Document text
1HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
TRADENAME safely and effectively. See full prescribing information for
TRADENAME.
TRADENAME (COVID-19 Vaccine, mRNA) suspension for r injection,
for intramuscular use
Initial U.S. Approval: YYYY
-------------------------------INDICATIONS AND USAGE ------------------------------
TRADENAME 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 -------------------------
TRADENAME is administered intramuscularly as a series of 2 doses
(0.3 mL each) 3 weeks apart. (2.3)
------------------------ DOSAGE FORMS AND STRENGTHS ------------------------
Suspension for injection. After preparation, a single dose is 0.3 mL. (3)
----------------------------------CONTRAINDICATIONS ---------------------------------
Known history of a severe allergic reaction (e.g., anaphylaxis) to any
component of TRADENAME. (4)-------------------------- W ARNINGS AND PRECAUTIONS --------------------------
Postmarketing reports of adverse events suggest increased risks of myocard itis
and pericarditis, particularly following the sec ond dose. (5.X)
Syncope (fainting) may occur in association with administration of injectable
vaccines, including TRADENAME. Procedures s hould be in place to avoid
injury from fainting. (5.X)
---------------------------------- ADVERSE REACTIONS ----------------------------------
I inical studies of 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*
DICATIONS 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 Post Marketing Experience7
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fer tility
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. FULL
1IFULL
1 II-------
--------
I in-----
c l1
2
FDA-CBER-2021-5683-0652192
Summary of Comments on 36A_BLA 125742-0_07-28-2021_Telecon_Labeling Target Cl.pdf
Page: 1
Number: 1 Author: Author Date: Indeterminate
Pfizer: Please provide percentages for each adverse reaction—i e , “ were pain at the injection site (X%), fatigue (X%) broken out by age (16 through 55 yrs and 56 and older), “
Number: 2 Author: Author Date: Indeterminate
Pfizer: we have inserted a place holder W/P for myocarditis/pericarditis based on the fact sheet language We anticipate that this will be further revised
FDA-CBER-2021-5683-0652193
2 FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
TRADENAME 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
xTRADENAME 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 0.9% Sodium Chloride Injection, USP (provided but shipped
separately) to form TRADENAME. Do not add more than 1.8 mL of diluent.
xONLY use the provided 0.9% Sodium Chloride Injection, USP as the diluent.
xAfter dilution, 1 vial contains 6 doses of 0.3 mL.
xRefer to dilution and dose preparation instructions in the panels below.
THAWING PRIOR TO DILUTION
xThaw vial(s) of TRADENAME before use 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 5 days (120 hours).
oAllowing vial(s) to sit at room temperature [up to 25ºC (77ºF)] for 30 minutes.
xUsing either thawing method, vials must reach room
temperature before dilution and must be diluted
within 2 hours.
1
2
FDA-CBER-2021-5683-0652194
Page: 2
Number: 1 Author: Author Date: Indeterminate
Pfizer: based on information in the BLA the saline diluent will be provided separately from the vials of vaccine We have revi sed the text since the diluent is provided separately
Number: 2 Author: Author Date: Indeterminate
Pfizer: the storage time in the fact sheets is one month Please explain why this is 5 days
FDA-CBER-2021-5683-0652195
3 xBefore dilution invert vaccine vial gently 10 times.
xDo not shake.
xInspect the liquid in the vial prior to dilution. The
liquid is a white to off-white suspension and may
contain white to off-white opaque amorphous
particles.
xDo not use if liquid is discolored or if other particles
are observed.
DILUTION
xUse the provided sterile 0.9% Sodium Chloride Injection, USP. Use only this as the diluent.
xUsing aseptic technique, withdraw 1.8 mL of diluent
into a transfer syringe (21-gauge or narrower
needle).
xCleanse the vaccine vial stopper with a single-use
antiseptic swab.
xAdd 1.8 mL of 0.9% Sodium Chloride Injection,
USP into the vaccine vial.
xEqualize vial pressure before removing the needle from the vial by withdrawing 1.8 mL air into the
empty diluent syringe.
FDA-CBER-2021-5683-0652196
4 xGently invert the vial containing the TRADENAME
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 TRADENAME 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 TRADENAME
xUsing aseptic technique, cleanse the vial stopper
with a single-use antiseptic swab, and withdraw
0.3 mL of TRADENAME 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 the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
xAdminister immediately.
FDA-CBER-2021-5683-0652197
5 2.2 Administration Information
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,
x verify the final dosing volume of 0.3 mL.
x confirm there are no particulates and that no discoloration is observed.
x do not administer if vaccine is discolored or contains particulate matter.
Administer TRADENAME intramuscularly.
After dilution, vials of TRADENAME 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,
x each dose must contain 0.3 mL of vaccine.
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.
2.3 Vaccination Schedule
TRADENAME 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 TRADENAME with other COVID-19 vaccines to complete the vaccination series. Individuals who have received 1 dose of TRADENAME should receive a second dose of
TRADENAME to complete the vaccination series.
3 DOSAGE FORMS AND STRENGTHS
TRADENAME is a suspension for injection. After preparation, a single dose is 0.3 mL.
4 CONTRAINDICATIONS
Do not administer TRADENAME to individuals with known history of a severe allergic reaction (e.g.,
anaphylaxis) to any component of the TRADENAME [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 TRADENAME.
5.2 Myocarditis and Pericarditis
Text based on FS (changed “Pfizer-BioNTech CO VID-19 Vaccine” to “TRADENAME”
Reports of adverse events following use of TRADENAME under EUA suggest increased risks of myocarditis and pericarditis, particularly following the second dose. Typically, onset of symptoms has been within a few
days following receipt of TRADENAME. Available data from short-term follow-up suggest that most
FDA-CBER-2021-5683-0652198
6 individuals have had resolution of symptoms, but information is not yet available about potential long-term
sequelae. The decision to administer TRADENAME to an individual with a history of myocarditis or pericarditis should take into account the individual’s clinical circumstances. The CDC has published clinical
considerations relevant to myocarditis and pericarditis associated with administration of Tradename
(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 TRADENAME. Procedures should be in place to avoid injury from fainting.
5.4 Altered Immunocompetence Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a
diminished immune response to the TRADENAME.
5.5 Limitation of Effectiveness TRADENAME may not protect all vaccine recipients.
6 ADVERSE REACTIONS .
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 TRADENAME was evaluated in participants 16 years of age and older in 2 clinical studies
conducted in the United States, Europe, Turkey, South Africa, and South America. Study BNT162-01 (Study 1)
was a Phase 1/2, 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 Phase 1/2/3, mu lticenter,
multinational, randomized, saline placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection
(Phase 1) and efficacy (Phase 2/3) study that has enrolled approximately 46,000 participants, 12 years of age or
older. Of these, approximately 44,047 participants (22,026 TRADENAME; 22,021 placebo) in Phase 2/3 are
16 years of age or older (including 378 and 376 adoles cents 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.
At the time of the analysis of Study 2 for the Emergency Use Authorization (EUA) with a data cut-off of
November 14, 2020, there were 37,586 participants (18,801 TRADENAME and 18,785 placebo) 16 years of
age or older followed for a median of 2 months after the second dose of TRADENAME. At the time of the
analysis of Study 2 for the EUA with a data cut-off of March 13, 2021, there were 25,651 (58.2%) participants 1
FDA-CBER-2021-5683-0652199
Page: 6
Number: 1 Author: Author Date: Indeterminate
Pfizer: We have inserted the text in the current fact sheet for vaccination providers as a placeholder but we expect that this will be further revised
FDA-CBER-2021-5683-0652200
7 (13,031 TRADENAME and 12,620 placebo) \HDUVRIDJHDQGROGHUIROORZHGIRU months after the second
dose.
The safety evaluation in Study 2 is ongoing. The safety population includes participants enrolled by
October 9, 2020, and includes safety data accrued through March 13, 2021. Participants 16 years and older in the reactogenicity subset are monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination in an electronic diary. Participants are being monitored for unsolicited
adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month (all
unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination]. Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity
among participants who received TRADENAME and those who received placebo. Overall, among the total
participants who received either TRADENAME 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 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 TRADENAME 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 TRADENAME 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 TRADENAME 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 TRADENAME
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*
TRADENAME
Dose 1
N
a=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) TRADENAME
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
Swellin gc
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
2
FDA-CBER-2021-5683-0652201
Page: 7
Number: 1 Author: Author Date: Indeterminate
Pfizer: We have included a couple of very high level comments in this section of the PI Additional comments will be provided after review of this section
Number: 2 Author: Author Date: Indeterminate
Pfizer: Please revise text to clarify that Study 1 was conducted in Germany and that Study 2 was conducted in the United States , Argentina, Brazil, Turkey, South Africa, and Germany
FDA-CBER-2021-5683-0652202
8 TRADENAME
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) TRADENAME
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 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.
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, 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*
TRADENAME
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) TRADENAME
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)
FDA-CBER-2021-5683-0652203
9 TRADENAME
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) TRADENAME
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.
* Ra ndomized participants in the safety a nalysis population who received a t lea st 1 dose of the study intervention.
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 wa s not collected for use of antipyretic or pa in medication.
FDA-CBER-2021-5683-0652204
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*
TRADENAME
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) TRADENAME
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.
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*
TRADENAME
Dose 1
N
a=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) TRADENAME
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
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
FDA-CBER-2021-5683-0652205
11 TRADENAME
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) TRADENAME
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
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.
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.
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 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 was not collected for use of antipyretic or pain medication.
FDA-CBER-2021-5683-0652206
12
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 TRADENAME 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*
TRADENAME
Dose 1
Na=54
nb (%) Placebo
Dose 1
Na=56
nb (%) TRADENAME
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
Swellin gc
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 in jection 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.
* Ra ndomized participants in the safety a nalysis population who received a t lea st 1 dose of the study intervention. 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, 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*
TRADENAME
Dose 1
Na=54
nb (%) Placebo
Dose 1
Na=56
nb (%) TRADENAME
Dose 2
Na=60
nb (%) Placebo
Dose 2
Na=62
nb (%)
Fever
ႏ 1 (1.9) 4 (7.1) 9 (15.0) 5 (8.1)
ႏWRႏ 1 (1.9) 2 (3.6) 4 (6.7) 5 (8.1)
>ႏWR ႏ 0 0 4 (6.7) 0
> ႏWRႏ 0 2 (3.6) 1 (1.7) 0
!ႏ 0 0 0 0
FDA-CBER-2021-5683-0652207
13 TRADENAME
Dose 1
Na=54
nb (%) Placebo
Dose 1
Na=56
nb (%) TRADENAME
Dose 2
Na=60
nb (%) Placebo
Dose 2
Na=62
nb (%)
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)
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 HIV-positive participants 16 years of age and older.
* Ra ndomized participants in the safety a nalysis population who received a t lea st 1 dose of the study intervention. 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 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; Moder ate: >2 times in 24 hours; Severe: requires intravenous hydr ation.
FDA-CBER-2021-5683-0652208
14 TRADENAME
Dose 1
Na=54
nb (%) Placebo
Dose 1
Na=56
nb (%) TRADENAME
Dose 2
Na=60
nb (%) Placebo
Dose 2
Na=62
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 .
f. Severity wa s not collected for use of antipyretic or pa in medication.
Unsolicited Adverse Events
Upon issuance of the EUA for TRADENAME, participants were unblinded to offer pl acebo participants
TRADENAME. 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 (TRADENAME = 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
TRADENAME recipients and 2.4 per 100 person-years among placebo recipients. In a similar analysis, in
participants 56 years of age and older (TRADENAME =8931, placebo = 8895), serious adverse events were
reported at an incidence rate of 4.9 per 100 person-years among TRADENAME recipients and 4.6 per
100 person-years among placebo recipients who received at least 1 dose of TRADENAME 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 TRADENAME 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
TRADENAME.
Non-Serious Adverse Events
Overall in Study 2 in which 12,995 participants 16 through 55 years of age received TRADENAME 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 TRADENAME 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 (TRADENAME = 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
who received TRADENAME 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
FDA-CBER-2021-5683-0652209
15 TRADENAME 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 TRADENAME 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.
Throughout the placebo-controlled safety follow-up period to date, Bell’s palsy (facial paralysis) was reported
by 4 participants in the TRADENAME 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 TRADENAME.
6.2 Post Marketing Experience
The following adverse reactions have been identified during post marketing useof TRADENAME, 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 Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersens itivity reactions
(e.g., rash, pruritus, urticaria, angioedema)
Gastrointestinal Disorders: diarrhea, vomiting
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 TRADENAME 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 TRADENAME 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 below .]
Data
Animal Data
FDA-CBER-2021-5683-0652210
16 In a reproductive and 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 TRADENAME 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 TRADENAME is excreted in human milk. Data are not available to assess the effects
of TRADENAME 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 TRADENAME and any potential adverse effects on the breastfed child from TRADENAME 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 TRADENAME in adolescents 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)] .
The safety and effectiveness of TRADENAME in individuals younger than 16 years of age have not been
established.
8.5 Geriatric Use
Of the total number of TRADENAME 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
TRADENAME (COVID-19 Vaccine, mRNA) is a sterile suspension for injection for intramuscular use.
TRADENAME is supplied as a frozen suspension in multiple dose vials; each vial must be diluted with 1.8 mL
of the provided sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine. Each dose of
TRADENAME contains 30 mcg of a nucleoside-modified messenger RNA (mRNA) encoding the viral spike
(S) glycoprotein of SARS-CoV-2. Each dose of the TRADENAME also includes the following ingredients: lipids (0.43 mg (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2[(polyethylene
glycol)-2000]-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg
cholesterol), 0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 0.07 mg dibasic sodium phosphate dihydrate, and 6 mg sucrose. The diluent (0.9% Sodium Chloride Injection,
USP) contributes an additional 2.16 mg sodium chloride per dose.
TRADENAME does not contain preservative. The vial stoppers are not made with natural rubber latex.
1
FDA-CBER-2021-5683-0652211
Page: 16
Number: 1 Author: Author Date: Indeterminate
Pfizer- Please re-order list of systems alphabetically
FDA-CBER-2021-5683-0652212
17 12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The nucleoside-modified mRNA in TRADENAME 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
TRADENAME has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of
male fertility. In studies in rats with TRADENAME, there were no vaccine-related effects on female fertility
[see Use in Special Populations (8.1)] .
14 CLINICAL STUDIES
14.1 Efficacy in Participants 16 Years of Age and Older
Study 2 is a multicenter, multinational, Phase 1/2/3, 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
DQGROGHUZLWKDPLQLPXPRIRISDUWLFLSDQWVLQWKH -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 the Phase 2/3 portion of Study 2, based on data accrued through November 14, 2020, approximately 44,000 participants 12 years of age and older were randomized equally and received 2 doses of TRADENAME
or placebo. The efficacy analyses included participants that received their second vaccination within 19 to 42 days after their first vaccination. The majority (93.1%) of vaccine recipients received the second dose 19 days to 23 days after Dose 1. 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 TRADENAME 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. 1
FDA-CBER-2021-5683-0652213
Page: 17
Number: 1 Author: Author Date: Indeterminate
Pfizer: this was revised to be consistent with the NP name
FDA-CBER-2021-5683-0652214
18 Table 7: Demographics (Population For the Primary Efficacy E ndpoint)a
TRADENAME
(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
WKURXJK\HDUV 46 (0.3) 42 (0.2)
WKURXJK\HDUV 14,216 (77.9) 14,299 (77.8)
WKURXJK\HDUV 3176 (17.4) 3226 (17.6)
\HDUV 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)
Ethnicit y
Hispanic or Latino 4886 (26.8) 4857 (26.4)
Not His panic or Latino 13,253 (72.7) 13,412 (73.0)
Not re ported 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 othe r
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 multira cial a nd not reported.
c. Number of participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease:
x Chronic lung disease (e.g., emphysema a nd chronic bronchitis, idiopathic pulmonary fibrosis, a nd cystic fibrosis) or
moder ate to severe asthma
x Significant cardiac disease (e.g., heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and
pulmonary hypertension)
x 2EHVLW\ ERG\PDVVLQGH[NJP2)
x Diabetes (Type 1, Type 2, or gestational)
x Liver disease
x Human Immunodeficiency Virus (HIV) infection (not included in the efficacy evaluation)
Efficacy Against COVID-19
The population in the 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. 1
2
FDA-CBER-2021-5683-0652215
Page: 18
Number: 1 Author: Author Date: Indeterminate
Pfizer: Subsection 8 1 refers to a single study Please clarify if “studies” should be revised to “a study ”
Number: 2 Author: Author Date: Indeterminate
Pfizer: We have not reviewed this section Comments will be provided after review
FDA-CBER-2021-5683-0652216
19
The vaccine efficacy information is presented in Table 8.
Table 8: 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 TRADENAME
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 TRADENAME
Na=19,965
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=20,172
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI )
All partici pantse 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 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 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.
FDA-CBER-2021-5683-0652217
20 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.
Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued during blinded
placebo-controlled follow-up through March 13, 2021, representing up to 6 months of follow-up after Dose 2 for participants in the efficacy population.
The updated vaccine efficacy information is presented in Table 9.
Table 9: 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
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 TRADENAME
Na=20,998
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,096 Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All partici pantsf 77
6.247 (20,712 ) 850
6.003 (20,713 ) 91.3
(89.0, 93.2 )
16 throu gh 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)
65 through 74 years 6
0.994 (3350) 98
0.966 (3379) 94.1
(86.6, 97.9)
75 years and older 1
0.239 (842) 26
0.237 (847) 96.2
(76.9, 99.9 )
First COVID-19 occurrence from 7 days after Dose 2 in participants with or without* evidence of prior
SARS-CoV-2 infection
Subgroup TRADENAME
Na=22,166
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=22,320
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All partici pantsf 81
6.509 (21,642 ) 873
6.274 (21,689 ) 91.1
(88.8, 93.0 )
16 throu gh 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 )
65 throu gh 74 years 6
1.021 (3450 ) 102
0.992 (3468 ) 94.3
(87.1, 98.0 )
75 years and older 1
0.246 (865) 26
0.240 (858) 96.2
(77.2, 99.9 )
FDA-CBER-2021-5683-0652218
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 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.
f. Included confirmed cases in pa rticipants 12 through 15 years of a ge: 0 in the TRADENAME 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
Sub
group TRADENAME
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 )
Female 35
3.001 (10,075 ) 451
2.956 (10,280 ) 92.4
(89.2, 94.7 )
Ethnicit y
Hispanic or Latino 29
1.786 (5161 ) 241
1.711 (5120 ) 88.5
(83.0, 92.4 )
Not His panic or Latino 47
4.429 (15,449 ) 609
4.259 (15,484 ) 92.6
(90.0, 94.6 )
Race
Black or African American 4
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)
FDA-CBER-2021-5683-0652219
22 Subgroup TRADENAME
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 )
German y 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 )
Turke y 0
0.027 (228) 5
0.025 (222) 100.0
(-0.1, 100.0 )
United States 50
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 o r
increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
Included confirmed cases in pa rticipants 12 through 15 years of a ge: 0 in the TRADENAME group; 16 in the placebo group.
* 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 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
surveilla nce time.
f. All others = American Indian or Ala ska Na tive, Asia n, Na tive Hawaiia n or other Pa cific Islander, multiracial, a nd not report ed ra ce
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
Sub
group TRADENAME
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 )
Female 37
3.133 (10,539) 462
3.093 (10,769) 92.1
(88.9, 94.5)
FDA-CBER-2021-5683-0652220
23 Subgroup TRADENAME
Na=22,166
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=22,320
Cases
n1b
Surveillance Timec
(n2d) Vaccine Efficacy %
(95% CI )e
Ethnicit y
Hispanic or Latino 32
1.862 (5408 ) 245
1.794 (5391 ) 87.4
(81.8, 91.6 )
Not His panic or Latino 48
4.615 (16,128 ) 628
4.445 (16,186 ) 92.6
(90.1, 94.6 )
Race
Black or African American 4
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 )
Countr y
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 )
Turke y 0
0.029 (238) 6
0.026 (232) 100.0
(22.2, 100.0 )
United States 51
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 o r
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 TRADENAME group; 18 in the placebo group.
* 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 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
surveilla nce time.
f. All others = American Indian or Ala ska Na tive, Asia n, Na tive Hawaiia n or other Pa cific Islander, multiracial, a nd not report ed ra ce
categories.
The updated subgroup analyses of vaccine efficacy by risk status in participants are presented in Table 12 and Table 13.
FDA-CBER-2021-5683-0652221
24 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
Subgroup TRADENAME
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 2
f 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 throu gh 64 and not at risk 41
2.776 (8887 ) 385
2.661 (8886 ) 89.8
(85.9, 92.8 )
16 throu gh 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 obesit y status
16 throu gh 64 and not obese 46
3.178 (10,212 ) 444
3.028 (10,166 ) 90.1
(86.6, 92.9 )
16 throu gh 64 and obese 24
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 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 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
surveilla nce time.
f. Included confirmed cases in participants 12 through 15 years of age: 0 in the TRADENAME group; 16 in the placebo group.
FDA-CBER-2021-5683-0652222
25 Subgroup TRADENAME
Na=20,998
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,096
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI )e
g. At risk is defined as having at least 1 of the Charlson &RPRUELGLW\,QGH[ &0, FDWHJRU\RUREHVLW\ %0,NJP2 RU%0, th
percentile [12 through 15 years of age]).
h. 2EHVHLVGHILQHGDV%0,NJP2. For 12 through 15 years 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/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
Efficac
y (7 Da ys) Population Durin g the Placebo-Controlled Follow-u p Period
Subgroup TRADENAME
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 da
ys 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 throu gh 64 and not at risk 44
2.887 (9254 ) 397
2.779 (9289 ) 89.3
(85.4, 92.4 )
16 throu gh 64 and at risk 30
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 obesit y status
16 through 64 and not obese 49
3.303 (10,629) 458
3.158 (10,614) 89.8
(86.2, 92.5)
16 through 64 and obese 25
1.768 (5584) 269
1.719 (5649) 91.0
(86.4, 94.3)
65 and older and not obese 4
0.850 (2899 ) 82
0.811 (2864 ) 95.3
(87.6, 98.8 )
65 and older and obese 3
0.417 (1415 ) 46
0.420 (1462 ) 93.4
(79.5, 98.7 )
FDA-CBER-2021-5683-0652223
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 During the Placebo-Controlled Follow-up Period
Subgroup TRADENAME
N
a=22,166
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=22,320
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CI)e
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 a ny unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
a . N = number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
c. Tota l surveilla nce time in 1000 person-years for the given endpoint across all pa rticipants 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
surveilla nce time.
f. Included confirmed cases in participants 12 through 15 years of age: 0 in the TRADENAME group; 18 in the placebo group.
g. $WULVNLVGHILQHGDVKDYLQJDWOHDVWRIWKH&KDUOVRQ&RPRUEL GLW\,QGH[ &0, FDWHJRU\RUREHVLW\ %0,NJP
2 RU%0, th
percentile [12 through 15 years of age]).
h. 2EHVHLVGHILQHGDV%0,NJP2. 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/bmiagerev htm .
Efficacy Against Severe COVID-19
Updated efficacy analyses of secondary efficacy endpoints supported benefit of TRADENAME 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 TRADENAME and placebo groups.
Table 14: Vaccine Efficacy – First Severe COVID-19 Occurrence in Participants With or Without* Prior
SARS-CoV-2 Infection Based on FDA
† 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 Efficac y – First Severe COVID-19 Occurrence Based on FDA Definition
TRADENAME
Cases
n1a
Surveillance Time (n2b) Placebo
Cases
n1a
Surveillance Time (n2b) Vaccine Efficacy %
(95% CIc)
After Dose 1d 1
8.439e (22,505) 30
8.288e (22,435) 96.7
(80.3, 99.9)
7 days after Dose 2f 1
6.522g (21,649) 21
6.404g (21,730) 95.3
(70.9, 99.9)
FDA-CBER-2021-5683-0652224
27 Vaccine Efficac y – First Severe COVID-19 Occurrence Based on CDC Definition
TRADENAME
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 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 a s defined by FDA is confirmed COVID-19 a nd presence of a t lea st 1 of the following:
x Clinica l siJQVDWUHVWLQGLFDWLYHRIVHYHUHV\VWHPLFLOOQHVV UHVSLUDWRU\ UDWH EUHDWKVSHUPLQXWHKHDUWUDWH EHDWVSHU
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. n2 = Number of participants a t 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
surveilla nce time.
d. Efficacy assessed based on the Dose 1 a ll a vailable efficacy (modified intention-to-treat) population that included all ra nd omized
participants who received at least 1 dose of study intervention.
e. 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 Dose 1 to the end of the surveillance period.
f. Efficacy assessed based on the evaluable efficacy (7 Da ys) population that included all eligible ra ndomized participants who recei v e
all dose(s) of study intervention as randomized within the predefined window, have no other important protocol deviations as determined by the clinician.
g. 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.
16 HOW SUPPLIED/STORAGE AND HANDLING
TRADENAME 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. 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.
FDA-CBER-2021-5683-0652225
28 Frozen Vials Prior to Use
Cartons of TRADENAME 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) un til 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 TRADENAME 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 within this temperature range 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 5 days (120 hours). 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. Any hours used for transport at 2°C to 8°C (35°F to 46°F) count against the 120-hour limit for storage at 2°C to 8°C (35°F to 46°F).
1
FDA-CBER-2021-5683-0652226
Page: 28
Number: 1 Author: Author Date: Indeterminate
Pfizer: Please include instructions on how to store the provided saline diluent
FDA-CBER-2021-5683-0652227
29Vials 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 TRADENAME
Inform vaccine recipient of the importance of completing the two dose vaccination series
Advise vaccine recipient to report any adverse events to their healthcare provider or to the Vaccine Adverse
Event Reporting System at 1-800-822-7967 and www.vaers.hhs.gov
.
This product’s labeling may have been updated. For the most recent prescribing information, please visit
www.pfizer.com .
Manufactured forBioNTech Manufacturing GmbH An der Goldgrube 12
55131 Mainz, Germany
Manufactured by
Pfizer Inc., New York, NY 10017
LAB-1448-0.1
US Govt. License No. x
1
2
3
FDA-CBER-2021-5683-0652228
Page: 29
Number: 1 Author: Author Date: Indeterminate
Pfizer: This is not consistent with the FS which states “Storage of the vials between -96°C to -60°C (-141°F to -76°F) is not c onsidered an excursion from the recommended storage condition ” Please revise if necessary
Number: 2 Author: Author Date: Indeterminate
Pfizer: the storage time in the FS is “1 month” Please explain why this is 5 days
Number: 3 Author: Author Date: Indeterminate
Pfizer: This statement is not in the FS See comments above regarding whether storage of undiluted vials at 2-8C is for 5days o r one month
FDA-CBER-2021-5683-0652229