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1 HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
COM IRNATY safely and effectively. See full prescribing information for
COMIRNATY.
COMIRNATY® (COVID-19 V accine, mRNA) suspension for injection,
for intramuscular use
Initial U.S. Approval: 2021
------------------------------- INDICAT IONS AND USAGE ------------------------------
COMIRNATY is a vaccine indicated for active immunization to prevent
coronavirus disease 2019 (COVID -19) caused by severe acute respiratory
syndrome coronavirus 2 (SARS -CoV- 2) in individuals 16 years of age and
older. (1)
--------------------------DOSAGE AND ADMINISTRATION -------------------------
• For intramuscular injection only. (2.2)
• COMIRNATY is administered intramuscularly as a series of 2 doses
(0.3 mL each) 3 weeks apart. (2.3)
------------------------ DOSAG
E FORMS AND STRENGTHS ------------------------
Suspension for injection. After preparation, a single dose is 0.3 mL. (3)
---------------------------------- CONTRAI NDICATIONS ---------------------------------
Known history of a severe allergic reaction (e.g., anaphylaxis) to any
component of COMIRNATY. (4)
-------------------------- WARNING S 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 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 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 reactions (≥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)
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: 8/2021
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 L
actation
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
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescri bing information are
not listed .
FDA-CBER-2021-5683-0652357
2 FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
COMIRNATY is a vaccine indicated for a ctive immunization to prevent coronavirus disease 2019 (COVID -19)
caused by severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2) in individuals 16 years of age and
older.
2 DOSAGE AND ADMINISTRATION
For intramuscular injection only.
2.1 Preparation for Administration
Prior to Dilution
• COMIRNATY Multiple Dose Vial contains a volume of 0.45 mL, supplied as a frozen suspension that
does not contain preservative. Each vial must be thawed and diluted prior to administration.
• Vials may be thawed in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room temperature [up to 25ºC (77ºF) ] [see How Supplied/Storage and Handling (16)] .
• Refer to thawing instructions in the panels below.
Dilution
• Dilute the vial contents using 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP to form
COMIRNATY . Do not add more than 1.8 mL of diluent.
• ONLY use sterile 0.9% Sodium Chloride Injection, USP as the diluent. Do not use bacteriostatic 0.9%
Sodium Chloride Injection or any other diluent.
• Vials of sterile 0.9% Sodium Chloride Injection, USP are provided but shipped separately. Use the
provided diluent or another sterile 0.9% Sodium Chloride Injection, USP as the diluent.
o Provided diluent vials are single -use only; d iscard after 1.8 mL is withdrawn.
o If another sterile 0.9% Sodium Chloride Injection, USP is used as the diluent, discard after
1.8 mL is withdrawn.
o Do not dilute more than 1 vial of COMIRNATY using the same diluent vial.
• After dilution, 1 vial of COMIRNATY contains 6 doses of 0.3 mL each .
• Refer to dilution and dose preparation instructions in the panel s below.
FDA-CBER-2021-5683-0652358
3 THAWING PRIOR TO DILUTION
• Thaw vial(s) of COMIRNATY before dilution either
by:
o Allowing vial(s) to thaw in the refrigerator [2ºC
to 8ºC (35ºF to 46ºF)]. A carton of vials may take up to 3 hours to thaw, and thawed vials can be
stored in the refrigerator for up to 1 month.
o Allowing vial(s) to sit at room temperature [up to 25ºC (77ºF)] for 30 minutes.
• Using either thawing method, vials must reach room
temperature before dilution and must be diluted
within 2 hours.
• Before dilution invert vaccine vial gently 10 times.
• Do not shake.
• Inspect the liquid in the vaccine vial prior to
dilution. The liquid is a white to off -white
suspension and may contain white to off -white
opaque amorphous particles .
• Do not use if liquid is discolored or if other particles
are observed.
DILUTION
• ONLY use sterile 0.9% Sodium Chloride Injection, USP as the diluent.
• Withdraw 1.8 mL of diluent into a transfer syringe
(21-gauge or narrower needle).
• Add 1.8 mL of sterile 0.9% Sodium Chloride
Injection, USP into the vaccine vial.
FDA-CBER-2021-5683-0652359
4
• 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 -white suspension. Do not
use if vaccine is discolored or contains particulate matter.
• 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.
FDA-CBER-2021-5683-0652360
5 PREPARATION OF INDIVIDUAL 0.3 mL DOSES OF COMIRNATY
• Withdraw 0.3 mL of COMIRNATY 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.
After dilution, vials of COMIRNATY contain 6 doses of 0.3 mL of vaccine. Low dead -volume 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 sufficient volume to extract a sixth dose from a single vial. Irrespective of the type of syringe and needle ,
• each dose must contain 0.3 mL of vaccine.
• if the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and
any excess volume.
• do not pool excess vaccine from multiple vials.
2.2 Administration Information
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The vaccine will be an off -white suspension . Do not
administer if vaccine is discolored or contains particulate matter.
Administer a single 0.3 mL dose of COMIRNATY intramuscularly.
2.3 Vaccination Schedule
COMIRNATY is administered intramuscularly as a series of 2 doses (0.3 mL each) 3 weeks apart.
There are no data available on the interchangeability of COMIRNATY with other COVID -19 vaccines to complete
the vaccination series. Individuals who 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, a single dose is 0.3 mL.
4 CONTRAINDICATIONS
Do not administer COMIRNATY to indi viduals with known history of a severe allergic reaction (e.g.,
anaphylaxis) to any component of the COMIRNATY [see Description (1 1)].
FDA-CBER-2021-5683-0652361
6 5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
App
ropriate medical treatment used to manage immediate allergic reactions must be immediately available in
the event an acute anaphylactic reaction occurs following administration of COMIRNATY.
5.2 Myocarditis and Pericarditis
Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days
following the second dose. The observed risk is highe r among males 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, a vailable data from short -term follow -up suggest that most individuals have had
resolution of symptoms with conservative management . Information is not yet available about potential long -
term sequelae. The CDC has published considerations related to myocarditis and pericarditis after vaccination,
including for vaccination of individuals with a history of myocarditis or pericarditis
(https://www.cdc.gov/vaccines/covid -19/clinical-considerations/myocarditis.html ).
5.3 Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY . Procedures should be in place to avoid injury from fainting.
5.4 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the COMIRNATY.
5.5
Limitation of Effectiveness
COMIRNATY may not protect all vaccine recipients.
6 ADVERSE REACTIONS
In c
linical studies, the most commonly reported (≥ 10%) adverse reactions in participants 16 through 55 years of
age following any dose w ere 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 w ere 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 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may
not reflect the rates observed in practice .
FDA-CBER-2021-5683-0652362
7 The safety of COMIRNATY was evaluated in participants 16 years of age and older in 2 clinical studies
conducted in Germany (Study 1) , United States, Argentina, Brazil , Turkey, South Africa, and Germany
(Study 2). Study BNT162-01 (Study 1) was a Phase 2-part, dose -escalation trial that enrolled 60 participants ,
18 through 55 years of age and 36 participants, 5 6 through 85 years of age . Study C4591001 (Study 2) is a
Phase 1/2/3 multicenter, multinational, randomize d, saline placebo -controlled, double -blind ed (Phase 2/3) ,
dose -finding, vaccine candidate -selection and efficacy study that has enrolled approximately 44,047 participants
(22,026 COMIRNATY ; 22,021 placebo) 16 years of age or older (including 378 and 376 participants
16 through 17 years of age in the vaccine and placebo groups, respectively). Upon issuance of the Emergency
Use Authorization (December 11, 2020) 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 count >200 cells/mm3 within 6 months before enrollment, and on stable
antiretroviral therapy for at least 6 months.
At the time of the analysis of the ongoing Study 2 with a data cut -off of March 13, 2021, there were
25,651 (58.2%) participants (13,031 COMIRNATY and 12,620 placebo) 16 years of age and older followed for
≥4 months after the second dose .
Par
ticipants 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 unsolicited 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].
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received COMIRNATY 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 Systemic Adverse Reactions Solicited in the Study 2
Table 1 and Table 2 present the frequency and severity of report ed solicited local and systemic reactions,
respectively, within 7 days following each dose of COMIRNATY and placebo in the subset of participants
16 through 55 years of age included in the safety population who were monitored for reactogenicity with an
electronic diary.
Table 3 and Table 4 present the frequency and severity of reported solicited local and systemic reactions,
respectively, within 7 days of each dose of COMIRNATY and placebo for participants 56 years of age and
older.
In participants 16 th rough 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 participants 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 participant s in the COMIRNATY group.
FDA-CBER-2021-5683-0652363
8 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 Population *
COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Rednessc
Any (>2.0 cm) 156 (5.4) 28 (1.0) 151 (5.6) 18 (0.7)
Mild 113 (3.9) 19 (0.7) 90 (3.4) 12 (0.4)
Moderate 36 (1.2) 6 (0.2) 50 (1.9) 6 (0.2)
Severe 7 (0.2) 3 (0.1) 11 (0.4) 0
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
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
Note s: 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.
* Ra ndomized participants in the safety analysis population who received at least 1 dose of the study intervention. Pa rticipants
with chronic, stabl e HIV infection were excluded.
a. N = N umber 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; M oderate: >5.0 to ≤ 10.0 cm; S evere: >10.0 cm.
d. Mild: does not interfere with activity; Moderate: interferes with a ctivity; Severe: prevents daily a ctivity.
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 – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Fever
≥38.0℃ 119 (4.1) 25 (0.9) 440 (16.4) 11 (0.4)
≥38.0℃ to 38.4℃ 86 (3.0) 16 (0.6) 254 (9.5) 5 (0.2)
>38.4℃ to 38.9℃ 25 (0.9) 5 (0.2) 146 (5.4) 4 (0.1)
>38.9℃ to 40.0℃ 8 (0.3) 4 (0.1) 39 (1.5) 2 (0.1)
>40.0℃ 0 0 1 (0.0) 0
Fatiguec
Any 1431 (49.4) 960 (33.0) 1649 (61.5) 614 (22.9)
Mild 760 (26.2) 570 (19.6) 558 (20.8) 317 (11.8)
Moderate 630 (21.7) 372 (12.8) 949 (35.4) 283 (10.5)
Severe 41 (1.4) 18 (0.6) 142 (5.3) 14 (0.5)
FDA-CBER-2021-5683-0652364
9 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Headachec
Any 1262 (43.5) 975 (33.5) 1448 (54.0) 652 (24.3)
Mild 785 (27.1) 633 (21.8) 699 (26.1) 404 (15.1)
Moderate 444 (15.3) 318 (10.9) 658 (24.5) 230 (8.6)
Severe 33 (1.1) 24 (0.8) 91 (3.4) 18 (0.7)
Chillsc
Any 479 (16.5) 199 (6.8) 1015 (37.8) 114 (4.2)
Mild 338 (11.7) 148 (5.1) 477 (17.8) 89 (3.3)
Moderate 126 (4.3) 49 (1.7) 469 (17.5) 23 (0.9)
Severe 15 (0.5) 2 (0.1) 69 (2.6) 2 (0.1)
Vomitingd
Any 34 (1.2) 36 (1.2) 58 (2.2) 30 (1.1)
Mild 29 (1.0) 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 antipyretic or
pain medicationf 805 (27.8) 398 (13.7) 1213 (45.2) 320 (11.9)
Note s: Reactions a nd use of antipyretic or pa in 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.
* Ra ndomized participants in the safety a nalysis population who receive d at least 1 dose of the study intervention. Pa rticipants
with chronic, stable HIV infection were excluded.
a. N = N umber 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 a ctivity; S evere: prevents daily a ctivity.
d. Mild: 1 to 2 times in 24 hours; Moder ate: >2 times in 24 hours; Severe: requires intravenous hydration.
e. Mild: 2 to 3 loose stools in 24 hours; M oderate: 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.
FDA-CBER-2021-5683-0652365
10 Table 3: Study 2 – Frequency and Percentages of Parti cipants with Solicited Local Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and
Older – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Rednessc
Any (>2 .0 cm) 106 (5.3) 20 (1.0) 133 (7.2) 14 (0.8)
Mild 71 (3.5) 13 (0.7) 65 (3.5) 10 (0.5)
Moderate 30 (1.5) 5 (0.3) 58 (3.1) 3 (0.2)
Severe 5 (0.2) 2 (0.1) 10 (0.5) 1 (0.1)
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 injection sited
Any (>2 .0 cm) 1408 (70.1) 185 (9.3) 1230 (66.1) 143 (7.8)
Mild 1108 (55.2) 177 (8.9) 873 (46.9) 138 (7.5)
Moderate 296 (14.7) 8 (0.4) 347 (18.7) 5 (0.3)
Severe 4 (0.2) 0 10 (0.5) 0
Note s: 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.
* Ra ndomized participants in the safety analysis population who received at least 1 dose of the study intervention. Pa rticipants
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 , 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; M oderate: >5.0 to ≤ 10.0 cm; S evere: >10.0 cm.
d. Mild: does not interfere with activity; Moderate: interferes with a ctivity; Severe: prevents daily a ctivity.
Table 4: Study 2 – Frequency and Percentages of Participants 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
FDA-CBER-2021-5683-0652366
11 COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Fatiguec
Any 677 (33.7) 447 (22.5) 949 (51.0) 306 (16.7)
Mild 415 (20.7) 281 (14.1) 391 (21.0) 183 (10.0)
Moderate 259 (12.9) 163 (8.2) 497 (26.7) 121 (6.6)
Severe 3 (0.1) 3 (0.2) 60 (3.2) 2 (0.1)
Grade 4 0 0 1 (0.1) 0
Headachec
Any 503 (25.0) 363 (18.3) 733 (39.4) 259 (14.1)
Mild 381 (19.0) 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)
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 antipyretic or
pain medicationf 382 (19.0) 224 (11.3) 688 (37.0) 170 (9.3)
Note s: 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 was fatigue.
* Ra ndomized participants in the safety analysis population who received at least 1 dose of the study intervention. Pa rticipants
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. N for each
reaction or use of antipyretic or pain medication was the same, therefore was included in the col umn header.
b. n = Number of participants with the specified reaction.
FDA-CBER-2021-5683-0652367
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 (%)
c. Mild: does not interfere with activity; Moderate: some interference with a ctivity; Severe: prevents daily a ctivity ; Gra de 4
reactions were defined in the clinical study protocol as emergency room visit or hospitalization for severe fatigue, severe
headache, severe chills, severe muscle pain, or severe joint pain.
d. Mild: 1 to 2 times in 24 hours; Moder ate: >2 times in 24 hours; Severe: requires intravenous hydration ; Gra de 4 emerge ncy visit
or hospitalization for severe vomiting .
e. Mild: 2 to 3 loose stools in 24 hours; M oderate: 4 to 5 loose stools in 24 hours; S evere: 6 or more loose stools in 24 hours ;
Grade 4: emergency room or hospitalization for severe diarrhea.
f. Severity wa s not collected for use of antipyretic or pa in medication.
In participants with chronic, stable HIV infection the frequencies of solicited local and systemic adverse
reactions were similar to or lower than those observed for all participants 16 years of age and older .
Unsolicited Adverse Events
Overall , 11,253 (51.1% ) participants in the COMIRNATY group and 11,316 (51.4% ) participants in the
placebo group had follow -up time between ≥4 months to <6 months after Dose 2 in the blinded
placebo -controlled follow -up period with an additional 1, 778 (8.1% ) and 1,304 (5.9% ) with ≥6 months of
blinded follow -up time in the COMIRNATY and placebo groups, 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 following any dose, through 1 month after Dose 2, in
participants 16 years of age an d older (N=43,847 ; 21,926 COMIRNATY 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), de creased 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 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
55 years of age who received at least one dose of study vaccine, 12,995 of whom received COMIRNATY and
13,026 of whom received placebo , unsolicited adverse events were reported by 4 ,396 (33.8%) participants in
the COMIRNATY group and 2, 136 (16.4%) participants in the placebo group. In a similar analysis in
participants 56 years of age and older that included 8,931 COMIRNATY 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 participants with confirmed stable HIV
infection that included 100 COMIRNATY recipients and 100 placebo recipients , unsolicited adverse events
were reported by 29 (29%) participants in the COMIRNATY group and 15 (15%) participants in the placebo
group. The higher frequency of reported unsolicited non -serious adverse events among COMI RNATY
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. Currently available inform ation is insufficient to
determine a causal relationship with the vaccine. In the analysis of blinded, placebo -controlled follow -up, t here
FDA-CBER-2021-5683-0652368
13 were no other notable patterns or numerical imbalances between treatment groups for specific categories of
non-seriou s adverse events (including other neurologic or 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 categories of non -serious a dverse events that would suggest a causal relationship to
COMIRNATY.
Serious Adverse Events
In Study 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 analysis, in participants 56 years 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 part icipants had at least 4 months of follow -up after Dose 2. Among participants with confirmed
stable HIV infection serious adverse events from Dose 1 up to the participant unblinding date in ongoing
follow -up were reported by 2 (2%) COMIRNATY recipients and 2 (2%) placebo recipients.
In the analysis of blinded, placebo-controlled follow -up, t here were no notable patterns between treatment
groups for specific categories of serious adverse events (including neurologic, neuro -inflammatory, and
thrombotic event s) that would suggest a causal relationship to COMIRNATY. 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 COMIRNATY.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post mark eting 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 extremity (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 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
FDA-CBER-2021-5683-0652369
14 4% and 15% to 20%, respectively. Available data on COMIRNATY administered to pregnant women are
insufficient to inform vaccine -associated risks in pregnancy.
A developmental toxicity stud y has been performed in female rats administered the equivalent of a single
human dose of COMIRNATY on 4 occasions ; twice prior to mating and twice during gestation. These studies
revealed no evidence of harm to the fetus due to the vaccine (see Animal Data ).
Data
Animal Data
In a developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of
nucleoside -modified messenger ribonucleic acid (mRNA) (30 mcg) and other ingredients included in a single
human dose of COMIRNATY was administered to female rats by the intramuscular route on 4 occasions: 21
and 14 days prior to mating, and on gestation days 9 and 20. No vaccine -related adverse effects on female
fertility, fetal development, or postnatal development were reported in the study.
8.2 Lactation
Risk Summary
It is not known whether COMIRNATY is excreted in human milk. Data are not available to assess the effects of
COMIRNATY on the breastfed infant or on milk production/excretion. The developmental and health benefits
of breastfeeding should be considered along with the mother’s clinical need for COMIRNATY and any
potential adverse effects on the breastfed child from COMIRNATY or from the underlying maternal condition.
For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.
8.4 Pediatr ic Use
Safet
y and effectiveness of COMIRNATY in individuals 16 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 younger than 1 6 years of age have not been
established.
8.5 Geriatric Use
Of the total number of COMIRNATY recipients in Study 2 as of March 13, 2021 (N = 22,026),
20.7% (n = 4, 552) were 65 years of age and older and 4.2 % (n = 925) were 75 years of age and older [see
Clinical Studies (14.1)] . No overall differences in safety or effectiveness were observed between these
recipients and younger recipients.
11 DESCRIPTION
COMIRNATY (COVID-19 Vaccine, mRNA) is a ste
rile suspension for injection for intramuscular use.
COMIRNATY is supplied as a frozen suspension in multiple dose vials; 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 dose of COMIRNATY
contains 30 mcg of a nucleoside -modified messenger RNA ( mRNA ) encoding the viral spike (S) glycoprotein
of SARS-CoV-2.
FDA-CBER-2021-5683-0652370
15 Each 0.3 mL dose of the COMIRNATY 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 dihydrate, and 6 mg sucrose. The diluent (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 -m odified mRNA in COMIRNATY is formulated in lipid particles, which enable delivery of the
mRNA into host cells to allow expression of the SARS -CoV-2 S antigen. The vaccine elicits an immune
response to the S antigen, which protects against COVID -19.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
COMIRNATY has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of
male fertility. In a developmental toxicity study in rats with COMIRNATY t here were no vaccine-related
effects on female fertility [see Use in Speci fic Populations ( 8.1)].
14 CLINICAL STUDIES
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 years of age, or 56 years of age and older, with a
minimum of 40% of participants in the ≥56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID -19.
Participants with preexisting stable disease, defined as disease not requiring significant change in therapy or
hospitalization for worsening disease during the 6 weeks before enrollment, were included as were participants with known stable infection with HIV, he patitis C virus (HCV), or hepatitis B virus (HBV).
In Study 2, based on data accrued through March 13, 2021, approximately 44,000 participants 16 years of age
and older were randomized equally and received 2 doses of COMIRNATY or placebo. Participants ar e planned
to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.
Overall, among the total participants who received COMIRNATY or placebo, 51.4% or 50. 3% were male and
48.6% or 49. 7% were female, 79.1% or 79.2% were 16 through 64 years 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
FDA-CBER-2021-5683-0652371
16 comorbidities that increase the risk of severe COVID -19 disease: defined as subjects who had at least one of the
Charlson comorbidity index category or body mass index (BMI) ≥30 kg/m2], respectively. The mean age at
vaccination was 4 9.8 or 49.7 years and median age was 5 1.0 or 51 .0 in participants who received
COMIRNATY or placebo, respectively.
Efficacy Against COVID-19
The population for the analysis of the protocol pre -specified primary efficacy endpoint included
36,621 participants 12 years of age and older (18,242 in the COMIRNATY group and 18,379 in the placebo
group) who did not have evidence of prior infection with SARS -CoV-2 through 7 days after the second dose.
The population in the protocol pre -specified primary e fficacy analysis included all participants 12 years of age
and older who had been enrolled from July 27, 2020, and followed for the development of COVID -19 through
November 14, 2020. Participants 18 through 55 years of age and 56 years of age and older beg an 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 cr iterion . The case split was 8 COVID-19 cases in the
COMIRNATY group compared to 162 COVID -19 cases in the placebo group.
The population for the updated vaccine efficacy analysis included participants 16 years of age and older who
had been enrolled from July 27, 2020, and followed for the development of COVID -19 during blinded
placebo -controlled follow -up through March 13, 202 1, representing up to 6 months of follow -up after Dose 2.
There were 12,796 (60.8%) participants in the COMIRNATY group and 12, 449 ( 58.7%) in the placebo group
followed for ≥4 months after Dose 2 in the blinded placebo-controlled follow -up period .
SARS-CoV-2 variants of concern identified from COVID -19 cases in this study include B.1.1.7 ( Alpha ) and
B.1.351 ( Beta).
Representatio n 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 5. Table 5: 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 ing 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 participantsf 77
6.092 ( 19,711) 833
5.857 ( 19,741) 91.1
(88.8, 93.1)
16 through 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-2021-5683-0652372
17 First COVID -19 occurrence from 7 days after Dose 2 in participants 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) a nd a t lea st 1 symptom
consistent with COVID -19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased muscl e 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] neg ative 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 visi t
prior to 7 days after Dose 2 were included in the a nalysis.
a. N = Number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
c. Tota l surveilla nce 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 a djusted to the
surveilla nce time.
Subgroup analyses 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 or medical comorbidities associated with high risk of severe COVID-19 .
Efficacy Against Sev ere 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 6 ) as the COVID -19 case counts in participants without prior SARS -CoV-2
infection were the same as those in participants with or without prior SARS -CoV-2 infection in both the
COMIRNATY and placebo groups.
FDA-CBER-2021-5683-0652373
18 Table 6: Vaccine Efficacy – First Severe COVID-19 Occurrence in Par ticipants 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 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 CDC 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) a nd a t lea st 1 symptom
consistent with COVID -19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased mu scle 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] neg ative 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 defined in the protocol as confirmed COVID -19 and presence of at least 1 of the following:
• Clinic al 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
oxyge n <300 mm Hg);
• Respiratory failure [defined as needing high -flow oxygen, noninvasive ventilation, mechanical ventila tion 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 COVID -19 a nd presence of at least 1 of the following:
• Hospitalization;
• Admission to the Intensive Care Unit;
• Intubation or mechanical ventilation;
• Death.
a. n1 = Number of p articipants meeting the endpoint definition.
b. Tota l surveilla nce time in 1000 person -years for the given endpoint across all p a rticipants within each group a t 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
surveilla nce time.
16 HOW SUPPLIED/STORAGE AND HANDLING
COMIRNATY Suspe nsion for Intramuscular Injection, Multiple Dose Vials 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 In jection, 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 a s cartons of 10 mL single -use vial s manufactured by
FDA-CBER-2021-5683-0652374
19 Hospira, Inc (NDC 0409-4888 -10), or 2 mL single -use vial s manufactured by Fresenius Kabi USA, LLC
(NDC 63323-186 -02).
After dilution, 1 vial contains 6 doses of 0.3 mL.
During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Do not refreeze thawed vials.
Frozen Vials Prior to Use
Cartons of COMIRNATY Multiple Dose Vials arrive in thermal containers with dry ice. Once received, remove
the vial cartons immediately from the thermal container and preferably store in an ultra -low temperature freezer
between -90ºC 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 storage condition of -90 ºC 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 thermal 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 for instructions regarding the use of the thermal
container for temporary storage. The thermal container maintains 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 F rozen Vials
If local redistribution is needed and full cartons containing vials 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 ag ainst 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 be 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.
FDA-CBER-2021-5683-0652375
20 Undiluted vials may be stored at room temperature for no more than 2 hours.
Transportation of Thaw ed 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 exposure to direct sunlight and ultraviolet light. Any vaccine remaining in vials must be discarded after 6 hours. Do not refreeze.
17 PATIENT COUNSELING INFORMATION
Inform vaccine recipient of the potential benefits and risks of vaccination with COMIRNATY.
Infor
m vaccine recipient of the importance of completing the two 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/ .
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 .
This product’s label ing ma y have been upd ated. For the most recent 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 -1448-0. 8
US Govt. License No. x
FDA-CBER-2021-5683-0652376