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BNT162b2
Cumulative Review from Pharmacovigilance Database
CONFIDENTIAL
Page 1PREGNANCY AND LACTAT ION CUMULATIVE REVIEW
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Cumulative Review from Pharmacovigilance Database
CONFIDENTIAL
Page 21.INTRODUCTION
As part of the Biological Licensing Application (BLA) submission, the U.S. Food and Drug
Administration (FDA) has requested a cumulative review and summary of relevant cases
reported in Pfizer’s pharmacovigilance (Safet y) database from the time of drug product
development to 28-FEB-2021 .
2.METHODOLOGY
Pfizer’s safet y database contains cases of adverse events (AEs) reported spontaneousl y to
Pfizer, cases reported b y thehealth authorities (HAs) , cases published in the medical
literature, cases from Pfizer -sponsored marketing programs, non- interventional studies, and
cases of serious adverse events (SAEs) reported from clinical studies regardless of c ausalit y.
The safet y database was searched for all BNT162b2 vaccine cases reporting an y exposure to
vaccine during pregnancy (mother and/or baby ) or exposure to baby via lactation from all
time through 28 February 2021 . A search of the Pfizer safet y database identified 673 case
reports.
The limitations of post -marketing adverse drug event reporting should be considered when
interpreting these data:
Reports are submitted voluntarily , and the magnitude of underreporting 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 adverse
event, seriousness of the reaction, regulatory actions, awareness b y hea lth professionals
and consumers of adverse drug event reporting, and litigation.
Because man y external factors influence whether or not an adverse event is reported, the
spontaneous reporting s ystem y ields reporting proportion snot incidence rates. As a
result, it is generall y not appropriate to make between -drug comparisons using these
proportions ; the spontaneous reporting sy stem should be used for signal detection rather
than hy pothesis testing.
In some reports, clinical information (such as medical his tory, validation of diagnosis,
time from drug use to onset of illness, dose, and use of concomitant drugs) is missing or
incomplete, and follow -up information may not be available.
An accumulation of adverse event reports does not necessarily indicate that a particular
adverse event was caused by the drug; rather, the event may be due to an underly ing
disease or some other factor(s) such as past medical history or concomitant medication.
3.RESULTS
Of the 673case reports identified in the search, 458 involved BNT162b2 exposure during
pregnancy (mother/fetus) and 2 15 involved exposure during breast- feeding .
In 210 out of the 458 cases, maternal exposure (PTs Maternal exposure timing
unspecified, Maternal exposure during pregnancy , Maternal exposure before p regnancy ,
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Cumulative Review from Pharmacovigilance Database
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Page 3Exposure during pregnancy ) was reported either with no associated AEs or with AE
off-label use /product use issue for either the mother or the bab y.
Among the remaining 248 cases, the m ost commonly reported AEs were product use
issue (83), off -label use ( 81), pain (including but not limited to vaccination site
pain/pain/pain in extremity )(101), headache (5 7), abortion spontaneous (51), fatigue (43),
pyrexia (26), chills (24), myalgia (23), nausea (22), arthralgia (16), dizziness (1 5),
malaise ( 12), lymphadenopathy (11) and asthenia (11).
There were 6cases reporting AE(s) related to premature deliveries.
AER 2021166927 Baby report of fetal tach ycardia noted 1 week after the
neonate’s mother received the second dose of the vaccine. The bab y was
delivered at 35 weeks and 3 day s of gestation due to non- reassuring status during
monitoring post vaccination. The babywas hospitalized for 5 day s. The clinical
outcome of fetal tach ycardia was unknown.
AER 2021015910 Maternal report of a 29 -year old female who was pregnant
when receiving BNT162B2. She had spontaneous rupture of membranes at 36
weeks of gestation , one day after her 2nddose of vaccine . Unspecified
therapeutic measures were taken as a result of premature rupture of membranes
and the mo ther was recovering .
AER 2021191405 Baby case of a fetus of unspecified gender who received
BNT162B2 transplacental ly. The patient’s mother received vaccination during
the second trimester (13 -28 weeks) and experienced premature labor. A live
infant was delivered but passed away a day later. Cause of death was cited as
extreme prematurit y with severe respiratory distress and pneumothorax.
AER 2021182609 Maternal report ( AER 2021193635 associated Baby report) of
a 32-year-old female patient received BNT162B2 during the second -trimester
(13-28 weeks) and experienced p reterm premature rupture of membranes,
premature bab y/Premature delivery . Outcome of preterm premature rupture of
membranes and premature delivery was recovered with sequelae. Concomitant
medications included acety lsalicy lic acid and dalteparin sodium.
AER 2021155967 Baby report: A neonate patient's mother (mother was reported
as 37 -year-old) received BNT162B2 during 13- 28 weeks of gestation and
experienced foetal exposure during p regnancy , premature baby less than 26
weeks, respiratory distress and pneumothorax. Cause of death for the neonate
was premature bab y less than 26 weeks and severe respiratory distress and
pneumothorax.
AER 2021203938 Baby report : Patient ’s 33-year old mo therhad preterm delivery
at 24 weeks and 2 day s via emergency caesarean section. The fetus experienced
maternal exposure during pregnancy via transplacental route on an unspecified
date.
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Page 4There were 53reports of spontaneous abortion (51)/ abortion (1)/ abortion missed (1)
following BNT162b2 vaccination. Of these reports, 4 cases were COVID -19 positive
(including suspected) , and 1 3cases had relevant medical history of endometriosis (1),
abortion spontaneous ( 10), poly cystic ovaries (1), menstruation irre gular (1). These
cases were therefore excluded from the review. One patient had a medical history of
COVID -19 (unknown if ongoing) and was excluded from the review. The remaining
39cases are summarized in Table 1.
Table 1.Summary of Patients with Outcome of Pregnancy – Abortion
spontaneous
Age Medical History Outcom e of Pregnancy
40 years Not provided The patient w as unaware of her pregnancy at the time of
vaccination . Suspected abortion occurred at 6 w eeks of
pregnancy.
37 years Not provided Patient received vaccine during first trimester (1 -12 w eeks)
on 19 Jan2021 and suffered spontaneous abortion on 3 Feb
2021.
33years Not provided Patient received first dose of vaccine during first trimester
(1-12 w eeks) . Abortion occurred at 3 weeks of pregnancy.
32years Not provided Patient w as vaccinated during firsttrimester (1 -12 w eeks) on
23Dec2020 and suffered a spontaneous abortion on 06 Jan
2021.
39years Asthma / Eosinophilic
oesophagitisPatient received vaccination at gestation of 6 w eeks and
spontaneous abortion occurred 11 days post vaccination .
31years Not provided Patient experienced spontaneous abortion 8 days after
receiving 2nd vaccine at 6 weeks pregnant .
35years Asthma /
Gastrooesophageal
reflux diseasePatient experienced missed abortion in the 7th week of
pregnancy on an unspecified date w ith outcome of unknown.
33years Pregnancy The patient w as unaware of her pregnancy at the time of
vaccination, which occurred at gestational age of
approximately 3 weeks. Spontaneous abortion occurred at
gestational age of 6 weeks.
34years Pregnancy Patient was 3 w eeks pregnant at the time of the first
vaccin ation , without knowing she was pregnant. She found
out she was pregnant one week after the vaccination. She
then had a spontan eous abortion in week 6 of pregnancy.
Unknown Not provided Patient received vaccine at an unspecified time during
pregnancy Spontaneous abortion , gestational age unknown.
34years Continuous positive
airway pressure /
Overweight / Sleep
apnoea syndromePatient reported that she was unknowingly pregnant upon
receiving COVID -19 vaccine do se 1. Spontaneous abortion
occurred at 4 weeks of pregnancy.
Unknown Not provided Patient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred at 5 w eeks of gestation.
37 years Not provided Patient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred at 6 w eeks of pregnancy.
31 years Not provided Patient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred at 5 w eeks of gestation.
32 years Not provided Patient received her first vaccine dose at 3 weeks of
pregnancy and experienced spontaneous abortion about
5-6days before her second dose.
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Cumulative Review from Pharmacovigilance Database
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Page 5Table 1.Summary of Patients with Outcome of Pregnancy – Abortion
spontaneous
Age Medical History Outcom e of Pregnancy
23 years Not provided Patient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred at 1 month of pregnancy.
29 years Pregnancy Patient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred at 4 -5 weeks of gestation.
34 years Not provided The patient experienced spontaneous abortion at a routine
OBGYN visi t, gestational age unknown.
38 years Not provided Patient had spontaneous abortion at 12 w eeks after receiving
the second dose of vaccine.
29 years Anxiety/Seasonal
allergyPatient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred at 6 w eeks of gestation.
41 ye ars Pregnancy Patient was vaccinated during firsttrimester (6 w eeks, also
reported 1 -12 w eeks). Spontaneous abortion w as diagnosed
on 09 Jan2021 (17 days after vaccination administration).
32 years Pregnancy The patient had spontaneous abortion at 5.5 weeks, which
was conceived 3 days after receiving the vaccine .
36 years Allergy to animal/Food
allergy/Seasonal allergyThe patient w as unaware of her pregnancy at the time of
vaccination . Spontaneous abortion occurred during 5thweek
of pregnancy.
30 years Clinical trial participant Patient w as vaccinated during firsttrimester (1 -12 weeks) .
Spontaneous abortion occurred 1 w eek after first dose.
26 years Not provided Patient w as vaccinated during first trimester (1 -12 w eeks).
Spontaneous abortion occu rred 1 day after vaccination.
28 years Not provided Patient received vaccine at an unspecified time during
pregnancy. Spontaneous abortion, gestational age unknown.
Unknown Not provided Patient received vaccine at an unspecified time during
pregnancy. Sp ontaneous abortion, gestational age unknown.
25 years Not provided Patient received vaccine at an unspecified time during
pregnancy. Spontaneous abortion, gestational age unknown.
Unknown Not provided Patient received vaccine at an unspecified time during
pregnancy. Spontaneous abortion, gestational age unknown.
34 years Not provided Patient received vaccine at4 weeks 5 days of pregnancy.
Spontaneous abortion occurred during Week 8 of gestation.
29 years Pregnancy Patient experienced spontaneous abortion 10 days after first
dose of vaccine during first trimester of pregnancy .
21 years Not provided Patient w as vaccinated during first -trimester (1 -12 weeks)
and experienced spontaneous abortion after 12 days.
30 years Not provided Patient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred at 11 w eeks of pregnancy.
36 years Coronavirus test
negative/Deep vein
thrombosisPatient received vaccine at an unspecified time during
pregnancy. Spontaneous abortion occurred at 4 weeks of
pregnancy.
39 years Drug hypersensitivity Patient received vaccine during first trimester of pregnancy.
Spontaneous abortion occurred during Week 8 of gestation
26 years Not provided Patient received vaccine during first trimester of pregnanc y.
Spontaneous abortion occurred after 5 w eeks of pregnancy.
Unknown Not provided Spontaneous abortion occurred 3 days post first dose of
BNT162 b2.
Unknown Not provided Miscarriage after receiving both doses of COVID -19 vaccine
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Page 6The remaining 215 casesreported exposure via lactation. In 174of the 215reports, there
was no AE reported other than ‘Exposure via breast milk /maternal exposure during breast
feeding ’. In the remaining 41cases , AEs were reported in the infants following
BNT162b2 exposure via lactation (see Table 2).
Table 2. Number of Adverse Events Reported in Infants with ‘Exposure via
Lactation’
Preferred Term Number of Events
Pyrexia 9
Off label use 8
Product use issue 7
Infant irritability 5
Headache 5
Rash 5
Diarrhoea 3
Illness 3
Insomnia 3
Suppressed lactation 3
Breast milk discolouration 2
Infantile vomiting 2
Lethargy 2
Pain 2
Peripheral coldness 2
Urticaria 2
Vom iting 2
Abdominal discomfort 1
Agitation 1
Allergy to vaccine 1
Angioedema 1
Anxiety 1
Axill ary pain 1
Breast pain 1
Breast sw elling 1
Chills 1
Cough 1
Crying 1
Dysgeusia 1
Dysphonia 1
Eructation 1
Epistaxis 1
Eyelid ptosis 1
Facial paralysis 1
Fatigue 1
Increased appetite 1
Lymphadenopathy 1
Myalgia 1
Nausea 1
Paresis 1
Poor feeding infant 1
Poor quality sleep 1
Pruritis 1
Restlessness 1
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Page 7Table 2. Number of Adverse Events Reported in Infants with ‘Exposure via
Lactation’
Preferred Term Number of Events
Rhinorrhoea 1
Roseola 1
Skin exfoliation 1
Vision blurred 1
There were 10SAEs reporting with the PT E xposure via lactation. S ix of t hese SAEs were
reported in infants.
A 15 -month old infant with medical history of vomiting experienced skin
exfoliation and infant irritability while being breastfed (latency <7 day s). The
outcome of the event ‘skin exfoliation’ was not recovered and outcome of event
‘infant irritability ’ was unknown. No causality was reported by the ph ysician.
A 9-month old infant with a medical history of meningococcal vaccine and no
history of allergies, asthma, eczema or anaph ylaxis experienced rash and urticaria
a day after exposure via lactation. The outcome of the events was ‘resolved’ and
event did not happen after the second day .No causality assessment was provided.
A dayafter the mother received vaccination, a baby developed a rash after
breastfeeding. At the time of the report, the event was ‘not recovered. A causality
assessment was not provided.
An 8 -month old infant experienced angioe dema one day after his mother received
vaccination. The event was considered non -serious by health authority and the
outcome at the time of the report was unknown . No causality was provided .
There were 2 cases reporting ‘illness’ after exposure via breast milk’. In the first
case, a 6 -month old infant developed an unspec ified sickness 2 day s post mother’s
vaccination. The outcome of the event sickness was recovered, andno causality
assessment was provided. The second case, a 3 -month old infant developed an
unspecified illness and required hospitalization for 6 day s post exposure via breast
milk (>7 day s latency ). The event outcome was reported as ‘recovering’ and no
causality assessment was provided.
4. SUMMARY AND CONCLUSI ON
The cases reviewed above are indicative of what is in the Pfizer safety database as of
28February 2021. The sponsor (Pfizer/BioNTech) will continue to monitor and report on all
pregnancy exposure and lactation cases. It is important to note that the spontaneous safet y
database is intended for hy pothesis generation and not hypothesis testing.
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