Document text
Revised: 22 September 2021 1 FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE
(VACCINATION PROVIDERS)
EMERGENCY USE AUTHORIZATION (EUA) OF
THE PFIZER -BIONTECH COVID- 19 VACCINE TO PREVENT CORONAVIRUS
DISEASE 2019 (COVID -19)
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use
Authorization (EUA) to permit the emergency use of the unapproved product, Pfizer -BioNTech COVID- 19 Vaccine, for active immunization to prevent
COVID -19 in individuals 12 years of age and older .
Pfizer -BioNTech COVID- 19
Vaccine is authorized for use to provide :
• a two -dose primary series in individuals 12 years of age and older;
• a third primary series dose in individuals 12 years of age and older
who have been determined to have certain kinds of immunocompromise ; and
• a single booster dose in individuals :
o 65 years of age and older
o 18 through 64 years of age at high risk of severe COVID -19
o 18 through 64 years of age whose frequent institutional or
occupational exposure to SARS -CoV-2 puts them at high risk of
serious complications of COVID -19 including severe COVID -19
COMIRNATY (COVID- 19 Vaccine, mRNA) is an FDA -approved COVID -19
vaccine made by Pfizer for BioNTech that is indicated for active immunization
to prevent COVID -19 in individuals 16 years of age and older . It is approved
for use as a 2- dose primary series fo r the prevention of COVID -19 in
individuals 16 years of age and older . It is also authorized for emergency use
to provide :
• a two -dose primary series in individuals 12 through 15 years;
• a third primary series dose in individuals 12 years of age and older
who have been determined to have certain kinds of immunocompromise ; and
• a single booster dose in individuals :
o 65 years of age and older
o 18 through 64 years of age at high risk of severe COVID -19
o 18 through 64 years of age whose frequent institutional or
occupational exposure to SARS -CoV-2 puts them at high risk of
serious complications of COVID -19 including severe COVID -19
The FDA -approved COMIRNATY (COVID- 19 Vaccine, mRNA) and the
EUA- authorized Pfizer -BioNTech COVID- 19 Vaccine have the same
formulation and can be used interchangeably to provide the COVID -19
vaccination series.
1
1 The licensed vaccine has the same formulation as the EUA -authorized vaccine and the products
can be used interchangeably to provide the vaccination series without presenting any safety or
effectiveness concerns. The products are legally distinct with certain differences that do not impact safety or effectiveness.
FDA-CBER-2021-5683-0951745
Revised: 22 September 2021 2
SUMMARY OF INSTRUCTIONS FOR COVID- 19 VACCINATION 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 hospitalization or death following administration of
Pfizer -BioNTech COVID -19 Vaccine. See “MANDATORY REQUIREMENTS FOR
PFIZER -BIONTECH COVID- 19 VACCINE ADMINISTRATION UNDER
EMERGENCY USE AUTHORIZATION” for reporting requirements.
The Pfizer -BioNTech COVID- 19 Vaccine is a suspension for intramuscular
injection .
Primary Series :
The Pfizer -BioNTech COVID- 19 Vaccine is administered as a primary series of two
doses (0.3 mL each) 3 weeks apart in individuals 12 years of age or older .
A third dose of the Pfizer -BioNTech COVID- 19 Vaccine (0.3 mL) at least 28 days
following the second dose is authorized for administration to individuals at least 12 years of age who have undergone solid organ transplantation, or who are
diagnosed with
conditions that are considered to have an equivalent level of
immunocompromise.
Booster Dose:
A single Pfizer -BioNTech COVID -19 Vaccine booster dose (0.3 mL) may be
administered intramuscularly at least 6 months after completing the primary series
to individuals :
• 65 years of age and older
• 18 through 64 years of age at high risk of severe COVID -19
• 18 through 64 years of age whose frequent institutional or occupational exposure to SARS -CoV-2 puts them at high risk of serious complications of
COVID -19 including severe COVID -19
See this Fact Sheet for instructions for preparation and administration. This Fact
Sheet may have been updated. For the most recent Fact Sheet, please see www.cvdvaccine.com
.
For information on clinical trials that are testing the use of the Pfizer -BioNTech
COVID -19 Vaccine for active immunization against COVID -19, please see
www.clinicaltrials.gov
.
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
FDA-CBER-2021-5683-0951746
Revised: 22 September 2021 3 respiratory illness that can affect other organs. People with COVID -19 have
reported a wide range of symptoms, ranging from mild symptoms to severe illness.
Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may
include: fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhea.
DOSAGE AND ADMINISTRATION
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 use for
3 months beyond the printed date as long as approved storage conditions
between -90ºC to - 60ºC ( -130ºF to - 76ºF) have been maintained. Updated expiry
dates are shown below .
Printed Exp iry 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 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 -9 0ºC
FDA-CBER-2021-5683-0951747
Revised: 22 September 2021 4 to -60ºC ( -130ºF to -76ºF). Total cumulative time the vials are stored at - 25°C
to -15°C ( -13°F to 5°F) should be tracked and should not exceed 2 weeks.
If an ultra -low temperature freezer is not available, the thermal container in which
the Pfizer -BioNTech COVID -19 Vaccine arrives may be used as temporary storage
when consistently re- filled to the top of the container with dry ice. Refer to the
re-icing guidelines packed in the original thermal container for instructions
regarding the use of the thermal container for temporary storage. The thermal
container maintains a temperature range of - 90ºC to -60ºC ( -130ºF to -76ºF).
Storage of the vials between -96°C to -60°C ( -141°F to - 76°F) is not considered an
excursion from the recommended storage condition.
Transportation of Frozen Vials
If local redistribution is needed and full cartons containing vials cannot be transported at -90°C to - 60°C ( -130°F to -76°F), vials may be transported at -25°C
to -15°C ( -13°F to 5°F). Any hours used for transport at - 25°C to -15°C ( -13°F to
5°F) count against the 2- week limit for storage at - 25°C to - 15°C ( -13°F to 5°F).
Frozen vials transported at - 25°C to - 15°C ( -13°F to 5°F) may be returned one time
to the recommended storage condition of -9 0ºC to - 60ºC ( -130ºF to -76ºF).
Thawed Vials Before Dilution
Thawed Under Refrigeration
Thaw and then store undiluted vials in the refrigerator [ 2ºC to 8ºC (35ºF to 46ºF)]
for up to 1 month . A carton of 25 vials or 195 vials may take up to 2 or 3 hours,
respectively, to thaw in the refrigerator, whereas a fewer number of vials will thaw in less time.
Thawed at Room Temperature
For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for
30 minutes. Thawed vials can be handled in room light conditions. Vials must reach
room temperature before dilution.
Undiluted vials may be stored at room temperature for no more than 2 hours.
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.
FDA-CBER-2021-5683-0951748
Revised: 22 September 2021 5 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 and older .
A third dose of the Pfizer -BioNTech COVID- 19 vaccine (0.3 mL) at least 28 days
following the second dose is authorized for administration to individuals at least
12 years of age who have undergone solid organ transplantation, or who are
diagnosed with
conditions that are considered to have an equivalent level of
immunocompromise.
Booster Dose:
A single Pfizer -BioNTech COVID -19 Vaccine booster dose (0.3 mL) may be
administered intramuscularly at least 6 months after completing the primary series to individuals :
• 65 years of age and older
• 18 through 64 years of age at high risk of severe COVID -19
• 18 through 64 years of age whose frequent institutional or occupational exposure to SARS -CoV-2 puts them at high risk of serious complications of
COVID -19 including severe COVID -19
The FDA -approved COMIRNATY (COVID -19 Vaccine, mRNA) and the
EUA-authorized Pfizer -BioNTech COVID- 19 Vaccine have the same formulation
and can be used interchangeably to provide the COVID -19 primary vaccination
series or booster dose.
2
There are no data available on the interchangeability of the Pfizer -BioNTech
COVID -19 Vaccine or COMIRNATY (COVID- 19 Vaccine, mRNA) with other
authorized COVID -19 vaccines to complete the primary vaccination series or
booster dose.
2 The licensed vaccine has the same formulation as the EUA -authorized vaccine and the products
can be used interchangeably to provide the vaccination series without presenting any safety or
effect iveness concerns . The products are legally distinct with certain differences that do not impact
safety or effectiveness .
FDA-CBER-2021-5683-0951749
Revised: 22 September 2021 6 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. This diluent is not packaged with the vaccine
and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride
Injection or any other diluent . Do not add more than 1.8 mL of diluent.
After dilution, 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:
o Allowing 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.
o Allowing 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.
FDA-CBER-2021-5683-0951750
Revised: 22 September 2021 7 • 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 1.8
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
Injection, USP into the vaccine vial .
• Equalize vial pressure before removing
the needle from the vial by withdrawing
1.8 mL air into the empty diluent
syringe .
FDA-CBER-2021-5683-0951751
Revised: 22 September 2021 8 • 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 any unused vaccine 6 hours
after dilutio n.
PREPARATION 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 0.3 mL of the
Pfizer -BioNTech COVID- 19 Vaccine
preferentially using a low dead- volume
syringe and/or needle.
• Each dose must contain 0.3 mL of
vaccine.
• If the amount of vaccine remaining in
the vial cannot provide a full dose of 0.3 mL, discard the vial and any
excess volume.
• Administer immediately.
FDA-CBER-2021-5683-0951752
Revised: 22 September 2021 9 Administration
Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off -white suspension. During the visual inspection,
• verify the final dosing volume of 0.3 mL.
• confirm there are no particulates and that no discoloration is observed.
• do not administer if vaccine is discolored or contains particulate matter.
Administ er the Pfizer -BioNTech COVID -19 Vaccine intramuscularly .
After dilution , vials of Pfizer -BioNTech COVID -19 Vaccine contain six doses of
0.3 mL of vaccine. Low dead- volume syringes and/or needles can be used to
extract six doses from a single vial. If standard syringes and needles are used,
there may not be sufficient volume to extract a sixth dose from a single vial.
Irrespective of the type of syringe and needle:
• Each dose must contain 0.3 mL of vaccine.
• If the amount of vaccine remaining in the vial cannot provide a full dose of
0.3 mL, discard the vial and content .
• Do not pool excess vaccine from multiple vials .
Contraindications
Do not administer Pfizer -BioNTech COVID- 19 Vaccine to individuals with known
history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer -BioNTech COVID- 19 Vaccine (see Full EUA Prescribing Information) .
Warnings
Management of Acute Allergic Reactions
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of Pfizer -BioNTech COVID- 19 Vaccine.
Monitor Pfizer -BioNTech COVID- 19 Vaccine recipients for the occurrence of
immediate adverse reactions according to the Centers for Disease Control and Prevention (CDC) guidelines (
https://www.cdc.gov/vaccines/covid- 19/clinical-
considerations/managing- anaphylaxis.html ).
Myocarditis and Pericarditis
Postmarketing data demonstrate increased risks of myocarditis and pericarditis,
particularly within 7 days following the second dose. The observed risk is higher
among males under 40 years of age than among females and older males. The observed risk is highest in males 12 through 17 years of age. Although some
cases required intensive care support, available data from short -term follow -up
suggest that most individuals have had resolution of symptoms with conservative
FDA-CBER-2021-5683-0951753
Revised: 22 September 2021 10 management. Information is not yet available about potential long- term sequelae.
The CDC has published considerations related to myocarditis and pericarditis
after vaccination, including for vaccination of individuals with a history of
myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid- 19/clinical-
considerations/myocarditis.html ).
Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines, in particular in adolescents. Procedures should be in place to avoid injury from fainting.
Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer -BioNTech
COVID -19 Vaccine.
Limitation of Effectiveness
Pfizer
-BioNTech COVID -19 Vaccine may not protect all vaccine recipients.
Adverse Reactions
Adverse Reactions in Clinical Trials
Adverse reactions following 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 Authorization Experience
Severe allergic reactions, including anaphylaxis, and other hypersensitivity
reactions (e.g. , rash, pruritus, urticaria, angioedema ), diarrhea, vomiting, pain in
extremity (arm ), and syncope have been reported following administration of the
Pfizer -BioNTech COVID- 19 Vaccine outside of clinical trials .
Myocarditis and pericarditis have been reported following administration of the Pfizer -BioNTech COVID- 19 Vaccine outside of clinical trials.
Additional adverse reactions, some of which may be serious, may become
apparent with more widespread use of the Pf izer-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-2021-5683-0951754
Revised: 22 September 2021 11 INFORMATION TO PROVIDE TO VACCINE RECIPIENTS/ CAREGIVERS
As the vaccination provider, you must communicate to the recipient or their caregiver, information consistent with the “Vaccine Information Fact Sheet for
Recipients and Caregivers” (and provide a copy or direct the individual to the website www.cvdvaccine.com
to obtain the Vaccine Information Fact Sheet) prior to
the individual receiving each dose of 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 identify potential side effects after COVID -19
vaccination. V-safe asks questions that help CDC monitor the safety of COVID -19
vaccines. V-safe also provides second- dose reminders if needed and live
telephone follow -up by CDC if participants report a significant health impact
following COVID- 19 vaccination. For more information, visit: www.cdc.gov/vsafe
.
MANDATORY REQUIREMENTS FOR PFIZER- BIONTECH COVID- 19 VACCINE
ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION
3
In order to mitigate the risks of using this unapproved product under EUA and to
optimize the potential benefit of Pfizer -BioNTech COVID- 19 Vaccine, the following
items are required. Use of unapproved Pfizer -BioNTech COVID- 19 Vaccine for
active immunization to prevent COVID -19 under this EUA is limited to the following
(all requirements must be met):
1. Pfizer -BioNTech COVID -19 Vaccine is authorized for use in individuals
12 years of age and older.
3 Vaccin ation providers administering COMIRNATY (COVID -19 Vaccine, mRNA) must adhere to the
same reporting requirements.
FDA-CBER-2021-5683-0951755
Revised: 22 September 2021 12 2. The vaccination provider must communicate to the individual receiving the
Pfizer -BioNTech COVID -19 Vaccine or their caregiver, information
consistent with the “Vaccine Information Fact Sheet for Recipients and
Caregivers” prior to the individual receiving Pfizer -BioNTech COVID- 19
Vaccine .
3. The vaccination provider m ust include vaccination information in the
state/local jurisdiction’s Immunization Information System (IIS) or other designated system.
4. The vaccination provider is responsible for mandatory reporting of the following to the Vaccine Adverse Event Reporting System (VAERS):
• vaccine administration er rors whether or not associated with an
adverse event,
• serious adverse events* (irrespective of attribution to vaccination),
• cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and
• cases of COVID -19 that result in hospitalization or death.
Complete and submit reports to VAERS online at
https://vaers.hhs.gov/reportevent.html
. For further assistance with reporting
to VAERS call 1-800-822-7967. The reports should include the words
“Pfizer -BioNTech COVID- 19 Vaccine EUA” in the description section of the
report.
5. The vaccination provider is responsible for responding to FDA requests for information about vaccine administration errors, adverse events, cases of MIS in adults and children, and cases of COVID -19 that result in
hospitalization or death following administration of Pfizer -BioNTech
COVID -19 Vaccine to recipients.
* Serious adverse events are defined as:
• Death;
• A life -threatening adverse event;
• Inpatient hospitalization or prolongation of existing hospitalization;
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
• A congenital anomaly/birth defect;
• An important medical event that based on appropriate medical judgement
may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above.
FDA-CBER-2021-5683-0951756
Revised: 22 September 2021 13 OTHER ADVERSE EVENT REPORTING TO VAERS AND PFIZER INC.
Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.
To the extent feasible, report adverse events to Pfizer Inc. using the contact information below or by providing a co py of the VAERS form to Pfizer Inc.
Website Fax number Telephone number
www.pfizersafetyreporting.com 1-866-635-8337 1-800-438-1985
ADDITIONAL INFORMATION
For general questions, visit the website or call the telephone number provided below.
To access the most recent Pfizer -BioNTech COVID- 19 Vaccine Fact Sheets,
please scan the QR code provided below.
Global website Telephone number
www.cvdvaccine.com
1-877-829-2619
(1-877-VAX-CO19)
AVAILABLE ALTERNATIVES
COMIRNATY (COVID- 19 Vaccine, mRNA) is an FDA -approved COVID -19 vaccine
made by Pfizer for BioNTech. It is approved as a 2- dose primary series for use in
individuals 16 years of age and older. COMIRNATY (COVID -19 Vaccine, mRNA) is
also authorized for emergency use to provide:
• a two-dose primary series in individuals 12 through 15 years ;
• a third primary series dose in individuals 12 years of age and older who
have been determined to have certain kinds of immunocompromise; and
• a single booster dose in individuals :
o 65 years of age and older
o 18 through 64 years of age at high risk of severe COVID -19
o 18 through 64 years of age whose frequent institutional or occupational exposure to SARS -CoV-2 puts them at high risk of
serious complications of COVID -19 including severe COVID -19
FDA-CBER-2021-5683-0951757
Revised: 22 September 2021 14 COMIRNATY (COVID- 19 Vaccine, mRNA) has the same formulation as the
Pfizer -BioNTech COVID- 19 Vaccine. These vaccines can be used interchangeably
to provide the COVID -19 vaccination series.4
There may be clinical trials or availability under EUA of other COVID -19 vaccines.
FEDERAL COVID- 19 VACCINATION PROGRAM
This vaccine is being made available for emergency use exclusively through the CDC COVID- 19 Vaccination Program (the Vaccination Program). Healthcare
providers must enroll as providers in the Vaccination Program and comply with the provider requirements. Vaccination providers may not charge any fee for the
vaccine and may not charge the vaccine recipient any out -of-pocket charge for
administration. However, vaccination providers may seek appropriate reimbursement from a program or plan that covers COVID -19 vaccine
administration fees for the vaccine recipient (private insurance, Medicare, Medicaid, Health Resources & Services Administration [HRSA ] COVID -19
Uninsured Program for non- insured recipients). For information regarding provider
requirements and enrollment in the CDC COVID -19 Vaccination Program, see
https://www.cdc.gov/vaccines/covid- 19/provider -enrollment.html
.
Individuals becoming aware of any potential violations of the CDC COVID- 19
Vaccination Program requirements are encouraged to report them to the Office of the Inspector General, U.S. Department of Health and Human Services, at 1-800-HHS -TIPS or https://TIPS.HHS.GOV
.
AUTHORITY FOR ISSUANCE OF THE EUA
The Secretary of Health and Human Services (HHS) has declared a public health emergency that justifies the emergency use of drugs and biological products during the COVID -19 pandemic. In response, FDA has issued an EUA for the unapproved
product, Pfizer -BioNTech COVID -19 Vaccine , for active immunization against
COVID -19. Pfizer -BioNTech COVID- 19 Vaccine is authorized for use to provide:
• a two -dose primary series in individuals 12 years of age and older;
• a third primary series dose in individuals 12 years of age and older who
have been determined to have certain kinds of immunocompromise; and
• a single booster dose in individuals :
o 65 years of age and older
o 18 through 64 years of age at high risk of severe COVID -19
o 18 through 64 years of age whose frequent institutional or occupational exposure to SARS -CoV-2 puts them at high risk of
serious complications of COVID -19 including severe COVID -19
4 The licensed vaccine has the same formulation as the EUA -authorized vaccine and the products
can be used interchangeably to provide the vaccination series without presenting any safety or
effectiveness concerns . The products are legally distinct with certain differences that do not impact
safety or effectiveness .
FDA-CBER-2021-5683-0951758
Revised: 22 September 2021 15
FDA-approved COMIRNATY is also authorized for use to provide:
• a two -dose primary series in individuals 12 through 15 years;
• a third primary series dose in individuals 12 years of age and older who have been determined to have certain kinds of immunocompromise; and
• a single booster dose in individuals :
o 65 years of age and older
o 18 through 64 years of age at high risk of severe COVID -19
o 18 through 64 years of age whose frequent institutional or occupational exposure to SARS -CoV-2 puts them at high risk of
serious complications of COVID -19 including severe COVID -19
FDA issued this EUA, based on Pfizer -BioNTech’s request and submitted data.
For the authorized uses, although limited scientific information is available, based
on the totality of the scientific evidence available to date, it is reasonable to believe that the Pfizer -BioNTech COVID -19 Vaccine and COMIRNATY 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-2021-5683-0951759
Revised: 22 September 2021 16
Manufactured by
Pfizer Inc., New York, NY 10017
Manufactured for
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany
LAB- 1450- 14.0
Revised: 22 September 2021
END SHORT VERSION FACT SHEET
Long Version (Full EUA Prescribing Information) Begins On Next Page
FDA-CBER-2021-5683-0951760
Revised: 22 September 2021 17
FULL EMERGENCY USE
AUTHORIZATION (EUA) PRESCRIBING INFORMATION PFIZER -BIONTECH COVID- 19 VACCINE
FULL EMERGENCY USE AUTHORIZATION
PRESCRIBING INFORMATION: CONTENTS *
1 AUTHORIZED USE
2 DOSAGE AND ADMINISTRATION
2.1 Preparation for Administration
2.2 Administration Information
2.3 Vaccination Schedule
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
5.2 Myocarditis and Pericarditis
5.3 Syncope
5.4 Altered Immunocompetence
5.5 Limitation of Effectiveness
6 OVERALL SAFETY SUMMARY
6.1 Clinical Trials Experience
6.2 Post Authorization Experience
8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING
ADVERSE EVENTS AND VACCINE ADMINISTRATION
ERRORS
10 DRUG INTERACTIONS 11 USE IN SPECIFIC POPULATIONS
11.1 Pregnancy
11.2 Lactation
11.3 Pediatric Use
11.4 Geriatric Use
11.5 Use in Immunocompromised
13 DESCRIPTION
14 CLINICAL PHARMACOLOGY
14.1 Mechanism of Action
18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR
EUA
18.1 Efficacy of Primary Series in Participants 16 Years of Age and
Older
18.2 Efficacy of Primary Series in Adolescents 12 Through 15 Years of
Age
18.3 Immunogenicity of Primary Series in Adolescents 12 Through
15 Years of Age
18.4 Immunogenicity of Booster Dose in Participants 18 Through
55 Years of Age
18.5 Immunogenicity in Solid Organ Transplant Recipients
19 HOW SUPPLIED/STORAGE AND HANDLING
20 PATIENT COUNSELING INFORMATION
21 CONTACT INFORMATION
* Sections or subsections omitted from the full emergency use authorization
prescri bing information are not listed .
FDA-CBER-2021-5683-0951761
Revised: 22 September 2021 18
FULL 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 12 years 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 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 How Supplied/S torage 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 Injection, USP (not provided) to form the Pfizer -BioNTech COVID- 19 Vaccine. Do not add more than 1.8 mL of diluent.
• ONLY use 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is n ot packaged with the
vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or
any other 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 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-2021-5683-0951762
Revised: 22 September 2021 19 THAWING PRIOR TO DILUTION
• Thaw vial(s) of Pfizer -BioNTech COVID -19
Vaccine before use either by:
o Allowing 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.
o Allowing 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 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 1.8 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 Injection, USP into the vaccine vial .
FDA-CBER-2021-5683-0951763
Revised: 22 September 2021 20 • Equalize vial pressure before removing the needle
from the vial by withdrawing 1.8 mL air into the empty diluent syringe.
• 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 any unused vaccine 6 hours after dilution.
FDA-CBER-2021-5683-0951764
Revised: 22 September 2021 21 PREPARATION 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
0.3 mL of the Pfizer -BioNTech COVID -19 Vaccine
preferentially using low dead-volume syringes 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 any 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 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 0.3 mL of vaccine. Low
dead -volume syringes and/or needles can be used to extract six doses from a single vial . If standard syringes
and needles are used, there may not be sufficient volume to extract a sixth dose from a single vial. Irrespective
of the type of syringe and needle:
• Each dose must contain 0.3 mL of vaccine.
• If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
• Do not pool excess vaccine from multiple vials.
2.3 Vaccination Schedule
Primary Series :
The Pfizer -BioNTech COVID -19 Vaccine is administered intramuscularly as a primary series of two doses
(0.3 mL each) three weeks apart in individuals 12 years of age and older.
A third dose of the Pfizer- BioNTech COVID -19 v accine (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.
FDA-CBER-2021-5683-0951765
Revised: 22 September 2021 22 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 whose frequent institutional or occupational exposure to SARS-CoV-2 puts
them at high risk of serious complications of COVID-19 including severe COVID-19
The FDA -approved COMIRNATY (COVID-19 Vaccine, mRNA) and the EUA-authorized Pfizer- BioNTech
COVID-19 Vaccine have the same formulation and can be used interchangeably to provide the COVID-19 vaccination series.
5 There are no data available on the interchangeability of the Pfizer -BioNTech COVID -19
Vaccine or COMIRNATY (COVID -19 Vaccine, mRNA) with other authorized COVID -19 vaccines .
3 DOSAGE FORMS AND STRENGTHS
Pfizer -BioNTech COVID -19 Vaccine is a suspension for injection. After preparation, a single dose is 0.3 mL
[see Dosage and Administration (2.1)] .
4 CONTRAINDICATIONS
Do not administer Pfizer -BioNTech COVID -19 Vaccine to individuals with known history of a severe allergic
reaction (e.g., anaphylaxis) to any component of the Pfizer- BioNTech COVID -19 Vaccine [s ee Description
(13)] .
5 WARNINGS AND PRECAUTIONS
5.1 Management of Acute Allergic Reactions
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of Pfizer -BioNTech COVID-19
Vaccine.
Monitor Pfizer- BioNTech COVID- 19 Vaccine recipients for the occurrence of immediate adverse reactions
according to the Centers for Disease Control and Prevention (CDC) guidelines
(https://www.cdc.gov/vaccines/covid- 19/clinical -considerations/managing-anaphylaxis.html ).
5.2 Myocarditis and Pericarditis
Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 12 through 17 years of age. Although some cases required intensive care support, available data from short -term follow -up suggest that most individuals
have had resolution of symptoms with conservative man agement. Information is not yet available about
potential long- term sequelae. The CDC has published considerations related to myocarditis and pericarditis
after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis
(https://www.cdc.gov/vaccines/covid- 19/clinical -considerations/myocarditis.html
).
5 The licensed vaccine has the same formulation as the EUA -authorized vaccine and the products can be used interchangeably to
provide the vaccination series without presenting any safety or effectiveness concerns . The products are legally distinct with certain
differences that do not impact safety or effectiveness .
FDA-CBER-2021-5683-0951766
Revised: 22 September 2021 23
5.3 Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines, in particular in adolescents. Procedures should be in place to avoid injury from fainting. 5.4 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer -BioNTech COVID -19 Vaccine.
5.5 Limitation of Effectiveness
The Pfizer -BioNTech COVID -19 Vaccine may not protect all vaccine recipients.
6 OVERALL SAFETY SUMMARY
It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of 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.
6 To the extent feasible, provide a
copy of the VAERS form to Pfizer Inc. Please see the REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS section for details
on reporting to VAERS and Pfizer Inc. In clinical studies of 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 lymphadenopathy (0.3%). In a clinical study in adolescents 12 through 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 study of participants 18 through 55 years 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 anaphylaxis, have been reported following administration of the
Pfizer -BioNTech COVID- 19 Vaccine outside of clinical trials.
Myocarditis and pericarditis have been reported following administration of the Pfizer -BioNTech COVID -19
Vaccine outside of clinical trials.
6 Vaccin ation providers administering COMIRNATY (COVID -19 Vaccine, mRNA) must adhere to the s ame reporting requirements.
FDA-CBER-2021-5683-0951767
Revised: 22 September 2021 24 6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not
reflect the rates observed in practice.
Primary Series
The safety of the primary series Pfizer -BioNTech COVID-19 Vaccine was evaluated in participants 12 years of
age and older in two clinical studies conducted in the United States, Europe, Turkey, South Africa, and South
America. Study BNT162-01 (Study 1) was a Phase 1/2, 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 that has enrolled approximately 46,000 participants, 12 years of age or older. Of
these, approximately 43,448 participants (21,720 Pfizer- BioNTech COVID-19 Vaccine; 21,728 placebo) in
Phase 2/3 are 16 years of age or older (including 138 and 145 adolescents 16 and 17 years of age in the vaccine
and placebo groups, respectively) and 2,260 adolescents are 12 through 15 years of age (1,131 and 1,129 in the
vaccine and placebo groups, respectively).
In Study 2, all participants 12 to <16 years of age, and participants 16 years of age and older in the reactogenicity subset, were monitored for solicited local and systemic reactions and use of antipyretic
medication after each vaccination in an electronic diary . Participants are being monitored for unsolicited
adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month (all
unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination ]. Tables 1 through 6
present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of Pfizer- BioNTech COVID 19 Vaccine and placebo .
Participants 16 Years of Age and Older
At the time of the analysis of Study 2 for the EUA, 37,586 (18,801 Pfizer -BioNTech COVID -19 Vaccine and
18,785 placebo) participants 16 years of age or older had been followed for a median of 2 months after the
second dose of Pfizer -BioNTech COVID -19 Vaccine.
The safety evaluation in Study 2 is ongoing. The safety population includes participants 16 years and older enrolled by October 9, 2020, and includes safety data accrued through November 14, 2020. Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received Pfizer -BioNTech COVID-19 Vaccine and those who received placebo.
Overall, among the total participants who received either the Pfizer -BioNTech COVID -19 Vaccine or placebo ,
50.6% were male and 49.4% were female, 83.1% were White , 9.1% were Black or African American, 28.0%
were Hispanic/Latino , 4.3% were Asian , and 0.5 % were American Indian /Alaska 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 days (range 1 to 36 days), for redness 2.6 days (range 1 to 34 days), and for
swelling 2.3 days (range 1 to 34 days) for participants in the Pfizer- BioNTech COVID -19 Vaccine group.
Solicited r eactogenicity data in 16 and 17 year-old participants are limited .
FDA-CBER-2021-5683-0951768
Revised: 22 September 2021 25 Table 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 Pop ulation*
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 (>2 cm) 104 (4.5) 26 (1.1) 123 (5.9) 14 (0.7)
Mild 70 (3.1) 16 (0.7) 73 (3.5) 8 (0.4)
Moderate 28 (1.2) 6 (0.3) 40 (1.9) 6 (0.3)
Severe 6 (0.3) 4 (0.2) 10 (0.5) 0 (0.0)
Swellingc
Any (>2 cm) 132 (5.8) 11 (0.5) 132 (6.3) 5 (0.2)
Mild 88 (3.8) 3 (0.1) 80 (3.8) 3 (0.1)
Moderate 39 (1.7) 5 (0.2) 45 (2.1) 2 (0.1)
Severe 5 (0.2) 3 (0.1) 7 (0.3) 0 (0.0)
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 = N umber of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.
b. n = N umber of participants with the specified reaction.
c. Mild: >2.0 to ≤5.0 cm; M oderate: >5.0 to ≤ 10.0 cm; S evere: >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-2021-5683-0951769
Revised: 22 September 2021 26 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 (%)
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 antipyretic or
pain medicationf 638 (27.8) 332 (14.4) 945 (45.0) 266 (12.6)
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose.
a. N = N umber 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; S evere: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; M oderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e. Mild: 2 to 3 loo se stools in 24 hours; M oderate: 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-2021-5683-0951770
Revised: 22 September 2021 27 Table 3: Study 2 – Frequency and Percentages of Participants with Solicited Local Rea ctions, 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 (>2 cm) 1282 (71.1) 166 (9.3) 1098 (66.1) 127 (7.7)
Mild 1008 (55.9) 160 (8.9) 792 (47.7) 125 (7.6)
Moderate 270 (15.0) 6 (0.3) 298 (18.0) 2 (0.1)
Severe 4 (0.2) 0 (0.0) 8 (0.5) 0 (0.0)
Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination.
a. N = N umber 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 c m; Moderate: >5.0 to ≤ 10.0 cm; S evere: >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 Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety Popu lation*
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-2021-5683-0951771
Revised: 22 September 2021 28 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 (%)
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 antipyretic or
pain medication 358 (19.9) 213 (11.9) 625 (37.7) 161 (9.8)
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose.
a. N = N umber 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; S evere: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; M oderate: >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-2021-5683-0951772
Revised: 22 September 2021 29 vaccine dose, the adverse event profile was similar to that after the second dose and no grade 3 or grade 4
events were reported in recipients who were followed for one month following post Dose 3.
Unsolicit ed Adverse Events
Serious Adverse Events
In Study 2, among participants 16 through 55 years of age who had received at least 1 dose of vaccine or
placebo ( Pfizer -BioNTech COVID- 19 Vaccine = 10,841; placebo = 10,851 ), serious adverse e vents from
Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer -BioNTech
COVID- 19 Vaccine recipients and by 0.3% of placebo recipients . In a similar analysis , in participants 56 years
of age and older (Pfizer -BioNTech COVID -19 Vaccine = 7,960, placebo = 7,934), serious a dverse e vents were
reported by 0.8% of Pfizer -BioNTech COVID -19 V accine recipients and by 0.6% of placebo recipients who
received at least 1 dose of Pfizer -BioNTech COVID -19 Vaccine or placebo , respectively. In these analyses,
91.6% of study participants had at least 30 days of follow-up after Dose 2.
Appendicitis was reported as a serious adverse event for 12 participants, and numerically higher in the vaccine
group, 8 vaccine participants and 4 placebo participants. Currently available information is insufficient to
determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances
between treatment groups for specific categories of serious adverse events (including neurologic,
neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Pfizer- BioNTech
COVID- 19 Vaccine.
Non-Serious Adverse Events
In Study 2 in which 10,841 participants 16 through 55 years of age received Pfizer -BioNTech COVID -19
Vaccine and 10,851 participants received placebo, non-serious adverse events from Dose 1 through up to
30 days after Dose 2 in ongoing follow-up were reported in 29.3% of participants who received
Pfizer -BioNTech COVID -19 Vaccine and 13.2% of participants in the placebo group, for participants who
received at least 1 dose. Overall in a similar analysis in which 7960 participants 56 years of age and older
received Pfizer -BioNTech COVID- 19 Vaccine, non-serious adverse events within 30 days were reported in
23.8% of partic ipants who received Pfizer -BioNTech COVID -19 Vaccine and 11.7% of participants in the
placebo group, for participants who received at least 1 dose. In these analyses, 91.6% of study participants had
at least 30 days of follow-up after Dose 2.
The higher frequency of reported unsolicited non-serious adverse events among P fizer-BioNTech COVID-19
Vaccine recipients compared to placebo recipients was primarily attributed to local and systemic adverse events
reported during the first 7 days following vaccination that are consistent with adverse reactions solicited among
participants in the reactog enicity subset and presented in Tables 3 and 4. From Dose 1 through 30 days after
Dose 2, reports of lymphadenopathy were imbalanced with notably more cases in the Pfizer -BioNTech
COVID-19 Vaccine group (64) vs. the placebo group (6), which is plausibly related to vaccination. Throughout
the safety follow-up period to date, Bell’s palsy (facial paralysis) was reported by four participants in the
Pfizer -BioNTech COVID-19 Vaccine group. Onset of facial paralysis was Day 37 after Dose 1 (participant did
not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of Bell’s palsy were reported in the placebo
group. Currently available information is insufficient to determine a causal relationship with the vaccine. There
were no other notable patterns or numerical imbalances between treatment groups for specific categories of
non-serious adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that
would suggest a causal relationship to Pfizer- BioNTech COVID -19 Vaccine.
FDA-CBER-2021-5683-0951773
Revised: 22 September 2021 30 Adolescents 12 Through 15 Years of Age
In an analysis of Study 2, based on data up to the cutoff date of March 13, 2021, 2,260 adolescents
(1,131 Pfizer -BioNTech COVID- 19 Vaccine; 1 ,129 placebo) were 12 through 15 years of age. Of these,
1,308 (660 Pfizer -BioNTech COVID -19 Vaccine and 648 placebo) adolescents have been followed for at least
2 months after the second dose of Pfizer- BioNTech COVID -19 Vaccine. The safety evaluation in Study 2 is
ongoing.
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among adolescents who received Pfizer -BioNTech COVID-19 Vaccine and those who received placebo.
Overall, among the adolescents who received the Pfizer -BioNTech COVID -19 Vaccine, 50.1% were male and
49.9% were female, 85.9 % were White , 4.6% were Black or African American, 11.7% were Hispanic/Latino ,
6.4% were Asian , and 0.4% were American Indian/Alaska N ative.
Solicited Local and Systemic Adverse Reactions
The mean duration of pain at the injection site after Dose 1 was 2.4 days (range 1 to 10 days), for redness
2.4 days (range 1 to 16 days), and for swelling 1.9 days (range 1 to 5 days) for adolescents in the
Pfizer -BioNTech COVID-19 Vaccine group.
Table 5: Study 2 – Frequency and Percentages of Adolescents With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Adolescents 12 Through 15 Years of
Age – Safety Population*
Pfizer -BioNTech
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 (>2 cm) 65 (5.8) 12 (1.1) 55 (5.0) 10 (0.9)
Mild 44 (3.9) 11 (1.0) 29 (2.6) 8 (0.7)
Moderate 20 (1.8) 1 (0.1) 26 (2.4) 2 (0.2)
Severe 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Swellingc
Any (>2 cm) 78 (6.9) 11 (1.0) 54 (4.9) 6 (0.6)
Mild 55 (4.9) 9 (0.8) 36 (3.3) 4 (0.4)
Moderate 23 (2.0) 2 (0.2) 18 (1.6) 2 (0.2)
Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
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 = N umber of participants reporting at least 1 yes or no response for the specified reaction after the specified dose.
b. n = N umber of participants with the specified reaction.
c. Mild: >2.0 to ≤5.0 cm; M oderate: >5.0 to ≤ 10.0 cm; S evere: >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-2021-5683-0951774
Revised: 22 September 2021 31 Table 6: Study 2 – Frequency and Percentages of Adolescents with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Adolescent s 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 (%)
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-2021-5683-0951775
Revised: 22 September 2021 32 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 (%)
New or worsened joint
painc
Any 109 (9.7) 77 (6.8) 173 (15.8) 51 (4.7)
Mild 66 (5.9) 50 (4.4) 91 (8.3) 30 (2.8)
Moderate 42 (3.7) 27 (2.4) 78 (7.1) 21 (1.9)
Severe 1 (0.1) 0 (0.0) 4 (0.4) 0 (0.0)
Use of antipyretic or
pain medicationf 413 (36.6) 111 (9.8) 557 (50.8) 95 (8.8)
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose.
a. N = N umber 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; S evere: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; M oderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e. Mild: 2 to 3 loo se stools in 24 hours; M oderate: 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.
Unsolicited Adverse Events
In the following analys es of Study 2 in adolescents 12 through 15 years of age (1,131 of whom received
Pfizer -BioNTech COVID -19 Vaccine and 1,129 of whom received placebo), 98.3% of study participants had at
least 30 days of follow- up after Dose 2 .
Serious Adverse Events
Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by
0.4% of Pfizer -BioNTech COVID- 19 Vaccine recipients and by 0.1% of placebo recipients. There were no
notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse
events that would suggest a c ausal relationship to Pfizer -BioNTech COVID-19 Vaccine.
Non- Serious Adverse Events
Non- serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported
by 5.8% of Pfizer -BioNTech COVID -19 Vaccine recipients and by 5.8% of placebo recipients. From Dose 1
through 30 days after Dose 2, reports of lymphadenopathy plausibly related to the study intervention were
imbalanced, with notably more cases in the Pfizer -BioNTech COVID -19 Vaccine group (7) vs. t he 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
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 years of
age and 12 participants 65 through 85 years of age) received a booster dose of Pfizer -BioNTech COVID -19
FDA-CBER-2021-5683-0951776
Revised: 22 September 2021 33 Vaccine 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 years of age, the median age was 69 years (range 65 through 75 years of age), 6 were
male and all were White and Not Hispanic/Latino. Following the booster dose, the median follow- up time was
2.6 months (range 2.1 to 2.9 months) for Phase 1 participants and 2.6 months (range 1.1 to 2.8 months) for Phase 2/3 participants.
Solicited Local and Systemic Adverse Reactions
Table 7 and Table 8 present the frequency and severity of reported solicited local and systemic reactions,
respectively, within 7 days of a booster dose of Pfizer -BioNTech COVID -19 Vaccine for Phase 2/3 participants
18 through 55 years of age.
In participants who received a booster dose, the mean duration of pain at the injection site after the booster dose
was 2.6 days (range 1 to 8 days), for redness 2.2 days (range 1 to 15 days), and for swelling 2.2 days (range 1 to
8 days).
Table 7: Study 2 – Frequency and Percentages of Participants With Solicited Local Reactions, By
Maximum Severity, Within 7 Days After the Booster Dose of Pfizer- BioNTech COVID-19
Vaccine – Participants 18 through 55 Years of Age*
Solicited Local Reaction Pfizer -BioNTech COVID -19 Vaccine
Booster Dose
Na = 289
nb (%)
Rednessc
Any (>2 cm) 17 (5.9)
Mild 10 (3.5)
Moderate 7 (2.4)
Severe 0
Swellingc
Any (>2 cm) 23 (8.0)
Mild 13 (4.5)
Moderate 9 (3.1)
Severe 1 (0.3)
FDA-CBER-2021-5683-0951777
Revised: 22 September 2021 34 Solicited Local Reaction Pfizer -BioNTech COVID -19 Vaccine
Booster Dose
Na = 289
nb (%)
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 of Phase 2/3 participants 18 through 55 years of age who received a booster dose of COMIRNATY approximately
6 months after completing the primary series .
a. N = N umber 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 specif ied reaction.
c. Mild: >2.0 to 5.0 cm; M oderate: >5.0 to 10.0 cm; S evere: >10.0 cm.
d. Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Table 8: Study 2 – Frequency and Percentages of Participants With Solicited Systemic Reactions , by
Maximum Severity, Within 7 Days After the Booster Dose of Pfizer- BioNTech COVID-19
Vaccine – Participants 18 through 55 Years of Age*
Solicited Systemic Reaction Pfizer -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
FDA-CBER-2021-5683-0951778
Revised: 22 September 2021 35 Solicited Systemic Reaction Pfizer -BioNTech COVID -19 Vaccine
Booster Dose
Na = 289
nb (%)
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)
New or worsened joint painc
Any 73 (25.3)
Mild 36 (12.5)
Moderate 36 (12.5)
Severe 1 (0.3)
Use of antipyretic or pain medicationf 135 (46.7)
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
the booster dose .
Note: No Grade 4 solicited systemic reaction s were reported .
* A subset of Phase 2/3 participants 18 through 55 years of age who received a booster dose of COMIRNATY approximately
6 months after completing the primary series .
a. N = N umber 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; S evere: prevents daily activity.
d. Mild: 1 to 2 times in 24 hours; M oderate: >2 times in 24 hours; S evere: requires intravenous hydration.
e. Mild: 2 to 3 loose stools in 24 hours; M oderate: 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 the booster dose. No participant in this age group
reported a severe systemic event or fever after the booster dose.
Unsolicited Adverse Events
Overall , the 306 participants who received a booster dose, had a median follow- up time of 2.6 months after the
booster dose to the cut-off date (June 17, 2021).
In an analysis of all unsolicited adverse events reported following the booster dose, through 1 month after the
booster dose, in participants 1 8 through 55 years of age (N = 306) , those assessed as adverse reactions not
already captured by solicited local and systemic reactions were lymphadenopathy (n = 16, 5.2% ), nausea ( n = 2,
0.7%), decreased appetite ( n = 1, 0.3%), rash (n = 1, 0.3%), and pain in extremity (n = 1, 0.3%).
Serious 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 days after the booster dose that was assessed as unrelated to vaccination.
FDA-CBER-2021-5683-0951779
Revised: 22 September 2021 36
6.2 Post Authorization Experience
The following adverse reactions have been identified during post authorization use of Pfizer -BioNTech
COVID- 19 Vaccine. Because these reactions are reported voluntarily, it is not always possible to reliably
estimate their frequency or establish a causal relationship to vaccine exposure. Cardiac Disorders: myocarditis, pericarditis
Gastrointestinal Disorders: diarrhea, v omiting
Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema )
Musculoskeletal and C onnective T issue D isorders: pain in extremity (arm)
Nervous System Disorders: syncope
8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND
VACCINE ADMINISTRATION ERRORS7
See Overall Safety Summary (Section 6) for additional information.
The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for MANDATORY reporting of the listed events following Pfizer -BioNTech COVID- 19 Vaccine to the Vaccine
Adverse Event Reporting System (VAERS) :
• Vaccine administration errors whether or not associated with an adverse event
• Serious adverse events* (irrespective of attribution to vaccination)
• Cases of M ultisystem I nflammatory 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 incapacity or substantial disruption of the ability to conduct normal life functions
• A congenital anomaly/birth defect
• An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above
Instructions for Reporting to VAERS
The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a VAERS form to FDA using one of the following methods:
• Complete and submit the report onli ne: https://vaers.hhs.gov/reportevent.html
, or
• If you are unable to submit this form electronically, you may fax it to VAERS at 1-877-721- 0366. If
you need additional help submitting a report you may call the VAERS toll- free information line at
1-800-822-7967 or send an email to [email protected].
7 Vaccination providers administering COMIRNATY (COVID -19 Vaccine, mRNA) must adhere to the same reporting requirements.
FDA-CBER-2021-5683-0951780
Revised: 22 September 2021 37 IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please
complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:
• Patient demographics (e.g., patient name, date of birth)
• Pertinent medical history
• Pertinent details regarding admission and course of illness
• Concomitant medications
• Timing of adverse event(s) in relationship to administration of the Pfizer- BioNTech COVID -19
Vaccine
• Pertinent laboratory and virology information
• Outcome of the event and any additional follow- up information if it is available at the time of the
VAERS report. Subsequent reporting of follow-up information should be completed if additional details become available.
The following steps are highlighted to provide the necessary information for safety tracking:
1. In Box 17, provide information on Pfizer -BioNTech COVID -19 Vaccine and any other vaccines
administered on the same day; and in Box 22, provide information on any other vaccines received within 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. It is important to provide detailed information regarding the patient and adve rse event/medication error for
ongoing safety evaluation of this unapproved vaccine. Please see information to include listed above.
3. Contact information:
a. In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
b. In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.
c. In Box 15, provide the address of the facility where vaccine was given (NO T the healthcare
provider’s office address).
Other Reporting Instructions
Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above. To the extent feasible, report adverse events to Pfizer Inc. using the contact information below or by providing a
copy of the VAERS form to Pfizer Inc.
Website Fax number Telephone number
www.pfizersafetyreporting.com 1-866-635-8337 1-800-438-1985
10 DRUG INTERACTIONS
There are no data to assess the co ncomitant administration of the Pfizer -BioNTech COVID -19 Vaccine with
other vaccines.
FDA-CBER-2021-5683-0951781
Revised: 22 September 2021 38 11 USE IN SPECIFIC POPULATIONS
11.1 Pregnancy
Risk Summary
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on Pfizer -BioNTech COVID- 19 Vaccine administered to
pregnant women are insufficient to inform vaccine-associated risks in pregnancy.
In a reproductive and developmental toxicity study , 0.06 mL of a vaccine formulation containing the same
quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (30 mcg) and other ingredients included in a single human dose of Pfizer -BioNTech COVID -19 Vaccine was administered to female rats by the
intramuscular route on four occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No vaccine -related adverse effects on female fertility, fetal development , or postnatal development were reported in
the study.
11.2 Lactation
Risk Summary
Data are not available to assess the effects of Pfizer -BioNTech COVID -19 Vaccine on the breastfed infant or on
milk production/excretion. 11.3 Pediatric Use
Emergency Use Authorization of Pfizer- BioNTech COVID-19 Vaccine in adolescents 12 through 17 years of
age is based on safety and effectiveness 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.
11.4 Geriatric Use
Clinical studies of Pfizer -BioNTech COVID -19 Vaccine include participants 65 years of age and older who
received the primary series and their data contributes to the overall assessment of safety and efficacy [see
Overall Safety Summary (6.1) and Clinical Trial Results and Supporting Data for EUA (18.1)] . Of the total
number of Pfizer- BioNTech COVID -19 Vaccine recipients in Study 2 (N=20,033), 21.4% (n= 4,294 ) were
65 years of age and older and 4.3% (n= 860) were 75 years of age and older.
The safety of a booster dose of Pfizer -BioNTech COVID- 19 Vaccine in individuals 65 years of age and older is
based on safety data in 12 booster dose recipients 65 through 85 years of age and 306 booster dose recipients 18
through 55 years of age in Study 2. The effectiveness of a booster dose of Pfizer -BioNTech COVID -19 Vaccine
in individuals 65 years of age and older is based on effectiveness data in 306 booster dose recipients 18 through
55 years of age in Study 2.
11.5
Use in Immunocompromised
From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid -organ transplant recipients. N Engl J Med) , safety and effectiveness of a third dose of the
FDA-CBER-2021-5683-0951782
Revised: 22 September 2021 39 Pfizer -BioNTech COVID-19 vaccine have been evaluated in persons that received solid organ transplants. The
administration of a third dose of vaccine appears to be only moderately effective in increasing potentially
protective antibody titers. Patients should still be counselled to maintain physical precautions to help prevent
COVID-19. In addition, close contacts of immunocompromised persons should be vaccinated as appropriate for their health status .
13 DESCRIPTION
The Pfizer -BioNTech COVID -19 Vaccine is supplied as a frozen suspension in multiple dose vials; each vial
must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine. Each dose of the Pfizer -BioNTech COVID -19 Vaccine contains 30 mcg of a nucleoside- modified messenger
RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2. Each dose of the Pfizer -BioNTech COVID -19 Vaccine also includes the following ingredients: lipids (0.43 mg
(4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2[(polyethylene glycol)-2000]-
N,N-ditetradecylacetamide, 0.09 mg 1,2- distearoyl -sn-glycero -3-phosphocholine, and 0.2 mg cholesterol),
0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 0.07 mg dibasic sodium phosphate dihydrate, and 6 mg sucrose. The diluent (0.9% Sodium Chloride Injection, USP )
contributes an additional 2.16 mg sodium chloride per dose. 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 elicits an
immune response to the S antigen , which protects against COVID -19.
18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA
18.1 Efficacy of Primary Series in Participants 16 Years of Age and Older
Study 2 is a multicenter, multinational, Phase 1/2/3, randomized, placebo-controlled, observer-blind,
dose-finding, vaccine candidate-selection, and efficacy study in participants 12 years of age and older.
Randomization was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19.
Participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, were included as were participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
In the Phase 2/3 portion of Study 2, based on data accrued through November 14, 2020, approximately 44,000 participants 12 years of age and older were randomized equally and received 2 doses of
Pfizer -BioNTech COVID- 19 Vaccine or placebo separated by 21 days. Particip ants are planned to be followed
for up to 24 months, for assessments of safety and efficacy against COVID -19.
FDA-CBER-2021-5683-0951783
Revised: 22 September 2021 40 The population for the analysis of the primary efficacy endpoint included, 36,621 participants 12 years of age
and older (18,242 in the Pfizer -BioNTech COVID- 19 Vaccine group and 18,379 in the placebo group) who did
not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. Table 9 presents
the specific demographic characteris tics in 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 (years)
Mean (SD) 50.6 (15.70) 50.4 (15.81)
Median 52.0 52.0
Min, max (12, 89) (12, 91)
Age group
≥12 through 15 yearsb 46 (0.3) 42 (0.2)
≥16 through 17 years 66 (0.4) 68 (0.4)
≥16 through 64 years 14,216 (77.9) 14,299 (77.8)
≥65 through 74 years 3176 (17.4) 3226 (17.6)
≥75 years 804 (4.4) 812 (4.4)
Race
White 15,110 (82.8) 15,301 (83.3)
Black or African American 1617 (8.9) 1617 (8.8)
American Indian or Alaska Native 118 (0.6) 106 (0.6)
Asian 815 (4.5) 810 (4.4)
Native Hawaiian or other Pacific Islander 48 (0.3) 29 (0.2)
Otherc 534 (2.9) 516 (2.8)
Ethnicity
Hispanic or Latino 4886 (26.8) 4857 (26.4)
Not Hispanic or Latino 13,253 (72.7) 13,412 (73.0)
Not reported 103 (0.6) 110 (0.6)
Comorbiditiesd
Yes 8432 (46.2) 8450 (46.0)
No 9810 (53.8) 9929 (54.0)
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
(49 in the vaccine group and 51 in the placebo group). Some of these participants were included in the efficacy evaluation
depending on the population analyzed. They contributed to exposure information but with no confirmed COVID -19 cases, and
did not affect efficacy conclusions.
c. Includes multiracial and not reported.
d. Number of participants who have 1 or more comorbidities that increase the risk of severe COVID -19 disease
• Chronic lung disease (e.g., emphysema and chronic bronchitis, idiopathic pulmonary fibrosis, and cystic fibrosis) or
moderate to severe asthma
• Significant cardiac disease (e.g., heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and
pulmonary hypertension)
• Obesity (body mass index ≥30 kg/m2)
• Diabetes (Type 1, Type 2 or gestational)
FDA-CBER-2021-5683-0951784
Revised: 22 September 2021 41 Pfizer -BioNTech
COVID-19 Vaccine
(N=18,242)
n (%) Placebo
(N=18,379)
n (%)
• Liver disease
• Human Immunodeficiency Virus (HIV) infection (not included in the efficacy evaluation)
The population in the prim ary efficacy analysis 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 years of age and older began enrollment from July 27, 2020, 16 through 17 years of age began enrollment from September 16, 2020, and 12 through 15 years of age began enrollment from October 15, 2020. The vaccine efficacy information is presented in Table 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 *
Subgroup Pfizer -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 subjectse 8
2.214 ( 17,411) 162
2.222 ( 17,511) 95.0 (90.3, 97.6)f
16 through 64 years 7
1.706 (13,549) 143
1.710 (13,618) 95.1 ( 89.6, 98.1)g
65 years and older 1
0.508 (3848) 19
0.511 ( 3880) 94.7 (66.7, 99.9)g
First COVID -19 occurrence from 7 days after Dose 2 in participants with or without evidence of prior
SARS -CoV -2 infection
Subgroup Pfizer -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 subjectse 9
2.332 ( 18,559) 169
2.345 ( 18,708) 94.6 ( 89.9, 97.3)f
16 through 64 years 8
1.802 ( 14,501) 150
1.814 (14,627) 94.6 (89.1, 97.7)g
65 years and older 1
0.530 (4044) 19
0.532 ( 4067) 94.7 (66.8, 99.9)g
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.
FDA-CBER-2021-5683-0951785
Revised: 22 September 2021 42 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 p articipants within each group at risk for the
endpoint. Time period for COVID -19 case accrual is from 7 days aft er Dose 2 to the end of the surveillance period.
d. n2 = Number of participants at risk for the endpoint.
e. No confirmed cases were identified in adolescents 12 through 15 years of age.
f. Credible interval for vaccine efficacy (VE) was calculated using a beta -binomial model with a beta (0.700102, 1) prior for θ=r(1-
VE)/(1+r(1 -VE)), where r is the ratio of surveillance time in the active vaccine group over that in the placebo group.
g. Confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the surveillance
time.
18.2 Efficacy of Primary Series in Adolescents 12 Through 15 Years of Age
A descriptive efficacy analysis of Study 2 has been performed in approximately 2,200 adolescents 12 through 15 years of age evaluating confirmed COVID -19 cases accrued up to a data cutoff date of March 13, 2021.
The efficacy information in adolescents 12 through 15 years of age is presented in Table 11.
Table 11: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2: Without Evidence of Infection and With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Blinded Placebo -Controlled Follow-up Period, Adolescents 12 T hrough 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
12 through 15 years of age 0
0.154 (1001 ) 16
0.147 (972)
100.0 (75.3, 100.0 )
First 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
12 through 15 years of age 0
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 p articipants within each group at risk for the
endpoint. Time period for COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period.
d. n2 = Number of participants at risk for the endpoint.
e. Confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted for surveillance time.
FDA-CBER-2021-5683-0951786
Revised: 22 September 2021 43
18.3 Immunogenicity of Primary Series in Adolescents 12 Through 15 Years of Age
In Study 2, an analysis of SARS-CoV-2 50% neutralizing titers 1 month after Dose 2 in a randomly selected subset of participants demonstrated non-inferior immune responses (within 1.5-fold) comparing adolescents 12 through 15 years of age to participants 16 through 25 years of age who had no serological or virological evidence of past SARS -CoV-2 infection up to 1 month after Dose 2 (Table 12).
Table 12: Summary of Geometric Mean Ratio for 50% Neutralizing Titer – Comparison of Adolescents 12 Through 15 Years of Age to Participants 16 Through 25 Years of Age (Immunogenicity Subset) –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 15 Years
na=190 16 Through 25 Years
na=170 12 Through 15 Years/
16 Through 25 Years
Assay Time
Pointb GMTc
(95% CIc) GMTc
(95% CIc) GMRd
(95% CId) Met
Noninferiority
Objectivee
(Y/N)
SARS -CoV -2
neutralization assay - NT50
(titer)f 1 month
after
Dose 2 1239.5
(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 = lower 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 were included in the analysis.
a. n = Number of participants with valid and determinate assay results for the specified assay at the given dose /sampling time
point.
b. Protocol -specified timing for blood sample collection.
c. GMTs and 2 -sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs
(based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.
d. GMRs and 2 -sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers (Group 1
[12 through 15 years of age] – Group 2 [16 through 25 years of age]) and the corresponding CI (based on the Student t
distribution).
e. Noninferiority is declared if the lower bound of the 2- sided 95% CI for the GMR is greater than 0.67.
f. SARS -CoV -2 50% neutralization titers (NT50) were determined using the SARS -CoV -2 mNeonGreen Virus
Microneutralization Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus
neutralization is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% of
the virus is neutralized.
18.4 Immunogenicity of Booster Dose 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, analyse s of NT50
1 month after the booster dose compared to 1 month after the primary series in individuals 18 through 55 years of age who had no serological or virological evidence of past SARS-CoV- 2 infectio n up to 1 month after the
booster vaccination demonstrated noninferiority for both geometric mean ratio (GMR) and difference in
seroresponse rates. Seroresponse for a participant was defined as achieving a ≥4- fold rise in NT50 from
baseline (before primary series ). These analyses are summarized in Table 13 and Table 14.
FDA-CBER-2021-5683-0951787
Revised: 22 September 2021 44 Table 13: Geometric Mean 50% Neutralizing Titer ( SARS -CoV-2 USA_WA1/2020) – Comparison of
1 Month After Booster Dose to 1 Month After Primary Series – Participants 18 Through
55 Years of Age Without Evidence of Infection up to 1 Month After Booster Dose* – Booster
Dose Evaluable Immunogenicity Population±
Assay na 1 Month After
Booster Dose
GMTb
(95% CIb) 1 Month After
Primary
Series
GMTb
(95% CIb) 1 Month After
Booster Dose/
1 Month After
Primary Series
GMRc
(97.5% CIc) Met
Noninferiority
Objectived
(Y/N)
SARS -CoV -2
neutralization assay -
NT50 (titer)e 212 2466.0
(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 = lower limit of
quantitation; N -binding = SARS -CoV -2 nucleoprotein -binding; NAAT = nucleic acid amplification test; NT50 = 50% neutralizing
titer; SARS- CoV -2 = severe acute respiratory syndrome coronavirus 2; Y/N = yes/no .
* Participants who had no serological or virological evidence (up to 1 month after rec eipt of a booster dose of Pfizer -BioNTech
COVID- 19 Vaccine) of past SARS -CoV -2 infection (i.e., N -binding antibody [serum] negative and SARS -CoV -2 not detected
by NAAT [nasal swab]) and had a negative NAAT (nasal swab) at any unscheduled visit up to 1 mont h 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 × LLO Q.
c. GMRs and 2 -sided 97.5% CIs were calculated by exponentiating the mean differences in the logarithms of the assay and the
corresponding CIs (based on the Student t distribution).
d. Noninferiority is declared if the lower bound of the 2- sided 97.5% CI for the GMR is > 0.67 and the point estimate of the GMR is
≥0.80.
e. SARS -CoV -2 NT50 were determined using the SARS -CoV -2 mNeonGreen Virus Microneutralization Assay. The assay uses a
fluorescent reporter virus derived from the USA _WA1/2020 strain and vir us 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.
FDA-CBER-2021-5683-0951788
Revised: 22 September 2021 45 Table 14: Seroresponse Rate for 50% Neutralizing Titer ( SARS -CoV-2 USA_WA1/2020) – Comparison
of 1 Month After Booster Dose to 1 Month After Primary Series – Participants 18 Through
55 Years of Age Without Evidence of Infection up to 1 Month After Booster Dose* – Booster
Dose Evaluable Immunogenicity Population±
Assay Na 1 Month After
Booster Dose
nb
% (95% CIc) 1 Month After
Primary Series
nb
% (95% CIc) Difference
(1 Month After
Booster Dose -
1 Month After
Primary Series)
%d (97.5% CIe) Met
Noninferiority
Objectivef
(Y/N)
SARS -CoV -2
neutralization assay -
NT50 (titer)g 200 199
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 = lower limit of quantitation; N -binding = SARS -CoV -2 nucleoprotein -binding;
NAAT = nucleic acid amplification test; NT50 = 50% neutralizing titer; SARS -CoV -2 = severe acute respiratory syndrome
coronavirus 2; Y/N = yes/no .
Note: Seroresponse is defined as achieving a ≥4 -fold rise from baseline (be fore 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 to 1 month after receipt of booster vaccination) of past
SARS -CoV -2 infection (i.e., N -binding antibody [serum] negative and SARS -CoV -2 not detected by NAAT [nasal swab]) and
had a negative NAAT (nasal swab) at any unscheduled visit up to 1 month after booster vaccination were included in the
analysis.
± All eligible participants who had received 2 doses of Pfizer -BioNTech COVID- 19 Vaccine as initially randomized, with Dose 2
received within the p redefined window (within 19 to 42 days after Dose 1), received a booster dose of Pfizer -BioNTech
COVID- 19 Vaccine, had at least 1 valid and determinate immunogenicity result after booster dose from a blood collection
within an appropriate window (within 28 to 42 days after the booster dose), and had no other important protocol deviations as
determined by the clinician.
a. N = number of participant s with valid and determinate assay results for the specified assay at baseline, 1 month after Dose 2 and
1 month after the booster dose within specified window. These values are the denominators for the percentage calculations.
b. n = Number of 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, expressed as a percentage (1 month after booster dose – 1 month after Dose 2).
e. Adjusted Wald 2 -sided CI for the difference in proportions, expressed as a percentage.
f. Noninferiority is dec lared if the lower bound of the 2- sided 97.5% CI for the percentage difference is > - 10%.
g. SARS -CoV -2 NT50 were determined using the SARS -CoV -2 mNeonGreen Virus Microneutralization Assay. The assay uses a
fluorescent reporter virus derived from the USA _WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The
sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.
18.5 Immunogenicity in S olid Organ Transplant R ecipients
From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid -organ transplant recipients. N Engl J Med) , a single arm study has been conducted in
101 individuals who had undergone various solid organ transplant procedures (heart, kidney, liver, lung, pancreas) 97±8 months previously. A third dose of the Pfizer- BioNTech COVID -19 v accine was administered
to 99 of these individuals approximately 2 months after they had received a second dose. Among the 59 patients who had been seronegative before the third dose, 26 (44%) were seropositive at 4 weeks after the third dose. All 40 patients who had been seropositive before the third dose were still seropositive 4 weeks later . The prevalence
of anti- SAR S-CoV-2 antibodies was 68% (67 of 99 patients) 4 weeks after the third dose.
19 HOW SUPPLIED/STORAGE AND HANDLING
Pfizer -BioNTech COVID-19 Vaccine Suspension for Intramuscular Injection, Multiple Dose Vials are supplied
in a carton containing 25 multiple dose vials (NDC 59267-1000- 3) or 195 multiple dose vials
(NDC 59267-1000- 2). After dilution, one vial contains 6 doses of 0.3 mL. Vial labels and c artons may state that
after dilution, a vial contains 5 doses of 0.3 mL. The information in this Full EUA Prescribing Information
FDA-CBER-2021-5683-0951789
Revised: 22 September 2021 46 regarding the number of doses per vial after dilution supersedes the number of doses stated on vial labels and
cartons.
Durin g 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 Febru ary
2022 printed on the label may remain in use for 3 months beyond the printed date as long as approved storage conditions between -90ºC to -60ºC (-130ºF to -76ºF) have been maintained. Updated expiry dates are shown below .
Printed 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 (-130ºF to -76ºF). Total cumulative time the vials are stored at -25°C
to -15°C (-13°F to 5°F) should be tracked and should not exceed 2 weeks.
If an ultra -low temperature freezer is not available, the thermal container in which the Pfizer -BioNTech
COVID- 19 Vaccine arrives may be used as temporary storage when consistently re-filled to the top of the
container with dry ice. Refer to the re-icing guidelines packed in the original thermal container for instructions
regarding the use of the thermal container for temporary storage. The thermal container maintains a temperature
range of -90ºC to -60ºC (-130ºF to -76ºF). Storage of the vials between -96°C to - 60°C ( -141°F to -76°F) is not
considered an excursion from the recommended storage condition.
Transportation of Frozen Vials
If local redistribution is needed and full cartons containing vials cannot be transported at -90°C to -60°C (-130°F to -76°F), vials may be transported at -25°C to - 15°C ( -13°F to 5°F). Any hours used for transport
at -25°C to - 15°C ( -13°F to 5°F) count against the 2- week limit for storage at -25°C to - 15°C ( -13°F to 5°F).
Frozen vials transported at -25°C to - 15°C ( -13°F to 5°F) may be returned one time to the recommended s torage
condition of -90ºC to -60ºC (-130ºF to -76ºF).
FDA-CBER-2021-5683-0951790
Revised: 22 September 2021 47
Thawed Vials Before Dilution
Thawed Under Refrigeration Thaw and then store undiluted vials in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] for up to 1 month. A carton of 25 vials or 195 vials may take up to 2 or 3 hours , respectively, to thaw in the refrigerator , whereas a fewer
number of vials will thaw in less time .
Thawed at Room Temperature For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for 30 minutes. Thawed vials
can be handled in room light conditions. Vials must reach room temperature before dilution.
Undiluted vials may be stored at room temperature for no more than 2 hours.
Transportation of Thawed Vials
Available data support transportation of one or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 12 hours.
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 caregiver to read the Vaccine Information Fact Sheet for Recipient s and Caregivers.
The vaccination provider must include vaccination information in the state/local jurisdiction’s Immunization Information System (IIS) or other designated system. Advise recipient or caregiver that more information about IISs can be found at : https://www.cdc.gov/vaccines/programs/iis/about.html
.
21 CONTACT INFORMATION
For general questions, visit the website or call the telephone number provided below.
Website Telephone number
www.cvdvaccine.com
1-877-829-2619
(1-877- VAX-CO19)
FDA-CBER-2021-5683-0951791
Revised: 22 September 2021 48 This Full EUA Prescribing Information may have been updated. For the most recent Full EUA Prescribing
Information, please see www.cvdvaccine.com .
Manufactured by Pfizer Inc., New York, NY 10017
Manufactured for BioNTech Manufacturing GmbH An der Goldgrube 12 55131 Mainz, Germany LAB -1457-14.0
Revised : 22 September 2021
FDA-CBER-2021-5683-0951792