Document text
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 Vaccine , mRNA) suspension for injection, for
intramuscular use
Initial U.S. Approval: YYYY
--------------------------- INDICATIONS 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)
--------------------- DOSAGE FORMS AND STRENGTHS ----------------------
Suspension for injection. After preparation, a single dose is 0.3 mL. (3)
------------------------------ CONTRAINDICATIONS ------------------------------
Known history of a severe allergic reaction (e.g., anaphylaxis) to any
component of COMIRNATY. (4)
----------------------- WARNINGS AND PRECAUTIONS -----------------------
• Postmarketing data demonstrate increased risks of myocarditis 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, fatigue, headache, muscle pain, chills, joint pain, fever , and
injection site swelling . (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, fatigue, headache, muscle pain, chills, joint pain, injection site
swelling , fever , and injection site redness . (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 *
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Preparation for Administration
2.2 Administration Information
2.3 Vaccination Schedule
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
5.2 Myocarditis and Pericarditis
5.3 Syncope
5.4 Altered Immunocompetence
5.5 Limitation of Effectiveness
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are
not listed .
FDA-CBER-2021-5683-0651670
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
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 an alternate brand of sterile 0.9% Sodium Chloride Injection, USP as the diluent.
• Provided diluent vials are single-use only and should be discarded after 1.8 mL is withdrawn. Do not use provided diluent vials to dilute multiple vials of COMIRNATY.
• After dilution , 1 vial contains 6 doses of 0.3 mL each .
• Refer to dilution and dose preparation instructions in the panels below.
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.
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3
• Before dilution invert vaccine vial gently 10 times.
• Do not shake.
• Inspect the liquid in the 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.
• Using aseptic technique, withdraw 1.8 mL of diluent into a transfer syringe (21 -gauge or narrower
needle).
• Cleanse the vaccine vial stopper with a single- use
antiseptic swab.
• Add 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP into the vaccine vial .
• Equalize vial pressure before removing the needle from the vial by withdrawing 1.8 mL air into the empty diluent syringe.
FDA-CBER-2021-5683-0651672
4
• Gently invert the vial containing the 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.
PREPARATION OF INDIVIDUAL 0.3 mL DOSES OF COMIRNATY
• Using aseptic technique, cleanse the vial stopper
with a single -use antiseptic swab, and 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.
FDA-CBER-2021-5683-0651673
5 2.2 Administration Information
For intramuscular injection only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off-white suspension. During the visual inspection,
• verify the final dosing volume of 0.3 mL.
• confirm there are no particulates and that no discoloration is observed.
• do not administer if vaccine is discolored or contains particulate matter.
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.
2.3 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 individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the COMIRNATY [s ee Description (1 1)].
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in
the event an acute anaphylactic reaction occurs following 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 has been highest in adolescent and young adult males under 40 years of age. Available data from short- term follow -up suggest that most individuals have had resolution of
symptoms. Information is not yet available about potential long-term sequelae. The CDC has published
FDA-CBER-2021-5683-0651674
6 considerations 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 clinical studies with a data cut-off of March 13, 2021, 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 with a data cut-off of March 13, 2021, 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%). In clinical studies with a data cut-off of March 13, 2021, the adverse reactions occurring in <10% of participants 16 through 55 years of age following any dose were injection site redness (9.5%), nausea (1.4%), malaise (0.7%), lymphadenopathy (0.5%), asthenia (0.4%), decreased appetite ( 0.2% ), hyperhidrosis (0.1% ),
lethargy (0.1%), and night sweats (0.1%). In clinical studies with a data cut-off of March 13, 2021, the adverse reactions occurring in <10% of participants 56 years of age and older following any dose were nausea (1.0%) , malaise ( 0.5%), asthenia (0. 3%),
lymphadenopathy (0.2%), lethargy (0.2%), decreased appetite ( 0.1%), hyperhidrosis (0.1%), and night sweats
(0.1%).
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 .
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
multicenter, multinational, randomized, saline placebo-controlled, observer-blind, dose-finding, vaccine
FDA-CBER-2021-5683-0651675
7 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). 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/mm
3 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 .
Participants 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 i n 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 reported 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 through 55 years of age after receiving Dose 2, the mean duration of pain at the injection site
was 2.5 days (range 1 to 70 days), for redness 2.2 days (range 1 to 9 days), and for swelling 2.1 days (range 1 to
8 days) for participants in the COMIRNATY group. In 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 participants in the COMIRNATY group.
FDA-CBER-2021-5683-0651676
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.
* 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 = 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 = N umber 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 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 – 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)
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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 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 received at least 1 dose of the study intervention. Participants
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 or use of antipyretic or pain medication was the same, therefore, this information was included in the column
header.
b. n = Number of participants with the specified reaction.
c. Mild: does not interfere with activity; M oderate: some interference with activity; S evere: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; M oderate: >2 times in 24 hours; S evere: 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-2021-5683-0651678
10 Table 3: Study 2 – Frequency and Percentages of Participants 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.
* 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, 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 activity; Severe: prevents daily activity.
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-2021-5683-0651679
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.
* 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. N for each
reaction or use of antipyretic or pain medication was the same, therefore was included in the column header.
b. n = Number of participants with the specified reaction.
FDA-CBER-2021-5683-0651680
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 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, severe chills, severe muscle pain, or severe joint pain.
d. Mild: 1 to 2 times in 24 hours; M oderate: >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; M oderat e: 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 was not collected for use of antipyretic or pain medication.
In participants with chronic, stable HIV infection after receiving Dose 2, local reactions and systemic events
were similar to those observed for all participants 16 years of age and older by severity, onset day, and median
duration. The frequency of pain at the injection site was similar after Dose 1 compared with Dose 2 of
COMIRNATY (63.0% v ersus 53.3%). The frequency of redness and swelling was similar after Dose 1
compared with Dose 2 of COMIRNATY (redness: 3.7% versu s 6.7%; swelling: 5.6% versu s 8.3%,
respectively). There was 1 (1.7%) severe reaction (pain at the injection site) reported after Dose 2 of COMIRNATY and no Grade 4 local reactions were reported. Fever, headache, chills, and joint pain increased in frequency from Dose 1 to Dose 2 while fatigue, vomiting, diarrhea, and muscle pain were similar after each dose of COMIRNATY. There were no severe systemic events after Dose 1 of COMIRNATY but after Dose 2, there was 1 (1.7%) severe fever (>38.9°C to 40.0°C), 3 (5.0%) participants with severe fatigue, 2 (3.3%) participants with severe headache, 1 (1.7%) participant with severe chills, and 1 (1.7%) participant with severe diarrhea. There were no G rade 4 systemic events reported after either dose.
Unsolicited Adverse Events
Upon issuance of the EUA for COMIRNATY, participants were unblinded to offer placebo participants
COMIRNATY. Unblinded participants originally randomized to COM IRNATY and placebo recipients
administered COMIRNATY continued to be followed for unsolicited adverse events including serious adverse
events , throughout the study [from Dose 1 of COMIRNATY through 1 month (all unsolicited adverse events)
and 6 months (serious adverse events) after the last vaccination]. Adverse events are reported as incidence rates
per 100 person-years to account for the variable exposure since unblinding began in a phased manner for
participants in the study. Adverse events detailed below for participants 16 years of age and older are for the
placebo -controlled blinded follow-up period up to the participants’ unblinding dates.
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 reported at an incidence rate of 2.1 per 100 person-years among
COMIRNATY recipients and 2.4 per 100 person-years among placebo recipients. In a similar analysis, in
participants 56 years of age and older ( COMIRNATY =8931, placebo = 8895), serious adverse events were
reported at an incidence rate of 4.9 per 100 person- years among COMIRNATY recipients and 4.6 per
100 person-years among placebo recipients who received at least 1 dose of COMIRNATY or placebo,
respectively. In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2.
Among participants with confirmed stable HIV infection serious adverse events from Dose 1 up to the
FDA-CBER-2021-5683-0651681
13 participant unblinding date in ongoing follow-up were reported at an incidence rate of 6.6 per 100 person- years
among COMIRNATY recipients and 6.9 per 100 person- years among placebo recipients.
There 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
COMIRNATY.
Non- Serious Adverse Events
Overall in Study 2 in which 12,995 participants 16 through 55 years of age received COMIRNATY and
13,026 participants received placebo , all events, which include non-serious adverse events from Dose 1 up to
the participant unblinding date in ongoing follow- up were reported at an incidence rate of 88.4 per
100 person-years among participants who received COMIRNATY and 43.5 per 100 person-years among
participants in the placebo group, for participants who received at least 1 dose. In a similar analysis, in
participants 56 years of age and older ( COMIRNATY = 8931, placebo = 8895), all events, which include
non-seriou s adverse events were reported at an incidence rate of 75.7 per 100 person-years among participants
who received COMIRNATY and 43.3 per 100 person-years among participants in the placebo group, for
participants who received at least 1 dose. Among participants with confirmed stable HIV infection, all events,
which include non-serious adverse events from Dose 1 up to the participant unblinding date in ongoing
follow-up were reported at an incidence rate of 95.8 per 100 person-years among participants who received
COMIRNATY and 52.0 per 100 person-years among participants in the placebo group, for participants who
received at least 1 dose.
In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2. The higher
frequency of reported unsolicited non- serious adverse events among COMIRNATY recipients (inclusive of
stable HIV infection) compared to placebo recipients was primarily attributed to local and systemic adverse
events reported during the first 7 days following each dose of vaccine that are consistent with adverse reactions
solicited among participants in the reactogenicity subset and presented in Table 3 and Table 4.
From Dose 1 up to the participant unblinding date, reports of lymphadenopathy were imbalanced with notably
more cases in the COMIRNATY group (87) v ersus the placebo group (8).
Throughout the placebo-controlled safety follow-up period to date, 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 information is insufficient to
determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances
between treatment groups for specific categories of non -serious adverse events (including other neurologic or
neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postmarketing 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 rel iably estimate their frequency or establish a causal relationship to
vaccine exposure.
FDA-CBER-2021-5683-0651682
14 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
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%, 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 four 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 preve nted by the vaccine.
8.4 Pediatric Use
Safety 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 16 years of age have not been established.
FDA-CBER-2021-5683-0651683
15 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 = 4552) 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 sterile 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.
Each 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
glycol2000)- 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-modified m RNA 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 Special Populations (8.1)] .
14 CLINICAL STUDIES
Efficacy in Participants 16 Years of Age and Older
Study 2 is a 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
FDA-CBER-2021-5683-0651684
16 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, hepatitis 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 are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19. The population for the analysis of the 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 wit h SARS -CoV-2 through 7 days after the second dose. Overall , among the total participants
who received COMIRNATY or placebo , 51.4% or 50.5% were male and 4 8.6% or 49.5% were female, 4.8% or
4.6% were 12 through 15 years of age, 75.1% or 75.1% were 16 through 64 years of age, 20.1% or 20.3% were 65 years of age and older, 16.1% or 16.3% were 65 through 74 years of age, 4.0% or 4.0% 75 years of age and
older, 82.9% or 83.1% were White, 8.5 % or 8.6% were Black or African American, 0.9% or 0.9% were
American Indian or Alaska Native, 4.6% or 4.5% were Asian, 0.3% or 0.1 % Native Hawaiian or other Pacific
Islander , 24.9% or 24.6% were Hispanic/Latino , 74.6% or 74.8% were non -Hispanic/Latino, 0.5% or 0.5% did
not report ethnicity, 44.6% or 44.4% had comor bidities [participants who have 1 or more 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/m
2 (16 years of age and older ) or BMI ≥95th
percentile (12 through 15 years of age) ], respectively. The mean age at vaccination was 48.3 or 48.2 years and
median age was 50.0 or 50.0 in participants who received COMIRNATY or placebo , respectively.
Efficacy Against COVID-19
The population in the protocol pre- specified primary efficacy 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 began enrollment from July 27, 2020, 16 through 17 years of age began enrollment from September 16, 2020, and 12 through 15 years of age began enrollment from October 15, 2020.
FDA-CBER-2021-5683-0651685
17 The 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 Without Evidence of Infection and Participants With or Without
Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population
First COVID -19 occurrence from 7 days after Dose 2 in participants without evidence of prior
SARS -CoV -2 infection *
Subgroup COMIRNATY
Na=18,198
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=18,325
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)
All participantse 8
2.214 (17,411) 162
2.222 (17,511) 95.0
(90.3, 97.6)f
16 to 64 years 7
1.706 (13,549) 143
1.710 (13,618) 95.1
(89.6, 98.1)g
65 years and older 1
0.508 (3848) 19
0.511 (3880) 94.7
(66.7, 99.9)g
65 to 74 years 1
0.406 (3074) 14
0.406 (3095) 92.9
(53.1, 99.8)g
75 years and older 0
0.102 (774) 5
0.106 (785) 100.0
(-13.1, 100.0)g
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=19,965
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=20,172
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)
All participantse 9
2.332 (18,559) 169
2.345 (18,708) 94.6
(89.9, 97.3)f
16 to 64 years 8
1.802 (14,501) 150
1.814 (14,627) 94.6
(89.1, 97.7)g
65 years and older 1
0.530 (4044) 19
0.532 (4067) 94.7
(66.8, 99.9)g
65 to 74 years 1
0.424 (3239) 14
0.423 (3255) 92.9
(53.2, 99.8)g
75 years and older 0
0.106 (805) 5
0.109 (812) 100.0
(-12.1, 100.0)g
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 [n asal 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.
e. No confirmed cases were identified in participants 12 to 15 years of age.
FDA-CBER-2021-5683-0651686
18 f. Two-sided credible interval for vaccine efficacy was calculated using a beta -binomial model with a beta (0.700102, 1) prior for
θ=r(1 -VE)/(1+r(1 -VE)), where r is the ratio of surveillance time in the active vaccine group over that in the placebo group.
g. Two-sided confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted t o the
surveillance time.
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, 2021, representing up to 6 months of follow-up after Dose 2.
Overall , 59.2% of participants in the COMIRNATY group and 57.3% of participants in the placebo group had
≥4 months of follow- up time after Dose 2 in the blinded placebo- controlled follow -up period.
The updated vaccine efficacy information is presented in Table 6. Table 6: 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 particip ants 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)
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) 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 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] 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.
a. N = Number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
FDA-CBER-2021-5683-0651687
19 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 b ased on the Clopper and Pearson method adjusted to the
surveillance time.
Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across genders,
ethnic groups, geographies , and participants with medical comorbidities and obesity associated with high risk of
severe COVID -19.
Efficacy Against S evere COVID -19
Updated 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 7) 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. Table 7: 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 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) 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 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] negative at Visit 1 and
SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
† Severe illness from COVID -19 is defined 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 arteri al oxygen partial pressure to fractional inspired
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;
• Death.
FDA-CBER-2021-5683-0651688
20 ‡ Severe illness from COVID -19 as defined by CDC is confirmed COVID -19 and presence of at least 1 of the following:
• Hospitalization;
• Admission to the Intensive Care Unit;
• Intubation or mechanical ventilation;
• Death.
a. n1 = Number of participants meeting the endpoint definition.
b. Total surveillance time in 1000 person -years for the given endpoint across all p articipants 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.
16 HOW SUPPLIED/STORAGE AND HANDLING
COMIRNATY Suspension 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 Injection, USP diluent is provided but shipped separately , and should be stored at controlled room
temperature 20 °C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. The provided 0.9% Sodium
Chloride Injection, USP diluent will be supplied either as a 10 mL single-use vial manufactured by Hospira, Inc
(NDC 0409-4888-10), or a 2 mL single-use vial 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 -80ºC to -60ºC (-112ºF 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 -80ºC to -60ºC (-112ºF 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 Frozen 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 against the 2- week limit for storage at -25°C to - 15°C ( -13°F to 5°F).
FDA-CBER-2021-5683-0651689
21 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 -80ºC to -60ºC (-112ºF to -76ºF).
Thawed Vials Before Dilution
Thawed Under Refrigeration
Thaw and then store undiluted vials in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] for up to 1 month. A carton of 25 vials or 195 vials may take up to 2 or 3 hours , respectively, to thaw in the refrigerator, whereas a fewer
number of vials will thaw in less time. Thawed at Room Temperature For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for 30 minutes. Thawed vials
can be handled in room light conditions. Vials must reach room temperature before dilution.
Undiluted vials may be stored at room temperature for no more than 2 hours.
Transportation of Thawed Vials
Available data support transportation of 1 or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 12 hours.
Vials After Dilution
After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within 6 hours from the time of dilution.
During storage, minimize exposure to room light, and avoid 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. Inform vaccine recipient of the importance of completing the two dose vaccination series. 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
.
FDA-CBER-2021-5683-0651690
22 This product’s labeling may have been updated. For the most recent prescribing information, please visit
www.comi rnatyglobal.com .
Manufactured for
BioNTech Manufacturing GmbH An der Goldgrube 12 55131 Mainz, Germany
Manufactured by Pfizer Inc., New York, NY 10017
LAB -1448-0.3
US Govt. License No. x CPT Code x
FDA-CBER-2021-5683-0651691