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Burk Declaration

Date
2021-12-17

Summary

Document 40-3 in Case 2:21-cv-00702-CLM, stamped by the U.S. District Court, N.D. of Alabama, and filed December 17, 2021 as Exhibit 3 to the Burk Declaration. The 54-page exhibit is the FDA Fact Sheet for Healthcare Providers Administering Vaccine for the Emergency Use Authorization of the Pfizer-BioNTech COVID-19 Vaccine for 12 years of age and older, revised 29 October 2021. It covers the purple-cap formulation that must be diluted, the 2-dose primary series, a third primary dose for certain immunocompromised individuals, and booster dose eligibility, and notes that COMIRNATY is FDA-approved for individuals 16 years of age and older. The fact sheet sets out storage, thawing, dilution and administration instructions and reporting requirements for vaccination providers.

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Full text

Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 1 of 54            FILED
                                                                   2021 Dec-17 PM 01:27
                                                                   U.S. DISTRICT COURT
                                                                       N.D. OF ALABAMA




              Burk Declaration
                 Exhibit 3
     Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 2 of 54



  FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE
                   (VACCINATION PROVIDERS)

             EMERGENCY USE AUTHORIZATION (EUA) OF
 THE PFIZER-BIONTECH COVID-19 VACCINE TO PREVENT CORONAVIRUS
                    DISEASE 2019 (COVID-19)

                           FOR 12 YEARS OF AGE AND OLDER
                                 DILUTE BEFORE USE

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use
Authorization (EUA) to permit the emergency use of the unapproved product,
Pfizer-BioNTech COVID-19 Vaccine, for active immunization to prevent
COVID-19 in individuals 5 years of age and older.

There are 2 formulations of Pfizer-BioNTech COVID-19 Vaccine authorized for
use in individuals 12 years of age of older:

        The formulation supplied in a multiple dose vial with a purple cap
        MUST BE DILUTED PRIOR TO USE.

        The formulation supplied in a multiple dose vial with a gray cap and
        label with a gray border IS NOT DILUTED PRIOR TO USE.

This Fact Sheet pertains only to Pfizer-BioNTech COVID-19 Vaccine supplied
in a multiple dose vial with a purple cap, which is authorized for use in
individuals 12 years of age and older, and MUST BE DILUTED PRIOR TO USE.

Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a
purple cap is authorized for use to provide:
   • a 2-dose primary series to individuals 12 years of age and older;
   • a third primary series dose to individuals 12 years of age and older
       who have been determined to have certain kinds of
       immunocompromise; and
   • a single booster dose to the following individuals who have completed
       a primary series with Pfizer-BioNTech COVID-19 Vaccine or
       COMIRNATY:
           o 65 years of age and older
           o 18 through 64 years of age at high risk of severe COVID-19
           o 18 through 64 years of age with frequent institutional or
              occupational exposure to SARS-CoV-2
   • a single booster dose to eligible individuals who have completed
       primary vaccination with a different authorized COVID-19 vaccine. The
       eligible population(s) and dosing interval for the heterologous booster
       dose are the same as those authorized for a booster dose of the
       vaccine used for primary vaccination.

Revised: 29 October 2021                                                       1
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COMIRNATY (COVID-19 Vaccine, mRNA) is an FDA-approved COVID-19
vaccine made by Pfizer for BioNTech that is indicated for active immunization
to prevent COVID-19 in individuals 16 years of age and older. It is approved
for use as a 2-dose primary series for the prevention of COVID-19 in
individuals 16 years of age and older. It is also authorized for emergency use
to provide:
    • a 2-dose primary series to individuals 12 through 15 years;
    • a third primary series dose to individuals 12 years of age and older
       who have been determined to have certain kinds of
       immunocompromise; and
    • a single booster dose to the following individuals who have completed
       a primary series with Pfizer-BioNTech COVID-19 Vaccine or
       COMIRNATY:
           o 65 years of age and older
           o 18 through 64 years of age at high risk of severe COVID-19
           o 18 through 64 years of age with frequent institutional or
              occupational exposure to SARS-CoV-2
    • a single booster dose to eligible individuals who have completed
       primary vaccination with a different authorized COVID-19 vaccine. The
       eligible population(s) and dosing interval for the heterologous booster
       dose are the same as those authorized for a booster dose of the
       vaccine used for primary vaccination.

The FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the two
EUA-authorized formulations of Pfizer-BioNTech COVID-19 Vaccine for ages
12 years and older when prepared according to their respective instructions
for use can be used interchangeably. 1

COMIRNATY (COVID-19 Vaccine, mRNA) and the two EUA-authorized
formulations of Pfizer-BioNTech COVID-19 Vaccine intended for individuals
ages 12 years and older should not be used for individuals 5 through 11
years of age because of the potential for vaccine administration errors,
including dosing errors. 2

SUMMARY OF INSTRUCTIONS FOR COVID-19 VACCINATION PROVIDERS

1 When prepared according to their respective instructions for use, the FDA-approved COMIRNATY

(COVID-19 Vaccine, mRNA) and the two EUA-authorized formulations of Pfizer-BioNTech COVID-
19 Vaccine for ages 12 years of age and older can be used interchangeably without presenting any
safety or effectiveness concerns.
2 Notwithstanding the age limitations for use of the different formulations and presentations

described above, individuals who will turn from 11 years to 12 years of age between their first and
second dose in the primary regimen may receive, for either dose, either: (1) the Pfizer-BioNTech
COVID-19 Vaccine formulation authorized for use in individuals 5 through 11 years of age (each 0.2
mL dose containing 10 mcg modRNA) (orange cap); or (2) COMIRNATY or one of the Pfizer-
BioNTech COVID-19 Vaccine formulations authorized for use in individuals 12 years of age and
older (each 0.3 mL dose containing 30 mcg modRNA) (gray and purple cap).



Revised: 29 October 2021                                                                          2
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Vaccination providers enrolled in the federal COVID-19 Vaccination Program must
report all vaccine administration errors, all serious adverse events, cases of
Multisystem Inflammatory Syndrome (MIS) in adults and children, and cases of
COVID-19 that result in hospitalization or death following administration of
Pfizer-BioNTech COVID-19 Vaccine. See “MANDATORY REQUIREMENTS FOR
PFIZER-BIONTECH COVID-19 VACCINE ADMINISTRATION UNDER
EMERGENCY USE AUTHORIZATION” for reporting requirements.

The Pfizer-BioNTech COVID-19 Vaccine is a suspension for intramuscular
injection.

Primary Series

The Pfizer-BioNTech COVID-19 Vaccine is administered as a primary series of
2 doses (0.3 mL each) 3 weeks apart in individuals 12 years of age or older.

A third primary series dose of the Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) at
least 28 days following the second dose is authorized for administration to
individuals at least 12 years of age who have undergone solid organ
transplantation, or who are diagnosed with conditions that are considered to have
an equivalent level of immunocompromise.

Booster Dose

A single Pfizer-BioNTech COVID-19 Vaccine booster dose (0.3 mL) may be
administered intramuscularly at least 6 months after completing the primary series
to individuals:
    • 65 years of age and older
    • 18 through 64 years of age at high risk of severe COVID-19
    • 18 through 64 years of age with frequent institutional or occupational
        exposure to SARS-CoV-2

A single booster dose of the Pfizer-BioNTech COVID-19 Vaccine may be
administered as a heterologous booster dose following completion of primary
vaccination with another authorized COVID-19 vaccine. The eligible population(s)
and dosing interval for the heterologous booster dose are the same as those
authorized for a booster dose of the vaccine used for primary vaccination.

See this Fact Sheet for instructions for preparation and administration. This Fact
Sheet may have been updated. For the most recent Fact Sheet, please see
www.cvdvaccine.com.

For information on clinical trials that are testing the use of the Pfizer-BioNTech
COVID-19 Vaccine for active immunization against COVID-19, please see
www.clinicaltrials.gov.




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DESCRIPTION OF COVID-19

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the
novel coronavirus, SARS-CoV-2, that appeared in late 2019. It is predominantly a
respiratory illness that can affect other organs. People with COVID-19 have
reported a wide range of symptoms, ranging from mild symptoms to severe illness.
Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may
include: fever or chills; cough; shortness of breath; fatigue; muscle or body aches;
headache; new loss of taste or smell; sore throat; congestion or runny nose;
nausea or vomiting; diarrhea.

DOSAGE AND ADMINISTRATION

The storage, preparation, and administration information in this Fact Sheet apply to
the Pfizer-BioNTech COVID-19 Vaccine for 12 years of age and older, which is
supplied in a multiple dose vial with a purple cap and MUST BE DILUTED before
use.

Pfizer-BioNTech COVID-19 Vaccine, Multiple Dose Vial with Purple Cap
                                                         Doses Per Vial    Dose
     Age Range                Dilution Information       After Dilution   Volume
                            Dilute with 1.8 mL sterile
    12 years and
                             0.9% Sodium Chloride              6          0.3 mL
        older
                           Injection, USP prior to use

Storage and Handling

During storage, minimize exposure to room light, and avoid exposure to direct
sunlight and ultraviolet light.

Do not refreeze thawed vials.

Frozen Vials Prior to Use

Cartons of Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with purple caps
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 -90ºC to -60ºC (-130ºF to -76ºF) until the expiry date
printed on the label. This information in the package insert supersedes the storage
conditions printed on the vial cartons.

Cartons and vials of Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose
vials with purple caps with an expiry date of July 2021 through February 2022
printed on the label may remain in use for 3 months beyond the printed date as
long as approved storage conditions between -90ºC to -60ºC (-130ºF to -76ºF)
have been maintained. Updated expiry dates are shown below.


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 Printed Expiry Date             Updated Expiry Date
 July 2021                      October 2021
 August 2021                    November 2021
 September 2021                 December 2021
 October 2021                   January 2022
 November 2021                  February 2022
 December 2021                  March 2022
 January 2022                   April 2022
 February 2022                  May 2022

If not stored between -90ºC to -60ºC (-130ºF to -76ºF), 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 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 one 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
the Pfizer-BioNTech COVID-19 Vaccine arrives may be used as temporary storage
when consistently re-filled to the top of the container with dry ice. Refer to the
re-icing guidelines packed in the original thermal container for instructions
regarding the use of the thermal container for temporary storage. The thermal
container maintains a temperature range of -90ºC to -60ºC (-130ºF to -76ºF).
Storage of the vials between -96°C to -60°C (-141°F to -76°F) is not considered an
excursion from the recommended storage condition.

Transportation of Frozen Vials

If local redistribution is needed and full cartons containing vials cannot be
transported at -90°C to -60°C (-130°F to -76°F), vials may be transported at -25°C
to -15°C (-13°F to 5°F). Any hours used for transport at -25°C to -15°C (-13°F to
5°F) count against the 2-week limit for storage at -25°C to -15°C (-13°F to 5°F).
Frozen vials transported at -25°C to -15°C (-13°F to 5°F) may be returned one 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,
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.


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Undiluted vials may be stored at room temperature for no more than 2 hours.

Transportation of Thawed Vials

Available data support transportation of one or more thawed vials at 2°C to 8°C
(35°F to 46°F) for up to 12 hours.

Vials After Dilution

    •    After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within
         6 hours from the time of dilution.
    •    During storage, minimize exposure to room light, and avoid exposure to
         direct sunlight and ultraviolet light.
    •    Any vaccine remaining in vials must be discarded after 6 hours.
    •    Do not refreeze.

Dosing and Schedule

Primary Series

The Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly as a
primary series of 2 doses (0.3 mL each) 3 weeks apart to individuals 12 years of
age and older.

A third primary series dose of the Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) at
least 28 days following the second dose is authorized for administration to
individuals at least 12 years of age who have undergone solid organ
transplantation, or who are diagnosed with conditions that are considered to have
an equivalent level of immunocompromise.

Booster Dose

A single Pfizer-BioNTech COVID-19 Vaccine booster dose (0.3 mL) may be
administered intramuscularly at least 6 months after completing the primary series
to individuals:
    • 65 years of age and older
    • 18 through 64 years of age at high risk of severe COVID-19
    • 18 through 64 years of age with frequent institutional or occupational
        exposure to SARS-CoV-2

A single booster dose of the Pfizer-BioNTech COVID-19 Vaccine may be
administered as a heterologous booster dose following completion of primary
vaccination with another authorized COVID-19 vaccine. The eligible population(s)
and dosing interval for the heterologous booster dose are the same as those
authorized for a booster dose of the vaccine used for primary vaccination.




Revised: 29 October 2021                                                                 6
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The FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the two
EUA-authorized formulations of Pfizer-BioNTech COVID-19 Vaccine for ages
12 years and older when prepared according to their respective instructions for
use, can be used interchangeably.

COMIRNATY (COVID-19 Vaccine, mRNA) and the two EUA-authorized
formulations of Pfizer-BioNTech COVID-19 Vaccine intended for individuals ages
12 years and older should not be used for individuals 5 through 11 years of age
because of the potential for vaccine administration errors, including dosing errors.

Dose Preparation

Each vial MUST BE DILUTED before administering the vaccine.

Prior to Dilution
    • The Pfizer-BioNTech COVID-19 Vaccine multiple dose vial with a purple cap
        contains a volume of 0.45 mL and is supplied as a frozen suspension that
        does not contain preservative.
    • Each vial must be thawed before dilution.
           o Vials may be thawed in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or
               at room temperature [up to 25ºC (77ºF)] (see Storage and Handling).
           o Refer to thawing instructions in the panels below.

Dilution
Dilute the vial contents using 1.8 mL of sterile 0.9% Sodium Chloride Injection,
USP (not provided) to form the Pfizer-BioNTech COVID-19 Vaccine. ONLY use
sterile 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not
packaged with the vaccine and must be sourced separately. Do not use
bacteriostatic 0.9% Sodium Chloride Injection or any other diluent. Do not add
more than 1.8 mL of diluent.

After dilution, 1 vial contains 6 doses of 0.3 mL.




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 Dilution and Preparation Instructions




                                         •   Before dilution invert vaccine vial
                                             gently 10 times.
                                         •   Do not shake.
                                         •   Inspect 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.
                                         •   Do not use if liquid is discolored or
                                             if other particles are observed.

                  Gently × 10
 Pfizer-BioNTech COVID-19 Vaccine Vial with Purple Cap –
 DILUTION




                                         •   Obtain sterile 0.9% Sodium
                                             Chloride Injection, USP. Use only
                                             this as the diluent.
                                         •   Using aseptic technique, withdraw
                                             1.8 mL of diluent into a transfer
                                             syringe (21-gauge or narrower
                                             needle).
                                         •   Cleanse the vaccine vial stopper
                                             with a single-use antiseptic swab.
                                         •   Add 1.8 mL of sterile 0.9% Sodium
                                             Chloride Injection, USP into the
                                             vaccine vial.

   Add 1.8 mL of sterile 0.9% sodium
        chloride injection, USP.




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 Dilution and Preparation Instructions




                                         Equalize vial pressure before
                                         removing the needle from the vial by
                                         withdrawing 1.8 mL air into the empty
                                         diluent syringe.




      Pull back plunger to 1.8 mL to
           remove air from vial.




                                         •   Gently invert the vial containing the
                                             Pfizer-BioNTech COVID-19
                                             Vaccine 10 times to mix.
                                         •   Do not shake.
                                         •   Inspect the vaccine in the vial.
                                         •   The vaccine will be an off-white
                                             suspension. Do not use if vaccine
                                             is discolored or contains particulate
                                             matter.



                  Gently × 10




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 Dilution and Preparation Instructions




                                            •   Record the date and time of
                                                dilution on the Pfizer-BioNTech
                                                COVID-19 Vaccine vial label.
                                            •   Store between 2°C to 25°C (35°F
                                                to 77°F).
                                            •   Discard any unused vaccine
                                                6 hours after dilution.
       Record the date and time of
                dilution.
        Use within 6 hours after
                dilution.
 Pfizer-BioNTech COVID-19 Vaccine Vial with Purple Cap –
 WITHDRAWAL OF INDIVIDUAL 0.3 mL DOSES
                                            • Using aseptic technique, cleanse
                                              the vial stopper with a single-use
                                              antiseptic swab, and withdraw
                                              0.3 mL of the Pfizer-BioNTech
                                              COVID-19 Vaccine preferentially
                                              using a low dead-volume syringe
                                              and/or needle.
                                            • Each dose must contain 0.3 mL of
                                              vaccine.
                                            • If the amount of vaccine remaining
                                              in the vial cannot provide a full
                                              dose of 0.3 mL, discard the vial
         Withdraw 0.3 mL dose of              and any excess volume.
                vaccine.                    • Administer immediately.

Administration

Visually inspect each dose in the dosing syringe prior to administration. The
vaccine will be an off-white suspension. During the visual inspection,
   • verify the final dosing volume of 0.3 mL.
   • confirm there are no particulates and that no discoloration is observed.
   • do not administer if vaccine is discolored or contains particulate matter.

Administer the Pfizer-BioNTech COVID-19 Vaccine intramuscularly.

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After dilution, vials of Pfizer-BioNTech COVID-19 Vaccine with purple caps 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 6 doses from a single vial.
Irrespective of the type of syringe and needle:

    •   Each dose must contain 0.3 mL of vaccine.
    •   If the amount of vaccine remaining in the vial cannot provide a full dose of
        0.3 mL, discard the vial and content.
    •   Do not pool excess vaccine from multiple vials.

Contraindications

Do not administer Pfizer-BioNTech COVID-19 Vaccine to individuals with known
history of a severe allergic reaction (e.g., anaphylaxis) to any component of the
Pfizer-BioNTech COVID-19 Vaccine (see Full EUA Prescribing Information).

Warnings

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 Pfizer-BioNTech COVID-19 Vaccine.

Monitor Pfizer-BioNTech COVID-19 Vaccine recipients for the occurrence of
immediate adverse reactions according to the Centers for Disease Control and
Prevention (CDC) guidelines (https://www.cdc.gov/vaccines/covid-19/clinical-
considerations/managing-anaphylaxis.html).

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, available 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 considerations 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/clinical-
considerations/myocarditis.html).




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Syncope

Syncope (fainting) may occur in association with administration of injectable
vaccines, in particular in adolescents. Procedures should be in place to avoid injury
from fainting.

Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressant
therapy, may have a diminished immune response to the Pfizer-BioNTech
COVID-19 Vaccine.

Limitation of Effectiveness

Pfizer-BioNTech COVID-19 Vaccine may not protect all vaccine recipients.

Adverse Reactions

Adverse Reactions in Clinical Trials
Adverse reactions following administration of the Pfizer-BioNTech COVID-19
Vaccine that have been reported in clinical trials include injection site pain, fatigue,
headache, muscle pain, chills, joint pain, fever, injection site swelling, injection site
redness, nausea, malaise, lymphadenopathy, decreased appetite, rash, and pain in
extremity (see Full EUA Prescribing Information).

Adverse Reactions in Post Authorization Experience
Severe allergic reactions, including anaphylaxis, and other hypersensitivity
reactions (e.g., rash, pruritus, urticaria, angioedema), diarrhea, vomiting, pain in
extremity (arm), and syncope have been reported following administration of the
Pfizer-BioNTech COVID-19 Vaccine outside of clinical trials.

Myocarditis and pericarditis have been reported following administration of the
Pfizer-BioNTech COVID-19 Vaccine outside of clinical trials.

Additional adverse reactions, some of which may be serious, may become
apparent with more widespread use of the Pfizer-BioNTech COVID-19 Vaccine.

Use with Other Vaccines

There is no information on the co-administration of the Pfizer-BioNTech COVID-19
Vaccine with other vaccines.




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INFORMATION TO PROVIDE TO VACCINE RECIPIENTS/CAREGIVERS

As the vaccination provider, you must communicate to the recipient or their
caregiver, information consistent with the “Vaccine Information Fact Sheet for
Recipients and Caregivers” (and provide a copy or direct the individual to the
website www.cvdvaccine.com to obtain the Vaccine Information Fact Sheet) prior to
the individual receiving each dose of the Pfizer-BioNTech COVID-19 Vaccine,
including:
    • FDA has authorized the emergency use of the Pfizer-BioNTech COVID-19
       Vaccine, which is not an FDA-approved vaccine.
    • The recipient or their caregiver has the option to accept or refuse
       Pfizer-BioNTech COVID-19 Vaccine.
    • The significant known and potential risks and benefits of the
       Pfizer-BioNTech COVID-19 Vaccine, and the extent to which such risks and
       benefits are unknown.
    • Information about available alternative vaccines and the risks and benefits of
       those alternatives.

For information on clinical trials that are testing the use of the Pfizer-BioNTech
COVID-19 Vaccine to prevent COVID-19, please see www.clinicaltrials.gov.

Provide a vaccination card to the recipient or their caregiver with the date when the
recipient needs to return for the second dose of Pfizer-BioNTech COVID-19
Vaccine.

Provide the v-safe information sheet to vaccine recipients/caregivers and
encourage vaccine recipients to participate in v-safe. V-safe is a new voluntary
smartphone-based tool that uses text messaging and web surveys to check in with
people who have been vaccinated to identify potential side effects after COVID-19
vaccination. V-safe asks questions that help CDC monitor the safety of COVID-19
vaccines. V-safe also provides second-dose reminders if needed and live
telephone follow-up by CDC if participants report a significant health impact
following COVID-19 vaccination. For more information, visit: www.cdc.gov/vsafe.

MANDATORY REQUIREMENTS FOR PFIZER-BIONTECH COVID-19 VACCINE
ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION 3

In order to mitigate the risks of using this unapproved product under EUA and to
optimize the potential benefit of Pfizer-BioNTech COVID-19 Vaccine, the following
items are required. Use of unapproved Pfizer-BioNTech COVID-19 Vaccine for
active immunization to prevent COVID-19 under this EUA is limited to the following
(all requirements must be met):

    1. Pfizer-BioNTech COVID-19 Vaccine is authorized for use in individuals
       5 years of age and older.

3 Vaccination providers administering COMIRNATY (COVID-19 Vaccine, mRNA) must adhere to the

same reporting requirements.

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    2. The vaccination provider must communicate to the individual receiving the
       Pfizer-BioNTech COVID-19 Vaccine or their caregiver, information
       consistent with the “Vaccine Information Fact Sheet for Recipients and
       Caregivers” prior to the individual receiving Pfizer-BioNTech COVID-19
       Vaccine.

    3. The vaccination provider must include vaccination information in the
       state/local jurisdiction’s Immunization Information System (IIS) or other
       designated system.

    4. The vaccination provider is responsible for mandatory reporting of the
       following to the Vaccine Adverse Event Reporting System (VAERS):
           • vaccine administration errors whether or not associated with an
              adverse event,
           • serious adverse events* (irrespective of attribution to vaccination),
           • cases of Multisystem Inflammatory Syndrome (MIS) in adults and
              children, and
           • cases of COVID-19 that result in hospitalization or death.

        Complete and submit reports to VAERS online at
        https://vaers.hhs.gov/reportevent.html. For further assistance with reporting
        to VAERS call 1-800-822-7967. The reports should include the words
        “Pfizer-BioNTech COVID-19 Vaccine EUA” in the description section of the
        report.

    5. The vaccination provider is responsible for responding to FDA requests for
       information about vaccine administration errors, adverse events, cases of
       MIS in adults and children, and cases of COVID-19 that result in
       hospitalization or death following administration of Pfizer-BioNTech
       COVID-19 Vaccine to recipients.

* Serious adverse events are defined as:
   • Death;
   • A life-threatening adverse event;
   • Inpatient hospitalization or prolongation of existing hospitalization;
   • A persistent or significant incapacity or substantial disruption of the ability to
       conduct normal life functions;
   • A congenital anomaly/birth defect;
   • An important medical event that based on appropriate medical judgement
       may jeopardize the individual and may require medical or surgical
       intervention to prevent 1 of the outcomes listed above.




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OTHER ADVERSE EVENT REPORTING TO VAERS AND PFIZER INC.

Vaccination providers may report to VAERS other adverse events that are not
required to be reported using the contact information above.

To the extent feasible, report adverse events to Pfizer Inc. using the contact
information below or by providing a copy of the VAERS form to Pfizer Inc.

                Website                  Fax number          Telephone number

  www.pfizersafetyreporting.com        1-866-635-8337          1-800-438-1985

ADDITIONAL INFORMATION

For general questions, visit the website or call the telephone number provided
below.

To access the most recent Pfizer-BioNTech COVID-19 Vaccine Fact Sheets,
please scan the QR code provided below.

               Global website                         Telephone number

            www.cvdvaccine.com
                                                        1-877-829-2619
                                                       (1-877-VAX-CO19)



AVAILABLE ALTERNATIVES

COMIRNATY (COVID-19 Vaccine, mRNA) is an FDA-approved vaccine to prevent
COVID-19 caused by SARS-CoV-2. There may be clinical trials or availability under
EUA of other COVID-19 vaccines.

COMIRNATY (COVID-19 Vaccine, mRNA) and the two EUA-authorized
formulations of Pfizer-BioNTech COVID-19 Vaccine intended for individuals ages
12 years and older should not be used for individuals 5 through 11 years of age
because of the potential for vaccine administration errors, including dosing errors.

FEDERAL COVID-19 VACCINATION PROGRAM

This vaccine is being made available for emergency use exclusively through the
CDC COVID-19 Vaccination Program (the Vaccination Program). Healthcare
providers must enroll as providers in the Vaccination Program and comply with the
provider requirements. Vaccination providers may not charge any fee for the
vaccine and may not charge the vaccine recipient any out-of-pocket charge for

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administration. However, vaccination providers may seek appropriate
reimbursement from a program or plan that covers COVID-19 vaccine
administration fees for the vaccine recipient (private insurance, Medicare,
Medicaid, Health Resources & Services Administration [HRSA] COVID-19
Uninsured Program for non-insured recipients). For information regarding provider
requirements and enrollment in the CDC COVID-19 Vaccination Program, see
https://www.cdc.gov/vaccines/covid-19/provider-enrollment.html.

Individuals becoming aware of any potential violations of the CDC COVID-19
Vaccination Program requirements are encouraged to report them to the Office of
the Inspector General, U.S. Department of Health and Human Services, at
1-800-HHS-TIPS or https://TIPS.HHS.GOV.

AUTHORITY FOR ISSUANCE OF THE EUA

The Secretary of Health and Human Services (HHS) has declared a public health
emergency that justifies the emergency use of drugs and biological products during
the COVID-19 pandemic. In response, FDA has issued an EUA for the unapproved
product, Pfizer-BioNTech COVID-19 Vaccine, and for certain uses of
FDA-approved COMIRNATY for active immunization against COVID-19.

FDA issued this EUA, based on Pfizer-BioNTech’s request and submitted data.

For the authorized uses, although limited scientific information is available, based
on the totality of the scientific evidence available to date, it is reasonable to believe
that the Pfizer-BioNTech COVID-19 Vaccine and COMIRNATY (COVID-19
Vaccine, mRNA) may be effective for the prevention of COVID-19 in individuals as
specified in the Full EUA Prescribing Information.

This EUA for the Pfizer-BioNTech COVID-19 Vaccine and COMIRNATY
(COVID-19 Vaccine, mRNA) will end when the Secretary of HHS determines that
the circumstances justifying the EUA no longer exist or when there is a change in
the approval status of the product such that an EUA is no longer needed.

For additional information about Emergency Use Authorization visit FDA at:
https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-
and-policy-framework/emergency-use-authorization.

The Countermeasures Injury Compensation Program

The Countermeasures Injury Compensation Program (CICP) is a federal program
that has been created to help pay for related costs of medical care and other
specific expenses to compensate people injured after use of certain medical
countermeasures. Medical countermeasures are specific vaccines, medications,
devices, or other items used to prevent, diagnose, or treat the public during a public
health emergency or a security threat. For more information about CICP regarding
the Pfizer-BioNTech COVID-19 Vaccine used to prevent COVID-19, visit
www.hrsa.gov/cicp, email cicp@hrsa.gov, or call: 1-855-266-2427.
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    Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 19 of 54




Manufactured by
Pfizer Inc., New York, NY 10017


Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany

LAB-1450-15.2

Revised: 29 October 2021

                      END SHORT VERSION FACT SHEET
       Long Version (Full EUA Prescribing Information) Begins On Next Page




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                Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 20 of 54


FULL EMERGENCY USE
AUTHORIZATION (EUA) PRESCRIBING
INFORMATION

PFIZER-BIONTECH COVID-19 VACCINE
                                                      11.2 Lactation
                                                      11.3 Pediatric Use
FULL EMERGENCY USE AUTHORIZATION
                                                      11.4 Geriatric Use
PRESCRIBING INFORMATION: CONTENTS*                    11.5 Use in Immunocompromised
                                                   13 DESCRIPTION
1  AUTHORIZED USE                                  14 CLINICAL PHARMACOLOGY
2  DOSAGE AND ADMINISTRATION                          14.1 Mechanism of Action
   2.1  Preparation for Administration             18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR
   2.2  Administration Information                    EUA
   2.3  Vaccination Schedule                          18.1 Efficacy of Primary Series in Participants 16 Years of Age and
3 DOSAGE FORMS AND STRENGTHS                               Older
4 CONTRAINDICATIONS                                   18.2 Efficacy of Primary Series in Adolescents 12 Through 15 Years of
5 WARNINGS AND PRECAUTIONS                                 Age
   5.1  Management of Acute Allergic Reactions        18.3 Immunogenicity of Primary Series in Adolescents 12 Through
   5.2  Myocarditis and Pericarditis                       15 Years of Age
   5.3  Syncope                                       18.4 Immunogenicity of a Booster Dose Following a Pfizer-BioNTech
   5.4  Altered Immunocompetence                           COVID-19 Vaccine Primary Series in Participants 18 Through
   5.5  Limitation of Effectiveness                        55 Years of Age
6 OVERALL SAFETY SUMMARY                              18.5 Immunogenicity in Solid Organ Transplant Recipients
   6.1  Clinical Trials Experience                    18.6 Immunogenicity of a Booster Dose Following Primary Vaccination
   6.2  Post Authorization Experience                      with Another Authorized COVID-19 Vaccine
8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING      19 HOW SUPPLIED/STORAGE AND HANDLING
   ADVERSE EVENTS AND VACCINE ADMINISTRATION       20 PATIENT COUNSELING INFORMATION
   ERRORS                                          21 CONTACT INFORMATION
10 DRUG INTERACTIONS
11 USE IN SPECIFIC POPULATIONS                     * Sections or subsections omitted from the full emergency use authorization
   11.1 Pregnancy                                  prescribing information are not listed.




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FULL EMERGENCY USE AUTHORIZATION (EUA) PRESCRIBING INFORMATION

1          AUTHORIZED USE

Pfizer-BioNTech COVID-19 Vaccine is authorized for use under an Emergency Use Authorization (EUA) for
active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) in individuals 5 years of age and older.

This Fact Sheet pertains only to Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a
purple cap, which is authorized for use in individuals 12 years of age and older.

2          DOSAGE AND ADMINISTRATION

For intramuscular injection only.

The storage, preparation, and administration information in this Prescribing Information apply to the
Pfizer-BioNTech COVID-19 Vaccine for 12 years of age and older, which is supplied in a multiple dose vial
with a purple cap and MUST BE DILUTED before use.

Pfizer-BioNTech COVID-19 Vaccine, Multiple Dose Vial with Purple Cap
                                                                Doses Per Vial
          Age Range             Dilution Information            After Dilution          Dose Volume
                            Dilute with 1.8 mL sterile 0.9%
    12 years and older      Sodium Chloride Injection, USP              6                  0.3 mL
                                      prior to use

2.1        Preparation for Administration

Dose Preparation

Each vial MUST BE DILUTED before administering the vaccine.

Prior to Dilution

      •    The Pfizer-BioNTech COVID-19 Vaccine multiple dose vial with a purple cap contains a volume of
           0.45 mL and is supplied as a frozen suspension that does not contain preservative.
      •    Each vial must be thawed before dilution.
               o Vials may be thawed in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room temperature [up to
                  25ºC (77ºF)] [see How Supplied/Storage and Handling (19)].
               o Refer to thawing instructions in the panels below.

Dilution

      •    Dilute the vial contents using 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP (not provided) to
           form the Pfizer-BioNTech COVID-19 Vaccine. Do not add more than 1.8 mL of diluent.
      •    ONLY use sterile 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged
           with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride


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 Dilution and Preparation Instructions

 Pfizer-BioNTech COVID-19 Vaccine Vial with Purple Cap –
 DILUTION




                                                •   Obtain sterile 0.9% Sodium Chloride Injection,
                                                    USP. Use only this as the diluent.
                                                •   Using aseptic technique, withdraw 1.8 mL of
                                                    diluent into a transfer syringe (21-gauge or
                                                    narrower needle).
                                                •   Cleanse the vaccine vial stopper with a single-use
                                                    antiseptic swab.
                                                •   Add 1.8 mL of sterile 0.9% Sodium Chloride
                                                    Injection, USP into the vaccine vial.


         Add 1.8 mL of sterile 0.9% sodium
              chloride injection, USP.




                                                Equalize vial pressure before removing the needle
                                                from the vial by withdrawing 1.8 mL air into the
                                                empty diluent syringe.




       Pull back plunger to 1.8 mL to remove
                    air from vial.




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                Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 24 of 54

 Dilution and Preparation Instructions




                                                •   Gently invert the vial containing the
                                                    Pfizer-BioNTech COVID-19 Vaccine 10 times to
                                                    mix.
                                                •   Do not shake.
                                                •   Inspect the vaccine in the vial.
                                                •   The vaccine will be an off-white suspension. Do
                                                    not use if vaccine is discolored or contains
                                                    particulate matter.



                       Gently × 10




                                                •   Record the date and time of dilution on the
                                                    Pfizer-BioNTech COVID-19 Vaccine vial label.
                                                •   Store between 2°C to 25°C (35°F to 77°F).
                                                •   Discard any unused vaccine 6 hours after dilution.


            Record the date and time of
                      dilution.
          Use within 6 hours after dilution.




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 Dilution and Preparation Instructions

 Pfizer-BioNTech COVID-19 Vaccine Vial with Purple Cap –
 WITHDRAWAL OF INDIVIDUAL 0.3 mL DOSES



                                                        • Using aseptic technique, cleanse the vial stopper
                                                          with a single-use antiseptic swab, and withdraw
                                                          0.3 mL of the Pfizer-BioNTech COVID-19
                                                          Vaccine preferentially using a low dead-volume
                                                          syringe and/or needle.
                                                        • Each dose must contain 0.3 mL of vaccine.
                                                        • If the amount of vaccine remaining in the vial
                                                          cannot provide a full dose of 0.3 mL, discard the
                                                          vial and any excess volume.
                                                        • Administer immediately.
               Withdraw 0.3 mL dose of
                      vaccine.

2.2     Administration Information

Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off-white
suspension. During the visual inspection,
   • verify the final dosing volume of 0.3 mL.
   • confirm there are no particulates and that no discoloration is observed.
   • do not administer if vaccine is discolored or contains particulate matter.

Administer the Pfizer-BioNTech COVID-19 Vaccine intramuscularly.

After dilution, vials of Pfizer-BioNTech COVID-19 Vaccine with purple caps 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 6 doses from a single vial.
Irrespective of the type of syringe and needle:
    • Each dose must contain 0.3 mL of vaccine.
    • If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and
        any excess volume.
    • Do not pool excess vaccine from multiple vials.

2.3     Vaccination Schedule

Primary Series

The Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly as a primary series of 2 doses
(0.3 mL each) 3 weeks apart in individuals 12 years of age and older.

A third primary series dose of the Pfizer-BioNTech COVID-19 vaccine (0.3 mL) at least 28 days following the
second dose is authorized for administration to individuals at least 12 years of age who have undergone solid


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organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of
immunocompromise.

Booster Dose

A single Pfizer-BioNTech COVID-19 Vaccine booster dose (0.3 mL) may be administered intramuscularly at
least 6 months after completing the primary series to individuals:
    • 65 years of age and older
    • 18 through 64 years of age at high risk of severe COVID-19
    • 18 through 64 years of age with frequent institutional or occupational exposure to SARS-CoV-2

A single booster dose of the Pfizer-BioNTech COVID-19 Vaccine may be administered as a heterologous
booster dose following completion of primary vaccination with another authorized COVID-19 vaccine. The
eligible population(s) and dosing interval for the heterologous booster dose are the same as those authorized for
a booster dose of the vaccine used for primary vaccination.

The FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the two EUA-authorized formulations of
Pfizer-BioNTech COVID-19 Vaccine for ages 12 years of age and older when prepared according to their
respective instructions for use, can be used interchangeably.

COMIRNATY (COVID-19 Vaccine, mRNA) and the two EUA-authorized formulations of Pfizer-BioNTech
COVID-19 Vaccine intended for individuals ages 12 years and older should not be used for individuals 5
through 11 years of age because of the potential for vaccine administration errors, including dosing errors.

3       DOSAGE FORMS AND STRENGTHS

Pfizer-BioNTech COVID-19 Vaccine is a suspension for injection.

After preparation, each dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in vials with purple caps is
0.3 mL for individuals 12 years of age and older [see Dosage and Administration (2.1)].

4       CONTRAINDICATIONS

Do not administer Pfizer-BioNTech COVID-19 Vaccine to individuals with known history of a severe allergic
reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 Vaccine [see Description
(13)].

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 Pfizer-BioNTech COVID-19
Vaccine.

Monitor Pfizer-BioNTech COVID-19 Vaccine recipients for the occurrence of immediate adverse reactions
according to the Centers for Disease Control and Prevention (CDC) guidelines
(https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html).




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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, available 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 considerations 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/clinical-considerations/myocarditis.html).

5.3       Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines, in particular in
adolescents. 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 Pfizer-BioNTech COVID-19 Vaccine.

5.5       Limitation of Effectiveness

The Pfizer-BioNTech COVID-19 Vaccine may not protect all vaccine recipients.

6         OVERALL SAFETY SUMMARY

It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System
(VAERS) all vaccine administration errors, all serious adverse events, cases of Multisystem
Inflammatory Syndrome (MIS) in adults and children, and hospitalized or fatal cases of COVID-19
following vaccination with the Pfizer-BioNTech COVID-19 Vaccine. 4 To the extent feasible, provide a
copy of the VAERS form to Pfizer Inc. Please see the REQUIREMENTS AND INSTRUCTIONS FOR
REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS section for details
on reporting to VAERS and Pfizer Inc.

Primary Series

In clinical studies of participants 16 years of age and older who received Pfizer-BioNTech COVID-19 Vaccine
containing 30 mcg of a nucleoside-modified messenger RNA encoding the viral spike (S) glycoprotein of
SARS-CoV-2 (30 mcg modRNA), adverse reactions following administration of the primary series included
pain at the injection site (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint
pain (23.6%), fever (14.2%), injection site swelling (10.5%), injection site redness (9.5%), nausea (1.1%),
malaise (0.5%), and lymphadenopathy (0.3%).

In a clinical study in adolescents 12 through 15 years of age who received Pfizer-BioNTech COVID-19 Vaccine
(30 mcg modRNA), adverse reactions following administration of the primary series included pain at the
injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%),


4
    Vaccination providers administering COMIRNATY (COVID-19 Vaccine, mRNA) must adhere to the same reporting requirements.

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joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and
nausea (0.4%).

Booster Dose

In a clinical study of participants 18 through 55 years of age, adverse reactions following administration of a
booster dose were pain at the injection site (83.0%), fatigue (63.7%), headache (48.4%), muscle pain (39.1%),
chills (29.1%), joint pain (25.3%), lymphadenopathy (5.2%), nausea (0.7%), decreased appetite (0.3%), rash
(0.3%), and pain in extremity (0.3%).

Post Authorization Experience

Severe allergic reactions, including anaphylaxis, have been reported following administration of the
Pfizer-BioNTech COVID-19 Vaccine outside of clinical trials.

Myocarditis and pericarditis have been reported following administration of the Pfizer-BioNTech COVID-19
Vaccine outside of clinical trials.

6.1     Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not
reflect the rates observed in practice.

Primary Series

The safety of the primary series Pfizer-BioNTech COVID-19 Vaccine was evaluated in participants 12 years of
age and older in two 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. Study C4591001 (Study 2) is a Phase 1/2/3, multicenter, 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 43,448 participants [21,720 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) encoding
the viral spike (S) glycoprotein of SARS-CoV-2; 21,728 placebo] in Phase 2/3 are 16 years of age or older
(including 138 and 145 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively) and
2,260 adolescents are 12 through 15 years of age (1,131 and 1,129 in the vaccine and placebo groups,
respectively).

In Study 2, all participants 12 to <16 years of age, and 16 years of age and older in the reactogenicity subset,
were monitored for solicited local and systemic reactions and use of antipyretic medication after each
vaccination in an electronic diary. Participants are being monitored for unsolicited adverse events, including
serious adverse events, throughout the study [from Dose 1 through 1 month (all unsolicited adverse events) or
6 months (serious adverse events) after the last vaccination]. Tables 1 through 6 present the frequency and
severity of solicited local and systemic reactions, respectively, within 7 days following each dose of
Pfizer-BioNTech COVID 19 Vaccine and placebo.




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Participants 16 Years of Age and Older

At the time of the analysis of Study 2 for the EUA, 37,586 (18,801 Pfizer-BioNTech COVID-19 Vaccine (30
mcg modRNA) and 18,785 placebo) participants 16 years of age or older had been followed for a median of 2
months after the second dose.

The safety evaluation in Study 2 is ongoing. The safety population includes participants 16 years and older
enrolled by October 9, 2020, and includes safety data accrued through November 14, 2020.

Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity
among participants who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo.
Overall, among the total participants who received either the Pfizer-BioNTech COVID-19 Vaccine or placebo,
50.6% were male and 49.4% were female, 83.1% were White, 9.1% were Black or African American,
28.0% were Hispanic/Latino, 4.3% were Asian, and 0.5% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

Across both age groups, 18 through 55 years of age and 56 years and older, the mean duration of pain at the
injection site after Dose 2 was 2.5 days (range 1 to 36 days), for redness 2.6 days (range 1 to 34 days), and for
swelling 2.3 days (range 1 to 34 days) for participants in the Pfizer-BioNTech COVID-19 Vaccine group.

Solicited reactogenicity data in 16 and 17 year-old participants are limited.

Table 1: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by
           Maximum Severity, Within 7 Days After Each Dose – Participants 18 Through 55 Years of
           Age‡ – Reactogenicity Subset of the Safety Population*
                            Pfizer-BioNTech                        Pfizer-BioNTech
                          COVID-19 Vaccine     †     Placebo      COVID-19 Vaccine†       Placebo
                                  Dose 1              Dose 1            Dose 2             Dose 2
                                 Na=2291             Na=2298           Na=2098            Na=2103
                                  nb (%)              nb (%)            nb (%)             nb (%)
         c
 Redness
    Any (>2 cm)                  104 (4.5)            26 (1.1)         123 (5.9)          14 (0.7)
       Mild                       70 (3.1)            16 (0.7)          73 (3.5)           8 (0.4)
       Moderate                   28 (1.2)             6 (0.3)          40 (1.9)           6 (0.3)
       Severe                      6 (0.3)             4 (0.2)          10 (0.5)           0 (0.0)
 Swellingc
    Any (>2 cm)                  132 (5.8)            11 (0.5)         132 (6.3)           5 (0.2)
       Mild                       88 (3.8)             3 (0.1)          80 (3.8)           3 (0.1)
       Moderate                   39 (1.7)             5 (0.2)          45 (2.1)           2 (0.1)
       Severe                      5 (0.2)             3 (0.1)           7 (0.3)           0 (0.0)




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                                   Pfizer-BioNTech                                      Pfizer-BioNTech
                                  COVID-19 Vaccine†                 Placebo            COVID-19 Vaccine†                 Placebo
                                        Dose 1                       Dose 1                  Dose 2                       Dose 2
                                       Na=2291                      Na=2298                 Na=2098                      Na=2103
                                        nb (%)                       nb (%)                  nb (%)                       nb (%)
 Pain at the injection sited
    Any                                 1904 (83.1)                322 (14.0)                1632 (77.8)                245 (11.7)
       Mild                             1170 (51.1)                308 (13.4)                1039 (49.5)                225 (10.7)
       Moderate                          710 (31.0)                 12 (0.5)                  568 (27.1)                 20 (1.0)
       Severe                             24 (1.0)                   2 (0.1)                   25 (1.2)                   0 (0.0)
 Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
 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. 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.
 ‡ Eight participants were between 16 and 17 years of age.
 * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).

Table 2: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by
          Maximum Severity, Within 7 Days After Each Dose – Participants 18 Through 55 Years of
          Age‡ – Reactogenicity Subset of the Safety Population*
                        Pfizer-BioNTech                           Pfizer-BioNTech
                       COVID-19 Vaccine†           Placebo       COVID-19 Vaccine†       Placebo
                              Dose 1                Dose 1              Dose 2            Dose 2
                             N =2291
                               a                   N =2298
                                                     a                 N =2098
                                                                         a               Na=2103
                              n (%)
                                b                   n (%)
                                                      b                 n (%)
                                                                          b               nb (%)
 Fever
    ≥38.0℃                   85 (3.7)               20 (0.9)          331 (15.8)          10 (0.5)
    ≥38.0℃ to 38.4℃          64 (2.8)               10 (0.4)           194 (9.2)           5 (0.2)
    >38.4℃ to 38.9℃          15 (0.7)                5 (0.2)           110 (5.2)           3 (0.1)
    >38.9℃ to 40.0℃           6 (0.3)                3 (0.1)            26 (1.2)           2 (0.1)
    >40.0℃                    0 (0.0)                2 (0.1)             1 (0.0)           0 (0.0)
 Fatiguec
    Any                    1085 (47.4)            767 (33.4)         1247 (59.4)        479 (22.8)
       Mild                 597 (26.1)            467 (20.3)          442 (21.1)        248 (11.8)
       Moderate             455 (19.9)            289 (12.6)          708 (33.7)        217 (10.3)
       Severe                33 (1.4)               11 (0.5)            97 (4.6)          14 (0.7)
 Headachec
    Any                     959 (41.9)            775 (33.7)         1085 (51.7)        506 (24.1)
       Mild                 628 (27.4)            505 (22.0)          538 (25.6)        321 (15.3)
       Moderate             308 (13.4)            251 (10.9)          480 (22.9)         170 (8.1)
       Severe                23 (1.0)               19 (0.8)            67 (3.2)          15 (0.7)
 Chillsc
    Any                     321 (14.0)             146 (6.4)          737 (35.1)          79 (3.8)
       Mild                 230 (10.0)             111 (4.8)          359 (17.1)          65 (3.1)
       Moderate              82 (3.6)               33 (1.4)          333 (15.9)          14 (0.7)
       Severe                 9 (0.4)                2 (0.1)            45 (2.1)           0 (0.0)




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                 Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 31 of 54

                               Pfizer-BioNTech                                        Pfizer-BioNTech
                              COVID-19 Vaccine†                  Placebo             COVID-19 Vaccine†                Placebo
                                    Dose 1                        Dose 1                   Dose 2                      Dose 2
                                   Na=2291                       Na=2298                  Na=2098                     Na=2103
                                    nb (%)                        nb (%)                   nb (%)                      nb (%)
 Vomitingd
    Any                        28 (1.2)                           28 (1.2)                   40 (1.9)                  25 (1.2)
       Mild                    24 (1.0)                           22 (1.0)                   28 (1.3)                  16 (0.8)
       Moderate                 4 (0.2)                            5 (0.2)                    8 (0.4)                   9 (0.4)
       Severe                   0 (0.0)                            1 (0.0)                    4 (0.2)                   0 (0.0)
         e
 Diarrhea
    Any                      255 (11.1)                         270 (11.7)                 219 (10.4)                 177 (8.4)
       Mild                   206 (9.0)                          217 (9.4)                  179 (8.5)                 144 (6.8)
       Moderate                46 (2.0)                           52 (2.3)                   36 (1.7)                  32 (1.5)
       Severe                   3 (0.1)                            1 (0.0)                    4 (0.2)                   1 (0.0)
                             c
 New or worsened muscle pain
    Any                      487 (21.3)                         249 (10.8)                 783 (37.3)                 173 (8.2)
       Mild                  256 (11.2)                          175 (7.6)                 326 (15.5)                 111 (5.3)
       Moderate               218 (9.5)                           72 (3.1)                 410 (19.5)                  59 (2.8)
       Severe                  13 (0.6)                            2 (0.1)                  47 (2.2)                    3 (0.1)
 New or worsened joint painc
    Any                      251 (11.0)                          138 (6.0)                 459 (21.9)                 109 (5.2)
       Mild                   147 (6.4)                           95 (4.1)                  205 (9.8)                  54 (2.6)
       Moderate                99 (4.3)                           43 (1.9)                 234 (11.2)                  51 (2.4)
       Severe                   5 (0.2)                            0 (0.0)                   20 (1.0)                   4 (0.2)
 Use of antipyretic or
 pain medicationf            638 (27.8)                         332 (14.4)                 945 (45.0)                266 (12.6)
 Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after
 each dose.
 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 times in 24 hours; Severe: requires intravenous hydration.
 e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
 f. Severity was not collected for use of antipyretic or pain medication.
 ‡ Eight participants were between 16 and 17 years of age.
 * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).




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                 Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 32 of 54

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*
                              Pfizer-BioNTech                         Pfizer-BioNTech
                             COVID-19 Vaccine†         Placebo       COVID-19 Vaccine†     Placebo
                                    Dose 1              Dose 1              Dose 2          Dose 2
                                   Na=1802             Na=1792             Na=1660        Na=1646
                                    nb (%)              nb (%)              nb (%)          nb (%)
          c
 Redness
    Any (>2 cm)                     85 (4.7)           19 (1.1)            120 (7.2)       12 (0.7)
       Mild                         55 (3.1)           12 (0.7)             59 (3.6)        8 (0.5)
       Moderate                     27 (1.5)            5 (0.3)             53 (3.2)        3 (0.2)
       Severe                        3 (0.2)            2 (0.1)              8 (0.5)        1 (0.1)
           c
 Swelling
    Any (>2 cm)                    118 (6.5)           21 (1.2)            124 (7.5)       11 (0.7)
       Mild                         71 (3.9)           10 (0.6)             68 (4.1)        5 (0.3)
       Moderate                     45 (2.5)           11 (0.6)             53 (3.2)        5 (0.3)
       Severe                        2 (0.1)            0 (0.0)              3 (0.2)        1 (0.1)
                           d
 Pain at the injection site
    Any (>2 cm)                  1282 (71.1)          166 (9.3)          1098 (66.1)      127 (7.7)
       Mild                      1008 (55.9)          160 (8.9)           792 (47.7)      125 (7.6)
       Moderate                   270 (15.0)            6 (0.3)           298 (18.0)        2 (0.1)
       Severe                        4 (0.2)            0 (0.0)              8 (0.5)        0 (0.0)
 Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
 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. 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.
 * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).

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*
                          Pfizer-BioNTech                         Pfizer-BioNTech
                        COVID-19 Vaccine†          Placebo       COVID-19 Vaccine†       Placebo
                                Dose 1              Dose 1              Dose 2            Dose 2
                               Na=1802             Na=1792             Na=1660           Na=1646
                                nb (%)              nb (%)              nb (%)            nb (%)
 Fever
    ≥38.0℃                     26 (1.4)             7 (0.4)           181 (10.9)          4 (0.2)
    ≥38.0℃ to 38.4℃            23 (1.3)             2 (0.1)            131 (7.9)          2 (0.1)
    >38.4℃ to 38.9℃             1 (0.1)             3 (0.2)             45 (2.7)          1 (0.1)
    >38.9℃ to 40.0℃             1 (0.1)             2 (0.1)              5 (0.3)          1 (0.1)
    >40.0℃                      1 (0.1)             0 (0.0)              0 (0.0)          0 (0.0)
        c
 Fatigue
    Any                       615 (34.1)          405 (22.6)          839 (50.5)        277 (16.8)
       Mild                   373 (20.7)          252 (14.1)          351 (21.1)         161 (9.8)
       Moderate               240 (13.3)           150 (8.4)          442 (26.6)         114 (6.9)
       Severe                   2 (0.1)             3 (0.2)             46 (2.8)          2 (0.1)

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                                 Pfizer-BioNTech                                      Pfizer-BioNTech
                                COVID-19 Vaccine†                 Placebo            COVID-19 Vaccine†                Placebo
                                      Dose 1                       Dose 1                  Dose 2                      Dose 2
                                     Na=1802                      Na=1792                 Na=1660                     Na=1646
                                      nb (%)                       nb (%)                  nb (%)                      nb (%)
 Headachec
    Any                       454 (25.2)                         325 (18.1)                647 (39.0)                229 (13.9)
        Mild                  348 (19.3)                         242 (13.5)                422 (25.4)                165 (10.0)
        Moderate               104 (5.8)                          80 (4.5)                 216 (13.0)                 60 (3.6)
        Severe                   2 (0.1)                           3 (0.2)                   9 (0.5)                   4 (0.2)
       c
 Chills
    Any                        113 (6.3)                          57 (3.2)                 377 (22.7)                  46 (2.8)
        Mild                    87 (4.8)                          40 (2.2)                 199 (12.0)                  35 (2.1)
        Moderate                26 (1.4)                          16 (0.9)                  161 (9.7)                  11 (0.7)
        Severe                   0 (0.0)                           1 (0.1)                   17 (1.0)                   0 (0.0)
           d
 Vomiting
    Any                          9 (0.5)                           9 (0.5)                   11 (0.7)                   5 (0.3)
        Mild                     8 (0.4)                           9 (0.5)                    9 (0.5)                   5 (0.3)
        Moderate                 1 (0.1)                           0 (0.0)                    1 (0.1)                   0 (0.0)
        Severe                   0 (0.0)                           0 (0.0)                    1 (0.1)                   0 (0.0)
 Diarrheae
    Any                        147 (8.2)                          118 (6.6)                 137 (8.3)                  99 (6.0)
        Mild                   118 (6.5)                          100 (5.6)                 114 (6.9)                  73 (4.4)
        Moderate                26 (1.4)                           17 (0.9)                  21 (1.3)                  22 (1.3)
        Severe                   3 (0.2)                            1 (0.1)                   2 (0.1)                   4 (0.2)
 New or worsened muscle painc
    Any                       251 (13.9)                          149 (8.3)                477 (28.7)                  87 (5.3)
        Mild                   168 (9.3)                          100 (5.6)                202 (12.2)                  57 (3.5)
        Moderate                82 (4.6)                           46 (2.6)                259 (15.6)                  29 (1.8)
        Severe                   1 (0.1)                            3 (0.2)                 16 (1.0)                    1 (0.1)
 New or worsened joint painc
    Any                        155 (8.6)                          109 (6.1)                313 (18.9)                  61 (3.7)
        Mild                   101 (5.6)                           68 (3.8)                 161 (9.7)                  35 (2.1)
        Moderate                52 (2.9)                           40 (2.2)                 145 (8.7)                  25 (1.5)
        Severe                   2 (0.1)                            1 (0.1)                  7 (0.4)                    1 (0.1)
 Use of antipyretic or
 pain medication              358 (19.9)                         213 (11.9)                625 (37.7)                 161 (9.8)
 Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after
 each dose.
 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 times in 24 hours; Severe: requires intravenous hydration.
 e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
 * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).

From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19
vaccine in solid-organ transplant recipients. N Engl J Med), in 99 individuals who had undergone various solid
organ transplant procedures (heart, kidney, liver, lung, pancreas) 97±8 months previously who received a third

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vaccine dose, the adverse event profile was similar to that after the second dose and no grade 3 or grade 4
events were reported in recipients who were followed for 1 month following post Dose 3.

Unsolicited Adverse Events

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 (Pfizer-BioNTech COVID-19 Vaccine = 10,841; placebo = 10,851), serious adverse events from
Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech
COVID-19 Vaccine recipients and by 0.3% of placebo recipients. In a similar analysis, in participants 56 years
of age and older (Pfizer-BioNTech COVID-19 Vaccine = 7,960, placebo = 7,934), serious adverse events were
reported by 0.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.6% of placebo recipients who
received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine or placebo, respectively. In these analyses,
91.6% of study participants had at least 30 days of follow-up after Dose 2.

Appendicitis was reported as a serious adverse event for 12 participants, and numerically higher in the vaccine
group, 8 vaccine participants and 4 placebo participants. 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 serious adverse events (including neurologic,
neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Pfizer-BioNTech
COVID-19 Vaccine.

Non-Serious Adverse Events
In Study 2 in which 10,841 participants 16 through 55 years of age received Pfizer-BioNTech COVID-19
Vaccine and 10,851 participants received placebo, non-serious adverse events from Dose 1 through up to
30 days after Dose 2 in ongoing follow-up were reported in 29.3% of participants who received
Pfizer-BioNTech COVID-19 Vaccine and 13.2% of participants in the placebo group, for participants who
received at least 1 dose. Overall in a similar analysis in which 7960 participants 56 years of age and older
received Pfizer-BioNTech COVID-19 Vaccine, non-serious adverse events within 30 days were reported in
23.8% of participants who received Pfizer-BioNTech COVID-19 Vaccine and 11.7% of participants in the
placebo group, for participants who received at least 1 dose. In these analyses, 91.6% of study participants had
at least 30 days of follow-up after Dose 2.

The higher frequency of reported unsolicited non-serious adverse events among Pfizer-BioNTech COVID-19
Vaccine recipients compared to placebo recipients was primarily attributed to local and systemic adverse events
reported during the first 7 days following vaccination that are consistent with adverse reactions solicited among
participants in the reactogenicity subset and presented in Tables 3 and 4. From Dose 1 through 30 days after
Dose 2, reports of lymphadenopathy were imbalanced with notably more cases in the Pfizer-BioNTech
COVID-19 Vaccine group (64) vs. the placebo group (6), which is plausibly related to vaccination. Throughout
the safety follow-up period to date, Bell’s palsy (facial paralysis) was reported by 4 participants in the
Pfizer-BioNTech COVID-19 Vaccine 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. No cases of Bell’s palsy were reported in the placebo
group. 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 Pfizer-BioNTech COVID-19 Vaccine.




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Adolescents 12 Through 15 Years of Age

In an analysis of Study 2, based on data up to the cutoff date of March 13, 2021, 2,260 adolescents
(1,131 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA); 1,129 placebo) were 12 through 15 years of
age. Of these, 1,308 (660 Pfizer-BioNTech COVID-19 Vaccine and 648 placebo) adolescents have been
followed for at least 2 months after the second dose. The safety evaluation in Study 2 is ongoing.

Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity
among adolescents who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo.
Overall, among the adolescents who received the Pfizer-BioNTech COVID-19 Vaccine, 50.1% were male and
49.9% were female, 85.9% were White, 4.6% were Black or African American, 11.7% were Hispanic/Latino,
6.4% were Asian, and 0.4% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

The mean duration of pain at the injection site after Dose 1 was 2.4 days (range 1 to 10 days), for redness
2.4 days (range 1 to 16 days), and for swelling 1.9 days (range 1 to 5 days) for adolescents in the
Pfizer-BioNTech COVID-19 Vaccine group.

Table 5: Study 2 – Frequency and Percentages of Adolescents With Solicited Local Reactions, by
             Maximum Severity, Within 7 Days After Each Dose – Adolescents 12 Through 15 Years of
             Age – Safety Population*
                              Pfizer-BioNTech                     Pfizer-BioNTech
                             COVID-19 Vaccine †    Placebo       COVID-19 Vaccine†        Placebo
                                    Dose 1          Dose 1              Dose 2             Dose 2
                                   N =1127
                                     a             N =1127
                                                     a                 N =1097
                                                                         a                Na=1078
                                    n (%)
                                      b             n (%)
                                                      b                 n (%)
                                                                          b                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)
           c
 Swelling
    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)
 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 the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
 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. 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.
 * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).




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Table 6: Study 2 – Frequency and Percentages of Adolescents with Solicited Systemic Reactions, by
           Maximum Severity, Within 7 Days After Each Dose – Adolescents 12 Through 15 Years of
           Age – Safety Population*
                          Pfizer-BioNTech                       Pfizer-BioNTech
                         COVID-19 Vaccine†       Placebo      COVID-19 Vaccine†          Placebo
                                 Dose 1           Dose 1              Dose 2              Dose 2
                                Na=1127          Na=1127             Na=1097             Na=1078
                                 nb (%)           nb (%)              nb (%)              nb (%)
 Fever
    ≥38.0℃                     114 (10.1)         12 (1.1)          215 (19.6)            7 (0.6)
    ≥38.0℃ to 38.4℃              74 (6.6)          8 (0.7)           107 (9.8)            5 (0.5)
    >38.4℃ to 38.9℃              29 (2.6)          2 (0.2)            83 (7.6)            1 (0.1)
    >38.9℃ to 40.0℃              10 (0.9)          2 (0.2)            25 (2.3)            1 (0.1)
    >40.0℃                        1 (0.1)          0 (0.0)             0 (0.0)            0 (0.0)
         c
 Fatigue
    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)          263 (24.4)
       Mild                    361 (32.0)       256 (22.7)          302 (27.5)          169 (15.7)
       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)           73 (6.8)
       Mild                    195 (17.3)         82 (7.3)          221 (20.1)           52 (4.8)
       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)
 Diarrheae
    Any                          90 (8.0)         82 (7.3)            65 (5.9)           43 (4.0)
       Mild                      77 (6.8)         72 (6.4)            59 (5.4)           38 (3.5)
       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)
                             c
 New or worsened muscle pain
    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)




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                           Pfizer-BioNTech                                            Pfizer-BioNTech
                         COVID-19 Vaccine†                        Placebo            COVID-19 Vaccine†                Placebo
                                 Dose 1                            Dose 1                  Dose 2                      Dose 2
                                Na=1127                           Na=1127                 Na=1097                     Na=1078
                                 nb (%)                            nb (%)                  nb (%)                      nb (%)
 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 after
 each dose.
 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 times in 24 hours; Severe: requires intravenous hydration.
 e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
 f. Severity was not collected for use of antipyretic or pain medication.
 * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).

Unsolicited Adverse Events

In the following analyses of Study 2 in adolescents 12 through 15 years of age (1,131 of whom received
Pfizer-BioNTech COVID-19 Vaccine and 1,129 of whom received placebo), 98.3% of study participants had at
least 30 days of follow-up after Dose 2.

Serious Adverse Events
Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by
0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.1% of placebo recipients. There were no
notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse
events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Non-Serious Adverse Events
Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported
by 5.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 5.8% of placebo recipients. From Dose 1
through 30 days after Dose 2, reports of lymphadenopathy plausibly related to the study intervention were
imbalanced, with notably more cases in the Pfizer-BioNTech COVID-19 Vaccine group (7) vs. the placebo
group (1). There were no other notable patterns or numerical imbalances between treatment groups for specific
categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech
COVID-19 Vaccine.

Booster Dose Following a Primary Series of Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY

A subset of Study 2 Phase 2/3 participants of 306 adults 18 through 55 years of age received a booster dose of
Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) approximately 6 months (range of 4.8 to 8.0 months)
after completing the primary series. Additionally, a total of 23 Study 2 Phase 1 participants (11 participants 18
through 55 years of age and 12 participants 65 through 85 years of age) received a booster dose of
Pfizer-BioNTech COVID-19 Vaccine approximately 8 months (range 7.9 to 8.8 months) after completing the

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primary series. Safety monitoring after the booster dose was the same as that in the reactogenicity subset who
received the primary series.

Among the 306 Phase 2/3 participants, the median age was 42 years (range 19 through 55 years of age), 45.8%
were male and 54.2% were female, 81.4% were White, 27.8% were Hispanic/Latino, 9.2% were Black or
African American, 5.2% were Asian, and 0.7% were American Indian/Alaska Native. Among the 12 Phase 1
participants 65 through 85 years of age, the median age was 69 years (range 65 through 75 years of age), 6 were
male and all were White and Not Hispanic/Latino. Following the booster dose, the median follow-up time was
2.6 months (range 2.1 to 2.9 months) for Phase 1 participants and 2.6 months (range 1.1 to 2.8 months) for
Phase 2/3 participants.

Solicited Local and Systemic Adverse Reactions

Table 7 and Table 8 present the frequency and severity of reported solicited local and systemic reactions,
respectively, within 7 days of a booster dose of Pfizer-BioNTech COVID-19 Vaccine for Phase 2/3 participants
18 through 55 years of age.

In participants who received a booster dose, the mean duration of pain at the injection site after the booster dose
was 2.6 days (range 1 to 8 days), for redness 2.2 days (range 1 to 15 days), and for swelling 2.2 days (range 1 to
8 days).

Table 7: Study 2 – Frequency and Percentages of Participants With Solicited Local Reactions, By
             Maximum Severity, Within 7 Days After the Booster Dose of Pfizer-BioNTech COVID-19
             Vaccine – Participants 18 through 55 Years of Age*
                                                             Pfizer-BioNTech COVID-19 Vaccine†
                                                                        Booster Dose
                                                                          Na = 289
 Solicited Local Reaction                                                  nb (%)
          c
 Redness
    Any (>2 cm)                                                            17 (5.9)
       Mild                                                                10 (3.5)
       Moderate                                                             7 (2.4)
       Severe                                                                  0
           c
 Swelling
    Any (>2 cm)                                                            23 (8.0)
       Mild                                                                13 (4.5)
       Moderate                                                             9 (3.1)
       Severe                                                               1 (0.3)
                           d
 Pain at the injection site
    Any                                                                  240 (83.0)
       Mild                                                              174 (60.2)
       Moderate                                                           65 (22.5)
       Severe                                                               1 (0.3)
 Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after the booster dose.
 Note: No Grade 4 solicited local reactions were reported.
 * A subset of Phase 2/3 participants 18 through 55 years of age who received a booster dose of COMIRNATY (COVID-19
    Vaccine, mRNA) approximately 6 months after completing the primary series.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 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. Mild: >2.0 to 5.0 cm; Moderate: >5.0 to 10.0 cm; Severe: >10.0 cm.

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                                                                              Pfizer-BioNTech COVID-19 Vaccine†
                                                                                         Booster Dose
                                                                                           Na = 289
 Solicited Local Reaction                                                                   nb (%)
 d. Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.



Table 8: Study 2 – Frequency and Percentages of Participants With Solicited Systemic Reactions, by
            Maximum Severity, Within 7 Days After the Booster Dose of Pfizer-BioNTech COVID-19
            Vaccine – Participants 18 through 55 Years of Age*
                                                           Pfizer-BioNTech COVID-19 Vaccine†
                                                                      Booster Dose
                                                                        Na = 289
 Solicited Systemic Reaction                                             nb (%)
 Fever
    ≥38.0℃                                                               25 (8.7)
    ≥38.0℃ to 38.4℃                                                      12 (4.2)
    >38.4℃ to 38.9℃                                                      12 (4.2)
    >38.9℃ to 40.0℃                                                       1 (0.3)
    >40.0℃                                                                   0
         c
 Fatigue
    Any                                                                184 (63.7)
        Mild                                                            68 (23.5)
        Moderate                                                       103 (35.6)
        Severe                                                           13 (4.5)
           c
 Headache
    Any                                                                140 (48.4)
        Mild                                                            83 (28.7)
        Moderate                                                        54 (18.7)
        Severe                                                            3 (1.0)
       c
 Chills
    Any                                                                 84 (29.1)
        Mild                                                            37 (12.8)
        Moderate                                                        44 (15.2)
        Severe                                                            3 (1.0)
           d
 Vomiting
    Any                                                                   5 (1.7)
        Mild                                                              5 (1.7)
        Moderate                                                             0
        Severe                                                               0
 Diarrheae
    Any                                                                  25 (8.7)
        Mild                                                             21 (7.3)
        Moderate                                                          4 (1.4)
        Severe                                                               0




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                                                                          Pfizer-BioNTech COVID-19 Vaccine†
                                                                                     Booster Dose
                                                                                       Na = 289
 Solicited Systemic Reaction                                                            nb (%)
 New or worsened muscle painc
    Any                                                                                     113 (39.1)
       Mild                                                                                  52 (18.0)
       Moderate                                                                              57 (19.7)
       Severe                                                                                 4 (1.4)
 New or worsened joint painc
    Any                                                                                      73 (25.3)
       Mild                                                                                  36 (12.5)
       Moderate                                                                              36 (12.5)
        Severe                                                                                1 (0.3)
 Use of antipyretic or pain medicationf                                                     135 (46.7)
 Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after
 the booster dose.
 Note: No Grade 4 solicited systemic reactions were reported.
 * A subset of Phase 2/3 participants 18 through 55 years of age who received a booster dose of COMIRNATY (COVID-19
    Vaccine, mRNA) approximately 6 months after completing the primary series.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 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 times in 24 hours; Severe: requires intravenous hydration.
 e. Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours.
 f. Severity was not collected for use of antipyretic or pain medication.

In Phase 1 participants ≥65 years of age (n = 12), local reaction pain at the injection site (n = 8, 66.7%) and
systemic reactions fatigue (n = 5, 41.7%), headache (n = 5, 41.7%), chills (n = 2, 16.7%), muscle pain (n = 4,
33.3%), and joint pain (n = 2, 16.7%) were reported after the booster dose. No participant in this age group
reported a severe systemic event or fever after the booster dose.

Unsolicited Adverse Events

Overall, the 306 participants who received a booster dose, had a median follow-up time of 2.6 months after the
booster dose to the cut-off date (June 17, 2021).

In an analysis of all unsolicited adverse events reported following the booster dose, through 1 month after the
booster dose, in participants 18 through 55 years of age (N = 306), those assessed as adverse reactions not
already captured by solicited local and systemic reactions were lymphadenopathy (n = 16, 5.2%), nausea (n = 2,
0.7%), decreased appetite (n = 1, 0.3%), rash (n = 1, 0.3%), and pain in extremity (n = 1, 0.3%).

Serious Adverse Events

Of the 306 participants who received a booster dose of Pfizer-BioNTech COVID-19 Vaccine, there were no
serious adverse events reported from the booster dose through 30 days after the booster dose. One participant
reported a serious adverse event 61 days after the booster dose that was assessed as unrelated to vaccination.




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Booster Dose Following Primary Vaccination with Another Authorized COVID-19 Vaccine

The safety of a Pfizer-BioNTech COVID-19 Vaccine booster dose (30 mcg modRNA) in individuals who
completed primary vaccination with another authorized COVID-19 Vaccine (heterologous booster dose) is
inferred from the safety of a Pfizer-BioNTech COVID-19 Vaccine booster dose administered following
completion of Pfizer-BioNTech COVID-19 Vaccine primary series (homologous booster dose) and from data
from an independent National Institutes of Health (NIH) study Phase 1/2 open-label clinical trial
(NCT04889209) conducted in the United States that evaluated a heterologous booster dose of the
Pfizer-BioNTech COVID-19 Vaccine. In this study, adults who had completed primary vaccination with a
Moderna COVID-19 Vaccine 2-dose series (N=151), a Janssen COVID-19 Vaccine single dose (N=156), or a
Pfizer-BioNTech COVID-19 Vaccine 2-dose series (N=151) at least 12 weeks prior to enrollment and who
reported no history of SARS-CoV-2 infection were randomized 1:1:1 to receive a booster dose of one of three
vaccines: Moderna COVID-19 Vaccine, Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine
(30 mcg modRNA). Adverse events were assessed through 28 days after the booster dose. An overall review of
adverse reactions reported in the study following the Pfizer-BioNTech COVID-19 Vaccine heterologous
booster dose did not identify any new safety concerns, as compared with adverse reactions reported following a
Pfizer-BioNTech COVID-19 Vaccine primary series doses or homologous booster dose.

6.2       Post Authorization Experience

The following adverse reactions have been identified during post authorization use of Pfizer-BioNTech
COVID-19 Vaccine. Because these reactions are reported voluntarily, it is not always possible to reliably
estimate their frequency or establish a causal relationship to vaccine exposure.

Cardiac Disorders: myocarditis, pericarditis
Gastrointestinal Disorders: diarrhea, vomiting
Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions
(e.g., rash, pruritus, urticaria, angioedema)
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
Nervous System Disorders: syncope

8       REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND
        VACCINE ADMINISTRATION ERRORS 5

See Overall Safety Summary (Section 6) for additional information.

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for
MANDATORY reporting of the listed events following Pfizer-BioNTech COVID-19 Vaccine to the Vaccine
Adverse Event Reporting System (VAERS):
    • Vaccine administration errors whether or not associated with an adverse event
    • Serious adverse events* (irrespective of attribution to vaccination)
    • Cases of Multisystem Inflammatory Syndrome (MIS) in children and adults
    • Cases of COVID-19 that result in hospitalization or death




5
    Vaccination providers administering COMIRNATY (COVID-19 Vaccine, mRNA) must adhere to the same reporting requirements.

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*
Serious adverse events are defined as:
    • Death
    • A life-threatening adverse event
    • Inpatient hospitalization or prolongation of existing hospitalization
    • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life
       functions
    • A congenital anomaly/birth defect
    • An important medical event that based on appropriate medical judgement may jeopardize the individual
       and may require medical or surgical intervention to prevent 1 of the outcomes listed above

Instructions for Reporting to VAERS

The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a
VAERS form to FDA using 1 of the following methods:
    • Complete and submit the report online: https://vaers.hhs.gov/reportevent.html, or
    • If you are unable to submit this form electronically, you may fax it to VAERS at 1-877-721-0366. If
       you need additional help submitting a report you may call the VAERS toll-free information line at
       1-800-822-7967 or send an email to info@vaers.org.

IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please
complete the entire form with detailed information. It is important that the information reported to FDA
be as detailed and complete as possible. Information to include:
    • Patient demographics (e.g., patient name, date of birth)
    • Pertinent medical history
    • Pertinent details regarding admission and course of illness
    • Concomitant medications
    • Timing of adverse event(s) in relationship to administration of the Pfizer-BioNTech COVID-19
        Vaccine
    • Pertinent laboratory and virology information
    • Outcome of the event and any additional follow-up information if it is available at the time of the
        VAERS report. Subsequent reporting of follow-up information should be completed if additional
        details become available.

The following steps are highlighted to provide the necessary information for safety tracking:
   1. In Box 17, provide information on Pfizer-BioNTech COVID-19 Vaccine and any other vaccines
       administered on the same day; and in Box 22, provide information on any other vaccines received within
       1 month prior.
   2. In Box 18, description of the event:
          a. Write “Pfizer-BioNTech COVID-19 Vaccine EUA” as the first line.
          b. Provide a detailed report of vaccine administration error and/or adverse event. It is important to
              provide detailed information regarding the patient and adverse event/medication error for
              ongoing safety evaluation of this unapproved vaccine. Please see information to include listed
              above.
   3. Contact information:
          a. In Box 13, provide the name and contact information of the prescribing healthcare provider or
              institutional designee who is responsible for the report.
          b. In Box 14, provide the name and contact information of the best doctor/healthcare professional
              to contact about the adverse event.


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            c. In Box 15, provide the address of the facility where vaccine was given (NOT the healthcare
               provider’s office address).

Other Reporting Instructions

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the
contact information above.

To the extent feasible, report adverse events to Pfizer Inc. using the contact information below or by providing a
copy of the VAERS form to Pfizer Inc.

              Website                        Fax number                 Telephone number

 www.pfizersafetyreporting.com             1-866-635-8337                 1-800-438-1985

10      DRUG INTERACTIONS

There are no data to assess the concomitant administration of the Pfizer-BioNTech COVID-19 Vaccine with
other vaccines.

11      USE IN SPECIFIC POPULATIONS

11.1    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 Pfizer-BioNTech COVID-19 Vaccine administered to
pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

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 Pfizer-BioNTech COVID-19 Vaccine was administered to female rats by the
intramuscular route on 4 occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No
vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in
the study.

11.2    Lactation

Risk Summary

Data are not available to assess the effects of Pfizer-BioNTech COVID-19 Vaccine on the breastfed infant or on
milk production/excretion.




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11.3    Pediatric Use

Emergency Use Authorization of this formulation of Pfizer-BioNTech COVID-19 Vaccine, supplied in multiple
dose vials with purple caps, in adolescents 12 through 17 years of age is based on safety and effectiveness data
in this age group and in adults.

For individuals 5 through 11 years of age, a different formulation of the Pfizer-BioNTech COVID-19 Vaccine
is authorized.

Emergency Use Authorization of Pfizer-BioNTech COVID-19 Vaccine does not include use in individuals
younger than 5 years of age.

11.4    Geriatric Use

Clinical studies of Pfizer-BioNTech COVID-19 Vaccine include participants 65 years of age and older who
received the primary series and their data contributes to the overall assessment of safety and efficacy [see
Overall Safety Summary (6.1) and Clinical Trial Results and Supporting Data for EUA (18.1)]. Of the total
number of Pfizer-BioNTech COVID-19 Vaccine recipients in Study 2 (N=20,033), 21.4% (n=4,294) were
65 years of age and older and 4.3% (n=860) were 75 years of age and older.

The safety of a booster dose of Pfizer-BioNTech COVID-19 Vaccine in individuals 65 years of age and older is
based on safety data in 12 booster dose recipients 65 through 85 years of age and 306 booster dose recipients 18
through 55 years of age in Study 2. The effectiveness of a booster dose of Pfizer-BioNTech COVID-19 Vaccine
in individuals 65 years of age and older is based on effectiveness data in 306 booster dose recipients 18 through
55 years of age in Study 2.

11.5    Use in Immunocompromised

From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19
vaccine in solid-organ transplant recipients. N Engl J Med), safety and effectiveness of a third dose of the
Pfizer-BioNTech COVID-19 vaccine have been evaluated in persons that received solid organ transplants. The
administration of a third dose of vaccine appears to be only moderately effective in increasing potentially
protective antibody titers. Patients should still be counselled to maintain physical precautions to help prevent
COVID-19. In addition, close contacts of immunocompromised persons should be vaccinated as appropriate for
their health status.

13      DESCRIPTION

The Pfizer-BioNTech COVID-19 Vaccine is supplied as a frozen suspension in multiple dose vials with purple
caps; each vial must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form
the vaccine. Each 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with
purple caps contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S)
glycoprotein of SARS-CoV-2.

Each 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with purple caps
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


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diluent (sterile 0.9% Sodium Chloride Injection, USP) contributes an additional 2.16 mg sodium chloride per
dose.

The Pfizer-BioNTech COVID-19 Vaccine does not contain preservative. The vial stoppers are not made with
natural rubber latex.

14      CLINICAL PHARMACOLOGY

14.1    Mechanism of Action

The modRNA in the Pfizer-BioNTech COVID-19 Vaccine is formulated in lipid particles, which enable
delivery of the RNA 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.

18      CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

18.1    Efficacy of Primary Series 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
and older, with a minimum of 40% of participants in the ≥56-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 human immunodeficiency virus (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
Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) or placebo separated by 21 days. 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 Pfizer-BioNTech COVID-19 Vaccine 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 9 presents
the specific demographic characteristics in the studied population.

Table 9: Demographics (population for the primary efficacy endpoint)a
                                                 Pfizer-BioNTech
                                               COVID-19 Vaccine*                            Placebo
                                                    (N=18,242)                            (N=18,379)
                                                       n (%)                                 n (%)
 Sex
     Male                                           9318 (51.1)                           9225 (50.2)
     Female                                         8924 (48.9)                           9154 (49.8)




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                                                                 Pfizer-BioNTech
                                                                COVID-19 Vaccine*                             Placebo
                                                                    (N=18,242)                              (N=18,379)
                                                                       n (%)                                   n (%)
 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
    ≥12 through 15 yearsb                                               46 (0.3)                              42 (0.2)
    ≥16 through 17 years                                                66 (0.4)                              68 (0.4)
    ≥16 through 64 years                                             14,216 (77.9)                         14,299 (77.8)
    ≥65 through 74 years                                              3176 (17.4)                           3226 (17.6)
    ≥75 years                                                          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)
    Otherc                                                             534 (2.9)                             516 (2.8)
 Ethnicity
    Hispanic or Latino                                                4886 (26.8)                           4857 (26.4)
    Not Hispanic or Latino                                           13,253 (72.7)                         13,412 (73.0)
    Not reported                                                       103 (0.6)                             110 (0.6)
 Comorbiditiesd
    Yes                                                               8432 (46.2)                           8450 (46.0)
    No                                                                9810 (53.8)                           9929 (54.0)
 *  Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 a. All eligible randomized participants who receive all vaccination(s) as randomized within the predefined window, have no other
    important protocol deviations as determined by the clinician, and have no evidence of SARS-CoV-2 infection prior to 7 days
    after Dose 2.
 b. 100 participants 12 through 15 years of age with limited follow-up in the randomized population received at least 1 dose (49 in
    the vaccine group and 51 in the placebo group). Some of these participants were included in the efficacy evaluation depending
    on the population analyzed. They contributed to exposure information but with no confirmed COVID-19 cases, and did not
    affect efficacy conclusions.
 c. Includes multiracial and not reported.
 d. Number of participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease
    • Chronic lung disease (e.g., emphysema and chronic bronchitis, idiopathic pulmonary fibrosis, and cystic fibrosis) or
         moderate to severe asthma
    • Significant cardiac disease (e.g., heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and
         pulmonary hypertension)
    • Obesity (body mass index ≥30 kg/m2)
    • Diabetes (Type 1, Type 2 or gestational)
    • Liver disease
    • Human Immunodeficiency Virus (HIV) infection (not included in the efficacy evaluation)

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.

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The vaccine efficacy information is presented in Table 10.

Table 10: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Age
          Subgroup – Participants Without Evidence of Infection and Participants With or Without
          Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population
      First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior
                                          SARS-CoV-2 infection*
                              Pfizer-BioNTech
                             COVID-19 Vaccine†                 Placebo
                                 Na=18,198                   Na=18,325
                                    Cases                       Cases
                                     n1 b                        n1b               Vaccine Efficacy %
 Subgroup                  Surveillance Time (n2 ) Surveillance Timec (n2d)
                                             c   d                                      (95% CI)
                                       8                         162                       95.0
 All subjectse                  2.214 (17,411)             2.222 (17,511)              (90.3, 97.6)f
                                       7                         143                       95.1
  16 through 64 years           1.706 (13,549)             1.710 (13,618)              (89.6, 98.1)g
                                       1                          19                       94.7
  65 years and older             0.508 (3848)               0.511 (3880)               (66.7, 99.9)g
  First COVID-19 occurrence from 7 days after Dose 2 in participants with or without evidence of prior
                                          SARS-CoV-2 infection
                              Pfizer-BioNTech
                             COVID-19 Vaccine†                 Placebo
                                 Na=19,965                   Na=20,172
                                    Cases                       Cases
                                     n1 b                        n1b               Vaccine Efficacy %
 Subgroup                  Surveillance Time (n2 ) Surveillance Timec (n2d)
                                             c   d                                      (95% CI)
                                       9                         169                       94.6
 All subjectse                  2.332 (18,559)             2.345 (18,708)              (89.9, 97.3)f
                                       8                         150                       94.6
  16 through 64 years           1.802 (14,501)             1.814 (14,627)              (89.1, 97.7)g
                                       1                          19                       94.7
  65 years and older             0.530 (4044)               0.532 (4067)               (66.8, 99.9)g
 Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom
 consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
 increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
 * Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
     SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled
     visit prior to 7 days after Dose 2 were included in the analysis.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 a. N = Number of participants in the specified group.
 b. n1 = Number of participants meeting the endpoint definition.
 c. Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the
     endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
 d. n2 = Number of participants at risk for the endpoint.
 e. No confirmed cases were identified in adolescents 12 through 15 years of age.
 f. Credible interval for vaccine efficacy (VE) was calculated using a beta-binomial model with a beta (0.700102, 1) prior for θ=r(1-
     VE)/(1+r(1-VE)), where r is the ratio of surveillance time in the active vaccine group over that in the placebo group.
 g. Confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the surveillance
     time.




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18.2    Efficacy of Primary Series in Adolescents 12 Through 15 Years of Age

A descriptive efficacy analysis of Study 2 has been performed in approximately 2,200 adolescents 12 through
15 years of age evaluating confirmed COVID-19 cases accrued up to a data cutoff date of March 13, 2021.

The efficacy information in adolescents 12 through 15 years of age is presented in Table 11.

Table 11: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2: Without Evidence
           of Infection and With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Blinded
           Placebo-Controlled Follow-up Period, Adolescents 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*
                                  Pfizer-BioNTech
                                COVID-19 Vaccine†                 Placebo
                                      Na=1005                     Na=978
                                        Cases                      Cases
                                         n1b                        n1b             Vaccine Efficacy %
                               Surveillance Time (n2 ) Surveillance Time (n2 )
                                                 c    d                     c  d         (95% CIe)
 Adolescents                              0                          16                    100.0
 12 through 15 years of age          0.154 (1001)               0.147 (972)             (75.3, 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
                                  Pfizer-BioNTech                 Placebo
                                COVID-19 Vaccine    †

                                      Na=1119                    Na=1110
                                        Cases                      Cases
                                         n1b                        n1b             Vaccine Efficacy %
                               Surveillance Timec (n2d) Surveillance Timec (n2d)         (95% CIe)
 Adolescents                              0                          18                    100.0
 12 through 15 years of age          0.170 (1109)              0.163 (1094)             (78.1, 100.0)
 Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom
 consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
 increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
 * Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and
     SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled
     visit prior to 7 days after Dose 2 were included in the analysis.
 † Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 a. N = Number of participants in the specified group.
 b. n1 = Number of participants meeting the endpoint definition.
 c. Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the
     endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
 d. n2 = Number of participants at risk for the endpoint.
 e. Confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted for surveillance time.

18.3    Immunogenicity of Primary Series in Adolescents 12 Through 15 Years of Age

In Study 2, an analysis of SARS-CoV-2 50% neutralizing titers (NT50) 1 month after Dose 2 in a randomly
selected subset of participants demonstrated non-inferior immune responses (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 SARS-CoV-2 infection up to 1 month after Dose 2 (Table 12).


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                Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 49 of 54

Table 12: Summary of Geometric Mean Ratio for 50% Neutralizing Titer – Comparison 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
                                 Pfizer-BioNTech COVID-19 Vaccine*
                             12 Through 15 Years 16 Through 25 Years           12 Through 15 Years/
                                     na=190                 na=170             16 Through 25 Years
                                                                                              Met
                                                                                        Noninferiority
                    Time             GMTc                   GMTc              GMRd         Objectivee
 Assay              Point  b       (95% CI )c             (95% CI )c        (95% CI )d       (Y/N)
 SARS-CoV-2
 neutralization    1 month
 assay - NT50        after           1239.5                  705.1              1.76
 (titer)f           Dose 2      (1095.5, 1402.5)        (621.4, 800.2)     (1.47, 2.10)        Y
 Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of
 quantitation; NAAT = nucleic-acid amplification test; NT50 = 50% neutralizing titer; SARS-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-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 up to 1 month after Dose 2 were included in the analysis.
 * Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 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-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs
      (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.
 d. GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers (Group 1
      [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-sided 95% CI for the GMR is greater than 0.67.
 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 and virus neutralization is read on Vero cell monolayers.
      The sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.

18.4    Immunogenicity of a Booster Dose Following a Pfizer-BioNTech COVID-19 Vaccine Primary
        Series in Participants 18 Through 55 Years of Age

Effectiveness of a booster dose of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) was based on an
assessment of 50% neutralizing antibody titers (NT50) against SARS-CoV-2 (USA_WA1/2020). In Study 2,
analyses of NT50 1 month after the booster dose compared to 1 month after the primary series in individuals
18 through 55 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to
1 month after the booster vaccination demonstrated noninferiority for both geometric mean ratio (GMR) and
difference in seroresponse rates. Seroresponse for a participant was defined as achieving a ≥4-fold rise in NT50
from baseline (before primary series). These analyses are summarized in Table 13 and Table 14.




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Table 13: Geometric Mean 50% Neutralizing Titer (SARS-CoV-2 USA_WA1/2020) – Comparison of
           1 Month After Booster Dose to 1 Month After Primary Series – Participants 18 Through
           55 Years of Age Without Evidence of Infection up to 1 Month After Booster Dose* – Booster
           Dose Evaluable Immunogenicity Population±
                                                                       1 Month After
                                                       1 Month After Booster Dose/
                                    1 Month After          Primary     1 Month After         Met
                                     Booster Dose           Series     Primary Series Noninferiority
                                        GMTb                GMTb            GMRc         Objectived
 Assay                     n a        (95% CI )b          (95% CI )b    (97.5% CI ) c       (Y/N)
 SARS-CoV-2
 neutralization assay -                 2466.0               750.6           3.29
              e
 NT50 (titer)             212      (2202.6, 2760.8)     (656.2, 858.6)   (2.77, 3.90)         Y
 Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of
 quantitation; N-binding = SARS-CoV-2 nucleoprotein-binding; NAAT = nucleic acid amplification test; NT50 = 50% neutralizing
 titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; Y/N = yes/no.
 Note: Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 * Participants who had no serological or virological evidence (up to 1 month after receipt of a booster dose of Pfizer-BioNTech
      COVID-19 Vaccine) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative and SARS-CoV-2 not detected
      by NAAT [nasal swab]) and had a negative NAAT (nasal swab) at any unscheduled visit up to 1 month after the booster dose
      were included in the analysis.
 ± All eligible participants who had received 2 doses of Pfizer-BioNTech COVID-19 Vaccine as initially randomized, with Dose 2
      received within the predefined window (within 19 to 42 days after Dose 1), received a booster dose of Pfizer-BioNTech
      COVID-19 Vaccine, had at least 1 valid and determinate immunogenicity result after booster dose from a blood collection within
      an appropriate window (within 28 to 42 days after the booster dose), and had no other important protocol deviations as
      determined by the clinician.
 a. n = Number of participants with valid and determinate assay results at both sampling time points within specified window.
 b. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based
      on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.
 c. GMRs and 2-sided 97.5% CIs were calculated by exponentiating the mean differences in the logarithms of the assay and the
      corresponding CIs (based on the Student t distribution).
 d. Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the GMR is >0.67 and the point estimate of the GMR is
      ≥0.80.
 e. 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 and virus neutralization is read on Vero cell monolayers. The
      sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.




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                 Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 51 of 54

Table 14: Seroresponse Rate for 50% Neutralizing Titer (SARS-CoV-2 USA_WA1/2020) – Comparison
           of 1 Month After Booster Dose to 1 Month After Primary Series – Participants 18 Through
           55 Years of Age Without Evidence of Infection up to 1 Month After Booster Dose* – Booster
           Dose Evaluable Immunogenicity Population±
                                                                         Difference
                                                                      (1 Month After
                                  1 Month After      1 Month After     Booster Dose -        Met
                                   Booster Dose      Primary Series    1 Month After Noninferiority
                                         nb                 nb        Primary Series)     Objectivef
 Assay                    N a      % (95% CI ) c      % (95% CI ) c   % (97.5% CI )
                                                                         d             e    (Y/N)
 SARS-CoV-2
 neutralization assay -                 199                196
              g
 NT50 (titer)             200    99.5 (97.2, 100.0) 98.0 (95.0, 99.5)   1.5 (-0.7, 3.7)       Y
 Abbreviations: CI = confidence interval; LLOQ = lower limit of quantitation; N-binding = SARS-CoV-2 nucleoprotein-binding;
 NAAT = nucleic acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome
 coronavirus 2; Y/N = yes/no.
 Note: Seroresponse is defined as achieving a ≥4-fold rise from baseline (before Dose 1). If the baseline measurement is below the
 LLOQ, a postvaccination assay result ≥4 × LLOQ is considered a seroresponse.
 Note: Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
 * Participants who had no serological or virological evidence (up to 1 month after receipt of booster vaccination) of past
     SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative and SARS-CoV-2 not detected by NAAT [nasal swab]) and
     had a negative NAAT (nasal swab) at any unscheduled visit up to 1 month after booster vaccination were included in the
     analysis.
 ± All eligible participants who had received 2 doses of Pfizer-BioNTech COVID-19 Vaccine as initially randomized, with Dose 2
     received within the predefined window (within 19 to 42 days after Dose 1), received a booster dose of Pfizer-BioNTech
     COVID-19 Vaccine, had at least 1 valid and determinate immunogenicity result after booster dose from a blood collection
     within an appropriate window (within 28 to 42 days after the booster dose), and had no other important protocol deviations as
     determined by the clinician.
 a. N = number of participants with valid and determinate assay results for the specified assay at baseline, 1 month after Dose 2 and
     1 month after the booster dose within specified window. These values are the denominators for the percentage calculations.
 b. n = Number of participants with seroresponse for the given assay at the given dose/sampling time point.
 c. Exact 2-sided CI based on the Clopper and Pearson method.
 d. Difference in proportions, expressed as a percentage (1 month after booster dose – 1 month after Dose 2).
 e. Adjusted Wald 2-sided CI for the difference in proportions, expressed as a percentage.
 f. Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the percentage difference is > -10%.
 g. 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 and virus neutralization is read on Vero cell monolayers. The
     sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.

18.5    Immunogenicity in Solid Organ Transplant Recipients

From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19
vaccine in solid-organ transplant recipients. N Engl J Med), a single arm study has been conducted in
101 individuals who had undergone various solid organ transplant procedures (heart, kidney, liver, lung,
pancreas) 97±8 months previously. A third dose of the Pfizer-BioNTech COVID-19 vaccine was administered
to 99 of these individuals approximately 2 months after they had received a second dose. Among the 59 patients
who had been seronegative before the third dose, 26 (44%) were seropositive at 4 weeks after the third dose. All
40 patients who had been seropositive before the third dose were still seropositive 4 weeks later. The prevalence
of anti-SARS-CoV-2 antibodies was 68% (67 of 99 patients) 4 weeks after the third dose.




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18.6    Immunogenicity of a Booster Dose Following Primary Vaccination with Another Authorized
        COVID-19 Vaccine

Effectiveness of a Pfizer-BioNTech COVID-19 Vaccine booster dose (30 mcg modRNA) in individuals who
completed primary vaccination with another authorized COVID-19 Vaccine (heterologous booster dose) is
inferred from immunogenicity data supporting effectiveness of a Pfizer-BioNTech COVID-19 Vaccine booster
dose administered following completion of Pfizer-BioNTech COVID-19 Vaccine primary series and from
immunogenicity data from an independent NIH study Phase 1/2 open-label clinical trial (NCT04889209)
conducted in the United States that evaluated a heterologous booster dose of the Pfizer-BioNTech COVID-19
Vaccine. In this study, adults who had completed primary vaccination with a Moderna COVID-19 Vaccine
2-dose series (N=151), a Janssen COVID-19 Vaccine single dose (N=156), or a Pfizer-BioNTech COVID-19
Vaccine 2-dose series (N=151) at least 12 weeks prior to enrollment and who reported no history of
SARS-CoV-2 infection were randomized 1:1:1 to receive a booster dose of one of three vaccines: Moderna
COVID-19 Vaccine, Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA).
Neutralizing antibody titers, as measured by a pseudovirus neutralization assay using a lentivirus expressing the
SARS-CoV-2 Spike protein with D614G mutation, were assessed on Day 1 prior to administration of the
booster dose and on Day 15 after the booster dose. A booster response to the Pfizer-BioNTech COVID-19
Vaccine was demonstrated regardless of primary vaccination.

19      HOW SUPPLIED/STORAGE AND HANDLING

The information in this section applies to the Pfizer-BioNTech COVID-19 Vaccine that is supplied in multiple
dose vials with a purple cap. These multiple dose vials are supplied in a carton containing 25 multiple dose vials
(NDC 59267-1000-3) or 195 multiple dose vials (NDC 59267-1000-2). After dilution, 1 vial contains 6 doses of
0.3 mL. Vial labels and cartons may state that after dilution, a vial contains 5 doses of 0.3 mL. The information
in this Full EUA Prescribing Information regarding the number of doses per vial after dilution supersedes the
number of doses stated on vial labels and cartons.

During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.

Do not refreeze thawed vials.

Frozen Vials Prior to Use

Cartons of Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with purple caps 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 -90ºC to -60ºC (-130ºF to -76ºF) until the expiry
date printed on the label. This information in the package insert supersedes the storage conditions printed on the
vial cartons.

Cartons and vials of Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with purple caps with
an expiry date of July 2021 through February 2022 printed on the label may remain in use for 3 months beyond
the printed date as long as approved storage conditions between -90ºC to -60ºC (-130ºF to -76ºF) have been
maintained. Updated expiry dates are shown below.




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                Case 2:21-cv-00702-CLM Document 40-3 Filed 12/17/21 Page 53 of 54

 Printed Expiry Date             Updated Expiry Date
 July 2021                      October 2021
 August 2021                    November 2021
 September 2021                 December 2021
 October 2021                   January 2022
 November 2021                  February 2022
 December 2021                  March 2022
 January 2022                   April 2022
 February 2022                  May 2022

If not stored between -90ºC to -60ºC (-130ºF to -76ºF), 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 one 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 the Pfizer-BioNTech
COVID-19 Vaccine arrives may be used as temporary storage when consistently re-filled to the top of the
container with dry ice. Refer to the re-icing guidelines packed in the original thermal container for instructions
regarding the use of the thermal container for temporary storage. The thermal container maintains a temperature
range of -90ºC to -60ºC (-130ºF to -76ºF). Storage of the vials between -96°C to -60°C (-141°F to -76°F) is not
considered an excursion from the recommended storage condition.

Transportation of Frozen Vials

If local redistribution is needed and full cartons containing vials cannot be transported at -90°C to -60°C
(-130°F to -76°F), vials may be transported at -25°C to -15°C (-13°F to 5°F). Any hours used for transport
at -25°C to -15°C (-13°F to 5°F) count against the 2-week limit for storage at -25°C to -15°C (-13°F to 5°F).
Frozen vials transported at -25°C to -15°C (-13°F to 5°F) may be returned one 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, 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.




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Transportation of Thawed Vials

Available data support transportation of one or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to
12 hours.

Vials After Dilution

After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within 6 hours from the time of dilution.
During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Any vaccine remaining in vials must be discarded after 6 hours. Do not refreeze.

20      PATIENT COUNSELING INFORMATION

Advise the recipient or caregiver to read the Vaccine Information Fact Sheet for Recipients and Caregivers.

The vaccination provider must include vaccination information in the state/local jurisdiction’s Immunization
Information System (IIS) or other designated system. Advise recipient or caregiver that more information about
IISs can be found at: https://www.cdc.gov/vaccines/programs/iis/about.html.

21      CONTACT INFORMATION

For general questions, visit the website or call the telephone number provided below.

                       Website                                            Telephone number
                  www.cvdvaccine.com

                                                                            1-877-829-2619
                                                                          (1-877-VAX-CO19)



This Full EUA Prescribing Information may have been updated. For the most recent Full EUA Prescribing
Information, please see www.cvdvaccine.com.




Manufactured by
Pfizer Inc., New York, NY 10017


Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany

LAB-1457-15.2

Revised: 29 October 2021

Revised: 29 October 2021                                                                                      53


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