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COVID-19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 –Clinical Information Amendment
PFIZER CONFIDENTIAL
Page 1COVID-19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
Request for Assay Qualification Information
July 09, 2020
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FDA-CBER-2021-5683-1072446
COVID-19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 –Clinical Information Amendment
PFIZER CONFIDENTIAL
Page 2TABLE OF CONTENTS
1.BACKGROUND ................................ ................................ ................................ ................... 3
1.1. Pfizer’s Response................................ ................................ ................................ ......3
2. REFERENCES ................................ ................................ ................................ ...................... 4
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FDA-CBER-2021-5683-1072447
COVID-19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 –Clinical Information Amendment
PFIZER CONFIDENTIAL
Page 31.BACKGROUND
Reference is made to BB- IND 19736 for the COVID -19 Vaccine (BNT162; PF -07302048),
whichPfizer and BioNTech are developing for the prevention of COVID- 19 in adults
≥18years of age. The IND was effective on April 29, 2020and Pfizer initiated a Phase 1/2
USclinical study (C4591001) on May 4, 2020.
The purpose of this submission is to provide clinical assay s (IgG binding and SARS -CoV-2
neutralizing antibod y assays) as requested b y CBER on 06 July 2020 in support of the
C4591001 Phase 2b/3 study start scheduled for the week of 20 July 2020.
1.1.Pfizer’s Response
The immune response to Pfizer/BNT’s COVID-19 vaccine candidates hasbeen assessed by
measuring serum IgG antibody responses to the RBD or S1 domains of SARS -CoV-2 spike
protein in Pfizer’s standardized direct Luminex based immunoassay (dLIA) platform and by
measuring neutralizing activity in an authentic functional SARS -CoV-2 neutralization assay
developed and qualified in the lab of Dr. Pei -Yong Shi at the University of Texas Medical
Branch (UTMB) in Galveston, TX (Xieet al,2020). Pfizer is submitting draft qualification
reports and associated test methods for all the above- mentioned assay s. Final qualification
reports will be sent to CBER once all quality control checks have been completed .
The RBD and S1 IgG dLIA procedure s have been developed and qualified in- house.Draft
qualification reports for each IgG dLIA (VR-MQR-10211for S1 IgG dLIA , and
VR-MQR-10212for RBD IgG dLIA ) are provided with this submission along with the test
method SOPs (VR-TM-10293and VR-TM-10294).An evaluation of sample
linearity, precision and standard curve bias were used to establish an assay range. From
these qualification data, a lower limit of quantitation, and descriptive statistics of assay
parameters were also determined for both assays. The qualification results from both assay s
confirmed that these d LIA assay s are suitable for their intended use in vaccine assessment
trials. At least one of the two assay s will be selected for formal assay validation based on
which vaccine construct (BNT162b1 or BNT162b2)is selected for efficacy trials. The
selected IgG dLIA will be validated as per Pfizer’s standard IgG dLIA validation protocol
prior to its use for clinical endpoints supporting licensure (eg,lot consistency and
immuno-bridging studies) .
Functional immune responses to SARS -CoV-2 have been assessed in an authentic SARS
CoV-2 neutralization assay that utilizes a green fluorescent reporter SARS -CoV-2 virus
(SARS-CoV-2 mNG) developed b y Dr. Pei-Yong Shi at the University of Texas Medical
Branch (UTMB) in Galveston, TX (Xie et al, 2020 ). The assay is currently also transferred
into BSL-3 laboratories leased by Pfizer at Hackensack Meridian Health in Nutley ,
NewJersey. The assay has been qualified in the BSL -3 laboratory at UTMB and the draft
qualification report ( VR-MQR-10214)and the test method
(VR-MQR-10214-ATT01 -SHI-SOP-10011)is provided along with this submission. The
main assay parameter sthat wereassessedduring qualification and other studieswere
precision (on a comprehensive panel of sera) and performance of the qualit y
control sera over time . Asshown in VR -MQR-10214, the assay exhibited good precision for
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FDA-CBER-2021-5683-1072448
COVID-19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 –Clinical Information Amendment
PFIZER CONFIDENTIAL
Page 4acell-based functional assay .Performance of quality control samples run subsequent to
qualification was also assessed (results described in VR -MQR-10214). The qualification
results confirmed that the neutralization assay is suitable for its intended use in vaccine
assessment trials. We do not plan to utilizethe SARS -CoV-2 neutralizing assay for clinical
endpoints supporting licensure , and therefore we do not plan to validate this assay. However,
prior to Phase 2b/3 clinical testing, the assay performed by Pfizer at Hackensack Meridian
Health will be bridged to the assay performed at U TMBusing a panel of human
and immune sera . When the work has been completed , the bridging report will be sent to
CBER.
During the vaccine efficacy trial, diagnosis of SARS -CoV-2 in participants will be
determined b y testing mid- turbinate swa bs using the Xpert® Xpress SARS -CoV-2 test from
Cepheid, which has received FDA Emergency Use Authorization. Testing of swab samples
will be performed using the GeneXpert S ystems at Pfizer’s laboratories in Pearl River, NY.
Results from performance assessments of assay sensitivity and specificit y at
Pfizer-Pearl River will be completed as part of an assay method validation. Detection limits
and overall assay performance will be summarized in a validation report and will be
submitted to the I ND prior to the use of this assay for clinical endpoints supporting licensure.
Detection of exposure to SAR -CoV-2 in study participants will be assessed by the Roche
Elecsys Anti-SARS-CoV-2 N-Protein Assay . The Roche assay has a reported overall
specificity of and a sensitivity of based on day s post PCR diagnosis.
Testing of serum samples will be performed using Roche Cobas Sy stem at Pfizer’s
laboratories in Pearl River, NY. Roche’s EUA information and results from assay
performance assessments at Pfizer -Pearl River will be provided to CBER prior to the use of
this assay in phase 2b/3.
2.REFERENCES
Xie X, Muruato A, Lokugamage KG, et al. An infectious cDNA clone of SARS -CoV-2. Cell
Host Microbe 2020;27(5):841- 848.e3.
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