2, an analysis of SARS-CoV-2 50% neutralizing titers ( NT50) 1 month after Dose 2 in a randomly
selected subset of participants demonstrated non-inferior immune responses (within 1.5-fold) comparing
adolescents 12 through 15 years of age to participants 16 throu gh 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 10).
FDA-CBER-2022-5812-0236023
23 Table 10: Summary of Geometric Mean Ratio for 50% Neutralizing Titer – Comparison of Adolescents
12 Through 15 Years of Age to Participants 16 Through 25 Years of Age (Immunogenicity
Subset) – Participants Without Evidence of Infection up to 1 Mo nth After Dose 2 – Dose 2
Evaluable Immunogenicity Population
COMIRNATY
12 Through 15 Years/
16 Through 25 Years 12 Through 15 Years
na=190 16 Through 25 Years
na=170
Assa y Time
Pointb GMTc
(95% CIc) GMTc
(95% CIc)GMRd
(95% CId)Met
Noninferiority
Objectivee
(Y/N)
SARS-CoV-2
neutralization
assay - NT50
(titer)f 1 month
after
Dose 2 123953.65
(1117095.75, 14026.51) 7058.1
(6215.49, 8001.21)1.767
(1.4750,
2.109) Y
Abbreviations: CI = confidence in terval GMR = geometric mean ratio GMT = geometric mean titer LLOQ = lower limit of
quantitation NAAT = nucleic-acid amplification test NT50 = 50 % neutralizing titer SARS-CoV-2 = severe acute respiratory
syndrome coronavirus 2
Note: Participants who had no se rological or virological eviden ce (up to 1 month after receipt of the last dose) of past SARS-CoV-2
infection (i e , N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not d etected by NAAT [nasal swab] at Visits 1 a nd
2), and had negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 were included in the analysis
a n = Number of participants with valid and determinate assay results for the specified assay at the given dose/sampling time point
b Protocol-specified timing for blood sample collection
c GMTs and 2-sided 95% CIs were calculated by exponentiating t he mean logarithm of the titers and the correspon ding CIs (base d
on the Student t distribution) A ssay results below the LLOQ we re set to 0 5 × LLOQ
d GMRs and 2-sided 95% CIs were calculated by exponentiating t he mean difference of the log arithms of the titers (Group 1
[12 through 15 years of age] – Group 2 [16 through 25 years of age]) and the corresponding CI (based on the Student t
distribution)
e Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0 67
f SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGr een Virus Microneutralization Assay The assay uses a
fluorescent reporter virus derived from the USA WA1/2020 strain and virus neutralization is read on Vero cell monolayers The
sample NT50 is defined as the r eciprocal serum dilution at whic h 50% of the virus is neutralized
16 HOW SUPPLIED/STORAGE AND HANDLING
COMIRNATY Suspension for Intramuscular Injection, multiple dose vials with gray caps and labels with gray
borders are supplied in a carton containing 10 multiple dose vi als (NDC 0069-2025-10) or 25 multiple dose
vials (NDC 0069-2025-25).
One vial contains 6 doses of 0.3 mL.
During storage, minimize exposure to room light, and avoid expo sure to direct sunlight and ultraviolet light.
Do not refreeze thawed vials.
Vial Storage Prior to Use
Cartons of COMIRNATY multiple dose vials with gray caps and lab els with gray borders will arrive frozen at
ultra-cold conditions in thermal containers with dry ice.
Once received, frozen vials may be immediately transferred to t he refrigerator [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. A carton of 10 vials may take up to 6 hou rs to thaw at this temperature.
FDA-CBER-2022-5812-0236024
24
Alternatively, frozen 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). Once vials are thawed, they should not be refrozen.
If cartons of COMIRNATY multiple dose vials with gray caps and labels with gray borders are received at 2°C
to 8°C, they should be stored at 2°C to 8°C. Check that the car ton has been updated to reflect the 10-week
refrigerated expiry date. Regardless of storage condition, the vaccine should not be used after the expiration date printed on the vial and
cartons.
Vial Storage During Use
If not previously thawed at 2ºC to 8ºC (35ºF to 46ºF), allow vials to thaw at room temperature [up to 25ºC
(77ºF)] for 30 minutes.
COMIRNATY multiple dose vials with gray caps and labels with gr ay borders may be stored at room
temperature [8°C to 25°C (46°F to 77°F)] for a total of 12 hour s prior to the first puncture. After first puncture,
the vial should be held between 2 ºC to 25°C (35 °F to 77°F). Vials should be discarded 12 hours after first
puncture.
DO NOT DILUTE PRIOR TO USE .
Transportation of Vials
If local redistribution is needed, vials may be transported at -90°C to -60°C (-130°F to -76°F), or at 2°C to 8°C
(35°F to 46°F).
17 PATIENT COUNSELING INFORMATION
Inform vaccine recipient of the potential benefits and risks of vaccination with COMIRNATY.
Inform vaccine recipient of the importance of completing the 2 dose vaccination series.
There is a pregnancy exposure registry for COMIRNATY. Encourage individuals exposed to COMIRNATY
around the time of conception or during pregnancy to register b y visiting https://mothertobaby.org/ongoing-
study/covid19-vaccines/ .
Advise vaccine recipient 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 .
Prior to administering the vaccine, give the vaccine recipient the Vaccine Information Fact Sheet for Recipients
and Caregivers about COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19
FDA-CBER-2022-5812-0236025
25 Vaccine to Prevent Coronavirus Disease 2019 (COVID-19) for Use in Individuals 12 Years of Age and Older.
The Vaccine Information Fact Sheet for Recipients and Caregiver s is available at www .cvdvaccine-us.com.
This product’s labeling may have been updated. For the most rec ent prescribing information, please visit
https://dailymed nlm.nih.gov/dailymed/.
Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12 55131 Mainz, Germany
Manufactured by
Pfizer Inc., New York, NY 10017
LAB-1490-1. 02
US Govt. License No. 2229
FDA-CBER-2022-5812-0236026