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)
12/2021M/YYYY
--------------------------- 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 REA CTIONS, 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-2022-5812-0235948
FDA-CBER-2022-5812-0235949
FDA-CBER-2022-5812-0235950
FDA-CBER-2022-5812-0235951
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-2022-5812-0235952
6 Dilution and Preparation Instructions
Record the date and time of
dilution.
Use within 6 hours after dilution.
• Record the date and time of dilution on the
COMIRNATY vial label.
• Store between 2°C to 25° C (35°F to 77°F).
• Discard any unused vaccine 6 hours after dilution.
COMIRNATY Multiple Dose Vial with Purple Cap and Lab el with Purple Border –
Preparation of Individual 0.3 mL Doses
Withdraw 0.3 mL dose of vaccine.
• Withdraw 0.3 mL of COM IRNATY preferentially
using low dead-volume syringes and/or needles.
• Each dose must contain 0.3 mL of vaccine.
• If the amount of vaccine remaining in a single vial
cannot provide a full dose of 0.3 mL, discard the vial
and any excess volume.
• Administer immediately.
2.2
Administration Information
Parenteral drug products should be inspected visually for parti culate matter and discoloration prior to
administration, whenever solution and container permit. The vac cine will be an off-white suspension. Do not
administer if vaccine is discolored or contains particulate mat ter.
Administer a single 0.3 mL dose of COMIRNATY intramuscularly.
After dilution, vials of COMIRNAT Y with purple caps and labels with purple borders contain 6 doses of
0.3 mL of vaccine. Low dead-volu me syringes and/or needles can be used to extract 6 doses from a single vial.
If standard syringes and needles are used, there may not be suf ficient 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.
FDA-CBER-2022-5812-0235953
7 • 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. After preparation, eac h dose of COMIRNATY supplied in vials
with purple caps and labels with purple 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. Informatio n is not yet available about potential long-
term sequelae. The CDC has published considerations related to myocarditis and pericarditis after vaccination,
including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/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.
FDA-CBER-2022-5812-0235954
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-2022-5812-0235955
9
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
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.
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
N
a=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) 5 0(1.9) 6(0.2)
Severe 7 (0.2) 3 (0.1) 11 (0.4) 0
Swellingc
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
FDA-CBER-2022-5812-0235956
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-2022-5812-0235957
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-2022-5812-0235958
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-2022-5812-0235959
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-2022-5812-0235960
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 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
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
FDA-CBER-2022-5812-0235961
15 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 (69.0%)
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
N
a=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Rednessc
Any (>2 cm ) 6 5 (5.8) 1 2 (1.1) 5 5 (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)
Severe 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Swellin gc
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) 1 8 (1.6) 2 (0.2)
Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
FDA-CBER-2022-5812-0235962
16 COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
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) 1 2 (1.1) 2 15 (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) 2 2 (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)
Vomitingd
Any 3 1 (2.8) 1 0 (0.9) 2 9 (2.6) 12 (1.1)
Mild 30 (2.7) 8 (0.7) 2 5 (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)
FDA-CBER-2022-5812-0235963
FDA-CBER-2022-5812-0235964
18 In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical
imbalances between treatment groups for specific categories of unsolicited adverse events (including other
neurologic or neuro-inflammatory, and thrombotic events) that w ould suggest a causal relationship to
COMIRNATY. In the analysis of unblinded follow-up, there were n o notable patterns of specific categories of
non-serious adverse events that would suggest a causal relation ship to COMIRNATY.
Serious Adverse Events
In Study 2, among participants 12 through 15 years of age who h ad received at least 1 dose of vaccine or
placebo (COMIRNATY = 1,131; placebo = 1,129), serious adverse e vents from Dose 1 up to the participant
unblinding date in ongoing follow-up were reported by 10 (0.9%) COMIRNATY recipients and 2 (0.2%)
placebo recipients. In these analyses, 69.0% of study participants had at least 4 months of follow-up after
Dose 2. In the analysis of blinded, placebo-controlled follow-u p, there were no notable patterns between
treatment groups for specific categories of serious adverse eve nts (including neurologic, neuro-inflammatory,
and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded
follow-up, there were no notable patterns of specific categorie s of serious adverse events that would suggest a
causal relationship to COMIRNATY.
6.2 Postmarketing Experience
The following adverse reactions have been identified during pos tmarketing use of COMIRNATY, including
under Emergency Use Authorization. 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 extrem ity (arm)
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to COMIRNATY
during pregnancy. Women who are vaccinated with COMIRNATY durin g pregnancy are encouraged to enroll
in the registry by visiting https://mothertobaby.org/ongoing-study/covid19-vaccines/ .
Risk Summary
All pregnancies have a risk of birth defect, loss, or other adv erse outcomes. In the US general population, the
estimated background risk of major birth defects and miscarriag e in clinically recognized pregnancies is 2% to
4% and 15% to 20%, respectively. Available data on COMIRNATY ad ministered to pregnant women are
insufficient to inform vaccine-associated risks in pregnancy.
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 a nd twice during gestation. These studies
revealed no evidence of harm to the fetus due to the vaccine (see Animal Data) .
FDA-CBER-2022-5812-0235965
19 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 12 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 12 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 purple caps and labels with purple
borders; each vial must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to
form the vaccine. Each 0.3 mL dose of COMIRNATY supplied in mul tiple dose vials with purple caps and
labels with purple borders contains 30 mcg of a nucleoside-modi fied 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 purple caps and labels with purple
borders also includes the following ingredients:
lipids (0.43 mg ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate),
0.05 mg 2-(polyethylene glycol 2000)-N,N-ditetradecylacetamide,
0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg cholesterol), 0.01 mg potassium chloride,
0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 0.07 mg dibasic sodium phosphate
FDA-CBER-2022-5812-0235966
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.
FDA-CBER-2022-5812-0235967
21
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 f or 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 ve rsus
placebo recipients did not suggest decreased vaccine effectiven ess against these variants.
The updated vaccine efficacy information is presented in Table 7.
Table 7: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After 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-2022-5812-0235968
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.
FDA-CBER-2022-5812-0235969
23 Table 8: 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 indicativ e 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-2022-5812-0235970
24 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 through 15 years of age 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 adolescen ts 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 throu
gh 15 years of a ge 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 The only
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-2022-5812-0235971
25 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 1253.6
(1117.7, 1406.1) 708.1
(625.9, 801.1)1.77
(1.50, 2.09) Y
Abbreviations: CI = confidence in terval; GMR = geometric mean r atio; GMT = geometric mean titer; LLOQ = lower limit of
quantitation; NAAT = n ucleic-acid amplification test; NT50 = 50% neutralizing titer; S ARS-CoV-2 = severe acute respi ratory
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 purple caps and labels with
purple borders are supplied in a carton containing 25 multiple dose vials (NDC 0069-1000-03) or 195 multiple
dose vials (NDC 0069-1000-02). A 0.9% Sodium Chloride Injection , USP diluent is provided but shipped
separately, and should be stored at controlled room temperature 20°C to 25°C (68°F to 77°F) [see USP
Controlled Room Temperature]. The provided 0.9% Sodium Chloride Injection, USP diluent will be supplied
either as cartons of 10 mL single-use vials manufactured by Hospira, Inc (NDC 0409-4888-10), or 2 mL single-use vials manufactured by Fresenius Kabi USA, LLC (NDC 63323-18 6-02).
After dilution, 1 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.
Frozen Vials Prior to Use
Cartons of COMIRNATY multiple dose vials with purple caps and labels with purple borders arrive in thermal
containers with dry ice. Once received, remove the vial cartons immediately from the thermal container and
FDA-CBER-2022-5812-0235972
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.
FDA-CBER-2022-5812-0235973
27
17 PATIENT COUNSELING INFORMATION
Inform vaccine recipient of th e 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
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-1448-2. 210
US Govt. License No. 2229
FDA-CBER-2022-5812-0235974