Document text
1HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
COMI RNATY safely and effectively. See full prescribing information 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) M/YYYY
--------------------------- INDICATIONS AND USAGE ----------------------------
COMI RNATY is a vaccine indicated for active immunization to prevent
coronavirus disease 2019 (COVI D-19) caused by severe acute respiratory
syndrome coronavirus 2 (SARS -CoV -2) in individuals 12years of age and
older. (1)
----------------------- DOSAGE AND ADMINISTRATION -----------------------
COMI RNATY supplied in multiple dose vials with gray caps and labels
with gray borders MUST NOT be diluted prior to use .(2.1)
For intramuscular injection only. (2.2)
COMI RNATY is administered intramuscularly as a series of 2doses
(0.3mLeach) 3 weeks apart. (2.3)
--------------------- DOSAGE FORMS AND STRENGTHS ----------------------
Suspension for injection. Asingle dose is 0.3 mL.(3)
------------------------------ CONTRAINDICATIONS ------------------------------
Known history of a severe allergic reaction (e.g., anaphylaxis) to any
component of COMI RNATY .(4)----------------------- WARNINGS AND PRECAUTIONS -----------------------
Postmarketing data demonstrate increased risks of myocarditis and
pericarditis, particularly within 7 days following the second dose. (5. 2)
Syncope (fainting) may occur in association with administration of
injectable vaccines, including COMIR NATY . 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 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%). (6.1)
In clinical studies of participants 56 years of age and older, the most
commonly reported adverse reaction s (≥10%) 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 site swelling (11.8%), fever
(11.5%), and injection site redness (10.4%). (6.1 )
In clinical studies of adolescents 12through 15years of age, the most
commonly reported adverse reactions (≥8%)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)
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: M/YYYY
FULL PRESCRIBING INFORMATION: CONTENTS *
1INDICATIONS AND USAGE
2DOSAGE AND ADMINISTRATION
2.1 Preparation for Administration
2.2 Administration I nformation
2.3 Vaccination Schedule
3DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS
5WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
5.2 Myocarditis and Pericarditis
5.3 Syncope
5.4 Altered I mmunocompetence
5.5 Limitation of Effectiveness
6ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
8USE IN SPECIFIC POPULATIONS
8.1 Pregnancy8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11DESCRIPTION
12CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, I mpairment of Fertility
14CLINICAL 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
16HOW SUPPLIED/STORAGE AND HANDLING
17PATIENT COUNSELING INFORMATION
* Sections or subsectio ns omitted from the full prescri bing information are not
listed.
FDA-CBER-2022-5812-0236027
FDA-CBER-2022-5812-0236028
FDA-CBER-2022-5812-0236029
FDA-CBER-2022-5812-0236030
5Vials of COMI RNATY with gray caps and labels with gray borders contain 6doses of 0.3 mL of vaccine. Low
dead -volume s yringes and/or needl es can be used to extract 6doses from a single vial. If standard s yringes and
needles are used, there may not be sufficient volume to extract 6 doses from a single vial. Irrespective of the
type of s yringe and needle ,
each dose must contain 0.3 mL of vaccine.
if the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL,discard the vial and
any excess volume.
do not pool excess vaccine from multiple vials.
2.3 Vaccination Schedule
COMI RNATY is administered intramuscularly as a series of 2doses (0.3 mL each) 3 weeks apart.
There are no data available on the interchangeability of COM IRNATY with COVID -19 vaccines from other
manufacturers to complete the vaccination series. Individuals who have received 1dose of COMIRNATY should
receive a second dose of COMI RNATY to complete the vaccination series.
3 DOSAGE FORMS AND STRENGTHS
COMI RNATY is a suspension for injection. Each dose of COMI RNATY supplied in vials with gray caps and
labels with gray borders is 0.3 mL.
4CONTRAINDICATIONS
Do not administer COMIRNATY to individuals with known history of a severe allergic reaction (e.g.,
anaph ylaxis) to any component of the COMIRNATY [see Description (1 1)].
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic React ions
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in
the event an acute anaphy lactic reaction occurs following administration of COMI RNATY .
5.2 Myocarditis and Pericarditis
Postmarketing data demonstrate increased risks of my ocarditis and pericarditis, particularly within 7 day s
following the second dose. The observed risk is highe ramong males under 40 years of age than among females
and older males. The observed risk is hig hest in males 12 through 17 years of age . Although some cases
required intensive care support, a vailable data from short -term follow -up suggest that most individuals have had
resolution of sy mptoms with conservative management. I nformation is not y et available about potential long -
term sequelae. The CDC has published considerations related to m yocarditis and pericarditis after vaccination,
including for vaccination of individuals with a history ofmyocarditis orpericarditis
(https://www.cdc.gov/vaccines/covid- 19/clinical -considerations/my ocarditis.html).
5.3 Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines, including
COMI RNATY . Procedures should be in place to avoid injury from fainting.
FDA-CBER-2022-5812-0236031
65.4 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressant therap y, ma y have a
diminished immune response to the COMI RNATY .
5.5 Limitation of Effectiveness
COMI RNATY may not protect all vaccine recipients.
6 ADVERSE REACTIONS
In clinical studies, the most commonly reported ( ≥10%) adverse reactions in participants 16 through 55 y ears of
age following an y dose were pain at the injection site ( 88.6%), fatigue (70.1%), headache (64.9%), muscle pain
(45.5%), chills (41.5%), joint pa in (27.5%), fever (17.8%), and injection site swelling (10.6%) .
In clinical studies, t he most commonly reported ( ≥10%) adverse reactions in participants 56 y ears of age and
older following an y 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 site swelling (11.8%), fever (11.5%), and injection
site redness (10.4%) .
In a clinical study , the most commonly reported ( ≥8%) adverse reactions in adolescents 12 through 15 years of
agefollowing an y 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
siteredness (8.6%) .
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely vary ing conditions, adverse reaction rates observed in the
clinical trials of a vaccine cannot be directl y compared to rates in the clinical trials of anot her vaccine and may
not reflect the rates observed in practice.
The safet y of COMI RNATY was evaluated in participants 12 years of age and older in 2clinical studies
conducted in German y (Study 1), United States, Argentina, Brazil , Turkey, South Africa, and Germany
(Study 2). Study BNT162 -01 (Study 1) was a Phase 1/2, 2-part, dose -escalation trial that enrolled
60participants, 18 through 55 years of age and 36 participants, 5 6through 85 y ears of age .Study C4591001
(Study 2) is a Phase 1/2/3 multicenter, multinational, randomized, saline placebo- controlled, double -blind ed
(Phase 2/3) , dose -finding, vaccine candidate -selection and efficacy study that has enrolled approximately
46,000 participants 12years of age or older .Of these, approximately 44,047 participants
(22,026 COMI RNATY; 22,021 placebo) in Phase 2/3 are 16 years of age or older (including 378 and
376participants 16through 17 years of age in the COMI RNATY and placebo groups, respectively )and
2,260 adolescents are 12 t hrough 15years of age (1 ,131 and 1,129 in the COMI RNATY and placebo groups,
respectivel y).Upon issuance of the Emergency Use Authorization for COMIRNATY , participants were
unblinded to offer placebo participants COMI RNATY . Participants were unblinded in a phased manner over a
period of months to offer placebo participants COMI RNATY . Study 2 also included 200 participants with
confirmed stable human immunodeficiency virus (HIV) infection; HI V-positive participants are included in
safet y population disposition but are summarized separately in safet y anal yses. Confirmed stable HIV infection
was defined as documented viral load <50 copies/mL and CD4 count >200 cells/mm3within 6 months before
enrollment, and on stable antiretroviral therap y for at least 6 months.
FDA-CBER-2022-5812-0236032
7In Stud y 2, all participants 12 through 15 years of age, and 16 y ears and older in the reactogenicit y subset were
monitored for solicited local and s ystemic reactions and use of antipy retic medication after each vaccination in
an electronic diary . Participants are being monitored for unsolicited adverse events, including serious adverse
events, throughout th e study [from Dose 1 through 1 month (all unsolicited adverse events) or 6 months (serious
adverse events) after the last vaccination]. Table s1 through 6 present the frequency and severity of solicited
local and s ystemic reactions, respectivel y, within 7 days following each dose of COMI RNATY and placebo .
Participants 16 Years of Age and Older
At the time of the anal ysis of the ongoing Study 2 with a data cutoff of March 13, 2021, there were
25,651 (58.2%) participants (13,031 COMI RNATY and 12,620 placebo) 16 years of age and older followed for
≥4 months after the second dose .
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity
among participants who received COM IRNATY and those who received placebo. Overall, among the total
participants who received either COMIRNATY or placebo , 50.9% were male ,49.1% were female, 79.3% were
16 through 64 years of age, 20.7 % were 65 years of age and older , 82.0 %were White, 9.6% were Black or
African American, 25.9% were Hispanic/Latino, 4.3% were Asian, and 1.0% were American Indian or Alaska
Native.
Local and S ystemic 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 day s (range 1 to 70 days), for redness 2.2 day s (range 1 to 9 day s), and for swelling 2.1 day s (range 1 to
8days) for participants in the COMI RNATY group. I n participants 56 years of age and older after receiving
Dose 2, the mean duration of pain at the injection site was 2.4 day s (range 1 to 36 days), for redness 3.0 days
(range 1 to 34 day s), and for swelling 2.6 day s (range 1 to 34 day s) for participants in t he COMI RNATY group.
Table 1: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of
Age –Reactogenicity Subset of the Safety Populatio n*
COMIRNATY
Dose 1
Na=2899
nb(%)Placebo
Dose 1
Na=2908
nb(%)COMIRNATY
Dose 2
Na=2682
nb(%)Placebo
Dose 2
Na=2684
nb(%)
Rednessc
Any (>2.0 cm) 156(5.4) 28(1.0) 151(5.6) 18(0.7)
Mild 113(3.9) 19(0.7) 90(3.4) 12(0.4)
Moderate 36(1.2) 6(0.2) 50(1.9) 6(0.2)
Severe 7(0.2) 3(0.1) 11(0.4) 0
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-2022-5812-0236033
8COMIRNATY
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 -diary) from Day 1 to Day 7 after vaccination.
No Grade 4 solicited local reactions were reported in participants 16 through 55 years of age.
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with
chronic, stable HIV infection were excluded.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The 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 activity; M oderate: interfer es with activity; Severe: prevents daily activity.
Table 2: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of
Age – Reactogenic ity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2899
nb(%)Placebo
Dose 1
Na=2908
nb(%)COMIRNATY
Dose 2
Na=2682
nb(%)Placebo
Dose 2
Na=2684
nb(%)
Fever
≥38.0℃ 119(4.1) 25(0.9) 440(16.4) 11(0.4)
≥38.0℃ to 38.4℃ 86(3.0) 16(0.6) 254(9.5) 5(0.2)
>38.4℃ to 38.9℃ 25(0.9) 5(0.2) 146(5.4) 4(0.1)
>38.9℃ to 40.0℃ 8(0.3) 4(0.1) 39(1.5) 2(0.1)
>40.0 ℃ 0 0 1(0.0) 0
Fatiguec
Any 1431 (49.4) 960(33.0) 1649 (61.5) 614(22.9)
Mild 760(26.2) 570(19.6) 558(20.8) 317(11.8)
Moderate 630(21.7) 372(12.8) 949(35.4) 283(10.5)
Severe 41(1.4) 18(0.6) 142(5.3) 14(0.5)
Headachec
Any 1262 (43.5) 975(33.5) 1448 (54.0) 652(24.3)
Mild 785(27.1) 633(21.8) 699(26.1) 404(15.1)
Moderate 444(15.3) 318(10.9) 658(24.5) 230(8.6)
Severe 33(1.1) 24(0.8) 91(3.4) 18(0.7)
Chillsc
Any 479(16.5) 199(6.8) 1015 (37.8) 114(4.2)
Mild 338(11.7) 148(5.1) 477(17.8) 89(3.3)
Moderate 126(4.3) 49(1.7) 469(17.5) 23(0.9)
Severe 15(0.5) 2(0.1) 69(2.6) 2(0.1)
FDA-CBER-2022-5812-0236034
9COMIRNATY
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) 58(2.0) 44(1.6) 35(1.3)
Severe 3(0.1) 1(0.0) 6(0.2) 1(0.0)
New or worsened muscle painc
Any 664(22.9) 329(11.3) 1055 (39.3) 237(8.8)
Mild 353(12.2) 231(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 342(11.8) 168(5.8) 638(23.8) 147(5.5)
Mild 200(6.9) 112(3.9) 291(10.9) 82(3.1)
Moderate 137(4.7) 55(1.9) 320(11.9) 61(2.3)
Severe 5(0.2) 1(0.0) 27(1.0) 4(0.1)
Use of antip yretic or
pain medicationf805(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 participants 16 through 55 years of age.
*Randomized participants in the safety analysis population who receive d at least 1 dose of the study intervention. Participants with
chronic, stable HIV infection were excluded.
a.N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each
reaction o r 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 activity; M oderate: some interference with activity; Severe: prevents daily activity.
d.Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e.Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; S evere: 6 or more loose stools in 24 hours.
f.Severity was not collected for use of antipyretic or pain medication.
Table 3: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, b y
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 (>2.0cm) 106(5.3) 20(1.0) 133(7.2) 14(0.8)
Mild 71(3.5) 13(0.7) 65(3.5) 10(0.5)
Moderate 30(1.5) 5(0.3) 58(3.1) 3(0.2)
Severe 5(0.2) 2(0.1) 10(0.5) 1(0.1)
FDA-CBER-2022-5812-0236035
10COMIRNATY
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 (>2.0cm) 141(7.0) 23(1.2) 145(7.8) 13(0.7)
Mild 87(4.3) 11(0.6) 80(4.3) 5(0.3)
Moderate 52(2.6) 12(0.6) 61(3.3) 7(0.4)
Severe 2(0.1) 0 4(0.2) 1(0.1)
Pain at the injection sited
Any (>2.0cm) 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) 347(18.7) 5(0.3)
Severe 4(0.2) 0 10(0.5) 0
Notes : Reactions were collected in the electronic diary (e -diary) from Day 1 to Day 7 after vaccination.
No Grade 4 solicited local reactions were reported in participants 56 years of age and older.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. P articipants with
chronic, stable HIV infection were excluded.
a.N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each
reaction w as 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; M oderate: interferes with activity; Severe: prevents daily activity.
Table 4: Study 2 – Frequency and Percentages of Participant s with 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-2022-5812-0236036
11COMIRNATY
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
Vomitingd
Any 10(0.5) 9(0.5) 13(0.7) 5(0.3)
Mild 9(0.4) 9(0.5) 10(0.5) 5(0.3)
Moderate 1(0.0) 0 1(0.1) 0
Severe 0 0 2(0.1) 0
Diarrheae
Any 168(8.4) 130(6.5) 152(8.2) 102(5.6)
Mild 137(6.8) 109(5.5) 125(6.7) 76(4.1)
Moderate 27(1.3) 20(1.0) 25(1.3) 22(1.2)
Severe 4(0.2) 1(0.1) 2(0.1) 4(0.2)
New or worsened muscle painc
Any 274(13.6) 165(8.3) 537(28.9) 99(5.4)
Mild 183(9.1) 111(5.6) 229(12.3) 65(3.5)
Moderate 90(4.5) 51(2.6) 288(15.5) 33(1.8)
Severe 1(0.0) 3(0.2) 20(1.1) 1(0.1)
New or worsened joint painc
Any 175(8.7) 124(6.2) 353(19.0) 72(3.9)
Mild 119(5.9) 78(3.9) 183(9.8) 44(2.4)
Moderate 53(2.6) 45(2.3) 161(8.7) 27(1.5)
Severe 3(0.1) 1(0.1) 9(0.5) 1(0.1)
Use of antip yretic or
pain medicationf382(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 systemic reaction reported in participants 56 years of age and older w as fatigue.
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. P articipants with
chronic, stable HIV infection were excluded.
a.N = Number of participants reporting at least 1 yes or no response for the s pecified reaction after the specified dose. N for each
reaction or use of antipyretic or pain medication was the same, therefore w as included in the column header.
b.n = Number of participants with the specified reaction.
c.Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity ;Grade 4 reactions
were defined in the clinical study protocol as emergency room visit or hospitalization for severe fatigue, severe headache, s evere
chills, severe muscl e pain, or severe joint pain.
d.Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; S evere: requires intravenous hydration ; Grade 4 emergency visit or
hospitalization for severe vomiting .
e.Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours ; Grade 4:
emergency room or hospitalization for severe diarrhea.
f.Severity was not collected for use of antipyretic or pain medication.
In participants with chronic, stable HIV infection the frequencies of solicited local and s ystemic adverse
reactions were similar to or lower than those observed for all participants 16 years of age and older .
FDA-CBER-2022-5812-0236037
12Unsolicited 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 ≥6months of
blinded follow -up time in the COMI RNATY and placebo groups, respectively .
A total of 12,006 (54.5%) participants originall y randomized to COMIRNATY had ≥6 months total (blinded
and unblinded) follow -up after Dose 2.
In an anal ysis of all unsolicited adverse events reported following an y dose, through 1 month after Dose 2 ,in
participants 16 years of age an dolder (N=43,847; 21,926 COMI RNATY group vs. 21,921 placebo group) ,
those assessed as adverse reactions not alrea dy captured by solicited local and sy stemic reactions were nausea
(274 vs. 87), malaise ( 130vs. 22), lymphadenopathy (83 vs. 7) ,asthenia ( 76vs. 25), decreased appetite
(39vs.9), hyperhidrosis (31vs. 9), lethargy (25vs. 6), and night sweats ( 17vs. 3).
In anal yses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date ,
58.2% of study participants had at least 4 months of follow -up after Dose 2. Among participants 16 through
55years of age who received at least 1dose of study vaccine, 12,995 of whom received COM IRNATY and
13,026 of whom received placebo , unsolicited adverse events were reported by 4,396 (33.8%) participants in
the COMI RNATY group and 2,136 (16.4%) participants in the place bo group. I n a similar anal ysis 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
COMI RNATY group and 1,432 (16.1%) participants in the placebo group. Among participants with confirmed
stable HIV infection that included 100 COMI RNATY recipients and 100 placebo recipients , unsolicited adverse
events were reported b y 29 (29%) participants in the COMI RNATY group and 15 (15%) participants in the
placebo group. The higher frequency of reported unsolicited adverse events among COMIRNATY recipients
compared to placebo recipients was primaril y attributed to events that are consistent with adverse reactions
solicited amon g participants in the reactogenicity subset (Table 3 and Table 4).
Throughout the placebo -controlled safet y follow -up period, Bell’s palsy (facial paral ysis) was reported by
4participants in the COMI RNATY group and 2 participants in the placebo group. Onset of facial paral ysis was
Day 37 after Dose 1 (participant did not receive Dose 2) and Day s 3, 9, and 48 after Dose 2. In the placebo
group the onset of facial paral ysis was Day 32 and Day 102. Currentl y available information is insufficient to
determine a causal relationship with the vaccine. In the anal ysis of blinded, placebo -controlled follow -up, t here
were no other notable patterns or numerical imbalances between treatment groups for specific categori es of
non-serious adverse events (including other neurologic or neuro- inflammatory , and thrombotic events) that
would suggest a causal relationship to COMI RNATY .In the analysis of unblinded follow -up, there were no
notable patterns of specific categories of non- serious adverse events that would suggest a causal relationship to
COMI RNATY.
Serious Adverse Events
In Stud y 2, among participants 16 through 55 years of age who had 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 reporte d by 103 (0.8%) COMIRNATY recipients and 117 (0.9%)
placebo recipients. In a similar anal ysis, in participants 56 years of age and older ( COMIRNATY = 8,931;
placebo = 8,895), serious adverse events were reported by 165 (1.8%) COMI RNATY recipients and 151 (1.7%)
placebo recipients who received at least 1 dose of COMI RNATY or placebo, respectivel y. In these anal yses,
58.2% of study participant s had at least 4 months of follow -up after Dose 2. Among participants with confirmed
FDA-CBER-2022-5812-0236038
13stable 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 anal ysis of blinded, placebo -controlled follow -up, t here were no notable patterns between treatment
groups for specific categories of serious adverse events (including neurologic, neuro -inflammatory , and
thrombotic events) that would suggest a causal relationship to COMI RNATY. In the analysis of unblinded
follow -up, there were no notable patterns of specific categories of serious adverse events that would suggest a
causal relationship to COMI RNATY.
Adolescents 12 Through 15 Years of Age
In Stud y 2, 2,260 adolescents (1,131 COMI RNATY; 1,129 placebo) were 12 through 15 years of age . At the
time of the anal ysis 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 with regard to age, gender, race, and ethnicity
among adolescents who received COM IRNATY and those who received placebo . Overall, among the
adolescents who received COMI RNATY ,50.1% were male and 49.9% were female, 85.8% were White , 4.6%
were Black or African American, 11.7% were Hispanic/Latino, 6.4% were Asian , and 0.4% were American
Indian /Alaska N ative.
Local and Systemic Adverse Reactions Solicited in Study 2
In adolescents 12 through 15 y ears of age after receiving Dose 2, the mean duration of pain at the injection site
was 2.5days (range 1 to 11 days), for redness 1.8 days (range 1 to 5 day s), and for swelling 1.6 days (range 1 to
5days) in the COMI RNATY group.
Table 5: Study 2 – Frequency and Percentages of Adolescents With Solicited Local Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Adolescents 12 Through 15 Years of
Age –Safety Population*
COMIRNATY
Dose 1
Na=1127
nb(%)Placebo
Dose 1
Na=1127
nb(%)COMIRNATY
Dose 2
Na=1097
nb(%)Placebo
Dose 2
Na=1078
nb(%)
Rednessc
Any (>2cm) 65 (5.8) 12 (1.1) 55 (5.0) 10 (0.9)
Mild 44 (3.9) 11 (1.0) 29 (2.6) 8 (0.7)
Moderate 20 (1.8) 1 (0.1) 26 (2.4) 2 (0.2)
Severe 1 (0.1) 0(0.0) 0(0.0) 0(0.0)
Swellingc
Any (>2cm) 78 (6.9) 11 (1.0) 54 (4.9) 6 (0.6)
Mild 55 (4.9) 9 (0.8) 36 (3.3) 4 (0.4)
Moderate 23 (2.0) 2 (0.2) 18 (1.6) 2 (0.2)
Severe 0(0.0) 0(0.0) 0(0.0) 0(0.0)
Pain at the injection sited
Any 971 (86.2) 263 (23.3) 866 (78.9) 193 (17.9)
Mild 467 (41.4) 227 (20.1) 466 (42.5) 164 (15.2)
Moderate 493 (43.7) 36 (3.2) 393 (35.8) 29 (2.7)
Severe 11 (1.0) 0(0.0) 7 (0.6) 0(0.0)
Note: Reactions were collected in the electronic diary (e -diary) from Day 1 to Day 7 after vaccination.
FDA-CBER-2022-5812-0236039
14*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 response 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 activity; Moderate: interferes with activity; Severe: prevents daily activity.
Table 6: Stud y 2 –Frequency and Percentages of Adolescents with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Adolescent s 12 Through 15 Years of
Age –Safety Population*
COMIRNATY
Dose 1
Na=1127
nb(%)Placebo
Dose 1
Na=1127
nb(%)COMIRNATY
Dose 2
Na=1097
nb(%)Placebo
Dose 2
Na=1078
nb(%)
Fever
≥38.0℃ 114 (10.1) 12 (1.1) 215 (19.6) 7 (0.6)
≥38.0℃ to 38.4℃ 74 (6.6) 8 (0.7) 107 (9.8) 5 (0.5)
>38.4℃ to 38.9℃ 29 (2.6) 2 (0.2) 83 (7.6) 1 (0.1)
>38.9℃ to 40.0℃ 10 (0.9) 2 (0.2) 25 (2.3) 1 (0.1)
>40.0 ℃ 1 (0.1) 0(0.0) 0(0.0) 0(0.0)
Fatiguec
Any 677 (60.1) 457 (40.6) 726 (66.2) 264 (24.5)
Mild 278 (24.7) 250 (22.2) 232 (21.1) 133 (12.3)
Moderate 384 (34.1) 199 (17.7) 468 (42.7) 127 (11.8)
Severe 15 (1.3) 8 (0.7) 26 (2.4) 4 (0.4)
Headachec
Any 623 (55.3) 396 (35.1) 708 (64.5) 264(24.5)
Mild 361 (32.0) 256 (22.7) 302 (27.5) 170(15.8)
Moderate 251 (22.3) 131 (11.6) 384 (35.0) 93 (8.6)
Severe 11 (1.0) 9 (0.8) 22 (2.0) 1 (0.1)
Chillsc
Any 311 (27.6) 109 (9.7) 455 (41.5) 74(6.9)
Mild 195 (17.3) 82 (7.3) 221 (20.1) 53(4.9)
Moderate 111 (9.8) 25 (2.2) 214 (19.5) 21 (1.9)
Severe 5 (0.4) 2 (0.2) 20 (1.8) 0(0.0)
Vomitingd
Any 31 (2.8) 10 (0.9) 29 (2.6) 12 (1.1)
Mild 30 (2.7) 8 (0.7) 25 (2.3) 11(1.0)
Moderate 0(0.0) 2 (0.2) 4 (0.4) 1 (0.1)
Severe 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Diarrheae
Any 90 (8.0) 82 (7.3) 65 (5.9) 44(4.1)
Mild 77 (6.8) 72 (6.4) 59 (5.4) 39(3.6)
Moderate 13 (1.2) 10 (0.9) 6 (0.5) 5 (0.5)
Severe 0 (0.0) 0 (0.0) 0(0.0) 0 (0.0)
New or worsened muscle painc
Any 272 (24.1) 148 (13.1) 355 (32.4) 90 (8.3)
Mild 125 (11.1) 88 (7.8) 152 (13.9) 51 (4.7)
Moderate 145 (12.9) 60 (5.3) 197 (18.0) 37 (3.4)
Severe 2 (0.2) 0(0.0) 6 (0.5) 2 (0.2)
FDA-CBER-2022-5812-0236040
15COMIRNATY
Dose 1
Na=1127
nb(%)Placebo
Dose 1
Na=1127
nb(%)COMIRNATY
Dose 2
Na=1097
nb(%)Placebo
Dose 2
Na=1078
nb(%)
New or worsened joint painc
Any 109 (9.7) 77 (6.8) 173 (15.8) 51 (4.7)
Mild 66 (5.9) 50 (4.4) 91 (8.3) 30 (2.8)
Moderate 42 (3.7) 27 (2.4) 78 (7.1) 21 (1.9)
Severe 1 (0.1) 0(0.0) 4 (0.4) 0(0.0)
Use of antip yretic or
pain medicationf413 (36.6) 111(9.8) 557 (50.8) 95(8.8)
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after each
dose.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
a.N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose.
b.n = Number of participants with the specified reaction.
c.Mild: does not interfere with activity; M oderate: some interference with activity; Severe: prevents daily activity.
d.Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e.Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; S evere: 6 or more loose stools in 24 hours.
f.Severity was not collected for use of antipyretic or pain medication.
Unsolicited Adverse Events
In Stud y 2, 2,260 adolescents (1,131 COMI RNATY; 1,129 placebo) were 12 through 15 years of age. Of these,
634 (56.1%) participants in the COMI RNATY group and 629 (55.7%) participants in the placebo group had
follow -up time between ≥4 months to <6 months after Dose 2 in the blinded placebo -controlled fol low-up
period with an additional 152 (13.4%) and 144 (12.8%) with ≥6months of blinded follow -up time in the
COMI RNATY and placebo groups, respectively .
A total of 1,113 (98.4%) participants 12 through 15 y ears of age originall y randomized to COMI RNATY had
≥6 months total (blinded and unblinded) follow -up after Dose 2.
An anal ysis of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date was
conducted. Among participants 12 through 15 years of age who received at least one dose of study vaccine,
unsolicited adverse events were reported b y 95 (8.4%) participants in the COMI RNATY group and
113(10.0%) participants in the placebo group.
In an anal ysis of all unsolicited adverse events reported during blinded follow -up from Dose 1 through 1 month
after Dose 2, in adolescents 12 to 15 years of age, those assessed as adverse reactions not alread y captured by
solicited local and s ystemic reactions were ly mphadenopathy (9 vs. 2) ,and nausea (5 vs. 2).
In the anal ysis of blinded, placebo -controlled follow -up, there were no other notable patterns or numerical
imbalances between treatment groups for specific categories of unsolicited adverse events (including other
neurologic or neuro -inflammatory , and thrombotic events) that would suggest a causal relationship to
COMI RNATY. In the analysis of unblinded follow -up, there were no notable patterns of specific categories of
non-serious adverse events that would suggest a causal relationship to COMI RNATY.
Serious Adverse Events
In Stud y 2, among participants 12 through 15 years of age who had received at least 1 dose of vaccine or
placebo ( COMIRNATY =1,131; placebo =1,129), serious adverse events from Dose 1 up to the participant
unblinding date in ongoing follow -up were report ed by 10 (0.9%) COMIRNATY recipients and 2 (0.2%)
placebo recipients. In these anal yses, 69.0% of study participants had at least 4months of follow -up after
FDA-CBER-2022-5812-0236041
16Dose 2. In the anal ysis of blinded, placebo -controlled follow -up, there were no notable patterns b etween
treatment groups for specific categories of serious adverse events (including neurologic, neuro -inflammatory ,
and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the anal ysis of unblinded
follow -up, there were no notable patterns of specific categories of serious adverse events that would suggest a
causal relationship to COMI RNATY.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post marketing use of COMI RNATY , including
under Emergency Use Authorization . Because these reactions are reported voluntarily from a population of
uncertain size, it is not alway s possible to reliabl y estimate their frequency or establish a causal relationship to
vaccine exposure.
Cardiac Disorders: my ocarditis, pericarditis
Gastrointestinal Disorders: diarrhea, vomiting
Immune Sy stem Disorders: severe allergic reactions, including anaphy laxis, and other hy persensitivity reactions
(e.g., rash, pruritus, urticaria, angioedema)
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
8USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to COMI RNATY
during pregnancy . Women who are vaccinated with COMI RNATY during 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 adverse outcomes. In the US general population, the
estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to
4% and 15% to 20%, respectivel y. Available data on COMI RNATY administered to pregnant women are
insufficient to inform vaccine -associated risks in pregnancy .
A developmental toxicity stud y has been performed in female rats administered the equivalent of a single
human dose of COMIRNATY on 4occasions, twice prior to mating and twice during gestation. These studies
revealed no evidence of harm to the fetus due to the vaccine (seeAnimal Data ).
Data
Animal Data
In a developmental toxicity study , 0.06 mL of a vaccine formulation containing the same quantity of
nucleoside -modified messenger ribonucleic acid (mRNA) (30 mcg) and other ingredients included in a single
human dose of COMIRNATY was administered to female rats by the intramuscular route on 4occasions: 21
and 14 day s prio r to mating, and on gestation day s 9 and 20. No vaccine -related adverse effects on female
fertility , fetal development ,or postnatal development were reported in the study .
FDA-CBER-2022-5812-0236042
178.2 Lactation
Risk Summary
It is not known whether COMI RNATY is excreted in human milk. Data are not available to assess the effects of
COMI RNATY on the breastfed infant or on milk production/excretion. The developmental and health benefits
of breastfeeding should be considered along with the mother’s clinical need for COMI RNATY and any
potential adverse effects on the breastfed child from COMI RNATY or from the underly ing maternal condition.
For preventive vaccines, the underl ying maternal condition is susceptibility to disease prevented by the vaccine.
8.4 Pediatr ic Use
Safety and effectiveness of COMI RNATY in individuals 12through 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 safet y and effectiveness of COMI RNATY in individuals y ounger than 12years of age have not been
established.
8.5 Geriatric Use
Of the total number of COMI RNATY recipients in Study 2 as of March 13, 2021 (N = 22,026 ),
20.7%(n= 4,552) were 65 years of age and older and 4.2% (n = 925 ) were 75 y ears of age and older [see
Clinical Studies (14.1) ].No overall differences in safet y or effectiveness were observed between these
recipients and younger recipients.
11DESCRIPTION
COMI RNATY (COVID -19 Vaccine, mRNA) is a sterile suspension for injection for intramuscular use.
COMI RNATY is supplied as a frozen suspension in multiple dose vials with gray caps and label s with gray
border s.Each 0.3mLdose of COMI RNATY supplied in multiple dose vials with gray caps and labels with gray
borders contains 30 mcg of a nucleoside -modified messenger RNA ( mRNA ) encoding the viral spike (S)
glycoprotein of SARS -CoV -2.
Each 0.3 mL dose of the COMI RNATY supplied in multiple dose vials with gray caps and labels with gray
borders also includes the following ingredients: lipids (0.43 mg
((4-hydroxybutyl)azanediy l)bis(hexane -6,1- diyl)bis(2 -hexyldecanoate), 0.05 mg 2 -(polyethylene
glycol 2000 )-N,N-ditetradecy lacetamide, 0.09 mg 1,2 -distearo yl-sn-glycero-3-phosphocholine, and 0. 19mg
cholesterol), 0.06 mg tromethamine, 0.4 mg tromethamine hy drochloride ,and 31mg sucrose.
COMI RNATY does not contain preservative.
The vial stoppers are not made with natural rubber latex.
12CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The nucleoside -modified mRNA in COMI RNATY is formulated in lipid particles, which enable delivery of the
mRNA into host cells to allow expressio n of the SARS- CoV -2 S antigen. The vaccine elicits an immune
response to the S antigen, which protects against COVID-19.
FDA-CBER-2022-5812-0236043
1813NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
COMI RNATY has not been evaluated for the potential to cause carcinogenicity , genotoxicity , or impairment of
male fertility . In a developmental toxicity study in rats with COMI RNATY there were no vaccine -related
effects on female fertility [see Use in Specific Populations ( 8.1)].
14CLINICAL STUDIES
14.1 Efficacy in Participants 16 Years of Age and Older
Study 2is an ongoing, multicenter, multinational, randomized, placebo -controlled, observer -blind, dose -finding,
vaccine candidate –selection, and efficacy study in participants 12 y ears of age and older. Randomization was
stratified by age: 12 through 15 y ears of age, 16 through 55 years of age, or 56 y ears of age and older, with a
minimum of 40% of participants in the ≥56-year stratum. The study excluded particip ants who were
immunocompromised and those who had previous clinical or microbiological diagnosis of COVID- 19.
Participants with preexisting stable disease, defined as disease not requiring significant change in therap y or
hospitalization for worsening dise ase 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 Stud y 2, based on data accrued through March 13, 2021 , approximately 44,000 participants 12years of age
and older were randomized equall y and received 2 doses of COMI RNATY or placebo. Participants are planned
to be followed for up to 24 months, for assessments of safet y and efficacy against COVID -19.
Overall, among the total participants who received COMI RNATY 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, 2 5.6% or 2 5.4% were Hispanic/Latino, 7 3.9% or 7 4.1% were non-Hispanic/Latino, 0.5% or
0.5% did not report ethnicity , 46.0% or 4 5.7% 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 bod y mass index (BMI) ≥30 kg/m2], respectively . The mean age at
vaccination was 4 9.8or 49.7years and median age was 5 1.0 or 51.0 in participants who received
COMI RNATY or placebo, respectivel y.
Efficacy Against COVID -19
The population for the analy sis of the protocol pre -specified primary efficacy endpoint included
36,621 participants 12 years of age and older (18,242 in the COMI RNATY group and 18,379 in the placebo
group) who did not have evidence of prior infection with SARS -CoV -2 through 7 day s after the second dose.
The population in the protocol pre -specified primary efficacy anal ysis included all participants 12 years of age
and older who had been enrolled from July 27, 2020, and followed for the development of COVID- 19 through
November 14, 2020. Participants 18 through 55years of age and 56 years of age and older began enrollment
from July 27, 2020, 16 through 17years of age be gan enrollment from September 16, 2020 ,and 12 through
15years 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 a t least 7 day s after Dose 2 was 95.0% (95% credible i nterval: 90.3,
FDA-CBER-2022-5812-0236044
1997.6), which met the pre- specified success criterion . The case split was 8 COVID -19 cases in the
COMI RNATY group compared to 162 COVID -19 cases in the placebo group.
The population for the updated vaccine efficacy analy sis included participants 16 years of age and older who
had been enrolled from July 27, 2020 , and followed for the development of COVID- 19 during blinded
placebo- controlled follow -up through March 13, 202 1, representing up to 6 months of follow -up after Dose 2.
There were 12,796 (60.8%) participants in the COMI RNATY groupand 12,449 ( 58.7%) in the placebo group
followed for ≥4 months after Dose 2 in the blinded placebo- controlled follow -up period.
SARS -CoV -2 variants of concern identified from COVID -19 cases for this age group from this data cutoff
include B.1.1.7 ( Alpha ) and B.1.351 ( Beta).Representation of identified variants among cases in vaccine v ersus
placebo recipients did not suggest decreased vaccine effectiveness 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 Evidence of Infection and
Participants With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population Dur ingthe Placebo -Controlled Follow -upPeriod
First COVID -19 occurrence from 7 days af ter Dose 2 in participants without evidence of prior
SARS -CoV -2 infection*
SubgroupCOMIRNATY
Na=19,993
Cases
n1b
Surveillance Timec(n2d)Placebo
Na=20,118
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CIe)
All participants77
6.092 ( 19,711)833
5.857 ( 19,741)91.1
(88.8, 93.1)
16 through 64 y ears70
4.859 (15,519)709
4.654 (15,515)90.5
(87.9, 92.7)
65 years and older7
1.233 (4192)124
1.202 (4226)94.5
(88.3, 97.8)
First COVID -19 occurrence from 7 days after Dose 2 in participants with or without* evidence of prior
SARS -CoV -2 infection
SubgroupCOMIRNATY
Na=21,047
Cases
n1b
Surveillance Timec(n2d)Placebo
Na=21,210
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CIe)
All participants81
6.340 ( 20,533)854
6.110 (20 ,595)90.9
(88.5, 92.8)
16 through 64 y ears74
5.073 (16,218)726
4.879 ( 16,269)90.2
(87.5, 92.4)
65 years and older7
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 (symptoms included: fever; new or increased 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 negativ e NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
FDA-CBER-2022-5812-0236045
20a.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 endpoint across all participants within each group at risk for the 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 derived based on the Clopper and Pearson method adjusted to the
surveillance time.
Subgroup anal yses of vaccine efficacy (although limited by small numbers of cases in some subgroups) did not
suggest meaningful differences in efficacy across genders, ethnic groups, geographies, or for participan ts with
obesity ormedical comorbidities associated with high risk of severe COVID -19.
Efficacy Against Severe COVID -19
Efficacy anal yses of secondary efficacy endpoints supported benefit of COMI RNATY in preventing severe
COVID -19. Vaccine efficacy against severe COVID-19 is presented onl y for participants with or without prior
SARS -CoV -2 infection (Table 8) as the COVID -19case counts in participants without prior SARS -CoV -2
infection were the same as those in participants with or without prior SARS -CoV -2 infection in both the
COMI RNATY and placebo groups.
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 Protocol†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 Efficacy – First Severe COVID -19 Occurrence
COMIRNATY
Cases
n1a
Surveillance Timeb(n2c)Placebo
Cases
n1a
Surveillance Timeb(n2c)Vaccine Efficacy %
(95% CId)
7 day s after Dose 2d1
6.353 (20 ,540)21
6.237 (20 ,629)95.3
(70.9, 99.9)
Vaccine Efficacy – First Severe COVID -19 Occurrence Based on CDC Definition
COMIRNATY
Cases
n1a
Surveillance Timeb(n2c)Placebo
Cases
n1a
Surveillance Timeb(n2c)Vaccine Efficacy %
(95% CId)
7 day s after Dose 2d0
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 (symptoms included: fever; new or increased 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.
†Severe illness from COVID -19 isdefined in the protocol as confirmed COVID- 19 and presence of at least 1 of the following:
Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥30 breaths per minute, heart rate ≥125 beats per
minute, saturation of oxygen ≤93% on room air at sea level, or ratio of arterial oxygen partial pressure to fractional inspir ed
oxygen <300 mm Hg);
Respiratory failure [defined as needing high -flow oxygen, noninvasive 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;
FDA-CBER-2022-5812-0236046
21Death.
‡Severe illness from COVID -19 as defined by CDC is confirmed COVID -19 and presence of at least 1 of the fol lowing:
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 endpoint across all participants within each group at risk for the 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 c onfidence interval (CI) for vaccine efficacy is derived 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 analy sis of Study 2 has been performed in 2,260 adolescents 12 through 15years 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 ispresented in Table 9.
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 adolescents 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
12through 15years of age0
0.343 (1043)28
0.322 (1019)100.0
(86.8, 100.0)
First COVID -19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age with or
without evidence of prior SARS -CoV -2 infection
COMIRNATY
Na=1119
Cases
n1b
Surveillance Timec(n2d)Placebo
Na=1109
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CIe)
Adolescents
12through 15years of age0
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 increased cough; new or increased shortness of breath; chills; new or
increa sed 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 endpoint across all participants within each group at risk for the 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.
FDA-CBER-2022-5812-0236047
22e.Two-side c onfidence interval (CI) for vaccine efficacy is derived 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 anal ysis 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 15years of age to participants 16 t hrough 25 years of age who had no serological or
virological evidence of past S ARS -CoV -2 infection up to 1 month after Dose 2 (Table 10).
Table 10: Summary of Geometric Mean Ratio for 50% Neutralizing Titer – Comparison of Adolescents
12 Through 15 Years of Age to Participants 16 T hrough 25 Years of Age (Immunogenicity
Subset) – Participants Without Evidence of Infection up to 1 Month After Dose 2 –Dose 2
Evaluable Immunogenicity Population
COMIRNATY
12 Through 15 Years/
16 Through 25 Years12 Through 15 Years
na=19016Through 25 Years
na=170
AssayTime
PointbGMTc
(95% CIc)GMTc
(95% CIc)GMRd
(95% CId)Met
Noninferiority
Objectivee
(Y/N)
SARS -CoV -2
neutralization
assay -NT50
(titer)f1 month
after
Dose 21253.6
(1117 .7,1406.1)708.1
(625.9,801.1)1.77
(1.50, 2. 09) Y
Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = low er limit of
quantitation; NAAT = n ucleic -acid amplification test; NT50 = 50% neutralizing titer; SARS -CoV- 2 = severe acute respiratory
syndrome coronavirus 2.
Note: Participants who had no serological or virological evidence (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 detected by NAAT [nasal swab] at Visits 1 and
2), and had ne gative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 w ere 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 p oint.
b.Protocol -specified timing for blood sample collection.
c.GMTs and 2 -sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based
on the Student t distribution). Assay results below the LLOQ w ere set to 0.5 × LLOQ .
d.GMRs and 2 -sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers (Group 1
[12through 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 low er bound of the 2 -sided 95% CI for the GMR is greater than 0.67.
f.SARS -CoV- 2 NT50 were determ ined using the SARS -CoV- 2 mNeonGreen Virus Microneutralization Assay. The assay uses a
fluorescent reporter virus deriv ed from the USA_WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The
sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.
16HOW SUPPLIED/STORAGE AND HANDLING
COMI RNATY Suspension for Intramuscular Injection, m ultiple dose vials with gray caps and labels with gray
borders are supplied in a carton containing 10 multiple dose vials (NDC 0069 -2025 -10) or25 multiple dose
vials (NDC 0069-2025- 25).
One vial contains 6 doses of 0.3 mL.
FDA-CBER-2022-5812-0236048
23During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Do not refreeze thawed vials.
Vial Storage Prior to Use
Cartons of COMI RNATY multiple dose vials with gray caps and labels with gray borders will arrive frozen at
ultra-cold conditions in thermal containers with dry ice.
Once received, frozen vials may be immediatel y transferred to the refrigerator [2ºC to 8ºC (35ºF to 46ºF)],
thawed and stored for up to 10weeks. The 10-week refrigerated expiry date should be recorded on the carton at
the time of transfe r. Acarton of 10vials may take up to 6 hours to thaw at this temperature .
Alternativel y, frozen vials may be stored in an ultra -low temperature freezer at -90ºC to - 60ºC ( -130ºF to - 76ºF).
Do not store vials at -25°C to -15°C ( -13°F to 5°F). Once vials are thawed ,they should not be refrozen.
If cartons of COMIRNATY multiple dose vials with gray caps and labels with gray borders are received at 2°C
to 8°C, they should be stored at 2°C to 8°C. Check that the carton has been updated to reflect the 10- week
refrigerated expiry date.
Regardless of storage condition, the vaccine should not be used after the expiration date printed on the vial and
cartons.
Vial Storage During Use
If not previousl y thawed at 2ºC to 8ºC (35ºF to 46ºF), allow vials to thaw at room temperature [up to 25ºC
(77ºF)] for 30 minutes.
COMI RNATY multiple dose vials with gray caps and labels with gray borders may be stored at room
temperature [8°C to 25°C (46°F to 77°F)] for a total of 12 hours prior to the first puncture. After first puncture,
the vial should be held between 2 ºCto 25°C (35°F to 77°F). Vials should be discarded 12hours after first
puncture.
DO NOT DILUTE PRIOR TO USE .
Transportation of Vials
If local redistribution is needed , vials may be transported at - 90°C to - 60°C ( -130°F to - 76°F), or at 2°C to 8°C
(35°F to 46°F) .
17PATIENT COUNSELING INFORMATION
Inform vaccine recipient of the potential benefits and risks of vaccination with COMI RNATY .
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 by visiting https://mothertobaby .org/ongoing -
study /covid19 -vaccines/ .
FDA-CBER-2022-5812-0236049
24Advise vaccine recipient to report an y adverse events to their healthcare provider or to the Vaccine Adverse
Event Reporting S ystem 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 COMI RNATY (COVID -19 Vaccine, mRNA) and the Pfizer -BioNTech COVID -19
Vaccine to Prevent Coronavirus Disease 2019 (COVID -19) for Use in Individuals 1 2Years of Age a nd Older.
The Vaccine Information Fact Sheet for Recipients and Caregivers is available at www.cvdvaccine -us.com.
This product’s label ingmay have been updated. For the most recent prescribing information, please visit
https://daily med.nlm.nih.gov/dail ymed/.
Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, German y
Manufactured b y
Pfizer I nc., New York, NY 10017
LAB -1490 -1.2
US Govt. L icense No. 2229
FDA-CBER-2022-5812-0236050