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1 HIGHLIGHTS 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 -------------------------
x For intramuscular injection only. (2.2)
x COMIRNATY is administered intramuscularly as a series of 2 doses
(0.3 mL each) 3 weeks apart. (2.3)
------------------------ DOSAGE FORMS AND STRENGTHS ------------------------
Suspension for injection. After preparation, a single dose is 0.3 mL. (3)
---------------------------------- CONTRAINDICATIONS ---------------------------------
Known history of a severe allergic reaction (e.g., ana phylaxis) to any
component of COMIRNATY. (4)
-------------------------- W ARNINGS AND PRECAUTIONS --------------------------
x Postmarketing data demonstrate increased risks of myocarditis and
pericarditis, particularly within 7 days following the sec ond dose. (5.2)
x Syncope (fainting) may occur in association with administration of
injectable vaccines, including COMIRNATY. Procedures s hould be in
place to avoid injury from fainting. (5.4)
---------------------------------- ADVERSE REACTIONS ----------------------------------
x 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)
x 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
2.2 Administration Information
2.3 Vaccination Schedule
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions 5.2 Myocarditis and Pericarditis
5.3 Syncope
5.4 Altered Immunocompetence
5.5 Limitation of Effectiveness
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fer tility
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-2021-5683-0652230
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
For intramuscular injection only.
2.1 Preparation for Administration
Prior to Dilution
xCOMIRNATY 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.
xVials 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)] .
xRefer to thawing instructions in the panels below.
Dilution
xDilute 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.
xONLY use sterile 0.9% Sodium Chloride Injection, USP as the diluent. Do not use bacteriostatic 0.9%
Sodium Chloride Injection or any other diluent.
xVials of sterile 0.9% Sodium Chloride Injection, USP are provided but shipped separately. Use the provided diluent or another sterile 0.9% Sodium Chloride Injection, USP as the diluent.
oProvided diluent vials are single-use only; discard after 1.8 mL is withdrawn.
oIf another sterile 0.9% Sodium Chloride Injection, USP is used as the diluent, discard after 1.8
mL is withdrawn.
oDo not use diluent vials to dilute multiple vials of COMIRNATY.
xAfter dilution, 1 vial of COMIRNATY contains 6 doses of 0.3 mL each.
xRefer to dilution and dose preparation instructions in the panels below.
THAWING PRIOR TO DILUTION
xThaw vial(s) of COMIRNATY before 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 3 hours 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.
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3 xUsing either thawing method, vials must reach room
temperature before dilution and must be diluted within 2 hours.
xBefore dilution invert vaccine vial gently 10 times.
xDo not shake.
xInspect 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.
xDo not use if liquid is discolored or if other particles are observed.
DILUTION
xONLY use sterile 0.9% Sodium Chloride Injection,
USP as the diluent.
xWithdraw 1.8 mL of diluent into a transfer syringe
(21-gauge or narrower needle).
xAdd 1.8 mL of sterile 0.9% Sodium Chloride
Injection, USP into the vaccine vial.
xEqualize vial pressure before removing the needle
from the vaccine vial by withdrawing 1.8 mL air into the empty diluent syringe.
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4 xGently invert the vial containing COMIRNATY 10
times to mix.
xDo not shake.
xInspect the vaccine in the vial.
xThe vaccine will be an off-white suspension. Do not use if vaccine is discolored or contains particulate matter.
xRecord the date and time of dilution on the COMIRNATY vial label.
xStore between 2°C to 25°C (35°F to 77°F).
xDiscard any unused vaccine 6 hours after dilution.
PREPARATION OF INDIVIDUAL 0.3 mL DOSES OF COMIRNATY
xWithdraw 0.3 mL of COMIRNATY preferentially
using low dead-volume syringes and/or needles.
xEach dose must contain 0.3 mL of vaccine.
xIf 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.
xAdminister immediately.
After dilution, vials of COMIRNATY contain 6 doses of 0.3 mL of vaccine. Low dead-volume syringes and/or
needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a sixth dose from a single vial. Irrespective of the type of syringe and needle,
xeach dose must contain 0.3 mL of vaccine.
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5 x 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.
x do not pool excess vaccine from mu ltiple 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. Indi viduals 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 years of age. Available data from short-term follow-up suggest that most individuals have had resolution of symptoms. Information is not yet available about potential long-term sequelae. The CDC has published
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. 1
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Summary of Comments on 72A_BLA 125742-0_08-13-2021_Telecon_Labeling via FAX_e.pdf
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Please note, we intend to communicate additional comments regarding Section 5 to you next week
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6 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 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%).
In clinical studies, the most commonly reported ( 10%) adverse reactions in participants 56 years of age and
older following any dose were pain at the injection site (78.2%), fatigue (56.9%), headache, (45.9%), muscle
pain (32.5%), chills (24.8%), joint pain (21.5%), injection site swelling (11.8%), fever (11.5%), and injection site redness (10.4%).
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, 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 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-pos itive
participants are included in safety population disposition but are summarized separately in safety analyses.
Confirmed stable HIV infection was defined as documented viral load <50 copies/mL and CD4 count
>200 cells/mm3 within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 months.
At the time of the analysis of the ongoing Study 2 with a data cut-off of March 13, 2021, there were
25,651 (58.2%) participants (13,031 COMIRNATY and 12,620 placebo) 16 years of age and older followed for
PRQWKVDIWHUWKHVHFRQGGRVH .
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].
1
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Please delete Our intent is to convey the most commonly reported adverse reactions in this section
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7 Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity
among participants who received COMIRNATY and those who received placebo. Overall, among the total participants who received either COMIRNATY or placebo, 50.9% were male, 49.1% were female, 79.3% were
16 through 64 years of age, 20.7% were 65 years of age and older, 82.0% were White, 9.6% were Black or
African American, 25.9% were Hispanic/Latino, 4.3% were Asian, and 1.0% were American Indian or Alaska Native.
Local and Systemic Adverse R eactions 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 Through 55 Years of
Age – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Rednessc
Any (>2.0 cm ) 156 (5.4) 28 (1.0) 151 (5.6) 18 (0.7)
Mild 113 (3.9) 19 (0.7) 90 (3.4) 12 (0.4)
Moderate 36 (1.2) 6 (0.2) 50 (1.9) 6 (0.2)
Severe 7 (0.2) 3 (0.1) 11 (0.4) 0
Swellingc
Any (>2.0 cm ) 184 (6.3) 16 (0.6) 183 (6.8) 5 (0.2)
Mild 124 (4.3) 6 (0.2) 110 (4.1) 3 (0.1)
Moderate 54 (1.9) 8 (0.3) 66 (2.5) 2 (0.1)
Severe 6 (0.2) 2 (0.1) 7 (0.3) 0
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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 in jection 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. * Ra ndomized participants in the safety a nalysis population who received a t lea st 1 dose of the study intervention. Pa rticipant s
with chronic, stable HIV infection were excluded.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for
each reaction was the same, therefore, this information was included in the column header.
b. n = Number of participants with the specified reaction. c. Mild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.
d. Mild: does not interfere with activity; 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
ႏ 119 (4.1) 25 (0.9) 440 (16.4) 11 (0.4)
ႏWRႏ 86 (3.0) 16 (0.6) 254 (9.5) 5 (0.2)
>ႏWR ႏ 25 (0.9) 5 (0.2) 146 (5.4) 4 (0.1)
> ႏWRႏ 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)
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9 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
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)
Vomitin gd
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 a nd use of antipyretic or pa in medication were collected in the electronic dia ry (e-diary) from Da y 1 to Da y 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. Participant s
with chronic, stable HIV infection were excluded.
a . N = Number of participants reporting a t lea st 1 yes or no response for the specified reaction a fter 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; Moder ate: >2 times in 24 hours; Severe: requires intravenous hydr ation.
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.
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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 in jection 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. Participant s
with chronic, stable HIV infection were excluded.
a . N = Number of participants reporting a t lea st 1 yes or no response for the specified reaction a fter 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 a ctivity; Moderate: interferes with a ctivity; Severe: prevents daily a ctivity.
Table 4: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and
Older – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Fever
ႏ 26 (1.3) 8 (0.4) 219 (11.8) 4 (0.2)
ႏWRႏ 23 (1.1) 3 (0.2) 158 (8.5) 2 (0.1)
!ႏWR ႏ 2 (0.1) 3 (0.2) 54 (2.9) 1 (0.1)
! ႏWRႏ 1 (0.0) 2 (0.1) 7 (0.4) 1 (0.1)
!ႏ 0 0 0 0
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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
Vomitin gd
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. Participant s
with chronic, stable HIV infection were excluded.
a . N = Number of participants reporting a t lea st 1 yes or no response for the specified reaction a fter the specified dose. N fo r 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-2021-5683-0652242
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 a ctivity; Moderate: some interference with a ctivity; Severe: prevents daily a ctivity; Gra de 4
reactions were defined in the clinical study protocol as emergency room visit or hospitalization for severe fatigue, severe
hea dache, severe chills, severe muscle pain, or severe joint pain.
d. Mild: 1 to 2 times in 24 hours; Moder ate: >2 times in 24 hours; Severe: requires intravenous hydr ation; Grade 4 emergency vi sit
or hospitalization for severe vomiting.
e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours ;
Grade 4: emergency room or hospitalization for severe diarrhea.
f. Severity wa s not collected for use of antipyretic or pa in medication.
In participants with chronic, stable HIV infection the frequencies of solicited local and systemic adverse
reactions were similar to or lower than those observed for all participants 16 years of age and older.
Unsolicited Adverse Events
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 at an incidence rate of 2.1 per 100 person-years among
COMIRNATY recipients and 2.4 per 100 person-years among placebo recipients. In a similar analysis, in
participants 56 years of age and older (COMIRNATY =8931, placebo = 8895), serious adverse events were
reported at an incidence rate of 4.9 per 100 person-years among COMIRNATY recipients and 4.6 per
100 person-years among placebo recipients who received at least 1 dose of COMIRNATY or placebo,
respectively. In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2.
Among participants with confirmed stable HIV infection serious adverse events from Dose 1 up to the
participant unblinding date in ongoing follow-up were reported at an incidence rate of 6.6 per 100 person-years
among COMIRNATY recipients and 6.9 per 100 person-years among placebo recipients.
There were no notable patterns between treatment groups for specific categories of serious adverse events
(including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to
COMIRNATY.
Non-Serious Adverse Events
Overall in Study 2 in which 12,995 participants 16 through 55 years of age received COMIRNATY and
13,026 participants received placebo, all events, which in clude non-serious adverse events from Dose 1 up to
the participant unblinding date in ongoing follow-up were reported at an incidence rate of 88.4 per
100 person-years among participants who received COMIRNATY and 43.5 per 100 person-years among
participants in the placebo group, for participants who received at least 1 dose. In a similar analysis, in
participants 56 years of age and older (COMIRNATY = 8931, placebo = 8895), all events, which include
non-serious adverse events were reported at an incidence rate of 75.7 per 100 person-years among participants 1
2
FDA-CBER-2021-5683-0652243
Page: 12
Number: 1 Author: Author Date: Indeterminate
Pfizer,
This description is redundant from the overall safety description provided above, so it has been deleted To clarify our request: please add a subsection to describe the frequencies of unsolicited non-serious and serious adverse even ts that occurred from Dose 1 through the March 2021 data cutoff, in the original vaccine recipients
that have follow-up for at least 6 months after Dose 2 (n 12,006)
Number: 2 Author: Author Date: Indeterminate
Pfizer, We do not think that the presentation of these data using incidence rates is helpful for the healthcare provider
Additionally, we do not agree with the method by which the incidence rates are calculated It appears that the incidence rate f or each event type is based on the number of subjects who reported at least one event divided by the
total person-years contributed by all subjects from Dose 1 to unblinding but does not account for the number of events a subjec t may report, or the timing of these events in deriving the total length of period “at risk ” This may
be misleading as it under-reports the true incidence rate In addition, we note that the total lengths of follow-up between arm s are within 2% in both age groups (18 through 55, 56 and above), thus differences in follow-up
appear to be minor Therefore, we continue to request the use of proportions to present safety data
FDA-CBER-2021-5683-0652244
13 who received COMIRNATY and 43.3 per 100 person-years among participants in the placebo group, for
participants who received at least 1 dose. Among participants with confirmed stable HIV infection, all events,
which include non-serious adverse events from Dose 1 up to the participant unblinding date in ongoing
follow-up were reported at an incidence rate of 95.8 per 100 person-years among participants who received
COMIRNATY and 52.0 per 100 person-years among participants in the placebo group, for participants who
received at least 1 dose.
In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2. The higher
frequency of reported unsolicited non-serious adverse events among COMIRNATY recipients (inclusive of
stable HIV infection) compared to placebo recipients was primarily attributed to local and systemic adverse
events reported during the first 7 days following each dose of vaccine that are consistent with adverse reactions
solicited among participants in the reactogenicity subset and presented in Table 3 and Table 4.
From Dose 1 up to the participant unblinding date, reports of lymphadenopathy were imbalanced with notably
more cases in the COMIRNATY group (87) versus 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. B ecause 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.
FDA-CBER-2021-5683-0652245
14 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) .
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 st udy.
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 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.
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 0.3 mL dose of the COMIRNATY also includes the following ingredients: lipids (0.43 mg
((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2-(polyethylene glycol
2000)-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg 1
FDA-CBER-2021-5683-0652246
Page: 14
Number: 1 Author: Author Date: Indeterminate
Pfizer,
We do not concur because it appears that OTIS is recruiting from a wide variety of sites We request that you include contact i nformation for the registry in the PI as follows:
“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 www ”
FDA-CBER-2021-5683-0652247
15 cholesterol), 0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride,
0.07 mg dibasic sodium phosphate dihydrate, and 6 mg sucrose. The diluent (0.9% Sodium Chloride Injection,
USP) contributes an additional 2.16 mg sodium chloride per dose.
COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The nucleoside-modified 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 v accine-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 an ongoing mu lticenter, multinational, randomized, pl acebo-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
PLQLPXPRIRISDUWLFLSDQWVLQWKH -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. Overall, among the total participants who received COMIRNATY or placebo, 51.4% or 50.5% were male and
48.6% or 49.5% were female, 75.1% or 75.1% were 16 through 64 years of age, 20.1% or 20.3% were 65 years
of age and older, 16.1% or 16.3% were 65 through 74 years of age, 4.0% or 4.0% 75 years of age and older,
82.9% or 83.1% were White, 8.5% or 8.6% were Black or African American, 0.9% or 0.9% were American
Indian or Alaska Native, 4.6% or 4.5% were Asian, 0.3% or 0.1% Native Hawaiian or other Pacific Islander,
24.9% or 24.6% were Hispanic/Latino, 74.6% or 74.8% were non-Hispanic/Latino, 0.5% or 0.5% did not report
ethnicity, 44.6% or 44.4% had 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
FDA-CBER-2021-5683-0652248
16 category or body mass index (BMI) NJP2], respectively. The mean age at vaccination was 48.3 or 48.2
years and median age was 50.0 or 50.0 in participants who received COMIRNATY or placebo, respectively.
Efficacy Against COVID-19
The population 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 Occu rrence 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 partici pantse 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 14 92.9 1
FDA-CBER-2021-5683-0652249
Page: 16
Number: 1 Author: Author Date: Indeterminate
Pfizer,
Please revise the demographics to describe the efficacy population used for the updated VE analyses in participants 16 years of age and older (please exclude participants 12-15 years of age) Results should be the same as those
provided in Shell Table F with STN 126472/0 32
FDA-CBER-2021-5683-0652250
17 0.424 (3239 ) 0.423 (3255 ) (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 o r
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Pa rticipants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding a ntibody [serum] negative a t Visit 1 a nd
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. Tota l surveilla nce time in 1000 person-years for the given endpoint across all pa rticipants within each group a t risk for th e
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
ș U -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 a djusted to the
surveilla nce time.
The population for the updated vaccine efficacy analysis included participants 16 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 during blinded placebo-controlled follow-up through March 13, 2021, representing up to 6 months of follow-up after Dose 2.
There were XX (X%) participants (XX COMIRNATY and XX placebo) followed for PRQWKV after Dose 2 in
the blinded placebo-controlled follow-up period.
The updated vaccine efficacy information is presented in Table 6.
Table 6: Vaccine Efficacy – First COVID-19 Occu rrence 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 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=19,993
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=20,118
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All partici pantsf 77
6.092 (19,711 ) 833
5.857 (19,741 ) 91.1
(88.8, 93.1 )
16 throu gh 64 years 70
4.859 (15,519 ) 709
4.654 (15,515 ) 90.5
(87.9, 92.7 )
65 years and older 7
1.233 (4192 ) 124
1.202 (4226 ) 94.5
(88.3, 97.8 )
FDA-CBER-2021-5683-0652251
18 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 partici pants 81
6.340 (20,533 ) 854
6.110 (20,595 ) 90.9
(88.5, 92.8 )
16 throu gh 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 o r
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] neg ative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
a . N = Number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
c. Tota l surveilla nce time in 1000 person-years for the given endpoint across all pa rticipants within each group a t risk for th e 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
surveilla nce time.
Efficacy Against Severe COVID-19
Efficacy analyses of secondary efficacy endpoints supported benefit of COMIRNATY in preventing severe COVID-19. Vaccine efficacy against se vere COVID-19 is presented only for participants with or without prior
SARS-CoV-2 infection (Table 7) as the COVID-19 case counts in participants without prior SARS-CoV-2
infection were the same as those in participants with or without prior SARS-CoV-2 infection in both the
COMIRNATY and placebo groups.
Table 7: Vaccine Efficacy – First Severe CO VID-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 Efficac y – 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 ) 1
2
FDA-CBER-2021-5683-0652252
Page: 18
Number: 1 Author: Author Date: Indeterminate
Pfizer:
We continue to request deletion of this Table because the information is redundant with the updated VE analysis that follows with additional confirmed cases Please insert the text requested below:
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 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 %, indicating that the true VE is at least 90 3% with a 97 5% probability, which met the pre-
specified success criterion
Number: 2 Author: Author Date: Indeterminate
Pfizer,
Revised the language to mirror description of the Safety population
We note that these numbers were derived from follow-up times, based on the safety population Please update the information, ba sed on the follow up time after Dose 2 for the efficacy population
FDA-CBER-2021-5683-0652253
19 Vaccine Efficac y – 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 o r
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Pa rticipants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding a ntibody [serum] negative a t Visit 1 a nd
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:
x ClinicDOVLJQVDWUHVWLQGLFDWLYHRIVHYHUHV\VWHPLFLOOQHVV UHVSLUD WRU\UDWHEUHDWKVSHUPLQXWHKHDUWUDWHEHDWVSHU
PLQXWHVDWXUDWLRQRIR[\JHQ RQURRPDLUDWVHDOHYHORU UDWLRRIDUWHULDOR[\JHQSDUWLDOSUHVVXUHWRIUDFWLRQDOLQVSLU ed
oxygen <300 mm Hg);
x Respira tory failure [defined a s needing high-flow oxygen, noninvasive ventilation, mechanical ventila tion or extracorporeal
membrane oxygenation (ECMO)];
x Evidence of shock (systolic blood pressure <90 mm Hg, diastolic blood pressure <60 mm Hg, or requiring vasopressors);
x Significa nt a cute renal, hepatic, or neurologic dysfunction;
x Admission to an Intensive Care Unit;
x Death.
‡ Severe illness from COVID-19 as defined by CDC is confirmed COVID-19 and presence of at least 1 of the following:
x Hospitalization;
x Admission to the Intensive Care Unit;
x Intubation or mechanical ventilation;
x Death.
a . n1 = Number of participants meeting the endpoint definition.
b. Tota l surveilla nce time in 1000 person-years for the given endpoint across all pa rticipants within each group a t risk for the endpoint.
Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
c. n2 = Number of participants a t risk for the endpoint.
d. Two-side confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the
surveilla nce time.
16 HOW SUPPLIED/STORAGE AND HANDLING
COMIRNATY 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 s upplied either as cartons of 10 mL single-use vials manufactured by
Hospira, Inc (NDC 0409-4888-10), or 2 mL single-use vials 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. 1
FDA-CBER-2021-5683-0652254
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Number: 1 Author: Author Date: Indeterminate
Pfizer,
This general statement is misleading because some of the subgroup analyses were limited by the size of the subgroup and low num ber of confirmed cases, which limits the interpretation of those analyses We disagree with this
addition and request deletion
FDA-CBER-2021-5683-0652255
20 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.
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.
1
FDA-CBER-2021-5683-0652256
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Number: 1 Author: Author Date: Indeterminate
Pfizer,
Please update this section to include information on the diluent manufactured at the Pfizer Healthcare India site
FDA-CBER-2021-5683-0652257
21Vials 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 ca lling ….. Advise v accine 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 labeling may have been updated. For the most recent prescribing in formation, please visit
www.comirnatyglobal.com .
Manufactured forBioNTech Manufacturing GmbH
An der Goldgrube 1255131 Mainz, Germany
Manufactured by
Pfizer Inc., New York, NY 10017
LAB-1448-0.3
US Govt. License No. x
CPT Code x
1
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Number: 1 Author: Author Date: Indeterminate
Pfizer,
Please see comment in Section 8 1
FDA-CBER-2021-5683-0652259