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 react ion (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 (54)
------------------------------ 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: M/YYYY
FULL PRESCRIBING INFORMATION: CONTENTS *
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2 1 Preparation for Administration
22 Administration Information
2 3 Vaccination Schedule
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
51 Management of Acute Allergic Reactions
5 2 Myocarditis and Pericarditis
53 Syncope
54 Altered Immunocompetence
55 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
8 6 Immunocompromised 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-2021-5683-0651783
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 ster ile 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; discard 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 use diluent vials to dilute multiple vials of COMIRNATY.
• After dilution, 1 vial of COMIRNATY 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.
FDA-CBER-2021-5683-0651784
3 • 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 .
• Equalize vial pressure before removing the needle from the vaccine vial by withdrawing 1.8 mL air
into the empty diluent syringe.
FDA-CBER-2021-5683-0651785
4
• 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.
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.
FDA-CBER-2021-5683-0651786
5 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.
A third dose of the COMIRNATY (0.3 mL) administered at least 28 days following the first 2 doses of this
vaccine is authorized for administration to individuals at least 16 years of age who have undergone solid organ
transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of
immunocompromise.
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
FDA-CBER-2021-5683-0651787
6 symptoms. Information is not yet available about potential long-term sequelae. The CDC has published
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 , 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.
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
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 inclu ded 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.
FDA-CBER-2021-5683-0651788
7 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 characterist ics 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 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.
Table 1: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 16 T hrough 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
FDA-CBER-2021-5683-0651789
8 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Pain at the injection sited
Any 2426 (83.7) 414 (14.2) 2101 (78.3) 312 (11.6)
Mild 1464 (50.5) 391 (13.4) 1274 (47.5) 284 (10.6)
Moderate 923 (31.8) 20 (0.7) 788 (29.4) 28 (1.0)
Severe 39 (1.3) 3 (0.1) 39 (1.5) 0
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)
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)
FDA-CBER-2021-5683-0651790
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 (%)
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-2021-5683-0651791
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-2021-5683-0651792
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-2021-5683-0651793
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 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 .
In clinical studies, 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, 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%).
From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19
vaccine in solid -organ transplant recipients. N Engl J Med) , in 99 individuals who had undergone various solid
organ transplant procedures (heart, kidney, liver, lung, pancreas) 97±8 months previously who received a third
vaccine dose, the adverse event profile was similar to that after the second dose and no grade 3 or grade 4
events were reported in recipients who were followed for 1 month following post Dose 3.
Unsolicited Adverse Events
Overall 51.1% of participants in the COMIRNATY group and 51.4% of 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 8.1% and 5.9% with ≥6 months of blinded follow -up time in the COMIRNATY and
placebo groups, respectively.
Upon issuance of the EUA for COMIRNATY, participants were unblinded to offer placebo participants
COMIRNATY. P articipants were unblinded in a phased manner over a period of months to offer placebo
participants COMIRNATY. At the time of the updated efficacy analysis 54.5% of participants originally
randomized to COMIRNATY had ≥6 months of follow -up from Dose 2 and 47.5% of original placebo
participants had follow- up time between ≥1 month to <2 months after Dose 2 of COMIRNATY. A dverse events
are reported as incidence rates per 100 person years to account for the variable exposure since unblinding began
FDA-CBER-2021-5683-0651794
13 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.
Adverse event s occurred in 28.8% of vaccine recipients who had a follow -up period of at least 6 months after
Dose 2; 1.6% of the recipients had serious adverse events.
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 by 103 (0.8%) at an incidence rate of 2.1 per 100 person
years among COMIRNATY recipients and 117 (0.9%) 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 by 165 (1.8%) at an incidence rate of 4.9 per 100 person years among
COMIRNATY recipients and 151 (1.7%) 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 participant unblinding date in ongoing follow-up were reported by 2
(2%)at an incidence rate of 6.6 per 100 person years among COMIRNATY recipients and 2 (2 %)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 by 4396 (33.8%) at an incidence rate of 88.4
per 100 person--years among participants who received COMIRNATY and 2136 (16.4%) 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 nonserious adverse events were reported by 2551 (28.6%) at an incidence rate of 75.7 per 100 person-
years among participants who received COMIRNATY and 1432 (16.1%) 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 by 29 (29%) at an incidence rate of 95.8 per 100
person years among participants who received COMIRNATY and 15 (15%) 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
FDA-CBER-2021-5683-0651795
14 events reported during the first 7 days following each dose of vaccine that are consistent with adverse reactions
solicite d 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 g roup ( 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 reliably estimate their frequency or establish a causal relationship to vaccine exposure.
Cardiac Disorders: myocarditis, p ericarditis
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 ).
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/ .
FDA-CBER-2021-5683-0651796
15 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.
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.
8.6 Immunocompromised Use
From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19
vaccine in solid -organ transplant recipients. N Engl J Med) , safety and effectiveness of a third dose of
COMIRNATY have been evaluated in persons that received solid organ transplants. The administration of a
third dose of vaccine appears to be only moderately effective in increasing potentially protective antibody titers.
Patients should still be counselled to maintain physical precautions to help prevent COVID-19. In addition,
close contacts of immunocompromised persons should be vaccinated as appropriate for their health status .
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
FDA-CBER-2021-5683-0651797
17 older, 8281.9% or 82.1% were White, 98.5% or 98.6% were Black or African American, 0.91.0% or 0.9% were
American Indian or Alaska Native, 4.46% or 4.35 % were Asian, 0.3% or 0. 12% Native Hawaiian or other
Pacific Islander, 2 54.96 % or 254.46% were Hispanic/Latino, 734.69% or 7 4.18% were non -Hispanic/Latino,
0.5% or 0.5% did not report ethnicity, 446.60% or 454.74% had comorbidities [participants who have 1 or more
comorbidities that increase the risk of severe COVID -19 disease: defined as subjects who had at least one of the
Charlson comorbidity index category or body mass index (BMI) ≥30 kg/m2], respectively. The mean age at
vaccination was 4 98.83 or 4 98.72 years and median age was 5 10.0 or 510.0 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 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.
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 a nd 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 9 169 94.6
FDA-CBER-2021-5683-0651799
18 2.332 (18,559) 2.345 (18,708) (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 [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 a nalysis.
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.
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 to the surveillance time.
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%. The case split was 8 COVID -19
cases in the BNT162b2 group compared to 162 COVID- 19 cases in the placebo group. The 95% credible
interval for the vaccine efficacy was 90.3% to 97.6%, i ndicating that the true vaccine efficacy is at least 90.3%
with a 97.5% probability, which met the pre -specified success criterion.
The population for the updated vaccine efficacy analysis included participants 16 years of age and older who
had been en rolled 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.
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.
The updated vaccine efficacy information is presented in Table 56.
FDA-CBER-2021-5683-0651800
19 Table 56: 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)
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 negative NAAT (nasal swab) at a ny 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 Two-sided confidence interval (CI) for vaccine efficacy is derived based 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
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
FDA-CBER-2021-5683-0651801
20 SARS -CoV-2 infection (Table 76) 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 67: 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
increa sed muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting)
* Participants who had no evidence of past SARS -CoV-2 infection (i e , N -binding antibody [serum] negative at Visit 1 and
SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis
† 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
‡ 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 -ye ars 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-s ide c onfidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the
surveillance time
Immunogenicity in Solid Organ Transplant Recipients
From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19
vaccine in solid -organ transplant recipients. N Engl J Med) , a single arm study has been conducted in
FDA-CBER-2021-5683-0651802
21 101 individuals who had undergone various solid organ transplant procedures (heart, kidney, liver, lung,
pancreas) 97±8 months previously. A third dose of COMIRNATY was administered to 99 of these individuals
approximately 2 months after they had received a second dose. Among the 59 patients who had been
seronegative before the third dose, 26 (44%) were seropositive at 4 weeks after the third dose. All 40 patients
who had been seropositive before the third dose were still seropositive 4 weeks later. The prevalence of
anti-SARS -CoV- 2 antibodies was 68% (67 of 99 patients) 4 weeks after th e third dose.
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 cartons of 10 mL single- use vial s manufactured by
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 - 8090 ºC to -60ºC (- 112ºF 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 - 8090ºC to -60ºC (- 112ºF 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 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).
Frozen vials transported at -25°C to - 15°C ( -13°F t o 5°F) may be returned 1 time to the recommended storage
condition of - 8090ºC to -60ºC (- 112ºF 130ºF to -76ºF).
FDA-CBER-2021-5683-0651803
22 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 .
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/ .
calling …..
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-2021-5683-0651804
23 This product’s labeling may have been updated. For the most recent prescribing information, please visit
www.comirnatyglobal.com .
Manufactured for
BioNTech Manufacturing GmbH An der Goldgrube 12 55131 Mainz, Germany
Manufactured by Pfizer Inc., New York, NY 10017
LAB -1448-0.34
US Govt. License No. x
FDA-CBER-2021-5683-0651805