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Revised: 2 0October 2021 1FACT SHEET FOR HEA LTHCA RE PROVIDERS A DMINISTERING VA CCINE
(VACCINA TION PROVIDERS)
EMERGENCY USE AUTHORIZA TION (EUA) OF
THE PFIZER -BIONTECH COVID -19 VA CCINE TO PREVENT CORONA VIRUS
DISEA SE 2019 (COVID -19)
The U.S. Food and Drug A dministration (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 ind ividuals 12years of age and older. Pfizer -BioNTech COVID -19
Vaccine is authorized for use to provide :
a two-dose primary series toindividuals 12 y ears of age and older;
a third primary series dose toindividuals 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 w ho have completed
a primary series with P fizer-BioNTech COVID- 19 Vaccine or
COMIRNA TY:
o65 years of age and older
o18 through 64 y ears of age at high risk of severe COVID- 19
o18 through 64 y ears of age with frequent institutional or
occupational exposure to SA RS-CoV-2
a single booster dose to eligible individuals who have completed
primary vaccination with a different authorized COVID -19vaccine . 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.
COMIRNA TY (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 y ears of age and older .It is approved
for use as a 2 -dose primary series for the prevention of COVID -19 in
individuals 16 y ears of age and older . Itis also authorized for emergency use
to provide :
a two-dose primary series toindividuals 12 through 15 years;
a third primary series dose toindividuals 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
COMIRNA TY:
o65 years of age and older
o18 through 64 y ears of age at high risk of severe COVID- 19
o18 through 64 y ears of age with frequent institutional or
occupational exposure to SA RS-CoV-2
a single booster dose to eligible individuals who have completed
primary vaccination with a different authorized COVID -19vaccine . The
FDA-CBER-2021-5683-0950628
Revised: 2 0October 2021 2eligible 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 COMIRNA TY (COVID -19 Vaccine, mRNA ) and the
EUA -authorized Pfizer- BioNTech COVID -19 Vaccine have the same
formulation and can be used interchangeably to provide doses for COVID -19
primary vaccination or a booster dose .1
SUMMA RY OF INSTRUCTIONS FOR COVID -19 VA CCINA TION PROVIDERS
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 hospita lization or death following administration of
Pfizer -BioNTech COVID -19Vaccine. See “MANDATORY REQUIREMENTS FOR
PFIZER -BIONTECH COVID -19 VACCINE ADMINISTRATION UNDER
EMERGENCY USE AUTHORIZATION” for reporting requirements.
The Pfizer -BioNTech COVID -19 Vac cine is a suspension for intramuscular
injection .
Primary Series :
The Pfizer -BioNTech COVID -19 Vaccine is administered as a primary series of two
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
toindividuals:
• 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 withfrequent institutional or occupational
exposure to SARS -CoV-2
1The licensed vaccine has the same formulation as the EUA -authorized vaccine and the products
can be used interchangeably to provide doses for primary vaccination or a booster dose without
presenting any safety or effectiveness concerns. The products are legally distinct with certain
differences that do not impact safety or effectiveness.
FDA-CBER-2021-5683-0950629
Revised: 2 0October 2021 3A 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 in terval 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 activ e immunization against COVID -19, please see
www.clinicaltrials.gov .
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.
DOSA GE A ND A DMINISTRA TION
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 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 with an expiry date of
May 2021 through February 2022 printed on the label may remain in u se 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 .
FDA-CBER-2021-5683-0950630
Revised: 2 0October 2021 4Printed Expiry Date Updated Expiry Date
May 2021 August 2021
June 2021 September 2021
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 2weeks . 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
2weeks may be returned one time to the recommended storage condition of -90ºC
to -60ºC ( -130ºFto -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 temperatu re 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 return ed one time
to the recommended storage condition of -90ºC to -60ºC ( -130ºFto -76ºF).
Thawed Vials Before Dilution
Thawed Under Refrigeration
Thaw and the nstore undiluted vials in the refrigerator [ 2ºC to 8ºC (35ºF to 46ºF)]
for up to 1month . 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.
FDA-CBER-2021-5683-0950631
Revised: 2 0October 2021 5Thawed at Room Temperature
For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for
30 minutes. Thawed vials can be handled in room light conditions. Vials must reach
room temperature before dilution.
Undiluted vials may be stored at room temperature for no more than 2 hours.
Transportation of Thawed Vials
Available data support transportation of 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 two doses (0.3 mL each) 3 weeks apart to individuals 12 years of
age andolder .
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 t hat 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 withfrequent 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)
FDA-CBER-2021-5683-0950632
Revised: 2 0October 2021 6and 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
EUA-authorized Pfizer -BioNTech COVID -19 Vaccine have th e same formulation
and can be used interchangeably to provide doses for COVID -19 primary
vaccination or a booster dose .2
Dose Preparation
Prior to Dilution
The Pfizer -BioNTech COVID -19 Vaccine Multiple Dose Vial contains a
volume of 0.45 mL, supplied as a frozen suspension that does not contain
preservative .Each vial must be thawed and diluted prior to administration.
Vials may be thawed in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room
temperature [up to 25ºC (77ºF)] (see Storage and Handling) .
Refer to thawing instructions in the panels below.
Dilution
Dilute the vial contents using 1.8 mL of 0.9% Sodium Chloride Injection, USP (not
provided) to form the Pfizer -BioNTech COVID -19 Vaccine. ONLY use 0.9% Sodium
Chloride Injection, USP as the diluent. Th isdiluent 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, one 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
Fact Sheet regarding the number of doses per vial after dilution supersedes the
number of doses stated on vial labels and cartons.
Refer to dilution and dose preparation instructions in the panels below.
THAWING PRIOR TO DILUTION
Thaw vial(s) of Pfizer -BioNTech
COVID -19 Vaccine before use either
by:
oAllowing vial(s) to thaw in the
refrigerator [2ºC to 8ºC (35ºF to
46ºF)]. A carton of vials may take up
to 3hours to thaw , and thawed vials
can be stored in the refrigerator for
up to 1month .
oAllowing vial(s) to sit at room
2The licensed vaccine has the same formulation as the EUA- authorized vaccine and the products
can be used interchangeably to provide doses for primary vaccination or a booster dose without
presenting any safety or effectiveness concerns . The product s are legally distinct with certain
differences that do not impact safety or effectiveness .
FDA-CBER-2021-5683-0950633
Revised: 2 0October 2021 7temperature [up to 25ºC (77ºF)] for
30 minutes.
Using either thawing method, vials
must reach room temperature before
dilution and must be diluted within
2hours.
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.
DILUTION
Obtain sterile 0.9% Sodium Chloride
Injection, USP. Use only this as the
diluent.
Using aseptic technique, withdraw
1.8mL of diluent into a transfer syringe
(21-gauge or narrower needle).
Cleanse the vaccine vial stopper with a
single -use antiseptic swab.
Add 1.8 mL of 0.9% Sodium Chloride
Injection, USP into the vaccine vial .
Equalize v ial pressure before removing
the needle from the vial by withdrawing
1.8mL air into the empty diluent
syringe .
FDA-CBER-2021-5683-0950634
Revised: 2 0October 2021 8Gently 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.
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 dilutio n.
PREPA RATION OF INDIVIDUA L 0.3 mL DOSES OF PFIZER -BIONTECH
COVID -19 VA CCINE
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 alow 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
0.3mL, discard the vial and any
excess volume.
Administer immediately.
FDA-CBER-2021-5683-0950635
Revised: 2 0October 2021 9Administration
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 contain six doses of
0.3mLof vaccine . Low dead -volume syringes and/or needles can be used to
extract six doses from a single vial . If standard syringes andneedles are used,
there may not be sufficient volume to extract a sixth dose from a single vial.
Irrespective of the type of syringe and needle:
Each dose must contain 0.3 mL of vaccine.
If the amount of vaccine remaining in the vial cannot provide a full dose of
0.3mL, 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 FullEUA 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 yea rs 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
FDA-CBER-2021-5683-0950636
Revised: 2 0October 2021 10management. 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 ).
Syncope
Syncope (fainting) may occur in association with administration of injectable
vaccines, in particular in adolescents. Procedures s hould 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 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 , and decreased appetite (see Full EUA Prescribing
Information ).
Adverse Reactions in Post Authoriz ation 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.
FDA-CBER-2021-5683-0950637
Revised: 2 0October 2021 11INFORMA TION TO PROVIDE TO VA CCINE 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 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 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 iden tify 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 .
MANDA TORY REQUIREMENTS FOR PFIZER -BIONTECH COVID -19 VA CCINE
ADMINISTRA TION UNDER EMERGENCY USE A UTHORIZA TION3
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
12years of age and older.
3Vaccin ation providers administering COMIRNAT Y (COVID- 19 Vaccine, mRNA) must adhere to the
same reporting requirements.
FDA-CBER-2021-5683-0950638
Revised: 2 0October 2021 122.The vaccination provider must communicate to the individual rec eiving 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 m ustinclude 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 Reportin g 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 adminis tration 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 s ubstantial 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 one of the outcomes listed above.
FDA-CBER-2021-5683-0950639
Revised: 2 0October 2021 13OTHER 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
ADDITIONA L INFORMA TION
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)
AVAI LABLE A LTERNA TIVES
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 o ther COVID -19 vaccines.
FEDERA L COVID -19 VA CCINA TION PROGRA M
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
administration. However, vaccination providers may seek approp riate
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 recip ients). For information regarding provider
FDA-CBER-2021-5683-0950640
Revised: 2 0October 2021 14requirements and enrollment in the CDC COVID -19 Vaccination Program, see
https://www.cdc.gov/vaccines/covid -19/provider- enrollment.htm l.
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 ISSUA NCE 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, a lthough limited scientific information is available, based
on the totality of the scientific evidence available to date, it is reasonable to believe
thatthe Pfizer -BioNTech COVID -19 Vaccine and COMIRNATY 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 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/emergenc y-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 c ountermeasures 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 [email protected] , or call: 1 -855-266-2427.
FDA-CBER-2021-5683-0950641
Revised: 2 0October 2021 15Manufactured by
Pfizer Inc., New York, NY 10017
Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany
LAB- 1450 -15.0
Revised: 20October 2021
END SHORT VERSION FACT SHEET
Long Version (Full EUA Prescribing Information) Begins On Next Page
FDA-CBER-2021-5683-0950642
Revised: 2 0October 2021 16FULL EMERGENCY USE
AUTHORIZATION (EUA) PRESCRIBING
INFORMATION
PFIZER -BIONTECH COVID -19 VACCINE
FULL EMERGENCY USE AUTHORIZATION
PRESCRIBING INFORMATION: CONTENTS *
1AUTHORIZED USE
2DOSAGE AND ADMINISTRATION
2.1 Preparation for Administration
2.2 Administration I nformation
2.3 Vaccination Schedule
3DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS
5WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
5.2 Myocarditis and Pericarditis
5.3 Syncope
5.4 Altered Immunocompetence
5.5 Limitation of Effectiveness
6OVERALL SAFETY SUMMARY
6.1 Clinical Trials Experience
6.2 Post Authorization Experience
8REQUIREMENTS AND INSTRUCTIONS FOR REPORTING
ADVERSE EVENTS AND VACCINE ADMINISTRATION
ERRORS
10DRUG INTERACTIONS
11USE IN SPECIFIC POPULATIONS
11.1Pregnancy11.2Lactation
11.3Pediatric Use
11.4Geriatric Use
11.5 Use in Immunocompromised
13DESCRIPTION
14CLINICAL PHARMACOLOGY
14.1Mechanism of Action
18CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR
EUA
18.1Efficacy of Primary Series in Participants 16 Years of Age and
Older
18.2 Efficacy of Primary Series in Adolescents 12 Through 15Years of
Age
18.3 Immunogenicity of Primary Series in Adolescents 12 Through
15Years of Age
18.4 Immunogenicity of a Booster Dose Following aPfizer -BioNTech
COVI D-19 Vaccine Primary Series in Participants 18 Through
55Years of Age
18.5 Immunogenicity in Solid Organ Transplant Recipients
18.6 Immunogenicity of a Booster Dose Following Primary Vaccination
with Another Authorized COVI D-19 Vaccine
19HOW SUPPLIED/STORAGE AND HANDLING
20PATIENT COUNSELING INFORMATION
21CONTACT INFORMATION
* Sections or subsections omitted from the full emergency use authorization
prescri bing information are not list ed.
FDA-CBER-2021-5683-0950643
Revised: 2 0October 2021 17FULL EMERGENCY USE AUTHORIZATION (EUA) PRESCRIBING INFORMATION
1 AUTHORIZED USE
Pfizer -BioNTech COVID- 19 Vaccine is authorized for use under an Emergency Use Authorization (E UA) for
active immunization to prevent coronavirus disease 2019 (COVID -19) caused by severe acute respiratory
syndrome coronavirus 2 (SARS -CoV -2)in individuals 12years of age and older .
2 DOSAGE AND ADMINISTRATION
For intramuscular injection only .
2.1 Preparation for Admin istration
Prior to Dilution
The Pfizer -BioNTech COVID -19 Vaccine Multiple Dose Vial contains a volume of 0.45 mL, supplied
as afrozen suspension that does not contain preservative .Each vial must be thawed and diluted prior to
administration.
Vials may be thawed in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room temperature [up to 25ºC
(77ºF)] [see How S upplied /Storage and Handling (19)].
Refer to thawing instructions in the panels below.
Dilution
Dilute the vial contents using 1.8 mL of 0.9% Sodium Chloride I njection, USP (not provided) to form
the Pfizer -BioNTech COVID- 19 Vaccine. Do not addmore than 1.8 mL of diluent.
ONLY use 0.9% Sodium C hloride I njection, USP as the diluent. This diluent is not packaged with the
vaccine and must be sourced separatel y. Do not use bacteriostatic 0.9% Sodium Chloride I njection or
any other diluent .
After dilution, o ne vial contains 6doses 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.
Refer to dilution and dose preparation instructions in the panels below.
FDA-CBER-2021-5683-0950644
Revised: 2 0October 2021 18THAWING PRIOR TO DILUTION
Thaw vial(s) of Pfizer -BioNTech COVID -19
Vaccine before use either by :
oAllowing vial(s) to thaw in the refrigerator [2ºC
to 8ºC (35ºF to 46ºF)]. A carton of vials may take
up to 3 hours to thaw , and thawed vials can be
stored in the refrigerator for up to 1 month .
oAllowing vial(s) to sit at room temperature [up to
25ºC (77ºF)] for 30 minutes.
Using either thawing method, vials must reach room
temperature before dilution and must be diluted
within 2 hours.
Before dilution invert vaccine vial gentl y 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.
DILUTION
Obtain sterile 0.9% Sodium Chloride I njection,
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 0.9% Sodium Chloride I njection,
USP into the vaccine vial .
FDA-CBER-2021-5683-0950645
Revised: 2 0October 2021 19Equalize vial pressure before removing the needle
from the vial b y withdrawing 1.8 mL air into the
empty diluent s yringe.
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.
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 an y unused vaccine 6 hours after dilution.
FDA-CBER-2021-5683-0950646
Revised: 2 0October 2021 20PREPARATION OF INDIVIDUAL 0.3 mL DOSES OF PFIZER -BIONTECH COVID -19
VACCINE
Using aseptic technique, cleanse the vial stopper
with a single -use antiseptic swab, and withdraw
0.3mLof the Pfizer -BioNTech COVID -19 Vaccine
preferentiall y using low dead -volume s yringes
and/or needles.
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 an y excess volume.
Administer immediately .
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 particulat es and that no discoloration isobserved.
do not administer if vaccine is discolored or contains particulate matter.
Administer the Pfizer -BioNTech COVID -19 Vaccine intramuscularl y.
After dilution , vials of Pfizer -BioNTech COVID- 19 Vaccine contain six doses of 0.3 mLof vaccine . Low
dead -volume s yringes and/or needle s can be used to extract six doses from a single vial . If standard sy ringes
andneedles are used, there may not be sufficient volume to extract a sixth dose from a single vial. Irrespective
of the ty pe of s yringe and needle:
Each dose must contain 0.3 mLof 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 two doses
(0.3mL each) three weeks apart in individuals 12 years of age andolder .
A third primary series dose of the Pfizer -BioNTech COVID- 19 vaccine (0.3 mL) at least 28 day s 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.
FDA-CBER-2021-5683-0950647
Revised: 2 0October 2021 21Booster Dose:
A single Pfizer-BioNTech COVID -19 Vaccine booster dose (0.3 mL) may be administered intramuscularl y 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 th e vaccine used for primary vaccination.
The FDA -approved COMI RNATY (COVID -19 Vaccine, mRNA) and the EUA -authorized Pfizer -BioNTech
COVID -19 Vaccine have the same formulation and can be used interchangeabl y to provide doses for
COVID -19 primary vaccination or a booster dose .4
3 DOSAGE FORMS AND STRENGTHS
Pfizer -BioNTech COVID -19 Vaccine is a suspension for injection .After preparation, a single dose is 0.3mL
[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., anaph ylaxis) 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 anaphy lactic 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 -anaph ylaxis.html).
5.2 Myocarditis and Pericarditis
Postmarketing data demonstrate increased risks of my ocarditis and pericarditis, particularly within 7 day s
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 y et available about
4The licensed vaccine has the same formulation as the EUA -authorized vaccine and the products can be used interchangeably to
provide doses for primary vaccination or a booster dose without presenting any safety or effec tiveness concerns . The products are
legally distinct with certain differences that do not impact safety or effectiveness .
FDA-CBER-2021-5683-0950648
Revised: 2 0October 2021 22potential long -term sequelae. The CDC has published considerations related to my ocarditis and pericarditis
after vaccination, including for vaccination of individuals with a history of my ocarditis or pericarditis
(https://www.cdc.gov/vaccines/covid- 19/clinical -considerations/my ocarditis.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 therap y, ma y 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 Multi system
Inflammatory Syndrome (MIS) in adults and children , and hospitalized or fatal cases of COVID-19
following vaccination with the Pfizer -BioNTech COVID- 19 Vaccine .5To 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.
In clinical studi esof participants 16 years of age and older , 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 l ymphadenopath y (0.3%).
In a clinical study in adolescents 12 t hrough 15 years of age , 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%), joint pain (20.2%), injection site swelling (9.2%), injection site redness
(8.6%), lymphadenopathy (0.8%), and nausea (0.4%) .
In a clinical stud y of participants 18 through 55 y ears of age, the most commonly reported adverse reactions
(≥10%) 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%), and joint pain (25.3%).
Severe allergic reactions , including anaphy laxis, have been reported following administration of the
Pfizer -BioNTech COVID -19 Vaccine outside of clinical t rials.
Myocarditis and pericarditis have been reported following administration of the Pfizer -BioNTech COVID -19
Vaccine outside of clinical trials.
5Vaccin ation providers administering COMIRNATY (COVID -19 Vaccine, mRNA) must adhere to the same reporting requirements.
FDA-CBER-2021-5683-0950649
Revised: 2 0October 2021 236.1 Clinical Trials Experience
Because clinical trials are conducted under widely vary ing conditions, adverse reaction rates observed in the
clinical trials of a drug cannot be directl y compared to rates in the clinical trials of another drug and may not
reflect the rates observed in practice .
Primary Series
The safet y of the primary series Pfizer -BioNT echCOVID -19Vaccine 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. Stud y BNT162- 01 (Study 1) was a Phase 1/2, two- 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 thathasenrolled approximately 46,000 participants , 12 y ears of age or older . Of
these, approximately 43,448 participants (21,720 Pfizer -BioNTech COVID- 19 Vaccine ; 21,728 placebo) in
Phase 2/3 are 16 years of age or older (including 138 and 145 adolescents 16 and 17 y ears of age in the vaccine
and placebo groups, respectivel y)and 2 ,260 adolescents are 12 t hrough 15 years of age (1,131 and 1 ,129 in the
vaccine and placebo groups, respectivel y).
In Stud y 2, all par ticipants 12 to <16 y ears of age, and participants 16 y ears of age and older in the
reactogenicity subset, were monitored for solicited local and s ystemic reactions and use of antip yretic
medication after each vaccination in an electronic diary . Participants are being monitored for unsolicited
adverse events, including serious adverse events, throughout the stud y [from Dose 1 through 1month (all
unsolicited adverse events) or 6months (serious adverse events) after the last vaccination]. Table s 1through 6
present the frequency and severit y of solicited local and systemic reactions, respectivel y, within 7 days
following each dose of Pfizer-BioNTech COVID 19 Vaccine and placebo.
Participants 16 Years of Age and Older
At the time of the anal ysis of Study 2 for the EUA, 37,586 (18,801 Pfizer -BioNTech COVID -19Vaccine and
18,785 placebo) participants 16 y ears of age or older hadbeen followed for a median of 2 months after the
second dose of Pfizer -BioNTech COVID -19Vaccine.
The safet y evaluation in Study 2 is ongoing. The safet y population includes participants 16 years and older
enrolled b y 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 -19Vaccine and those who received placebo .
Overall, among the total participants who received either the Pfizer -BioNTech COVID -19Vaccine orplacebo ,
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 N ative.
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 day s (range 1 to 36 days), for redness 2.6 days (range 1 to 34 days), and for
swelling 2.3 day s (range 1 to 34 day s) for participants in the Pfizer -BioNTech COVID -19 Vaccine group.
Solicited r eactogenicit ydata in 16 and 17 y ear-old participants are limited .
FDA-CBER-2021-5683-0950650
Revised: 2 0October 2021 24Table 1: Study 2 – Frequency and Pe rcentages 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
COVID -19 Vaccine
Dose 1
Na=2291
nb(%)Placebo
Dose 1
Na=2298
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=2098
nb(%)Placebo
Dose 2
Na=2103
nb(%)
Rednessc
Any (>2cm) 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 (>2cm) 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)
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; M oderate: 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.
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
COVID -19 Vaccine
Dose 1
Na=2291
nb(%)Placebo
Dose 1
Na=2298
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=2098
nb(%)Placebo
Dose 2
Na=2103
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)
FDA-CBER-2021-5683-0950651
Revised: 2 0October 2021 25Pfizer -BioNTech
COVID -19 Vaccine
Dose 1
Na=2291
nb(%)Placebo
Dose 1
Na=2298
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=2098
nb(%)Placebo
Dose 2
Na=2103
nb(%)
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)
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)
Diarrheae
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)
New or worsened
muscle painc
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 antip yretic or
pain medicationf638 (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; M oderate: some interference with activity; Severe: prevents daily activity.
d.Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e.Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; S evere: 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.
FDA-CBER-2021-5683-0950652
Revised: 2 0October 2021 26Table 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
COVID -19 Vaccine
Dose 1
Na=1802
nb(%)Placebo
Dose 1
Na=1792
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=1660
nb(%)Placebo
Dose 2
Na=1646
nb(%)
Rednessc
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)
Swellingc
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)
Pain at the injection
sited
Any (>2cm) 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; M oderate: interferes with activity; Severe: prevents daily activity.
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
Table 4:Study 2 – Frequency and Percentage sof 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
COVID -19 Vaccine
Dose 1
Na=1802
nb(%)Placebo
Dose 1
Na=1792
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=1660
nb(%)Placebo
Dose 2
Na=1646
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)
Fatiguec
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)
FDA-CBER-2021-5683-0950653
Revised: 2 0October 2021 27Pfizer -BioNTech
COVID -19 Vaccine
Dose 1
Na=1802
nb(%)Placebo
Dose 1
Na=1792
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=1660
nb(%)Placebo
Dose 2
Na=1646
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)
Chillsc
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)
Vomitingd
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 antip yretic 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; M oderate: some interference with activity; Severe: prevents dai ly activity.
d.Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; S evere: requires intravenous hydration .
e.Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; S evere: 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.
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
FDA-CBER-2021-5683-0950654
Revised: 2 0October 2021 28vaccine 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 one month following post Dose 3.
Unsolic itedAdverse Events
Serious Adverse Events
In Stud y 2,among participants 16 t hrough 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 e vents from
Dose 1 through up to 30 day s 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 anal ysis,in participants 56 years
of age and older ( Pfizer -BioNTech COVID -19 Vaccine = 7,960, placebo = 7,934), serious a dverse events were
reported b y 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 orplacebo , respectivel y.In these analy ses,
91.6% of study participants had at least 30 day s of follow -up af ter Dose 2.
Appendicitis was reported as a serious adverse event for 12 participants, and numericall y higher in the vaccine
group ,8 vaccine participants and 4 placebo participants. Currently available information is insufficient to
determine a causal relationship wit hthe vaccine. There were no other notable patterns or nu merical 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
30days 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
recei ved 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 day s were reported in
23.8% of partic ipants who received Pfizer -BioNTech COVID -19 Vaccine and 11.7% of participants in the
placebo group, for participants who received at least 1dose. In these analy ses, 91.6% of study participants had
at least 30 day s of follow -up after Dose 2.
The higher frequency of reported unsolicited non-serious adverse events among P fizer-BioNTech COVID -19
Vaccine recipients compared to placebo recipients was primaril y attributed to local and systemic adverse events
reported during the first 7 day s following vaccination that are consistent with advers e reactions solicited among
participants in the reactogenicity subset and presented in Tables 3and 4.From Dose 1 through 30 day s after
Dose 2, r eports of ly mphadenopathy were imbalanced with notabl y more cases in the Pfizer -BioNTech
COVID -19 Vaccine grou p (64) vs. the placebo group (6), which is plausibly related to vaccination. Throughout
the safet y follow- up period to date, Bell’s palsy (facial paral ysis) was reported by four participants in the
Pfizer -BioNTech COVID- 19 Vaccine group. Onset of facial paraly sis was Day 37 after Dose 1 (parti cipant did
not receive Dose 2) and Day s 3, 9, and 48 after Dose 2. No cases of Bell’s palsy were reported in the placebo
group. Currentl y 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 r elationship to Pfizer -BioNTech COVID -19 Vaccine .
FDA-CBER-2021-5683-0950655
Revised: 2 0October 2021 29Adolescents 12 Through 15Years of Age
In an anal ysis of Study 2, based on data up to the cutoff date of March 13, 2021 , 2,260 adolescents
(1,131Pfizer -BioNTech COVID- 19 Vaccine; 1 ,129 placebo) were 12 t hrough 15years of age. Of these,
1,308(660 Pfizer -BioNTech COVID -19 Vaccine and 648 placebo) adolescents have been followed for at least
2months after the second dose of Pfizer -BioNTech COVID -19Vaccine. The safet y evaluation in Study 2 is
ongoing.
Dem ographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity
among adolescents who received Pfizer -BioNTech COVID -19Vaccine and those who received placebo .
Overall, among the adolescents who received the Pfizer -BioNTech COVID -19Vaccine ,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 N ative.
Solicited Local and Systemic Adverse Reactions
Themean duration of pain at the injection site after Dose 1 was 2.4days (range 1 to 10 day s), for redness
2.4days (range 1 to 16 day s), 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
COVID -19 Vaccine
Dose 1
Na=1127
nb(%)Placebo
Dose 1
Na=1127
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=1097
nb(%)Placebo
Dose 2
Na=1078
nb(%)
Rednessc
Any (>2cm) 65 (5.8) 12 (1.1) 55 (5.0) 10 (0.9)
Mild 44 (3.9) 11 (1.0) 29 (2.6) 8 (0.7)
Moderate 20 (1.8) 1 (0.1) 26 (2.4) 2 (0.2)
Severe 1 (0.1) 0(0.0) 0(0.0) 0(0.0)
Swellingc
Any (>2cm) 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; M oderate: interferes with activity; Severe: prevents daily activity.
*Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.
FDA-CBER-2021-5683-0950656
Revised: 2 0October 2021 30Table 6: Study 2 – Frequency and Percentages of Adolescents with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Adolescent s 12 T hrough 15Years of
Age –Safety Population*
Pfizer -BioNTech
COVID -19 Vaccine
Dose 1
Na=1127
nb(%)Placebo
Dose 1
Na=1127
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=1097
nb(%)Placebo
Dose 2
Na=1078
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)
Fatiguec
Any 677 (60.1) 457 (40.6) 726 (66.2) 264 (24.5)
Mild 278 (24.7) 250 (22.2) 232 (21.1) 133 (12.3)
Moderate 384 (34.1) 199 (17.7) 468 (42.7) 127 (11.8)
Severe 15 (1.3) 8 (0.7) 26 (2.4) 4 (0.4)
Headachec
Any 623 (55.3) 396 (35.1) 708 (64.5) 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)
New or worsened
muscle painc
Any 272 (24.1) 148 (13.1) 355 (32.4) 90 (8.3)
Mild 125 (11.1) 88 (7.8) 152 (13.9) 51 (4.7)
Moderate 145 (12.9) 60 (5.3) 197 (18.0) 37 (3.4)
Severe 2 (0.2) 0(0.0) 6 (0.5) 2 (0.2)
FDA-CBER-2021-5683-0950657
Revised: 2 0October 2021 31Pfizer -BioNTech
COVID -19 Vaccine
Dose 1
Na=1127
nb(%)Placebo
Dose 1
Na=1127
nb(%)Pfizer -BioNTech
COVID -19 Vaccine
Dose 2
Na=1097
nb(%)Placebo
Dose 2
Na=1078
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 antip yretic or
pain medicationf413 (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; M oderate: some interference with activity; Severe: prevents daily activity.
d.Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e. Mild: 2 to 3 loo se stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; S evere: 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.
Unsolic ited Adverse Events
Inthe following analyses ofStudy 2 inadolescents 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 stud y participants had at
least 30 days of follow -up af ter Dose 2 .
Serious Adverse Events
Serious adverse events from Dose 1 through up to 30 day s 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 Pfi zer-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 b y 5.8% of placebo recipients. From Dose 1
through 30 day s after Dose 2, reports of l ymphadenopathy 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 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 y ears of
age and 12 participants 65 through 85 years of age) received a booster dose of Pfizer -BioNTech COVID -19
FDA-CBER-2021-5683-0950658
Revised: 2 0October 2021 32Vaccine approximately 8 months (range 7.9 to 8.8 months) after completing the 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 y ears of age, the median age was 69 years (range 65 through 75 y ears 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 par ticipants 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 s ystemic reactions,
respectivel y, within 7 day s 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 2.6days (range 1 to 8days), for redness 2.2 days (range 1to 15days), and for swelling 2.2 days (range 1 to
8days).
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*
Solicited Local ReactionPfizer -BioNTech COVID -19 Vaccine
Booster Dose
Na= 289
nb(%)
Rednessc
Any (>2cm) 17(5.9)
Mild 10(3.5)
Moderate 7(2.4)
Severe 0
Swellingc
Any (>2cm) 23(8.0)
Mild 13(4.5)
Moderate 9(3.1)
Severe 1(0.3)
Pain at the injection sited
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 ofPhase 2/3 participants 18through 55 years of age who received a booster dose of COMIRNATY approximately
6months after completing the primary series .
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 react ion.
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.
FDA-CBER-2021-5683-0950659
Revised: 2 0October 2021 33Table 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*
Solicited Systemic ReactionPfizer -BioNTech COVID -19 Vaccine
Booster Dose
Na= 289
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
Fatiguec
Any 184(63.7)
Mild 68(23.5)
Moderate 103(35.6)
Severe 13(4.5)
Headachec
Any 140(48.4)
Mild 83(28.7)
Moderate 54(18.7)
Severe 3(1.0)
Chillsc
Any 84(29.1)
Mild 37(12.8)
Moderate 44(15.2)
Severe 3(1.0)
Vomitingd
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
New or worsened muscle painc
Any 113(39.1)
Mild 52(18.0)
Moderate 57(19.7)
Severe 4(1.4)
FDA-CBER-2021-5683-0950660
Revised: 2 0October 2021 34Solicited Systemic ReactionPfizer -BioNTech COVID -19 Vaccine
Booster Dose
Na= 289
nb(%)
New or worsened joint painc
Any 73(25.3)
Mild 36(12.5)
Moderate 36(12.5)
Severe 1(0.3)
Use of antip yretic or pain medicationf135(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: NoGrade 4 solicited systemic reaction swere reported .
*A subset ofPhase 2/3 participants 18through 55 years of age who received a booster dose of COMIRNATY approximately
6months after completing the primary series .
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: doesnot interfere with activity; M oderate: some interference with activity; Severe: prevents daily activity.
d.Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e.Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; S evere: 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 thebooster dose. No participant in this age group
reported a severe s ystemic 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 anal ysis of all unsolicited adverse events reported following the booster dose, through 1 month after the
booster dose, in participants 1 8 through 55 years of age (N = 306) , those assessed as adverse reactions not
alread y captured b y solicited local and s ystemic reactions were ly mphadenopathy (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 A dverse 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 day s after the booster dose that was assessed as unrelated to vaccination.
Booster Dose Following Primary Vaccination with Another Authorized COVID- 19 Vaccine
The safet y of aPfizer -BioNTech COVID -19Vaccine booster dose in individuals who completed primary
vaccination with another authorized COVID -19 Vaccine (heterologous booster dose) is inferred from the safet y
of a Pfizer -BioNTech COVID -19Vaccine booster dose administered following completion of Pfizer -BioNTech
COVID -19Vaccine primary series (ho mologous 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 -19Vaccine. In this study ,
adults who had completed primary vaccination with a Moderna COVID -19 Vaccine 2-dose series (N=151), a
FDA-CBER-2021-5683-0950661
Revised: 2 0October 2021 35Janssen COVI D-19 Vaccine single dose (N=156) , or a Pfizer -BioNTech COVID -19 Vaccine 2-dose series
(N=151) at least 12 weeks prior to enrol lment 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 . Adverse events were assesse d through 28 day s
after the booster dose. An overall review of adverse reactions reported in the study following the
Pfizer -BioNTech COVID -19Vaccine heterologous booster dose did not identify any new safet y concerns, as
compared with adverse reactions rep orted following a Pfizer -BioNTech COVID -19Vaccine 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 voluntaril y, it is not alway s possible to reliably
estimate their frequency or establish a causal relationship to vaccine exposure.
Cardiac Disorders: my ocarditis, pericarditis
Gastrointestinal Disorders: diarrhea, v omiting
Immune Sy stem Disorders: severe allergic reactions, including anaphy laxis, and other hypersensitivity reactions
(e.g., rash, pruritus, urticaria, angioedema )
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
Nervous Sy stem Disorders: sy ncope
8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND
VACCINE ADMINISTRATION ERRORS6
See Overall Safet y 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 Sy stem (VAERS) :
Vaccine administrati on errors whether or not associated with an adverse event
Serious adverse events* (irrespective of attribution to vaccination)
Cases of Multisy stem Inflammatory Syndrome (MIS) in children and adults
Cases of COVID -19 that result in hospitalization or death
*Serious adverse events are defined as:
Death
A life -threatening adverse event
Inpatient hospitalization or prolongation of existing hospitalization
A persistent or significant incapacit y or substantial disruption of the ability to conduct normal life
functions
A congenital anomal y/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 one of the outcomes listed above
6Vaccination providers administering COMIRNATY (COVID -19 Vaccine, mRNA) must adhere to the same reporting requirements.
FDA-CBER-2021-5683-0950662
Revised: 2 0October 2021 36Instructions 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 one 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 y ou may call the VAERS toll -free information lin e at
1-800-822-7967 or send an email to [email protected].
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 r eporting of follow -up information should be completed if additional
details become available.
The following steps are highlighted to provide the necessary information for safet y 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
one 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. I t is important to
provide detailed information regarding the patient and adverse event/medication error for
ongoing safet y evaluation of this unapproved vaccine. Please see information t o 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.
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.
FDA-CBER-2021-5683-0950663
Revised: 2 0October 2021 37To the extent feasible, r eport 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.pfizersafet yreporting.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 Pregnanc y
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%, respectivel y. 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 four occasions: 21 and 14 day s prior to mating, and on gestation day s 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.
11.3Pediatric Use
Emergency Use Authorization of Pfizer -BioNTech COVID-19 Vaccine in adolescents 12 through 17years of
age is based on safet y and effe ctiveness data in this age group and in adults.
Emergency Use Authorization of Pfizer -BioNTech COVID- 19 Vaccine does not include use in individuals
younger than 12 years of age.
11.4Geriatric Use
Clinical studies of Pfizer -BioNTech COVID -19 Vaccine include participants 65 y ears of age and older who
received the primary series and their data contributes to the overall assessment of safet y and efficacy [see
Overall Safety Summary (6.1) and Clinical Trial Results and Supporting Data for EUA (18.1)] .Of the total
FDA-CBER-2021-5683-0950664
Revised: 2 0October 2021 38number of Pfizer -BioNTech COVID -19 Vaccine recipients in Study 2 (N= 20,033 ), 21.4% (n= 4,294 ) were
65years of age and older and 4.3% (n= 860) were 75 y earsof age and older .
The safet y of a booster dose of Pfizer -BioNTech COVID -19 Vaccine in individuals 65 y ears of age and older is
based on safet y 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
55years 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 moderatel y effective in increasing potentially
protective antibody titers. P atients should still be counselled to maintain physical precauti ons 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; each vial
must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride I njection, USP prior to use to form the vaccine.
Each dose of the Pfizer- BioNTech COVID -19 Vaccine contains 30 mcg of a nucleoside-modified messenger
RNA (modRNA) encoding the vir al spike (S) gl ycoprotein of SARS -CoV -2.
Each dose of the Pfizer- BioNTech COVID -19 Vaccine also includes the following ingredients: lipids (0.43 mg
(4-hydroxybutyl)azanediy l)bis(hexane -6,1-diyl)bis(2 -hexyldecanoate), 0.05 mg 2[(poly ethylene gl ycol)-2000]-
N,N-ditetradecy lacetamide, 0.09 mg 1,2- distearo yl-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 dihy drate, and 6 mg sucros e. The diluent (0.9% Sodium Chloride I njection , 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 SAR S-CoV -2 S antigen . The vaccine elicit san
immune response to the S antigen , which protect sagainst 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 2is 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: 12through 15 years of age, 16 through 55years of age ,or 56 years of age
FDA-CBER-2021-5683-0950665
Revised: 2 0October 2021 39and 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 therap y 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
44,000participants 12 years of age and older were randomized equally and received 2 doses of
Pfizer -BioNTech COVID- 19 Vaccine or placebo separated b y 21 days .Particip antsare planned to be followed
for up to 24 months, for assessments of safety and efficacy against COVID -19.
The population for the analy sis of the primary efficacy endp oint included , 36,621 participants 12 years of age
and older (18,242 in the Pfizer -BioNTech COVID- 19 Vaccine group and 18,379in the placebo group ) who did
not have evidence of prior infection with SARS- CoV -2 through 7 day s after the second dose. Table 9presents
the specific demographic characteris ticsin the studied population.
Table 9: Demographics (population for the primary efficacy endpoint)a
Pfizer -BioNTech
COVID -19 Vaccine
(N=18,242)
n (%)Placebo
(N=18,379)
n (%)
Sex
Male 9318 (51.1) 9225 (50.2)
Female 8924 (48.9) 9154 (49.8)
Age (y ears)
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 yearsb46 (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 y ears 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)
Otherc534 (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)
FDA-CBER-2021-5683-0950666
Revised: 2 0October 2021 40Pfizer -BioNTech
COVID -19 Vaccine
(N=18,242)
n (%)Placebo
(N=18,379)
n (%)
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 one dose
(49in 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 e fficacy 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 anal ysis included all part icipants 12 years of age and older who had been
enrolled from July 27, 2020 ,and followed for the development of C OVID -19 through November 14, 2020.
Participants 18 through 55 years of age and 56 y ears of age and older began enrollment from July 27, 2020,
16 through 17years of age began enrollment from September 16, 2020 ,and 12 through 15 years of age began
enrollment from October 15, 2020 .
The vaccine efficacy information is presented in Table 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 *
SubgroupPfizer -BioNTech
COVID -19 Vaccine
Na=18,198
Cases
n1b
Surveillance Timec(n2d)Placebo
Na=18,325
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CI)
All subjectse8
2.214 ( 17,411)162
2.222 ( 17,511) 95.0 (90.3,97.6)f
16 through 64 years7
1.706(13,549)143
1.710 (13,618) 95.1 ( 89.6, 98.1)g
65 years and older1
0.508 (3848)19
0.511 ( 3880) 94.7 (66.7, 99.9)g
FDA-CBER-2021-5683-0950667
Revised: 2 0October 2021 41First COVID -19 occurrence from 7 days after Dose 2 in participants with or without evidence of prior
SARS -CoV -2 infection
SubgroupPfizer -BioNTech
COVID -19 Vaccine
Na=19,965
Cases
n1b
Surveillance Timec(n2d)Placebo
Na=20,172
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CI)
All subjectse9
2.332 ( 18,559)169
2.345 ( 18,708) 94.6 ( 89.9, 97.3)f
16 through 64 years8
1.802 ( 14,501)150
1.814 (14,627) 94.6 (89.1, 97.7)g
65 years and older1
0.530 (4044)19
0.532 ( 4067) 94.7 (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).
* P articipants who had no evidence of past SARS -CoV- 2 infection (i .e., N-binding antibody [serum] negative at Visit 1 and
SARS -CoV- 2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled
visit prior to 7 days after Dose 2 were included in the analysis.
a.N = Number of participants in the specified group.
b.n1 = Number of participants meeting the endpoint definition.
c.Total surveillance time in 1000 person -years for the given endpoint across all participants within each group at risk for the
endpoint. Time period for COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
d.n2 = Number of participants at risk for the endpoint.
e.No confirmed cases wereidentified 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.
18.2Efficacy of Primary Series in Adolescents 12 Through 15 Years of Age
A descriptive efficacy analy sis of Study 2 has been performed in approximately 2,200 adolescents 12 through
15years 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 ispresented 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
Na=1005
Cases
n1b
Surveillance Timec(n2d)Placebo
Na=978
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CIe)
Adolescents
12through 15years of age0
0.154 (1001 )16
0.147 (972) 100.0 (75.3, 100.0 )
FDA-CBER-2021-5683-0950668
Revised: 2 0October 2021 42First COVID -19 occurrence from 7 days after Dose 2 in adolescents 12 t hrough 15 years of age with or
without evidence of prior SARS -CoV -2 infection
Pfizer -BioNTech
COVID -19 Vaccine
Na=1119
Cases
n1b
Surveillance Timec(n2d)Placebo
Na=1110
Cases
n1b
Surveillance Timec(n2d)Vaccine Efficacy %
(95% CIe)
Adolescents
12through 15years of age0
0.170 (1109 )18
0.163 (1094 ) 100.0 (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
increa sed muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
*Participants who had no evidence of past SARS -CoV- 2 infection (i .e., N-binding antibody [serum] negative at Visit 1 and
SARS -CoV- 2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled
visit prior to 7 days after Dose 2 were included in the analysis.
a.N = Number of participants in the specified group.
b.n1 = Number of participants meeting the endpoint definition.
c.Total surveillance time in 1000 person -years for the given endpoint across all participants within each group at risk for the
endpoint. Time period for COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
d.n2 = Number of participants at risk for the endpoint.
e.Confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted forsurveillance time.
18.3 Immunogenicity of Primary Series in Adolescents 12 Through 15 Years of Age
In Study 2,an anal ysis of SARS -CoV -2 50% neutralizing titers 1 month after Dose 2 in a randoml y selected
subset of participants demonstrated non -inferior immune responses (within 1.5-fold) comparing adolescents
12 through 15years of age to participants 16 t hrough 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).
Table 12:Summary of Geometric Mean Ratio for 50% Neutralizing Titer –Comparison of Adolescents
12 Through 15 Years of Age to Participants 16 T hrough 25 Years of Age (Immunogenicity
Subset) –Participan ts Without Evidence of Infection up to 1 Month After Dose 2 –Dose 2
Evaluable Immunogenicity Population
Pfizer -BioNTech COVID -19 Vaccine
12 Through 15Years
na=19016 T hrough 25Years
na=17012 Through 15 Years/
16 T hrough 25 Years
AssayTime
PointbGMTc
(95% CIc)GMTc
(95% CIc)GMRd
(95% CId)Met
Noninferiority
Objectivee
(Y/N)
SARS -CoV -2
neutralization
assay -NT50
(titer)f1 month
after
Dose 21239.5
(1095.5, 1402.5)705.1
(621.4, 800.2)1.76
(1.47, 2.10) Y
Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = low er limit of
quantitation; NAAT = n ucleic -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 w ere included in the analysis.
a.n = Number of participants wi th valid and determinate assay results for the specified assay at the given dose/sampling time
point.
b.Protocol -specified timing for blood sample collection.
FDA-CBER-2021-5683-0950669
Revised: 2 0October 2021 43c.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
[12through 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 low er bound of the 2 -sided 95% CI for the GMR is greater than 0.67.
f.SARS -CoV- 2 50% neutralization titers (NT50) w ere 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 aPfizer -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 was based on an assessment of 50%
neutralizing antibody titers (NT50) against SARS -CoV -2 (USA _WA1/2020) . In Study 2, anal yses of NT50
1month after thebooster dose compared to 1 month after the primary series in individuals 1 8through 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 noninferiorit y for bot h 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 analy ses are summarized in Table 13 and Table 14.
Table 13:Geom etric Mean 50% Neutralizing Titer (SARS -CoV -2 USA _WA1/2020) –Comparison of
1Month After Booster Dose to 1 Month After Primary Series – Participants 18 Through
55Years of Age Without Evidence of Infection up to 1 Month After Booster Dose* –Booster
Dose Evaluable Immunogenicity Population±
Assay na1 Month After
Booster Dose
GMTb
(95% CIb)1 Month After
Primary
Series
GMTb
(95% CIb)1 Month After
Booster Dose /
1Month After
Primary Series
GMRc
(97.5%CIc)Met
Noninferiority
Objectived
(Y/N)
SARS -CoV -2
neutralization assay -
NT50 (titer)e2122466.0
(2202.6, 2760.8)750.6
(656.2, 858.6)3.29
(2.77, 3.90) Y
Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = low er 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 .
*Participants who had no serological or virological evidence (up to 1 mont h 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 u p 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 coll ection 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.
FDA-CBER-2021-5683-0950670
Revised: 2 0October 2021 44e.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.
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
55Years of Age Without Evidence of Infection up to 1 Month After Booster Dose * –Booster
Dose Evaluable Immunogenicity Population±
Assay Na1 Mo nth After
Booster Dose
nb
% (95% CIc)1 Month After
Primary Series
nb
% (95% CIc)Difference
(1 Month After
Booster Dose -
1Month After
Primary Series)
%d (97.5%CIe)Met
Noninferiority
Objectivef
(Y/N)
SARS -CoV -2
neutralization assay -
NT50 (titer)g200199
99.5 (97.2, 100.0)196
98.0 (95.0, 99.5) 1.5 (-0.7, 3.7) Y
Abbreviations: CI = confidence interval; LLOQ = low er 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.
*Participants who had no serological or virological evidence (up t o 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 boos ter 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 w ithin the predefined w indow (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 w indow (within 28 to 42 days after the booster dose), and had no other importan t 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
1month after the booster dose within specified window. These values are the denominators for the percentage calculations.
b.n = Number of participant s 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, expr essed 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 monola yers. The
sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.
18.5Immunogenicity 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 ), asingle arm study has been conducted in
101individuals 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 serone gative 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 -SAR S-CoV-2 antibodies was 68% (67 of 99 patients) 4 weeks after the third dose.
FDA-CBER-2021-5683-0950671
Revised: 2 0October 2021 4518.6 Immunogenicity of a Booster Dose Following Primary Vaccination with Another Authorized
COVID -19 Vaccine
Effectiveness of a Pfizer -BioNTech COVID -19 Vaccine booster dose in individuals who completed primary
vaccination with another authorized COVID -19 Vaccine (heterologous booster dose) is inferred from
immunogenicit y 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
immunogenicit y data from a n 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 COVI D-19 Vaccine single dose (N=156), or a Pfizer -BioNTech COVID-19
Vaccine 2-dose series (N=151) at least 12 weeks prior to enroll ment 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. Neutralizing
antibody titers, as me asured 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
Pfizer -BioNTech COVID- 19 Vaccine Suspension for Intramuscular Injection, Multiple Dose Vials aresupplied
in a carton containing 25 multiple dose vials (NDC 59267 -1000 -3) or 195 multiple dose vials
(NDC 59267 -1000 -2).After dilution, one vial contains 6doses 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 arrive in thermal containers with dry ice.
Once received, remove the vial cartons immediately from the thermal container and preferabl y 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 vi als of Pfizer -BioNTech COVID -19 Vaccine with an expiry date of May 2021 through February
2022 printed on the label may remain in use for 3 months bey ond 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 .
FDA-CBER-2021-5683-0950672
Revised: 2 0October 2021 46Printed Expiry Date Updated Expiry Date
May 2021 August 2021
June 2021 September 2021
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 ( -130ºFto -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 ( -130ºFto -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 cond ition.
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). An y 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 -9 0ºC to -60ºC ( -130ºFto -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 1month . A carton of
25 vials or 195 vials may take up to 2 or 3hours , respectivel y,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 m inutes. 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.
FDA-CBER-2021-5683-0950673
Revised: 2 0October 2021 47Transportation ofThawed 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
12hours.
Vials A fter 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 re freeze.
20 PATIENT COUNSELING INFORMATION
Advise the recipient or careg iverto read the Vaccine I nformation Fact Sheet for Recipient sand Caregivers.
The vaccination provider must include vaccination information in the state/local jurisdiction’s I mmunization
Information Sy stem (IIS) or other designated s ystem. 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 b y
Pfizer I nc., New York, NY 10017
Manufactured for
BioNTech Manufacturing GmbH
An der G oldgrube 12
55131 Mainz, German y
LAB -1457 -15.0
Revised : 20October 2021
FDA-CBER-2021-5683-0950674