Document text
From: Smith, Michael (CBER)
Sent: Tuesday, May 10, 2022 11:53 AM
To:'Collins, Kathleen Mary Catherine'
Cc:Naik, Ramachandra <[email protected]>; Gottschalk, Laura
<[email protected]>; 'MaguireThon, Meghan' <[email protected]>;
'Mineo, Gosia' ; 'Harkins Tull, Elisa' <Elisa. [email protected]>; 'Devlin,
Carmel M' <[email protected]>Subject: STN 125742/45: Revised PI labeling
Kate,
We have reviewed the Package Insert that was submitted to STN 125742.45 on April
29thand we have a couple of additional proposed revisions in the attached
document. Also, we discussed Pfizer’s proposal to maintain the originally used chemical name and we are in agreement at this time. The review team has requested that the PI be sent back by Monday, May 16
th. In addition, please also submit a
Tris/Sucrose version of the PI (tracked changes and clean running).
Regards,
Mike
- Please confirm receipt of this email and let us know if you have any questions.
Mike Smith, Ph.D.
Captain, USPHS
Senior Regulatory Review Officer
Food and Drug AdministrationCenter for Biologics Evaluation & ResearchOffice of Vaccines Research & Review
Division of Vaccines and Related Products Applications
Tel: [email protected]
THIS MESSAGE IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT IS
ADDRESSED AND MAY CONTAIN INFORMATION THAT IS PRIVILEGED, CONFIDENTIAL, AND
PROTECTED FROM DISCLOSURE UNDER LAW. If you are not the addressee, or a
person authorized to deliver the document to the addressee, you are hereby
notified that any review, disclosure, dissemination, copying, or other action
based on the content of this communication is not authorized. If you have
received this document in error, please immediately notify the sender immediately by e-mail or phone.
Michael J.
Smith -S4Digitally signed by Michael J. Smith -S4 Date: 2022.05.10 14:29:29 -04'00'
(b) (6)
(b) (6)
FDA-CBER-2022-5812-0500450
FDA-CBER-2022-5812-0500451
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: 2021
--------------------------- RECENT MAJOR CHANGES ---------------------------
Indications and Usage (1) M/YYYY
Dosage and Administration, Preparation for Administration (2.1) 12/2021
--------------------------- 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 12 years of age and
older. (1)
----------------------- DOSAGE AND ADMINISTRATION -----------------------
x COMIRNATY supplied in multiple dose vials with purple caps and
labels with purple borders MUST BE DILUTED before use. (2.1)
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., anaphylaxis) to any
component of COMIRNATY. (4) ----------------------- WARNINGS AND PRECAUTIONS -----------------------
x Postmarketing data demonstrate increased risks of myocarditis and
pericarditis, particularly within 7 days following the second dose. (5.2)
x Syncope (fainting) may occur in association with administration of
injectable vaccines, including COMIRNATY. Procedures should be in
place to avoid injury from fainting. (5.4)
------------------------------ ADVERSE REACTIONS ------------------------------
x In clinical studies of participants 16 through 55 years of age, the most
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VLWH IDWLJXH KHDGDFKH PXVFOHSDLQ
FKLOOV MRLQWSDLQ IHYHU DQGLQMHFWLR QVLWH
swelling (10.
x In clinical studies of participants 56 years of age and older, the most
FRPPRQO\UHSRUWHGDGYHUVHUHDFWLRQV ZHUHSDLQDWWKHLQM HFWLRQ
VLWH IDWLJXH KHDGDFKH PXVFOHSDLQ
FKLOOV MRLQWSDLQ LQMHFWLRQVLWHVZHOOLQJ IHYHU
DQGLQMHFWLRQVLWHUHGQHVV )
x In clinical studies of adolescents 12 through 15 years of age, the most
commonly reported adverse reactions 8 were pain at the injection
site (90.5), IDWLJXH KHDGDFKH FKLOOV PXVFOH
SDLQ IHYHU joint pain (20.2 , injection site swelling
DQGLQMHFWLRQVLWHUHGQHVV . (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at
1-800-438-1985 or VAERS at 1-800-822-7967 or http://vaers.hhs.gov .
See 17 for PATIENT COUNSELING INFORMATION.
Revised: M/YYYY
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Preparation for Administration
2.2 Administration Information
2.3 Vaccination Schedule
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions 5.2 Myocarditis and Pericarditis
5.3 Syncope 5.4 Altered Immunocompetence 5.5 Limitation of Effectiveness
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience 6.2 Postmarketing Experience
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.2 Lactation 8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Efficacy in Participants 16 Years of Age and Older
14.2 Efficacy in Adolescents 12 Through 15 Years of Age
14.3 Immunogenicity in Adolescents 12 Through 15 Years of Age
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are not
listed.
FDA-CBER-2022-5812-0500452
2 FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
COMIRNATY is a vaccine indicated for active immuni zation to prevent coronavirus disease 2019 (COVID-19)
caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and
older.
2 DOSAGE AND ADMINISTRATION
For intramuscular injection only.
2.1 Preparation for Administration
The storage, preparation, and administration inform ation in this Prescribing Information apply to
COMIRNATY for individuals 16 years of age and older supplied in multiple dose vials with purple caps and
labels with purple borders, which MUST BE DILUTED before use.
COMIRNATY Multiple Dose Vial with a Purp le Cap and Label with a Purple Border
Age Range Dilution Information Doses Per Vial
After Dilution Dose Volume
16 years and older Dilute with 1.8 P/VWHULOH
Sodium Chloride Injection, USP prior
to use 6 0.3 mL
Dose Preparation
Each vial MUST BE DILUTED before administering the vaccine.
Prior to Dilution
x COMIRNATY multiple dose vial with a purple cap and label with a purple border contains a volume of
0.45 mL, supplied as a frozen suspension that does not contain preservative.
x Each vial must be thawed before dilution.
x Vials may be thawed in the refrigerator [2ºC to 8º C (35ºF to 46ºF)] or at room temperature [up to 25ºC
(77ºF)] [see How Supplied/Storage and Handling (16)] .
x Refer to thawing instructions in the panels below.
Dilution
x Dilute the vial contents using 1.8 mL of sterile 6RGLXP&KORULGH,QMHFWLRQ863 to form COMIRNATY. Do not add more than 1.8 mL of diluent.
x ONLY use sterile 6RGLXP&KORULGH,QMHFWLR Q863DVWKHGLOXHQW'RQRWXVH EDFWHULRVWDWLF
Sodium Chloride Injection or any other diluent.
x 9LDOVRIVWHULOH 6RGLXP&KOR ULGH,QMHFWLRQ863DUHSURYLG HGEXWVKLSSHGVHSDUDWHO\8VHWKH
provided diluent or another VWHULOH 6RGLXP&KORULGH,Q MHFWLRQ863DVWKHGLOXHQW
o Provided diluent vials are single-use only; discard after 1.8 mL is withdrawn.
o ,IDQRWKHUVWHULOH 6RGLXP&KO RULGH,QMHFWLRQ863LVXVHG DVWKHGLOXHQWGLVFDUGDIWHU
1.8 mL is withdrawn.
FDA-CBER-2022-5812-0500453
3oDo not dilute more than 1 vial of COMIRNATY using the same diluent vial.
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.
Dilution and Preparation Instructions
COMIRNATY Vial with Purple Cap and Label with Purple Border –
Vial Verification
9Purple plastic cap and label with
purple border.xVerify that the vial of COMIRNATY has a purple
plastic cap and a label with a purple border.
COMIRNATY Vial with Purple Cap a nd Label with Purple Border –
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.
xUsing either thawing method, vials must reach room temperature before dilution and must be diluted within 2 hours.
No more than
2 hours at room
temperature (up
to 25°C/77°F).Purple cap
FDA-CBER-2022-5812-0500454
4 Dilution and Preparation Instructions
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 discol ored or if other particles
are observed.
COMIRNATY Vial with Purple Cap a nd Label with Purple Border –
Dilution
xONLY use VWHULOH 6RGLXP&KORULGH,QMHFWLRQ
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 6RGLXP&KORULGH
Injection, USP into the vaccine vial.
Gently × 10
Add 1.8 mL of sterile 0.9% sodium
chloride injection, USP.
FDA-CBER-2022-5812-0500455
5 Dilution and Preparation Instructions
xEqualize vial pressure before removing the needle
from the vaccine vial by withdrawing 1.8 mL air
into the empty diluent syringe.
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.
Pull back plunger to 1.8 mL to remove
air from vial.
Gently × 10
FDA-CBER-2022-5812-0500456
6 Dilution and Preparation Instructions
Record the date and time of
dilution.
Use within 6 hour s after dilution.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.
COMIRNATY Vial with Purple Cap a nd Label with Purple Border –
Preparation of Individual 0.3 mL Doses
Withdraw 0.3 mL dose of vaccine.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 re maining in a single vial
cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
xAdminister immediately.
2.2 Administration Information
Parenteral drug products should be in spected visually for particulate matter and discolor ation 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. After dilution, vials of COMIRNATY with purple caps a nd labels with purple borders contain 6 doses of
0.3 mL of vaccine. Low dead-volume syri nges and/or needles can be used to extract 6 doses fr om a single vial.
If standard syringes and needles are used, there may not be sufficient volume to ex tract 6 doses from a single
vial. Irrespective of the type of syringe and needle,
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.
FDA-CBER-2022-5812-0500457
7 x do not pool excess vaccine from multiple vials.
2.3 Vaccination Schedule COMIRNATY is administered intramuscularly as a series of 2 doses (0.3 mL each) 3 weeks apart.
There are no data available on the interchangeability of COMIRNATY with COVID-19 vaccines from other manufacturers to complete the vaccination series. Individuals who have received 1 dose of COMIRNATY should receive a second dose of COMIRNATY to complete the vaccination series.
3 DOSAGE FORMS AND STRENGTHS
COMIRNATY is a suspension for injection. After prep aration, each dose of COMIRNATY supplied in vials
with purple caps and labels with purple borders 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 Acut e 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 is higher among males under 40 years of age than among females
and older males. The observed risk is highest in males 12 through 17 years of age. Although some cases
required intensive care support, availabl e data from short-term follow-up suggest that most individuals have had
resolution of symptoms with conservative management. Information is not yet available about potential long-
term sequelae. The CDC has published c onsiderations related to myocarditis and pericarditis after vaccination,
including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clin ical-considerations/myocarditis.html ).
5.3 Syncope Syncope (fainting) may occur in a ssociation with administration of injectable vaccines, including
COMIRNATY. Procedures should be in place to avoid injury from fainting. 5.4 Altered Immunocompetence Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a
diminished immune response to the COMIRNATY.
FDA-CBER-2022-5812-0500458
8 5.5 Limitation of Effectiveness
COMIRNATY may not protect all vaccine recipients.
6 ADVERSE REACTIONS In clinical studies, the most commonly reported ( DGYHUVHUHDFWLRQVLQSD UWLFLSDQWVWKURXJK\HDUVRI
age following any dose were pain at the injection site (88.6 IDWLJXH KHDGDFKH PXVFOHSDLQ
FKLOOV MRLQW SDLQ IHYHU and injection site VZHOOLQJ .
In clinical studies, the most commonly reported ( DGYHUVHUHDFWLRQVLQSDUWLFLSDQWV\HDUVRIDJHDQG
older following any dose were pain at the injection site ( IDWLJXH KHDGDFKH PXVFOH
SDLQ FKLOOV MRLQWSDLQ LQMHFWLRQVLW HVZHOOLQJ IHYHU and injection
site redness (10.4 .
In a clinical study, the most commonly reported 8 adverse reactions in adolescents 12 through 15 years of
age following any dose were pain at the injection site (90.5 IDWLJXH KHDGDFKH FKLOOV
PXVFOHSDLQ IHYHU MRLQWSDLQ LQMHFWLRQVLWHVZHOOLQJ and injection
VLWHUHGQHVV .
6.1 Clinical Trials Experience
Because clinical trials are conducte d under widely varying conditions, ad verse reaction rates observed in the
clinical trials of a vaccine cannot be directly compared to rates in the clin ical trials of another vaccine and may
not reflect the rates observed in practice.
The safety of COMIRNATY was evaluated in participan ts 12 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 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 multicenter, multinationa l, randomized, saline place bo-controlled, double-blinded
(Phase 2/3), dose-finding, vaccine ca ndidate-selection and efficacy study that has enrolled approximately
46,000 participants 12 years of age or older. Of these, approximate ly 44,047 participants
(22,026 COMIRNATY; 22,021 placebo) in Phase 2/3 are 16 years of age or older (including 378 and
376 participants 16 through 17 years of age in th e COMIRNATY and placebo groups, respectively) and
2,260 adolescents are 12 through 15 years of age ( 1,131 and 1,129 in the COMIRNATY and placebo groups,
respectively). Upon issuance of the Emergency Use Au thorization for COMIRNAT Y, participants were
unblinded to offer placebo participants COMIRNATY. Pa rticipants were unblinded in a phased manner over a
period of months to offer placebo participants COMIRNATY. Study 2 al so included 200 participants with
confirmed stable human immunodeficiency virus (HIV) in fection; HIV-positive participants are included in
safety population disposition but are summa rized separately in safety analys es. 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. In Study 2, all participants 12 through 15 years of age, and 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 vacci nation]. Tables 1 through 6 present th e frequency and seve rity of solicited
local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo.
FDA-CBER-2022-5812-0500459
9
Participants 16 Years of Age and Older
At the time of the analysis of the ongoing Study 2 with a data cutoff of March 13, 2021, there were
25,651 SDUWLFLSDQWV (13,031 COMIRNATY and 12,620 placebo) 16 y ears of age and older followed for
PRQWKVDIWHUWKHVHFRQGGRVH .
Demographic characteristics in Study 2 we re generally similar with regard to age, gender, race, and ethnicity
among participants who received COMIRNATY and thos e who received placebo. Overall, among the total
participants who received either COMIRNATY or placebo ZHUHPDOH , ZHUHIHPDOH 79.3 were
16 through 64 years of age, 20.7 ZHUH years of age and older, 82.0 were White, 9.6 ZHUH%ODFNRU
$IULFDQ$PHULFDQ ZHUH+LV SDQLF/DWLQRZHUH$VLDQ DQGZHUH$PHULFDQ,QGLDQRU$ODVND
Native.
Local and Systemic Adverse Reac tions Solicited in the Study 2
In participants 16 through 55 years of age after receiving Dose 2, the mean duration of pa in at the injection site
was 2.5 days (range 1 to 70 days), fo r 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 D ays After Each Dose – Partic ipants 16 Through 55 Years of
Age – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
N
a=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Rednessc
Any (>2.0 cm) 156 (5.4) 28 (1.0) 151 (5.6) 18 (0.7)
Mild 113 (3.9) 19 (0.7) 90 (3.4) 12 (0.4)
Moderate 36 (1.2) 6 (0.2) 50 (1.9) 6 (0.2)
Severe 7 (0.2) 3 (0.1) 11 (0.4) 0
Swellingc
Any (>2.0 cm) 184 (6.3) 16 (0.6) 183 (6.8) 5 (0.2)
Mild 124 (4.3) 6 (0.2) 110 (4.1) 3 (0.1)
Moderate 54 (1.9) 8 (0.3) 66 (2.5) 2 (0.1)
Severe 6 (0.2) 2 (0.1) 7 (0.3) 0
FDA-CBER-2022-5812-0500460
10 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Pain at the injection sited
Any 2426 (83.7) 414 (14.2) 2101 (78.3) 312 (11.6)
Mild 1464 (50.5) 391 (13.4) 1274 (47.5) 284 (10.6)
Moderate 923 (31.8) 20 (0.7) 788 (29.4) 28 (1.0)
Severe 39 (1.3) 3 (0.1) 39 (1.5) 0
Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
No Grade 4 solicited local reactions were reported in participants 16 through 55 years of age.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participant s with
chronic, stable HIV in fection 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 D ays After Each Dose – Partic ipants 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)
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)
FDA-CBER-2022-5812-0500461
11 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Vomitingd
Any 34 (1.2) 36 (1.2) 58 (2.2) 30 (1.1)
Mild 29 (1.0) 30 (1.0) 42 (1.6) 20 (0.7)
Moderate 5 (0.2) 5 (0.2) 12 (0.4) 10 (0.4)
Severe 0 1 (0.0) 4 (0.1) 0
Diarrheae
Any 309 (10.7) 323 (11.1) 269 (10.0) 205 (7.6)
Mild 251 (8.7) 264 (9.1) 219 (8.2) 169 (6.3)
Moderate 55 (1.9) 58 (2.0) 44 (1.6) 35 (1.3)
Severe 3 (0.1) 1 (0.0) 6 (0.2) 1 (0.0)
New or worsened muscle painc
Any 664 (22.9) 329 (11.3) 1055 (39.3) 237 (8.8)
Mild 353 (12.2) 231 (7.9) 441 (16.4) 150 (5.6)
Moderate 296 (10.2) 96 (3.3) 552 (20.6) 84 (3.1)
Severe 15 (0.5) 2 (0.1) 62 (2.3) 3 (0.1)
New or worsened joint painc
Any 342 (11.8) 168 (5.8) 638 (23.8) 147 (5.5)
Mild 200 (6.9) 112 (3.9) 291 (10.9) 82 (3.1)
Moderate 137 (4.7) 55 (1.9) 320 (11.9) 61 (2.3)
Severe 5 (0.2) 1 (0.0) 27 (1.0) 4 (0.1)
Use of antipyretic or
pain medicationf 805 (27.8) 398 (13.7) 1213 (45.2) 320 (11.9)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after
each dose.
No Grade 4 solicited systemic reactions were reported in participants 16 through 55 years of age.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participant s with
chronic, stable HIV in fection 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 or use of antipyretic or pain medication was the same, therefore, this information was included in the column header.
b. n = Number of participants with the specified reaction. c. Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; Moderate: >2 time s in 24 hours; Severe: requires intravenous hydration.
e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours .
f. Severity was not collected for use of antipyretic or pain medication.
Table 3: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by
Maximum Severity, Within 7 D ays After Each Dose – Partic ipants 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)
FDA-CBER-2022-5812-0500462
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 (%)
Swellingc
Any (>2.0 cm) 141 (7.0) 23 (1.2) 145 (7.8) 13 (0.7)
Mild 87 (4.3) 11 (0.6) 80 (4.3) 5 (0.3)
Moderate 52 (2.6) 12 (0.6) 61 (3.3) 7 (0.4)
Severe 2 (0.1) 0 4 (0.2) 1 (0.1)
Pain at the injection sited
Any (>2.0 cm) 1408 (70.1) 185 (9.3) 1230 (66.1) 143 (7.8)
Mild 1108 (55.2) 177 (8.9) 873 (46.9) 138 (7.5)
Moderate 296 (14.7) 8 (0.4) 347 (18.7) 5 (0.3)
Severe 4 (0.2) 0 10 (0.5) 0
Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
No Grade 4 solicited local reactions were reported in participants 56 years of age and older.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participant s with
chronic, stable HIV in fection were excluded.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each
reaction was the same, therefore, the information was included in the column header.
b. n = Number of participants with the specified reaction. c. Mild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.
d. Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Table 4: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by
Maximum Severity, Within 7 D ays After Each Dose – Partic ipants 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
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)
FDA-CBER-2022-5812-0500463
13 COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Chillsc
Any 130 (6.5) 69 (3.5) 435 (23.4) 57 (3.1)
Mild 102 (5.1) 49 (2.5) 229 (12.3) 45 (2.5)
Moderate 28 (1.4) 19 (1.0) 185 (9.9) 12 (0.7)
Severe 0 1 (0.1) 21 (1.1) 0
Vomitingd
Any 10 (0.5) 9 (0.5) 13 (0.7) 5 (0.3)
Mild 9 (0.4) 9 (0.5) 10 (0.5) 5 (0.3)
Moderate 1 (0.0) 0 1 (0.1) 0
Severe 0 0 2 (0.1) 0
Diarrheae
Any 168 (8.4) 130 (6.5) 152 (8.2) 102 (5.6)
Mild 137 (6.8) 109 (5.5) 125 (6.7) 76 (4.1)
Moderate 27 (1.3) 20 (1.0) 25 (1.3) 22 (1.2)
Severe 4 (0.2) 1 (0.1) 2 (0.1) 4 (0.2)
New or worsened muscle painc
Any 274 (13.6) 165 (8.3) 537 (28.9) 99 (5.4)
Mild 183 (9.1) 111 (5.6) 229 (12.3) 65 (3.5)
Moderate 90 (4.5) 51 (2.6) 288 (15.5) 33 (1.8)
Severe 1 (0.0) 3 (0.2) 20 (1.1) 1 (0.1)
New or worsened joint painc
Any 175 (8.7) 124 (6.2) 353 (19.0) 72 (3.9)
Mild 119 (5.9) 78 (3.9) 183 (9.8) 44 (2.4)
Moderate 53 (2.6) 45 (2.3) 161 (8.7) 27 (1.5)
Severe 3 (0.1) 1 (0.1) 9 (0.5) 1 (0.1)
Use of antipyretic or
pain medicationf 382 (19.0) 224 (11.3) 688 (37.0) 170 (9.3)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after
each dose.
The only Grade 4 solicited systemic reaction reported in participants 56 years of age and older was fatigue.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participant s with
chronic, stable HIV in fection were excluded.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after 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 vi sit or hospitalization for severe fatigue, severe headache, sev ere
chills, severe muscle pain, or severe joint pain.
d. Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 ho urs; Severe: requires intravenous hydration; 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.
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.
FDA-CBER-2022-5812-0500464
14 Unsolicited Adverse Events
Overall, 11,253 ( ) participants in the COMIRNATY group and 11,316 ( ) participants in the
placebo group had follow- XSWLPHEHWZHHQPRQWKVWR PRQWKVDIWHU'RVHLQWKHEOLQ GHG
placebo-controlled follow-up peri od with an additional 1,778 ( ) and 1,304 ( ) ZLWK months of
blinded follow-up time in the COMIRN ATY and placebo groups, respectively.
A total of 12,006 ( ) SDUWLFLSDQWVRULJLQDOO\UDQGR PL]HGWR&20,51$7<KDGPRQWKV total (blinded
and unblinded) follow-up after Dose 2.
In an analysis of all unsolicited adverse events repo rted following any dose, through 1 month after Dose 2, in
participants 16 years of age and older (N =43,847; 21,926 COMIRNATY group vs. 21,921 placebo group),
those assessed as adverse reactions not already captured by solicited local a nd systemic reactions were nausea
(274 vs. 87), malaise (130 vs. 22), lymphadenopathy (83 vs. 7), asthenia (76 vs. 25), decreased appetite
(39 vs. 9), hyperhidrosis (31 vs. 9), lethar gy (25 vs. 6), and night sweats (17 vs. 3).
In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date,
RIVWXG\SDUWLFLSDQWVKDGD WOHDVWPRQWKVRIIROORZ -up after Dose 2. Among participants 16 through
55 years of age who received at least 1 dose of study vaccine, 12,995 of whom received COMIRNATY and
13,026 of whom received placebo, unsolicite d adverse events were reported by participants in
the COMIRNATY group and participants in the placebo group. In a similar analysis in
participants 56 years of age a nd older that included 8,931 COMIRNATY recipients and 8,895 placebo
recipients, unsolicited adverse events were reported by participants in the COMIRNATY group
and participants in the placebo group. Among partic ipants with confirmed stable HIV infection
that included 100 COMIRNATY recipients and 100 pl acebo recipients, unsolicited adverse events were
UHSRUWHGE\ SDUWLFLSDQWV in the COMIRNATY group DQG SDUWLFLSDQWVLQWKHSODFHERJURXS
The higher frequency of reported unsolicited adverse events among COMI RNATY recipients compared to
placebo recipients was primarily attributed to events th at are consistent with a dverse reactions solicited among
participants in the reactogenicity subset (Table 3 and Table 4).
Throughout the placebo-controlled safety follow-up period, Bell’s palsy (facial para lysis) 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 informa tion is insufficient to
determine a causal relationship with the vaccine. In the analysis of blinded, pla cebo-controlled follow-up, there
were no other notable patterns or numer ical imbalances between treatment groups for specific categories of
non-serious adverse events (including other neurologic or neur o-inflammatory, and thrombotic events) that
would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no
notable patterns of specific categories of non-serious adverse events that wo uld suggest a causal relationship to
COMIRNATY.
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 a dverse events from Dose 1 up to the participant
unblinding date in ongoing follow-up were reporte GE\ COMIRNATY UHFLSLHQWVDQG
placebo recipients. In a similar analysis, in partic ipants 56 years of age and older (COMIRNATY = 8,931;
placebo = 8, VHULRXVDGYHUVHHYHQWVZHUHUHSRUWHGE\ COMIRNATY UHFLSLHQWVDQG
placebo recipients who received at l east 1 dose of COMIRNATY or placebo, respectively. In these analyses,
RIVWXG\SDUWLFLSDQWVKDGD WOHDVWPRQWKVRIIROORZ -up after Dose 2. Among par ticipants with confirmed
FDA-CBER-2022-5812-0500465
15 stable HIV infection serious adverse events from Do se 1 up to the participan t unblinding date in ongoing
follow-XSZHUHUHSRUWHGE\ COMIRNATY UHFLSLHQWVDQG SODFHERUHFLSLHQWV
In the analysis of blinded, placebo-controlled follow- up, there were no notable pa tterns between treatment
groups for specific categories of serious adverse ev ents (including neurologic , neuro-inflammatory, and
thrombotic events) that would suggest a causal relati onship to COMIRNATY. In the analysis of unblinded
follow-up, there were no notable patterns of specific cate gories of serious adverse events that would suggest a
causal relationship to COMIRNATY.
Adolescents 12 Through 15 Years of Age
In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. At the time of the analysis of the ongoing Study 2 with a data cutoff of September 2, 2021, there were 1,559 (69.0
adolescents (786 COMIRNATY and 773 placebo) 12 through 15 years of age followed for months after the
second dose. The safety evaluation in Study 2 is ongoing. Demographic characteristics in Study 2 we re generally similar with regard to age, gender, race, and ethnicity
among adolescents who received COMIRNATY and t hose who received placebo. Overall, among the
adolescents who received COMIRNATY, 50.1 were male and 49.9 were female, 85.8 ZHUH White, 4.6
were Black or African American, 11.7 ZHUH Hispanic/Latino, 6.4 ZHUH Asian, and 0.4 ZHUH American
Indian/Alaska Native.
Local and Systemic Adverse Re actions Solicited in Study 2
In adolescents 12 through 15 years of age after receiving Dose 2, the mean duration of pain at the injection site
was 2.5 days (range 1 to 11 days), fo r redness 1.8 days (range 1 to 5 days), and for swelling 1.6 days (range 1 to
5 days) in the COMIRNATY group.
Table 5: Study 2 – Frequency and Percentages of Adolescents With Solicited Local Reactions, by
Maximum Severity, Within 7 D ays After Each Dose – Adoles cents 12 Through 15 Years of
Age – Safety Population*
COMIRNATY
Dose 1
N
a=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Rednessc
Any (>2 cm) 65 (5.8) 12 (1.1) 55 (5.0) 10 (0.9)
Mild 44 (3.9) 11 (1.0) 29 (2.6) 8 (0.7)
Moderate 20 (1.8) 1 (0.1) 26 (2.4) 2 (0.2)
Severe 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Swellingc
Any (>2 cm) 78 (6.9) 11 (1.0) 54 (4.9) 6 (0.6)
Mild 55 (4.9) 9 (0.8) 36 (3.3) 4 (0.4)
Moderate 23 (2.0) 2 (0.2) 18 (1.6) 2 (0.2)
Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
FDA-CBER-2022-5812-0500466
16 COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Pain at the injection sited
Any 971 (86.2) 263 (23.3) 866 (78.9) 193 (17.9)
Mild 467 (41.4) 227 (20.1) 466 (42.5) 164 (15.2)
Moderate 493 (43.7) 36 (3.2) 393 (35.8) 29 (2.7)
Severe 11 (1.0) 0 (0.0) 7 (0.6) 0 (0.0)
Note: Reactions were collected in th e electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
a. N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.
b. n = Number of participants with the specified reaction. c. 0LOG !WRFP 0RGHUDWH !WRFP 6HYHUH ! FP
d. Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Table 6: Study 2 – Frequency and Percentages of Adolescents with Solicited Systemic Reactions, by
Maximum Severity, Within 7 D ays After Each Dose – Adoles cents 12 Through 15 Years of
Age – Safety Population*
COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Fever
ႏ 114 (10.1) 12 (1.1) 215 (19.6) 7 (0.6)
ႏWRႏ 74 (6.6) 8 (0.7) 107 (9.8) 5 (0.5)
>ႏWR ႏ 29 (2.6) 2 (0.2) 83 (7.6) 1 (0.1)
> ႏWRႏ 10 (0.9) 2 (0.2) 25 (2.3) 1 (0.1)
!ႏ 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Fatiguec
Any 677 (60.1) 457 (40.6) 726 (66.2) 264 (24.5)
Mild 278 (24.7) 250 (22.2) 232 (21.1) 133 (12.3)
Moderate 384 (34.1) 199 (17.7) 468 (42.7) 127 (11.8)
Severe 15 (1.3) 8 (0.7) 26 (2.4) 4 (0.4)
Headachec
Any 623 (55.3) 396 (35.1) 708 (64.5) 264 (24.5)
Mild 361 (32.0) 256 (22.7) 302 (27.5) 170 (15.8)
Moderate 251 (22.3) 131 (11.6) 384 (35.0) 93 (8.6)
Severe 11 (1.0) 9 (0.8) 22 (2.0) 1 (0.1)
Chillsc
Any 311 (27.6) 109 (9.7) 455 (41.5) 74 (6.9)
Mild 195 (17.3) 82 (7.3) 221 (20.1) 53 (4.9)
Moderate 111 (9.8) 25 (2.2) 214 (19.5) 21 (1.9)
Severe 5 (0.4) 2 (0.2) 20 (1.8) 0 (0.0)
Vomitingd
Any 31 (2.8) 10 (0.9) 29 (2.6) 12 (1.1)
Mild 30 (2.7) 8 (0.7) 25 (2.3) 11 (1.0)
Moderate 0 (0.0) 2 (0.2) 4 (0.4) 1 (0.1)
Severe 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
FDA-CBER-2022-5812-0500467
17 COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Diarrheae
Any 90 (8.0) 82 (7.3) 65 (5.9) 44 (4.1)
Mild 77 (6.8) 72 (6.4) 59 (5.4) 39 (3.6)
Moderate 13 (1.2) 10 (0.9) 6 (0.5) 5 (0.5)
Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
New or worsened muscle painc
Any 272 (24.1) 148 (13.1) 355 (32.4) 90 (8.3)
Mild 125 (11.1) 88 (7.8) 152 (13.9) 51 (4.7)
Moderate 145 (12.9) 60 (5.3) 197 (18.0) 37 (3.4)
Severe 2 (0.2) 0 (0.0) 6 (0.5) 2 (0.2)
New or worsened joint painc
Any 109 (9.7) 77 (6.8) 173 (15.8) 51 (4.7)
Mild 66 (5.9) 50 (4.4) 91 (8.3) 30 (2.8)
Moderate 42 (3.7) 27 (2.4) 78 (7.1) 21 (1.9)
Severe 1 (0.1) 0 (0.0) 4 (0.4) 0 (0.0)
Use of antipyretic or
pain medicationf 413 (36.6) 111 (9.8) 557 (50.8) 95 (8.8)
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 aft er each
dose.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. a. N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. b. n = Number of participants with the specified reaction. c. Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; Moderate: >2 time s in 24 hours; Severe: requires intravenous hydration.
e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours .
f. Severity was not collected for use of antipyretic or pain medication.
Unsolicited Adverse Events
In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. Of these,
634 SDUWLFLSDQWVLQWKH&20,51$7<JURXSDQG ) participants in the placebo group had
follow-XSWLPHEHWZHHQPRQWKVWR PRQW KVDIWHU'RVHLQWKHEOLQ GHGSOD cebo-controlled follow-up
period with an DGGLWLRQDO and ZLWK months of blinded follow-up time in the
COMIRNATY and placebo groups, respectively.
A total of 1, SDUWLFLSDQWVWKURXJK \HDUVRIDJHRULJLQDOO\UDQGRPL]HGWR&20,51$7<KDG
PRQWKVWRWDO EO inded and unblinded) follow-up after Dose 2.
An analysis of all unsolicited adverse events in Study 2 from Dose 1 up to the par ticipant unblinding date was
conducted. Among participants 12 through 15 years of age who received at least one dose of study vaccine,
unsolicited adverse events were reported by 95 (8.4 participants in the COMIRNATY group and
113 (10.0 participants in the placebo group.
In an analysis of all unsolicited adverse events repo rted during blinded follow-up from Dose 1 through 1 month
after Dose 2, in adolescents 12 to 15 years of age, those assessed as adverse reacti ons not already captured by
solicited local and systemic reac tions were lymphadenopathy (9 vs. 2), and nausea (5 vs. 2).
FDA-CBER-2022-5812-0500468
18 In the analysis of blinded, placebo-controlled follow- up, there were no other notable patterns or numerical
imbalances between treatment groups for specific categor ies of unsolicited adverse events (including other
neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to
COMIRNATY. In the analysis of unblinded follow-up, ther e were no notable patterns of specific categories of
non-serious adverse events that would suggest a causal relationship to COMIRNATY.
Serious Adverse Events
In Study 2, among participants 12 through 15 years of age who had received at least 1 dose of vaccine or
placebo (COMIRNATY = 1,131; placebo = 1,129), serious a dverse events from Dose 1 up to the participant
unblinding date in ongoing follow-up were reported by 10 (0.9 COMIRNATY recipients and 2 (0.2
placebo recipients. In these analyses, 69.0 RIVWXG\SDUWLFLSDQWVKDGDWOHDVW 4 months of follow-up after
Dose 2. In the analysis of blinded, placebo-controll ed follow-up, there were no notable patterns between
treatment groups for specific categorie s of serious adverse events (including neurologic, neuro-inflammatory,
and thrombotic events) that would suggest a causal rela tionship to COMIRNATY. In the analysis of unblinded
follow-up, there were no notable patterns of specific cate gories of serious adverse events that would suggest a
causal relationship to COMIRNATY.
6.2 Postmarketin g Experience
The following adverse reactions have been identifie d during postmarketing use of COMIRNATY, including
under Emergency Use Authorization. Because these re actions 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, in cluding 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
There is a pregnancy exposure registry that monito rs pregnancy outcomes in women exposed to COMIRNATY
during pregnancy. Women who are vaccinated with COMIRNATY during pregnancy are encouraged to enroll in the registry by visiting https://mothertobaby.org/ongoi ng-study/covid19-vaccines/ .
Risk Summary
All pregnancies have a risk of birth defect, loss, or other adverse outco mes. In the US general population, the
HVWLPDWHGEDFNJURXQGULVNRIPDMRU ELUWKGHIHFWVDQGPLVFDUULDJ HLQFOLQLFDOO\UHFRJQL]HGSUHJQDQFLHVLVWR
DQGWRUHVSHFWLY HO\$YDLODEOHGDWDRQ COMIRNATY administered to pregnant women are
insufficient to inform vaccine-a ssociated risks in pregnancy.
A developmental toxicity study has been performed in female rats administered th e equivalent of a single
human dose of COMIRNATY on 4 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) .
FDA-CBER-2022-5812-0500469
19 Data
Animal Data In a developmental toxicity study, 0.06 mL of a vacci ne formulation containi ng the same quantity of
nucleoside-modified messenger ribonucl eic acid (mRNA) (30 mcg) and othe r 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 ge station days 9 and 20. No vaccine- related adverse effects on female
fertility, fetal development, or postnatal development were reported in the study.
8.2 Lactation
Risk Summary
It is not known whether COMIRNATY is excreted in human milk. Data are not available to assess the effects of
COMIRNATY on the breastfed infant or on milk production/ excretion. The developmenta l and health benefits
of breastfeeding should be considered along with th e mother’s clinical need for COMIRNATY and any
potential adverse effects on the breastfed child fro m 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 12 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 indi viduals younger than 12 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 = 4,552) were 65 years of age and older and 4.2 Q = 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 with purple caps and labels with purple borders; each vial must be diluted with 1.8 P/RIVWHULOH 6RGLXP&KORULGH,QMHFWLRQ863SULRUWRXVH WR
form the vaccine. Each 0.3 mL dose of COMIRNATY supplied in multiple dose vials with purple caps and labels with purple borders 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 supplied in multiple dose vials with purple caps and labels with purple borders 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
FDA-CBER-2022-5812-0500470
20 dihydrate, and 6 mg sucrose. The diluent (sterile 6RGLXP 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, Mutagenesi s, Impairment of Fertility
COMIRNATY has not been evaluated for the potential to cause carcinogenicity, genot oxicity, or impairment of
male fertility. In a develo pmental toxicity study in rats with CO MIRNATY there were no vaccine-related
effects on female fertility [see Use in Specific Populations (8.1)] .
14 CLINICAL STUDIES
14.1 Efficacy in Participants 16 Years of Age and Older
Study 2 is an ongoing, multicenter, multinational, rando mized, 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 y ears of age, or 56 years of age and older, with a
PLQLPXPRIRISDUWLF LSDQWVLQWKH -year stratum. The study excluded participants who were
immunocompromised and those who had previous clinical or microbiologica l diagnosis of COVID-19.
Participants with preexisting stable disease, defined as disease not requiring signifi cant 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 12 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 assessm ents of safety and efficacy against COVID-19.
Overall, among the tota l participants who r HFHLYHG&20,51$7<RUSODFHERRU 3ZHUHPDOHDQG
RU 7ZHUHIHPDOH 79RU 79.2ZHUHWKURXJK\HDUVRIDJH9RU8ZHUH\HDUV
of age and older, 81.9 RU 82.1ZHUH:KLWH 9RU 9ZHUH%ODFNRU$IULFDQ$PHULFDQ 1.0RU 0.9
were American Indian or Alaska Native, 4.4 RU 3ZHUH$VLDQRU 21DWLYH+DZDLLDQRURWKHU
Pacific Islander, 25.6RU5.4ZHUH+LVSDQLF/DWLQR3.9RU4.1ZHUHQRQ- +LVSDQLF/DWLQRRU
0GLGQRWUHSRUWHWKQLFLW\ 6.0RU5.7KDGFRPRUELGLWLHV>SDU WLFLSDQWVZKRKDYHRUPRUH
comorbidities that increase the risk of severe COVID-19 disease: defined as subjects who had at least 1 of the &KDUOVRQFRPRUELGLW\LQGH[FDW HJRU\RUERG\PDVVLQGH[ %0, NJP
2], respectively. The mean age at
vaccination was 49.8 or 49.7 years and median age was 51.0 or 51.0 in participants who received
COMIRNATY or placebo, respectively.
FDA-CBER-2022-5812-0500471
21
Efficacy Against COVID-19
The population for the analysis of the protocol pre-specified pr imary efficacy endpoint included
36,621 participants 12 years of age and older (18,2 42 in the COMIRNATY group and 18,379 in the placebo
group) who did not have evidence of prior infection w ith SARS-CoV-2 through 7 days after the second dose.
The population in the protocol pre-specified primary efficacy analysis incl uded 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. For participants without evidence of SARS-CoV-2 infec tion prior to 7 days after Dose 2, vaccine efficacy
against confirmed COVID- RFFXUULQJDWOHDVWGD\VDIWHU'RVHZDV credible interval: 90.3,
97.6), which met the pre-specified success criteri on. The case split was 8 COVID-19 cases in the
COMIRNATY group compared to 162 COVID-19 cases in the placebo group. 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 fo r the development of COVID-19 during blinded
placebo-controlled follow-up through Ma rch 13, 2021, representing up to 6 months of follow-up after Dose 2.
There were 12,796 participants in the COMIRNATY group and 12,449 ( in the placebo group
followed for PRQWKVDIWHU'RVHLQWKHEOLQGHGSODFHER -controlled follow-up period.
SARS-CoV-2 variants of concern identified from COVI D-19 cases for this age group from this data cutoff
include B.1.1.7 (Alpha) and B.1.351 (Beta).
Representation of identified varian ts among cases in vaccine versus
placebo recipients did not suggest decreased va ccine effectiveness against these variants.
The updated vaccine efficacy informa tion is presented in Table 7.
Table 7: Vaccine Efficacy – First COVID-19 O ccurrence From 7 Days After Dose 2, by Age
Subgroup – Participants 16 Years of Age and Older Without Evidence of Infection and Participants With or Wi thout 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 participants 77
6.092 (19,711) 833
5.857 (19,741) 91.1
(88.8, 93.1)
16 through 64 years 70
4.859 (15,519) 709
4.654 (15,515) 90.5
(87.9, 92.7)
65 years and older 7
1.233 (4192) 124
1.202 (4226) 94.5
(88.3, 97.8)
FDA-CBER-2022-5812-0500472
22 First COVID-19 occurrence from 7 days after Dose 2 in participants with or without* evidence of prior
SARS-CoV-2 infection
Subgroup COMIRNATY
Na=21,047
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,210
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All participants 81
6.340 (20,533) 854
6.110 (20,595) 90.9
(88.5, 92.8)
16 through 64 years 74
5.073 (16,218) 726
4.879 (16,269) 90.2
(87.5, 92.4)
65 years and older 7
1.267 (4315) 128
1.232 (4326) 94.7
(88.7, 97.9)
Note: Confirmed cases were determined by Reverse Transcriptio n-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom
consistent with COVID-19 (symptoms included: fever; new or incr eased 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] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
a. N = Number of participants in the specified group.
b. n1 = Number of participants meeting the endpoint definition.
c. Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for 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
surveillance time.
Subgroup analyses of vaccine efficacy (although limited by small numbers of cases in some subgroups) did not
suggest meaningful differen ces in efficacy across genders, ethnic groups , geographies, or for participants with
obesity or medical comorbidities associated with high risk of severe COVID-19.
Efficacy Against Severe COVID-19
Efficacy analyses of secondary ef ficacy endpoints supported benefit of COMIRNATY in preventing severe
COVID-19. Vaccine efficacy against severe COVID-19 is pr esented only for participants with or without prior
SARS-CoV-2 infection (Table 8) as the COVID-19 cas e counts in participants without prior SARS-CoV-2
infection were the same as those in participants with or without prio r SARS-CoV-2 infection in both the
COMIRNATY and placebo groups.
FDA-CBER-2022-5812-0500473
23 Table 8: Vaccine Efficacy – First Severe COVID-19 Occurrence in Participants 16 Years of Age and
Older With or Without* Prior SARS-CoV-2 Infect ion Based on Protocol† or Centers for
Disease Control and Prevention (CDC)‡ Definition From 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population During the Placebo-Controlled Follow-up
Vaccine Efficacy – First Severe COVID-19 Occurrence
COMIRNATY
Cases
n1a
Surveillance Timeb (n2c) Placebo
Cases
n1a
Surveillance Timeb (n2c) Vaccine Efficacy %
(95% CId)
7 days after Dose 2d 1
6.353 (20,540) 21
6.237 (20,629) 95.3
(70.9, 99.9)
Vaccine Efficacy – First Severe COVID-19 Occurrence Based on CDC Definition
COMIRNATY
Cases
n1a
Surveillance Timeb (n2c) Placebo
Cases
n1a
Surveillance Timeb (n2c) Vaccine Efficacy %
(95% CId)
7 days after Dose 2d 0
6.345 (20,513) 31
6.225 (20,593) 100
(87.6, 100.0)
Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom
consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new 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] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis.
† Severe illness from COVID-19 is defined in the protocol as conf irmed COVID-19 and presence of at least 1 of the following:
x ClinicDOVLJQVDWUHVWLQGLFDWLYHRIVHYHUHV\VWHPLFLOOQHVV UHVSLUD WRU\UDWHEUHDWKVSHUPLQXW HKHDUWUDWHEHDWVSHU
PLQXWHVDWXUDWLRQRIR[\JHQ RQURRPDLUDWVHDOHYHORU UDWLRRIDUWHULDOR[\JHQSDUWLDOSUHVVXUHWRIUDFWLRQDOLQVSLU ed
oxygen <300 mm Hg);
x Respiratory failure [defined as needing high-flow oxygen, noni nvasive ventilation, mechanical ventilation 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 Significant acute renal, hepatic, or neurologic dysfunction;
x Admission to an Intensive Care Unit;
x Death.
‡ Severe illness from COVID-19 as defined by CDC is confirme d 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. Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the endpoint.
Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
c. n2 = Number of participants at 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
surveillance time.
14.2 Efficacy in Adol escents 12 Through 15 Years of Age
A descriptive efficacy analysis of Study 2 has been performed in 2,260 adolescents 12 through 15 years of age
evaluating confirmed COVID-19 cases accrued up to a data cuto ff date of September 2, 2021.
The vaccine efficacy information in adolescents 12 through 15 years of age is presented in Table 9.
FDA-CBER-2022-5812-0500474
24 Table 9: Vaccine Efficacy – First COVID-19 Occurren ce From 7 Days After Dose 2: Without Evidence
of Infection and With or Withou t Evidence of Infection Prior to 7 Days After Dose 2 – Blinded
Placebo-Controlled Follow-up Period, Adolesce nts 12 Through 15 Years of Age Evaluable
Efficacy (7 Days) Population
First COVID-19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age without
evidence of prior SARS-CoV-2 infection*
COMIRNATY
Na=1057
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=1030
Cases
n1b
Surveillance Timec (n2d) 9DFFLQH(IILFDF\
&,e)
Adolescents
12 through 15 years of age 0
0.343 (1043) 28
0.322 (1019) 100.0
(86.8, 100.0)
First COVID-19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age with or
without evidence of prior SARS-CoV-2 infection
COMIRNATY
Na=1119
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=1109
Cases
n1b
Surveillance Timec (n2d) 9DFFLQH(IILFDF\
&,e)
Adolescents 12 through 15 years of age 0
0.362 (1098) 30
f
0.345 (1088) 100.0
(87.5, 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).
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.
a. N = Number of participants in the specified group. b. n1 = Number of participants meeting the endpoint definition.
c. Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for 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-side confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted for
surveillance time.
f. The only
SARS-CoV-2 variant of concern identified from COVID-19 cases in this age group from this data cutoff was B.1.1.7
(Alpha).
14.3 Immunogenicity in Adolescen ts 12 Through 15 Years of Age
In Study 2, an analysis of SARS-CoV-2 neutralizing titers (NT50) 1 month after Dose 2 in a randomly
selected subset of participants demonstrated non-inferior immune re sponses (within 1.5-fold) comparing
adolescents 12 through 15 years of age to participants 16 through 25 years of age who had no serological or virological evidence of past SA RS-CoV-2 infection up to 1 month after Dose 2 (Table 10).
FDA-CBER-2022-5812-0500475
25 Table 10: Summary of Geometric Mean Ratio for 50% Neutralizing Titer – Comp arison of Adolescents
12 Through 15 Years of Age to Participants 16 Through 25 Years of Age (Immunogenicity
Subset) – Participants Without Evidence of Infection up to 1 Month After Dose 2 – Dose 2
Evaluable Immunogenicity Population
COMIRNATY
12 Through 15 Years/
16 Through 25 Years 12 Through 15 Years
na=190 16 Through 25 Years
na=170
Assay Time
Pointb GMTc
(95% CIc) GMTc
(95% CIc) GMRd
(95% CId) Met
Noninferiority
Objectivee
(Y/N)
SARS-CoV-2 neutralization assay - NT50 (titer)
f 1 month
after
Dose 2 1253.6
(1117.7, 1406.1) 708.1
(625.9, 801.1) 1.77
(1.50, 2.09) Y
Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of
quantitation; NAAT = n ucleic-acid amplification test; 17 QHXWUDOL]LQJWLWHU 6$56 -CoV-2 = severe acute respiratory
syndrome coronavirus 2.
Note: Participants who had no serological or virological evidence (up to 1 month after receipt of the last dose) of past SARS-C oV-2
infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not dete cted by NAAT [nasal swab] at Visits 1 an d
2), and had negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 were included in the analysis.
a. n = Number of participants with valid and determinate assay results for the specified assay at the given dose/sampling time point.
b. Protocol-specified timing for blood sample collection.
c. GMTs and 2- VLGHG &,VZHUHFDOFXODWHGE\H[SRQHQWLDWLQJWKHPHDQORJDUL WKPRIWKHWLWHUVDQG the corresponding CIs (based
on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.
d. GMRs and 2- VLGHG &,VZHUHFDOFXODWHGE\H[SRQHQWLDWLQJWKHPHDQGLIIHU HQFHRIWKHORJDULWKPVRIWKHWLWHUV *URXS
[12 through 15 years of age] – Group 2 [16 through 25 years of age]) and the corresponding CI (based on the Student t
distribution).
e. Noninferiority is declared if the lower bound of the 2- VLGHG &,IRUWKH*05LVJUHDWHUWKDQ
f. SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization Assay. The assay uses a
fluorescent reporter virus derived from the USA_WA1/2020 strain a nd virus neutralization is read on Vero cell monolayers. The
sample NT50 is defined as the reciprocal serum di OXWLRQDWZKLFKRIWKHYLUXVLVQHXWUDOL]HG
16 HOW SUPPLIED/STORAGE AND HANDLING
COMIRNATY Suspension for Intramuscular Injection, multiple dose vials with purple caps and labels with purple borders are supplied in a carton containing 25 multiple dose vials (NDC 0069-1000-03) or 195 multiple
dose vials (NDC 0069-1000-02). $ 6RGLXP&KORULGH,QMHFWLRQ863GLOXHQWLV 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]. 7KHSURYLGHG 6RGLXP Chloride Injection, USP d iluent will be supplied
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 Freseniu s 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 avoi d exposure to direct sunlight and ultraviolet light.
Do not refreeze thawed vials. Frozen Vials Prior to Use
Cartons of COMIRNATY multiple dose vials with purple caps labels with purple borders arrive in thermal containers with dry ice. Once received, remove the vi al cartons immediately from the thermal container and
FDA-CBER-2022-5812-0500476
26 preferably store in an ultra-low te mperature freezer between -90ºC to -60º C (-130ºF to -76ºF) until the expiry
date printed on the label.
Alternatively, vials may be stored at -25°C to -15°C (-13° F to 5°F) for up to 2 weeks. Vials must be kept frozen
and protected from light, in the original cartons, until ready to use. Vials stored at -25°C to -15°C (-13°F to 5°F) for up to 2 weeks may be returned 1 time to the recommended storage condition of -90ºC to -60ºC (-130ºF
to -76ºF). Total cumulative time the vials are stored at -25°C to -15°C (-13°F to 5°F) should be tracked and
should not exceed 2 weeks. If an ultra-low temperature freezer is not available, the thermal container in which COMIRNATY arrives may be used as temporary storage when consistently re-filled to the top of the container with dry ice. Refer to the
re-icing guidelines packed in the original thermal contai ner for instructions regarding the use of the thermal
container for temporary storage. The thermal container maintain s 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 a nd 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 -90ºC to -60ºC (-130ºF 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, respec tively, 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 temper ature [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 trans portation of 1 or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 12 hours.
Vials After Dilution
After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within 6 hours from the time of dilution.
During storage, minimize exposure to room light, and avoi d exposure to direct sunlight and ultraviolet light.
Any vaccine remaining in vials must be discarded after 6 hours. Do not refreeze.
FDA-CBER-2022-5812-0500477
2717 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 2 dose vaccination series. There is a pregnancy exposure registry for COMIR NATY. Encourage individuals exposed to COMIRNATY
around the time of conception or during pregnancy to register by visiting https://mothertobaby.org/ongoing-
study/covid19-vaccines/ .
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 .
Prior to administering the vaccine, give the vaccine recipient the Vaccine Information Fact Sheet for Recipients and Caregivers about COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Dis ease 2019 (COVID-19) for Use in Individuals 12 Years of Age and Older.
The Vaccine Information Fact Sheet for Recipients and Caregivers is available at www.cvdvaccine-us.com.
This product’s labeling may have been updated. For the most recent prescribing information, please visit
https://dailymed.n lm.nih.gov/dailymed/ .
Manufactured for BioNTech Manufacturing GmbH An der Goldgrube 12 55131 Mainz, Germany
Manufactured by
Pfizer Inc., New York, NY 10017
LAB-1448-2.1 US Govt. License No. 2229
FDA-CBER-2022-5812-0500478