Document text
1 HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to u se
COMIRNATY safely and effectively. See full prescribing informat ion for
COMIRNATY.
COMIRNATY® (COVID-19 Vaccine, mRNA) suspension for injection,
for intramuscular use
Initial U.S. Approval: 2021
--------------------------- RECENT MAJOR CHANGES ---------------------------
Indications and Usage (1) M/YYYY Dosage and Administration, Preparation for Administration (2 1) 12/2021
--------------------------- INDICATIONS AND USAGE ------------ ----------------
COMIRNATY is a vaccine indicated for active immunization to prevent
coronavirus disease 2019 (COVID-19) caused by severe acute resp iratory
syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and
older (1)
----------------------- DOSAGE AND ADMINISTRATION ------------ -----------
• COMIRNATY supplied in multiple dose vials with purple caps and
labels with purple borders MUST BE DILUTED before use (2 1)
• For intramuscular injection only (2 2)
• COMIRNATY is administered intram uscularly as a series of 2 dose s
(0 3 mL each) 3 weeks apart (2 3)
--------------------- DOSAGE FORMS AND STRENGTHS ------------- ---------
Suspension for injection After preparation, a single dose is 0 3 mL (3)
------------------------------ CONTRAINDICATIONS ------------- -----------------
Known history of a severe allergic reaction (e g , anaphylaxis) to any
component of COMIRNATY (4)
----------------------- WARNINGS AND PRECAUTIONS ------------- ----------
• Postmarketing data demonstrate increased risks of myocarditis a nd
pericarditis, particularly within 7 days following the second d ose (5 2)
• 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)
------------------------------ ADVERSE REACTIONS ------------------------------
• In clinical studies of participants 16 through 55 years of age, the most
commonly reported adverse reactions (≥10%) were pain at the inj ection
site (88 6%), fatigue (70 1%), headache (64 9%), muscle pain (4 5 5%),
chills (41 5%), joint pain (27 5%), fever (17 8%), and injectio n site
swelling (10 6%) (6 1)
• In clinical studies of participants 56 years of age and older, the most
commonly reported adverse reactions (≥10%) were pain at the inj ection
site (78 2%), fatigue (56 9%), headache, (45 9%), muscle pain ( 32 5%),
chills (24 8%), joint pain (21 5%), injection site swelling (11 8%), fever
(11 5%), and injection site redness (10 4%) (6 1)
• In clinical studies of adolescents 12 through 15 years of age, the most
commonly reported adverse reactions (≥8%) were pain at the inje ction
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)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at
1-800-438-1985 or VAERS at 1-800-822-7967 or http://vaers.hhs.gov .
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 12/2021M/YYYY
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2 1 Preparation for Administration
2 2 Administration Information
2 3 Vaccination Schedule
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5 1 Management of Acute Allergic Reactions 5 2 Myocarditis and Pericarditis 5 3 Syncope
5 4 Altered Immunocompetence
5 5 Limitation of Effectiveness
6 ADVERSE REACTIONS
6 1 Clinical Trials Experience
6 2 Postmarketing Experience
8 USE IN SPECIFIC POPULATIONS
8 1 Pregnancy 8 2 Lactation
8 4 Pediatric Use 8 5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12 1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13 1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14 1 Efficacy in Participants 16 Years of Age and Older
14 2 Efficacy in Adolescents 12 Through 15 Years of Age
14 3 Immunogenicity in Adolescents 12 Through 15 Years of Age
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing inf ormation are not
listed
FDA-CBER-2022-5812-0235623
FDA-CBER-2022-5812-0235624
FDA-CBER-2022-5812-0235625
4 Dilution and Preparation Instructions
• Before dilution invert vaccine vial gently 10 times.
• Do not shake.
• Inspect the liquid in the vaccine vial prior to
dilution. The liquid is a white to off-white
suspension and may contain white to off-white
opaque amorphous particles.
• Do not use if liquid is discolored or if other particles
are observed.
COMIRNATY Vial with Purple Cap an d Label with Purple Border –
Dilution
• ONLY use sterile 0.9% Sodium Chloride Injection,
USP as the diluent.
• Withdraw 1.8 mL of diluent into a transfer syringe
(21-gauge or narrower needle).
• Add 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP into the vaccine vial.
Gently × 10
Add 1.8 mL of sterile 0.9% sodium
chloride injection, USP.
FDA-CBER-2022-5812-0235626
5 Dilution and Preparation Instructions
• Equalize vial pressure before removing the needle
from the vaccine vial by withdrawing 1.8 mL air into the empty diluent syringe.
• Gently invert the vial containing COMIRNATY
10 times to mix.
• Do not shake.
• Inspect the vaccine in the vial.
• The vaccine will be an off-w hite suspension. Do not
use if vaccine is discolored or contains particulate matter.
Pull back plunger to 1.8 mL to remove
air from vial.
Gently × 10
FDA-CBER-2022-5812-0235627
FDA-CBER-2022-5812-0235628
FDA-CBER-2022-5812-0235629
8 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 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
46,000 participants 12 years of age or older. Of these, approxi mately 44,047 participants
(22,026 COMIRNATY; 22,021 placebo) in Phase 2/3 are 16 years of age or older (including 378 and
376 participants 16 through 17 years of age in the COMIRNATY an d placebo groups, respectively) and
2,260 adolescents are 12 through 15 years of age (1,131 and 1,1 29 in the COMIRNATY and placebo groups,
respectively). Upon issuance of the Emergency Use Authorization for COMIRNATY, participants were
unblinded to offer placebo participants 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 participants 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 coun t >200 cells/mm
3 within 6 months before
enrollment, and on stable antiretroviral therapy for at least 6 months.
In Study 2, all participants 12 through 15 years of age, and 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 monitored for unsol icited adverse events, including serious adverse
events, throughout the study [from Dose 1 through 1 month (all unsolicited adverse events) or 6 months (serious
adverse events) after the last vaccination]. Tables 1 through 6 present the frequency and severity of solicited
local and systemic reactions, respectively, within 7 days follo wing each dose of COMIRNATY and placebo.
FDA-CBER-2022-5812-0235630
FDA-CBER-2022-5812-0235631
10 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
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) 1 6 (0.6) 2 54(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) 1 8 (0.6) 1 42(5.3) 14(0.5)
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 4 79 (16.5) 1 9 9 (6.8) 1 0 1 5 (37.8) 114(4.2)
Mild 338 (11.7) 148 (5.1) 477 (17.8) 89 (3.3)
Moderate 126 (4.3) 49 (1.7) 469 (17.5) 23 (0.9)
Severe 15 (0.5) 2 (0.1) 69 (2.6) 2 (0.1)
FDA-CBER-2022-5812-0235632
11 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Vomitingd
Any 34 (1.2) 36 (1.2) 58 (2.2) 30 (1.1)
Mild 29 (1.0) 30 (1.0) 42 (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 309 (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) 5 8 (2.0) 4 4(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) 96 (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 3 42 (11.8) 1 6 8 (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
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) 5 8(3.1) 3(0.2)
Severe 5 (0.2) 2 (0.1) 1 0(0.5) 1(0.1)
FDA-CBER-2022-5812-0235633
12 COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Swellingc
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 in jection 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
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) 267 (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)
FDA-CBER-2022-5812-0235634
13 COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Chillsc
Any 130 (6.5) 69 (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 2 74 (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) 7 8 (3.9) 183(9.8) 44(2.4)
Moderate 53 (2.6) 4 5 (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 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.
FDA-CBER-2022-5812-0235635
14 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, 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 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 group. Among part icipants with confirmed stable HIV infection
that included 100 COMIRNATY recipients and 100 placebo recipien ts, 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 amo ng COMIRNATY recipients compared to
placebo recipients was primarily attributed to events that are consistent with adverse reactions solicited among
participants in the reactogenicity subset (Table 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 Da ys 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
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
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20 dihydrate, and 6 mg sucrose. The diluent (sterile 0.9% Sodium Chloride Injection, USP) contributes an
additional 2.16 mg sodium chloride per dose.
COMIRNATY does not contain preservative.
The vial stoppers are not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The nucleoside-modified mRNA in COMIRNATY is formulated in lipi d particles, which enable delivery of the
mRNA into host cells to allow expression of the SARS-CoV-2 S an tigen. The vaccine elicits an immune
response to the S antigen, which protects against COVID-19.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
COMIRNATY has not been evaluated for the potential to cause car cinogenicity, genotoxicity, or impairment of
male fertility. In a developmental toxicity study in rats with COMIRNATY there were no vaccine-related
effects on female fertility [see Use in Specific Populations (8.1)] .
14 CLINICAL STUDIES
14.1 Efficacy in Participants 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 ye ars of age, or 56 years of age and older, with a
minimum of 40% of participants in the ≥56-year stratum. The stu dy excluded participants who were
immunocompromised and those who had previous clinical or microbiological diagnosis of COVID -19.
Participants with preexisting stable disease, defined as diseas e 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, appro ximately 44,000 participants 12 years of age
and older were randomized equally and received 2 doses of COMIR NATY or placebo. Participants are planned
to be followed for up to 24 months, for assessments of safety a nd efficacy against COVID-19.
Overall, among the total participants who received COMIRNATY or placebo, 51.4% or 50.3% were male and
48.6% or 49.7% were female, 79.1% or 79.2% were 16 through 64 y ears of age, 20.9% or 20.8% were 65 years
of age and older, 81.9% or 82.1% were White, 9.5% or 9.6% were Black or African American, 1.0% or 0.9%
were American Indian or Alaska Native, 4.4% or 4.3% were Asian, 0.3% or 0.2% Native Hawaiian or other
Pacific Islander, 25.6% or 25.4% were Hispanic/Latino, 73.9% or 74.1% were non-Hispanic/Latino, 0.5% or
0.5% did not report ethnicity, 46.0% or 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) ≥3 0 kg/m
2], respectively. The mean age at
vaccination was 49.8 or 49.7 years and median age was 51.0 or 5 1.0 in participants who received
COMIRNATY or placebo, respectively.
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22 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 8) as the COVID-19 case counts in p articipants without prior SARS-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.
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26 preferably store in an ultra-low temperature freezer between -9 0ºC to -60ºC (-130ºF to -76ºF) until the expiry
date printed on the label.
Alternatively, vials may be stored at -25°C to -15°C (-13°F to 5°F) for up to 2 weeks. Vials must be kept frozen
and protected from light, in the original cartons, until ready to use. Vials stored at -25°C to -15°C (-13°F to 5°F)
for up to 2 weeks may be returned 1 time to the recommended sto rage condition of -90ºC to -60ºC (-130ºF
to -76ºF). Total cumulative time the vials are stored at -25°C to -15°C (-13°F to 5°F) should be tracked and
should not exceed 2 weeks.
If an ultra-low temperature freezer is not available, the therm al container in which COMIRNATY arrives may
be used as temporary storage when consistently re-filled to the top of the container with dry ice. Refer to the
re-icing guidelines packed in the original thermal container fo r instructions regarding the use of the thermal
container for temporary storage. The thermal container maintain s a temperature range of -90ºC to -60ºC (-130ºF
to -76ºF). Storage of the vials between -96°C to -60°C (-141°F to -76°F) is not considered an excursion from
the recommended storage condition.
Transportation of Frozen Vials
If local redistribution is needed and full cartons containing v ials cannot be transported at -90°C to -60°C
(-130°F to -76°F), vials may be transported at -25°C to -15°C ( -13°F to 5°F). Any hours used for transport
at -25°C to -15°C (-13°F to 5°F) count against the 2-week limit for storage at -25°C to -15°C (-13°F to 5°F).
Frozen vials transported at -25°C to -15°C (-13°F to 5°F) may b e returned 1 time to the recommended storage
condition of -90ºC to -60ºC (-130ºF to -76ºF).
Thawed Vials Before Dilution
Thawed Under Refrigeration
Thaw and then store undiluted vials in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] for up to 1 month. A carton of
25 vials or 195 vials may take up to 2 or 3 hours, respectively , to thaw in the refrigerator, whereas a fewer
number of vials will thaw in less time.
Thawed at Room Temperature
For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for 30 minutes. Thawed vials
can be handled in room light conditions.
Vials must reach room temperature before dilution.
Undiluted vials may be stored at room temperature for no more than 2 hours.
Transportation of Thawed Vials
Available data support transportation of 1 or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 12 hours.
Vials After Dilution
After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within 6 hours from the time of dilution.
During storage, minimize exposure to room light, and avoid expo sure to direct sunlight and ultraviolet light.
Any vaccine remaining in vials must be discarded after 6 hours. Do not refreeze.
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