Pfizer Biontech Covid-19 Vaccine

Patient Information

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

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

Contact Information

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

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

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.

Indications

Authorized Use

Pfizer-BioNTech COVID-19 Vaccine is authorized for use under an Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older.

Dosage And Admintisration

For intramuscular injection only.

Preparation For Administration

Prior To Dilution

• The Pfizer-BioNTech COVID-19 Vaccine Multiple Dose Vial contains a frozen suspension that does not contain preservative and must be thawed and diluted prior to administration.
• Vials may be thawed in the refrigerator [2°C to 8°C (35°F to 46°F)] or at room temperature [up to 25°C (77°F)] [see HOW SUPPLIED/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.
• 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:
  • Allowing vial(s) to thaw in the refrigerator [2°C to 8°C (35°F to 46°F)]. A carton of vials may take up to 3 hours to thaw, and thawed vials can be stored in the refrigerator for up to five days (120 hours).
  • Allowing vial(s) to sit at room temperature [up to 25°C (77°F)] 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.

 

 

• 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.

Dilution

 

 

• 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.

 

 

Preparation of Individual 0.3 mL Doses of -Biontech COVID-19 Vaaccine

• 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.
• Administer immediately.

 

 

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.

Vaccination Schedule For Individuals 16 Years Of Age And Older

The Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly as a series of two doses (0.3 mL each) three weeks apart.

There are no data available on the interchangeability of the Pfizer-BioNTech COVID-19 Vaccine with other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose of Pfizer-BioNTech COVID-19 Vaccine should receive a second dose of Pfizer-BioNTech COVID-19 Vaccine to complete the vaccination series.

How Supplied

Dosage Forms And Strengths

Pfizer-BioNTech COVID-19 Vaccine is a suspension for injection. After preparation, a single dose is 0.3 mL.

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).

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 store in an ultra-low temperature freezer between -80°C to -60°C (-112°F to -76°F). Vials must be kept frozen between -80°C to -60°C (-112°F to -76°F) and protected from light, in the original cartons, until ready to use.

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 -90°C to -60°C (-130°F to -76°F). Storage within this temperature range is not considered an excursion from the recommended storage condition.

Thawed Vials Before Dilution

Thawed Under Refrigeration

Thaw and then store undiluted vials in the refrigerator [2°C to 8°C (35°F to 46°F)] for up to 5 days (120 hours). A carton of 25 vials or 195 vials may take up to 2 or 3 hours, respectively, to thaw in the refrigerator, whereas a fewer number of vials will thaw in less time.

Thawed At Room Temperature

For immediate use, thaw undiluted vials at room temperature [up to 25°C (77°F)] 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.

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.

Manufactured by :Pfizer Inc., New York, NY 10017. Manufactured for : BioNTech Manufacturing GmbH, An der Goldgrube 12 55131 Mainz, Germany, LAB-1457-1.0. Revised: Dec 2020

Side Effects

Overall Safety Summary

It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and hospitalized or fatal cases of COVID-19 following vaccination with the Pfizer-BioNTech COVID-19 Vaccine. 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, adverse reactions in participants 16 years of age and older 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%).

Severe allergic reactions have been reported following the Pfizer-BioNTech COVID-19 Vaccine during mass vaccination outside of clinical trials.

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.

The safety of Pfizer-BioNTech COVID-19 Vaccine was evaluated in participants 16 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 ½, 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 44,000 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).

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 have 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 enrolled by October 9, 2020, and includes safety data accrued through November 14, 2020. Participants 18 years and older in the reactogenicity subset are monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination in an electronic diary. Participants are being monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month (all unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination].

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

Local And Systemic Adverse Reactions Solicited In The Study 2

Table 1 and Table 2 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 in the subset of participants 18 to 55 years of age included in the EUA safety population who were monitored for reactogenicity with an electronic diary.

Table 3 and Table 4 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of each dose of Pfizer-BioNTech COVID-19 Vaccine and placebo for participants 56 years of age and older.

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

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

Table 1: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 18-55 Years of Age‡ – Reactogenicity Subset of the Safety Population*

	Pfizer-BioNTech COVID-19 Vaccine Dose 1 Na=2291 nb (%)	Placebo Dose 1 Na=2298 nb (%)	Pfizer-BioNTech COVID-19 Vaccine Dose 2 Na=2098 nb (%)	Placebo Dose 2 Na=2103 nb (%)
Rednessc
Any (>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 = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. b n = Number of participants with the specified reaction. c Mild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. d Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity. ‡ Eight participants were between 16 and 17 years of age. * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.

 

Table 2: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 18-55 Years of Age‡ – 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°C	85 (3.7)	20 (0.9)	331 (15.8)	10 (0.5)
≥38.0°C to 38.4C	64 (2.8)	10 (0.4)	194 (9.2)	5 (0.2)
>38.4C to 38.9C	15 (0.7)	5 (0.2)	110 (5.2)	3 (0.1)
>38.9°C to 40.0C	6 (0.3)	3 (0.1)	26 (1.2)	2 (0.1)
>40.0°C	0 (0.0)	2 (0.1)	1 (0.0)	0 (0.0)
Fatiguec
Any	1085 (47.4)	767 (33.4)	1247 (59.4)	479 (22.8)
Mild	597 (26.1)	467 (20.3)	442 (21.1)	248 (11.8)
Moderate	455 (19.9)	289 (12.6)	708 (33.7)	217 (10.3)
Severe	33 (1.4)	11 (0.5)	97 (4.6)	14 (0.7)
Headachec
Any	959 (41.9)	775 (33.7)	1085 (51.7)	506 (24.1)
Mild	628 (27.4)	505 (22.0)	538 (25.6)	321 (15.3)
Moderate	308 (13.4)	251 (10.9)	480 (22.9)	170 (8.1)
Severe	23 (1.0)	19 (0.8)	67 (3.2)	15 (0.7)
Chillsc
Any	321 (14.0)	146 (6.4)	737 (35.1)	79 (3.8)
Mild	230 (10.0)	111 (4.8)	359 (17.1)	65 (3.1)
Moderate	82 (3.6)	33 (1.4)	333 (15.9)	14 (0.7)
Severe	9 (0.4)	2 (0.1)	45 (2.1)	0 (0.0)
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 = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. b n = Number of participants with the specified reaction. c Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. d Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. e Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours. f Severity was not collected for use of antipyretic or pain medication. ‡ Eight participants were between 16 and 17 years of age. * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.

 

Table 3: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – 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 = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. b n = Number of participants with the specified reaction. c Mild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. d Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity. * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.

 

Table 4: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety Population*

	Pfizer-BioNTech 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°C	26 (1.4)	7 (0.4)	181 (10.9)	4 (0.2)
≥38.0°C to 38.4C	23 (1.3)	2 (0.1)	131 (7.9)	2 (0.1)
>38.4°C to 38.9C	1 (0.1)	3 (0.2)	45 (2.7)	1 (0.1)
>38.9°C to 40.0C	1 (0.1)	2 (0.1)	5 (0.3)	1 (0.1)
>40.0°C	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)
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 = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. b n = Number of participants with the specified reaction. c Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. d Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. e Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours. * Randomized participants in the safety analysis population who received at least 1 dose of the study intervention.

 

Unsolicited Adverse Events

Serious Adverse Events

In Study 2, among participants 16 to 55 years of age who had received at least 1 dose of vaccine or placebo (Pfizer-BioNTech COVID-19 Vaccine = 10,841; placebo = 10,851), serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.3% of placebo recipients. In a similar analysis, in participants 56 years of age and older (Pfizer-BioNTech COVID-19 Vaccine = 7960, placebo = 7934), serious adverse events were reported by 0.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.6% of placebo recipients who received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine or placebo, respectively. In these analyses, 91.6% of study participants had at least 30 days of follow-up after Dose 2. Appendicitis was reported as a serious adverse event for 12 participants, and numerically higher in the vaccine group, 8 vaccine participants and 4 placebo participants. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.

Non-Serious Adverse Events

Overall in Study 2 in which 10,841 participants 16 to 55 years of age received Pfizer-BioNTech COVID-19 Vaccine and 10,851 participants received placebo, non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported in 29.3% of participants who received Pfizer-BioNTech COVID-19 Vaccine and 13.2% of participants in the placebo group, for participants who received at least 1 dose. Overall in a similar analysis in which 7960 participants 56 years of age and older received Pfizer-BioNTech COVID-19 Vaccine, non-serious adverse events within 30 days were reported in 23.8% of participants who received Pfizer-BioNTech COVID-19 Vaccine and 11.7% of participants in the placebo group, for participants who received at least 1 dose. In these analyses, 91.6% of study participants had at least 30 days of follow-up after Dose 2. The higher frequency of reported unsolicited non-serious adverse events among Pfizer BioNTech COVID-19 Vaccine recipients compared to placebo recipients was primarily attributed to local and systemic adverse events reported during the first 7 days following vaccination that are consistent with adverse reactions solicited among participants in the reactogenicity subset and presented in Tables 3 and 4. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy were imbalanced with notably more cases in the Pfizer-BioNTech COVID-19 Vaccine group (64) vs. the placebo group (6), which is plausibly related to vaccination. Throughout the safety follow-up period to date, Bell’s palsy (facial paralysis) was reported by 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.

Requirements And Instructions For Reporting Adverse Events And Vaccine Administration Errors

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

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for MANDATORY reporting of the listed events following Pfizer-BioNTech COVID-19 Vaccine to the Vaccine Adverse Event Reporting System (VAERS):

• Vaccine administration errors whether or not associated with an adverse event
• Serious adverse events* (irrespective of attribution to vaccination)
• Cases of Multisystem Inflammatory Syndrome (MIS) in children and adults
• Cases of COVID-19 that result in hospitalization or death

*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 online: https://vaers.hhs.gov/reportevent.html, or
• If you are unable to submit this form electronically, you may fax it to VAERS at 1-877-721-0366. If you need additional help submitting a report you may call the VAERS toll-free information line at 1-800-822-7967 or send an email to info@vaers.org.

IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

• Patient demographics (e.g., patient name, date of birth)
• Pertinent medical history
• Pertinent details regarding admission and course of illness
• Concomitant medications
• Timing of adverse event(s) in relationship to administration of the Pfizer-BioNTech COVID-19 Vaccine
• Pertinent laboratory and virology information
• Outcome of the event and any additional follow-up information if it is available at the time of the VAERS report. Subsequent reporting of follow-up information should be completed if additional details become available.

The following steps are highlighted to provide the necessary information for safety tracking:

1. In Box 17, provide information on Pfizer-BioNTech COVID-19 Vaccine and any other vaccines administered on the same day; and in Box 22, provide information on any other vaccines received within one month prior.
2. In Box 18, description of the event:
   1. Write “Pfizer-BioNTech COVID-19 Vaccine EUA” as the first line.
   2. Provide a detailed report of vaccine administration error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved vaccine. Please see information to include listed above.
3. Contact information:
   1. In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
   2. In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.
   3. In Box 15, provide the address of the facility where vaccine was given (NOT the healthcare provider’s office address).

Other Reporting Instructions

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

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

 

Website	Fax number	Telephone number
www.pfizersafetyreporting.com	1-866-635-8337	1-800-438-1985

 

Drug Interactions

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

WarningS

Included as part of the PRECAUTIONS section.

Precautions

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.

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

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

Use In Specific Populations

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.

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.

Pediatric Use

Emergency Use Authorization of Pfizer-BioNTech COVID-19 Vaccine in adolescents 16 and 17 years of age is based on extrapolation of safety and effectiveness from adults 18 years of age and older. Emergency Use Authorization of Pfizer BioNTech COVID-19 Vaccine does not include use in individuals younger than 16 years of age.

Geriatric Use

Clinical studies of Pfizer-BioNTech COVID-19 Vaccine include participants 65 years of age and older and their data contributes to the overall assessment of safety and efficacy [see Overall Safety Summary and Clinical Trial Results and Supporting Data for EUA]. 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.

Overdose

No Information provided

Contraindications

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

Mechanism Of Action

The modRNA in the Pfizer-BioNTech COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.

Clinical Trial Results And Supporting Data For Eua

Efficacy In Participants 16 Years Of Age And Older

Study 2 is a multicenter, multinational, Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate–selection, and efficacy study in participants 12 years of age and older. Randomization was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age 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 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. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.

The population for the analysis of the primary efficacy endpoint included, 36,621 participants 12 years of age and older (18,242 in the Pfizer-BioNTech COVID-19 Vaccine group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. Table 5 presents the specific demographic characteristics in the studied population.

Table 5: 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 years	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)
Otherb	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)
Comorbiditiesc
Yes	8432 (46.2)	8450 (46.0)
No	9810 (53.8)	9929 (54.0)
a All eligible randomized participants who receive all vaccination(s) as randomized within the predefined window, have no 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 Includes multiracial and not reported. c Number of participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease Chronic lung disease (e.g., emphysema and chronic bronchitis, idiopathic pulmonary fibrosis, and cystic fibrosis) or moderate to severe asthma Significant cardiac disease (e.g., heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and pulmonary hypertension) Obesity (body mass index ≥ 30 kg/m²) Diabetes (Type 1, Type 2 or gestational) Liver disease Human Immunodeficiency Virus (HIV) infection (not included in the efficacy evaluation)

 

Efficacy Against COVID-19

The population in the primary efficacy analysis included all participants 12 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 through November 14, 2020. Participants 18 to 55 years of age and 56 years of age and older began enrollment from July 27,2020, 16 to 17 years of age began enrollment from September 16, 2020 and 12 to 15 years of age began enrollment from October 15, 2020.

The vaccine efficacy information is presented in Table 6.

Table 6: 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 to 64 years	7 1.706 (13,549)	143 1.710 (13,618)	95.1 (89.6, 98.1)g
65 years and older	1 0.508 (3848)	19 0.511 (3880)	94.7 (66.7, 99.9)g
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 to 64 years	8 1.802 (14,501)	150 1.814 (14,627)	94.6 (89.1, 97.7)g
65 years and older	1 0.530 (4044)	19 0.532 (4067)	94.7 (66.8, 99.9)g
Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting). * Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis. a N = number of participants in the specified group. b n1 = Number of participants meeting the endpoint definition. c Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period. d n2 = Number of participants at risk for the endpoint. e No confirmed cases were identified in participants 12 to 15 years of age. f Credible interval for 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.