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BNT162b2
1.16 Risk Management Plan (Non-REMS) for Biologic License Application # 125742
CONFIDENTIAL
Page 1PHARMACOVIGILANCE PLAN FOR
BIOLOGIC LICENSE APPLICATION #125742
OF
COVID-19 mRNA vaccine (nucleoside modified) (BNT162b2, PF -07302048)
Date of Report: 17MAY2021
Version 1.0
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Page 2TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ..................... 3
LIST OF FIGURES ................................ ................................ ................................ ................... 5
LIST OF ABBREVIATION S................................ ................................ ................................ ....6
1. INTRODUCTION ................................ ................................ ................................ ................. 8
1.1. Product Details ................................ ................................ ................................ ..........8
2. SAFETY SPECIFICAT ION................................ ................................ ................................ ..9
2.1. Eleme nts of the Safety Specification ................................ ................................ .........9
2.1.1. Non- Clinical................................ ................................ ................................ .9
2.1.2. Clinical ................................ ................................ ................................ ........12
2.1.2.a. L imitations of the Human Safet y Database............................... 12
2.1.2.b. Populations Not Studied in the Pre- Approval Phase ................. 45
2.1.2.c. Adverse Events / Adverse Reactions................................ .........46
2.1.2.d. Identified and Potential I nteractions, Including Food -
Biologic Product and Drug -Biologic Product Interactions ...............55
2.1.2.e. Epidemiology of Indication and Target Population .................. 56
2.1.2.f. Pharmacological Class Effects ................................ ................... 67
3. PHARMACOVIGILANCE PLAN................................ ................................ ...................... 68
3.1. Structure of the Pharmacovigilance Plan ................................ ................................ 68
3.1.1. Summary of Ongoing Safety Concerns ................................ ...................... 68
3.1.2. Routine Pharmacovigilance Practices................................ ......................... 68
3.1.3. Action Plan for Safety Issues................................ ................................ ......70
3.1.4. Summary of Actions to be Completed, I ncluding Milestones.................... 80
3.2. Pharmacovigilance Methods ................................ ................................ ................... 86
3.2.1. List of Studies Included in the Pharmacovigilance Plan ............................ 86
REFERENCES ................................ ................................ ................................ ........................ 87
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Page 3LIST OF TABLES
Table1. Product Details ................................ ................................ ............................ 8
Table2. Key Safety Findings and Relevance to Human Usage ............................. 11
Table3. Exposure to BNT162b2 by Age Group and Dose (C4591001) –
Blinded Placebo -Controlled Follow- up Period ................................ ........16
Table4. Exposure to BNT162b2 by Age Group and Dose (C4591001) –
Open-Label Follow -up Period –Subjects Who Originall y Received
BNT162b2 ................................ ................................ ................................ 17
Table5. Exposure to BNT162b2 by Age Group and Dose (C4591001) –
Open-Label Follow -up Period –Subjects Who Originall y Received
Placebo and Then Received BNT162 b2 After Unblinding ...................... 18
Table6. Exposure to BNT162b2 by Age Group and Dose (BNT162 -01)............. 19
Table7. Exposure to BNT162b2 by Dose (Totals) (C4591001) –Blinded
Placebo-Controlled Follow -up Period ................................ ...................... 22
Table8. Exposure to BNT162b2 by Dose (Totals) (C4591001) –Open-
Label Follow -up Period –Subjects Who Originally Received
BNT162b2 ................................ ................................ ................................ 22
Table9. Exposure to BNT162b2 by Dose (Totals) (C4591001) –Open-
Label Follow -up Period –Subjects Who Originally Received
Placebo and Then Received BNT162b2 Af ter Unblinding ...................... 22
Table10. Exposure to BNT162b2 by Dose (Totals) (BNT162-01).........................24
Table11. Exposure to BNT162b2 by Dose, Age Group, and Gender
(C4591001) – Blinded Placebo -Controlled Follow -up Period ................. 25
Table12. Exposure to BNT162b2 by Dose, Age Group, and Gender
(C4591001) – Open-Label Follow -up Period – Subjects Who
Originally Received BNT162b2 ................................ ............................... 25
Table13. Exposure to BNT162b2 by Dose, Age Group, and Gender
(C4591001) – Open-Label Follow -up Period – Subjects Who
Originally Received Plac ebo and Then Received BNT162b2 After
Unblinding ................................ ................................ ................................ 26
Table14. Exposure to BNT162b2 by Dose, Age Group, and Gender
(BNT162 -01)................................ ................................ ............................ 27
Table15. Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic
Origin (C4591001) – Blinded Placebo -Controlled Follow -up Period ......28
Table16. Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic
Origin (C4591001) – Open-Label Follow -up Period –Subjects
Who Originally Received BNT162b2 ................................ ...................... 32
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Page 4Table17. Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic
Origin (C4591001) – Open-Label Follow -up Period –Subjects
Who Originally Received Placebo and Then Received BNT162b2
After Unblinding ................................ ................................ ....................... 33
Table18. Exposure to BNT162b2 by Dose and Race/Ethnic Origin
(C4591001) – Blinded Placebo -Controlled Follow -up Period ................. 36
Table19. Exposure to BNT162b2 by Dose and Race/Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who
Originally Received BNT162b2 ................................ ............................... 37
Table20. Exposure to BNT162b2 by Dose and Race/ Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who
Originally Received Placebo and Then Received BNT162b2 After
Unblinding ................................ ................................ ................................ 38
Table21. Exposure to BNT162b2 by Dose and Race/Ethnic Origin (BNT162-
01)................................ ................................ ................................ .............39
Table22. Exposure to BNT1 62b2 (30 μg) b y Special Population (C4591001)
–Blinded Placebo -Controlled Follow- up Period ................................ .....40
Table23. Exposure to BNT162b2 (30 μg) by Special Population (C4591001)
–Open-Label Follow -up Period –Subjects Who Originall y
Received Placebo and Then Received BNT162b2 After Unblinding...... 41
Table24. Cumulative Estimated Shipped Doses of BNT162b2 by Region
Worldwide ................................ ................................ ................................ 44
Table25. Exposure of Special Populations I ncluded or not in Clinical Trial
Development Programs ................................ ................................ ............45
Table26. Anaphylaxis................................ ................................ .............................. 47
Table27. Vaccine-Associated Enhanced Disease (VAED), including
Vaccine-Associated Enhanced Respiratory Disease (VAERD) ...............50
Table28. Use in Pregnancy and Lactation ................................ ............................... 53
Table29. Vaccine Effectiveness ................................ ................................ ...............54
Table30. Use in Paediatric Individuals <12 Years of Age................................ ......55
Table31. Incidence, Prevalence, and Mortality of COVID -19 as of
03March2021 ................................ ................................ ......................... 57
Table32. Distributions of Cases (n=21,895,936) and Deaths (n=382,009) b y
Age, Sex, Race, and Cross -Tabulated Age and Sex – United States
as of 08March 2021,................................ ................................ ................ 59
Table33. Risk for COVID -19 Infection, Hospitalization, and Death by Age
Group and b y Race/Ethnicity ................................ ................................ ..61
Table34. Hazard Ratios and 95% Conf idence Intervals for COVID -19-related
Death................................ ................................ ................................ .........62
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Page 5Table35. Signs and s ymptoms among 291 pediatric (age <18 y ears) and
10,944 adult (age 18–64 years) patients with laboratory confirmed
COVID-19 —United States, 12 February –2April 2020 ......................... 64
Table36. Preconditions among COVID -19 Patients in EU/EEA and UK, by
Severity of Disease. Case -based Data from TESS y Produced 04
March 2021 ................................ ................................ ............................... 66
Table 37. Comorbidit ies in individuals tested for COVID -19 in the
Providence St. Joseph Health Sy stem –States of California,
Oregon, and Washington, 01 March–31 December 2020 ........................ 67
Table38. Ongoing Safet y Concerns ................................ ................................ .........68
Table39. Action Plan for Important I dentified Risk “Anaphy laxis”....................... 70
Table40. Action Plan for Important Potential Risk “Vaccine -associated
enhanced disease (VAED) including Vaccine -associated enhanc ed
respiratory disease (VAERD)” ................................ ................................ .72
Table41. Action Plan for Missing Information “Use in Pregnancy and
Lactation” ................................ ................................ ................................ .74
Table42. Action Plan for Missing Information “Vaccine Effectiveness” ...............76
Table43. Action Plan for Missing Information “Use in Paediatric Individuals
<12Years of Age” ................................ ................................ .................... 76
Table44. Summary of Safety Concerns and Action Plans ................................ .......80
LIST OF FIGURES
Figure1. Age-Sex distribution of COVID-19 Cases as Different Levels of
Severity, EU/EEA and UK. Case -based Data from TESSy produced
on 04 March 2021a................................ ................................ .................... 59
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Page 6LIST OF ABBREVIATIONS
Abbreviation Definition of Term
AE adverse event
AESI adverse event of special interest
A:G albumin:globulin
ARDS acute respiratory distress sy ndrome
BALB/c bagg albino
BC Brighton Collaboration
BEST biologics effectiveness and safet y
BLA biologics license application
BMI body mass index
BP blood pressure
CD4, CD8 cluster of differentiation -4, 8
CDC Centers for Disease Control and Prevention
CI confidence interval
COPD chronic obstructive pulmonary disease
COVID-19 coronavirus disease 2019
CSR clinical study report
CT clinical trial
DART developmental and reproductive toxicology
DCA data capture aid
DLP data-lock point
DoD Department of Defense
ECDC European Center for Disease Control
EEA European Economic Area
eGFR estimated glomerular filtration rate
EU European Union
EUA emergency use authorization
FDA (US) Food and Drug Administration
GLP good laboratory practice
HbA1c glycated hemoglobin
HBV hepatitis b virus
HCV hepatitis c virus
HIV human immunodeficiency virus
IA interim analy sis
ICU intensive care unit
IFN interferon
IL-4 interleukin -4
IM intramuscular(l y)
IMD index of multiple deprivation
IND investigational new drug
LNP lipid nanoparticle
MAA marketing authorization applicant
MedDRA Medical Dictionary for Regulatory Activities
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Page 7Abbreviation Definition of Term
MERS-CoV Middle East respiratory syndrome–coronavirus
MHS Military Health Sy stem
MIS-C multisystem inflammatory syndrome in children
modRNA nucleoside -modified messenger ribonucleic acid
mRNA messenger ribonucleic acid
NDA new drug application
NHP nonhuman primate
NICE National Institute for Health and Care Excellence
OCS oral corticosteroids
PK pharmacokinetic
PVP pharmacovigilance plan
RBC red blood cell
RNA ribonucleic acid
RR relative risk
SAE serious adverse event
SARS severe acute respiratory syndrome
SARS-CoV-1 severe acute respiratory syndrome coronavirus 1
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
siRNA small-interfering RNA
SMQ standardised MedDRA query
Tdap tetanus, diphtheria, and acellular pertussis
TESSy TheEuropean Surveillance Sy stem
Th1 T helper cell type 1
Th2 T helper cell type 2
UK United Kingdom
US United States
USP United States pharmacopeia
V8 variant 8
V9 variant 9
VAED vaccine-associated enhanced disease
VAERD vaccine-associated enhanced respiratory disease
WBC white blood cells
WHO World Health Organization
WOCBP women of childbearing potential
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Page 81.INTRODUCTION
1.1.Product Details
Table1.Product Detailsa
Product COVID-19 mRNA Vaccine (nucleoside modified), herein after referred to as
BNT162b2 isanucleoside -modified messenger RNA –(modRNA)encoding
the viral spike (S) glycoprote in of severe acute respiratory syndrome
coronavirus ( SARS-CoV-2).
Brief description of the
productChemical class:
Nucleoside -modRNA formu lated in lipid particles .
Mechanism ofAction:
The modRNA in the BNT162b2 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.
Important information about its c omposition:
The BNT162b2 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 BNT162b2 contains 30 mcg of a nucleoside -modified
messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of
SARS-CoV-2.
Each dose of the BNT162b2 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, 0.0 7
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 BNT162b2 does not contain preservative.
The vial stoppers are not made w ith natural rubber latex.
Indication Proposed:
Active immunization to prevent COVID -19 caused by SARS -CoV-2 in
individuals 16 years of age and older.
Dosage and route of
administrationProposed:
Series of two doses (0.3 mL each) 3 weeks apart ,intramuscular ly.
a.COVID-19 mRNA vaccine (nucleoside -modified) USPrescribing Information
Data Lock
Point / Data
cut-off:16 years
and older13 March 2021 (Pfizer Clinical Database)
23October 2020 (BioNTech Clinical Database)
28 February 2021 (Pfizer Safety Database )
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Page 92.SAFETY SPECIFICATION
2.1.Elements of the Safety Specification
2.1.1.Non-Clinical
Nonclinical evaluation of BNT162b2 included pharmacology (mouse immunogenicity and
NHP immunogenicit y and challenge studies), pharmacokinetic (series of biodistribution,
metabolism and pharmacokinetic studies), and toxicity (2 GLP rat repeat -dose toxicity and a
GLP DART) studies in vitro and invivo. No additional toxicity studies are planned for
BNT162b2 .
Nonclinical studies in mice and NHP for BNT162b2 demonstrated both a strong neutralizing
antibody response and a Th1 -type CD4+and an IFN +CD8+T-cell response. The Th1
profile is char acterized by a strong IFNγ, but not IL -4, response indicating the absence of a
potentially deleterious Th2 immune response and is a pattern favored for vaccine safet y and
efficacy.1 Rhesus macaques (Study VR-VRT-10671) that had received two IM
immunizatio ns with 100 µg BNT162b2 or saline 21 day s apart were challenged with 1.05 ×
106plaque forming units of SARS- CoV-2 (strain USA -WA1/2020), split equally between the
intranasal and intratracheal routes.2 BNT162b2 provided complete protection from the
presence of detectable viral RNA in the lungs compared to the saline control with no clinical,
radiological or histopathological evidence of vaccine -elicited disease enhancement.
An intravenous rat PK study , using an LNP with the identical lipid composition
asBNT162b2 , demonstrated that the novel lipid excipients in the L NP formulation, AL C-
0315 and AL C-0159, distribute from the plasma to the liver. While there was no detectable
excretion of either lipid in the urine, the percent of dose excreted unchanged in feces was
~1% for ALC -0315 and ~50% for ALC -0159. Further studies indicated metabolism played a
role in the elimination of AL C-0315. Biodistribution was assessed using luciferase
expression as a surrogate reporter formulated like BNT162b2 , with the identi cal lipid
composition. After IM injection of the LNP- formulated RNA encoding luciferase in
BALB/c mice, luciferase protein expression was demonstrated at the site of injection 6 hours
post dose and expression decreased over time to almost reach background levels after 9 day s.
Luciferase was detected to a lesser extent in the liver; expression was present at 6 hours after
injection and was not detected b y 48hours after injection. After IM administration of a
radiolabeled LNP -mRNA formulation containing A LC-0315 and ALC -0159 to rats, the
percent of administered dose was also greatest at the injection site. Outside of the injection
site, total recovery of radioactivity was greatest in the liver and much lower in the spleen,
with very little recovery in the adrenal glands and ovaries. The metabolism of AL C-0315
and ALC-0159 was evaluated in blood, liver microsomes, S9 fractions, and hepatocy tes from
mice, rats, monkey s, and humans. The in vivo metabolism was examined in rat plasma,
urine, feces, and liver s amples from the PK study. AL C-0315 and ALC -0159 are
metabolized by hydrolytic metabolism of the ester and amide functionalities, respectivel y,
and this hy drolytic metabolism is observed across the species evaluated.
In GLP toxicity studies, two variants o f the BNT162b2 candidate were tested, designated
“variant 8” and “variant 9” (V8 and V9, respectively ). The variants differ only in their codon
optimization sequences which are designed to improve antigen expression, otherwise the
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Page 10amino acid sequences of the encoded antigens are identical. BNT162b2 (V9) was evaluated
clinically and submitted for application. Two GLP-compliant repeat -dose toxicity studies
were performed in Wistar Han rats; one with each variant. Both studies were 17 day s in
duration with a 3-week recovery period. A GL P-compliant DART study in Wistar Han rats
has also been completed. Safety pharmacology , genotoxicity and carcinogenicity studies
have not been conducted, in accordance with the 2005 WHO vaccine guideline.3
The IMroute of exposure was selected for nonclinical investigations as it is the clinical route
of administration. Rats were selected as the toxicology test species as they demonstrated an
antigen-specific immune response to the vaccine and are routinel y used for regula tory
toxicity studies with an extensive historical safety database.
Administration of up to 100 µg BNT162b2 by IM injection to male and female Wistar Han
rats once every week, for a total of 3 doses, was tolerated without evidence of sy stemic
toxicity. Expected inflammatory responses to the vaccine were evident such as edema and
erythema at the injection sites, transient elevation in body temperature, elevations in WBC
count and acute phase reactants, and lower A:G ratios. I njection site reactions were co mmon
in all vaccine -administered animals and were greater after boost immunizations. Changes
secondary to inflammation included slight and transient reduction in body weights and
transient reduction in reticulocytes, platelets and RBC mass parameters. De creased
reticulocy tes were reported in rats treated with the licensed LNP- siRNA pharmaceutical
Onpattro™ (NDA # 210922) but have not been observed in humans treated with this
biotherapeutic4suggesting this is a species -specific effect. Decreased platele t counts were
noted after repeat administration, but were small in magnitude of change, likely related to
inflammation -related platelet activation and consumption, and unassociated with other
alterations in hemostasis. Elevated levels of gamma -glutamyl transferase were observed in
the first repeat -dose toxicity study with BNT162b2 (V8) without evidence of cholestasis or
hepatobiliary injury but was not recapitulated in the second repeat dose- toxicity study with
BNT162b2 (V9), the final clinical candidate. All changes in clinical pathology parameters
and acute phase proteins were reversed at the end of the recovery phase for BNT162b2 , with
the exception of low magnitude higher red cell distribution width (consistent with a
regenerative ery throid response) a nd lower A:G ratios (resulting from acute phase response)
in animals administered BNT162b2 . Macroscopic pathology and organ weight changes were
also consistent with immune activation and inflammatory response and included increased
size and/or weight of d raining iliac l ymph nodes and spleen. Vaccine -related microscopic
findings at the end of the dosing phase consisted of edema and inflammation in injection sites
and surrounding tissues, increased cellularity in the draining iliac l ymph nodes, bone marrow
and spleen and hepatocyte vacuolation in the liver. Vacuolation of periportal hepatocy tes,
the only test article -related liver microscopic finding, was not associated with any
microscopic evidence of hepatic injury or hepatic functional effects (i.e., liv er functional
enzymes were not elevated) and may be associated with hepatocy te uptake of the LNP
lipids.5 Microscopic findings at the end of the dosing phase were partially or completel y
recovered in all animals at the end of the 3 -week recovery period fo r BNT162b2 . A robust
immune response was elicited to the BNT162b2 antigen.
Administration of BNT162b2 to female rats twice before the start of mating and twice during
gestation at the human clinical dose (30 µg) was associated with non -adverse effects (bod y
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Page 11weight, food consumption and effects localized to the injection site) after each dose
administration. However, there were no effects of BNT162b2 administration on mating
performance, fertility , or any ovarian or uterine parameters in the F0 female rats nor on
embryo-fetal or postnatal survival, growth, or development in the F1 offspring. An immune
response was confirmed in F0 female rats following administration of each vaccine candidate
and these responses were also detectable in the F1 offspring (fetus es and pups).
In summary , the nonclinical safety findings related to BNT162b2 administration primarily
represent an expected immune reaction to vaccine administration and are clinically
manageable or acceptable risks in the intended population. The key safety findings regarding
BNT162b2 from nonclinical studies and their relevance to human usage are presented in
Table2. There was no evidence of vaccine -elicited disease enhancement.
Table2. Key Safety Findings and Relevance to Human Usage
Key Safety findings from Nonclinical StudiesaRelevance to Hum an Usage
Pharmacology
NHP Challenge Model
No evidence of vaccine -elicited disease
enhancement.Suggests low risk of vaccine- enhanced disease
in humans; being investigated in CTs.
Toxicity
Injection site reactions:
Injection site reactions were common and
reversible or showed signs of reversibility at the
end of the 3 -week recovery period in nonclinical
studies. In common with other vaccines, BNT162b2
administration has the potential to generate
injection site reac tions such as edema and
erythema at the injection sites.
Inflammation and immune activation:
Evidence of inflammation or immune activation
was common, reversible, and included transiently
higher body temperature, higher circulating
WBCs, and higher acute phase reactants.
Secondarily, transiently low er body weights,
reticulocytes, platelets, and RBC mass parameters
were observed.In common with all vaccines, BNT162b2
administration has the potential to generate
inflammation which can lead to increased
body temperature, higher circulating WBCs
and higher acute phase proteins.
Decreased reticulocytes have not been
observed in humans treated w ith the
LNP-siRNA pharmaceutical Onpattro4,
suggesting this finding in rats is a species -
specific effect.
BNT162b2administration has the potential to
transiently decrease platelets and RBC mass
parameters. These slight decreases are not
likely to be clinically m eaningful due to their
small magnitude.
Developmental and Reproductive Toxicity
No vaccine -related effects on female fertility or the
development of fetuses or offspring were observed
in a DART study of BNT162b2in rats.No effects are anticipated in WOCBP,
pregnant w omen or their offspring.
a.Safety pharmacology, genotoxicity, and carcinogenicity studies were not conducted, in accordance w ith
2005 WHO vaccine guideline, as they are generally not considered necessary to support development and
licensure of vaccines for infectious diseases.3 In addition, the components of the va ccine construct are lipids
and RNA and are not expected to have carcinogenic or genotoxic potential.
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Page 122.1.2.Clinical
2.1.2.a. Limitations of the Human Safety Database
The pivotal study was initially planned to enroll approximately 30,000 participants, which
would have a probability of 78% of detecting an AE with a frequency of 0.01% (1/1000) and
a probability of 95% of detecting an AE with a frequency of 0.02% (1/500). The protocol
was amended to enroll approximately 46,000participants, which would slightly enhance the
ability to detect AEs. However, rarer events might not be detected.
Participants in the pivotal study were initially planned to be followed for up to 24 months in
order to assess the potential for late -occurring adverse reactions, such as the theoretical risk
of VAED. After completing the final efficacy analysis with vaccine efficacy shown to be
95%, and obtaining regulatory authorization to vaccinate in many countries,
Pfizer-BioNTech started to unblind all participants to determine those randomized to placebo
so that they could be offered vaccine in accordance with local authorization. To date, most
placebo subjects have been unblinded to receive act ive vaccine at or prior to 6 months after
the second dose, therefore, a placebo group for comparison of safety data is only available
for up to 6 months post Dose 2.
2.1.2.a.1. Clinical Trial Exposure
Brief Overview of Development
BioNTech is conducting a first-in-human dose level –finding Phase 1/2 study (BNT162 -01) in
Germany to gather safet y and immunogenicit y data to enable evaluation of 4 vaccines
candidates individually to inform the overall clinical development of a BNT162b2 .
BNT162-01 isnot conducted under the US IND application but is being conducted under a
German Clinical Trial Application.
Four vaccine candidates were evaluated in Stud y BNT162-01. Based on safet y and
immunogenicit y results from this study , 2 vaccine candidates, BNT162b1 and BNT162b2,
wereselected for evaluation in Study C4591001, which is a Phase 1/2/3 randomized,
placebo-controlled, observer -blind, dose -finding, vaccine candidate -selection, and efficacy
study in healthy adults (conducted under IND 019736).
Phase 1 of Study C4591001 compr ised dose- level–finding evaluations of the 2 selected
vaccine candidates; multiple dose levels (some corresponding to those evaluated in
StudyBNT162-01) were evaluated. Stud y vaccine was administered using the same 2 -dose
schedule as in Study BNT162 -01 (21 days apart). Dose levels were administered first to an
18-to 55-year age cohort, then to a 65 -to 85-year age cohort.
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Page 13Both vaccine candidate constructs were safe and well tolerated. BNT162b2 at the 30-µg
dose level was selected and advanced to the Phase 2/3 expanded cohort and efficacy
evaluation primaril y because:
the reactogenicit y profile for BNT162b2 was more favorable than BNT162b1 in both
younger and older adults with similar immunogenicity results;
in the NHP challenge study (VR-VTR-10671,see Section 2.1.1), a trend toward
earlier clearance of BNT162b2 was observed in the nose.
Phase 2 of the stud y(forwhichenrollment has completed) comprised the evaluation of safet y
and immunogenicit y data for the first 360 participants (180 from the active vaccine group
and 180 from theplacebo group ,with each group dividedbetween the younger and older age
cohorts)entering the study after completion of Phase 1.
The Phase 3 part of the study (which is ongoing) evaluates the efficacy and safet y in all
participants (including the first 360 participants from Phase 2). Phase 3 introduced:
enrollment ofparticipants 16 to 17 years of ageto be evaluated with the 18 -to 55-
year-old cohort,
enrollment of a 12-to 15-year-old cohort ,
immunogenicit y data from the 12-to15-year-old cohort ( Table3,Table5,Table11,
Table13, Table15, and Table17),anticipated to bridgeto the16-to 25-year-old
cohort.
Participants in the pivotal study were initially planned to be followed for up to 24 months in
order to assess the potential for late -occurring adverse reactions, such as the theoretical risk
of VAED including VAERD . After completing the final efficacy analysis with vaccine
efficacy shown to be 95%, and obtaining regulatory authorisation to vaccinate in many
countries, Pfizer-BioNTech started to unblind all participants to determine those participants
randomised to placebo so that they could be offered vaccine in acco rdance with local
authorisation. To date, most placebo subjects have been unblinded to receive active vaccine
at or prior to 6 months after the second dose, therefore, a placebo group for comparison of
safety data is onl y available for up to 6 months post Dose 2.
The initial efficacy analysis on the 16 y ears and older population wasevent-driven, with
prespecified interim analy ses after accrual of at least 62, 92, and 120 cases and a final
analysis at 164 cases.
A further efficacy analysis has been conduct ed on 12-to ≤15-year-old cohort participants and
on 16 years and older participants cohort participants reported b y 13 March 2021.
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Page 14Ongoing BNT162b2 studies at the cut-offof the clinical database (13 March 2021) also
include:
C4591005: A phase 1/2 study t o evaluate the safety, tolerability, and immunogenicity
of an RNA vaccine candidate against COVID- 19 in healthy Japanese adults.
One hundred sixty participants were randoml y assigned in a 3:1 ratio to study
intervention (candidate vaccine: 120, placebo: 4 0).
C4591015: A phase 2/3 study to evaluate the safety, tolerability, and immunogenicity
of SARS-CoV-2 RNA vaccine candidate (BNT162b2) against COVID- 19 in healthy
pregnant women 18 years of age and older.
Approximately 4000 pregnant women at 24 to 34 we eks gestation are being
randomized in a 1:1 ratio to vaccine or placebo.
C4591017: A phase 3 study to evaluate the safety, tolerability, and immunogenicity of
multiple production lots and dose levels of BNT162b2 against COVID -19 in healthy
participants.
Approximately 340 participants were randoml y assigned to each of 3 US lots and to a
20-μg arm and approximately 170 participants were randoml y assigned an EU lot, for
a total of approximately 1530 randomized participants in 5 study arms.
Clinical Trial Exp osure
Population for anal ysis of CTs data in this US Pharmacovigilance Plan includes the
following 2 studies:
C4591001: Phase 1/2/3, placebo -controlled, randomized, observer -blind, dose finding,
study to evaluate the safety, tolerability, immunogenicity, and efficacy of SARS -CoV-2
RNA vaccine candidates against COVID -19 in healthy individuals .
BNT162-01: A multi-site, phase I/II, 2- part, dose -escalation trial investigating the safety
and immunogenicity of four prophylactic SARS -CoV-2 RNA vaccines against CO VID-19
using different dosing regimens in healthy adults.
Participants 16 years of age and older
At the cut -offdate of 13 March2021, a total of 46,505 participants were vaccinated in the
BNT162b2 clinical development program:
21,745 participants received 2 doses and 360received 1 dose of BNT162b2 during the
blinded follow -up period; 96 participants from study BNT162-01received 2 doses of the
vaccine.
19,647 participants, who originall y received placebo, then received 1 dose of BNT162b2
in the Open-Label Follow -up period after unblinding. (none from study BNT162 -01).
Exposure to BNT162b2 for participants aged 16 years and older in the 2 ongoing studies by
number of doses, and demographic characteristics is shown in Table3through Table21.
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Page 15In addition, exposure in clinical studies in special populations is provided in Table22and
Table23.
Participants 12 to 15years of age
At the cut -off date of 13 March 2021, a total of 2260participants were vaccinated in the
BNT162b2 clinical development program:
Clinical study exposure data for the 12 -to 15 years of age areprovided for the ongoing stud y
C4591001 at the cut-offdate of 13 March 2021.
In thisstudy
1124participants received 2 doses and 7 received 1 dose of BNT162b2 in the Blinded -
Placebo Controlled F ollow-up period.
49participants who originally received placebo, then received 1 dose of BNT162b2 in
the Open-Label Follow-up period after unblinding.
Exposure to BNT162b2 for participants aged 12 -to 15 years of age by number of doses and
demographic characteristics is shown in Table 3,Table5,Table11, Table13, Table15,
Table17. In addition, exposure in clinical studies in special populations is provided in
Table22andTable23.
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Page 16Table3.Exposure to BNT162b2 by Age Group and Dose (C4591001) –Blinded
Placebo-Controlled Follow -up Period
Age Group
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
≥12 years to ≤15 years
Vaccine 30 µg
1 Dose 7 7
2 Doses 1124 2248
Total 1131 2255
≥16 years to ≤17 years
Vaccine 30 µg
1 Dose 4 4
2 Doses 374 748
Total 378 752
≥18 years to ≤55 years
Vaccine 10 µg
2 Doses 12 24
Total 12 24
Vaccine 20 µg
2 Doses 12 24
Total 12 24
Vaccine 30 µg
1 Dose 267 267
2Doses 12438 24876
Total 12705 25143
>55 years to ≤64 years
Vaccine 30 µg
1 Dose 67 67
2 Doses 4341 8682
Total 4408 8749
≥65 years to ≤74 years
Vaccine 10 µg
2 Doses 12 24
Total 12 24
Vaccine 20 µg
2 Doses 9 18
Total 9 18
Vaccine 30 µg
1 Dose 17 17
2 Doses 3624 7248
Total 3641 7265
≥75 years to ≤84 years
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Page 17Table3.Exposure to BNT162b2 by Age Group and Dose (C4591001) –Blinded
Placebo-Controlled Follow -up Period
Age Group
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Vaccine 20 µg
2 Doses 3 6
Total 3 6
Vaccine 30µg
1 Dose 3 3
2 Doses 899 1798
Total 902 1801
≥85 years
Vaccine 30 µg
1 Dose 2 2
2 Doses 21 42
Total 23 44
Note: 30 μg includes data from phase 1 and phase 2/3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:42)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s912
Table4.Exposure to BNT162b2 by Age Group and Dose (C4591001) – Open-Label
Follow-up Period – Subjects Who Originally Received BNT162b2
Age Group
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
≥16 years to ≤17 years
Vaccine 30 µg
1 Dose 3 3
≥18 years to ≤55 years
Vaccine 30 µg
1 Dose 58 58
>55 years to ≤64 years
Vaccine 30 µg
1 Dose 17 17
≥65 years to ≤74 years
Vaccine 30 µg
1 Dose 8 8
≥75 years to ≤84 years
Vaccine 30 µg
1 Dose 1 1
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Page 18Table4.Exposure to BNT162b2 by Age Group and Dose (C4591001) – Open-Label
Follow-up Period – Subjects Who Originally Received BNT162b2
Age Group
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
≥85 years
Vaccine 30 µg
1 Dose 2 2
Note: 30 μg includes data from phase 1 and phase 2/3.
Note: Subjects who received 2ndDose of BNT162b2 after unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s9123
Table5.Exposure to BNT162b2 by Age Group and Dose (C4591001) –Open-Label
Follow-up Period – Subjects Who Originally Received Placebo and Then
Received BNT162b2 After Unblinding
Age Group
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
≥12 years to ≤15 yearsa
Vaccine 30 µg
1 Dose 30 30
2 Doses 19 38
Total 49 68
≥16 years to ≤17 years
Vaccine 30 µg
1Dose 107 107
2 Doses 186 372
Total 293 479
≥18 years to ≤55 years
Vaccine 30 µg
1 Dose 2713 2713
2 Doses 8419 16838
Total 11132 19551
>55 years to ≤64 years
Vaccine 30 µg
1 Dose 655 655
2 Doses 3330 6660
Total 3985 7315
≥65 years to ≤74 years
Vaccine 30 µg
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Page 19Table5.Exposure to BNT162b2 by Age Group and Dose (C4591001) –Open-Label
Follow-up Period – Subjects Who Originally Received Placebo and Then
Received BNT162b2 After Unblinding
Age Group
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
1 Dose 128 128
2 Doses 3286 6572
Total 3414 6700
≥75 years to ≤84 years
Vaccine 30 µg
1 Dose 23 23
2 Doses 783 1566
Total 806 1589
≥85 years
Vaccine 30 µg
1 Dose 1 1
2 Doses 16 32
Total 17 33
Note: 30 μg includes data from phase 1 and phase 2/3.
a.Includes subjects who became eligible for unblinding at 16 years of age, confirmed to have received
placebo originally and then received BNT162b2 post unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MA R2021) Output File:
./nda2 unblinded/C4591001 PVP BLA/adsl s9122
Table6.Exposure to BNT162b2 by Age Group and Dose (BNT162 -01)
Age Group
Dose
Exposure (Number of Doses
Received)No. of Subjects
Exposed to BNT162b2Total No. of Vaccine Doses
≥18 years to ≤ 64years
Vaccine 1 µg
1 Dose 1 1
2 Doses 11 22
Total 12 23
Vaccine 3 µg
1 Dose 0 0
2 Doses 12 24
Total 12 24
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Page 20Table6.Exposure to BNT162b2 by Age Group and Dose (BNT162 -01)
Age Group
Dose
Exposure (Number of Doses
Received)No. of Subjects
Exposed to BNT162b2Total No. of Vaccine Doses
Vaccine 10 µg
1 Dose 1 1
2 Doses 11 22
Total 12 23
Vaccine 20 µg
1 Dose 0 0
2 Doses 17 34
Total 17 34
Vaccine30 µg
1 Dose 0 0
2 Doses 18 36
Total 18 36
≥65 yearsto ≤74 years
Vaccine 1 µg
1 Dose 0 0
2 Doses 0 0
Total 0 0
Vaccine 3 µg
1 Dose 0 0
2 Doses 0 0
Total 0 0
Vaccine 10 µg
1 Dose 0 0
2 Doses 5 10
Total 5 10
Vaccine 20 µg
1 Dose 0 0
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Page 21Table6.Exposure to BNT162b2 by Age Group and Dose (BNT162 -01)
Age Group
Dose
Exposure (Number of Doses
Received)No. of Subjects
Exposed to BNT162b2Total No. of Vaccine Doses
2 Doses 6 12
Total 6 12
Vaccine 30 µg
1 Dose 0 0
2 Doses 6 12
Total 6 12
≥75 years to ≤84 years
Vaccine 1 μg
1 Dose 0 0
2 Doses 0 0
Total 0 0
Vaccine 3 μg
1 Dose 0 0
2 Doses 0 0
Total 0 0
Vaccine 10 µg
1 Dose 0 0
2 Doses 1 2
Total 1 2
Vaccine 20 µg
1 Dose 0 0
2 Doses 1 2
Total 1 2
Vaccine 30 µg
1 Dose 0 0
2 Doses 0 0
Total 0 0
PFIZER CONFIDENTIAL SDTM Creation: 24NOV2020 (15:06) Source Data: adsl Table Generation: 10MAR2021
(11:32) (Cutoff date:23OCT2020, Snapshot Date: 23OCT2020)
Output File: ex_b2_age_dose2 rtf
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Page 22Table7.Exposure to BNT162b2 by Dose (Totals) (C4591001) –Blinded Placebo -
Controlled Follow -up Period
Dose
Exposure (Number of
Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Vaccine 10 µg
2 Doses 24 48
Total 24 48
Vaccine 20 µg
2 Doses 24 48
Total 24 48
Vaccine 30 µg
1 Dose 367 367
2 Doses 22821 45642
Total 23188 46009
Note: 30 μg includes data from phase 1 and phase 2/3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s922
Table8.Exposure to BNT162b2 by Dose (Totals) (C4591001) – Open-Label Follow -
up Period – Subjects Who Originally Received BNT162b2
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Vaccine 30 µg
1 Dose 89 89
Note: 30 μg includes data from phase 1 and phase 2/3.
Note: Subjects who received 2ndDose of BNT162b2 after unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 PVP BLA/adsl s9223
Table9.Exposure to BNT162b2 by Dose (Totals) (C4591001) –Open-Label Follow -
up Period – Subjects Who Originally Received Placebo and Then Received
BNT162b2 After Unblinding
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Vaccine 30 µg
1 Dose 3657 3657
2 Doses 16039 32078
Total 19696 35735
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Page 23Table9.Exposure to BNT162b2 by Dose (Totals) (C4591001) –Open-Label Follow -
up Period – Subjects Who Originally Received Placebo and Then Received
BNT162b2 After Unblinding
Dose
Exposure (Number of Doses Received)Number of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Note: 30 μg includes data from phase 1 and phase 2/3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 PVP BLA/adsl s9222
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Page 24Table10.Exposure to BNT162b2 by Dose (Totals) (BNT162-01)
Dose
Exposure (Number of Doses Received)No. of Subjects
Exposed to
BNT162b2Total No. of Vaccine Doses
Vaccine 1 µg
1 Dose 1 1
2 Doses 11 22
Total 12 23
Vaccine 3 µg
1 Dose 0 0
2 Doses 12 24
Total 12 24
Vaccine 10 µg
1 Dose 1 1
2 Doses 23 46
Total 24 47
Vaccine 20 µg
1 Dose 0 0
2 Doses 24 48
Total 24 48
Vaccine 30 µg
1 Dose 0 0
2 Doses 24 48
Total 24 48
PFIZER CONFIDENTIAL SDTM Creation: 24NOV2020 (15:06) Source Data: adsl Table Generation: 10MAR2021
(11:49) (Cutoff date:23OCT2020, Snapshot Date: 23OCT2020)
Output File: ex_b2_dose.rtf
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Page 25Table11.Exposure to BNT162b2 by Dose, Age Group, and Gender (C4591001) –
Blinded Placebo -Controlled Follow -up Period
Number of Subjects Exposed
to BNT162b2Total Number of Vaccine
Doses
Dose
Age GroupMale Female Male Female
Vaccine 10 µg
≥18 years to ≤55 years 5 7 10 14
≥65 years to ≤74 years 2 10 4 20
Total 7 17 14 34
Vaccine 20 µg
≥18 years to ≤55 years 6 6 12 12
≥65 years to ≤74 years 4 5 8 10
≥75 years to ≤84 years 1 2 2 4
Total 11 13 22 26
Vaccine 30 µg
≥12 years to ≤15 years 567 564 1128 1127
≥16 years to ≤17 years 187 191 373 379
≥18 years to ≤55 years 6456 6249 12770 12373
>55 years to ≤64 years 2231 2177 4421 4328
≥65 years to ≤74 years 1934 1707 3858 3407
≥75 years to ≤84 years 511 391 1020 781
≥85 years 12 11 23 21
Total 11898 11290 23593 22416
Note: 30 μg includes data from phase 1 and phase 2/3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s932
Table12.Exposure to BNT162b2 by Dose, Age Group, and Gender (C4591001) –
Open-Label Follow -up Period – Subjects Who Originally Received
BNT162b2
Number of Subjects
Exposed to BNT162b2Total Number of Vaccine
Doses
Dose
Age GroupMale Female Male Female
Vaccine 30 µg
≥16 years to ≤17 years 0 3 0 3
≥18 years to ≤55 years 24 34 24 34
>55 years to ≤64 years 12 5 12 5
≥65 years to ≤74 years 4 4 4 4
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Page 26Table12.Exposure to BNT162b2 by Dose, Age Group, and Gender (C4591001) –
Open-Label Follow -up Period – Subjects Who Originally Received
BNT162b2
Number of Subjects
Exposed to BNT162b2Total Number of Vaccine
Doses
Dose
Age GroupMale Female Male Female
≥75 years to ≤84 years 0 1 0 1
≥85 years 1 1 1 1
Total 41 48 41 48
Note: 30 μg includes data from phase 1 and phase 2/3.
Note: Subjects who received 2ndDose of BNT162b2 after unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s9323
Table13.Exposure to BNT162b2 by Dose, Age Group, and Gender (C4591001) –
Open-Label Follow -up Period – Subjects Who Originally Received Placebo
and Then Received BNT162b2 After Unblinding
Number of Subjects
Exposed to BNT162b2Total Number of Vaccine
Doses
Dose
Age GroupMale Female Male Female
Vaccine 30 µg
≥12 years to ≤15 yearsa26 23 36 32
≥16 years to ≤17 years 152 141 250 229
≥18 years to ≤55 years 5424 5708 9450 10101
>55 years to ≤64 years 1973 2012 3602 3713
≥65 years to ≤74 years 1801 1613 3530 3170
≥75 years to ≤84 years 495 311 976 613
≥85 years 13 4 25 8
Total 9884 9812 17869 17866
Note: 30 μg includes data from phase 1 and phase 2/3.
a.Includes subjects who became eligible for unblinding at 16 years of age, confirmed to have received
placebo originally and then received BNT162b2 post unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output F ile:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s932_open
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Page 27Table14.Exposure to BNT162b2 by Dose, Age Group, and Gender (BNT162- 01)
No. of Subjects Exposed to
BNT162b2Total No. of Vaccine Doses
Dose
Age GroupMale Female Male Female
Vaccine1µg
≥18 years to ≤ 64 years7 5 14 9
≥65 years to ≤74 years0 0 0 0
≥75 years to ≤84 years0 0 0 0
Total7 5 14 9
Vaccine3µg
≥18 years to ≤64 years5 7 10 14
≥65 years to ≤74 years0 0 0 0
≥75 years to ≤84 years0 0 0 0
Total5 7 10 14
Vaccine10µg
≥18 years to ≤ 64 years 8 10 16 19
≥65 years to ≤74 years 3 2 6 4
≥75 years to ≤84 years 1 0 2 0
Total12 12 24 23
Vaccine20µg
≥18 years to ≤ 64 years 7 10 14 20
≥65 years to ≤74 years 1 5 2 10
≥75 years to ≤84 years 0 1 0 2
Total 8 16 16 32
Vaccine30µg
≥18 years to ≤ 64 years 10 8 20 16
≥65 years to ≤74 years 2 4 4 8
≥75 years to ≤84 years 0 0 0 0
Total 12 12 24 24
PFIZER CONFIDENTIAL SDTM Creation: 24NOV2020 (15:06) Source Data: adsl Table Generation: 10MAR2021
(11:53) (Cutoff date:23OCT2020, Snapshot Date: 23OCT2020)
Output File: ex_b2_age_dose_sex rtf
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FDA-CBER-2021-5683-0950798
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Page 28Table15.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Blinded Placebo -Controlled Follow -up Period
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
≥12 years to ≤15 years
Vaccine30µg
Racial origin
White 971 1937
Black or African American 52 103
Asian 72 143
American Indian or Alaska Native 4 8
Native Haw aiian or other Pacific Islander 3 6
Multiracial 23 46
Not reported 6 12
Total 1131 2255
Ethnic origin
Hispanic/Latino 132 263
Non-Hispanic/non -Latino 997 1988
Not reported 2 4
Total 1131 2255
≥16 years to ≤17 years
Vaccine 30 µg
Racial origin
White 309 614
Black or African American 30 60
Asian 22 44
American Indian or Alaska Native 4 8
Native Haw aiian or other Pacific Islander 3 6
Multiracial 10 20
Total 378 752
Ethnic origin
Hispanic/Latino 49 98
Non-Hispanic/non -Latino 329 654
Total 378 752
≥18 years to ≤55 years
Vaccine 10 µg
Racial origin
White 11 22
Asian 1 2
Total 12 24
Ethnic origin
Hispanic/Latino 1 2
Non-Hispanic/non -Latino 11 22
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950799
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Page 29Table15.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Blinded Placebo -Controlled Follow -up Period
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Total 12 24
Vaccine 20 µg
Racial origin
White 10 20
Black or African American 2 4
Total 12 24
Ethnic origin
Hispanic/Latino 1 2
Non-Hispanic/non -Latino 11 22
Total 12 24
Vaccine 30 µg
Racial origin
White 9923 19637
Black or African American 1400 2764
Asian 683 1358
American Indian or Alaska Native 161 311
Native Haw aiian or other Pacific Islander 40 80
Multiracial 427 851
Not reported 71 142
Total 12705 25143
Ethnic origin
Hispanic/Latino 4000 7874
Non-Hispanic/non -Latino 8650 17160
Not reported 55 109
Total 12705 25143
>55 years to ≤64 years
Vaccine 30 µg
Racial origin
White 3719 7388
Black or African American 430 849
Asian 135 267
American Indian or Alaska Native 30 58
Native Haw aiian or other Pacific Islander 8 15
Multiracial 76 152
Not reported 10 20
Total 4408 8749
Ethnic origin
Hispanic/Latino 965 1903
Non-Hispanic/non -Latino 3413 6786
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950800
BNT162b2
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Page 30Table15.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Blinded Placebo -Controlled Follow -up Period
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Not reported 30 60
Total 4408 8749
≥65 years to ≤74 years
Vaccine 10 µg
Racial origin
White 12 24
Total 12 24
Ethnic origin
Non-Hispanic/non -Latino 12 24
Total 12 24
Vaccine 20 µg
Racial origin
White 9 18
Total 9 18
Ethnic origin
Non-Hispanic/non -Latino 9 18
Total 9 18
Vaccine 30 µg
Racial origin
White 3272 6528
Black or African American 219 437
Asian 82 164
American Indian or Alaska Native 22 44
Native Haw aiian or other Pacific Islander 6 12
Multiracial 30 60
Not reported 10 20
Total 3641 7265
Ethnic origin
Hispanic/Latino 583 1158
Non-Hispanic/non -Latino 3038 6067
Not reported 20 40
Total 3641 7265
≥75 years to ≤84 years
Vaccine 20 µg
Racial origin
White 3 6
Total 3 6
Ethnic origin
Non-Hispanic/non -Latino 3 6
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950801
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Page 31Table15.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Blinded Placebo -Controlled Follow -up Period
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Total 3 6
Vaccine 30 µg
Racial origin
White 838 1673
Black or African American 22 44
Asian 31 62
American Indian or Alaska Native 3 6
Native Haw aiian or other Pacific Islander 1 2
Multiracial 7 14
Total 902 1801
Ethnic origin
Hispanic/Latino 107 213
Non-Hispanic/non -Latino 789 1576
Not reported 6 12
Total 902 1801
≥85 years
Vaccine 30 µg
Racial origin
White 20 38
Asian 1 2
American Indian or Alaska Native 1 2
Multiracial 1 2
Total 23 44
Ethnic origin
Hispanic/Latino 2 4
Non-Hispanic/non -Latino 21 40
Total 23 44
Note: 30 μg includes data from phase 1 and phase 2/3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s942
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950802
BNT162b2
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Page 32Table16.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who Originally
Received BNT162b2
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
≥16 years to ≤17 years
Vaccine 30 µg
Racial origin
White 3 3
Total 3 3
Ethnic origin
Non-Hispanic/non -Latino 3 3
Total 3 3
≥18 years to ≤55 years
Vaccine 30 µg
Racial origin
White 46 46
Black or African American 2 2
Asian 2 2
American Indian or Alaska Native 8 8
Total 58 58
Ethnic origin
Hispanic/Latino 31 31
Non-Hispanic/non -Latino 27 27
Total 58 58
>55 years to ≤64 years
Vaccine 30 µg
Racial origin
White 14 14
Asian 1 1
American Indian or Alaska Native 2 2
Total 17 17
Ethnic origin
Hispanic/Latino 10 10
Non-Hispanic/non -Latino 7 7
Total 17 17
≥65 years to ≤74 years
Vaccine 30 µg
Racial origin
White 8 8
Total 8 8
Ethnic origin
Hispanic/Latino 5 5
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950803
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Page 33Table16.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who Originally
Received BNT162b2
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Non-Hispanic/non -Latino 3 3
Total 8 8
≥75 years to ≤84 years
Vaccine 30 µg
Racial origin
White 1 1
Total 1 1
Ethnic origin
Non-Hispanic/non -Latino 1 1
Total 1 1
≥85 years
Vaccine 30 µg
Racial origin
White 2 2
Total 2 2
Ethnic origin
Non-Hispanic/non -Latino 2 2
Total 2 2
Note: 30 μg includes data from phase 1 and phase 2/3.
Note: Subjects who received 2ndDose of BNT162b2 after unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s9423
Table17.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who Originally
Received Placebo and Then Received BNT162b2 After Unblinding
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
≥12 years to ≤15 yearsa
Vaccine 30 µg
Racial origin
White 45 62
Asian 3 5
Multiracial 1 1
Total 49 68
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950804
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Page 34Table17.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who Originally
Received Placebo and Then Received BNT162b2 After Unblinding
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Ethnic origin
Hispanic/Latino 2 4
Non-Hispanic/non -Latino 47 64
Total 49 68
≥16 years to ≤17 years
Vaccine 30 µg
Racial origin
White 251 410
Black or African American 11 19
Asian 14 25
American Indian or Alaska Native 2 4
Native Haw aiian or other Pacific Islander 1 2
Multiracial 12 16
Not reported 2 3
Total 293 479
Ethnic origin
Hispanic/Latino 26 43
Non-Hispanic/non -Latino 266 434
Not reported 1 2
Total 293 479
≥18 years to ≤55 years
Vaccine 30 µg
Racial origin
White 8806 15340
Black or African American 1087 1899
Asian 619 1136
American Indian or Alaska Native 128 236
Native Haw aiian or other Pacific Islander 17 32
Multiracial 405 781
Not reported 70 127
Total 11132 19551
Ethnicorigin
Hispanic/Latino 3441 5300
Non-Hispanic/non -Latino 7635 14157
Not reported 56 94
Total 11132 19551
>55 years to ≤64 years
Vaccine 30 µg
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950805
BNT162b2
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Page 35Table17.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who Originally
Received Placebo and Then Received BNT162b2 After Unblinding
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Racial origin
White 3416 6271
Black or African American 331 592
Asian 120 227
American Indian or Alaska Native 35 67
Native Haw aiian or other Pacific Islander 4 7
Multiracial 63 120
Not reported 16 31
Total 3985 7315
Ethnic origin
Hispanic/Latino 901 1560
Non-Hispanic/non -Latino 3067 5724
Not reported 17 31
Total 3985 7315
≥65 years to ≤74 years
Vaccine 30 µg
Racial origin
White 3093 6076
Black or African American 187 360
Asian 78 154
American Indian or Alaska Native 20 39
Native Haw aiian or other Pacific Islander 6 12
Multiracial 22 43
Not reported 8 16
Total 3414 6700
Ethnic origin
Hispanic/Latino 547 1060
Non-Hispanic/non -Latino 2842 5590
Not reported 25 50
Total 3414 6700
≥75 years to ≤84 years
Vaccine 30 µg
Racial origin
White 752 1483
Black or African American 22 42
Asian 17 34
American Indian or Alaska Native 4 8
Multiracial 6 12
Not reported 5 10
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950806
BNT162b2
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CONFIDENTIAL
Page 36Table17.Exposure to BNT162b2 by Age Group, Dose, and Race/Ethnic Origin
(C4591001) – Open-Label Follow -up Period – Subjects Who Originally
Received Placebo and Then Received BNT162b2 After Unblinding
Age Group
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Total 806 1589
Ethnic origin
Hispanic/Latino 89 174
Non-Hispanic/non -Latino 706 1393
Not reported 11 22
Total 806 1589
≥85 years
Vaccine 30 µg
Racial origin
White 15 29
Asian 1 2
Multiracial 1 2
Total 17 33
Ethnic origin
Non-Hispanic/non -Latino 17 33
Total 17 33
Note: 30 μg includes data from phase 1 and phase 2/3.
a.Includes subjects who became eligible for unblinding at 16 years of age, confirmed to have received
placebo originally and then received BNT162b2 post unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12 :46)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s942_open
Table18.Exposure to BNT162b2 by Dose and Race/Ethnic Origin (C4591001) –
Blinded Placebo -Controlled Follow -up Period
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Vaccine 10 µg
Racial origin
White 23 46
Asian 1 2
Total 24 48
Ethnic origin
Hispanic/Latino 1 2
Non-Hispanic/non -Latino 23 46
Total 24 48
Vaccine 20 µg
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950807
BNT162b2
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Page 37Table18.Exposure to BNT162b2 by Dose and Race/Ethnic Origin (C4591001) –
Blinded Placebo -Controlled Follow -up Period
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Racial origin
White 22 44
Black or African American 2 4
Total 24 48
Ethnic origin
Hispanic/Latino 1 2
Non-Hispanic/non -Latino 23 46
Total 24 48
Vaccine 30 µg
Racial origin
White 19052 37815
Black or African American 2153 4257
Asian 1026 2040
American Indian or Alaska Native 225 437
Native Haw aiian or other Pacific Islander 61 121
Multiracial 574 1145
Not reported 97 194
Total 23188 46009
Ethnic origin
Hispanic/Latino 5838 11513
Non-Hispanic/non -Latino 17237 34271
Not reported 113 225
Total 23188 46009
Note: 30 μg includes data from phase 1 and phase 2/3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:47)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s952
Table19.Exposure to BNT162b2 by Dose and Race/Ethnic Origin (C4591001) –
Open-Label Follow -up Period – Subjects Who Originally Received
BNT162b2
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Vaccine 30 µg
Racial origin
White 74 74
Black or African American 2 2
Asian 3 3
American Indian or Alaska Native 10 10
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950808
BNT162b2
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Page 38Table19.Exposure to BNT162b2 by Dose and Race/Ethnic Origin (C4591001) –
Open-Label Follow -up Period – Subjects Who Originally Received
BNT162b2
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Total 89 89
Ethnic origin
Hispanic/Latino 46 46
Non-Hispanic/non -Latino 43 43
Total 89 89
Note: 30 μg includes data from phase 1 and phase 2/3.
Note: Subjects who received 2ndDose of BNT162b2 after unblinding.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:47)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 PVP BLA/adsl s9523
Table20.Exposure to BNT162b2 by Dose and Race/Ethnic Origin (C4591001) –
Open-Label Follow-up Period – Subjects Who Originally Received Placebo
and Then Received BNT162b2 After Unblinding
Dose
Race/Ethnic OriginNumber of Subjects
Exposed to BNT162b2Total Number of
Vaccine Doses
Vaccine 30 µg
Racial origin
White 16378 29671
Black or African American 1638 2912
Asian 852 1583
American Indian or Alaska Native 189 354
Native Haw aiian or other Pacific Islander 28 53
Multiracial 510 975
Not reported 101 187
Total 19696 35735
Ethnic origin
Hispanic/Latino 5006 8141
Non-Hispanic/non -Latino 14580 27395
Not reported 110 199
Total 19696 35735
Note: 30 μg includes data from phase 1 and phase 2/3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
27MAR2021 (12:47)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/adsl_s952_open
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950809
BNT162b2
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CONFIDENTIAL
Page 39Table21.Exposure to BNT162b2 by Dose and Race/Ethnic Origin (BNT162-01)
Dose
Race/Ethnic OriginNo. of Subjects Exposed to
BNT162b2Total No. of Vaccine Doses
Vaccine1µg
RacialOrigin
White 12 23
Total 12 23
EthnicOrigin
Non-Hispanic/non -Latino 12 23
Total 12 23
Vaccine3µg
RacialOrigin
White 12 24
Total 12 24
EthnicOrigin
Non-Hispanic/non -Latino 12 24
Total 12 24
Vaccine10µg
RacialOrigin
White 24 47
Total 24 47
EthnicOrigin
Non-Hispanic/non -Latino 24 47
Total 24 47
Vaccine20µg
RacialOrigin
White 24 48
Total 24 48
EthnicOrigin
Non-Hispanic/non -Latino 24 48
Total 24 48
Vaccine30µg
RacialOrigin
White 24 48
Total 24 48
EthnicOrigin
Non-Hispanic/non -Latino 24 48
Total 24 48
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950810
BNT162b2
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CONFIDENTIAL
Page 40Table21.Exposure to BNT162b2 by Dose and Race/Ethnic Origin (BNT162-01)
Dose
Race/Ethnic OriginNo. of Subjects Exposed to
BNT162b2Total No. of Vaccine Doses
Only race, ethnic origins collected on the case report form with a count of at least one in either column are displayed.
PFIZER CONFIDENTIAL SDTM Creation: 24NOV2020 (15:06) Source Data: adsl Table Generation: 10MAR2021
(12:27) (Cutoff date:23OCT2020, Snapshot Date: 23OCT2020)
Output File: ex_b2_dose_race rtf
Table22. Exposure to BNT162b2 (30 μg) by Special Population (C4591001) – Blinded
Placebo-Controlled Follow -up Period
Population Number of Subjects
Exposed
to BNT162b2 (30 μg)
(Na=23188)
nbTotal Number
of
Vaccine Doses
Subjects with any baseline comorbidity 10371 26487
AIDS/HIV 100 196
Any Malignancy + Metastatic Solid Tumor + Leukemia +
Lymphoma852 1696
Chronic Pulmonary Disease 1901 3774
Renal Disease 140 279
Rheumatic Disease 75 147
Mild Liver Disease + Moderate or Severe Liver Disease 154 302
Cerebrovascular Disease + Peripheral Vascular Disease +
Myocardial Infarction + Congestive Heart Failure651 1298
Dementia 7 14
Diabetes With/Without Chronic Complication 1706 3385
Hemiplegia or Paraplegia 4 8
Peptic Ulcer Disease 63 126
Obese 7689 15262
Note: Comorbidity is based on Charlson Comorbidity Index categories. Participants identified as belonging to
these categories were identified by medical history data collected during the study.
Note: 30 μg includes data from phase 1 and phase 2/3.
Note: Hemiplegia or Parapl egia only includes preferred terms Hemiplegia and Paraplegia.
a.N = number of subjects in the specified group.
b.n = Number of subjects reporting at least 1 occurrence of any comorbidity or obese (BMI ≥30 kg/m2[≥16
Years of age] or BMI ≥95thpercentile [12 -15 Years of age]).
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:25) Source Data: admh Table Generation:
27MAR2021 (12:47)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/admh_s953
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950811
BNT162b2
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Page 41Table23. Exposure to BNT162b2 (30 μg) by Special Population (C4591001) – Open-
Label Follow -up Period – Subjects Who Originally Received Placebo and
Then Received BNT162b2 After Unblinding
Population Number of Subjects
Exposed
to BNT162b2 (30 μg)
(Na=19696)
nbTotal Number
of
Vaccine Doses
Subjects with any baseline comorbidity 8981 21590
AIDS/HIV 86 161
Any Malignancy + Metastatic Solid Tumor + Leukemia +
Lymphoma734 1406
Chronic Pulmonary Disease 1590 2953
Renal Disease 139 262
Rheumatic Disease 66 122
Mild Liver Disease + Moderate or Severe Liver Disease 102 193
Cerebrovascular Disease + Peripheral Vascular Disease +
Myocardial Infarction + Congestive Heart Failure567 1075
Dementia 9 17
Diabetes With/Without Chronic Complication 1555 2928
Hemiplegia or Paraplegia 4 8
Peptic Ulcer Disease 76 145
Obese 6760 12320
Note: Comorbidity is based on Charlson Comorbidity Index categories. Participants identified as belonging to
these categories were identified by medical history data collected during the study.
Note: 30 μg includes data from phase 1 and phase 2/3.
Note: Hemiplegia or Paraplegia only includes preferred terms Hemiplegia and Paraplegia.
a.N = number of subjectsin the specified group.
b.n = Number of subjects reporting at least 1 occurrence of any comorbidity or obese (BMI ≥30 kg/m2[≥16
Years of age] or BMI ≥95thpercentile [12 -15 Years of age]).
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:25) Source Data: admh Table Generation:
27MAR2021 (12:47)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_PVP_BLA/admh_s953_open
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950812
BNT162b2
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Page 422.1.2.a.2. Inclusion and Exclusion Criteria
Detailed descriptions of allinclusion and exclusion criteria for clinical studies are provided
in the individual CSRs which were filed to IND 019736 .
Inclusion criteria
Healthy participants who are determined b y medical history, ph ysical examination
(ifrequired), and clinical judgm ent of the investigator to be eligible for inclusion in the
study.
Healthy participants with pre -existing stable disease, defined as disease not requiring
significant change in therapy or hospitalization for worsening disease during the 6 weeks
before enr ollment, can be included. In order for the overall Phase 3 stud y population to
be as representative and diverse as possible, the inclusion of participants with known
chronic stable infection with HIV, HCV, or HBV waspermitted as the study progressed.
Specific criteria for these Phase 3 participants can be found in the C4591001 protocol,
Section 10. 8.
Phase 2/3 only :Participants who, in the judgment of the investigator, are at higher risk
for acquiring COVID -19 (including, but not limited to, use of ma ss transportation,
relevant demographics, front-lineessential workers ,and others).
The participants enrolled were 12 years of age and older; the 12 -to 15-year-old cohort
was included in the protocol in October 2020.
Exclusion criteria
Phase 1 exclusion criteria were stricter than criteria in Phases 2 and 3 of the study.
Participants were excluded from the studies according to the general criteria listed below :
Previous vaccination with any coronavirus vaccine
Reason for exclusion :To avoid confounding the assessment of serological or clinic al
immune response in the study population.
Is it considered to be included as missing information ? No.
Rationale : Minimal potential clinical impact on the target population .
Previous clinical or microbiological diagnosis of COVID-19
Reason for exclusion: Phase 1 excluded participants with a previous clinical or
microbiological diagnosis of COVID -19 because these participants may have some
degree of protection from subsequent infection by SARS-CoV-2 and therefore would
confound the pivotal efficacy endpoint. DuringPhase 2/3, participants with prior
undiagnosed infecti on wereallowed to be enrolled. Screening for SAR S-CoV-2 with
nucleic acid amplificat ion test by nasal swab or antibodies to non -vaccine SARS -CoV-2
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950813
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Page 43antigen by serology wasnot conducted before vaccine administration in Phase 2/3, but
samplesweretaken to run these assay s after vaccination, thus identifying participants
with unidentified prior infection. This group will be assessed to identify whether prior
infection affect s safety.
Is it considered to be included as missing information? No.
Rationale :Safety in study participants with prior infection will be assessed in the pivotal
study.
Immunocompromised individuals with known or suspected immunodeficiency, as
determined by history and/or laboratory/physical examination.
Reason for exclusion :Immunocompromised participants may have impaired immune
responses to vaccines and would therefore limit the ability to demonstrate efficacy ,
which is t he primary pivotal endpoint.
Is it considered to be included as missing information ? No.
Rationale : Participants with potential immunodeficient status were not specifically
included in the study population. However, since the study population is intended to be
as representative as possible of the vulnerable population to COVI D-19 illness ,
sub-analyses of immunogenicity data in future studies may provide further understanding
of immune responses in this population.
Receipt of blood/plasma products or immun oglobulin, from 60 days before study
intervention administration or planned receipt throughout the study
Reason for exclusion :To avoid confounding the assessment of serological or clinical
immune response in the study population.
Is it considered to be included as missing information ?No.
Rationale :No impact on the safet y of the target population.
Women who are pregnant or breastfeeding
Reason for exclusion :To avoid use in a vulnerable population .
Is it considered to be included as missing information? Yes.
Rationale :It is not known if maternal vaccination with BNT162b2 would have
unexpected negative consequences to the embry o or fetus.
090177e1970d7583\Approved\Approved On: 17-May-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950814
BNT162b2
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CONFIDENTIAL
Page 44Other medical or psychiatric condition including recent (within the past year) or
active suicidal ideation/behavior o r laboratory abnormality that may increase the
risk of study participation or, in the investigator’s judgment, make the participant
inappropriate for the study
Reason for exclusion :To avoid misleading results deriving from non -compliance to
study procedur es.
Is it considered to be included as missing information ? No.
Rationale :Safety profile of BNT162b2 is not expected to differ in these subjects when
properly administered.
2.1.2.a.2.1. Non-Study Post -Authorization Exposure
It is not possible to determine with certaint y the number of individuals who received
BNT162b2 since itwas first authorized for emergency use on 01 December 2020. Estimated
worldwide shipped doses may serve as a reasonable indicator of subject exposure b y region
and countries; the estimated exposure by gender and age group is not available.
Cumulatively , through the DL P (28 February 2021) approximately 126,212,580 doses of
BNT162b2 were shipped worldwide. The estimated cumulative number of shipped doses of
BNT162b2 by region, are summarized in Table24.
Table24. Cumulative Estimated Shipped Dosesaof BNT162b2 by Region Worldwide
Region/Country Total Number of Shipped
Doses% of Doses
Europe 51,545,325 40.8%
European Union (27) 36340590 28.8%
European Free Trade Association (3) 513825 0.4%
Switzerland 767520 0.6%
UK 13643175 10.8%
Other Countries 280215 0.2%
Commonwealth of Independent Statesb0 0.0%
North Am erica 56577885 44.8%
US 54326415 43.0%
Canada 2251470 1.8%
Central and South America 2965170 2.3%
Asia 14467830 11.5%
Oceania 656370 0.5%
Africa 0 0.0%
Total 126,212,580 100.0%
a.Data for US are based on Order Management Dashboard, while for the remaining Regions and Countries are based
on the Order Book which is the most accurate tracker of shipment data.
b.Includes: Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan,
Turkmenistan, Ukraine, Uzbekistan;
Method Used to Calculate Exposure
Not applicable.
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Page 45Exposure
Not applicable.
2.1.2.a.3. Regulatory Actions Related to Safety
There were no withdrawals for safety reasons up to 28 February 2021.
2.1.2.b.Populations Not Studied in the Pre -Approval Phase
There has been limited exposure to BNT162b2 in some special pop ulations and no
epidemiologic studies have been conducted in pregnant/lactating women, pediatric
participants (<12 years of age), and specific subpopulation sthat were initially excluded from
the BNT162b2 program.
Table25.Exposure of Special Populations Included or n ot in Clinical Trial
Development Programs
Type of special population Exposure
Pregnant women Available data on BNT162b2 administered to pregnant w omen are
insufficient to inform on vaccine-associated risks in pregnancy. In a
reproductive and developmental toxicity study , no vaccine -related
adverse effects on female fertility, fetal development , or postnatal
development were reported.
Through the cut-off date of 13March2021, there were 50cases (52
events) originating from Study C4591001 inparticipant 16 years of
age and older , and allwereunique pregnancies.
Breastfeeding w omen Breastfeeding w omenwere not initially included in the BNT162b2
clinical development program .
Data are not available to assess the effects of BNT162b2 on the
breastfed infant or on milk production/excretion.
The developmental and health benefits of breastfeeding should be
considered along with the mother’s clinical need for BNT162b2 and
any potenti al adverse effects on the breastfed childfrom BNT162b2
or from the underlying maternal condition. For preventive vaccines,
the underlying maternal condition is susceptible to disease prevented
by the vaccine.
Through the cut-off date of 13March2021, there were no CT cases
indicative of exposure during breastfeeding from study C4591001 in
participants 16 years of age and older .
Participants with relevant
comorbidities:
•Participants with hepatic
impairment
•Participants with renal impairment
•Participants with cardiovascular
disease
• Immunocompromised participants
•Participants with a disease
severity different from inclusion
criteria in CTsHealthy participants with pre- existing stable disease, defined as
disease not requiring significant change in therapy or hospitalization
for worsening disease during the 6 weeks before enrollment, were
included. Thisallowedenrollment of a proportion of participants
with common comorbiditiessuch ascardiovascular diseases including
hypertension, chronic pulmonary diseases ,asthma,chronic liver
disease, BMI >30 kg/m2, participants with stage 3 or w orse chronic
kidney disease ,and participants with varying disease severity .
Participants with potential immunodeficient status were not
specifically included in the study population .
Please refer to Table22and Table23for the exposure of special
populations.
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Page 46Table25.Exposure of Special Populations Included or n ot in Clinical Trial
Development Programs
Type of special population Exposure
Participants of different racial
and/or ethnic originPlease refer to Table21for exposure information by ethnic origin
from the studies.
Subpopulations carrying known and
relevant polymorphismsNo data available.
Pediatric participants The safety and effectiveness of BNT162b2 in individuals younger
than 16 years of age have not been established.
Participants 16 years of age and older
A total of 671 pediatric participants 16 to 17 years of age received
BNT162b2 through the DLP of 13 March 2021 :
378 participants in the blinded -placebo controlled follow -up
period (Table3).
293 partic ipants in the open -label follow -up period after the
unblinding ( Table5).
Participants 12 to 15years of age
One thousand andhundred eighty (1180) pediatric participants 12 to
15 years of age received BNT162b2 throughthe cut-off date of 13
March 2021 (Table3and Table5).
Elderly (≥6 5 years old) The safety and effectiveness of BNT162b2 in elderly participants was
consistent with that seen in younger adult participants.
Clinical studies of BNT162b2 includeda total of 8846 participants 65
years of age and over ; of these, 8827were from study C4591001 ,
through the cut -off date of 13 March 2021:
4590participants intheblinded-placebo controlled follow -
up period (Table3)
4237 participants in the open -label follow -up period after
unblinding (Table5).
Nineteen(19) participants 65 years of age and over were from study
BNT162- 01studythrough the cut -off date of 23 October 2020
(Table6).
Abbreviations: EUA = emergency use authorization ;BMI = body mass index; COVID-19= coronavirus
disease 2019 ; CT = clinical trial
2.1.2.c.Adverse Events / Adverse Reactions
2.1.2.c.1. Identification of Safety Concern in the Initial PVP Submission
2.1.2.c.1.1. Risks not Considered Important for Inclusion in the List of Safety Concerns
in the PVP
Not all potential or identified risks for the vaccine are considered to meet the level of
importance necessitatinginclusion in the list of safety concerns in the P VP:
Risks with minimal and temporary clinicalimpact on patients (in relation to the severit y
of the disease prevented) .
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Page 47The following reactogenicity events are identified risks not included in the list of safet y
concerns in the PVP: Injection site pain, Fever, Chills, Fatigue, Headache, Muscle pain,
and Joint pain.
Very rare potential risks for any medicinal treatment, including vaccines whichare well
known to healthcare professionals are not included in the list of safety concerns.
2.1.2.c.2. Important Identified and Potential Risks and Missing Information
2.1.2.c.2.1. Presentation of Important Identified Risks and Important Potential Risks
Important Identified Risk s
Anaphylaxis
Table26.Anaphylaxis
Potential
mechanisms,
evidence source and
strength of evidenceInteraction of an allergen with IgE on basophils and mast cells triggers release of
histamine, leukotrienes and other mediators that cause diffuse smooth muscle
contraction and vasodilation with plasma leakage. This can manifest clinically with
dyspnea, hypotension, swelling (sometimes leading to airw ay compromise), and
rash (including hives).
Characterisation of
the riskData from the CT database
Information pertinent to the anaphylactic reactions observed participants 16 years
and older in the ongoing Phase 3 clinical study C4591001 through the cut -off date
of 13 March 2021 , are summarized below :
Five (5) serious events [Acute respiratory failure, Cardiac arrest, Anaphylactic
reaction, Anaphylactoid reaction (post bee sting), and Anaphylactic shock] were
reported. The Anaphylactoid r eaction, occurred to a participant in the age group
16-55 years, was assessed as related to study treatment by the Investigator. The
remaining 4 events were deemed not related to study treatment by the Investigator.
Data from the safety database:
Since the first temporary authorization for emergency supply under Regulation 174
in the UK (01 December 2020) and through 28 February 2021 , 1833 potentially
relevant casesa, were retrieved from the Anaphylactic reaction SMQ (Narrow and
Broad) search strategy, applying the MedDRA algorithm. These 1833 cases w ere
individually reviewed and assessed according to Brighton Collaboration (BC)
definition and level of diagnostic certainty as shown in the Table below :
Brighton Collaboration Level Number of cases
BC 1 290
BC 2 311
BC 3 10
BC 4 391
BC 5 831
Total 1833
Level 1 indicates a case with the highest level of diagnostic certainty of
anaphylaxis, whereas the diagnostic certainty is lowest for Level 3. Level 4 is
defined as “reported event of anaphylaxis with insufficient evidence to meet the
case definition” and Level 5 as not a case of anaphylaxis.
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Page 48Table26.Anaphylaxis
There were 1002 cases (54.0% of the potentially relevant cases retrieved), 2958
potentially relevant events, from the Anaphylactic reaction SMQ (Broad and
Narrow) search strategy , meeting BC Level 1 to 4. Country of incidence: UK
(261), US (184), Mexico (99), Italy (82) , Germany (67), Spain (38), France (36),
Portugal (22), Denmark (20), Finland, Greece (19 each), Sweden (17), Czech
Republic, Netherlands (16 each), Belgium, Ireland (13 each), Poland (12), Austria
(11); the remaining 57 cases originated from 15 different countries.
Gender: Females (876), Males (106), Unknown (20);
Age (n=961) ranged from 16 to 98 years (mean = 54.8 years, median = 42.5 years);
Overall event seriousness and outcome of these 1002 cases are summarized below .
Total Events
N = 2958(%)
Serious events 2341 (79.1)
Events with Criterion of Hospitalization 752 (25.4)
Distribution of events by Outcom e*
Outcome∞: Death§9(0.3)
Outcome: Resolved/Resolving 1922 (65.0)
Outcome: Not resolved 229(7.7)
Outcome: Resolved with sequelae 48(1.6)
Outcome: Unknown/No data 754(25.5)
*For the outcome count, the multiple Lowest Level Terms that code to the same PT
within a case are counted and presented individually. Therefore, for selected PTs the total
count of the event outcome may exceed the total number of events.
∞ Different clinical outcomes may be reported for an event occurred more than once to
the same individual.
§There were 4 individuals in the anaphylaxis evaluation who died on the same day
they were vaccinated. Although these patients experienced adverse events (9) that are
potential symptoms of anaphylaxis, they all had serious underlying medical conditions,
and one individual appeared to also have COVID -19 pneumonia, that likely contributed
to their deaths.
The most frequently reported relevant PTs ( ≥2%), from the Anaphylactic reaction
SMQ (Broad and Narrow ) search strategy were: Anaphylactic reaction (435),
Dyspnoea (356), Rash (190), Pruritus (175), Erythema (159), Urticaria (133),
Cough (115), Respiratory distress, Throat tightness (97 each), Sw ollen tongue (93),
Anaphylactic shock (80), Hypotension (72), Chest discomfort (71), Sw elling face
(70), Pharyngeal swelling (68), and Lip swelling (64).
Conclusion: Evaluation of BC cases Level 1 – 4 did not reveal any significant ne w
safety information. Anaphylaxis is appropriately described in the product labeling
as are non -anaphylactic hypersensitivity events. Surveillance w ill continue.
Risk factors and risk
groupsKnown hypersensitivity to any components of the vaccine.
Preventability Prevention of anaphylaxis may not be possible, particularly with the 1stdose of a
vaccine; therefore, healthcare professionals administering the vaccine must be
vigilant for early signs and symptoms.
Impact on the risk -
benefit balance of the
biologic productAnaphylactic reaction in an individual can be impactful (medically important)
because it is a potentially life -threatening event requiring medical intervention.
Public health impact Minimal due to rarity of the event. Although the potential clinical consequences of
an anaphylactic reaction are severe, this is a known ri sk of vaccines to healthcare
professionals with negligible public health impact.
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Page 49Table26.Anaphylaxis
a.Search criteria Anaphylactic reaction SMQ (Narrow and Broad, with the MedDRA algorithm applied), with releva nt
cases assessed according to Brighton Collaboration (BC) criteria .
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Page 50Important Potential Risks
Table27.Vaccine-Associated Enhanced Disease (VAED), including Vaccine -
Associated Enhanced Respiratory Disease (VAERD)
Potential
mechanisms,
evidence source
and strength of
evidenceThis potential risk is theoretical because it has not been described in association with
the BNT162b2 or it has not been reported from any other late phase clinical trial of
other human vaccine. Animal models of SARS -CoV-2 infection have not shown
evidence of VAED after immunization, whereas cellular immunopathology has been
demonstrated after viral challenge in some animal models administered SARS -CoV-1
(murine, ferret and non -human primate models) or MERS-CoV (mice model)
vaccines.1,6This potential risk has been included based on these animal data with
these related betacoronaviruses. Histo rically, disease enhancement in vaccinated
children following infection with natural virus has been observed w ith an inactivated
respiratory syncytial virus vaccine.7
Potential mechanisms of enhanced disease may include both T cell -mediated [an
immunopatho logical response favoring T helper cell type 2 (T H2) over T helper cell
type 1 (T H1)] and antibody -mediated activity (antibody responses with insufficient
neutralizing activity leading to formation of immune complexes and activation of
complement or allow ing for Fc-mediated increase in viral entry to cells).8
Characterization
of the riskData from the CT database (Participant 16 years and older)
Confirmed Case of Postvaccination Severe COVID -19 –Blinded Placebo -
Controlled Follow -up Period -Safety Population (C4591001)
BNT162b2 (30 μg)
(Na=23164)Placebo
(Na=23155)
Timing nb(%) (95%CIc)nb(%) (95%CIc)
PD1 Before Dose
20 (0.0,0.0) 6(0.0) (0.0,0.0)
Within 7 days
PD10 (0.0,0.0) 0 (0.0,0.0)
PD2 1(0.0) (0.0,0.0) 25(0.1) (0.1,0.2)
Within 7 days
PD20 (0.0,0.0) 2(0.0) (0.0,0.0)
Totald1(0.0) (0.0,0.0) 31(0.1) (0.1,0.2)
Note: This table includes subjects from Phase 2/3 only.
Abbreviations: PD1 = post -dose 1; PD2 = post -dose 2.
a.N = number of subjects in the specified group. This value is the denominator for the
percentage calculations.
b.n = Number of subjects reporting at least 1 occurrence of the specified event.
c.Exact 2-sided CI based on the Clopper and Pearson method.
d.Total is the s um of PD1 and PD2.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data:
adc19ef Table Generation: 27MAR2021 (12:47) (Cutoff date: 13MAR2021, Snapshot Date:
25MAR2021)
Output File: /nda2_unblinded/C4591001_PVP_BLA/adeff_s901
If VAED/VAERD were to occur in vaccinated individuals, it may manifest as a
modified and/or more severe clinical presentation of SARS -CoV-2 viral infection
upon subsequent natural infection. This may result in individuals assumed to be at
lower risk for severe COVID -19having more severe disease, for individuals at known
risk for severe COVID -19 (e.g. older or immunocompromised) having higher rates of
fatal outcomes, or for observation of an unfavorable imbalance in severe COVID -19
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Page 51Table27.Vaccine-Associated Enhanced Disease (VAED), including Vaccine -
Associated Enhanced Respiratory Disease (VAERD)
cases in vaccinated individuals when c ompared to those not vaccinated. It is
challenging to assess for VAED/VAERD on an individual case basis, given the lack of
specific clinical or laboratory markers at this time, rather surveillance for this
theoretical risk is best performed at a populatio n level,9as noted above. The table
above shows a favorable balance of severe COVID -19 cases in participants receiving
BNT162b2 versus those receiving placebo, providing reassurance against the potential
risk of VAED/VAERD at this time.
Data from the saf ety database
No post-authorized AE reports have been identified as cases of VAED/VAERD,
therefore, t here is no observed d ataat this time. An expected rate of VAED is
difficult to establish so a meaningful observed/expected analysis cannot be conducted
at this point based on available data. The feasibility of conducting such an analysis
will be re- evaluated on an ongoing basis as data on the virus grows and the vaccine
safety data continues to accrue.
The search criteria utilised to identify potential cases of VAED for this report includes
PTs indicating a lack of effect of the vaccine and PTs potentially indicative of severe
or atypical COVID -19a.
Since the first temporary authorization for emergency supply under Regulation 174 in
the UK (01 December 2020) and through 28 February 2021, the following numbers of
potentially relevant cases were retrieved:
138 cases [0.25% of the total post-authorization dataset], reporting 317 potentially
relevant events.
Seriousness criteria for the total 138 cases: Medically significant (71, of which 8 also
serious for disability), Hospitalization required (non -fatal/non-life threatening) (16, of
which 1 also serious for disability), Life threatening (13, of which 7 w ere also serious
for hospitalization), Death (38).
Gender: Females (73), Males (57), Unknown (8) .
Age (n=132) ranged from 21 to 100 years (mean = 57.2 years , median = 59.5) .
Overall event seriousness and outcome are summarized below.
Total Events
N = 317 (%)
Serious events 279 (88.0)
Events with Criterion of Hospitalization 91 (28.7)
Distribution of events by Outcom ea
Outcome: Death 62 (19.6)
Outcome: Resolved/Resolving 61 (19.2)
Outcome: Not resolved 90 (28.4)
Outcome: Resolved with sequelae 1 (0.3)
Outcome: Unknown/No data 106 (33.4)
a. For the outcome count, the multiple Lowest Level Terms that code to the same PT within
a case are counted and presented individually. Therefore, for selected PTs the total count of
the event outcome may exceed the total number of events.
The most frequently reported relevant PTs ( ≥5 events) were: Drug ineffective (135),
Dyspnoea (53), Diarrhoea (30), COVID -19 pneumonia (23), Vomiting (20),
Respiratory failure (8), Seizure (7), Hypoxia (6), Abdominal pain, and Pulmonary
embolism (5 each).
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Page 52Table27.Vaccine-Associated Enhanced Disease (VAED), including Vaccine -
Associated Enhanced Respiratory Disease (VAERD)
Conclusion: VAED may present as severe or unusual clinical manifestations of
COVID-19. Overall, there were 37 subjects w ith suspected COVID -19 and 101
subjects with confirmed COVID 19 follow ing one or both doses of the vaccine; 75 of
the 101 cases w ere severe, resulting in hospitalisation, disability, life threatening
consequences or death. None of the 75 cases could be definitiv ely considered as
VAED/VAERD. In this review of subjects with COVID- 19 following vaccination,
based on the current evidence, VAED/VAERVAED remains a theoretical risk for the
vaccine. Surveillance will continue.
Risk factors and
risk groupsIt is postulated that the potential risk may be increased in individuals producing low er
neutralizing antibody titers or in those demonstrating waning immunity.8,9
Preventability An effective vaccine against COVID- 19 that produces high neutralizing titers and a
TH1 predominant CD4+T cell response and strong CD8+T cell response, is expected
to mitigate the risk of VAED/VAERD;1,8that immune profile is elicited by BNT162b2
in clinical and preclinical studies.10,11
Impact on the
risk-benefit
balance of the
biologic productIf there were an unfavorable balance in COVID -19 cases, including severe cases, in
the pivotal clinical study b etween the vaccine and placebo groups, that may signal
VAED/VAERD.
Public health
impactThe potential risk of VAED/VAERD could have a public health impact if large
populations of individuals are affected.
a. Standard Decreased Therapeutic Response Search AND at least 1 of the following PTs Dyspnoea;
Tachypnoea; Hypoxia; COVID 19 pneumonia; Respiratory Failure; Acute Respiratory Distress Syndrome;
Cardiac Failure; Cardiogenic shock; Acute myoca rdial infarction; Arrhythmia; Myocarditis; Vomiting;
Diarrhoea; Abdominal pain; Jaundice; Acute hepatic failure; Deep vein thrombosis; Pulmonary embolism;
Peripheral Ischaemia; Vasculitis; Shock; Acute kidney injury; Renal failure; Altered state of conscio usness;
Seizure; Encephalopathy; Meningitis; Cerebrovascular accident; Thrombocytopenia; Disseminated
intravascular coagulation; Chillblains; Erythema multiforme; Multiple organ dysfunction syndrome;
Multisystem inflammatory syndrome in children.
Note: the “Standard Decreased Therapeutic Response” search includes the Lack of efficacy PTs (Drug
ineffective/Vaccination failure).
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Page 532.1.2.c.2.2. Presentation of Missing Information
Table28.Use in Pregnancy and Lactation
Evidence source:
The safety profile of the vaccine is not known in pregnant or lactating w omen due to their exclusion from the
pivotal clinical study. There may be pregnant women who choose to be vaccinated despite the lack of safety
data. It w ill be important to follow these women for pregnancy and birth outcomes. The timing of
vaccination in a pregnant woman and the subsequent immune response may have varying favorable or
unfavorable impacts on the embryo/fetus. The clinical consequences of SARS -CoV-2 infection to the
woman and fetus during pregnancy is not yet fully understood and the pregnant woman’s baseline health
status may affect both the clinical course of her pregnancy and the severity of COVID -19 disease. These
factors and the extent to which the pregnant w oman may be at risk of exposure to SARS -CoV-2 will
influence the benefit risk considerations for use of the vaccine.
Population in need of further characterization:
The lack of data w ill be communicated in product labeling; one clinical study of the safety and
immunoge nicity of the BNT162b2 in pregnant women is ongoing (C4591015); 2 non -interventional studies
(C4591009 and C4591011) to assess whether sub -cohorts of interest, such as pregnant women, experience
increased risk of safety events of interest following receipt of the BNT162b2 are planned (see3.1.3–Action
plan for safety issues ).
Data from the Safety Databasea
Since the first temporary authorization for emergency supply under Regulation 174 in the UK
(01December 2020) and through 28 February 2021 , there were 413 cases ( 1.0 % of the total P ost-
authorization dataset)reporting use duringpregnancy orlactation.
Overall event seriousness and outcome are summarized below:
Total Events
N = 1122 (%)
Serious events 270 (24.1)
Events with Criterion of Hospitalization 14 (1.2)
Distribution of events by Outcom e*
Outcome: Death§5 (0.4)
Outcome: Resolved/Resolving 205 (18.3)
Outcome: Not resolved 64 (5.7)
Outcome: Resolved with sequelae 4 (0.4)
Outcome: Unknown/No data 849 (75.7)
*For the outcome count, the multiple Lowest Level Terms that code to the same PT within a case are counted and
presented individually. Therefore, for selected PTs the total count of the event outcome may exceed the total number
of events.
§ Two babies whose mothers were vacc inated during their second trimester of gestation, were pre-maturelydelivered
5 days after vaccination and died on their second day of life .
The most frequently reported relevant PTs ( ≥2%) were: Maternal exposure during pregnancy ( 187), Product
use issue (148), Off label use (147), Exposure via breast milk (133), Exposure during pregnancy (55),
Headache (33), Abortion spontaneous (25), Vaccination site pain (24), Pain in extremity , Pyrexia (23 each)
and Fatigue (22).
a.Cumulative RMP tables on Missing information are provided as per FDA’s request to include a
cumulative analysis, from post -authorization experience, of the Important Missing Information identified in
thePharmacovigilance Plan. More detailed information is available in the cumulative analysis of post -
authorization data provided as a standalone document with the BLA submission.
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Page 54Table29.Vaccine Effectiveness
Evidence source:
Although vaccine efficacy in acontrolled clinical stud yis the objective of the pivotal stud y, real-world
vaccine effectiveness when the BNT162b2is used in a large and more diverse population is unknown.
Anticipated risk/consequence of missing informatio n:
Efficacy information obtained from clinical study data will be communicated in the product labeling. Three
post-authorization effectiveness studies in real-world use are planned: 1 non -interventional study (C4591014)
and 2 low -interventional studies (WI235284 and WI255886) to determine the effectiveness of BNT162b2
when administered outside of the clinical setting (see 3.1.3–Action plan for safety issues ).
Data from the Safety Databasea
Since the first temporary authorization for emergency supply under Regulation 174 in the UK
(01December 2020) and through 28 February 2021 , there were 1665cases (3.9% of the total P ost-
authorization dataset) reporting lack of efficacy .
Overall event seriousness and outcome are summarized below:
Total Events
N = 1665(%)
Serious events 1644(98.7)
Events with Criterion of Hospitalization 65 (3.9)
Distribution of events by Outcom e*
Outcome: Death 65(4.0)
Outcome: Resolved/Resolving 164(9.8)
Outcome: Not resolved 205(12.3)
Outcome: Resolved with sequelae 0(0)
Outcome: Unknown/No data 1231(73.9)
*For the outcome count, the multiple Lowest Level Terms that code to the same PT within a case are counted and
presented individually. Therefore, for selected PTs the total count of the event outcome may exceed the total number
of events.
The PT Drug ineffective was reported in 1646 cases, Vaccination failure was reported in 19 cases; t he most
frequently co-reported PTs ( ≥2%) were: COVID 19 ( 1244), SARS -CoV-2 test positive(219), Suspected
COVID-19(161), Pyrexia (134), and Headache (110).
a.Cumulative RMP tables on Missing information are provided as per FDA’s re quest to include a
cumulative analysis, from post -authorization experience, of the Important Missing Information identified in
the Pharmacovigilance Plan. More detailed information is available in the cumulative analysis of post -
authorization data provided as a standalone document with the BLA submission .
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Page 55Table30.Use in Paediatric I ndividuals <12 Years of Age
Evidence source:
BNT162b2 has not been initially studied in pediatric individuals younger than 12 years of age due to their
exclusion from the pivotal clinical study .
Paediatric individuals may display different reactogenicity and safety profiles compared to adults, due to
lower body mass and differently matured immunological responses.
Population in need of further characterization :
Theare no data in individuals less than 12 years of age ; aclinical study of the safety, tolerability,
immunogenicity and efficacy of BNT162b2 in individual syounger than 12 years [C4591007 (< 12 years of
age)]ais ongoing(see 3.1.3–Action plan for safety issues); a non-interventional study (C4591009) is
planned to assess the occurrence of safety events of interest in a general US population (< 12 and ≥12 to ≤15
years of age)(see 3.1.3–Action plan for safety issues ).
Data from the Safety Databaseb
Since the first temporary authorization for emergency supply under Regulation 174 in the UK
(01December 2020) and through 28 February 2021 , there were 34cases (0.08% of the total Post -
authorization dataset) involving indivi duals below 12 years of age .
Overall event seriousness and outcome are summarized below:
Total Events
N =132 (%)
Serious events 66 (50)
Events with Criterion of Hospitalization 19 (14.4)
Distribution of events by Outcom e*
Outcome: Death 0
Outcome: Resolved/Resolving 25 (18.9)
Outcome: Not resolved 42 (31.8)
Outcome: Resolved with sequelae 0
Outcome: Unknown/No data 65 (49.2)
*For the outcome count, the multiple Lowest Level Terms that code to the same PT within a case are counted and
presented individually. Therefore, for selected PTs the total count of the event outcome may exceed the total number
of events.
The most freque ntly reported PTs ( ≥2%) were: Product administered to patient of inappropriate age (27), Off
label use (11), Pyrexia ( 6), Product use issue (5), Fatigue, Headache, Nausea ( 4each) and Vaccination site
pain (3).
a.Phase 1 open label dose- finding study to evaluate safety, tolerability, and immunogenicity and phase 2/3
placebo-controlled, observer blinded safety, tolerability, and immunogenicity, study of a SARS -CoV-2 RNA
vaccine candidate against COVID 19 in healthy children <12 years of age.
b.Cumulative RMP tables on Missing information are provided as per FDA’s request to include a
cumulative analysis, from post-authorization experience, of the Important Missing Information identified in
the Pharmacovigilance Plan. More detailed information is available in the cumulative analysis of post -
authorization data provided as a standalone document with the BLA submis sion.
2.1.2.d.Identified and Potential Interactions , Including Food -Biologic Productand
Drug-Biologic ProductInteractions
As noted in the WHO Guidelines on Nonclinical Evaluation of Vaccines,3pharmacokinetics
testing is n ot required for final formulation. No interaction linked to metabolism is expected
with vaccines. The only potential for interaction is with other vaccines administered
concomitantly and with immunosuppressive drugs.
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Page 56Co-administration studies with BNT162b2 have not been done, therefore th ere is not
sufficient data to understand the effect o nvaccineeffectiveness of BNT162b2 or co-
administered vaccines. A co-administration study with seasonal influenza vaccine is
planned. If BNT162b2 is given at the same time as other injectable vaccine(s), the vaccine(s)
should be administered at different injection sites.
2.1.2.e.Epidemiology of Indication and Target Population
Indication
Active immunization against COVI D-19 disease caused by SARS-CoV-2 virus in individuals
≥ 16years of age .
Incidence:
The COVID -19 is caused by a novel coronavirus labeled as SARS- CoV-2. The disease first
emerged in December 2019, when a cluster of patients with pneumonia of unknown cause
was recognized in Wuhan City, Hubei Province, China .12 The number of infected cases
rapidly increased and spread bey ond China throughout the world. On 30 January 2020, the
WHO declared COVID -19 a Public Health Emergency of International Concern and thus a
pandemic.13
Estimates of SARS -CoV-2 incidence change rapidly . We obtained incidence and prevalence
estimates using data from Worldometer, a trusted independent organization that collects
COVID-19 data from official reports and publishes current global and country -specific
statistics online.14
As of 03 March 2021, the overall number of people who had been infected with
SARS-CoV-2 was over 115 million worldwide,15an increase of nearl y 100 million in the 7
months since 28 July 2020.16 Table31shows the incidence and prevalence as of 03 March
2021 for the US, UK, and EU -27 countries. In the EU and the UK, b y 03 March 2021 the
total number of confirmed cases had accumulated to almost 27million people, or 5,226 per
100,000 people (from 1.7 million, or 337 per 100,000 by 28July 2020). Across countries in
the EU, the number of confirmed cases ranged from 1,072 to 11,836 cases per 100,000
people. Finland and Greece reported the lowest incidence rates while Czech Republic,
Slovenia, and Luxembourg reported the highest.15
In the US, the number of confirmed cases had reached over 29 million (8,864 per 100,000
people) b y 03 March 2021.15 This is an increase from 4 .5million (1,3 57per 100,000) b y
28July 2020.17
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Page 57Table31.Incidence, Prevalence, and Mortality of COVID -19 as of 03 March2021 15
Total
CasesIncidence:
Total Cases/
100,000Active
CasesaPrevalence:
Active Cases/
100,000Total
DeathsMortality:
Deaths /
100,000Population
Global 115,760,943 1,485 21,707,680 278 2,571,518 33 7,794,824,793
EU-27 22,642,536 5,083 6,113,464 1,462 553,363 124 445,424,167
UK 4,194,785 6,157 1,065,282 1,564 123,783 182 68,125,249
EU-27 + UK 26,837,321 5,226 7,178,746 1,398 677,146 132 513,549,416
US 29,456,377 8,864 8,921,400 2,685 531,652 160 332,304,437
EU-27 Countries
Austria 465,322 5,147 21,028 233 8,625 95 9,040,866
Belgium 774,344 6,662 699,566 6,019 22,141 191 11,623,476
Bulgaria 253,183 3,662 33,770 488 10,413 151 6,913,156
Croatia 244,205 5,973 3,322 81 5,555 136 4,088,197
Cyprus 35,620 2,936 33,331 2,747 232 19 1,213,250
Czech Republic 1,269,058 11,836 154,580 1,442 20,941 195 10,722,330
Denmark 212,798 3,665 6,995 120 2,370 41 5,805,897
Estonia 69,193 5,214 17,938 1,352 615 46 1,327,135
Finland 59,442 1,072 12,683 229 759 14 5,546,504
France 3,810,316 5,829 3,461,485 5,295 87,542 134 65,370,546
Germany 2,472,896 2,945 126,785 151 71,711 8583,963,843
Greece 197,279 1,899 21,157 204 6,597 6410,388,744
Hungary 439,900 4,561 98,361 1,020 15,324 159 9,643,837
Ireland 221,189 4,446 193,468 3,889 4,357 88 4,974,683
Italy 2,976,274 4,927 437,421 724 98,635 163 60,401,999
Latvia 88,022 4,702 9,233 493 1,654 88 1,872,109
Lithuania 200,349 7,430 10,859 403 3,281 122 2,696,596
Luxembourg 55,902 8,834 3,074 486 643 102 632,773
Malta 23,226 5,251 3,000 678 321 73 442,333
Netherlands 1,101,430 6,418 - -15,697 9217,160,343
Poland 1,735,406 4,589 249,567 660 44,360 117 37,818,722
Portugal 806,626 7,926 64,797 637 16,430 161 10,176,690
Romania 812,318 4,242 44,953 235 20,586 108 19,151,141
Slovakia 314,359 5,756 51,570 944 7,489 137 5,461,420
Slovenia 192,266 9,247 10,751 517 3,874 186 2,079,130
Spain 3,136,321 6,706 343,770 735 70,247 150 46,766,954
Sweden 675,292 6,659 - -12,964 128 10,141,493
a. Active case counts were not available for Netherlands and Sweden; therefore, those two countries are excluded from
the overall prevalence calculationsfor EU-27 and EU -27 + UK.
The reported numbers refer only to cases that have been tested and confirmed to be carry ing
the virus. There are large geographic variations in the proportion of the population tested as
well as in the quality of reporting across countries. People who ca rry the virus but remain
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Page 58asymptomatic are less likely to be tested and therefore mild cases are likel y underreported.
The numbers should therefore be interpreted with caution.18
Prevalence:
The prevalence of SARS-CoV-2 infection is defined as active cases per 100,000 people
including confirmed cases in people who have not recovered or died. On 03 March 2021, the
overall prevalence for the EU and UK (though not available for Sweden and the Netherlands)
was 1,398active cases per 100,000 ,15compared to 51 per 100,000 on 28 July 2020.16 The
range of reported prevalence wa s 81 to 6,019 per 100,000: Croatia, Denmark, and Germany
reported the lowest prevalence while Belgium, France and Ireland reported the highest
(Table31).
In the US, the prevalence on 03 March 2021 was nearl y twice as high as the combined
EU+UK estimates, with 2,685 active cases per 100,000.15 The prevalence in the US was 653
per 100,000 on 28 July 2020.16
Demographics of the population in the proposed indication and risk factors for t he
disease:
Since the beginning of the pandemic, the ECDC has continuously collected COVID -19
information from all countries who are members of EU/EEA and the UK. I n the ECDC’s
TESSy database, COVID -19 case-based data, including age and gender, are avail able for
over 80% of the official number of cases reported by ECDC epidemic intelligence,19enabling
estimates of age and gender distribution representative of the European population. TESSy
data on age and sex distributions by severity of symptoms as post ed on 04 March 2021 are
shown in Figure 1.20
The top half of the figure represents data ending on 31 July 2020 and the bottom half
presents data from01 August 2020 to 04 March 2021 (Figure1). In general, the age -sex
patterns before 01 August 2020 have remained the same since then. The gender distri bution
of persons testing positive for SARS- CoV-2 in the European population is similar for most
age groups. Cases reported in TESSy have been older than the general population
throughout the pandemic, with few cases observed in people aged younger than 2 0 years.
This likely reflects the age distribution of people who met the requirements for being tested
and is unlikely to reflect the actual distribution of infections in the population. Those with
severe outcomes (hospitalized, severel y hospitalized, or fatal) have been disproportionately
older and male compared to COVI D-19 cases overall. While age -sex patterns have remained
consistent throughout the pandemic, a notable difference between the periods before and
since 01 August 2020 is that the absolute n umbers of cases have increased dramaticall y in the
latter period compared to the earlier one.
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Page 59Figure1.Age-Sex distribution of COVID -19 Cases as Different Levels of Severity,
EU/EEA and UK. Case -based Data from TESSy produced on
04 March 2021a
Note: ”mild”= a case that has not been reported as hospitalized or a case that resulted in death.
a.Data from ECDC. COVID -19 Surveillance report. Week 8, 2021. 4 March 2021. “2.2 Age -sex pyramids” Accessed 6
March 202120
US distributions of COVID cases and deaths by age, sex, and race, as well as the cross -
tabulation of age and sex, are shown in Table32.21Those under age 50 account for 65% of
cases but less than 5% of deaths. For ages 18 -74, males account for less than half of cases
but over 60% of deaths.
Table32. Distributions of Cases (n=21,895,936) and Deaths (n=382,009) by Age, Sex,
Race, and Cross -Tabulated Age and Sex –United States as of
08March 202121,a
Age x Sex %
Event Age
GroupAge
%Sex Sex
%RacebRace
%Age
GroupMales Females
Cases 0-4 2Males 47.8 H/L 20.7 0-4 51.7 48.3
5-17 9.5Females52.2AI/AN 1.2 5-17 49.8 50.2
18-2922.4 Asian 3.6 18-2947.1 52.9
30-3916.3 Black 12.2 30-3948.2 51.8
40-4914.9 NH/PI 0.4 40-4947.7 52.3
50-6420.5 White 56 50-6448.5 51.5
65-747.8 M/O 665-74 49 51
75-844.1 75-8445.7 54.3
85+ 2.4 85+ 33.9 66.1
Deaths 0-4 <0.1 Males 54.3 H/L 12.2 0-4 47.6 52.4
5-17 0.1Females45.7AI/AN 1 5-17 57.7 42.3
18-290.5 Asian 4.3 18-29 63 37
30-391.1 Black 14.7 30-39 66 34
40-492.8 NH/PI 0.2 40-4966.5 33.5
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Page 60Table32. Distributions of Cases (n=21,895,936) and Deaths (n=382,009) by Age, Sex,
Race, and Cross -Tabulated Age and Sex –United States as of
08March 202121,a
Age x Sex %
Event Age
GroupAge
%Sex Sex
%RacebRace
%Age
GroupMales Females
50-6414.5 White 63.1 50-64 65 35
65-7421.3 M/O 4.4 65-7461.4 38.6
75-8427.7 75-8455.8 44.2
85+ 32.1 85+ 41.8 58.2
a. Percentage of missing demographic data varied by types of event and demographic.
b.Except for Hispanics/Latinos, all categories refer to non -Hispanics
Abbreviations: AI/AN=American Indian/Alaska Native, H/L=Hispanic/Latino, M/O=Multiple/Other, NH/PI=Native
Hawaiian/Other Pacific Islander
In general, d isease has been much less severe among ages 0- 24 compared to ages ≥25 years,
with 2.5% hospitalized, 0.8% admitted to an intensive care unit, and <0.1% dying among
ages 0-24, versus 16.6% hospitalized, 8.6% intensive care, and 5% d ying among ages
≥25years.22Among hospitalized cases with COVID -19 in the US, approximately 90% are
over 40 years old, and between 58% to 66% are at least 60 years old.23 The majority
(approximately 60%) of COVID -19 patients admitted to hospitals in the US have been
male.23,24,25,26,27
African American COVID- 19 patients have been reported to have an increased risk of
hospitalization24,28and mortality ,29compared to white patients in the United States. A CDC
report examined demographic trends among US COVID- 19 deaths from May to August of
2020.30 During the observation period, the percentage of US COVID -19 deaths that were
Hispanic increased from 16.3% in May to 26.4% in August, the onl y racial or ethnic group
among whom the percentage of deaths increased during that time. In terms of setting, 6 4.3%
of deaths occurred in inpatient hospitals and 21.5% in nursing homes or long -term care
facilities.
As of 08 March 2021, the CDC estimated that the total number of excessdeaths (as opposed
to overall deaths in the preceding paragraph) across the US fr om 01 February 2020 to the
present from all causes (COVID -19 and otherwise) ranged from 509,890-624,307.31 A CDC
report examining US excess deaths associated with race and age, restricted to the period
26January 2020 to 03 October 2020, estimated that 66% of US excess deaths during that
period were attributable to COVID -19.32 By age, the largest increase in deaths compared to
average expected deaths occurred among adults aged 25 -44 (26.5% increase). By race,
increases in deaths compared to expectation wer e largest among Hispanics (53.6% increase),
Asian Americans (36.6% increase), African Americans (32.9% increase), and Native
Americans and Native Alaskans (28.9% increase), all compared to an excess 11.9% deaths
among non -Hispanic whites.
Risk Factors
While anyone can become infected with SARS -CoV-2, symptoms of COVID -19 disease can
range from very mild (or no sy mptoms) to severe or fatal. A person’s risk of initial infection
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Page 61increases through spending time in close ph ysical proximity to others, especially in indoor
spaces with poor ventilation.33 People living in long- term care facilities or high- density
apartment homes, or working in occupations with close proximity to others (e.g. healthcare,
transportation), have a higher risk of infection.33,34,35According to the CDC, people ages
18-29 have the highest risk of initial infection, while children age 4 and under have the
lowest rate ( Table33).36 Risk of infection is also higher among some ethnic minority
groups.37,38
Table33.Risk for COVID -19 Infection, Hospitalization, and Death by Age Group 36
and by Race/Ethnicity37
Rate ratios
Age Group (years) Cases Hospitalization Death
0-4 <1 2 2
5-17 a1 1 1
18-29 3 7 15
30-39 2 10 45
40-49 2 15 130
50-64 2 25 400
65-74 2 35 1100
75-84 2 55 2800
85+ 2 80 7900
Race/Ethnicity
Non-Hispanic White b1 1 1
American Indian or Alaska Native, non -Hispanic 1.9 3.7 2.4
Asian, non -Hispanic 0.7 1.1 1.0
Black or African American, non -Hispanic 1.1 2.9 1.9
Hispanic or Latino 1.3 3.2 2.3
a. Rate ratios for each age group are relative to the 5— 17-year age category.
b.Rate ratios for each race/ethnicity group are relative to the Non -Hispanic White category.
Risk for severe or fatal COVID -19 disease has been shown to increase with older age, male
sex, or ethnic minority status.36,37,38,39,40,41 Risks of hospitalization and death increase
dramaticall y for every 10 -year age group above age 17 ( Table33).36,41 Table33alsogives
estimated rate ratios for COVID -19 hospitalization and death by race/ethnicity relative to
white, non- Hispanic persons in the US. The highest risks of hospitalization and death were
observed among American Indian or Alaska native persons (RR = 3.7 for hospitalization and
2.4 for death) and Hispanic or Latino persons (RR = 3.2 for hospitalization and 2.3 for
death). These differences in risk among ethnic groups may be attributed to differences in
underlying factors that are correlated with race/ethnicity including socioeconomic status,
access to health care, and occupation -related virus exposure.37
Risk of severe or fatal COVID -19 disease is higher among persons who are current or former
smokers, have lower socioeconomic status, have no or public insurance, or live in
neighborhoods with higher rates of limited English proficiency .38,40,41,42The CDC has also
recognized other socio -demographic groups who may need to take extra precautions against
COVID-19 due to increased risk for severe illness: pregnant women; breastfeeding mothers;
people with disabilities or developmental/behavioral disorde rs; people living in rural
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Page 62communities, nursing homes, long -term care facilities, or prisons; people experiencing
homelessness; and newl y resettled refugee populations.43
Risk for severe or fatal COVID -19 disease also increases with the presence of chroni c
medical conditions, including obesit y, respiratory diseases (e.g., COPD or asthma),
cardiovascular disease, diabetes, cancer, liver disease, neurological diseases (e.g., stroke or
dementia), chronic kidney disease, sickle cell disease, autoimmune conditi ons and
immunosuppression, or higher scores on the WHO Clinical Progression Scale and Charlson
Comorbidity Index.38,39,40,41,42 Table34showsthe estimated hazard ratios of COVID -19
mortality associated with these chronic conditions and socio-demographics from a cohort
study of 17 million adults in England.41
Table34.Hazard R atios and 95% Confidence I ntervals for COVID -19-related
Death41
COVID-19 death H azard Ratio
Characteristic Category Adjusted for
age and sexFully adjusted
Age 18-39 0.05 (0.04 -0.07) 0.06 (0.04 -0.08)
40-49 0.28 (0.23 -0.33) 0.30 (0.25 -0.36)
50-59 1.00 (ref) 1.00 (ref)
60-69 2.79 (2.52 -3.10) 2.40 (2.16 -2.66)
70-79 8.62 (7.84 -9.46) 6.07 (5.51 -6.69)
80+ 38.29 (35.02 -41.87) 20.60 (18.70-22.68)
Sex Female 1.00 (ref) 1.00 (ref)
Male 1.78 (1.71 -1.85) 1.59 (1.53 -1.65)
BMI (kg/m2) Not obese 1.00 (ref) 1.00 (ref)
30-34.9 (obese class I) 1.23 (1.17 –1.30) 1.05 (1.00 –1.11)
35-39.9 (obese class II) 1.81 (1.68 –1.95) 1.40 (1.30 –1.52)
40+ (obese class III) 2.66 (2.39 –2.95) 1.92 (1.72 –2.13)
Smoking Never 1.00 (ref) 1.00 (ref)
Former 1.43 (1.37 –1.49) 1.19 (1.14 –1.24)
Current 1.14 (1.05 –1.23) 0.89 (0.82 –0.97)
EthnicityaWhite 1.00 (ref) 1.00 (ref)
Mixed 1.62 (1.26 –2.08) 1.43 (1.11 –1.84)
South Asian 1.69 (1.54 –1.84) 1.45 (1.32 –1.58)
Black 1.88 (1.65 –2.14) 1.48 (1.29 –1.69)
Other 1.37 (1.13–1.65) 1.33 (1.10 –1.61)
IMD quintilee1 (least deprived) 1.00 (ref) 1.00 (ref)
2 1.16 (1.08 -1.23) 1.12 (1.05 –1.19)
3 1.31 (1.23 –1.40) 1.22 (1.15 –1.30)
4 1.69 (1.59 –1.79) 1.51 (1.42 –1.61)
5 (most deprived) 2.11(1.98–2.25) 1.79 (1.68 –1.91)
Blood pressure Normal 1.00 (ref) 1.00 (ref)
High BP or diagnosed
hypertension1.09 (1.05 –1.14) 0.89 (0.85 –0.93)
Respiratory disease excluding asthma 1.95 (1.86 –2.04) 1.63 (1.55 –1.71)
Asthmab(vs. none) With no recent OCS use 1.13 (1.07 –1.20) 0.99 (0.93 –1.05)
With recent OCS use 1.55 (1.39 –1.73) 1.13 (1.01 –1.26)
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Page 63Table34.Hazard R atios and 95% Confidence I ntervals for COVID -19-related
Death41
COVID-19 death H azard Ratio
Characteristic Category Adjusted for
age and sexFully adjusted
Chronic heart disease 1.57 (1.51 –1.64) 1.17 (1.12 –1.22)
Diabetesc(vs. none) With HbA1c < 58 mmol/mol 1.58 (1.51 –1.66) 1.31 (1.24 –1.37)
With HbA1c ≥ 58 mmol/mol 2.61 (2.46 –2.77) 1.95 (1.83 –2.08)
With no recent HbA1c measure 2.27 (2.06 –2.50) 1.90 (1.72 –2.09)
Cancer (non -
hematological, vs. none)Diagnosed <1 year ago 1.81 (1.58 –2.07) 1.72 (1.50 –1.96)
Diagnosed 1 -4.9 years ago 1.20 (1.10 –1.32) 1.15 (1.05 –1.27)
Diagnosed ≥ 5 years ago 0.99 (0.93 –1.06) 0.96 (0.91 –1.03)
Hematological
malignancy (vs. none)Diagnosed <1 year ago 3.02 (2.24 –4.08) 2.80 (2.08 –3.78)
Diagnosed 1 -4.9 years ago 2.56 (2.14 –3.06) 2.46 (2.06 –2.95)
Diagnosed ≥ 5 years ago 1.70 (1.46 –1.98) 1.61 (1.39 –1.87)
Reduced kidney
functiond(vs. none)eGFR 30-60 1.56 (1.49 –1.63) 1.33 (1.28 –1.40)
eGFR < 30 3.48 (3.23 –3.75) 2.52 (2.33 –2.72)
Liver disease 2.39 (2.06–2.77) 1.75 (1.51 –2.03)
Stroke or dementia 2.57 (2.46 –2.70) 2.16 (2.06 –2.27)
Other neurological disease 3.08 (2.85 –3.33) 2.58 (2.38 –2.79)
Organ transplant 6.00 (4.73 –7.61) 3.53 (2.77 –4.49)
Asplenia 1.62 (1.19 –2.21) 1.34 (0.98 –1.83)
Rheumatoid arthritis, lupus, or psoriasis 1.30 (1.21 –1.38) 1.19 (1.11 –1.27)
Other immunosuppressive condition 2.75 (2.10 –3.62) 2.21 (1.68 –2.90)
a.Ethnicity hazard ratios w ere estimated from a model restricted to those w ith recorded ethnicity.
b.For OCS use, ‘recent’ refers to during the year before baseline.
c.Classificati on by HbA1c is based on measurements within 15 months of baseline.
d.eGFR is measured in ml min −1 per 1.73 m2and taken from the most recent serum creatinine
measurement.
e.Index of Multiple Deprivation
Models w ere adjusted for age using a four -knot cubic spline for age, except for estimation of age -group
hazard ratios. Ref, reference group; 95% CI, 95% confidence interval.
Themain existing treatment options:
Through28 February 2021, other COVID-19 vaccines were authorized and recommended for
use in the United States including vaccines from Moderna (NCT04470427), and Johnson &
Johnson/Janssen(NCT04505722) . Othersmay subsequently be approved.
Natural history of the indicated condition in the untreated population, including
mortality and morbidity:
Symptoms of COVID -19
The clinical manifestations of COVID -19 varywidely, from asymptomatic infection in
17-20%,44,45to critical illness and death. The most common sy mptoms of COVID -19 are
fever, cough, and shortness of breath ( Table35).46
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Page 64Table35.Signs and symptoms among 291 pediatric (age <18 years) and 10,944 adult
(age 18–64 years) patientsawith laboratory confirmed COVID -19 —
United States, 12 February– 2 April 202046
No. (%) with sign/symptom
Sign/Symptom Pediatric Adult
Fever, cough, or shortness of breathb 213 (73) 10,167 (93)
Feverd 163 (56) 7,794 (71)
Cough 158 (54) 8,775 (80)
Shortness of breath 39 (13) 4,674 (43)
Myalgia 66 (23) 6,713 (61)
Runny nosec 21 (7.2) 757 (6.9)
Sore throat 71 (24) 3,795 (35)
Headache 81 (28) 6,335 (58)
Nausea/Vomiting 31 (11) 1,746 (16)
Abdominal paind17 (5.8) 1,329 (12)
Diarrhea 37 (13) 3,353 (31)
a.Cases were included in the denominator if they had a known symptom status for fever, cough, s hortness
of breath, nausea/vomiting, and diarrhea. Total number of patients by age group: <18 years (N = 2,572), 18 –
64 years (N = 113,985).
b.Includes all cases with one or more of these sy mptoms.
c.Runny nose and abdominal pain were less frequently completed than other symptoms; therefore,
percentages with these symptoms are likely underestimates.
d.Patients were included if they had information for eith er measured or subjective fever variables and were considered
to have a fever if “yes” was indicated for either variable.
Progression and Timeline of Mild to Moderate Disease
Mild to moderate disease is defined as the absence of viral pneumonia and hy poxia. For those
who develop s ymptoms, the incubation period is usually 4 to 5 day s, with 97.5%
experiencing s ymptoms within 11 day s of exposure.47,48Those with mild COVID -19recover
at home with supportive care and guidance to self -isolate. Those with moderate disease are
monitored at home and are sometimes recommended to be hospitalized if conditions
worsen.48Data on rates of re -infection are limited but variants that are not neutralized by
immune antisera, such as the recent South African variant, may lead to increased risk of re -
infection in the futur e.47
Progression and Timeline of Severe Disease Requiring Hospitalization
Those with severe disease will require hospitalization to manage their illness. Based on data
that have been sy stematically collected for the US by the CDC between 01 August 2020 and
02 March 2021, there were 1,814,606 new hospital admissions for patients with confirmed
COVID-19 in the US.49For the week ending 28 February 2021, 10 patients per 100,000
population were hospitalized due to COVID-19 in 22 countries of the EU/EEA with available
data.50
The most common sy mptoms in patients are fever (42-80%), shortness of breath (35 -71%),
fatigue (33- 62%), cough (77- 84%), chills (63%), my algias (63%), headache (59%), and
diarrhea (33%) .51,52,53,54 Approximately 17% to 40% of those hospitalized with COVID -19
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Page 65experience severe s ymptoms necessitating intensive care .23,28,51 More than 75% of patients
hospitalized with COVID -19 require supplemental -oxygen.55
Studies early in the pandemic demonstrated that time from onset of illness to ARDS was 8-
12 -days and time from onset of illness to ICU admission was 9.5–12 day s.47In 17 countries
of the EU/EEA with available data, 1.8 patients per 100,000 population were in the I CU due
to COVID-19 for the week endin g 28 February 2021.50A recent meta -analysis found that, of
patients <19 y ears of age, 11% went to the ICU, non -invasive ventilation was administered
among 12%, and 4% required mechanical ventilation.45
Mortality
As of 07 March 2021, there were 522,973 deaths reported in the US for all age groups among
28,771,749 cases (1.8% of cases).49As of 28 February 2021 there were 547,267 deaths
reported for all age groups in the EU/EEA among 22,527,370 cases (2.4% of cases).56As of
7 March 2021, the UK has seen 124,736 deaths from COVI D-19 in all age groups among
4,231,166 cases (2.9% of cases).57According to a recent meta -analysis of pediatric studies
published through October 2020, the mortalit y for patients <19 years of age is 2%.45
Mortality data are also presented from Worldometer, an independent organization that
publishes current, reliable COVID -19 statistics online.17The mortality of SARS -CoV-2
infection is defined as the cumulative number of deaths among detected cases.
As of 03 March 2021, the overall SARS -CoV-2 mortality for the EU + UK was 677,146
deaths, or 132 per 100,000 people. Reported mortality among EU countries and the UK
ranged from 14 to 195 deaths per 100,000 ( Table31). Finland and C yprus reported the
lowest mortality ; Czech Republic, Belgium and Slovenia reported the highest.15
In the US, as of 03 March 2021, the mortality was 531,652 deaths (160 per 100,000 people).
Mortality in the US was similar to that of EU countries Hungary , Portugal, and I taly.15
Overall reported mortality among hospitalized COVID-19 patients varies from 12.8% to 26%
in the EU and UK.28,30,58,59 Mortality rates are declining over time, presumably due to an
improved understanding of COVID -19 and its management.58,60
Complications of COVID -19 and Long- COVID
Complications of COVID- 19 include impaired function of the heart, brain, lung, liver,
kidney, and coagulation sy stem.23,25,54 Based on a meta -analysis of 42 studies, the risk of
thromboembolism was 21% overall and 31% in the I CU, with the pooled odds of mortality
being 74% higher among those who experienced thromboembolism compared to those who
did not.61
COVID-19 symptoms can persist weeks or months bey ond the acute infection.62,63The
NICE guideline scope published on 30 October 2020 defined “Long COVID” signs and
symptoms that continue or develop after acute COVID ‑19. It includes both ongoing
symptomatic COVID ‑19 (from 4 to 12 weeks) and post‑COVID‑19 s yndrome (12 weeks or
more and for which signs and sy mptoms are not explained by an alternative diagnosis).64
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Page 66A metaanalysis of 31 studies among patients between 18 to 49 y ears of age found that
COVID-19 symptoms were experienced for 14 day s to 3 months post -infection, including
persistent fatigue (39 –73%), breathlessness (39 –74%), decrea se in quality of life (44–69%),
impaired pulmonary function, abnormal CT findings including pulmonary fibrosis (39–83%),
evidence of peri -/perimyo-/myocarditis (3–26%), changes in microstructural and functional
brain integrity with persistent neurological sy mptoms (55%), increased incidence of
psychiatric diagnoses (5.8% versus 2.5 –3.4% in controls), and incomplete recovery of
olfactory and gustatory dysfunction (33 –36%).65 Children who are infected with COVI D-19
are at risk of subsequent multisy stem inflam matory syndrome (MIS- C) and often develop a
rash following resolution of COVID -19.66,67,45
Important co -morbidities:
Important comorbidities in hos pitalized COVI D-19 patients include hy pertension, diabetes,
obesity, cardiovascular disease, chronic pulmonary disease or asthma, chronic kidney
disease, cancer, and chronic liver disease.24,25,26,51,54Prevalence of these conditions have
been reported to be lower in mild cases and higher among fatal cases, as shown as shown for
European countries in Table36below.
Table36. Preconditions among COVID-19 Patients in EU/EEA and UK, by Severity
ofDisease. Case -based Data from TESSy Produced 0 4 March 2021
EU/EEA, produced on 04 March 2021
Mild Hosp Severe Fatal
Total N 1,155,969 214,784 35,468 67,011
Asplenia (%) 0 0 0 0
Asthma (%) 0.5 1.6 1.7 1.6
Cancer, malignancy (%) 2.1 7.2 9.7 9.3
Cardiac disorder, excluding hypertension (%) 6.2 18.4 20.7 24.7
Chronic lung disease, excluding asthma (%) 1.8 4.7 5.3 5.3
Current smoking (%) 0.9 0.3 0.4 0.1
Diabetes (%) 3.3 13.9 18.9 15.6
Haematological disorders (%) 0 0.3 0.1 0.2
HIV/other immune deficiency (%) 0.1 0.9 1 0.8
Hypertension (%) 0.7 3.9 4.4 6.3
Kidney-related condition, renal disease (%) 0.3 2.3 2.2 3.7
Liver-related condition, liver disease (%) 0.2 0.7 0.7 0.6
Neuromuscular disorder, chronic neurological (%) 0.6 2.4 1.6 4.2
Obesity (%) 0.2 0.2 0.4 0.2
Other endocrine disorder, excluding diabetes (%) 0.4 0.2 0.1 0.1
Rheumatic diseases including arthritis (%) 0 0 0 0
Tuberculosis (%) 0 0 0 0
None (%) 82.5 42.8 32.7 27.3
Abbreviation: Hosp = Hospitalized
Table37below summarizes comorbidities among US COVID -19 patients in a retrospective
cohort study conducted among 629,953 individuals tested for COVID- 19 in a large health
system in the US Northwest between 01 March and 31 December 2020 .38 The most common
comorbidities were similar in the full cohort and among those who tested positive: obesity ,
hypertension, diabetes, and asthma. Among those hospitalized for COVID -19, a large
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Page 67number of comorbidities had elevated prevalence compared to the full cohort and those who
tested positive: obesity , hypertension, diabetes, kidney disease, congestive heart failure,
coronary artery disease, and chronic obstructive pulmonary disease.
Table37. Comorbidities in individuals tested for COVID- 19 in the Providence St.
Joseph Health S ystem – States of California, Oregon, and Washington,
01March–31 December 202038
ComorbidityTested
(N= 629,953)
%Positive
(N= 54,645)
%Hospitalized
(N= 8,536)
%
Hypertension 23.3 19.8 40.2
Diabetes 9.4 10.9 28.3
Weight
Underweight 2.1 1.7 3.1
Normal 29.0 23.9 24.3
Overweight 31.7 32.6 30.3
Class 1 Obesity 19.8 22.3 21.2
Class 2 Obesity 9.6 11.1 10.9
Class 3 Obesity 7.7 8.6 10.3
Asthma 6.5 5.3 6.7
Chronic Obstructive Pulmonary Disease 4.0 2.6 8.3
Coronary Artery Disease 5.5 3.6 9.7
Myocardial Infarction 2.2 1.6 5.5
Congestive Heart Failure 5.3 3.9 13.2
Kidney Disease 5.6 5.3 17.2
Liver Disease 3.1 2.5 4.0
Cancer 6.1 3.0 6.3
2.1.2.f.Pharmacological Class Effects
There are 2 vaccines (including BNT162b2 ) with a mRNA platform authorized for
emergency use in multiple US jurisdictions since 11 December 2020. Theoretical concerns
in mRNA vaccines have included the risk of the presence of naked extracellular RNA in the
body which may lead to edema or coagula tion and concerns about aberrant immune
responses to the RNA or lipid particles. The immunogenicity and efficacy data from study
C4591001 are indicative of the vaccine delivery system’s success in transfecting the RNA
into the appropriate target cells to stimulate an immune response. The RNA itself cannot
integrate into the DNA genome.68,69 The probabilit y of any sequences from the vaccine RNA
being integrated into the human genome b y a reverse transcription mediated mechanism is
considered remote, no high er than the probability of host RNA sequences being re -inserted
into the genome, especially given the small quantity of RNA in the vaccine, the barriers to
transfected RNA reaching the nucleus, the non -replicating nature of the vaccine RNA, the
limited sta bility of RNA in a cellular context, and the expected targeting of transfected cells
for elimination by T cells elicited by the vaccine antigen expressed from the RNA.
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Page 683.PHARMACOVIGILANCE PLAN
3.1.Structure of the Pharmacovigilance Plan
3.1.1. Summary of Ongoing Safety Concerns
Table38. Ongoing Safety Concerns
Important Identified Risks Anaphylaxis
Important Potential Risks Vaccine-associated enhanced disease (VAED) including Vaccine -
associated enhanced respiratory disease (VAERD)
Missing Information Use in pregnancy and lactation
Vaccine effectiveness
Use in pediatric individuals <1 2years of age
3.1.2.Routine Pharmacovigilance Practice s
Routine pharmacovigilance activities is a critical component of activities relating to the
detection, assessment, understanding and prevention of risks. The objective of routine
pharmacovigilance is to haveprocesses in place to assure the ongoing and timely
collection, processing, follow-up , and anal ysis of individual AE reports globally ,
following global safet y Standard Operating Procedures and regulatory guidance.
Pfizer, on behalf of the marketing authorization applicant ( MAA), monitors the safet y
profile of its products, evaluates issue s potentially impacting product benefit -risk profiles
in a timely manner, and ensures that appropriate communication of relevant information
is convey ed in a timel y manner to regulatory authorities and other interested parties as
appropriate and in accorda nce with international principles and prevailing regulations.
Pfizer, on behalf of the MAA, conducts scientific data gathering activities for the
detection and evaluation of AEs in order to ensure safet y monitoring, which is
commensurate with product cha racteristics.
Signal detection activities include periodic literature review for the life cy cle of the
product. This includes reviewing the medical literature for individual case reports that
should be entered into the safet y database as well as periodic aggregate literature review
for broader signal detection.
Safety signal evaluation requires the collection, analy sis and assessment of information to
evaluate whether there is a potential causal association between an event and the
administration of the product and includes subsequent qualitative or quantitative
characterization of the relevant safet y risk to determine appropriate pharmacovigilance
and risk mitigation actions.
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Page 69Routine pharmacovigilance activities will include the use of DCAs. They are intended to
facilitate the capture of clinical details about:
the nature and severit y of COVID- 19 illness in individuals who have received the
COVID-19 vaccine and is anticipated to provide insight into potential cases of
vaccine lack of effect or VAED.
potential anaph ylactic reactions in individuals who have received the COVID-19
vaccine.
A web-based AE reporting portal will be available for vaccine providers and recipients,
to assist with anticipated high volume of reports (based on expected large target
population). The portal will capture key adverse event data in the initial interaction and
will provide automated intake into the Pfizer safety database via E2B for safety review.
At the country level, the Drug Safet y Unit performs routine pharmaco vigilance activities
including the collection of AEs from various sources and the reporting of AEs to the
regulatory authority as per local regulatory guidelines.
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Page 703.1.3. Action Plan for Safety Issues
Action Plan for Important I dentified Risks
Table39. Action Plan for Important Identified Risk “Anaphylaxis ”
Actions proposed Communication of this important identified risk via label (Sections 4 -
Contraindications , 5.1 -Management of Acute Allergic Reactions ,
Section6-Adverse reactions -and 6.2-Post Authorization Experience ).
C4591001 :Phase 1/2/3, placebo -controlled, randomized, observer -blind,
dose-finding study to evaluate the safety, tolerability, immunogenicity, and
efficacy of SARS -CoV-2 RNA vaccine candidates against COVID -19 in
healthy individuals.
C4591009 :A non-interventional post-approval safety study of the
Pfizer--BioNTech COVID -19 mRNA vaccine in the United States.
C4591011 :Active safety surveillance of the P fizer-BioNTech COVID -19
vaccinein the US Department of Defense population following Emergency
Use Authorization.
C4591012:Post-emergency use authorization active safety surveillance
study among individuals in the Veteran’s Affairs Health System receiving
Pfizer-BioNTech Coronavirus Disease 2019 (COVID- 19) vaccine.
Objective of proposed
actionsLabelling communicates the risk of anaphylaxis.
C4591001: To evaluate the safety, tolerability, immunogenicity, and efficacy
of BNT162b2. Further, an unfavorable imbalance between the vaccine and
control groups in the frequency of COVID- 19 disease, in particular for
severe COVID -19 disease, may indicate the occurrence of VAED/VAERD.
Surveillance is planned for 2 years following Dose 2.
C4591009: To assess the occurrence of safety events of interest in the
general US population, pregnant women, the immunocompromised and
persons with a prior history of COVID- 19 within selected data sources
participating in the USSentinel System.
C4591011: To assess whether individuals in the US DoD Military Health
System (MHS) experience increased risk of safety events of interest,
following receipt of the BNT162b2 .
C4591012: To assess whether individuals in the USVeteran’s Affairs Health
System experience increased risk of safety events of interest, following
receipt of theBNT162b2.
Rationale for proposed
actionsLabeling communicates to health care provider the risk of anaphylaxis.
C4591001: Long -term monitoring throughout the clinical study for up to 2
years to assess the risk for vaccine -associated enhanced disease.
C4591009: Robustsurveillance is needed to ensure comprehensive
understanding of real -world safety of the BNT162b2in the general US
population and in subcohor ts of interest, including pregnant w omen,
immunocompromised individuals and persons with a prior history of
COVID-19 infection.
C4591011 and C4591012: Robust surveillance is needed to ensure
comprehensive understanding of real -world safety. This surveillance strategy
consists of complementary approaches to ensure timely signal identification
and evaluation in populations expected to receive the B NT162b2under an
Emergency Use Authorization (EUA).
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Page 71Table39. Action Plan for Important Identified Risk “Anaphylaxis ”
Monitoring by the
sponsor for safety issue
and proposed actionsC4591001: Safety evaluations w ill include AE SI, including anaphylaxis;
these will be collected systemically and monitored throughout the Phase 3
study.
C4591009: Post -approval observational studies using real -world data are
needed to assess the association betw een BNT162b2 and safety events of
interest, among persons administered the vaccine in both the overall US
population and in populations of interest (e.g., pregnant w omen, the
immunocompromised and persons with a prior history of COVID -19
infection). This observational study will capture safety events (based on
AESI) including anaphylaxis, in individuals of any age who received the
BNT162b2 since its availability under an EUA usingelectronic health
records and claims data from data partners participating in the Sentinel
System. This study, will capture hospitalizations, deaths and serious safety
events of interest, including anaphylaxis, as well as selected pregnancy -
related and b irth outcomes.
C4591011 and C4591012 :
1.The collection of safety data in vaccine recipients is critical to our
understanding of the vaccine safety profile and to enable safety signal
detection and, if needed, further risk mitigation during the EUA. In
addition to the collection and monitoring o f AEs reported voluntarily by
healthcare professionals providing the vaccine and by individuals
receiving the vaccine, active surveillance studies of the BNT162b2 under
EUA are also planned.
2.Active surveillance of large numbers of individuals vaccinated with the
BNT162b2 is necessary to confirm the safety profile demonstrated in the
clinical study in a broader population under real -world conditions.
Pfizer-BioNTech plans to conduct active surveillance studies of
individuals vaccinated with the BNT162b2 under an EUA in populations
prioritized in the early stages of the EUA, e.g. , active military and
elderly, as described in the study protocols C4591011 and C4591012
submitted to FDA on 29 January 2021. The study period w ill be
approximately 30 months follo wing availability of vaccine under EUA.
The studies will capture hospitalizations, deaths and serious safety events
of interest, including anaphylaxis.
Milestones for
evaluation and
reporting C4591001 (ongoing Study):
•CSR submission upon regulatory req uest: at any time
•CSR submission 6 months post Dose 2: 31 May2021
•Final CSR submission with supplemental follow -up: 31 August 2023.
C4591009:
•Protocol submission: 31 August 2021
•Monitoring report submission: 31 October 2022
•Interim Analysis submission: 31 October 2023
•Final study report submission: 31 October 2025.
C4591011 and C4591012:
•Interim study reports w ill be submitted on the following dates based on
data collected post -EUA in target populations:
30 June 2021
31 December 2021
30 June 2022
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Page 72Table39. Action Plan for Important Identified Risk “Anaphylaxis ”
31 December 2022
•Final study reports submission: 31 December 2023 .
Action Plan for Important Potential Risks
Table40. Action Plan for Important Potential Risk “ Vaccine-associated enhanced
disease (VAED) including Vaccine-associated enhanced respiratory
disease (VAERD)”
Actions proposed C4591001 :Phase 1/2/3, placebo -controlled, randomized, observer -blind, dose-
finding study to evaluate the safety, tolerability, immunogenicity, and efficacy of
SARS-CoV-2 RNA vaccine candidates against COVID -19 in healthy individuals.
C4591008 : HERO Together: A pos t-Emergency Use Authorization observational
cohort study to evaluate the safety of the Pfizer -BioNTech COVID -19 Vaccine in
US healthcare w orkers, their families, and their communities.
C4591009 :A non-interventional post -approval safety study of the
Pfizer--BioNTech COVID -19 mRNA vaccine in the United States.
C4591011: Active safety surveillance of the P fizer--BioNTech COVID -19 vaccine
in the US Department of Defense population following Emergency Use
Authorization.
C4591012: Post -emergency use authorization active safety surveillance study
among individuals in the Veteran’s Affairs Health System receiving
Pfizer--BioNTech Coronavirus Disease 2019 (COVID- 19) vaccine.
Objective of
proposed actionsC4591001: to evaluate the safety, tolerability, i mmunogenicity, and efficacy of
BNT162b2 . An unfavorable imbalance between the vaccine and control groups in
the frequency of COVID -19 disease, in particular for severe COVID -19 disease,
may indicate the occurrence of VAED/VAERD. Surveillance is planned f or 2
years following Dose 2.
C4591008, C4591009 , C4591011, and C4591012: to characterize the real -world
incidence of safety events of interest, including events indicative of severe or
atypical COVID -19 disease, among individuals vaccinated with the BNT162 b2
sinceEUA.
Rationale for
proposed actionsC4591001: Robust and long -term monitoring throughout the clinical study for up
to 2 years to assess the risk for vaccine -associated enhanced disease.
C4591008, C4591009 , C4591011 and C4591012: Robust surveillance is needed
to ensure comprehensive understanding of real -world safety. This surveillance
strategy consists of complementary approaches to ensure timely signal
identification and evaluation in populations expecte d to receive the vaccine in the
early stages of an EUAas well as with broader vaccination roll -out.
Monitoring by the
sponsor for safety
issue and proposed
actionsC4591001: Protocol prespecified stopping and alert rules were set for detecting
enhanced COVID -19.
Participants in all stages of the study will be monitored for COVID -19 illness
including severe COVID -19 from Visit 1 onward. Cases will undergo blinded
review to identify whether any features of each case appear unusual, in particular
greater severity. Indicators of severity may include accelerated deterioration,
need for hospitalization, need for ventilation, or death. The Data Monitoring
Committee, supported by an unblinded medical monitor, w ill look for adverse
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Page 73Table40. Action Plan for Important Potential Risk “ Vaccine-associated enhanced
disease (VAED) including Vaccine-associated enhanced respiratory
disease (VAERD)”
Monitoring by the
sponsor for safety
issue and proposed
actions
(Cont’d)imbalances between vaccine and control groups in COVID -19 disease outcomes,
in particular for cases of severe COVID -19, that may be a signal for vaccine -
associated enhanced disease on an ongoing basis and at interim analyses. Stopping
rules were set so that enrollment could be paused in the event of an adverse
imbalance.
Additional safety evaluations will include AE SIthat could represent symptoms of
severe COVID- 19 disease; these will be collected systemica lly and monitored
throughout the Phase 3 study.
C4591008, C4591011, C4591012: The collection of safety data in vaccine
recipients is critical to our understanding of the vaccine safety profile and to
enable efficient safety signal detection and, if needed, further risk mitigation
during the EUA. In addition to the collection and monit oring of AEs reported
voluntarily by healthcare professionals providing the vaccine and by individuals
receiving the vaccine, active surveillance studies of the BNT162b2 under EUA are
also planned. Active surveillance of large numbers of individuals vacci nated with
the BNT162b2 is necessary to confirm the safety profile demonstrated in the
clinical study in a broader population under real -world conditions. Pfizer -
BioNTech plans to conduct active surveillance studies of vaccinated individuals in
population s prioritized in the early stages of the EUA, e .g., healthcare w orkers,
active military, and elderly, as described in C4591008 protocol submitted to FDA
on 28 January 2021; C4591011 protocol submitted to FDA on 29 January 2021
and C4591012 protocol submitted to FDA on 29 January 2021. The study period
will be approximately 30 months following availability of vaccine under EUA.
The studies will capture hospitalizations, deaths and serious safety events of
interest, including severe COVID -19 (which, if asso ciated with vaccination, may
indicate VAED/VAERD).
C4591009: Surveillance of large numbers of individuals vaccinated with the
BNT162b2 is necessary to confirm the safety profile demonstrated in the clinical
study in a broader population under real -world conditions. This study is intended
to capture a broader sample of vaccinated individuals of any age in the general US
population using large scale data sources.
Milestones for
evaluation and
reporting C4591001 (ongoing Study):
•CSR submission upon regula tory request: at any time
•CSR submission 6 months post Dose 2: 31 May2021
•Final CSR submission with supplemental follow -up: 31 August 2023 .
Threeobservational post-authorization safety studies for EUA
(C4591008, C4591011, and C4591012):
•Interim study reports w ill be submitted on the following dates based on data
collected post -EUA in target populations:
30 June 2021
31 December 2021
30 June 2022
31 December 2022
•Final study reports submission: 31 December2023.
C4591009:
•Protocol submission: 31 Augus t 2021
•Monitoring report submission: 31 October 2022
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Page 74Table40. Action Plan for Important Potential Risk “ Vaccine-associated enhanced
disease (VAED) including Vaccine-associated enhanced respiratory
disease (VAERD)”
•Interim Analysis submission: 31 October 2023
•Final study report submission: 31 October 2025.
Action Plan for Missing Information
Table41. Action Plan for Missing Information “Use in Pregnancy and L actation”
Actions proposed C4591015 :A phase 2/3, placebo -controlled, randomized, observer blind study to
evaluate the safety, tolerability, and immunogenicity of a SARS-CoV-2 RNA
vaccine candidat e (BNT162b2) against COVID -19 in healthy pregnant women 18
years of age and older .
C4591009 : A non-interventional post -approval safety study of the
Pfizer--BioNTech COVID -19 mRNA vaccine in the United States.
C4591011 :Active safety surveillance of the Pfizer -BioNTech COVID -19 Vaccine
in the US Department of Defense population following Emergency Use
Authorization.
C4591022 : Pfizer-BioNTech COVID -19 Vaccine exposure during pregnancy: A
non-interventional post -approval safety study of pregnancy and infant outcomes in
the Organization of Teratology Information Specialists (OTIS)/MotherToBaby
Pregnancy Registry .
Objective of
proposed actionsC4591015: To assess safety and immunogenicity of BNT162b2 in pregnant
women.
In addition ,exploratory objectives include:
To describe the immune response in infants born to breastfeeding maternal
participants vaccinated with prophylactic BNT162b2 during pregnancy.
To describe the safety of maternal immunization in infants born to breastfeedin g
maternal participants vaccinated w ith prophylactic BNT162b2 during pregnancy.
C4591009a: Toassess whether pregnant womenexperience increased risk of
safety events of interest following receipt of the BNT162b2 .
C4591011a: To assess whether sub -cohorts of interest, such as pregnant women, in
the MHS experience increased risk of safety events of interest following receipt of
the BNT162b2 .
C4591022a: To assess whether pregnant women receiving BNT162b2 experience
increased risk of pregnancy and infant safety outcomes, including major
congenital malformations, spontaneous abortion, stillbirth, preterm delivery, small
for gestatio nal age, and small for age postnatal growth to one year of age.
Rationale for
proposed actionsAcquisition of data in an unstudied population with potentially different safety
considerations from the time vaccine is available.
Monitoring by the
sponsor for safety
issue and proposed
actionsC4591015: Monitoring via ongoingclinical study.
C4591009: The collection of safety data in vaccine recipients ,including pregnant
women,is critical to our understanding of the vaccine safety profile and to enable
robust safety signal detection and evaluation and, if needed, further risk mitigation
under BLA.
C4591011:
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1.The collection of safety data in vaccine recipients is critical to our
understanding of the vaccine safety profile and to enable efficient safety
signal detection and, if needed, further risk mitigation. Active surveillance
studies of the BNT162b2 under EUA are also planned.
2.Activesurveillance of large numbers of individuals vaccinated w ith the
BNT162b2 is necessary to confirm the safety profile demonstrated in the
clinical study in a broader population under real -world conditions. Pfizer -
BioNTech plans to conduct active surveillance studies of individuals
vaccinated w ith the BNT162b2 under an EUA in p opulations prioritized in
the early stages of the EUA, e .g., active military and their family members , as
described in C4591011 (protocol submitted to FDA on 29 January 2021).
The study period w ill be approximately 30 months following availability of
vaccine under EUA. The study will capture hospitalizations, deaths and
serious safety events of interest, including anaphylaxis.
C4591022: This study will monitor rates of pregnancy and infant outcomes in
planned and unplanned pregnancies exposed to BNT162b2 using an established
pregnancy registry. Women receiving BNT162b2 during pregnancy will be
followed from exposure to one -year post-partum. Analyses will be conducted to
evaluate if the pregnant women receiving the vaccine during pregnancy
experience increased risk of pregnancy and infant outcomes compared with 1)
pregnant w omen who are unvaccinated and 2) pregnant women who have received
an influenza or tetanus, diphtheria, and acellular pertussis ( Tdap)vaccine during
pregnancy.
Milestones for
evaluation and
reporting C4591015:
Primary endpoints completion: 30 April 2023 .
C4591009:
•Protocol submission: 31 August 2021
•Monitoring report submission: 31 October 2022
•Interim Analysis submission: 31 October 2023
•Final study report submission: 31 October 2025 .
C4591011:
•Interim study reports w ill be submitted on the following dates based on data
collected post -EUA in target populations:
o30 June 2021
o31 December 2021
o30 June 2022
o31 December 2022
• Final study report submission: 31 December2023.
•C4591022 :
•Protocol submission: 01 July2021
•Interim reports submission :
o31 January2022
o31 January 2023
o31 January2024
o31 January 2025
•Final study report submission: 01 December 2025
a.Study assesses pregnancy only.
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Action proposed C4591014: Pfizer-BioNTech COVID -19 BNT162b2 Vaccine Effectiveness Study
-Kaiser Permanente Southern California.
WI235284: Determining RSV Burden and Outcomes in Pregnant Women and
Older Adults Requiring Hospitalization . COVID-19 Amendment for COVID
VE/Sub-study 6.
WI255886: Avon Community Acquired Pneumonia Surveillance Study: A Pan -
pandemic Acute Low er Respiratory Tract Disease Surveillance Study .
BNT162-01 cohort 13: Immunogenicity of Pfizer-BioNTech COVID -19 Vaccine
in immunocompromised subjects, including assessment of antibody responses and
cell-mediated responses.
Objective of
proposed actionsC4591014: To estimate the effectiveness of 2 doses of BNT162b2 against
hospitalization and emergency department admission for acute respiratory illness
due to SARS -CoV-2 infection.
WI235284: To estimate the effectiveness of 2 doses of BNT162b2 against
hospitalization for acute respiratory illness due to SARS -CoV-2 infection.
WI255886: To estimate the effectiveness of 2 doses of BNT162b2 against
hospitalization for acute respiratory illness due to SARS -CoV-2 infection.
BNT-162-01 cohort 13: To assess potentially protective immun e responses in
immunocompromised adults.
Rationale for
proposed actionsC4591014: To determine the effectiveness of BNT162b2 when administered
outside of the clinical setting.
WI235284: To determine the effectiveness of BNT162b2 when administered
outside of the clinical setting.
WI255886: To determine the effectiveness of BNT162b2 when administered
outside of the clinical setting.
BNT-162-01 cohort 13: To determine whether the BNT162b2 has potential to
protect immunocompromised adults.
Monitoring by the
sponsor for safety
issue and proposed
actionsC4591014: Use of primary and secondary data sources to monitor COVID -19
infection in vaccinated individuals.
WI235284: Use of primary and secondary data sources to monitor COVID -19
infection in vaccinated indivi duals.
WI255886: Use of primary and secondary data sources to monitor COVID -19
infection in vaccinated individuals.
BNT-162-01 cohort 13: Reactogenicity, AE and SAE assessment.
Milestones for
evaluation and
reporting C4591014: Final CSR submission: 30 June 2023 .
WI235284: Final CSR submission: 30 June 2023 .
WI255886: Final CSR submission: 30 June 2023 .
BNT-162-01 cohort 13: First IA submission: 30 September 2021 .
Table43. Action Plan for Missing Information “ Use in Pa ediatric Individuals
<12Years of Age ”
Actions proposed C4591001 ≥12 to ≤15 years of age: Phase 1/2/3, placebo -controlled, randomized,
observer-blind, dose -finding study to evaluate the safety, tolerability,
immunogenicity, and efficacy of SARS -CoV-2 RNA vaccine c andidates against
COVID-19 in healthy individualsa.
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<12Years of Age ”
Randomised placebo -controlled study in 2000 participants (1000 active recipients)
of 2 doses of BNT162b2 at a 21-day interval.
C4591007 <12 years of age: Phase 1 open label dose- finding study to evaluate
safety, tolerability, and immunogenicity and phase 2/3 placebo -controlled,
observer-blinded safety, tolerability, and immunogenicity study of a
SARS-CoV-2 RNA vaccine candidate against COVID -19 in healthy children <12
years of age.
Phase 1: open -label dose finding portion up to 3 age groups (participants ≥5 to
<12 years, ≥2 to <5 years, and ≥6 months to <2 years of age) with 16 participants
per dose level. Dose finding is being initiated in this study in participants ≥5 to
<12 years of age based on the acceptable blinded safety assessment of the 30 -μg
dose in 12 -to 15-year-olds in the C4591001 study. The purpose of Phas e 1 is to
identify preferred dose level(s) of BNT162b2 from up to 3 different dose levels in
each age group.
Phase 2/3: Children ≥5 to <12 years of age are randomized 2:1 at selected dose
level of BNT162b2 at a 21-day interval (2250 total subjects; 1500 a ctive vaccine).
Children 2 to < 5 years and 6 to 23 months of age randomized 2:1 placebo
controlled at selected dose level of BNT162b2 at a 21-day interval (1125 total
subjects per age group; 750 active vaccine per age group).
C4591009 :A non-interventi onal post-approval safety study of the
Pfizer-BioNTech COVID -19 mRNA vaccine in the United States.
Objective of
proposed actionsC4591001 ≥12 to ≤15 years of age: Safety compared to placebo and immune -non-
inferiority of neutralizing antibody immune response compared to subjects 16 -25
years of age.
C4591007 < 12 years of age: Dose selection. Safety compared to placebo and
immune-non-inferiority by 3 age cohorts of neutralizing antibody immune
response compared to subjects 16 -25 years of age. Efficacy if sufficient cases
accrue.
C4591009 : To assess the occurrence of safety events of interest in a general US
population (<12 and ≥ 12 to ≤15 yearsof age) within selected data sources
participating in the Sentinel System.
Rationale for
proposed actionsC4591001 ≥12 to ≤15 years of age: Need to collect evidence of safety and
effectiveness to support immunization in this age group.
C4591007 < 12 years of age: Need to collect evidence of safety and effectiveness
to support immunization in this age group.
C4591009 : Long-term surveillance of large numbers of individuals (<12 and ≥ 12
to ≤15 years of age) vaccinated w ith the BNT162b2 is necessary to confirm the
safety profile demonstrated in the clinical study in a broader population under
real-world condition s.
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<12Years of Age ”
Monitoring by the
sponsor for safety
issue and proposed
actionsC4591001 ≥12 to ≤15 years of age:
•Electronic diary for reactogenicity 7 days following each dose of vaccine.
•Adverse events for one month after second dose.
•Serious Adverse Events for 6 months after the second dose.
•Related SAEs and related deaths for 24 months after the second dose.
•Collection of COVID -19 and MIS -C cases up to 24 months after the second
dose.
C4591007 < 12 years of age:
•Electronic diary for reactogenicity 7 days followin g each dose of vaccine.
•Adverse events for one month after second dose.
•Serious Adverse Events for 6 months after the second dose.
•Related SAEs and related deaths for 24 months after the second dose.
•Collection of COVID -19 and MIS -C cases up to 24 months after the second
dose.
C4591009 :< 12 and ≥12 to ≤15 years of age
•Longitudinal medical care information on outpatient medication dispensing ,
vaccine administrations, and inpatient and outpatient diagnoses and procedures
in addition to adjudication of select events via medical records .
•Incidence rates and comparative incidence rate ratios ofsafety events of
interest (AESIs from FDA’s BEST System70and CDC’s V accine Safety
Datalink71in addition to vaccine -associated enhanc ed respirator disease ).
• Studyperiod to start on date that BNT162b2 became available under EUA
(December 11, 2020) and w ill end a m inimum of 3 years after this date.
•Risk windows will be defined for safety events of interest that have a
hypothesized increased risk during specific time periods follow ing vaccination.
For other safety events of interest, patients will be followed for a maximum of
1 year.
Milestones for
evaluation and
reporting C4591001 ≥12 to ≤15 years of age:
•First report w ith up to 1-month post dose 2 (safety): 30 April 2021
•Further reports:
6-month post dose 2 (safety): 31 July 2021
24-month post dose 2 (safety): 31 January 2023 .
C4591007 <12 years of age:
•First report w ith up to 1 -month post dose 2 in ≥5 to <12 years of age (safety):
30 September 2021
•Further reports:
6-month post dose 2 (safety): 31 March 2022
24-month post dose 2 (safety): 30 September 2023 .
C4591009:
•Protocol submission: 31 August 2021
•Monitoring report submission: 31 October 2022
•Interim Analysis submission: 31 October 2023
•Final study report submission: 31 October 2025 .
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<12Years of Age ”
a.Study originally included in the PVP to address the Missing Information “Use in pediatric individuals < 16 years of
age”.
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Table44.Summary of Safety Concerns and Action Plans
Safety Concerns Ongoing/Planned Action Summary of Objectives Milestones Due dates
Anaphylaxis C4591001: Phase 1/2/3, placebo -
controlled, randomized, observer -blind,
dose-finding study to evaluate the
safety, tolerability, immunogenicity,
and efficacy of SARS -CoV-2 RNA
vaccine candidates against COVID -19
in healthy individuals.
OngoingTo evaluate the safety, tolerability,
immunogenicity, and efficacy of
BNT162b2 .
An unfavorable imbalance between
the vaccine and control groups in the
frequency of COVID -19 disease, in
particular for severe COVID- 19
disease, may indicate the occurrence
of VAED/VAER D. Surveillance is
planned for 2 years following Dose
2.CSR submission upon
regulatory request:
CSR submission
6-month post Dose 2:
Final CSR submission
with supplemental
follow-up:At any time
31 May 2021
31 August 2023
C4591009: A non-interventional
post-approval safety study of the Pfizer -
BioNTech COVID -19 mRNA Vaccine
in the United States.
PlannedTo assess the occurrence of safety
events of interest in the general US
population, pregnant w omen, the
immunocompromised and persons
with a prior history of COVID -19
within selected data sources
participating in the US Sentinel
System.Protocol submission:
Monitoring report
submission:
Interim analysis
submission:
Final study report
submission:31 August 2021
31 October 2022
31 October 2023
31 October 2025
C4591011: Active safety surveillance
of the Pfizer-BioNTech COVID -19
Vaccinein the US Department of
Defense population following
Emergency Use Authorization.
PlannedTo assess whether individuals in the
US DoD Military Health System
(MHS) experience increased risk of
safety events of interest, following
receipt of the BNT162b2 . Interim reports
submission:
Final study report
submission:30 June 2021
31 December 2021
30 June 2022
31 December 2022
31 December 2023
Anaphylaxis
(Cont’d)C4591012: Post -emergency use
authorization active safety surveillance
study among individuals in the
Veteran’s Affairs Health System
receiving Pfizer-BioNTech COVID -19
Vaccine. To assess whether individuals in the
US Veteran’s Affairs Health System
experience increased risk of safety
events of interest, following receipt
of theBNT162b2 .Interim reports
submission :
Final study report
submission:30 June 2021
31 December 2021
30 June 2022
31 December 2022
31 December 2023
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Safety Concerns Ongoing/Planned Action Summary of Objectives Milestones Due dates
Planned
Vaccine-
associated
enhanced disease
(VAED)
including
vaccine-
associated
enhanced
respiratory
disease (VAERD)C4591001: Phase 1/2/3, placebo -
controlled, randomized, observer -blind,
dose-finding study to evaluate the
safety, tolerability, immunogenicity,
and efficacy of SARS -CoV-2 RNA
vaccine candidates against COVID -19
in healthy individuals.
OngoingTo evaluate the safety, tolerability,
immunogenicity, and efficacy of
BNT162b2 .
An unfavorable imbalance between
the vaccine and control groups in the
frequency of COVID -19 disease, in
particular for severe COVID- 19
disease, may suggest the occurrence
of VAED/VAERD . Surveillance is
planned for 2 years following Dose 2CSR submission u pon
regulatory request:
CSR submission
6-month post Dose 2:
Final CSR submission
with supplemental
follow-up:Any time
31 May 2021
31 August 2023
C4591008/C4591011/C4591012:
Post-authorization epidemiological
safety studies using active and passive
surveillance strategies for safety events,
including severe or atypical
COVID-19, among individuals
receiving Pfizer-BioNTech COVID -19
Vaccine
C4591008: Ongoing
C4591011/C4591012: PlannedTo characterize the real -world
incidence of safety events of interest,
including events indicative of severe
or atypical COVID -19 disease,
among individuals vaccinated with
the BNT162b2 since EUAInterim reports
submission:
Final study report
submission:30 June 2021
31 December 2021
30 June 2022
31 December 2022
31 December 2023
Vaccine-
associated
enhanced disease
(VAED)
including
vaccine-
associated
enhanced C4591009 : A non-interventional
post-approval safety study of the
Pfizer-BioNTech COVID -19 mRNA
Vaccine in the United States
PlannedTo characterize the real -world
incidence of safety events of interest,
including events indicative of severe
or atypical COVID -19 disease,
among individuals vaccinated with
the BNT162b2Protocol submission:
Monitoring report
submission:
Interim analysis
submission:
Final study report
submission:31 August 2021
31 October 2022
31 October 2023
31 October 2025
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Safety Concerns Ongoing/Planned Action Summary of Objectives Milestones Due dates
respiratory
disease (VAERD)
(Cont’d)
Use in pregnancy
and lactationC4591015: A phase 2/3,
placebo-controlled, randomized,
observer-blind study to evaluate the
safety, tolerability, and immunogenicity
of a SARS-CoV-2 RNA vaccine
candidate (BNT162b2) against
COVID-19 in healthy pregnant w omen
18 years of age and older.
OngoingTo assess safety and immunogenicity
of BNT162b2 in pregnant women.
Exploratory objectives include:
To describe the immune response in
infants born to breastfeeding maternal
participants vaccinated with
prophylactic BNT162b2 during
pregnancy.
To describe the safety of maternal
immunization in infants b orn to
breastfeeding maternal participants
vaccinated w ith prophylactic
BNT162b2 during pregnancy .Primary endpoints
completion:30 April 2023
Use in pregnancy
and lactation
(Cont’d)C4591011: Active safety surveillance
of the Pfizer -BioNTech COVID -19
Vaccine in the United States
Department of Defense population
following Emergency Use
Authorization
PlannedTo assess whether sub -cohorts of
interest, such as pregnant women, in
the MHS experience increased risk of
safety events of interest following
receipt of the BNT162b2 .Interim reports
submission:
Final study report
submission:30 June 2021
31 December 20 21
30 June 2022
31 December 2022
31 December 2023
C4591009 : A non-interventional post -
approval safety study of the Pfizer -
BioNTech COVID -19 mRNA Vaccine
in the United States.
PlannedTo assess whether pregnant women,
experience increased risk of safety
events of interest following receipt of
the BNT162b2 .Protocol submission:
Monitoring report
submission:
Interim analysis
submission:
Final study report
submission: 31 August 2021
31 October 2022
31 October 2023
31 October 2025
C4591022: Pfizer-BioNTech COVID -19
Vaccine exposure during pregnancy: A
non-interventional post -approval safety
study of pregnancy and infant outcomes To assess whether pregnant women
receiving BNT162b2 experience
increased risk of pregnancy and
infant safety outcomes, including Protocol submission:
Interim reports
submission:01 July2021
31 January2022
31 January 2023
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Safety Concerns Ongoing/Planned Action Summary of Objectives Milestones Due dates
in the Organization of Teratology
Information Specialists
(OTIS)/MotherToBaby Pregnancy
Registrymajor congenital malformations,
spontaneous abortion, stillbirth,
preterm delivery, smal l for
gestational age, and small for age
postnatal growth to one year of age.Final study report
submission:31January2024
31 January 2025
01 December 2025
Vaccine
effectivenessC4591014: Pfizer -BioNTech COVID -
19 BNT162b2 Vaccine Effectiveness
Study -Kaiser Permanente Southern
California .
PlannedTo estimate the effectiveness of 2
doses of BNT162b2 against
hospitalization and emergency
department admission for acute
respiratory illness due to SARS -
CoV-2 infection.Final CSR
submission:30 June 2023
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Page 84Table44.Summary of Safety Concerns and Action Plans
Safety Concerns Ongoing/Planned Action Summary of Objectives Milestones Due dates
Vaccine
effectiveness
(Cont’d)WI235284: Determining RSV Burden
and Outcomes in Pregnant Women and
Older Adults Requiring Hospitalization .
Amendment for COVID VE /Sub-
study 6.
PlannedTo estimate the effectiveness of 2
dosed of BNT162b2 against
hospitalization for acute respiratory
illness due to SARS -CoV-2
infection.Final CSR
submission:30 June 2023
WI255886: Avo n Community Acquired
Pneumonia Surveillance Study: A Pan -
pandemic Acute Low er Respiratory
Tract Disease Surveillance .
PlannedTo estimate the effectiveness of 2
doses of BNT162b2 against
hospitalization for acute respiratory
illness due to SARS -CoV-2
infection.Final CSR
submission:30 June 2023
BNT162-01 cohort 13: Immunogenicity
of Pfizer-BioNTech COVID -19
Vaccinein immunocompromised
subjects, including assessment of
antibody responses and cell -mediated
responses.
OngoingTo assess potentially protective
immune responses in
immunocompromised adults.First IA submission: 30 September 2021
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Safety Concerns Ongoing/Planned Action Summary of Objectives Milestones Due dates
Use in pediatric
individuals <12
years of ageC4591001 ≥ 12 to ≤15 years of age :
Phase 1/2/3, placebo -controlled,
randomized, observer -blind, dose -
finding study to evaluate the safety,
tolerability, immunogenicity, and
efficacy of SARS -CoV-2 RNA vaccine
candidates against COVID -19 in
healthy individualsa.
OngoingSafety compared to placebo and
immune-non-inferiority of
neutralizing antibody immune
response compared to subjects 16 -25
years of age.First report w ith up to
1-month post dose 2
(safety):
Report 6-month post
dose 2 (safety):
Report 24 -monthpost
dose 2 (safety):30 April 2021
31 July 2021
31 January 2023
C4591007 <12 years of age:
Phase 1 open label dose- finding study to
evaluate safety, tolerability, and
immunogenicity and phase 2/3 placebo -
controlled, observer blinded safety,
tolerability, and immunogenicity, study
of a SARS -CoV-2 RNA vaccine
candidate against COVID -19 in healthy
children <12 years of age.
Ongoing (started in March)Dose selection. Safety compared to
placebo and immune -non-inferiority
by 3 age cohorts of neutralizing
antibody immune response compared
to subjects 16 -25 years of age.
Efficacy if sufficient cases accrue.First report w ith up to
1-month post dose 2
(safety) in ≥5 to <12
years of age:
Report 6-month post
dose 2 (safety) in ≥5
to <12 years of age:
Report 24 -month post
dose 2 (safety) in ≥5
to <12 years of age:30 September 2021
31 March 2022
30 September 2023
C4591009 : A non-interventional post -
approval safety study of the Pfizer -
BioNTech COVID -19 mRNA vaccine
in the United States.
PlannedTo assess the occurrence of safety
events of interest in a general US
population (< 12 and ≥12 to ≤15
years of age) within selected data
sources participating in the Sentinel
System. Protocol submission:
Monitoring report
submission:
Interim analysis
submission:
Final study report
submission: 31 August 2021
31 October 2022
31 October 2023
31 October 2025
a.Study originally included in the PVP to address the Missing Information “Use in pediatric individuals < 16 years of age.
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Page 86ANNEX
3.2.Pharmacovigilance Methods
BNT162b2 Vaccine: BNT162b2 Data Capture Aid s:
oPfizer-BioNTech COVID- 19 Vaccine VAED Data Capture Aid.
oPfizer-BioNTech COVID- 19 Vaccine Anaph ylactic Reaction Data Capture
Aid.
3.2.1.List of Studies I ncluded in the Pharmacovigilance Plan
C4591001
C4591007
C4591008
C4591009
C4591011
C4591012
C4591014
C4591015
C4591022
BNT162-01 cohort 13
WI235284
WI255886
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Page 87REFERENCES
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