Document text
1HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
COMIRNATY 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 administration only.
COMIRNATY is administered intramuscularly as a series of 2 doses
(0.3mL each) 3 weeks apart. (2.3)
------------------------DOSAGE FORMS AND STRENGTHS------------------------
Suspension for injection. After preparation, a single dose is 0.3mL. (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 studiesof participants 16 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, fever, and injection site
swelling. (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 Concurrent Illness at Time of Vaccination
5.4 Syncope
5.5 Altered Immunocompetence
5.6 Bleeding Precautions
5.7 Limitation of Effectiveness
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Efficacy in Participants 16 Years of Age and Older
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are
not listed. ------------------------------------------------------------------------------------------------------
1 INDICATIONS AND USAGE1 INDICATIONS AND USAGEINDICATIONS AND USAGEINDICATIONS AND USAGE1
2
FDA-CBER-2021-5683-1024730
Summary of Comments on 48A_BLA 125742-0_08-05-2021_Telecon_Labeling via FAX_e.pdf
Page: 1
Number: 1 Author: Author Date: Indeterminate
Pfizer,
Please see section 6 for a statement to include in highlights
Number: 2 Author: Author Date: Indeterminate
Pfizer,
Please make table of contents consistent with Full PI
FDA-CBER-2021-5683-1024731
2 FULL PRESCRIBING INFORMATION
1 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.
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 sterile0.9% Sodium Chloride Injection, USP to form
COMIRNATY. Do not addmore than 1.8mL 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.
After dilution, 1 vial contains 6doses of 0.3mLeach.
Refer to dilution and dose preparation instructions in the panels below.
THAWING PRIOR TO DILUTION
Thaw vial(s) of COMIRNATYbefore dilution either
by:
oAllowing vial(s) to thaw in the refrigerator [2ºC
to 8ºC (35ºF to 46ºF)]. A carton of vials may take
up to 3hours to thaw, and thawed vials can be
stored in the refrigerator for up to 1 month.
oAllowing 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.
FDA-CBER-2021-5683-1024732
3 Before dilution invert vaccine vial gently 10times.
Do not shake.
Inspect the liquid in the vial prior to dilution. The
liquid is a white to off-white suspension and may
containwhite 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 1.8mL of diluent
into a transfer syringe (21-gauge or narrower
needle).
Cleanse the vaccine vial stopper with a single-use
antiseptic swab.
Add 1.8mL of sterile 0.9% Sodium Chloride
Injection, USP into the vaccine vial.
Equalize vial pressure before removing the needle
from the vial by withdrawing 1.8mL air into the
empty diluent syringe.
FDA-CBER-2021-5683-1024733
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 6hours after dilution.
PREPARATION OF INDIVIDUAL 0.3mL DOSES OF COMIRNATY
Using aseptic technique, cleanse the vial stopper
with a single-use antiseptic swab, and withdraw
0.3mLof COMIRNATY preferentially using low
dead-volume syringes and/or needles.
Each dose must contain 0.3mL of vaccine.
If the amount of vaccine remaining in a singlevial
cannot provide a full dose of 0.3mL, discard the
vial and any excess volume.
Administer immediately.
FDA-CBER-2021-5683-1024734
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 [see Description (11)] .
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in
the event an acute anaphylactic reaction occurs following 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
FDA-CBER-2021-5683-1024735
6 yearsof age. Availabledata 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
considerations for vaccination of individuals with a history of myocarditis or pericarditis
(https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html#underlying-
conditions ).
5.4 Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines, including
COMIRNATY. Procedures should be in place to avoid injury from fainting.
5.5 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a
diminished immune response to the COMIRNATY.
5.7 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 frequently reported (>10%) adverse reactions
in participants 16 through 55 years of age following any dose included… The most frequently reported (>10%)
adverse reactions in participants 56 years of age and older following any dose included…
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 2-part, dose-escalation trial that enrolled 60 participants,
18 through 55 years of age and 36 participants, 56 through 85 years of age. Study C4591001 (Study 2) is a
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
TRADENAME; 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 disease
was defined as documented viral load <50 copies/mL and CD4 count >200 cells/mm3 within 6 months before
enrollment, and on stable antiretroviral therapy for at least 6 months 1
2
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Pfizer,
To be consistent with the Prescribing Information for other vaccines which generally do not address concurrent illness at time of vaccination, we have deleted this subsection General vaccine administration practices, including
considerations for vaccination of individuals with acute illness, are comprehensively addressed in the ACIP’s General Best Practice Guidelines for Immunization
Number: 2 Author: Author Date: Indeterminate
Pfizer,
To be consistent with the Prescribing Information for other intramuscularly administered vaccines which generally do not address use in individuals with increased bleeding risk, we have deleted this subsection General vaccine
administration practices, including considerations for intramuscular administration in persons with increased bleeding risk, are comprehensively addressed in the ACIP’s General Best Practice Guidelines for Immunization
FDA-CBER-2021-5683-1024737
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
.
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 inStudy 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 and 49.1% were female,
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 7days 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 to 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 7Days 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) 1
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Pfizer,
Please complete the sentences and include in the Highlights
FDA-CBER-2021-5683-1024739
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 (%)
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
Notes: Reactions were collected in the electronic diary (e -diary) from Day 1 to Day 7 after vaccination.
No Grade 4 solicited local reactions were reported in participants 16 through 55 years of age.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for
each reaction was the same, therefore, this information was included in the column header.
b. n = Number of participants with the specified reaction.
c. Mild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.
d. Mild: does not interfere with activity; 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 7Days 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
119 (4.1) 25(0.9) 440 (16.4) 11 (0.4)
86 (3.0) 16(0.6) 254 (9.5) 5(0.2)
> 25 (0.9) 5 (0.2) 146 (5.4) 4(0.1)
> 8 (0.3) 4 (0.1) 39 (1.5) 2(0.1)
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) 1
2
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Number: 1 Author: Author Date: Indeterminate
Pfizer: Please also include the age demographics for percentages of participants who are 16 through 64 years and 65 years of age
Number: 2 Author: Author Date: Indeterminate
Pfizer: Please add footnotes to Tables 1-4, that participants with chronic, stable HIV disease were excluded
FDA-CBER-2021-5683-1024741
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)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose.
No Grade 4 solicited systemic reactions were reported in participants 16 through 55 years of age.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. 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; Moderate: some interference with activity; Severe: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.
e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
f. Severity was not collected for use of antipyretic or pain medication.
FDA-CBER-2021-5683-1024742
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 (>2.0cm) 106(5.3) 20(1.0) 133(7.2) 14(0.8)
Mild 71 (3.5) 13 (0.7) 65 (3.5) 10 (0.5)
Moderate 30 (1.5) 5 (0.3) 58 (3.1) 3 (0.2)
Severe 5 (0.2) 2 (0.1) 10 (0.5) 1 (0.1)
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
Notes: Reactions were collected in the electronic diary (e -diary) from Day 1 to Day 7 after vaccination.
No Grade 4 solicited local reactions were reported in participants 56 years of age and older.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
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; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.
d. Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Table 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
26 (1.3) 8 (0.4) 219 (11.8) 4(0.2)
23 (1.1) 3 (0.2) 158 (8.5) 2(0.1)
2(0.1) 3 (0.2) 54 (2.9) 1(0.1)
1(0.0) 2 (0.1) 7 (0.4) 1(0.1)
0 0 0 0
Fatiguec
Any 677 (33.7) 447 (22.5) 949 (51.0) 306 (16.7)
Mild 415 (20.7) 281 (14.1) 391 (21.0) 183 (10.0)
Moderate 259 (12.9) 163(8.2) 497 (26.7) 121 (6.6)
Severe 3(0.1) 3 (0.2) 60 (3.2) 2(0.1)
FDA-CBER-2021-5683-1024743
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 (%)
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)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose.
The only Grade 4 solicited systemic reaction reported in participants 56 years of age and older was fatigue.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. N for each
reaction or use of antipyretic or pain medication was the same, therefore was included in the column header.
b. n = Number of participants with the specified reaction.
c. Mild: does not interfere with 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; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration; Grade 4 emergency visit
or hospitalization for severe vomiting.
FDA-CBER-2021-5683-1024744
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 (%)
e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours ;
Grade 4: emergency room or hospitalization for severe diarrhea.
f. Severity was not collected for use of antipyretic or pain medication.
Table 5 and Table 6 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 16 years of age and
older with confirmed stable HIV infection.
Table 5: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by
Maximum Severity, Within 7 Days After Each Dose – HIV-Positive Participants 16 Years of
Age and Older – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=54
nb (%) Placebo
Dose 1
Na=56
nb (%) COMIRNATY
Dose 2
Na=60
nb (%) Placebo
Dose 2
Na=62
nb (%)
Rednessc
Any (>2.0 cm) 2 (3.7) 3 (5.4) 4(6.7) 1(1.6)
Mild 2 (3.7) 1 (1.8) 3(5.0) 1(1.6)
Moderate 0 0 1(1.7) 0
Severe 0 2 (3.6) 0 0
Swellingc
Any (>2.0 cm) 3 (5.6) 1 (1.8) 5(8.3) 0
Mild 2 (3.7) 0 2(3.3) 0
Moderate 1 (1.9) 0 3(5.0) 0
Severe 0 1 (1.8) 0 0
Pain at the injection sited
Any 34 (63.0) 9(16.1) 32(53.3) 5(8.1)
Mild 26(48.1) 8(14.3) 22(36.7) 5(8.1)
Moderate 8(14.8) 1(1.8) 9(15.0) 0
Severe 0 0 1(1.7) 0
Notes: Reactions were collected in the electronic diary (e -diary) from Day 1 to Day 7 after vaccination.
No Grade 4 solicited local reactions were reported in HIV-positive participants 16 years of age and older.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for
each reaction was the same, therefore, this information was included in the column header.
b. n = Number of participants with the specified reaction.
c. Mild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.
d. Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Table 6: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – HIV-Positive Participants 16 Years of
Age and Older – Reactogenicity Subset of the Safety Population*
FDA-CBER-2021-5683-1024745
13 COMIRNATY
Dose 1
Na=54
nb (%) Placebo
Dose 1
Na=56
nb (%)COMIRNATY
Dose 2
Na=60
nb (%) Placebo
Dose 2
Na=62
nb (%)
Fever
1 (1.9) 4 (7.1) 9 (15.0) 5(8.1)
1 (1.9) 2 (3.6) 4(6.7) 5(8.1)
> 0 0 4(6.7) 0
> 0 2 (3.6) 1(1.7) 0
0 0 0 0
Fatiguec
Any 22 (40.7) 15 (26.8) 24(40.0) 12(19.4)
Mild 15 (27.8) 9 (16.1) 12(20.0) 5(8.1)
Moderate 7 (13.0) 5 (8.9) 9 (15.0) 7 (11.3)
Severe 0 1 (1.8) 3(5.0) 0
Headachec
Any 11 (20.4) 18 (32.1) 18(30.0) 12(19.4)
Mild 7 (13.0) 10 (17.9) 8 (13.3) 8 (12.9)
Moderate 4 (7.4) 7 (12.5) 8 (13.3) 4(6.5)
Severe 0 1 (1.8) 2(3.3) 0
Chillsc
Any 6 (11.1) 5 (8.9) 14(23.3) 4(6.5)
Mild 5 (9.3) 4 (7.1) 5(8.3) 3(4.8)
Moderate 1 (1.9) 1 (1.8) 8 (13.3) 1(1.6)
Severe 0 0 1(1.7) 0
Vomitingd
Any 1 (1.9) 3 (5.4) 2(3.3) 2(3.2)
Mild 1 (1.9) 1 (1.8) 1(1.7) 1(1.6)
Moderate 0 0 1(1.7) 1(1.6)
Severe 0 2 (3.6) 0 0
Diarrheae
Any 5 (9.3) 8 (14.3) 4(6.7) 9 (14.5)
Mild 5 (9.3) 6 (10.7) 1(1.7) 6(9.7)
Moderate 0 1 (1.8) 2(3.3) 3(4.8)
Severe 0 1 (1.8) 1(1.7) 0
New or worsened muscle painc
Any 9 (16.7) 10 (17.9) 10(16.7) 5(8.1)
Mild 7 (13.0) 7 (12.5) 5(8.3) 1(1.6)
Moderate 2 (3.7) 3 (5.4) 5(8.3) 4(6.5)
Severe 0 0 0 0
New or worsened joint painc
Any 5 (9.3) 7 (12.5) 10(16.7) 5(8.1)
Mild 5 (9.3) 4 (7.1) 4(6.7) 1(1.6)
Moderate 0 3 (5.4) 6 (10.0) 4(6.5)
Severe 0 0 0 0
Use of antipyretic or
pain medicationf 7 (13.0) 8 (14.3) 16(26.7) 7 (11.3)
FDA-CBER-2021-5683-1024746
14 COMIRNATY
Dose 1
Na=54
nb (%) Placebo
Dose 1
Na=56
nb (%)COMIRNATY
Dose 2
Na=60
nb (%) Placebo
Dose 2
Na=62
nb (%)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose.
No Grade 4 solicited systemic reactions were reported in HIV-positive participants 16 years of age and older.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for
each event 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; Moderate: some interference with activity; Severe: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration.
e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
f. Severity was not collected for use of antipyretic or pain medication.
Unsolicited Adverse Events
Upon issuance of the EUA for COMIRNATY, participants were unblinded to offer placebo participants
COMIRNATY. 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 by 103 (0.8%) COMIRNATY recipients and 117 (0.9%)
placebo recipients. In a similar analysis, in participants 56 years of age and older (COMIRNATY =8931,
placebo = 8895), serious adverse events were reported by 165 (1.8%) COMIRNATY recipients and 151 (1.7%)
placebo recipients who received at least 1 dose of COMIRNATY or placebo, respectively. In these analyses,
58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants with confirmed
stable HIV infection serious adverse events from Dose 1 up to the participant unblinding date in ongoing
follow-up were reported by 2 (2%) COMIRNATY recipients and 2 (2%) placebo recipients.
Therewere 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%) participants who received
COMIRNATY and 2136 (16.4%) 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%) participants who received
COMIRNATY and 1432 (16.1%) 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
FDA-CBER-2021-5683-1024747
15 events from Dose 1 up to the participant unblinding date in ongoing followup were reported by 29 (29%)
participants who received COMIRNATY and 15 (15%) 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) vs. 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 reliably estimate their frequency or establish a causal relationship to
vaccine exposure.
Cardiac Disorders: myocarditis, pericarditis
Gastrointestinal Disorders: diarrhea, vomiting
Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions
(e.g., rash, pruritus, urticaria, angioedema)
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
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 study 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). 1
2
3
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Page: 15
Number: 1 Author: Author Date: Indeterminate
Pfizer: Please describe local and systemic reactogenicity for the stable, chronic HIV+ participants in text to indicate that the frequencies of local and solicited reactions were generally the same or less frequent as compared to the
overall safety population described in Tables 1-4
Number: 2 Author: Author Date: Indeterminate
Pfizer: Please add a subsection to provide a description of the safety evaluation for the original BNT162b2 recipients who have at least 6 months of follow up post dose 2, through blinded and unblinded time periods
Number: 3 Author: Author Date: Indeterminate
Pfizer: Please delete this sentence and revise this introduction to describe the variable exposure caused by the unblinding that occurred in a phased manner, to include the actual difference in duration of follow up between
groups We will then report the following events as frequencies n/N (%) rather than incidence rates, as revised below
FDA-CBER-2021-5683-1024749
16 Data
Animal Data
In a developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of
nucleoside-modified messenger ribonucleic acid (mRNA) (30 mcg) and other ingredients included in a single
human dose of COMIRNATY was administered to female rats by the intramuscular route on 4 occasions: 21
and 14 days prior to mating, and on gestation days 9 and 20. No vaccine-related adverse effects on female
fertility, fetal development, or postnatal development were reported in the study.
8.2 Lactation
Risk Summary
It is not known whether COMIRNATY is excreted in human milk. Data are not available to assess the effects of
COMIRNATY on the breastfed infant or on milk production/excretion. The developmental and health benefits
of breastfeeding should be considered along with the mother’s clinical need for COMIRNATY and any
potential adverse effects on the breastfed child from COMIRNATY or from the underlying maternal condition.
For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.
8.4 Pediatric Use
Safety and effectiveness of COMIRNATY in individuals16 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
recipientsand 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 (0.43mg
((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2-(polyethylene glycol
2000)-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg
cholesterol), 0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 1 2
3
FDA-CBER-2021-5683-1024750
Page: 16
Number: 1 Author: Author Date: Indeterminate
Pfizer,
This subsection should focus on adverse reactions not observed in clinical trials Please provide a rationale for inclusion of diarrhea, vomiting and pain in extremity (arm)
Number: 2 Author: Author Date: Indeterminate
Pfizer,
Please add the PTs for "Dizziness" and "Dyspnea" and their corresponding SOCs to section 62
Number: 3 Author: Author Date: Indeterminate
Pfizer,
Please include information regarding Pregnancy Exposure Registry for COMIRNATY to monitor pregnancy outcomes in women exposed to COMIRNATY during pregnancy Please list the telephone number for the health care
providers to call and register women who receive COMIRNATY during pregnancy
FDA-CBER-2021-5683-1024751
17 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 mRNA in COMIRNATY is formulated in lipid particles, which enable delivery of the
mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune
response to the S antigen, which protects against COVID-19.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
COMIRNATY has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of
male fertility. In a developmental toxicity study in rats with COMIRNATY. There 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
-year stratum. The study excluded participants who were immunocompromised
and those who had previous clinical or microbiological diagnosis of COVID-19. Participants with preexisting
stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening
disease during the 6 weeks before enrollment, were included as were participants with known stable infection
with HIV, 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 with SARS-CoV-2 through 7 days after the second dose. Table 7 presents the specific
demographic characteristics in the studied population.
FDA-CBER-2021-5683-1024752
18 Table 7: Demographics (Population For the Primary Efficacy Endpoint)a
COMIRNATY
(N=18,242)
n (%) Placebo
(N=18,379)
n (%)
Sex
Male 9318 (51.1) 9225 (50.2)
Female 8924 (48.9) 9154 (49.8)
Age (years)
Mean (SD) 50.6 (15.70) 50.4 (15.81)
Median 52.0 52.0
Min, max (12, 89) (12, 91)
Age group
46 (0.3) 42 (0.2)
14,216 (77.9) 14,299 (77.8)
3176 (17.4) 3226 (17.6)
804 (4.4) 812 (4.4)
Race
White 15,110 (82.8) 15,301 (83.3)
Black or African American 1617 (8.9) 1617 (8.8)
American Indian or Alaska Native 118 (0.6) 106 (0.6)
Asian 815 (4.5) 810 (4.4)
Native Hawaiian or other Pacific Islander 48 (0.3) 29 (0.2)
Otherb 534 (2.9) 516 (2.8)
Ethnicity
Hispanic or Latino 4886 (26.8) 4857 (26.4)
Not Hispanic or Latino 13,253 (72.7) 13,412 (73.0)
Not reported 103 (0.6) 110 (0.6)
Comorbiditiesc
Yes 8432 (46.2) 8450 (46.0)
No 9810 (53.8) 9929 (54.0)
a. All eligible randomized participants who receive all vaccination(s) as randomized within the predefined window, have no other
important protocol deviations as determined by the clinician, and have no evidence of SARS-CoV-2 infection prior to 7 days
after Dose 2.
b. Includes multiracial and not reported.
c. Number of participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease:
Chronic lung disease (e.g., emphysema and chronic bronchitis, idiopathic pulmonary fibrosis, and cystic fibrosis) or
moderate to severe asthma
Significant cardiac disease (e.g., heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and
pulmonary hypertension)
2)
Diabetes (Type 1, Type 2, or gestational)
Liver disease
Human Immunodeficiency Virus (HIV) infection (not included in the efficacy evaluation)
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
FDA-CBER-2021-5683-1024753
19 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 8.
Table 8: 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 [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled
visit prior to 7 days after Dose 2 were included in the analysis.
a. N = Number of participants in the specified group.
FDA-CBER-2021-5683-1024754
20 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
-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.
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, 2020, representing up to 6 months of follow up after Dose 2.
The updated vaccine efficacy information is presented in Table 9.
Table 9: 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
During the Placebo-Controlled Follow-up Period
First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior
SARS-CoV-2 infection*
Subgroup COMIRNATY
Na=20,998
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,096 Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All participantsf 77
6.247 (20,712)850
6.003 (20,713) 91.3
(89.0, 93.2)
16 through 64 years 70
4.859 (15,519)710
4.654 (15,515) 90.6
(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 from7 days after Dose 2 in participants with or without* evidence of prior
SARS-CoV-2 infection
Subgroup COMIRNATY
Na=22,166
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=22,320
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All participantsf 81
6.509 (21,642)873
6.274 (21,689) 91.1
(88.8, 93.0)
16 through 64 years 74
5.073 (16,218)727
4.879 (16,269) 90.2
(87.6, 92.4)
65 years and older 7
1.267 (4315)128
1.232 (4326)94.7
(88.7, 97.9)
1
FDA-CBER-2021-5683-1024755
Page: 20
Number: 1 Author: Author Date: Indeterminate
Pfizer: Please delete this table and describe demographics of the efficacy population using the March 2021 data cutoff, to also include percentages of the participants in the age group 65 years, and those with comorbidities
(with a definition)
FDA-CBER-2021-5683-1024756
21
Note: Confirmed cases were determined by Reverse Transcription -Polymerase Chain Reaction (RT -PCR) and at least 1 symptom
consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
a. N = Number of participantsin the specified group.
b. n1 = Number of participantsmeeting 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.
f. Included confirmed cases in participants 12 through 15 years of age: 0 in the COMIRNATY group (both without and with or without
evidence of prior SARS-CoV-2 infection); 16 and 18 in the placebo group (without and with or without evidence of prior SARS-
CoV-2 infection, respectively).
The updated subgroup analyses of vaccine efficacy by demographic characteristics are presented in Table 10
and Table 11.
Table 10: Vaccine Efficacy– First COVID-19 Occurrence From 7 Days After Dose 2 – Participants
Without Evidence of Infection* Prior to 7 Days After Dose 2 by Demographic Characteristics –
Evaluable Efficacy (7 Days) Population During the Placebo-Controlled Follow-up Period
Subgroup COMIRNATY
Na=20,998
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,096
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)e
Sex
Male 42
3.246 (10,637) 399
3.047 (10,433)90.1
(86.4, 93.0)
Female35
3.001 (10,075) 451
2.956 (10,280)92.4
(89.2, 94.7)
Ethnicity
Hispanic or Latino 29
1.786 (5161) 241
1.711 (5120) 88.5
(83.0, 92.4)
Not Hispanic or Latino 47
4.429 (15,449) 609
4.259 (15,484)92.6
(90.0, 94.6)
Race
Black or African American4
0.545 (1737) 48
0.527 (1737) 91.9
(78.0, 97.9)
White 67
5.208 (17,186) 747
5.026 (17,256)91.3
(88.9, 93.4)
All othersf 6
0.494 (1789) 55
0.451 (1720) 90.0
(76.9, 96.5) 1
2
3
FDA-CBER-2021-5683-1024757
Page: 21
Number: 1 Author: Author Date: Indeterminate
Pfizer: Please describe the primary efficacy analysis in text as outlined below and remove Table 8
For participants without evidence of SARS-CoV-2 infection prior to 7 days after Dose 2, VE against confirmed COVID-19 occurring at least 7 days after Dose 2 was 950% 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 903% to 976%, indicating that the true VE is at least 903% with a 975% probability, which met the pre-
specified success criterion
Number: 2 Author: Author Date: Indeterminate
Pfizer: Please insert a sentence describing the percentage of participants with blinded placebo-controlled follow up 4months, to mirror the description of the Safety population
Number: 3 Author: Author Date: Indeterminate
Pfizer: Please revise Updated VE tables to display VE for participants 16 years of age and older (exclude participants 12-15 years of age) for only confirmed cases that we agree upon (exclude participant 10031167 from all
analyses, as previously communicated)
Please also delete the last 2 rows of each portion of the table: 65 through 74 years and 75 years and older
FDA-CBER-2021-5683-1024758
22 Subgroup COMIRNATY
Na=20,998
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,096
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)e
Country
Argentina 15
1.012 (2600) 108
0.986 (2586) 86.5
(76.7, 92.7)
Brazil 12
0.406 (1311) 80
0.374 (1293) 86.2
(74.5, 93.1)
Germany 0
0.047 (236) 1
0.048 (242) 100.0
(-3874.2, 100.0)
South Africa 0
0.080 (291) 9
0.074 (276) 100.0
(53.5, 100.0)
Turkey0
0.027 (228) 5
0.025 (222) 100.0
(-0.1, 100.0)
United States50
4.674 (16,046) 647
4.497 (16,094)92.6
(90.1, 94.5)
Notes: 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).
Included confirmed cases in participants 12 through 15 years of age: 0 in the COMIRNATY group; 16 in the placebo group.
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
a. N = Number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
c. Total surveillance time in 1000 person- years for the given endpoint across all participants within each group at risk for the endpoint.
Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
d. n2 = Number of participants at risk for the endpoint.
e. Two-sided confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the
surveillance time.
f. All others = American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, multiracial, and not reported race
categories.
Table 11: Vaccine Efficacy– First COVID-19 Occurrence From 7 Days After Dose 2 – Participants With
or Without* Evidence of Infection Prior to 7 Days After Dose 2 by Demographic
Characteristics – Evaluable Efficacy (7 Days) Population During the Placebo-Controlled
Follow-up Period
Subgroup COMIRNATY
Na=22,166
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=22,320
Cases
n1b
Surveillance Timec
(n2d)Vaccine Efficacy %
(95% CI)e
Sex
Male 44
3.376 (11,103) 411
3.181 (10,920)89.9
(86.2, 92.8)
Female37
3.133 (10,539) 462
3.093 (10,769)92.1
(88.9, 94.5) 1
FDA-CBER-2021-5683-1024759
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Number: 1 Author: Author Date: Indeterminate
Pfizer: This footnote should be removed based on our comment above to exclude all participants 12-15 years of age from this analysis
FDA-CBER-2021-5683-1024760
23 Subgroup COMIRNATY
Na=22,166
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=22,320
Cases
n1b
Surveillance Timec
(n2d)Vaccine Efficacy %
(95% CI)e
Ethnicity
Hispanic or Latino32
1.862 (5408)245
1.794 (5391)87.4
(81.8, 91.6)
Not Hispanic or Latino 48
4.615 (16,128) 628
4.445 (16,186)92.6
(90.1, 94.6)
Race
Black or African American4
0.611 (1958) 49
0.601 (1985) 92.0
(78.1, 97.9)
White 69
5.379 (17,801) 768
5.191 (17,880)91.3
(88.9, 93.3)
All othersf 8
0.519 (1883) 56
0.481 (1824) 86.8
(72.1, 94.5)
Country
Argentina 16
1.033 (2655) 110
1.017 (2670) 85.7
(75.7, 92.1)
Brazil 14
0.441 (1419) 82
0.408 (1401) 84.2
(71.9, 91.7)
Germany 0
0.047 (237) 1
0.048 (243) 100.0
(-3868.6, 100.0)
South Africa 0
0.099 (358) 10
0.096 (358) 100.0
(56.6, 100.0)
Turkey0
0.029 (238) 6
0.026 (232) 100.0
(22.2, 100.0)
United States51
4.861 (16,735) 664
4.678 (16,785)92.6
(90.2, 94.6)
Notes: 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).
Included confirmed cases in participants 12 through 15 years of age: 0 in the COMIRNATY group; 18 in the placebo group.
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
SARS-CoV- 2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
a. N = Number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
c. Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the endpoint.
Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
d. n2 = Number of participants at risk for the endpoint.
e. Two-sided confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the
surveillance time.
f. All others = American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, multiracial, and not reported race
categories.
FDA-CBER-2021-5683-1024761
24 The updated subgroup analyses of vaccine efficacy by risk status in participants arepresented in Table 12 and
Table 13.
Table 12: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Risk Status –
Participants Without Evidence of Infection*Prior to 7 Days After Dose 2 – Evaluable Efficacy
(7 Days) Population During the Placebo-Controlled Follow-up Period
SubgroupCOMIRNATY
Na=20,998
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,096
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)e
First COVID- 19 occurrence from
7 days after Dose 2f 77
6.247 (20,712) 850
6.003 (20,713) 91.3
(89.0, 93.2)
At riskg
Yes 35
2.797 (9167) 401
2.681 (9136) 91.6
(88.2, 94.3)
No 42
3.450 (11,545) 449
3.322 (11,577) 91.0
(87.6, 93.6)
Age group (years) and risk status
16 through 64 and not at risk 41
2.776 (8887) 385
2.661 (8886) 89.8
(85.9, 92.8)
16 through 64 and at risk 29
2.083 (6632) 325
1.993 (6629) 91.5
(87.5, 94.4)
65 and older and not at risk 1
0.553 (1870) 53
0.546 (1922) 98.1
(89.2, 100.0)
65 and older and at risk 6
0.680 (2322) 71
0.656 (2304) 91.8
(81.4, 97.1)
Obeseh
Yes 27
2.103 (6796) 314
2.050 (6875) 91.6
(87.6, 94.6)
No 50
4.143 (13,911) 536
3.952 (13,833) 91.1
(88.1, 93.5)
Age group (years) and obesity status
16 through 64 and not obese 46
3.178 (10,212) 444
3.028 (10,166) 90.1
(86.6, 92.9)
16 through 64 and obese24
1.680 (5303) 266
1.624 (5344) 91.3
(86.7, 94.5)
65 and older and not obese 4
0.829 (2821) 79
0.793 (2800) 95.2
(87.1, 98.7)
65 and older and obese 3
0.404 (1370) 45
0.410 (1426) 93.2
(78.9, 98.7)
Note: Confirmed cases were determined by Reverse Transcription -Polymerase Chain Reaction (RT -PCR) and at least 1 symptom
consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
a. N = Number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
FDA-CBER-2021-5683-1024762
25 SubgroupCOMIRNATY
Na=20,998
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,096
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)e
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 for
surveillance time.
f. Included confirmed cases in participants 12 through 15 years of age: 0 in the COMIRNATY group; 16 in the placebo group.
g. At risk is defined as having at least 1 of the Charlson2 th
percentile [12 through 15 years of age]).
h. 2. For 12 through 15 years age group, obesity is defined as a BMI at or above the 95thpercentile.
Refer to the CDC growth charts at https://www.cdc.gov/growthcharts/html charts/bmiagerev.htm .
Table 13: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Risk Status –
Participants With or Without* Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population Duringthe Placebo-Controlled Follow-up Period
SubgroupCOMIRNATY
Na=22,166
Cases
n1b
Surveillance Timec (n2d)Placebo
Na=22,320
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)e
First COVID- 19 occurrence from
7 days after Dose 2f 81
6.509 (21,642) 873
6.274 (21,689)91.1
(88.8, 93.0)
At riskg
Yes 36
2.925 (9601) 410
2.807 (9570) 91.6
(88.1, 94.2)
No 45
3.584 (12,041) 463
3.466 (12,119)90.6
(87.2, 93.2)
Age group (years) and risk status
16 through 64 and not at risk 44
2.887 (9254) 397
2.779 (9289) 89.3
(85.4, 92.4)
16 through64 and at risk30
2.186 (6964)330
2.100 (6980)91.3
(87.3, 94.2)
65 and older and not at risk 1
0.566 (1920) 55
0.559 (1966) 98.2
(89.6, 100.0)
65 and older and at risk 6
0.701 (2395) 73
0.672 (2360) 92.1
(82.0, 97.2)
Obeseh
Yes 28
2.207 (7139) 319
2.158 (7235) 91.4
(87.4, 94.4)
No 53
4.301 (14,497) 554
4.114 (14,448)90.8
(87.9, 93.2)
Age group (years) and obesity status
16 through 64 and not obese 49
3.303 (10,629) 458
3.158 (10,614)89.8
(86.2, 92.5)
FDA-CBER-2021-5683-1024763
26 Table 13: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Risk Status –
Participants With or Without* Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population Duringthe Placebo-Controlled Follow-up Period
SubgroupCOMIRNATY
Na=22,166
Cases
n1b
SurveillanceTimec (n2d)Placebo
Na=22,320
Cases
n1b
SurveillanceTimec (n2d) Vaccine Efficacy %
(95% CI)e
16 through 64 and obese25
1.768 (5584) 269
1.719 (5649) 91.0
(86.4, 94.3)
65 and older and not obese4
0.850 (2899)82
0.811 (2864)95.3
(87.6, 98.8)
65 and older and obese3
0.417 (1415) 46
0.420 (1462) 93.4
(79.5, 98.7)
Note: Confirmed cases were determined by Reverse Transcription -Polymerase Chain Reaction (RT -PCR) and at least 1 symptom
consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
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 for
surveillance time.
f. Included confirmed cases in participants 12 through 15 years of age: 0 in the COMIRNATY group; 18 in the placebo group.
g. 2 th
percentile [12 through 15 years of age]).
h. 2. For the 12 through 15 years of age group, obesity is defined as a BMI at or above the 95th
percentile. Refer to the CDC growth charts at https://www.cdc.gov/growthcharts/html charts/bmiagerevhtm .
Efficacy Against Severe 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 14) 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 14: Vaccine Efficacy – First Severe COVID-19 Occurrence in Participants With or Without* Prior
SARS-CoV-2 Infection Based on Protocol† or Centers for Disease Control and Prevention
(CDC)‡ Definition After Dose 1 or From 7 Days After Dose 2 in the Placebo-Controlled Follow-
up Vaccine Efficacy – First Severe COVID -19 Occurrence
COMIRNATY
Cases
n1a
Surveillance Time(n2b) Placebo
Cases
n1a
Surveillance Time (n2b) Vaccine Efficacy %
(95% CIc)
After Dose 1d 1 30 96.7
FDA-CBER-2021-5683-1024764
27 8.439e (22,505) 8.288e (22,435) (80.3, 99.9)
7 days after Dose 2f1
6.522g(21,649)21
6.404g(21,730)95.3
(70.9, 99.9)
Vaccine Efficacy – First Severe COVID-19 Occurrence Based on CDC Definition
COMIRNATY
Cases
n1a
Surveillance Time(n2b) Placebo
Cases
n1a
Surveillance Time (n2b) Vaccine Efficacy %
(95% CIc)
After Dose 1d 1
8.427e (22,473) 45
8.269e (22,394)97.8
(87.2, 99.9)
7 days after Dose 2f 0
6.514g (21,620) 32
6.391g (21,693) 100
(88.0, 100.0)
Note: Confirmed cases were determined by Reverse Transcription -Polymerase Chain Reaction (RT -PCR) and at least 1 symptom
consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
† Severe illness from COVID-19 is defined in the protocol as confirmed COVID-19 and presence of at least 1 of the following:
per
nspired
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. n2 = Number of participants at risk for the endpoint.
c. Two-side confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the
surveillance time.
d. Efficacy assessed based on the Dose 1 all available efficacy (modified intention-to-treat) population that included all randomized
participants who received at least 1 dose of study intervention.
e. 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 Dose 1 to the end of the surveillance period.
f. Efficacy assessed based on the evaluable efficacy (7 Days) population that included a ll eligible randomized participants who receive
all dose(s) of study intervention as randomized within the predefined window, have no other important protocol deviations as
determined by the clinician.
g. 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.
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 1
FDA-CBER-2021-5683-1024765
Page: 27
Number: 1 Author: Author Date: Indeterminate
Pfizer: Please delete Table 10-13
FDA-CBER-2021-5683-1024766
28 temperature 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. 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).
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. 1
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Pfizer: Please revise this table as follows:
Remove the rows for severe cases after Dose 1
Remove the specification of the FDA Definition of Severe Disease, as revised
FDA-CBER-2021-5683-1024768
29Undiluted vials may be stored at room temperature for no more than 2hours.
Transportationof ThawedVials
Available data support transportation of 1 or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 12hours.
Vials After Dilution
After dilution, storevials between 2°Cto 25°C (35°F to 77°F) and use within 6hours 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 6hours. Do not refreeze.
17 PATIENTCOUNSELING 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 registryfor COMIRNATY. Encourageindividuals exposed to COMIRNATY
around the time of conception or during pregnancy to register by 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 .
This product’s labelingmay have been updated. For the most recentprescribing information, please visit
www.pfizer.com .
Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany
Manufactured by
Pfizer Inc.,New York, NY 10017
LAB-1448-0.2
US Govt. License No. x
CPT Code x
1
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Number: 1 Author: Author Date: Indeterminate
Pfizer,
Please include a description of the vials from each of the two suppliers and include NDC numbers for cartons and containers of diluent from each of the manufacturers
FDA-CBER-2021-5683-1024770