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sϰͺϮϬϭϵϭϭϬϳͺ>, WĂŐĞϭŽĨϮOffice of Biostatistics and Epidemiology/Division of Epidemiology
3HULRGLF 6DIHW\ 5HSRUW 5HYLHZ &KHFNOLVW
Completed by Reviewer
Product Name
Manufacturer
STN #
DCC Login ID #
Submission Type PAER PSUR
PBRER PADER
Submission Format ELECTRONIC
PAPER
Reporting Period FROM
TO
Date Received by FDA
Date Routed to Reviewer
Regulatory Information Specialist (RIS) - Name
Reviewer - Name
Reviewer Signature
(electronic signature)
COMMENTSPfizer-BioNTech COVID-19 Vaccine (BNT162b2)
Pfizer
19736.366
June 15, 2021
June 15, 2021
Ramachandra Naik
Deborah Thompson✔
April 30, 2021
May 31, 2021
Deborah L.
Thompson -SD gitally signed by Deborah L Thompson S
DN: c=US o=U S Government ou=HHS ou=FDA ou=People 0 9 2342 19200300 100 1 1=2002552931 cn=Deborah L Thompson S Date: 2021 06 24 07 41 45 04 00'
FDA-CBER-2021-5683-1150406
Reference Documents (X:\DE\MEDICAL OFFICER\Guidance Documents):
1. E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs 1996
2. Addendum to E2C Safety Data Management: Periodic Safety Update Reports for Marketed Drugs 2004
sϰͺϮϬϭϵϭϭϬϳͺ>, WĂŐĞϮŽĨϮOffice of Biostatistics and Epidemiology/Division of Epidemiology
3HULRGLF 6DIHW\ 5HSRUW 5HYLHZ &KHFNOLVW
1. Countries where the product is licensed or authorized for distribution:
Not Reported US Worldwide
2. Estimated number of doses distributed by reporting period/cumulative:
Not5eported US
WorldwideNot Applicable
3. Does this report describe any actions taken by the manufacturer or other regulatory agency for
this product (e.g. labeling changes)? Yes No
4. Have there been any new safety issues identified by the reviewer in this PSUR? Yes No
If YES, please provide pertinent information below AND notify/discuss safety issues with the Team Lead
and/or Branch Chief.
Conclusions:
The contents of this PSUR/PAER do not i ndicate a need for further regulatory action.
Please see the following comments and recommendations:Safety-related changes to the Core Data Sheet include the addition of asthenia, lethargy, decreased appetite, hyperhidrosis, and night sweats as adverse drug
reactions and addi ion of "special warnings and precautions for use" text for vaccine stress-related responses, including dizziness, fain ing, palpitations, increasesin heart rate, alterations in blood pressure, feeling short of breath, ingling sensations, swea ing and/or anxiety.
During he reporting period, the following signals were addressed by the company as follows: ongoing evaluation of myocarditis and pericarditis; appendicitis and
dizziness were evaluated and determined not to be a risk. The following safety topics were addressed and determined not to be validated signals: abnormalbehavior/mental disorder, acquired hemophilia, acute disseminated encephalomyelitis, acute pancreati is, Guillain-Barre syndrome (GBS), menstrual cycleabnormalities, and transverse myelitis (TM).
A review of cumulative reports of hrombosis with hrombocytopenia syndrome (TTS) was provided; among 85 reports of potential TTS two reports met Brighton
Level 1 with positive PF4 antibodies, both reports from the UK and post-1st dose (one 31-yr male with no PMH had deep vein hrombosis and platelets=135 a nd
one 47-yr female with PMH of pulmonary embolus and concomitant an icoagulation/anti-platelet medication had cerebral venous sinus hrombosis, mul iplearterial/venous thromboses, and platelets=10. The company stated that given he hundreds of millions of Pfizer-BioNTech vaccine doses administer ed, it cannot be
concluded that the vaccine is causally associated with vaccine induced thrombo ic thrombocytopenia.
Age stratified Observed to Expected (O/E) analyses showed an O/E ra io exceeding 1 for at least one age group for GBS, multisystem inflammatory syndro me, and
TM; there were no trends noted across age groups. The company will continue to monitor these events.
The Information Request below was sent to the company; await response with the next Summary Monthly Safety Report.
This information request (IR) is in reference to the Pfizer-BioNTech COVID-19 Vaccine Summary Monthly Safety Report (SMSR) for April 30, 2021to May 31, 2021 (IND 19736.366) and the IR response (IND 19736.367) regarding the Observed to Expected (O/E) analysis for myocarditis andpericarditis. We acknowledge that you aim to refine the O/E analysis to provide smaller age categories for the next reporting period.
We note that in the April SMSR a myocarditis background rate of 4.4 per 100,000 person-years (py) was used for both the 18-64 year and 65+
year age groups. In the May SMSR background rates (per 100,000 py) of 12.38 for 18-24 year, 10.54 for 25-49 year, and 10.05 for 50+ year agegroups were used for myocarditis based on data from ACCESS IT_ARS. The ACCESS report indicates that the ARS background rates used inyour O/E analysis are relatively high for myocarditis and there are a wide range of reported background rates for myocarditis. Please perform anO/E analysis for myocarditis using various background rates (i.e., lower, mid-range, and higher background rate estimates) to provide a morecomprehensive range of O/E results. In addition, please perform an O/E analysis for myocarditis stratified by U.S. vs European vaccination rates(doses), age, gender, and vaccine dose. Please submit these O/E analyses for myocarditis in the SMSR for the next reporting period.✔✔
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period / cum
220,976,340 period
/ 639,868,710 cum
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150407