Document text
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 1BNT162b2 (COMIRNATY)
BLA STN 125742/0
Response to CBER 21 August2021 Information Request Regarding
Postmarketing Requirement/Postmarketing Commitment S tudies
21August 2021
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FDA-CBER-2021-5683-0950412
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 2TABLE OF CONTENTS
1. INTRODUCTION ................................ ................................ ................................ ................. 3
2. CBER REQUESTS AND SPONSOR RESPONSES ................................ ............................ 3
2.1. CBER Request ................................ ................................ ................................ ...........3
3. SPONSOR REVI EW OFPOSTMARKETING REQUI REMENTS AND
POSTMARKETI NG COMMI TMENTS................................ ................................ ..............4
3.1. Study C4591001 ................................ ................................ ................................ ........4
3.2. Study C4591007 ................................ ................................ ................................ ........4
3.3. Study C4591023 ................................ ................................ ................................ ........4
3.4. Study C4591009 ................................ ................................ ................................ ........5
3.5. Study C4591021 ................................ ................................ ................................ ........5
3.6. Study C4591021 (Substudy of the natural history of myocarditis and
pericarditis) ................................ ................................ ................................ .................. 6
3.7. Study C4591036 ................................ ................................ ................................ ........6
3.8. Study C4591007 (Substudy of subclinical m yocarditis) ................................ ...........7
3.9. Study C4591031 (Substudy to prospectively assess the incidence of
subclinical my ocarditis) ................................ ................................ ............................... 7
3.10. Study C4591022 ................................ ................................ ................................ ......7
3.11. Study C4591007 (Substudy evaluatio n of lower doses) ................................ .........8
3.12. Study C4591012 ................................ ................................ ................................ ......8
3.13. Study C4591014 ................................ ................................ ................................ ......8
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BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 31.INTRODUCTION
Reference is made to BLA STN 125742/0 for COVID -19 mRNA Vaccine (COMI RNATY),
for active immunization to prevent COVID -19 caused by SARS-CoV-2 in individuals
≥16years of age and to CBER’s Information Request sent via e -mail at 10:22 AM (original)
and then at 10:49 AM (revised) on 21August2021.
CBER requests are presented in bold italics followed b y Pfizer-BioNTech response in plain
text.
2.CBER REQUESTS AND SPONSOR RESPONSES
2.1.CBER R equest
There have been numerous information requests and amendments regarding the PMR’s
and PMC’s for t his BLA. I have a generated the below list of PMR’s and PMC’s that we
have received from you. Please review and submit the list of studies and dates in an
amendment to the BLA by COB today containing your commitment to conduct all of these
studies in the timeframes noted.
Based on our preliminary review, we do not consider the amendment you submitted on
August 10, 2021 as adequate for the final protocol for PMC Study C4591007 substudy to
evaluate the immunogenicity and safety of lower dose levels of COMIR NATY in
individuals 12 through <30 years of age. Therefore, we are using the future date of
September 30, 2021 for Final Protocol Submission. In the coming weeks we will provide
comments on the amendment submitted on August 10, 2021. Please acknowledge our
revision to the Final Protocol Submission date for this PMC (highlighted in yellow below
for #11). Please also propose any revisions that you anticipate may be needed for Study
Completion Date and Final Report Submission for this PMC.
Sponsor Response
Our review of the list of studies and dates is provided below. The final list of studies and
dates is attached. Pfizer/BioNTech acknowledge the revision to the Final Protocol
Submission date for P MC Study C4591007 substudy to evaluate the immunogenicity and
safety of lower dose levels
of COMI RNATY in individuals 12 through <30 y ears of age . We
updated the Study Completion Date and Final Report Submission date for study C4591007
based upon Protocol Amendment 2, however, additional amendments may extend study
completion.
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BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 43.SPONSOR REVIEW OF PO STMARKETING REQUIREM ENTS AND
POSTMARKETING COMMIT MENTS
3.1. Study C45910 01
Deferred pediatric Study C4591001 to evaluate the safety and effectiveness of
COMIRNATY in children 12 years through 15 years of age.
Final Protocol Submission: October 7, 2020
Study Completion Date: May 31, 2023
Final Report Submission: October 31, 2023
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591001 are correct.
3.2. Study C45910 07
Deferred pediatric Study C4591007 to evaluate the safety and effectiveness of
COMIRNATY in infants and children 6 months to <12 years of age.
Final Protocol Submission: February 8, 2021
Study Completion: October 31, 2023
Final Report Submission: March 31, 2024
Sponsor Re view
Pfizer/BioNTech confirm the Final Protocol Submission Date for Study C4591007,
08February 2021, is correct.
The Study Completion Date and the Final Report Submission Date for Study C4591007 need
to be updated. The dateswill be rev ised to 30 November 2023(Study Completion Date) and
31May 2024 (Final Report Submission Date) in the next version of the Pharmacovigilance
Plan. Submission of the updated Pharmacovigilance Plan is anticipated to be post -approval
given our understanding o f the imminence of approval of the BLA. The updated dates are
based on the Protocol Amendment 2. Additional amendments may extend study completion .
3.3.Study C4591023
Deferred pediatric Study C4591023 to evaluate the safety and effectiveness of
COMIRNATY in infants <6 months of age.
Final Protocol Submission: January 31, 2022
Study Completion: July 31, 2024
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BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 5Final Report Submission: October 31, 2024
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591023 are correct.
3.4.Study C4591009
Study C4591009, entitled “A Non -Interventional Post-Approval Safety Study of the Pfizer-
BioNTech COVID -19 mRNA Vaccine in the United States,” to evaluate the occurrence of
myocarditis and pericarditis following administration of COMIRNATY.
We acknowledge the timetable you submitted on August 16, 2021, which states that you
will conduct this study according to the following schedule:
Final Protocol Submission: August 31, 2021
Monitoring Report Submission: October 31, 2022
Interim Report Submission: Octo ber 31, 2023
Study Completion Date: June 30, 2025
Final Report Submission: October 31, 2025
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591009are correct.
3.5. Study C459102 1
Study C4591021, entitled “Post Conditional Approval Active Surveillance Study Among
Individuals in Europe Receiving the Pfizer -BioNTech Coronavirus Disease 2019 (COVID -
19) Vaccine,” to evaluate the occurrence of myocarditis and pericarditis following
administration of COMIRNATY.
We acknowledge the timetable you submitted on August 16, and 19, 2021, which states that
you will conduct this study according to the following schedule:
Final Protocol Submission: August 11, 2021
Progress Report Submission: Sept ember 30, 2021
Interim Report 1 Submission: March 31, 2022
Interim Report 2 Submission: September 30, 2022
Interim Report 3 Submission: March 31, 2023
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BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 6Interim Report 4 Submission: September 30, 2023
Interim Report 5 Submission: March 31, 2024
Study Completion Date: March 31, 2024
Final Report Submission: September 30, 2024
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591021are correct.
3.6. Study C459 1021(Substudy ofthe natural history of myocarditis and pericarditis )
Study C4591021 substudy to describe the natural history of myocarditis and pericarditis
following administration of COMIRNATY.
We acknowledge the timetable you submitted on August 16, and 19, 2021, which states that
you will conduct this study according to the following schedule:
Final Protocol Submission: January 31, 2022
Study Completion Date: March 31, 2024
Final Report Submission: September 30, 2024
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591021are correct.
3.7. Study C4591036
Study C4591036, a prospective cohort study with at least 5 years of follow -up for potential
long-term sequelae of myocarditis after vaccination (in collaboration with Pediatric Heart
Network).
We acknowledge the timetable you submitted on August 16, and 19, 2021, which stat es that
you will conduct this study according to the following schedule:
Final Protocol Submission: November 30, 2021
Study Completion Date: December 31, 2026
Final Report Submission: May 31, 2027
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591036are correct.
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BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 73.8. Study C4591007 (Substudy of subclinical myocarditis )
Study C4591007 substudy to prospectively assess the incidence of subclinical myocarditis
following administration of the second dose of COMIRNATY in a subset of participants 5
through 15 years of age.
We acknowledge the timetable you submitted on August 18, and 19, 2021, which states that
you will conduct this assessment according to the following schedule:
Final Protocol Submission: September 30, 2021
Study Completion Date: November 30, 2023
Final Report Submission: May 31, 2024
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591007 are correct.These dates are based on
Protocol Amendment 2, additional amendments may extend study completion
3.9. Study C4591031 (Substudyto prospectively assess the incidence of subclinical
myocarditis)
Study C4591031 substudy to prospectively assess the incidence of subclinical myocarditis
following administration of a third dose of COMIRNATY in a subset of participants 16 to
30 years of age.
We acknowledge the timetable you submitted on August 16, 2021, which states that you
will conduct this study according to the following schedule:
Final Protocol Submission: November 30, 2021
Study Completion Date: June 30, 2022
Final Report Submission: December 31, 2022
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591031 are correct.
3.10. Study C4591022
Study C4591022, entitled “Pfizer- BioNTech COVID -19 Vaccine Exposure during
Pregnancy: A Non -Interventional Post -Approval Safety Study of Pregnancy and Infant
Outcomes in the Organization of Teratology Information Specialists
(OTIS)/MotherToBaby Pregnancy Registry.”
Final Protocol Submission: July 1, 2021
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BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 8Study Completion Date: June 30, 2025
Final Report Submission: December 31, 2025
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591022are correct.
3.11. Study C4591007 (Substudy evaluation of lower doses)
Study C4591007 substudy to evaluate the immunogenicity and safety of lower dose levels
of COMIRNATY in individuals 12 through <30 years of age in.
Final Protocol Submission: September 30, 2021
Study Completion Date: November 30, 2023
Final Report Submission: May 31, 2024
Sponsor Re view
Pfizer/BioNTech acknowledge CBER’s comment and will incorporate the Agency ’s
feedback in Protocol A mendment 3 by 30 September 2021.
3.12. Study C4591012
Study C4591012, entitled “Post -emergency Use Authorization Active Safety Surveillance
Study Among Individuals in the Veteran’s Affairs Health System Receiving Pfizer -
BioNTech Coronavirus Disease 2019 (COVID -19) Vaccine.”
Final Protocol Submission: January 29, 2021
Study Completion Date: June 30, 2023
Final Report Submission: December 31, 2023
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591012are correct.
3.13.Study C4591014
Study C4591014, entitled “Pfizer- BioNTech COVID -19 BNT162b2 Vaccine Effectiveness
Study -Kaiser Permanente Southern California.”
Final Protocol Submission: March 22, 2021
Study Completion Date: December 31, 2022
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BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 9Final Report Submission: June 30, 2023
Sponsor Re view
Pfizer/BioNTech confirm the dates for Study C4591014are correct.
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