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Pfizer Global Regulatory Affairs
Pfizer Inc.
235 East 42ndStreet/New York , NY 10017 -5755
Global Product Developm ent
30August2021
Marion Gruber, Ph.D.
Director
Office of Vaccines Research and Review
Food and Drug Administration
Center for Bi ologics Evaluation and Research
DocumentControl Center
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SN0469
Re:COVID-19Vaccine(BNT162/ PF-07302048)BB-IND 19736
IND Amendment –
Protocol Amendment for Study C45910 12
New Study C4591009 Protocol
Dear Dr. Gruber ,
Reference is made to BB- IND 19736 for the COVID -19 Vaccine (BNT162; PF -07302048),
which Pfizer and BioNTech are dev eloping for the indication of active immunization to
prevent corona virus disease 2 019 (COVID-19) caused by severe acute respiratory syndrome
coronavirus 2 (SARS -CoV-2).The IND was effective on 29 April 2020 and the Emergency
Use Authorization (EUA) for Pfizer- BioNTech COVID -19 Vaccine issued on 23August
2021.
Reference is also made to the Post-Authorization Safety Study (PASS) C4591012entitled,
“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 ”submitted to the BB-IND 19736 (SN 0195)and EUA 27034 on 29
January2021.
The present submission prov idesC4591012 Clinical Protocol Amendment 1 (version 2.0) ,
Clean cop yandTracked change cop y.
ProtocolAmendme nt 1includesthe following key changes:
Section 6: UpdatedtheMilestones section.
FDA-CBER-2021-5683-1072537
Marion Gruber, Ph.D. ,Director Page 2of 3
BB-IND 19736 30August2021
Pfizer Confid ential
Page 2Section 9.1.1:
oAdded clarification on the self-controlled risk interval ( SCRI)design,
including a description of the measurements when there is a gap between risk
intervals for the first and second dose and an illustration (new Figure 2B) .
oAdded that a dditional doses of the Pfizer -BioNTech COVID -19 vaccine may
be included in the analy sis.
Sections 9.1.1, 9.3.3, 9.7.3, 9.7.5 and9.9:
oRemoved SCRI designwith pre-vaccination control interval and added SCRI
design with post -vaccination control interval for 2 safet y events of interest
(severe COVID -19, multisystem inflammatory syndrome in adults [MIS-A])
that could not be evaluated with the seasonal influen za vaccinated
comparators.
oRevised Figures 1 -5 to remove pre- vaccination control interval and provide
examples for post -vaccination interval.
Sections 9.2.3 and9.4:
oAdded clarification for the identification of subgroups who are
immunocompromised sand individuals with specific comorbidities .
oAdded one additional subgroup of interest (individuals with Medicare
coverage for whom Veterans Health Administration [VH A] records can be
linked to their Medicare claims).
Section 9.3.1: All measurement details concerning how Pfizer -BioNTech COVID-19
vaccine and seasonal influenza vaccine will be identified in the data to an Appendix
Table 3 in Section 18. Appendix Table 3 includes all specific CPT/HCPCS/NDC
codes previousl y listed in Section 9.3.1 as wel l as additi onal codes identified at the
time of the data analy sis.
Sections 9.3.1 and18: Added Appendix Table 4 in Section 18 regarding the LOINC
codes used to identify COVID-19 RT-PCR Test among the study population and
corresponding reference.
Sections 9.3.2 and18: Added frailt y index as a baseline characteristic of interest.
Sections 9.3.3 and18:
oAdded fouradditional safety events of interest : thrombosis with
thrombocy topenia sy ndrome, convulsions/seizures in individuals with
controlled epileps y, Steven-Johnson syndrome/Toxic epidermal necrol ysis,
and hemoly tic anemia (increasing the number of safet y events of interest from
42 to 46).
oReclassified COVID -19-related safet y events of interest to be measured
independentl y of the patient ’sCOVID-19 infection status; this change had no
impact on the number of safet y events of interest (reflected both in the revised
text and revised Table 1).
oAdded that the clean window may be extended (e.g., 2 y ears).
Section 9.7.3.2 : Clarified in the Signal Evaluation section that thesignal evaluation
analyses will beconducted every six months.
Sections 9.1.3and9.7.3.2.5: Added self-controlled case s eries (SCCS) design with
fullpost-vaccination period as an additional analysis in the Si gnal Evaluation
analysis. Added that Signal Evaluation anal yses may also be conducted based on
FDA-CBER-2021-5683-1072538
Marion Gruber, Ph.D. ,Director Page 3of 3
BB-IND 19736 30August2021
Pfizer Confid ential
Page 3signals detected in external sources or based on r egulatory request(e.g.,
myocarditis/pericarditis) .
Section 9.7.3.2.6: Added a comparison group of contemporary unvaccinated controls
in the Signal Evaluation analysis.
Section 9.7.8: Added new section on my ocarditis/pericarditis safety analysis and risk
factor anal ysis.
Section 9.9: Added strengths and limitations associated with the addition of the SCCS
design, contemporaneous unvaccinated controls, andsubgroup anal ysis of individuals
with linkage to Medicare claims data.
In addition, this submission also provides thefinal protocol for the new Post-Authorization
Safety Study (PASS) C4591009entitled, “A Non-Interventional Post -Approval Safety Study
of Pfizer-BioNTech COVID -19 Vaccine in the United States” .This studyis planned to
initiate in Q2 of 2022.
Thisisbeing submitted to both BB-IND 19736 and EUA 27034 in parallel.
This submission has been scanned for vir uses using McAfee VirusS can Enterprise Version
8.8 and is virus free . The submission is be ing sent via the Gateway.
Should you have any quest ions regarding this submission, or require additional info rmation,
please contact me via phone at 214-918-5262 or via e-mail at [email protected].
Sincerely,
Amit Patel
Director
Global Regulatory Affairs-Vaccines
CC: Ramac handra S. Naik, Ph.D.
CC: Laura Gottschalk, Ph .D.
CC: Captain Michael Smith, Ph.D.
FDA-CBER-2021-5683-1072539