Document text
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 15.3.6 CUMULATIVE ANALYSIS OF POST-AUTHORIZATION ADVERSE EVENT
REPORTS OF PF-07302048 (BNT162B2) RECEIVED THROUGH 28-FEB-2021
Report Prepared by:
Worldwide Safety Pfizer
The information contained in this document is proprietary and confidential. Any disclosure, reproduction,
distribution, or other dissemination of this information outside of Pfizer, its Affiliates, its Licensees, or
Regulatory Agencies is strictly prohibited. Except as may be ot herwise agreed to in writing, by accepting or
reviewing these materials, you agree to hold such information in confidence and not to disclose it to others
(except where required by applicable law), nor to use it for un authorized purposes.090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000054
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 2TABLE OF CONTENTS
LIST OF TABLES................................................. ....................................................................3
LIST OF FIGURES ................................................ ...................................................................3
APPENDICES ...........................................................................................................................3
LIST OF ABBREVIATIONS....................................................................................................41. INTRODUCTION ................................................ .................................................................5
2. METHODOLOGY ................................................. ...............................................................5
3. RESULTS ..............................................................................................................................6
3.1. Safety Database ........................................... ..............................................................6
3.1.1. General Overview........................................ .................................................6
3.1.2. Summary of Safety Concerns in the US Pharmacovigilance P lan ...............9
3.1.3. Review of Adverse Events of Special Interest (AESIs) .... .........................16
3.1.4. Medication error ........................................ .................................................26
4. DISCUSSION.................................................. ....................................................................28
5. SUMMARY AND CONCLUSION ...................................... ..............................................29090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000055
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 3LIST OF TABLES
Table 1. General Overview: Selected Characteristics of All Cases Received
During the Reporting Interval.................................. ...................................7
Table 2. Events Reported in ≥2% Cases........................... ........................................8
Table 3. Safety concerns........................................ ...................................................9
Table 4. Important Identified Risk.............................. ............................................10
Table 5. Important Potential Risk...........................................................................11
Table 6. Description of Missing Information .........................................................12Table 7. AESIs Evaluation for BNT162b2.......................... ...................................16
Table 8. ME PTs by seriousness with or without harm co-associati on
(Through 28 February 2021) ..................................... ...............................27
LIST OF FIGURES
Figure 1. Total Number of 13vPnC AEs by System Organ Classes and Event
Seriousness .................................................................................................8
APPENDICES
APPENDIX 1 LIST OF ADVERSE EVENTS OF SPECIAL INTEREST ........... .................30090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000056
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 4LIST OF ABBREVIATIONS
Acronym Term
AE adverse event
AESI adverse event of special interest
BC Brighton Collaboration
CDC Centers for Disease Control and Prevention
COVID-19 coronavirus disease 2019
DLP data lock point
EUA emergency use authorisation
HLGT (MedDRA) High Group Level Term
HLT (MedDRA) High Level Term
MAH marketing authorisation holde r
MedDRA medical dictionary for regulatory activities
MHRA Medicines and Healthcare products Regulatory Agency
PCR Polymerase Chain Reaction
PT (MedDRA) Preferred Term
PVP pharmacovigilance plan
RT-PCR Reverse Transcription-Polymerase Chain Reaction
RSI reference safety information
TME targeted medically event
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
SMQ standardised MedDRA query
SOC (MedDRA) System Organ Class
UK United Kingdom
US United States
VAED vaccine-associated enhanced disease
VAERD vaccine-associated enhanced respiratory disease
VAERS vaccine adverse event reporting system090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000057
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 51. INTRODUCTION
Reference is made to the Request for Comments and Advice submit ted 04 February 2021
regarding Pfizer/BioNTech’s proposal for the clinical and post-a uthorization safety data
package for the Biologics License Application (BLA) for our inve stigational COVID-19
Vaccine (BNT162b2). Further reference is made to the Agency’s 0 9 March 2021 response to
this request, and specifically, the following request from the Agency.
“Monthly safety reports primarily focus on events that occurred during the reporting interval
and include information not relevant to a BLA submission such as line lists of adverse events by country. We are most interested in a cumulative analysis of post-authorization safety data to support your future BLA submission. Please submit an integrated analysis of your cumulative post-authorization safety data, including U.S. and foreign post-authorization experience, in your upcoming BLA submission. Please include a cumulative analysis of the Important Identified Risks, Important Potential Risks, and areas of Important Missing Information identified in your Pharmacovigilance Plan, as well as adverse events of special interest and vaccine administration errors (whether or not associated with an adverse event). Please also include distribution data and an analysis of the most common adverse events. In addition, please submit your updated Pharmacovigilance Plan with your BLA submission.”
This document provides an integrated analysis of the cumulative post-authorization safety
data, including U.S. and foreign post-authorization adverse eve nt reports received through 28
February 2021.2. METHODOLOGY
Pfizer is responsible for the management post-authorization saf ety data on behalf of the
MAH BioNTech according to the Pharmacovigilance Agreement in place. Data from
BioNTech are included in the report when applicable.
Pfizer’s safety database contains cases of AEs reported spontan eously to Pfizer, cases
reported by the health authorities, cases published in the medi cal literature, cases from
Pfizer-sponsored marketing programs, non-interventional studies , and cases of serious AEs
reported from clinical studies regardless of causality assessme nt.
The limitations of post-marketing adverse drug event reporting should be considered when
interpreting these data:
•Reports are submitted voluntarily, and the magnitude of underre porting is unknown.
Some of the factors that may influence whether an event is reported include: length of
time since marketing, market share of the drug, publicity about a drug or an AE,
seriousness of the reaction, regulatory actions, awareness by h ealth professionals and
consumers of adverse drug event reporting, and litigation.
•Because many external factors influence whether or not an AE is reported, the
spontaneous reporting system yields reporting proportions not i ncidence rates. As a
result, it is generally not appropriate to make between-drug co mparisons using these 090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000058
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 6proportions; the spontaneous reporting system should be used for signal detection
rather than hypothesis testing.
•In some reports, clinical information (such as medical history, validation of diagnosis,
time from drug use to onset of illness, dose, and use of concom itant drugs) is missing
or incomplete, and follow-up information may not be available.
•An accumulation of adverse event reports (AERs) does not necess arily indicate that a
particular AE was caused by the drug; rather, the event may be due to an underlying
disease or some other factor(s) such as past medical history or concomitant
medication.
•Among adverse event reports received into the Pfizer safety dat abase during the
cumulative period, only those having a complete workflow cycle in the safety database
(meaning they progressed to Distribution or Closed workflow sta tus) are included in the
monthly SMSR. This approach prevents the inclusion of cases tha t are not fully processed
hence not accurately reflecting final information. Due to the l arge numbers of
spontaneous adverse event reports received for the product, the M AH has prioritised the
processing of serious cases, in order to meet expedited regulatory reporting timelines and ensure these reports are available for signal detection and eva luation activity. The
increased volume of reports has not impacted case processing fo r serious reports, and
compliance metrics continue to be monitored weekly with prompt action taken as needed
to maintain compliance with expedited reporting obligations. No n-serious cases are
entered into the safety database no later than 4 calendar days from receipt. Entrance into the database includes the coding of all adverse events; this all ow for a manual review of
events being received but may not include immediate case proces sing to completion.
Non-serious cases are processed as soon as possible and no late r than 90 days from
receipt. Pfizer has also taken a multiple actions to help allev iate the large increase of
adverse event reports. This includes significant technology enha ncements, and process
and workflow solutions, as well as increasing the number of dat a entry and case
processing colleagues. To date, Pfizer has onboarded approximat ely additional full-
time employees (FTEs). More are joining each month with an expe cted total of more than
additional resources by the end of June 2021.
3. RESULTS
3.1. Safety Database 3.1.1. General OverviewIt is estimated that approximately doses of BNT162b 2 were shipped worldwide
from the receipt of the first temporary authorisation for emerg ency supply on 01 December
2020 through 28 February 2021.
Cumulatively, through 28 February 2021, there was a total of 42,086 ca se reports (25,379
medically confirmed and 16,707 non-medically confirmed) containi ng 158,893 events. Most
cases (34,762) were received from United States (13,739), United Kingdom (13,404) Italy
(2,578), Germany (1913), France (1506), Portugal (866) and Spain (756); the remaining
7,324 were distributed among 56 other countries.090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-0000059
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 7Table 1 below presents the main characteristics of the overall cas es.
Table 1. General Overview: Selected Characteristics of All Cases Received During
the Reporting Interval
Characteristics Relevant cases (N=42086)
Gender: Female 29914
Male 9182
No Data 2990
Age range (years):0.01 -107 yearsMean = 50.9 years
n = 34952≤1 7
18-3031-50
51-64
65-74≥7 5Unknown175
a
4953
13886
7884309852146876
Case outcome: Recovered/Recovering 19582
Recovered with sequelae 520
Not recovered at the time of report 11361
Fatal 1223
Unknown 9400
a. in 46 cases reported age was <16-year-old and in 34 cases <12 -year-old.
As shown in Figure 1, the System Organ Classes (SOCs) that contained the greatest nu mber
(≥2%) of events, in the overall dataset, were General disorders an d administration site
conditions (51,335 AEs), Nervous system disorders (25,957), Musc uloskeletal and
connective tissue disorders (17,283), Gastrointestinal disorder s (14,096), Skin and
subcutaneous tissue disorders (8,476), Respiratory, thoracic an d mediastinal disorders
(8,848), Infections and infestations (4,610), Injury, poisoning and procedural complications
(5,590), and Investigations (3,693).090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000060
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 8Figure 1. Total Number of BNT162b2 AEs by System Organ Classes a nd Event
Seriousness
Table 2 shows the most commonly (≥2%) reported MedDRA (v. 23.1) PTs in the overall
dataset (through 28 February 2021),
Table 2. Events Reported in ≥2% Cases
Cumulatively Through 28
February 2021
MedDRA SOC MedDRA PT AEs (AERP%)
N = 42086
Blood and lymphatic system
disorders
Lymphadenopath y 1972 (4.7%)
Cardiac disorders
Tachycardia 1098 (2.6%)
Gastrointestinal disorders
Nausea 5182 (12.3%)
Diarrhoea 1880 (4.5%)
Vomiting 1698 (4.0%)
General disorders and administration site conditions
Pyrexia 7666 (18.2%)
Fatigue 7338 (17.4%)
Chills 5514 (13.1%)
Vaccination site pain 5181 (12.3%)
090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000061
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 9Table 2. Events Reported in ≥2% Cases
Cumulatively Through 28
February 2021
MedDRA SOC MedDRA PT AEs (AERP%)
N = 42086
Pain 3691 (8.8%)
Malaise 2897 (6.9%)
Asthenia 2285 (5.4%)
Drug ineffective 2201 (5.2%)
Vaccination site erythema 930 (2.2%)
Vaccination site swelling 913 (2.2%)
Influenza like illness 835 (2%)
Infections and infestations
COVID-19 1927 (4.6%)
Injury, poisoning and procedural complications
Off label use 880 (2.1%)
Product use issue 828 (2.0%)
Musculoskeletal and connective tissue disorders
Myalgia 4915 (11.7%)
Pain in extremity 3959 (9.4%)
Arthralgia 3525 (8.4%)
Nervous system disorders
Headache 10131 (24.1%)
Dizziness 3720 (8.8%)
Paraesthesia 1500 (3.6%)
Hypoaesthesia 999 (2.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 2057 (4.9%)
Cough 1146 (2.7%)
Oropharyngeal pain 948 (2.3%)
Skin and subcutaneous tissue disorders
Pruritus 1447 (3.4%)
Rash 1404 (3.3%)
Erythema 1044 (2.5%)
Hyperhidrosis 900 (2.1%)
Urticaria 862 (2.1%)
Total number of events 93473
3.1.2. Summary of Safety Concerns in the US Pharmacovigilance Plan
Table 3. Safety concerns
Important identified risks Anaphylaxis
Important potential risks Vaccine-Associated Enhanced Disease (VAED), Including Vaccine-a ssociated
Enhanced Respiratory Disease (VAERD)
Missing information Use in Pregnancy and lactation
Use in Paediatric Individuals <1 2Years of Age
Vaccine Effectiveness090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000062
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 10Table 4. Important Identified Risk
Topic Description
Important
Identified
RiskPost Authorization Cases Evaluation (cumulative to 28 Feb 2021)
Total Number of Cases in the Reporting Period (N=42086)
Anaphylaxis Since the first temporary authorization for emergenc y supply under Regulation 174 in the UK
(01 December 2020) and through 28 February 2021, 1833 potentially relevant cases were retrieved from
the Anaphylactic reaction SMQ (Narrow and Broad) search strateg y, applying the MedDRA algorithm.
These cases were 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 cas e definition” and Level
5 as not a case of 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), S weden (17), Czech Republic ,
Netherlands (16 each), Belgium, Ireland (13 each), Poland (12), Austria (11); the remaining 57 cases
originated from 15 different countries.
Relevant event seriousness: Serious (2341), Non-Serious (617);
Gender: Females (876), Males (106), Unknown (20);
Age (n=961) ranged from 16 to 98 years (mean = 54.8 years, medi an = 42.5 years);
Relevant even outcome
a: fatal (9)b, resolved/resolving (1922), not resolved (229), resolved with sequelae
(48), unknown (754);
Most frequently reported relevant PTs (≥2%), from the Anaphylact ic reaction SMQ (Broad and Narrow)
search strategy: Anaphylactic reaction (435), Dyspnoea (356), R ash (190), Pruritus (175), Erythema
(159), Urticaria (133), Cough (115), Respiratory distress, Throat tightness (97 each), Swollen tongue
(93), Anaphylactic shock (80), Hypotension (72), Chest discomfort (71), Swelling face (70), Pharyngeal
swelling (68), and Lip swelling (64).
Conclusion: Evaluation of BC cases Level 1 - 4 did not reveal any significant new safety information.
Anaphylaxis is appropriately described in the product labeling as are non-anaphylactic hypersensitivity
events. Surveillance will continue.
a Different clinical outcome may be reported for an event that o ccurred more than once to the same individual.
b There were 4 individuals in the anaphylaxis evaluation who die d 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 a lso have COVID-19 pneumonia, that likely contributed to
their deaths090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000063
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 11Table 5. Important Potential Risk
Topic Description
Important
Potential
RiskPost Authorization Cases Evaluation (cumulative to 28 Feb 2021)
Total Number of Cases in the Reporting Period (N=42086)
Vaccine-
Associated Enhanced Disease
(VAED),
including Vaccine-Associated
Enhanced
Respiratory Disease (VAERD)No post-authorized AE reports have been identified as cases of VAED/VAERD, therefore, there is no
observed data at 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 VAE D for this report includes PTs indicating a
lack of effect of the vaccine and PTs potentially indicative o f severe or atypical COVID-19
a.
Since the first temporary authorization for emergency supply under Regulation 174 in the UK (01
December 2020) and through 28 February 2021, 138 cases [0.33% of the total PM dataset], reporting 317 potentially relevant events were retrieved:
Country of incidence: UK (71), US (25), Germany (14), France, Italy, Mexico, Spain, (4 each), Denmark
(3); the remaining 9 cases originated from 9 different countrie s;
Cases Seriousness: 138;
Seriousness criteria for the total 138 cases: Medically signifi cant (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 were 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, med ian = 59.5);
Case outcome: fatal (38), resolved/resolving (26), not resolved (65), resolved with sequelae (1), unknown
(8);
Of the 317 relevant events, the most frequently reported PTs (≥2%) were: Drug ineffective (135),
Dyspnoea (53), Diarrhoea (30), COVID-19 pneumonia (23), Vomitin g (20), Respiratory failure (8), and
Seizure (7).
Conclusion: VAED may present as severe or unusual clinical manif estations of COVID-19. Overall, there
were 37 subjects with suspected COVID-19 and 101 subjects with c onfirmed COVID-19 following one
or both doses of the vaccine; 75 of the 101 cases were severe, resulting in hospitalisation, disability,
life-threatening consequences or death. None of the 75 cases co uld be definitively considered as
VAED/VAERD.In this review of subjects with COVID-19 following vaccination, based on the current evidence,
VAED/VAERD remains a theoretical risk for the vaccine. Surveillance will continue.
a. Search criteria: Standard Decreased Therapeutic Response Search AND PTs Dyspnoea; Tachypnoea; Hypoxia;
COVID 19 pneumonia; Respiratory Failure; Acute Respiratory Distress Syndrome; Cardiac Failure; Cardiogenic shock;
Acute myocardial infarction; Arrhythmia; Myocarditis; Vomiting; Diarrhoea; Abdominal pain; Jaundice;
Acute hepatic failure; Deep vein thrombosis; Pulmonary embolism; Per ipheral Ischaemia; Vasculitis; Shock;
Acute kidney injury; Renal failure; Altered state of consciousness; Seizure; Encephalopathy; Meningitis;
Cerebrovascular accident; Thrombocytopenia; Disseminated intravas cular coagulation; Chillblains;
Erythema multiforme; Multiple organ dysfunction syndrome; Multisys tem inflammatory syndrome in children.090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000064
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 12Table 6. Description of Missing Information
Topic Description
Missing
InformationPost Authorization Cases Evaluation (cumulative to 28 Feb 2021)
Total Number of Cases in the Reporting Period (N=42086)
Use in
Pregnancy and lactation• Number of cases: 413
a(0.98% of the total PM dataset); 84 serious and 329 non-serious;
• Country of incidence: US (205), UK (64), Canada (31), Germany (30), Poland (13), Israel (11); Italy (9), Portugal (8), Mexico (6), Estonia, Hungary and Ireland, (5 each), Romania (4),
Spain (3), Czech Republic and France (2 each), the remaining 10 cases were distributed among
10 other countries.
Pregnancy cases: 274 cases including:
• 270 mother cases and 4 foetus/baby cases representing 270 uniqu e pregnancies (the 4
foetus/baby cases were linked to 3 mother cases; 1 mother case involved twins).
• Pregnancy outcomes for the 270 pregnancies were reported as spontaneous abortion (23), outcome pending (5), premature birth with neonatal death, spontaneous abortion with intrauterine death (2 each), spontaneous abortion with neonatal death, and normal outcome (1
each). No outcome was provided for 238 pregnancies (note that 2 different outcomes were
reported for each twin, and both were counted).
• 146 non-serious mother cases reported exposure to vaccine in utero without the occurrence of
any clinical adverse event. The exposure PTs coded to the PTs M aternal exposure during
pregnancy (111), Exposure during pregnancy (29) and Maternal exposure timing unspecified
(6). Trimester of exposure was reported in 21 of these cases: 1st trimester (15 cases), 2nd trimester (7), and 3rd trimester (2).
• 124 mother cases, 49 non-serious and 75 serious, reported clinica l events, which occurred in
the vaccinated mothers. Pregnancy related events reported in th ese cases coded to the PTs
Abortion spontaneous (25), Uterine contraction during pregnancy , Premature rupture of
membranes, Abortion, Abortion missed, and Foetal death (1 each). Other clinical events which occurred in more than 5 cases coded to the PTs Headache (33), Vaccination site pain (24), Pain in extremity and Fatigue (22 each), Myalgia and Pyrexia (1 6 each), Chills (13) Nausea
(12), Pain (11), Arthralgia (9), Lymphadenopathy and Drug ineffective (7 each), Chest pain, Dizziness and Asthenia (6 each), Malaise and COVID-19 (5 each). Trimester of exposure was
reported in 22 of these cases: 1st trimester (19 cases), 2nd trim ester (1 case), 3rd trimester (2
cases).
• 4 serious foetus/baby cases reported the PTs Exposure during pregnancy, Foetal growth restriction, Maternal exposure during pregnancy, Premature baby (2 each), and Death neonatal
(1). Trimester of exposure was reported for 2 cases (twins) as occurring during the 1st
trimester.
Breast feeding baby cases: 133, of which:
• 116 cases reported exposure to vaccine during breastfeeding (PT Exposure via breast milk)
without the occurrence of any clinical adverse events;
• 17 cases, 3 serious and 14 non-serious, reported the following clinical events that occurred in the infant/child exposed to vaccine via breastfeeding: Pyrexia (5), Rash (4), Infant irritability
(3), Infantile vomiting, Diarrhoea, Insomnia, and Illness (2 each), Poor feeding infant,
Lethargy, Abdominal discomfort, Vomiting, Allergy to vaccine, Increased appetite, Anxiety, Crying, Poor quality sleep, Eructation, Agitation, Pain and Urticaria (1 each).
Breast feeding mother cases (6):
• 1 serious case reported 3 clinical events that occurred in a mother during breast feeding (PT Maternal exposure during breast feeding); these events coded to the PTs Chills, Malaise, and
Pyrexia
• 1 non-serious case reported with very limited information and w ithout associated AEs. 090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000065
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 13Table 6. Description of Missing Information
Topic Description
Missing
InformationPost Authorization Cases Evaluation (cumulative to 28 Feb 2021)
Total Number of Cases in the Reporting Period (N=42086)
• In 4 cases (3 non-serious; 1 serious) Suppressed lactation occurred in a breast feeding women
with the following co-reported events: Pyrexia (2), Paresis, Headache, Chills, Vomiting, Pain in extremity, Arthralgia, Breast pain, Scar pain, Nausea, Migraine, Myalgia, Fatigue and
Breast milk discolouration (1 each).
Conclusion: There were no safety signals that emerged from the review of these cases of use in
pregnancy and while breast feeding.
Use in
Paediatric Individuals <12 Years of
AgePaediatric individuals <12 years of age
• Number of cases: 34d(0.1% of the total PM dataset), indicative of administration in paediatric
subjects <12 years of age;
• Country of incidence: UK (29), US (3), Germany and Andorra (1 each);
• Cases Seriousness: Serious (24), Non-Serious (10);
• Gender: Females (25), Males (7), Unknown (2);
• Age (n=34) ranged from 2 months to 9 years, mean = 3.7 years, median = 4.0;
• Case outcome: resolved/resolving (16), not resolved (13), and unknown (5).
• Of the 132 reported events, those reported more than once were as follows: Product
administered to patient of inappropriate age (27, see Medication Error), Off label use (11),
Pyrexia (6), Product use issue (5), Fatigue, Headache and Nausea (4 each), Vaccination site pain (3), Abdominal pain upper, COVID-19, Facial paralysis, Lym phadenopathy, Malaise,
Pruritus and Swelling (2 each).
Conclusion: No new significant safety information was identifie d based on a review of these cases
compared with the non-paediatric population.
Vaccine EffectivenessCompany conventions for coding cases indicative of lack of efficacy:
The coding conventions for lack of efficacy in the context of a dministration of the COVID-19 vaccine
were revised on 15 February 2021, as shown below:
• PT “Vaccination failure” is coded when ALL of the following criteria are met:
o The subject has received the series of two doses per the dosing regimen in local
labeling.
o At least 7 days have elapsed since the second dose of vaccine h as been administered.
o The subject experiences SARS-CoV-2 infection (confirmed laborat ory tests).
• PT “Drug ineffective” is coded when either of the following applies:
o The infection is not confirmed as SARS-CoV-2 through laboratory tests
(irrespective of the vaccination schedule). This includes scena rios where LOE is
stated or implied, e.g., “the vaccine did not work”, “I got COV ID-19”.
o It is unknown:
Whether the subject has received the series of two doses per th e dosing
regimen in local labeling;
How many days have passed since the first dose (including unspecified number of days like” a few days”, “some days”, etc.);
If 7 days have passed since the second dose;
o The subject experiences a vaccine preventable illness 14 days after receiving the
first dose up to and through 6 days after receipt of the second dose.
Note: after the immune system as had sufficient time (14 days) to respond to the vaccine, a report of
COVID-19 is considered a potential lack of efficacy even if the vaccination course is not complete.
Summary of the coding conventions for onset of vaccine preventable disease versus the vaccination
date:090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000066
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 14Table 6. Description of Missing Information
Topic Description
Missing
InformationPost Authorization Cases Evaluation (cumulative to 28 Feb 2021)
Total Number of Cases in the Reporting Period (N=42086)
1st dose (day 1-13) From day 14 post 1st dose to
day 6 post 2nd doseDay 7 post 2nd dose
Code only the events
describing the SARS-CoV-2
infectionCode “Drug ineffective” Code “Vaccination failure”
Scenario Not considered
LOEScenario considered LOE as “Drug ineffective”Scenario considered LOE as “Vaccination failure”
Lack of efficacy cases
• Number of cases: 1665b(3.9 % of the total PM dataset) of which 1100 were medically
confirmed and 565 non medically confirmed;
• Number of lack of efficacy events: 1665 [PT: Drug ineffective (16 46) and Vaccination failure
(19)f].
• Country of incidence: US (665), UK (405), Germany (181), France (85), Italy (58), Romania
(47), Belgium (33), Israel (30), Poland (28), Spain (21), Austria (18), Portugal (17), Greece
(15), Mexico (13), Denmark (8), Canada (7), Hungary, Sweden and United Arab Emirates (5 each), Czech Republic (4), Switzerland (3); the remaining 12 cas es originated from 9 different
countries.
• COVID-19 infection was suspected in 155
cases, confirmed in 228 cases, in 1 case it was
reported that the first dose was not effective (no other informa tion).
• COVID-19 infection (suspected or confirmed) outcome was reporte d as resolved/resolving
(165), not resolved (205) or unknown (1230) at the time of the reporting; there were 65 cases where a fatal outcome was reported.
Drug ineffective cases (1649)
• Drug ineffective event seriousness: serious (1625), non-serious (21)
e;
• Lack of efficacy term was reported:
o after the 1st dose in 788 cases
o after the 2nd dose in 139 cases
o in 722 cases it was unknown after which dose the lack of efficacy occurred.
• Latency of lack of efficacy term reported after the first dose was known for 176 cases:
o Within 9 days: 2 subjects;
o Within 14 and 21 days: 154 subjects;
o Within 22 and 50 days: 20 subjects;
• Latency of lack of efficacy term reported after the second dose was known for 69 cases:
o Within 0 and 7 days: 42 subjects;
o Within 8 and 21 days: 22 subjects;
o Within 23 and 36 days: 5 subjects.
• Latency of lack of efficacy term reported in cases where the number of doses administered was
not provided, was known in 409 cases:
o Within 0 and 7 days after vaccination: 281 subjects.
o Within 8 and 14 days after vaccination: 89 subjects.
o Within 15 and 44 days after vaccination: 39 subjects.
According to the RSI, individuals may not be fully protected un til 7 days after their second dose of
vaccine, therefore for the above 1649 cases where lack of effica cy was reported after the 1st dose or the 090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000067
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 15Table 6. Description of Missing Information
Topic Description
Missing
InformationPost Authorization Cases Evaluation (cumulative to 28 Feb 2021)
Total Number of Cases in the Reporting Period (N=42086)
2nd dose, the reported events may represent signs and symptoms of intercurrent or undiagnosed COVID-
19 infection or infection in an individual who was not fully vaccinated, rather than vaccine ineffectiveness.
Vaccination failure cases (16)
• Vaccination failure seriousness: all serious;
• Lack of efficacy term was reported in all cases after the 2nd dose:
• Latency of lack of efficacy was known for 14 cases:
o Within 7 and 13 days: 8 subjects;
o Within 15 and 29 days: 6 subjects.
COVID-19 (10) and Asymptomatic COVID-19 (6) were the reported vaccine preventable infections that
occurred in these 16 cases.
Conclusion: No new safety signals of vaccine lack of efficacy h ave emerged based on a review of these
cases.
a. From a total of 417 cases, 4 cases were excluded from the analysis. In 3 cases, the MAH was informed
that a 33-year-old and two unspecified age pregnant female pati ents were scheduled to receive bnt162b2 (PT
reported Off label use and Product use issue in 2 cases; Circumstance or information capable of leading to medication error in one case). One case reported the PT Morning sickness; however, pregnancy was not
confirmed in this case. b. 558 additional cases retrieved in this dataset were excluded f rom the analysis; upon review, 546 cases
cannot be considered true lack of efficacy cases because the PT Drug ineffective was coded but the subjects
developed SARS-CoV-2 infection during the early days from the f irst dose (days 1 – 13); the vaccine has not
had sufficient time to stimulate the immune system and, consequently, the development of a vaccine preventable disease during this time is not considered a potential lack of effect of the vaccine; in 5 cases the
PT Drug ineffective was removed after data lock point (DLP) bec ause the subjects did not develop COVID-
19 infection; in 1 case, reporting Treatment failure and Transi ent ischaemic attack, the Lack of efficacy PT
did not refer to BNT162b2 vaccine; 5 cases have been invalidated in the safety database after DLP; 1 case
has been deleted from the discussion because the PTs reported Pat hogen resistance and Product preparation
issue were not indicative of a lack of efficacy. to be eliminated. c. Upon review, 31 additional cases were excluded from the analysis as the data reported (e.g. clinical
details, height, weight, etc.) were not consistent with paediatric subjects
d. Upon review, 28 additional cases were excluded from the analy sis as the data reported (e.g. clinical
details, height, weight, etc.) were not consistent with paediat ric subjects.
e. Different clinical outcomes may be reported for an event that occurred more than once to the same individual
f. In 2 cases the PT Vaccination failure was replaced with Drug i neffective after DLP. Another case was
not included in the discussion of the Vaccination failure cases because correct schedu ling (21 days apart
between the first and second dose) cannot be confirmed.090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000068
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 163.1.3. Review of Adverse Events of Special Interest (AESIs)
Please refer to Appendix 1 for the list of the company’s AESIs for BNT162b2.
The company’s AESI list takes into consideration the lists of A ESIs from the following
expert groups and regulatory authorities: Brighton Collaboratio n (SPEAC), ACCESS
protocol, US CDC (preliminary list of AESI for VAERS surveillan ce), MHRA (unpublished
guideline).
The AESI terms are incorporated into a TME list and include events of interest due to their
association with severe COVID-19 and events of interest for vacc ines in general.
The AESI list is comprised of MedDRA PTs, HLTs, HLGTs or MedDRA SM Qs and can be
changed as appropriate based on the evolving safety profile of t he vaccine.
Table 7 provides a summary review of cumulative cases within AESI categories in the Pfizer safety database. This is distinct from safety signal evaluations which are conducted and included, as appropriate, in the Summary Monthly Safety Reports submitted regularly to the
FDA and other Health Authorities.
Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
Anaphylactic Reactions
Search criteria: Anaphylactic
reaction SMQ (Narrow and Broad, with the algorithm applied), selecting relevant cases according to BC criteriaPlease refer to the Risk ‘Anaphylaxis’ included above in Table 4.
Cardiovascular AESIs
Search criteria: PTs Acute
myocardial infarction;
Arrhythmia; Cardiac failure; Cardiac failure acute; Cardiogenic shock; Coronary artery disease; Myocardial infarction; Postural orthostatic
tachycardia syndrome; Stress
cardiomyopathy; Tachycardia•Number of cases: 1403 (3.3% of the total PM dataset), of which 241 are medically confirmed and 1162 are non-medically
confirmed;
•Country of incidence: UK (268), US (233), Mexico (196), Italy
(141), France (128), Germany (102), Spain (46), Greece (45), Portugal (37), Sweden (20), Ireland (17), Poland (16), Israel (13), Austria, Romania and Finland (12 each), Netherlands (11), Belgium and Norway (10 each), Czech Republic (9), Hungary and
Canada (8 each), Croatia and Denmark (7 each), Iceland (5); the
remaining 30 cases were distributed among 13 other countries;
•Subjects’ gender: female (1076), male (291) and unknown (36);
•Subjects’ age group (n = 1346): Adult
c(1078), Elderlyd(266)
Childeand Adolescentf(1 each);
•Number of relevant events: 1441, of which 946 serious, 495 non-serious; in the cases reporting relevant serious events;
•Reported relevant PTs: Tachycardia (1098), Arrhythmia (102), Myocardial infarction (89), Cardiac failure (80), Acute myocard ial
infarction (41), Cardiac failure acute (11), Cardiogenic shock and Postural orthostatic tachycardia syndrome (7 each) and Coronary
artery disease (6);
•Relevant event onset laten cy (n = 1209): Range from <24 hours to
21 days, median <24 hours;090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000069
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 17Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
•Relevant event outcomeg: fatal (136), resolved/resolving (767),
resolved with sequelae (21), not resolved (140) and unknown
(380);
Conclusion: This cumulative case review does not raise new safet y
issues. Surveillance will continue
COVID-19 AESIs
Search criteria: Covid-19 SMQ
(Narrow and Broad) OR PTs
Ageusia; Anosmia•Number of cases: 3067 (7.3% of the total PM dataset), of which 1013 are medically confirmed and 2054 are non-medically
confirmed;
•Country of incidence: US (1272), UK (609), Germany (360),
France (161), Italy (94), Spain (69), Romania (62), Portugal (5 1),
Poland (50), Mexico (43), Belgium (42), Israel (41), Sweden (30 ),
Austria (27), Greece (24), Denmark (18), Czech Republic and
Hungary (17 each), Canada (12), Ireland (11), Slovakia (9), Lat via
and United Arab Emirates (6 each); the remaining 36 cases were
distributed among 16 other different countries;
•Subjects’ gender: female (1650), male (844) and unknown (573);
•Subjects’ age group (n= 1880) : Adult (1315), Elderly (560),
Infant
hand Adolescent (2 each), Child (1);
•Number of relevant even ts: 3359 , of which 2585 serious, 774
non-serious;
•Most frequently reported relevant PTs (> 1 occurrence): COVID-
19 (1927), SARS-CoV-2 test positive (415), Suspected COVID-19 (270), Ageusia (228), Anosmia (194), SARS-CoV-2 antibody test negative (83), Exposure to SARS-CoV-2 (62), SARS-CoV-2 antibody test positive (53), COVID-19 pneumonia (51),
Asymptomatic COVID-19 (31), Coronavirus infection (13),
Occupational exposure to SARS-CoV-2 (11), SARS-CoV-2 test false positive (7), Coronavirus test positive (6), SARS-CoV-2 te st
negative (3) SARS-CoV-2 antibody test (2);
•Relevant event onset latency (n = 2070): Range from <24 hours to
374 days, median 5 days;
•Relevant event outcome: fatal (136), not resolved (547), resolved/resolving (558), resolved with sequelae (9) and unknow n
(2110).
Conclusion: This cumulative case review does not raise new safet y
issues. Surveillance will continue
Dermatological AESIs
Search criteria: PT Chillblains;
Erythema multiforme•Number of cases: 20 cases (0.05% of the total PM dataset), of which 15 are medically confirmed and 5 are non-medically confirmed;
•Country of incidence: UK (8), France and Poland (2 each), and t he
remaining 8 cases were distributed among 8 other different countries;
•Subjects’ gender: female (17) male and unknown (1 each);
•Subjects’ age group (n=19): Adult (18), Elderly (1);
•
Number of relevant events: 20 events, 16 serious, 4 non-serious 090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000070
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 18Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
•Reported relevant PTs: Erythema multiforme (13) and Chillblains
(7)
•Relevant event onset latency (n = 18): Range from <24 hours to 17
days, median 3 days;
•Relevant event outcome: resolved/resolving (7), not resolved (8 )
and unknown (6).
Conclusion: This cumulative case review does not raise new safet y
issues. Surveillance will continue.
Haematological AESIs
Search criteria: Leukopenias NEC
(HLT) (Primary Path) OR Neutropenias (HLT) (Primary Path) OR PTs Immune thrombocytopenia ,
Thrombocytopenia OR SMQ
Haemorrhage terms (excl
laboratory terms•Number of cases: 932 (2.2 % of the total PM dataset), of which
524 medically confirmed and 408 non-medically confirmed;
•Country of incidence: UK (343), US (308), France (50), Germany
(43), Italy (37), Spain (27), Mexico and Poland (13 each), Sweden (10), Israel (9), Netherlands (8), Denmark, Finland, Portugal and Ireland (7 each), Austria and Norway (6 each), Croatia (4), Greece, Belgium, Hungary and Switzerland (3 each),
Cyprus, Latvia and Serbia (2 each); the remaining 9 cases originated from 9 different countries;
•Subjects’ gender (n=898): female (676) and male (222);
•Subjects’ age group (n=837): Adult (543), Elderly (293), Infant (1);
•Number of relevant events: 1080, of which 681 serious, 399 non-serious;
•Most frequently reported relevant PTs (≥15 occurrences) include :
Epistaxis (127), Contusion (112), Vaccination site bruising (96), Vaccination site haemorrhage (51), Petechiae (50), Haemorrhage (42), Haematochezia (34), Thrombocytopenia (33), Vaccination
site haematoma (32), Conjunctival haemorrhage and Vaginal
haemorrhage (29 each), Haematoma, Haemoptysis and Menorrhagia (27 each), Haematemesis (25), Eye haemorrhage (23), Rectal haemorrhage (22), Immune thrombocytopenia (20), Blood urine present (19), Haematuria, Neutropenia and Purpura
(16 each) Diarrhoea haemorrhagic (15);
•Relevant event onset latency (n = 787): Range from < 24 hours to
33 days, median = 1 day;
•Relevant event outcome: fatal (34), resolved/resolving (393),
resolved with sequelae (17), not resolved (267) and unknown (371).
Conclusion: This cumulative case review does not raise new safety
issues. Surveillance will continue
Hepatic AESIs
Search criteria: Liver related
investigations, signs and symptoms (SMQ) (Narrow and Broad) OR PT Liver injury•Number of cases: 70 cases (0.2% of the total PM dataset), of which 54 medically confirmed and 16 non-medically confirmed;
•Country of incidence: UK (19), US (14), France (7), Italy (5), Germany (4), Belgium, Mexico and Spain (3 each), Austria, and Iceland (2 each); the remaining 8 cases originated from 8 different
countries;
•Subjects’ gender: female (43), male (26) and unknown (1);
•Subjects’ age group (n=64): Adult (37), Elderly (27);090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000071
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 19Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
•Number of relevant events: 94, of which 53 serious, 41 non-serious;
•Most frequently reported relevant PTs (≥3 occurrences) include:
Alanine aminotransferase increased (16), Transaminases increase d
and Hepatic pain (9 each), Liver function test increased (8), Aspartate aminotransferase increased and Liver function test abnormal (7 each), Gamma-glutamyltransferase increased and Hepatic enzyme increased (6 each), Blood alkaline phosphatase
increased and Liver injury (5 each), Ascites, Blood bilirubin
increased and Hypertransaminasaemia (3 each);
•Relevant event onset latency (n = 57): Range from <24 hours to 20
days, median 3 days;
•Relevant event outcome: fatal (5), resolved/resolving (27), resolved with sequelae (1), not resolved (14) and unknown (47).
Conclusion: This cumulative case review does not raise new safety issues. Surveillance will continue
Facial ParalysisSearch criteria: PTs Facial paralysis, Facial paresis•Number of cases: 449
i(1.07% of the total PM dataset), 314
medically confirmed and 135 non-medically confirmed;
•Country of incidence: US (124), UK (119), Italy (40), France (27), Israel (20), Spain (18), Germany (13), Sweden (11), Ireland (9) ,
Cyprus (8), Austria (7), Finland and Portugal (6 each), Hungary and Romania (5 each), Croatia and Mexico (4 each), Canada (3),Czech Republic, Malta, Netherlands, Norway, Poland and Puerto Rico (2 each); the remaining 8 cases originated from 8 different countries;
•Subjects’ gender: female (295), male (133), unknown (21);
•Subjects’ age group (n=411): Adult (313), Elderly (96), Infant
j
and Child (1 each);
•Number of relevant eventsk: 453, of which 399 serious, 54
non-serious;
•Reported relevant PTs: Facial paralysis (401), Facial paresis ( 64);
•Relevant event onset latency (n = 404): Range from <24 hours to
46 days, median 2 days;
•Relevant event outcome: resolved/resolving (184), resolved with
sequelae (3), not resolved (183) and unknown (97);
Overall Conclusion: This cumulative case review does not raise new
safety issues. Surveillance will continue. Causality assessment will be
further evaluated following availability of additional unblinde d data
from the clinical study C4591001, which will be unblinded for f inal
analysis approximately mid-April 2021. Additionally, non-interventional post-authorisation safety studies, C4591011 and
C4591012 are expected to capture data on a sufficiently large
vaccinated population to detect an increased risk of Bell’s pal sy in
vaccinated individuals. The timeline for conducting these analyses will be established based on the size of the vaccinated population captured in the study data sources by the first interim reports (due 30 June 090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000072
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 20Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
2021). Study C4591021, pending protocol endorsement by EMA, is also intended to inform this risk.
Immune-Mediated/Autoimmune
AESIs
Search criteria: Immune-
mediated/autoimmune disorders (SMQ) (Broad and Narrow) OR Autoimmune disorders HLGT (Primary Path) OR PTs Cytokine
release syndrome; Cytokine storm;
Hypersensitivity•Number of cases: 1050 (2.5 % of the total PM dataset), of which
760 medically confirmed and 290 non-medically confirmed;
•Country of incidence (>10 cases): UK (267), US (257), Italy (70 ),
France and Germany (69 each), Mex ico (36), Sweden (35), Spain
(32), Greece (31), Israel (21), Denmark (18), Portugal (17),
Austria and Czech Republic (16 each), Canada (12), Finland (10).
The remaining 74 cases were from 24 different countries.
•Subjects’ gender (n=682): female (526), male (156).
•Subjects’ age group (n=944): Adult (746), Elderly (196),Adolescent (2).
•Number of relevant even ts: 1077 , of which 780 serious, 297
non‑serious.
•Most frequently reported relevant PTs (>10 occurrences): Hypersensitivity (596), Neuropathy peripheral (49), Pericarditis (32), Myocarditis (25), Dermatitis (24), Diabetes mellitus and Encephalitis (16 each), Psoriasis (14), Dermatitis Bullous (13), Autoimmune disorder and Raynaud’s phenomenon (11 each);
•Relevant event onset latency (n = 807): Range from <24 hours to
30 days, median <24 hours.
•Relevant event outcome
l: resolved/resolving (517), not resolved
(215), fatal (12), resolved with sequelae (22) and unknown (312 ).
Conclusion: This cumulative case review does not raise new safety issues. Surveillance will continue
Musculoskeletal AESIs
Search criteria: PTs Arthralgia;
Arthritis; Arthritis bacterialn;
Chronic fatigue syndrome; Polyarthritis; Polyneuropathy;
Post viral fatigue syndrome;
Rheumatoid arthritis•Number of cases: 3600 (8.5% of the total PM dataset), of which 2045 medically confirmed and 1555 non-medically confirmed;
•Country of incidence: UK (1406), US (1004), Italy (285), Mexico (236), Germany (72), Portugal (70), France (48), Greece and Poland (46), Latvia (33), Czech Republic (32), Israel and Spain
(26), Sweden (25), Romania (24), Denmark (23), Finland and Ireland (19 each), Austria and Belgium (18 each), Canada (16), Netherlands (14), Bulgaria (12), Croatia and Serbia (9 each), Cyprus and Hungary (8 each), Norway (7), Estonia and Puerto Rico (6 each), Iceland and Lithuania (4 each); the remaining 21
cases originated from 11 different countries;
•Subjects’ gender (n=3471): female (2760), male (711);
•Subjects’ age group (n=3372): Adult (2850), Elderly (515), Child
(4), Adolescent (2), Infant (1);
•Number of relevant events: 3640, of which 1614 serious, 2026 non-serious;
•Reported relevant PTs: Arthralgia (3525), Arthritis (70), Rheumatoid arthritis (26), Polyarthritis (5), Polyneuropathy, Post viral fatigue s yndrome , Chronic fatigue syndrome (4 each),
Arthritis bacterial (1);
•Relevant event onset latency (n = 2968): Range from <24 hours to
32 days, median 1 day;090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000073
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 21Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
•Relevant event outcome: resolved/resolving (1801), not resolved
(959), resolved with sequelae (49), and unknown (853).
Conclusion: This cumulative case review does not raise new safety
issues. Surveillance will continue.
Neurological AESIs (including demyelination)
Search criteria: Convulsions
(SMQ) (Broad and Narrow) OR
Demyelination (SMQ) (Broad and
Narrow) OR PTs Ataxia; Cataplexy; Encephalopathy ;
Fibromyalgia; Intracranial pressure increased; Meningitis; Meningitis aseptic; Narcolepsy•Number of cases: 501 (1.2% of the total PM dataset), of which 365 medically confirmed and 136 non-medically confirmed.
•Country of incidence (≥9 cases): UK (157), US (68), Germany (49), Mexico (35), Italy (31), France (25), Spain (18), Poland (17),
Netherlands and Israel (15 each), Sweden (9). The remaining 71
cases were from 22 different countries.
•Subjects’ gender (n=478): female (328), male (150).
•Subjects’ age group (n=478): Adult (329), Elderly (149);
•Number of relevant events: 542, of which 515 serious, 27
non‑serious.
•Most frequently reported relevant PTs (˃2 occurrences) included:
Seizure (204), Epilepsy (83), Generalised tonic-clonic seizure
(33), Guillain-Barre syndrome (24), Fibromyalgia and Trigeminal
neuralgia (17 each), Febrile convulsion, (15), Status epilepticus (12), Aura and Myelitis transverse (11 each), Multiple sclerosi s
relapse and Optic neuritis (10 each), Petit mal epilepsy and To nic
convulsion (9 each), Ataxia (8), Encephalopathy and Tonic clonic
movements (7 each), Foaming at mouth (5), Multiple sclerosis, Narcolepsy and Partial seizures (4 each), Bad sensation, Demyelination, Meningitis, Postictal state, Seizure like
phenomena and Tongue biting (3 each);
•Relevant event onset latency (n = 423): Range from <24 hours to
48 days, median 1 day;
•Relevant events outcome: fatal (16), resolved/resolving (265),
resolved with sequelae (13), not resolved (89) and unknown (161);
Conclusion: This cumulative case review does not raise new safety
issues. Surveillance will continue
Other AESIs
Search criteria: Herpes viral
infections (HLT) (Primary Path)
OR PTs Adverse event following
immunisation; Inflammation; Manufacturing laboratory analytical testing issue; Manufacturing materials issue; Manufacturing production issue;
MERS-CoV test; MERS-CoV test
negative; MERS-CoV test positive; Middle East respiratory syndrome; Multiple organ dysfunction syndrome; Occupational exposure to communicable disease; Patient •Number of cases: 8152 (19.4% of the total PM dataset), of which
4977 were medically confirmed and 3175 non-medically confirmed;
•Country of incidence (> 20 occurrences): UK (2715), US (2421), Italy (710), Mexico (223), Portugal (210), Germany (207), Franc e
(186), Spain (183), Sweden (133), Denmark (127), Poland (120), Greece (95), Israel (79), Czech Republic (76), Romania (57), Hungary (53), Finland (52), Norway (51), Latvia (49), Austria (47), Croatia (42), Belgium (41), Canada (39), Ireland (34), Serbia
(28), Iceland (25), Netherlands (22). The remaining 127 cases
were from 21 different countries;
•Subjects’ gender (n=7829): female (5969), male (1860);
•Subjects’ age group (n=7479): Adult (6330), Elderly (1125), Adolescent, Child (9 each), Infant (6);090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000074
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 22Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
isolation; Product availability issue; Product distribution issue;
Product supply issue; Pyrexia;
Quarantine; SARS-CoV-1 test; SARS-CoV-1 test negative; SARS-CoV-1 test positive•Number of relevant events: 8241, of which 3674 serious, 4568 non‑serious;
•Most frequently reported relevant PTs (≥6 occurrences) included:
Pyrexia (7666), Herpes zoster (259), Inflammation (132), Oral herpes (80), Multiple organ dysfunction syndrome (18), Herpes virus infection (17), Herpes simplex (13), Ophthalmic herpes zoster (10), Herpes ophthalmic and Herpes zoster reactivation ( 6
each);
•Relevant event onset laten cy (n =6836): Range from <24 hours to
61 days, median 1 day;
•Relevant events outcome: fatal (96), resolved/resolving (5008),
resolved with sequelae (84), not resolved (1429) and unknown (1685).
Conclusion: This cumulative case review does not raise new safety
issues. Surveillance will continue
Pregnancy Related AESIs
Search criteria: PTs Amniotic
cavity infection; Caesarean section; Congenital anomaly;
Death neonatal; Eclampsia;
Foetal distress syndrome; Low birth weight baby; Maternal exposure during pregnancy; Placenta praevia; Pre-eclampsia; Premature labour; Stillbirth; Uterine rupture; Vasa praeviaFor relevant cases, please refer to Table 6, Description of Missing
Information, Use in Pregnancy and While Breast Feeding
Renal AESIs
Search criteria: PTs Acute kidney
injury; Renal failure.•Number of cases: 69 cases (0.17% of the total PM dataset), of which 57 medically confirmed, 12 non-medically confirmed;
•Country of incidence: Germany (17), France and UK (13 each), US (6), Belgium, Italy and Spain (4 each), Sweden (2), Austria, Canada, Denmark, Finland, Luxembourg and Norway (1 each);
•Subjects’ gender: female (46), male (23);
•Subjects’ age group (n=68): Adult (7), Elderly (60), Infant (1) ;
•Number of relevant events: 70, all serious;
•Reported relevant PTs: Acute kidney injury (40) and Renal failure (30);
•Relevant event onset latency (n = 42): Range from <24 hours to 15
days, median 4 days;
•Relevant event outcome: fatal (23), resolved/resolving (10), no t
resolved (15) and unknown (22).
Conclusion: This cumulative case review does not raise new safety
issues. Surveillance will continue.
Respiratory AESIs
Search criteria: Lower respiratory
tract infections NEC (HLT) •Number of cases: 130 cases (0.3% of the total PM dataset), of which 107 medically confirmed;090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000075
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 23Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
(Primary Path) OR Respiratory failures (excl neonatal) (HLT)
(Primary Path) OR Viral lower
respiratory tract infections (HLT) (Primary Path) OR PTs: Acute respiratory distress syndrome; Endotracheal intubation; Hypoxia; Pulmonary haemorrhage;
Respiratory disorder; Severe acute
respiratory syndrome•Countries of incidence: United Kingdom (20), France (18), Unite d
States (16), Germany (14), Spain (13), Belgium and Italy (9),
Denmark (8), Norway (5), Czech Republic, Iceland (3 each); the
remaining 12 cases originated from 8 different countries.
•Subjects’ gender (n=130): female (72), male (58).
•Subjects’s age group (n=126): Elderly (78), Adult (47), Adolescent (1).
•Number of relevant events: 137, of which 126 serious, 11
non-serious;
•Reported relevant PTs: Respiratory failure (44), Hypoxia (42),
Respiratory disorder (36), Acute respiratory distress syndrome (10), Chronic respiratory syndrome (3), Severe acute respirator y
syndrome (2).
•Relevant event onset latency (n=102): range from < 24 hours to 18 days, median 1 day;
•Relevant events outcome: fatal (41), Resolved/resolving (47), not recovered (18) and unknown (31).
Conclusion: This cumulative case review does not raise new safety issues. Surveillance will continue.
Thromboembolic Events
Search criteria: Embolism and
thrombosis (HLGT) (Primary Path), excluding PTs reviewed as
Stroke AESIs, OR PTs Deep vein
thrombosis; Disseminated intravascular coagulation; Embolism; Embolism venous; Pulmonary embolism•Number of cases: 151 (0.3% of the total PM dataset), of which 111 medically confirmed and 40 non-medically confirmed;
•Country of incidence: UK (34), US (31), France (20), Germany (15), Italy and Spain (6 each), Denmark and Sweden (5 each),
Austria, Belgium and Israel (3 each), Canada, Cyprus, Netherlands
and Portugal (2 each); the remaining 12 cases originated from 12
different countries;
•Subjects’ gender (n= 144): female (89), male (55);
•Subjects’ age group (n=136): Adult (66), Elderly (70);
•Number of relevant events: 168, of which 165 serious, 3 non-serious;
•Most frequently reported relevant PTs (> 1 occurrence) included:
Pulmonary embolism (60), Thrombosis (39), Deep vein thrombosis (35), Thrombophlebitis superficial (6), Venous thrombosis limb (4), Embolism, Microembolism, Thrombophlebitis and Venous thrombosis (3 each) Blue toe syndrome (2);
•Relevant event onset latency (n = 124): Range from <24 hours to
28 days, median 4 days;
•Relevant event outcome: fatal (18), resolved/resolving (54), resolved with sequelae (6), not resolved (49) and unknown (42).
Conclusion: This cumulative case review does not raise new safet y
issues. Surveillance will continue.
Stroke
Search criteria: HLT Central
nervous system haemorrhages and cerebrovascular accidents •Number of cases: 275 (0.6% of the total PM dataset), of which 180 medically confirmed and 95 non-medically confirmed;
•Country of incidence: UK (81), US (66), France (32), Germany (21), Norway (14), Netherlands and Spain (11 each), Sweden (9), 090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000076
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 24Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
(Primary Path) OR HLTCerebrovascular venous and sinus thrombosis (Primary Path)Israel (6), Italy (5), Belgium (3), Denmark, Finland, Poland an d
Switzerland (2 each); the remaining 8 cases originated from 8
different countries;
•Subjects’ gender (n= 273): female (182), male (91);
•Subjects’ age group (n=265): Adult (59), Elderly (205), Child
m
(1);
•Number of relevant events: 300, all serious;
•Most frequently reported relevant PTs ( >1 occurrence) included:
oPTs indicative of Ischaemic stroke: Cerebrovascular accident (160), Ischaemic stroke (41), Cerebral infarction
(15), Cerebral ischaemia, Cerebral thrombosis, Cerebral venous sinus thrombosis, Ischaemic cerebral infarction and Lacunal infarction (3 each) Basal ganglia stroke, Cerebellar infarction and Thrombotic stroke (2 each);
oPTs indicative of Haemorrhagic stroke: Cerebral
haemorrhage (26), Haemorrhagic stroke (11),
Haemorrhage intracranical and Subarachnoid haemorrhage (5 each), Cerebral haematoma (4), Basal ganglia haemorrhage and Cerebellar haemorrhage (2 each);
•Relevant event onset latency (n = 241): Range from <24 hours to
41 days, median 2 days;
•Relevant event outcome: fatal and resolved/resolving (61 each),
resolved with sequelae (10), not resolved (85) and unknown (83).
Conclusion: This cumulative case review does not raise new safety
issues. Surveillance will continue.
Vasculitic Events
Search criteria: Vasculitides HLT•Number of cases: 32 cases (0.08% of the total PM dataset), of
which 26 medically confirmed and 6 non-medically confirmed;
•Country of incidence: UK (13), France (4), Portugal, US and Spain (3 each), Cyprus, Germany, Hungary, Italy and Slovakia and Costa rica (1 each);
•Subjects’ gender: female (26), male (6);
•Subjects’ age group (n=31): Adult (15), Elderly (16);
•Number of relevant events: 34, of which 25 serious, 9 non-serio us;
•Reported relevant PTs: Vasculitis (14), Cutaneous vasculitis and Vasculitic rash (4 each), (3), Giant cell arteritis and Peripher al
ischaemia (3 each), Behcet’s syndrome and Hypersensitivity vasculitis (2 each) Palpable purpura, and Takayasu’s arteritis (1 each);
•Relevant event onset latency (n = 25): Range from <24 hours to 19
days, median 3 days;
•Relevant event outcome: fatal (1), resolved/resolving (13), not
resolved (12) and unknown (8).
Conclusion: This cumulative case review does not raise new safet y
issues. Surveillance will continue090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000077
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 25Table 7. AESIs Evaluation for BNT162b2
AESIsa
CategoryPost-Marketing Cases Evaluationb
Total Number of Cases (N=42086)
a. For the complete list of the AESIs, please refer to Appendix 5;b. Please note that this corresponds to evidence from post-EUA/c onditional marketing authorisation
approval data sources;c. Subjects with age ranged between 18 and 64 years;d. Subjects with age equal to or above 65 years;e. Subjects with age ranged between 2 and 11 years;f. Subjects with age ranged between 12 and less than 18 years;g. Multiple episodes of the same PT event were reported with a d ifferent clinical outcome within some
cases hence the sum of the events outcome exceeds the total num ber of PT events;
h. Subjects with age ranged between 1 (28 days) and 23 months;i. Twenty-four additional cases were excluded from the analysis a s they were not cases of peripheral facial
nerve palsy because they described other disorders (stroke, cerebral haemorrhage or transient ischaemic attack); 1 case was excluded from the analysis because it was invalid due to an unidentifiable reporter;j. This UK case report received from the UK MHRA described a 1-y ear-old subject who received the
vaccine, and had left postauricular ear pain that progressed to left-sided Bell’s palsy 1 day following
vaccination that had not resolved at the time of the report;k. If a case included both PT Facial paresis and PT Facial paralysis, only the PT Facial paralysis was considered in the descriptions of the events as it is most clin ically important;
l. Multiple episodes of the same PT event were reported with a d ifferent clinical outcome within some
cases hence the sum of the events outcome exceeds the total number of PT eventsm. This UK case report received from the UK MHRA described a 7-y ear-old female subject who received
the vaccine and had stroke (unknown outcome); no follow-up is p ossible for clarification.
n. This PT not included in the AESIs/TME list was included in th e review as relevant for ACCESS
protocol criteria;090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000078
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 263.1.4. Medication error
Cases potentially indicative of medication errors1that cumulatively occurred are summarized
below.
•Number of relevant medication error cases: 20562(4.9%) of which 1569 (3.7%) are
medically confirmed.
•Number of relevant events: 2792
•Top 10 countries of incidence:
−US (1201), France (171), UK (138), Germany (88), Czech Republic (87), Sweden
(49), Israel (45), Italy (42), Canada (35), Romania (33), Finla nd (21), Portugal (20),
Norway (14), Puerto Rico (13), Poland (12), Austria and Spain (10 e ach).
Medication error case outcomes:
•Fatal (7)3,
•Recovered/recovering (354, of which 4 are serious),
•Recovered with sequelae (8, of which 3 serious)
1MedDRA (version 23.1) Higher Level Terms: Accidental exposures to product; Product administration
errors and issues; Product confusion errors and issues; Product dispensing errors and issues; Product label
issues; Product monitoring errors and issues; Product preparation errors and issues; Product selection errors and
issues; Product storage errors and issues in the product use system; Product transcribing errors and communication issues, OR Preferred Terms: Accidental poisoning; Circumstance or information capable of
leading to device use error; Circumstance or information capabl e of leading to medication error;
Contraindicated device used; Deprescribing error; Device use error; Dose calculation error; Drug titration error; Expired device used; Exposure via direct contact; Exposure via eye contact; Exposure via mucosa; Exposure via
skin contact; Failure of child resistant product closure; Inadequate aseptic technique in use of product; Incorrect
disposal of product; Intercepted medication error; Intercepted product prescribing error; Medication error;
Multiple use of single-use product; Product advertising issue; Product distribution issue; Product prescribing error; Product prescribing issue; Product substitution error; Product temperature excursion issue; Product use in unapproved therapeutic environment; Radiation underdose; Underd ose; Unintentional medical device removal;
Unintentional use for unapproved indication; Vaccination error; Wrong device used; Wrong dosage form;
Wrong dosage formulation; Wrong dose; Wrong drug; Wrong patient ; Wrong product procured; Wrong product
stored; Wrong rate; Wrong route; Wrong schedule; Wrong strength; Wrong technique in device usage process;
Wrong technique in product usage process.
2Thirty-five (35) cases were exclude from the analysis because de scribing medication errors occurring in
an unspecified number of individuals or describing medication e rrors occurring with co suspects were
determined to be non-contributory.
3All the medication errors reported in these cases were assessed as non-serious occurrences with an
unknown outcome; based on the available information including the causes of death, the relationship between the medication error and the death is weak. . 090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000079
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 27•Not recovered (189, of which 84 are serious),
•Unknown (1498, of which 33 are serious).
1371 cases reported only MEs without any associated clinical adve rse event. The PTs most
frequently reported (≥12 occurrences) were: Poor quality product administered (539),
Product temperature excursion issue (253), Inappropriate schedule of product administration
(225), Product preparation error (206), Underdose (202), Circum stance or information
capable of leading to medication error (120), Product preparati on issue (119), Wrong
technique in product usage process (76), Incorrect route of pro duct administration (66),
Accidental overdose (33), Product administered at inappropriate site (27), Incorrect dose
administered and Accidental exposure to the product (25 each), Ex posure via skin contact
(22), Wrong product administered (17), Incomplete course of vaccination, and Product administration error (14 each) Product administered to patient o f inappropriate age (12).
In 685 cases, there were co-reported AEs. The most frequently co- associated AEs (˃ 40 occurrences) were: Headache (187), Pyrexia (161), Fatigue (135) , Chills (127), Pain (107),
Vaccination site pain (100), Nausea (89), Myalgia (88), Pain in extremity (85) Arthralgia
(68), Off label use (57), Dizziness (52), Lymphadenopathy (47), Asthenia (46) and Malaise
(41). These cases are summarized in Table 8.
Table 8. ME PTs by seriousness with or without harm co-association (Through 28
February 2021)
Serious Non-Serious
ME PTs With Harm Without Harm With Harm Without Harm
Accidental exposure to
product00 0 5
Accidental overdose 4 1 9 6
Booster dose missed 0 0 0 1
Circumstance or information
capable of leading to medication error00 5 1 1
Contraindicated product administered10 0 2
Expired product administered 0 0 0 2
Exposure via skin contact 0 0 0 5
Inappropriate schedule of product administration0 2 8 264
Incorrect dose administered 1 1 0 0090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000080
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 28Table 8. ME PTs by seriousness with or without harm co-association (Through 28
February 2021)
Serious Non-Serious
ME PTs With Harm Without Harm With Harm Without Harm
Incorrect route of product
administration2 6 16 127
Lack of vaccination site rotation10 0 0
Medication error 0 0 0 1
Poor quality product administered10 0 3 4
Product administered at
inappropriate site2 1 13 29
Product administered to
patient of inappropriate age04 0 4 0
Product administration error 1 0 0 3
Product dose omission issue 0 1 0 3
Product preparation error 1 0 4 11
Product preparation issue 1 1 0 14
Overall, there were 68 cases with co-reported AEs reporting Harm and 599 cases with co-
reported AEs without harm. Additionally, Intercepted medication e rrors was reported in 1
case (PTs Malaise, clinical outcome unknow) and Potential medica tion errors were reported
in 17 cases.
4. DISCUSSION
Pfizer performs frequent and rigorous signal detection on BNT162b2 cases. The findings of
these signal detection analyses are consistent with the known s afety profile of the vaccine.
This cumulative analysis to support the Biologics License Appli cation for BNT162b2, is an
integrated analysis of post-authorization safety data, from U.S . and foreign experience,
focused on Important Identified Risks, Important Potential Risks, and areas of Important
Missing Information identified in the Pharmacovigilance Plan, as well as adverse events of special interest and vaccine administration errors (whether or not associated with an adverse event). The data do not reveal any novel safety concerns or risks requiring label changes and support a favorable benefit risk profile of to the BNT162b2 vacc ine.090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000081
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 295. SUMMARY AND CONCLUSION
Review of the available data for this cumulative PM experience, confirms a favorable
benefit: risk balance for BNT162b2.
Pfizer will continue routine pharmacovigilance activities on be half of BioNTech according to
the Pharmacovigilance Agreement in place, in order to assure pa tient safety and will inform
the Agency if an evaluation of the safety data yields significant new information for
BNT162b2.090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000082
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 1APPENDIX 1. LIST OF ADVERSE EVENTS OF SPECIAL INTEREST
1p36 deletion syndrome;2-Hydroxyglutaric aciduria;5'nucleotidas e increased;Acoustic
neuritis;Acquired C1 inhibitor deficiency;Acquired epidermolysi s bullosa;Acquired epileptic
aphasia;Acute cutaneous lupus erythematosus;Acute disseminated encephalomyelitis;Acute
encephalitis with refractory, repetitive partial seizures;Acute febrile neutrophilic dermatosis;Acute flaccid myelitis;Acute haemorrhagic leukoencep halitis;Acute
haemorrhagic oedema of infancy;Acute kidney injury;Acute macula r outer retinopathy;Acute
motor axonal neuropathy;Acute motor-sensory axonal neuropathy;A cute myocardial
infarction;Acute respiratory distress syndrome;Acute respirator y failure;Addison's
disease;Administration site thrombosis;Administration site vasculitis;Adrenal thrombosis;Adverse event following immunisation;Ageusia;Agranul ocytosis;Air
embolism;Alanine aminotransferase abnormal;Alanine aminotransferase increased;Alcoholic seizure;Allergic bronchopulmonary mycosis;Allergic oedema;Alloi mmune
hepatitis;Alopecia areata;Alpers disease;Alveolar proteinosis;Ammonia abnormal;Ammonia increased;Amniotic cavity infection;Amygdalohippocampectomy;Amy loid
arthropathy;Amyloidosis;Amyloidosis senile;Anaphylactic reactio n;Anaphylactic
shock;Anaphylactic transfusion reaction;Anaphylactoid reaction; Anaphylactoid
shock;Anaphylactoid syndrome of pregnancy;Angioedema;Angiopathic neuropathy;Ankylosing spondylitis;Anosmia;Antiacetylcholine rec eptor antibody
positive;Anti-actin antibody positive;Anti-aquaporin-4 antibody positive;Anti-basal ganglia antibody positive;Anti-cyclic citrullinated peptide antibody po sitive;Anti-epithelial antibody
positive;Anti-erythrocyte antibody positive;Anti-exosome comple x antibody positive;Anti-
GAD antibody negative;Anti-GAD antibody positive;Anti-gangliosi de antibody
positive;Antigliadin antibody positive;Anti-glomerular basement membrane antibody
positive;Anti-glomerular basement membrane disease;Anti-glycyl- tRNA synthetase antibody
positive;Anti-HLA antibody test positive;Anti-IA2 antibody posi tive;Anti-insulin antibody
increased;Anti-insulin antibody positive;Anti-insulin receptor antibody increased;Anti-
insulin receptor antibody positive;Anti-interferon antibody neg ative;Anti-interferon antibody
positive;Anti-islet cell antibody positive;Antimitochondrial an tibody positive;Anti-muscle
specific kinase antibody positive;Anti-myelin-associated glycop rotein antibodies
positive;Anti-myelin-associated glycoprotein associated polyneu ropathy;Antimyocardial
antibody positive;Anti-neuronal antibody positive;Antineutrophi l cytoplasmic antibody
increased;Antineutrophil cytoplasmic antibody positive;Anti-neu trophil cytoplasmic
antibody positive vasculitis;Anti-NMDA antibody positive;Antinuc lear antibody
increased;Antinuclear antibody positive;Antiphospholipid antibo dies
positive;Antiphospholipid syndrome;Anti-platelet antibody positive;Anti-prothrombin antibody positive;Antiribosomal P antibody positive;Anti-RNA polymerase III antibody positive;Anti-saccharomyces cerevisiae antibody test positive;Anti-sperm antibody positive;Anti-SRP antibody positive;Antisynthetase syndrome;Ant i-thyroid antibody
positive;Anti-transglutaminase antibody increased;Anti-VGCC antibody positive;Anti-VGKC antibody positive;Anti-vimentin antibody positive;Antivira l prophylaxis;Antiviral
treatment;Anti-zinc transporter 8 antibody positive;Aortic embo lus;Aortic
thrombosis;Aortitis;Aplasia pure red cell;Aplastic anaemia;Appl ication site
thrombosis;Application site vasculitis;Arrhythmia;Arterial bypa ss occlusion;Arterial bypass
thrombosis;Arterial thrombosis;Arteriovenous fistula thrombosis;Arteriovenous graft site stenosis;Arteriovenous graft thrombosis;Arteritis;Arteritis
Page 30090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000083
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 2coronary;Arthralgia;Arthritis;Arthritis enteropathic;Ascites;As eptic cavernous sinus
thrombosis;Aspartate aminotransferase abnormal;Aspartate aminot ransferase
increased;Aspartate-glutamate-transporter deficiency;AST to pla telet ratio index
increased;AST/ALT ratio abnormal;Asthma;Asymptomatic COVID-
19;Ataxia;Atheroembolism;Atonic seizures;Atrial thrombosis;Atro phic thyroiditis;Atypical
benign partial epilepsy;Atypical pneumonia;Aura;Autoantibody po sitive;Autoimmune
anaemia;Autoimmune aplastic anaemia;Autoimmune arthritis;Autoim mune blistering
disease;Autoimmune cholangitis;Autoimmune colitis;Autoimmune demyelinating disease;Autoimmune dermatitis;Autoimmune disorder;Autoimmune encephalopathy;Autoimmune endocrine disorder;Autoimmune enterop athy;Autoimmune eye
disorder;Autoimmune haemolytic anaemia;Autoimmune heparin-induc ed
thrombocytopenia;Autoimmune hepatitis;Autoimmune hyperlipidaemia;Autoimmune hypothyroidism;Autoimmune inner ear disease;Autoimmune lung disease;Autoimmune lymphoproliferative syndrome;Autoimmune myocarditis;Autoimmune myositis;Autoimmune
nephritis;Autoimmune neuropathy;Autoimmune neutropenia;Autoimmune pancreatitis;Autoimmune pancytopenia;Autoimmune pericarditis;Au toimmune
retinopathy;Autoimmune thyroid disorder;Autoimmune thyroiditis; Autoimmune
uveitis;Autoinflammation with infantile enterocolitis;Autoinfla mmatory disease;Automatism
epileptic;Autonomic nervous system imbalance;Autonomic seizure; Axial
spondyloarthritis;Axillary vein thrombosis;Axonal and demyelina ting
polyneuropathy;Axonal neuropathy;Bacterascites;Baltic myoclonic epilepsy;Band
sensation;Basedow's disease;Basilar artery thrombosis;Basophilopenia;B-cell aplasia;Behcet's syndrome;Benign ethnic neutropenia;Benign fami lial neonatal
convulsions;Benign familial pemphigus;Benign rolandic epilepsy; Beta-2 glycoprotein
antibody positive;Bickerstaff's encephalitis;Bile output abnorm al;Bile output
decreased;Biliary ascites;Bilirubin conjugated abnormal;Bilirub in conjugated
increased;Bilirubin urine present;Biopsy liver abnormal;Biotini dase deficiency;Birdshot
chorioretinopathy;Blood alkaline phosphatase abnormal;Blood alk aline phosphatase
increased;Blood bilirubin abnormal;Blood bilirubin increased;Blood bilirubin unconjugated increased;Blood cholinesterase abnormal;Blood cholinesterase decreased;Blood pressure decreased;Blood pressure diastolic decreased;Blood pressure sys tolic decreased;Blue toe
syndrome;Brachiocephalic vein thrombosis;Brain stem embolism;Brain stem thrombosis;Bromosulphthalein test abnormal;Bronchial oedema;Bro nchitis;Bronchitis
mycoplasmal;Bronchitis viral;Bronchopulmonary aspergillosis all ergic;Bronchospasm;Budd-
Chiari syndrome;Bulbar palsy;Butterfly rash;C1q nephropathy;Cae sarean section;Calcium
embolism;Capillaritis;Caplan's syndrome;Cardiac amyloidosis;Car diac arrest;Cardiac
failure;Cardiac failure acute;Cardiac sarcoidosis;Cardiac ventricular thrombosis;Cardiogenic shock;Cardiolipin antibody positive;Cardiopulmonary failure;Car dio-respiratory
arrest;Cardio-respiratory distress;Cardiovascular insufficiency ;Carotid arterial
embolus;Carotid artery thrombosis;Cataplexy;Catheter site throm bosis;Catheter site
vasculitis;Cavernous sinus thrombosis;CDKL5 deficiency disorder ;CEC syndrome;Cement
embolism;Central nervous system lupus;Central nervous system va sculitis;Cerebellar artery
thrombosis;Cerebellar embolism;Cerebral amyloid angiopathy;Cere bral arteritis;Cerebral
artery embolism;Cerebral artery thrombosis;Cerebral gas embolis m;Cerebral
microembolism;Cerebral septic infarct;Cerebral thrombosis;Cereb ral venous sinus
thrombosis;Cerebral venous thrombosis;Cerebrospinal thrombotic
Page 31090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000084
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 3tamponade;Cerebrovascular accident;Change in seizure presentati on;Chest discomfort;Child-
Pugh-Turcotte score abnormal;Child-Pugh-Turcotte score
increased;Chillblains;Choking;Choking sensation;Cholangitis scl erosing;Chronic
autoimmune glomerulonephritis;Chronic cutaneous lupus erythemat osus;Chronic fatigue
syndrome;Chronic gastritis;Chronic inflammatory demyelinating polyradiculoneuropathy;Chronic lymphocytic inflammation with po ntine perivascular
enhancement responsive to steroids;Chronic recurrent multifocal osteomyelitis;Chronic
respiratory failure;Chronic spontaneous urticaria;Circulatory collapse;Circumoral oedema;Circumoral swelling;Clinically isolated syndrome;Clonic convulsion;Coeliac disease;Cogan's syndrome;Cold agglutinins positive;Cold type ha emolytic
anaemia;Colitis;Colitis erosive;Colitis herpes;Colitis microscopic;Colitis ulcerative;Collagen disorder;Collagen-vascular disease;Complement factor abnormal;C omplement factor C1
decreased;Complement factor C2 decreased;Complement factor C3 d ecreased;Complement
factor C4 decreased;Complement factor decreased;Computerised tomogram liver abnormal;Concentric sclerosis;Congenital anomaly;Congenital bil ateral perisylvian
syndrome;Congenital herpes simplex infection;Congenital myasthe nic syndrome;Congenital
varicella infection;Congestive hepatopathy;Convulsion in childh ood;Convulsions
local;Convulsive threshold lowered;Coombs positive haemolytic a naemia;Coronary artery
disease;Coronary artery embolism;Coronary artery thrombosis;Coro nary bypass
thrombosis;Coronavirus infection;Coronavirus test;Coronavirus test negative;Coronavirus test positive;Corpus callosotomy;Cough;Cough variant asthma;COV ID-19;COVID-19
immunisation;COVID-19 pneumonia;COVID-19 prophylaxis;COVID-19 t reatment;Cranial
nerve disorder;Cranial nerve palsies multiple;Cranial nerve par alysis;CREST
syndrome;Crohn's disease;Cryofibrinogenaemia;Cryoglobulinaemia; CSF oligoclonal band
present;CSWS syndrome;Cutaneous amyloidosis;Cutaneous lupus erythematosus;Cutaneous sarcoidosis;Cutaneous vasculitis;Cyanosis;Cyclic neutropenia;Cy stitis interstitial;Cytokine
release syndrome;Cytokine storm;De novo purine synthesis inhibi tors associated acute
inflammatory syndrome;Death neonatal;Deep vein thrombosis;Deep vein thrombosis
postoperative;Deficiency of bile secretion;Deja vu;Demyelinating polyneuropathy;Demyelination;Dermatitis;Dermatitis bullous;Derm atitis
herpetiformis;Dermatomyositis;Device embolisation;Device relate d thrombosis;Diabetes
mellitus;Diabetic ketoacidosis;Diabetic mastopathy;Dialysis amy loidosis;Dialysis membrane
reaction;Diastolic hypotension;Diffuse vasculitis;Digital pitti ng scar;Disseminated
intravascular coagulation;Disseminated intravascular coagulation in newborn;Disseminated neonatal herpes simplex;Disseminated varicella;Disseminated var icella zoster vaccine virus
infection;Disseminated varicella zoster virus infection;DNA ant ibody positive;Double cortex
syndrome;Double stranded DNA antibody positive;Dreamy state;Dre ssler's syndrome;Drop
attacks;Drug withdrawal convulsions;Dyspnoea;Early infantile ep ileptic encephalopathy with
burst-suppression;Eclampsia;Eczema herpeticum;Embolia cutis med icamentosa;Embolic
cerebellar infarction;Embolic cerebral infarction;Embolic pneumonia;Embolic stroke;Embolism;Embolism arterial;Embolism venous;Encephalitis; Encephalitis
allergic;Encephalitis autoimmune;Encephalitis brain stem;Encephalitis haemorrhagic;Encephalitis periaxialis diffusa;Encephalitis post
immunisation;Encephalomyelitis;Encephalopathy;Endocrine disorde r;Endocrine
ophthalmopathy;Endotracheal intubation;Enteritis;Enteritis leuk openic;Enterobacter
pneumonia;Enterocolitis;Enteropathic spondylitis;Eosinopenia;Eo sinophilic
Page 32090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000085
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 4fasciitis;Eosinophilic granulomatosis with polyangiitis;Eosinop hilic
oesophagitis;Epidermolysis;Epilepsy;Epilepsy surgery;Epilepsy with myoclonic-atonic
seizures;Epileptic aura;Epileptic psychosis;Erythema;Erythema i nduratum;Erythema
multiforme;Erythema nodosum;Evans syndrome;Exanthema subitum;Ex panded disability
status scale score decreased;Expanded disability status scale s core increased;Exposure to
communicable disease;Exposure to SARS-CoV-2;Eye oedema;Eye prur itus;Eye
swelling;Eyelid oedema;Face oedema;Facial paralysis;Facial pare sis;Faciobrachial dystonic
seizure;Fat embolism;Febrile convulsion;Febrile infection-relat ed epilepsy syndrome;Febrile
neutropenia;Felty's syndrome;Femoral artery embolism;Fibrillary
glomerulonephritis;Fibromyalgia;Flushing;Foaming at mouth;Focal cortical resection;Focal
dyscognitive seizures;Foetal distress syndrome;Foetal placental thrombosis;Foetor
hepaticus;Foreign body embolism;Frontal lobe epilepsy;Fulminant type 1 diabetes
mellitus;Galactose elimination capacity test abnormal;Galactose elimination capacity test
decreased;Gamma-glutamyltransferase abnormal;Gamma-glutamyltran sferase
increased;Gastritis herpes;Gastrointestinal amyloidosis;Gelastic seizure;Generalised onset non-motor seizure;Generalised tonic-clonic seizure;Genital herp es;Genital herpes
simplex;Genital herpes zoster;Giant cell arteritis;Glomerulonep hritis;Glomerulonephritis
membranoproliferative;Glomerulonephritis membranous;Glomerulonephritis rapidly progressive;Glossopharyngeal nerve paralysis;Glucose transporte r type 1 deficiency
syndrome;Glutamate dehydrogenase increased;Glycocholic acid incr eased;GM2
gangliosidosis;Goodpasture's syndrome;Graft thrombosis;Granulocytopenia;Granulocytopenia neonatal;Granuloma tosis with
polyangiitis;Granulomatous dermatitis;Grey matter heterotopia;G uanase increased;Guillain-
Barre syndrome;Haemolytic anaemia;Haemophagocytic lymphohistiocytosis;Haemorrhage;Haemorrhagic ascites;Haemorrhag ic
disorder;Haemorrhagic pneumonia;Haemorrhagic varicella syndrome ;Haemorrhagic
vasculitis;Hantavirus pulmonary infection;Hashimoto's encephalopathy;Hashitoxicosis;Hemimegalencephaly;Henoch-Schonle in purpura;Henoch-
Schonlein purpura nephritis;Hepaplastin abnormal;Hepaplastin de creased;Heparin-induced
thrombocytopenia;Hepatic amyloidosis;Hepatic artery embolism;He patic artery flow
decreased;Hepatic artery thrombosis;Hepatic enzyme abnormal;Hepa tic enzyme
decreased;Hepatic enzyme increased;Hepatic fibrosis marker abno rmal;Hepatic fibrosis
marker increased;Hepatic function abnormal;Hepatic hydrothorax; Hepatic
hypertrophy;Hepatic hypoperfusion;Hepatic lymphocytic infiltrat ion;Hepatic mass;Hepatic
pain;Hepatic sequestration;Hepatic vascular resistance increased;Hepatic vascular thrombosis;Hepatic vein embolism;Hepatic vein thrombosis;Hepati c venous pressure
gradient abnormal;Hepatic venous pressure gradient increased;He patitis;Hepatobiliary scan
abnormal;Hepatomegaly;Hepatosplenomegaly;Hereditary angioedema with C1 esterase inhibitor deficiency;Herpes dermatitis;Herpes gestationis;Herpe s oesophagitis;Herpes
ophthalmic;Herpes pharyngitis;Herpes sepsis;Herpes simplex;Herpes simplex cervicitis;Herpes simplex colitis;Herpes simplex encephalitis;H erpes simplex gastritis;Herpes
simplex hepatitis;Herpes simplex meningitis;Herpes simplex meningoencephalitis;Herpes simplex meningomyelitis;Herpes simplex necrotising retinopathy; Herpes simplex
oesophagitis;Herpes simplex otitis externa;Herpes simplex phary ngitis;Herpes simplex
pneumonia;Herpes simplex reactivation;Herpes simplex sepsis;Herpes simplex viraemia;Herpes simplex virus conjunctivitis neonatal;Herpes simplex visceral;Herpes virus
Page 33090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000086
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 5infection;Herpes zoster;Herpes zoster cutaneous disseminated;He rpes zoster infection
neurological;Herpes zoster meningitis;Herpes zoster meningoencephalitis;Herpes zoster
meningomyelitis;Herpes zoster meningoradiculitis;Herpes zoster necrotising retinopathy;Herpes zoster oticus;Herpes zoster pharyngitis;Herp es zoster
reactivation;Herpetic radiculopathy;Histone antibody positive;H oigne's syndrome;Human
herpesvirus 6 encephalitis;Human herpesvirus 6 infection;Human herpesvirus 6 infection reactivation;Human herpesvirus 7 infection;Human herpesvirus 8 infection;Hyperammonaemia;Hyperbilirubinaemia;Hypercholia;Hyper gammaglobulinaemia
benign monoclonal;Hyperglycaemic seizure;Hypersensitivity;Hyper sensitivity
vasculitis;Hyperthyroidism;Hypertransaminasaemia;Hyperventilation;Hypoalbuminaemia;Hypocalcaemic seizure;Hypogammaglobulinaemia;Hypoglossal nerve paralysis;Hypoglossal nerve paresis;Hypoglycaemic seizure;Hyponatraemic seizure;Hypot ension;Hypotensive
crisis;Hypothenar hammer syndrome;Hypothyroidism;Hypoxia;Idiopa thic CD4
lymphocytopenia;Idiopathic generalised epilepsy;Idiopathic inte rstitial pneumonia;Idiopathic
neutropenia;Idiopathic pulmonary fibrosis;IgA nephropathy;IgM nephropathy;IIIrd nerve paralysis;IIIrd nerve paresis;Iliac artery embolism;Immune thro mbocytopenia;Immune-
mediated adverse reaction;Immune-mediated cholangitis;Immune-me diated
cholestasis;Immune-mediated cytopenia;Immune-mediated encephali tis;Immune-mediated
encephalopathy;Immune-mediated endocrinopathy;Immune-mediated e nterocolitis;Immune-
mediated gastritis;Immune-mediated hepatic disorder;Immune-medi ated hepatitis;Immune-
mediated hyperthyroidism;Immune-mediated hypothyroidism;Immune- mediated
myocarditis;Immune-mediated myositis;Immune-mediated nephritis; Immune-mediated
neuropathy;Immune-mediated pancreatitis;Immune-mediated pneumon itis;Immune-mediated
renal disorder;Immune-mediated thyroiditis;Immune-mediated uvei tis;Immunoglobulin G4
related disease;Immunoglobulins abnormal;Implant site thrombosi s;Inclusion body
myositis;Infantile genetic agranulocytosis;Infantile spasms;Inf ected vasculitis;Infective
thrombosis;Inflammation;Inflammatory bowel disease;Infusion sit e thrombosis;Infusion site
vasculitis;Injection site thrombosis;Injection site urticaria;I njection site vasculitis;Instillation
site thrombosis;Insulin autoimmune syndrome;Interstitial granul omatous
dermatitis;Interstitial lung disease;Intracardiac mass;Intracar diac thrombus;Intracranial
pressure increased;Intrapericardial thrombosis;Intrinsic factor antibody abnormal;Intrinsic
factor antibody positive;IPEX syndrome;Irregular breathing;IRVA N syndrome;IVth nerve
paralysis;IVth nerve paresis;JC polyomavirus test positive;JC v irus CSF test positive;Jeavons
syndrome;Jugular vein embolism;Jugular vein thrombosis;Juvenile idiopathic
arthritis;Juvenile myoclonic epilepsy;Juvenile polymyositis;Juv enile psoriatic
arthritis;Juvenile spondyloarthritis;Kaposi sarcoma inflammator y cytokine
syndrome;Kawasaki's disease;Kayser-Fleischer ring;Keratoderma b lenorrhagica;Ketosis-
prone diabetes mellitus;Kounis syndrome;Lafora's myoclonic epil epsy;Lambl's
excrescences;Laryngeal dyspnoea;Laryngeal oedema;Laryngeal rheu matoid
arthritis;Laryngospasm;Laryngotracheal oedema;Latent autoimmune diabetes in adults;LE
cells present;Lemierre syndrome;Lennox-Gastaut syndrome;Leucine aminopeptidase
increased;Leukoencephalomyelitis;Leukoencephalopathy;Leukopenia ;Leukopenia
neonatal;Lewis-Sumner syndrome;Lhermitte's sign;Lichen planopil aris;Lichen planus;Lichen
sclerosus;Limbic encephalitis;Linear IgA disease;Lip oedema;Lip swelling;Liver function
test abnormal;Liver function test decreased;Liver function test increased;Liver
induration;Liver injury;Liver iron concentration abnormal;Liver iron concentration
Page 34090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000087
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 6increased;Liver opacity;Liver palpable;Liver sarcoidosis;Liver scan abnormal;Liver
tenderness;Low birth weight baby;Lower respiratory tract herpes infection;Lower respiratory
tract infection;Lower respiratory tract infection viral;Lung ab scess;Lupoid hepatic
cirrhosis;Lupus cystitis;Lupus encephalitis;Lupus endocarditis;Lupus enteritis;Lupus hepatitis;Lupus myocarditis;Lupus myositis;Lupus nephritis;Lupu s pancreatitis;Lupus
pleurisy;Lupus pneumonitis;Lupus vasculitis;Lupus-like syndrome ;Lymphocytic
hypophysitis;Lymphocytopenia neonatal;Lymphopenia;MAGIC syndrom e;Magnetic
resonance imaging liver abnormal;Magnetic resonance proton dens ity fat fraction
measurement;Mahler sign;Manufacturing laboratory analytical tes ting issue;Manufacturing
materials issue;Manufacturing production issue;Marburg's variant multiple sclerosis;Marchiafava-Bignami disease;Marine Lenhart syndrome;M astocytic
enterocolitis;Maternal exposure during pregnancy;Medical device site thrombosis;Medical
device site vasculitis;MELAS syndrome;Meningitis;Meningitis ase ptic;Meningitis
herpes;Meningoencephalitis herpes simplex neonatal;Meningoencep halitis
herpetic;Meningomyelitis herpes;MERS-CoV test;MERS-CoV test negative;MERS-CoV test positive;Mesangioproliferative glomerulonephritis;Mesenteric ar tery embolism;Mesenteric
artery thrombosis;Mesenteric vein thrombosis;Metapneumovirus infection;Metastatic cutaneous Crohn's disease;Metastatic pulmonary embolism;Microangiopathy;Microembolism;Microscopic polyangiitis ;Middle East
respiratory syndrome;Migraine-triggered seizure;Miliary pneumon ia;Miller Fisher
syndrome;Mitochondrial aspartate aminotransferase increased;Mix ed connective tissue
disease;Model for end stage liver disease score abnormal;Model for end stage liver disease score increased;Molar ratio of total branched-chain amino acid to tyrosine;Molybdenum
cofactor deficiency;Monocytopenia;Mononeuritis;Mononeuropathy multiplex;Morphoea;Morvan syndrome;Mouth swelling;Moyamoya dise ase;Multifocal
motor neuropathy;Multiple organ dysfunction syndrome;Multiple sclerosis;Multiple sclerosis relapse;Multiple sclerosis relapse prophylaxis;Multiple subpial transection;Multisystem
inflammatory syndrome in children;Muscular sarcoidosis;Myasthenia gravis;Myasthenia gravis crisis;Myasthenia gravis neonatal;Myasthenic syndrome;My elitis;Myelitis
transverse;Myocardial infarction;Myocarditis;Myocarditis post in fection;Myoclonic
epilepsy;Myoclonic epilepsy and ragged-red fibres;Myokymia;Myos itis;Narcolepsy;Nasal
herpes;Nasal obstruction;Necrotising herpetic retinopathy;Neona tal Crohn's disease;Neonatal
epileptic seizure;Neonatal lupus erythematosus;Neonatal mucocut aneous herpes
simplex;Neonatal pneumonia;Neonatal seizure;Nephritis;Nephrogen ic systemic
fibrosis;Neuralgic amyotrophy;Neuritis;Neuritis cranial;Neuromy elitis optica pseudo
relapse;Neuromyelitis optica spectrum disorder;Neuromyotonia;Ne uronal
neuropathy;Neuropathy peripheral;Neuropathy, ataxia, retinitis pigmentosa
syndrome;Neuropsychiatric lupus;Neurosarcoidosis;Neutropenia;Ne utropenia
neonatal;Neutropenic colitis;Neutropenic infection;Neutropenic sepsis;Nodular rash;Nodular
vasculitis;Noninfectious myelitis;Noninfective encephalitis;Non infective
encephalomyelitis;Noninfective oophoritis;Obstetrical pulmonary embolism;Occupational
exposure to communicable disease;Occupational exposure to SARS- CoV-2;Ocular
hyperaemia;Ocular myasthenia;Ocular pemphigoid;Ocular sarcoidos is;Ocular
vasculitis;Oculofacial paralysis;Oedema;Oedema blister;Oedema due to hepatic disease;Oedema mouth;Oesophageal achalasia;Ophthalmic artery th rombosis;Ophthalmic
herpes simplex;Ophthalmic herpes zoster;Ophthalmic vein thrombo sis;Optic neuritis;Optic
Page 35090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000088
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 7neuropathy;Optic perineuritis;Oral herpes;Oral lichen planus;Or opharyngeal
oedema;Oropharyngeal spasm;Oropharyngeal swelling;Osmotic demye lination
syndrome;Ovarian vein thrombosis;Overlap syndrome;Paediatric au toimmune
neuropsychiatric disorders associated with streptococcal infect ion;Paget-Schroetter
syndrome;Palindromic rheumatism;Palisaded neutrophilic granulom atous
dermatitis;Palmoplantar keratoderma;Palpable
purpura;Pancreatitis;Panencephalitis;Papillophlebitis;Paracance rous pneumonia;Paradoxical
embolism;Parainfluenzae viral laryngotracheobronchitis;Paraneop lastic
dermatomyositis;Paraneoplastic pemphigus;Paraneoplastic thrombo sis;Paresis cranial
nerve;Parietal cell antibody positive;Paroxysmal nocturnal haem oglobinuria;Partial
seizures;Partial seizures with secondary generalisation;Patient isolation;Pelvic venous thrombosis;Pemphigoid;Pemphigus;Penile vein thrombosis;Pericarditis;Pericarditis lupus;Perihepatic discomfort;Periorbital oedema;Periorbital swelling;Peripheral artery thrombosis;Peripheral embolism;Peripheral ischaemia;Peripheral vein thrombus
extension;Periportal oedema;Peritoneal fluid protein abnormal;Peritoneal fluid protein decreased;Peritoneal fluid protein increased;Peritonitis lupus;Pernicious anaemia;Petit mal epilepsy;Pharyngeal oedema;Pharyngeal swelling;Pityriasis liche noides et varioliformis
acuta;Placenta praevia;Pleuroparenchymal fibroelastosis;Pneumob ilia;Pneumonia;Pneumonia
adenoviral;Pneumonia cytomegaloviral;Pneumonia herpes viral;Pneumonia influenzal;Pneumonia measles;Pneumonia mycoplasmal;Pneumonia ne crotising;Pneumonia
parainfluenzae viral;Pneumonia respiratory syncytial viral;Pneu monia viral;POEMS
syndrome;Polyarteritis nodosa;Polyarthritis;Polychondritis;Poly glandular autoimmune
syndrome type I;Polyglandular autoimmune syndrome type II;Polyg landular autoimmune
syndrome type III;Polyglandular disorder;Polymicrogyria;Polymya lgia
rheumatica;Polymyositis;Polyneuropathy;Polyneuropathy idiopathi c progressive;Portal
pyaemia;Portal vein embolism;Portal vein flow decreased;Portal vein pressure
increased;Portal vein thrombosis;Portosplenomesenteric venous t hrombosis;Post procedural
hypotension;Post procedural pneumonia;Post procedural pulmonary embolism;Post stroke
epilepsy;Post stroke seizure;Post thrombotic retinopathy;Post t hrombotic syndrome;Post viral
fatigue syndrome;Postictal headache;Postictal paralysis;Postict al psychosis;Postictal
state;Postoperative respiratory distress;Postoperative respirat ory failure;Postoperative
thrombosis;Postpartum thrombosis;Postpartum venous thrombosis;P ostpericardiotomy
syndrome;Post-traumatic epilepsy;Postural orthostatic tachycard ia syndrome;Precerebral
artery thrombosis;Pre-eclampsia;Preictal state;Premature labour ;Premature
menopause;Primary amyloidosis;Primary biliary cholangitis;Primary progressive multiple sclerosis;Procedural shock;Proctitis herpes;Proctitis ulcerativ e;Product availability
issue;Product distribution issue;Product supply issue;Progressi ve facial
hemiatrophy;Progressive multifocal leukoencephalopathy;Progress ive multiple
sclerosis;Progressive relapsing multiple sclerosis;Prosthetic cardiac valve thrombosis;Pruritus;Pruritus allergic;Pseudovasculitis;Psoriasis;Psoriatic arthropathy;Pulmonary amyloidosis;Pulmonary artery thrombosis;Pulmonary embolism;Pulmonary fibrosis;Pulmonary haemorrhage;Pulmonary mic roemboli;Pulmonary
oil microembolism;Pulmonary renal syndrome;Pulmonary sarcoidosi s;Pulmonary
sepsis;Pulmonary thrombosis;Pulmonary tumour thrombotic microangiopathy;Pulmonary vasculitis;Pulmonary veno-occlusive disease;Pulmonary venous th rombosis;Pyoderma
gangrenosum;Pyostomatitis vegetans;Pyrexia;Quarantine;Radiation leukopenia;Radiculitis
Page 36090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000089
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 8brachial;Radiologically isolated syndrome;Rash;Rash erythematou s;Rash pruritic;Rasmussen
encephalitis;Raynaud's phenomenon;Reactive capillary endothelia l proliferation;Relapsing
multiple sclerosis;Relapsing-remitting multiple sclerosis;Renal amyloidosis;Renal
arteritis;Renal artery thrombosis;Renal embolism;Renal failure; Renal vascular
thrombosis;Renal vasculitis;Renal vein embolism;Renal vein thrombosis;Respiratory
arrest;Respiratory disorder;Respiratory distress;Respiratory failure;Respiratory paralysis;Respiratory syncytial virus bronchiolitis;Respiratory syncytial virus
bronchitis;Retinal artery embolism;Retinal artery occlusion;Ret inal artery thrombosis;Retinal
vascular thrombosis;Retinal vasculitis;Retinal vein occlusion;Retinal vein thrombosis;Retinol binding protein decreased;Retinopathy;Retrograde portal vein fl ow;Retroperitoneal
fibrosis;Reversible airways obstruction;Reynold's syndrome;Rheu matic brain
disease;Rheumatic disorder;Rheumatoid arthritis;Rheumatoid factor increased;Rheumatoid factor positive;Rheumatoid factor quantitative increased;Rheumatoid lung;Rheumatoid neutrophilic dermatosis;Rheumatoid nodule;Rheumatoid nodule removal;Rheumatoid scleritis;Rheumatoid vasculitis;Saccadic eye movement;SAPHO syndrome;Sarcoidosis;SARS-CoV-1 test;SARS-CoV-1 test negative;S ARS-CoV-1 test
positive;SARS-CoV-2 antibody test; SARS-CoV-2 antibody test nega tive;SARS-CoV-2
antibody test positive;SARS-CoV-2 carrier;SARS-CoV-2 sepsis;SARS-CoV-2 test;SARS-CoV-2 test false negative;SARS-CoV-2 test false positive;SARS-C oV-2 test negative;SARS-
CoV-2 test positive;SARS-CoV-2 viraemia;Satoyoshi syndrome;Schizencephaly;Scleritis;Sclerodactylia;Scleroderma;Sc leroderma associated
digital ulcer;Scleroderma renal crisis;Scleroderma-like reactio n;Secondary
amyloidosis;Secondary cerebellar degeneration;Secondary progres sive multiple
sclerosis;Segmented hyalinising vasculitis;Seizure;Seizure anox ic;Seizure cluster;Seizure
like phenomena;Seizure prophylaxis;Sensation of foreign body;Septic embolus;Septic pulmonary embolism;Severe acute respiratory syndrome;Severe myo clonic epilepsy of
infancy;Shock;Shock symptom;Shrinking lung syndrome;Shunt throm bosis;Silent
thyroiditis;Simple partial seizures;Sjogren's syndrome;Skin swelling;SLE arthritis;Smooth muscle antibody positive;Sneezing;Spinal artery embolism;Spinal artery thrombosis;Splenic
artery thrombosis;Splenic embolism;Splenic thrombosis;Splenic v ein
thrombosis;Spondylitis;Spondyloarthropathy;Spontaneous heparin- induced
thrombocytopenia syndrome;Status epilepticus;Stevens-Johnson sy ndrome;Stiff leg
syndrome;Stiff person syndrome;Stillbirth;Still's disease;Stoma site thrombosis;Stoma site
vasculitis;Stress cardiomyopathy;Stridor;Subacute cutaneous lup us erythematosus;Subacute
endocarditis;Subacute inflammatory demyelinating polyneuropathy ;Subclavian artery
embolism;Subclavian artery thrombosis;Subclavian vein thrombosi s;Sudden unexplained
death in epilepsy;Superior sagittal sinus thrombosis;Susac's sy ndrome;Suspected COVID-
19;Swelling;Swelling face;Swelling of eyelid;Swollen tongue;Sym pathetic
ophthalmia;Systemic lupus erythematosus;Systemic lupus erythema tosus disease activity
index abnormal;Systemic lupus erythematosus disease activity index decreased;Systemic lupus erythematosus disease activity index increased;Systemic l upus erythematosus
rash;Systemic scleroderma;Systemic sclerosis pulmonary;Tachycardia;Tachypnoea;Takayasu's arteritis;Temporal lobe epilepsy;Terminal
ileitis;Testicular autoimmunity;Throat tightness;Thromboangiiti s
obliterans;Thrombocytopenia;Thrombocytopenic purpura;Thrombophlebitis;Thrombophlebitis migrans;Thrombophlebitis
Page 37090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000090
BNT162b2
5.3.6 Cumulative Analysis of Post-authorization Adverse Event Re ports
CONFIDENTIAL
Page 9neonatal;Thrombophlebitis septic;Thrombophlebitis superficial;T hromboplastin antibody
positive;Thrombosis;Thrombosis corpora cavernosa;Thrombosis in device;Thrombosis
mesenteric vessel;Thrombotic cerebral infarction;Thrombotic microangiopathy;Thrombotic stroke;Thrombotic thrombocytopenic purpura;Thyroid disorder;Thy roid stimulating
immunoglobulin increased;Thyroiditis;Tongue amyloidosis;Tongue biting;Tongue oedema;Tonic clonic movements;Tonic convulsion;Tonic posturing; Topectomy;Total bile
acids increased;Toxic epidermal necrolysis;Toxic leukoencephalo pathy;Toxic oil
syndrome;Tracheal obstruction;Tracheal oedema;Tracheobronchitis;Tracheobronchitis mycoplasmal;Tracheobronchitis viral;Transaminases abnormal;Transaminases increased;Transfusion-related alloimmune neutropenia;Transient epileptic
amnesia;Transverse sinus thrombosis;Trigeminal nerve paresis;Trigeminal neuralgia;Trigeminal palsy;Truncus coeliacus thrombosis;Tuberous sclerosis complex;Tubulointerstitial nephritis and uveitis syndrome;Tumefactive multiple sclerosis;Tumour embolism;Tumour thrombosis;Type 1 diabetes mell itus;Type I
hypersensitivity;Type III immune complex mediated reaction;Uhth off's
phenomenon;Ulcerative keratitis;Ultrasound liver abnormal;Umbil ical cord
thrombosis;Uncinate fits;Undifferentiated connective tissue disease;Upper airway obstruction;Urine bilirubin increased;Urobilinogen urine decreased;Urobilinogen urine increased;Urticaria;Urticaria papular;Urticarial vasculitis;Uterine rupture;Uveitis;Vaccination site thrombosis;Vaccination site vasculitis;Vagus nerve paralysis;Varicella;Varicella keratitis;Varicella post vaccine; Varicella zoster
gastritis;Varicella zoster oesophagitis;Varicella zoster pneumonia;Varicella zoster sepsis;Varicella zoster virus infection;Vasa praevia;Vascular graft thrombosis;Vascular pseudoaneurysm thrombosis;Vascular purpura;Vascular stent throm bosis;Vasculitic
rash;Vasculitic ulcer;Vasculitis;Vasculitis gastrointestinal;Vasculitis necrotising;Vena cava embolism;Vena cava thrombosis;Venous intravasation;Venous recanalisation;Venous thrombosis;Venous thrombosis in pregnancy;Venous thrombosis lim b;Venous thrombosis
neonatal;Vertebral artery thrombosis;Vessel puncture site throm bosis;Visceral venous
thrombosis;VIth nerve paralysis;VIth nerve paresis;Vitiligo;Voc al cord paralysis;Vocal cord
paresis;Vogt-Koyanagi-Harada disease;Warm type haemolytic anaem ia;Wheezing;White
nipple sign;XIth nerve paralysis;X-ray hepatobiliary abnormal;Y oung's syndrome;Zika virus
associated Guillain Barre syndrome.
Page 38090177e196ea1800\A pproved\A pproved On: 30-A pr-2021 09:26 (GMT )
FDA-CBER-2021-5683-0000091