Document text
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 1SARS -CoV -2 mRNA VACCINE (BNT162, PF -07302048)
BB-IND 19736
Response to CBER Request for Information Received on 29 July 2020 –
Questions Regarding Clinical Assay Qualification
21August 2020
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
FDA-CBER-2021-5683-1072455
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 2TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ..................... 4
LIST OF FIGURES ................................ ................................ ................................ ................... 4
1. INTRODUCTION ................................ ................................ ................................ ................. 5
2. REQUESTS ................................ ................................ ................................ ........................... 5
2.1. CBER Request 1 ................................ ................................ ................................ ........ 5
2.1.1. Sponsor’s Response................................ ................................ ...................... 5
2.2. CBER Request 2 ................................ ................................ ................................ ........ 6
2.2.1. Sponsor’s Response................................ ................................ ...................... 6
2.3. CBE R Request 3 ................................ ................................ ................................ ........ 6
2.3.1. Sponsor’s Response................................ ................................ ...................... 6
2.4. CBER Request 4 ................................ ................................ ................................ ........ 7
2.4.1. Sponsor’s Response................................ ................................ ...................... 7
2.5. CBER Request 5 ................................ ................................ ................................ ........ 7
2.5.1. CBER Re quest 5a ................................ ................................ ......................... 7
2.5.1.1. Sponsor’s Response................................ ................................ .....7
2.5.2. CBER Request 5b ................................ ................................ ......................... 8
2.5.2.1. Sponsor’s Response................................ ................................ .....8
2.5.3. CBER Request 5c ................................ ................................ ......................... 8
2.5.3.1. Sponsor’s Response ................................ ................................ .....8
2.6. CBER Request 6 ................................ ................................ ................................ ........ 8
2.6.1. Sponsor’s Response................................ ................................ ...................... 8
2.7. CBER Request 7 ................................ ................................ ................................ ........ 9
2.7.1. Sponsor’s Response................................ ................................ ...................... 9
2.8. CBE R Request 8 ................................ ................................ ................................ ......13
2.8.1. Sponsor’s Response................................ ................................ .................... 13
2.9. CBER Request 9 ................................ ................................ ................................ ......14
2.9.1. Sponsor’s Response................................ ................................ .................... 14
2.10. CBER Request 10 ................................ ................................ ................................ ..15
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
FDA-CBER-2021-5683-1072456
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 32.10.1. Sponsor’s Response................................ ................................ .................. 15
2.11. CBER Request 11 ................................ ................................ ................................ ..15
2.11.1. CBER Request 11a ................................ ................................ ................... 15
2.11.1.1. Sponsor’s Response................................ ................................ .15
2.11.2. Request 11b ................................ ................................ .............................. 15
2.11.2.1. Sponsor’s Response ................................ ................................ .15
2.12. CBER Request 12 ................................ ................................ ................................ ..16
2.12.1. Sponsor’s Response................................ ................................ .................. 16
2.13. CBER Request 13 ................................ ................................ ................................ ..16
2.13.1. CBER Request 13a ................................ ................................ ................... 16
2.13.1.1 . Sponsor’s Response................................ ................................ .16
2.13.2. CBER Request 13b ................................ ................................ ................... 16
2.13.2.1. Sponsor’s Response................................ ................................ .16
2.14. CBER Request 14 ................................ ................................ ................................ ..17
2.14.1. Sponsor’s Response................................ ................................ .................. 17
2.15. CBER Request 15 ................................ ................................ ................................ ..17
2.15.1. Sponsor’s Response................................ ................................ .................. 17
2.16. CBER Request 16 ................................ ................................ ................................ ..17
2.16.1. Sponsor’s Response................................ ................................ .................. 17
2.17. CBER Request 17 ................................ ................................ ................................ ..18
2.17.1. Sponsor’s Response ................................ ................................ .................. 18
2.18. CBER Request 18 ................................ ................................ ................................ ..18
2.18.1. Sponsor’s Response................................ ................................ .................. 18
2.19. CBER Request 19 ................................ ................................ ................................ ..18
2.19.1. Sponsor’s Response................................ ................................ .................. 18
2.20. CBER Request 20 ................................ ................................ ................................ ..18
2.20.1. Sponsor’s Response................................ ................................ .................. 18
3. REFERENCES ................................ ................................ ................................ .................... 19
4. SUPPORTING DOCUME NTATION ................................ ................................ ................. 20
4.1. New, Appended, or Replaced Supporting Documentation ................................ .....20
4.2. Previously Submitted Supporting Documentation ................................ .................. 20
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
FDA-CBER-2021-5683-1072457
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 4LIST OF TABLES
Table 1. SARS -COV -2 IgG d LIA –Calculated for S1 Sample SAN96935 ............. 11
Table 2. S1 Protein – Neat Estimates ................................ .............................. 12
Table 3. SARS -CoV -2 RBD IgG Luminex Assay ................................ ............................. 13
Table 4. SARS -CoV -2 S1 IgG Luminex Assay ................................ ................................ .14
LIST OF FIGURES
Figure 1. Linearity of Sample SAN96935 for SARS -COV -2 IgG dLIA –
S1................................ ................................ ................................ .......................... 10
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1072458
FDA-CBER-2021-5683-1072459
FDA-CBER-2021-5683-1072460
FDA-CBER-2021-5683-1072461
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 82.5.2. CBER Request 5b
Please clarify how the pre-pandemic samples were used to assess precision.
2.5.2.1. Sponsor’s Response
In the RBD and S1 IgG Luminex assay qual ifications, Pfizer used sera and
pre-pandemic sera to assess the assay precision, as these were the sera available at the
time. The pre -pandemic serum samples had measurable low concentrations to S1 and RBD
IgG that were reproducible. Excluding these samples does not appreciabl y affect assay
precision (overall assay precision changes from and for S1 and
RBD, respectivel y).
2.5.3. CBER Request 5c
Please submit the precision data in analyzable format, eg, excel, xpt , etc.
2.5.3.1. Sponsor’s Response
Previously wesubmitted draft versions of the RBD and S1 IgG Luminex assay
Qualifications. The final versions of both the RBD and S1 IgG Luminex assay
Qualifications are being provided in this submission. Within the final qualif ication report,
attachment 1 is included. This attachment provides data tables that are inclusive of all assay
results (including precision anal yses) obtained during the qualifications. The precision data
in an excel file are also included as requested.
2.6.CBER Request 6
Your qualification assessments did not include assessments of the performance of the
assay at the lower range (ie, sensitivity) or determination of the lower limit of detection
(LOD). Please explain how the assay will be used (eg, if it wil l be used to categorize
seropositive and seronegative samples). If needed, establish an LOD based on the lowest
concentration that may be detected above the background with a defined probability.
2.6.1. Sponsor’s Response
The RBD and S1 IgG Luminex assays are quantitative assay s used for measuring specific
IgG levels in serum samples from subjects who have received a candidate SARS -CoV -2
vaccine. Limits of Quantitation (L OQ) are assessed. Pfizer does not intend to use the RBD
and S1 IgG Luminex assay s to categorize seropositive and seronegative samples as we plan
to use a commercial test (Roche Elecsy s Anti- SARS CoV -2 submitted on 31 July 2020 under
EUA2000514/A001) for that purpose; therefore, each assay ’s Limit of Detection (LOD) was
not assessed.
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1072462
FDA-CBER-2021-5683-1072463
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 10Figure 1. Linearity of Sample SAN96935 for SARS-COV- 2 IgG dLIA – S1
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1072464
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 11For S1 sample SAN96935 in the SARS -COV -2 IgG dLIA plotted in Figure 1,
Table 1.SARS -COV-2 IgG dLIA – Calculated for S1 Sample SAN96935
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1072465
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 12Table 1.SARS -COV-2 IgG dLIA – Calculated for S1 Sample SAN96935
Table 2.S1 Protein – SAN96935 Neat Estimate s
Batch Analyst Plate Number Neat
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1072466
FDA-CBER-2021-5683-1072467
FDA-CBER-2021-5683-1072468
FDA-CBER-2021-5683-1072469
FDA-CBER-2021-5683-1072470
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 172.14. CBER Request 14
In your validation protocol, please include details about the assay -critical reagents to be
used in the validation studies, their source and preparation for use. For each validation
assessment, please describe the serum panels used and the dilution scheme including
dilution matrix used.
2.14.1. Sponsor’s Response
Pfizer will include details about the critical reagents in the validation protocol.
2.15. CBER Request 15
We recommend that you submit the validation protocol for the selected dLIA(s) for our
review before starting the validation studies.
2.15.1. Sponsor’s Response
Pfizer will submit the validation protocol prior to start of the validation studies. We like to
note however, that since the SARS -CoV -2 Luminex assay s are platform assay s, we plan to
validate these assay s in the same way we have done successfully in the past for other
programs.
REQUESTS 16-20: Regarding the qualification report for the SARS-CoV-2 mNeonGreen
virus microneutralization (MN) assay (VR -MQR-10214)7performed at the University of
Texas Medical Branch (UTMB):
Given that the qualification only included a preliminary precision assessment and trend
analysis of control sera, at this time we are only providing general input for your
consideration.
2.16. CBER Request 16
We acknowledge that in your current plans the MN assay will not be used to assess Phase
3 endpoints to support licensure. However, since a neutralization assay is used to assess
functional antibody, we strongly encourage that the assay be validated at your Hackensack
Meridian Health site.
2.16.1. Sponsor’s Response
Pfizer acknowledges CBER’s comment. Pfizer intends to use the microneutralization assay
to support exploratory endpoints in the phase 2/3 stage of the C4591001 study and will use
the qualified assay for this purpose. Pfizer intends to validate the microneutralizatio n assay
at the Hackensack Meridian Health site, if there is a potential need to support future licensing
studies.
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
FDA-CBER-2021-5683-1072471
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 182.17. CBER Request 17
Please evaluate the linearity of your assay and provide the assay range for the test samples
based on linearity and precision results.
2.17.1. Sponsor’s Response
Pfizer acknowledges CBER’s comment and will evaluate linearity of the assay to
inform the assay range.
2.18. CBER Request 18
We are concerned with your precision assessment of the the is
higher than your proposed target of Please comment.
2.18.1. Sponsor’s Response
Pfizer acknowledges CBER’s comment. The relatively high for
was impacted b y the low number of assay runs included in the dataset. The inclusion of
additional datapoints from additional runs would be expected to lower the . Pfizer
will re -evaluate QCS ranges prior to testing clinical samples at HMH.
2.19. CBER Request 19
For validation of the MN assay, please consider performing prelim inary qualifications at
the laboratory where the assay will be validated and further developing the assay
procedures and submitting the qualification information and validation protocol for our
input.
2.19.1. Sponsor’s Response
Pfizer agrees that preliminary asses sments of assay performance in the new laboratory at
Hackensack Meridian Health (where the assay will be validated) is important and submit the
requested data and the validation protocol for CBER’s review and comment.
2.20. CBER Request 20
We recommend that you submit the validation protocol for the SARS -CoV-2 MN assay for
our review before starting the validation studies.
2.20.1. Sponsor’s Response
Pfizer will provide a validation protocol for CBER’s review and comment prior to validation.
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1072472
FDA-CBER-2021-5683-1072473
SARS -CoV- 2 mRNA Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 204. SUPPORTING DOCUMENTA TION
None.
4.1. New, Appended, or Replaced Supporting Documentation
None.
4.2. Previously Submitted Supporting Documentation
None.
090177e194b449b7\Approved\Approved On: 20-Aug-2020 13:42 (GMT)
FDA-CBER-2021-5683-1072474