Document text
Page 1of 13Reason for Submission
܆For Release
For Surveilla nce
܈For Licensing Action*
STN: 125742_0
܈ Corrected Protocol
Date : 18 Aug 21
Subject: Electronic Protocol Signature Page
License No.: 2229
Company Name: Pharmacia & Upjohn Company LLC for BioNTech Manufacturing GmbH
Pharmacia & Upjohn Company LLC for BioNTech Manufacturing GmbH hereby submits the
following lot as an electronic submission by Electronic Submissions Gateway (ESG). All test
conducted on this lot are reported and pass specifications as required.
COVID-19 Vaccine, mRNA
Electronic Protocol
STN Lot Number Lot Type Filename
125742_0 FE3592 FC 20219002.PC1
Sample Status
Sample Not Required
Sample Submitted with Protocol
܈ Sample Previous Submitted: 16-Aug-2021
Virus Verification
Software Name: Symantec Web Security Service
Company Name: Symantec Version: 7.2.1
Date of Definitions: 16-Aug-2021 Date of Scan: 16-Aug-2021
I certify that the submission is virus-free.
The approximate file size of this submission is 1.25MB.
Comments:
The following corrections were made:
1) The reason for submission designation included on the top right of page 1 of the protocol.
2) The proper name of the product stated on the electronic protocol signature.
3) Inclusion of cc: STN 125742-0/2229/FC on page 7 & 13 of the protocol
Signature of Authorized Official
Printed Name and Title of Signatory Title
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bcf9b9f3-dcbe-4cfe-a38a-d0dfba6a6f4c18 Aug 2021 08:57:050-0400
REASON: I approve this document.
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FDA-CBER-2021-5683-1149992
Page 2of 13Reason for Submission
܆For Release
For Surveilla nce
܈For Licensing Action*
STN: 125742_0
܈ Corrected Protocol
cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Manufacturer Name: Pharmacia & Upjohn Company LLC for BioNTech Manufacturing GmbH
Ma nufacturer Address: 7000 Portage Rd., Ka lamazoo, MI 49001 USA
Trade name: COMIRNATY
Da te of Manufacturing: 30-Jun-2021 Expira tion Date: 30-Nov-2021
Fill Information
Container Type: Vial Volume per container: 0.45mL
Approved Storage Period: 6 months Storage Temperature: -90°C to -60°C
Number of containers manufactured:
Number of Dosesper
container:6
Number of containers for release:
Volume of singlehuman dose: 30μg/DoseStartDate of periodof
Validity:Date of
Manufacture
All tests conducted on this lot are reported and pass specifications as required.
Signature: Date:
Title:
Electronic Protocol # - 20219002.PC1
DocUUID : 62ef52b2-1b0d-4987-b89c-36af069cc96f
bcf9b9f3-dcbe-4cfe-a38a-d0dfba6a6f4c18 Aug 2021 08:57:050-0400
REASON: I approve this document.
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FDA-CBER-2021-5683-1149993
Page 3 of 13
cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Manufacturing Site: Pha rmacia & Upjohn Company LLC, 7000 Portage Rd., Ka lamazoo, MIC 49001 USA
Date of Manufacture: 30-Jun-2021 Date of Expiry: 30-Nov-2021
Date of Fill: 30-Jun-2021
Product Information :
COMPONENTS
Component
Description Batch Number Date of
Manuf. Manufacture Site Quantity Target
Concentration
BNT162b2 Drug Substance
Pfizer
BNT162b2 Drug
Substance Pfizer
LNP Fabrication Pharmacia &
Upjohn Company
LLC
Formulated Bulk
Batch 30-Jun- 2021 Pharmacia &
Upjohn Company
LLC
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Page 4 of 13
cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Table 1. Filled Vaccine Quality Control Tests
Test Test Method Specification Date of Test Result
Appear ance Appear ance (Visual) White to off-white
suspension MEETS TEST
Appea rance (Visible
Particulates) Appearance (ParticlesMay contain white to off
white opa que amorphous
pa rticles MEETS TEST
Subvisible Particles Subvisible Particulate
Matter
pH 6.9 - 7.9
Osmolality Osmome try mOsmol/kg
LNP Size Dynamic Light
Scattering (DLS) nm
LNP Polydispersity Dynamic Light
Scattering (DLS)
RNA Encapsulation Fluorescence assay %
RNA content Fluorescence assay mg/mL
ALC- 0315 content HPLC-CAD mg/mL
ALC- 0159 content HPLC-CAD mg/mL
DSPC content HPLC-CAD mg/mL
Cholesterol content HPLC-CAD mg/mL
Vial content Container Content Not less than mL
Lipid identities HPLC-CAD Retention times
consistent with
references (ALC -0315,
ALC -0159, Cholesterol,
DSPC) Positive
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FDA-CBER-2021-5683-1149995
Page 5 of 13
cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Table 1 (Continued) Filled Vaccine Quality Control Tests
Test Test Method Specification Date of Test Result
Identity of encoded
RNA sequence RT-PCR Identity confirmed Positive
In Vitro Expression Cell-based Flow
Cytometry % Cells Positive
RNA Integrity Ca pilla ry Gel
Electrophoresis % intact RNA
Ba cteria l Endotoxin Endotoxin (LAL) EU/mL
Abbreviations: LNP = Lipid nanoparticles; CAD = charged aerosol detector; RT-PCR = reverse transcription
polymerase chain reaction; LAL = Limulus amebocyte lysate; EU = endotoxin unit
Filled Vaccine Quality Control Tests (cont.)
Sterility
Method: Type: Fina l Container
Container: Sterility-
Date On Test Medium/Temperature Date Off Test Specification Test Result
No growth observed No growth observed
No growth observed No growth observed
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cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Filled Vaccine Quality Control Tests (Continued)
Lipid Identity
Specification Limit Result _____Pass_ ________
Lipid Standard
Retention
Times (RT) Sample
Retention Time
ALC -0315 content
ALC -0159 content
DSPC content
Cholesterol content
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FDA-CBER-2021-5683-1149997
Page 7 of 13
cc: STN 125742-0/2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Filled Vaccine Quality Control Tests (Continued)
RNA encapsulation and content test
Test date
Test method ____ TM8940A
Specification: RNA Encapsulation Result ___
Specification: Content RNA Content mg/mL Result ___
Sample/Control Acceptance Criteria
Result
R2 for Standard A
R2 for Standard B
Total RNA (mg/mL)
Enca psulated RNA (mg/mL)
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FDA-CBER-2021-5683-1149998
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cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Filled Vaccine Quality Control Tests (Continued)
Identity of encoded RNA sequence test
Test method __RT-PCR_________
Test date
Specification Identity confirmed Result Positive
Sample/Control Lot number Replicate Ct value Acceptance
criteria Pass/Fail
DP Sample
FE3592 1 Pass
2
3
Positive PCR Control
1 Pass
2
3
Positive
Control
PF-
07302048-
DP-RM
1 Pass
2
3
Negative PCR Control
NA 1 Pass
2
3
Negative
Control NA 1 Pass
2
3
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FDA-CBER-2021-5683-1149999
Page 9 of 13
cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Filled Vaccine Quality Control Tests (Continued)
In Vitro Expression Assay
Test date
Test method _____LAB-3 8621
Specification cells positive
Acceptance Criteria
Result
Lot number
Positive Control lot number
% cell via bility
Average Number of Cells Counted for Sample
Test Result (% positive cells)
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FDA-CBER-2021-5683-1150000
Page 10 of 13
cc: S
TN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
Filled Vaccine Quality Control Tests (Continued)
Limulus Amebocyte Lysate Test
Ca
lculations or additional comments
N/A
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FDA-CBER-2021-5683-1150001
Page 11 of 13
cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
BNT162b2 Drug Substance
Lot Number:
Date of Manufacture: Date of Expiry:
Storage Temperature: - 25˚C to - 15˚C Approved Storage Period: months
Consumed Quantity:
Table 1. Drug Substance Quality Control Tests
Test Test Method Specification Date of Test Result
Clarity Appearance (Clarity)
Colora tion Appear ance
(Coloration)
pH
Content (RNA
Concentration) UV Spectroscopy
Identity of Encoded
RNA Sequence RT-PCR
RNA Integrity Ca pilla ry Gel
Electrophoresis
5’- Cap RP-HPLC
Poly(A) Tail ddPCR
Residual DNA Template qPCR
Residual dsRNA Immunoblot
Ba cteria l Endotoxin Endotoxin (LAL)
Bioburden Bioburden
Abbreviations: NTU = Nephelometric Turbidity
chain reaction; ddP CR = droplet digital PCR; qPCR = quantitative PCR; dsRNA = double stranded RNA;
LAL = Limulus amebocyte lysate; EU = endotoxin unit; CFU = colony forming unit
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FDA-CBER-2021-5683-1150002
Page 12 of 13
cc: STN 125742-0/ 2229/FC
Lot Number: FE3592
License Name of Product: COVID-19 mRNA Vaccine (nucleoside modified)
BNT162b2 Drug Substance
Lot Number:
Date of Manufacture: Date of Expiry:
Storage Temperature: - 25˚C to - 15˚C Approved Storage Period: months
Consumed Quantity:
Table 1. Drug Substance Quality Control Tests
Test Test Method Specification Date of Test Result
Clarity Appearance (Clarity)
Colora tion Appear ance
(Coloration)
pH
Content (RNA
Concentration) UV Spectroscopy
Identity of Encoded
RNA Sequence RT-PCR
RNA Integrity Ca pilla ry Gel
Electrophoresis
5’- Cap RP-HPLC
Poly(A) Tail ddPCR
Residual DNA Template qPCR
Residual dsRNA Immunoblot
Ba cteria l Endotoxin Endotoxin (LAL)
Bioburden Bioburden
Abbreviations: NTU = Nephelometric Turbidity
chain reaction; ddP CR = droplet digital PCR; qPCR = quantitative PCR; dsRNA = double stranded RNA;
LAL = Limulus amebocyte lysate; EU = endotoxin unit; CFU = colony forming unit
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FDA-CBER-2021-5683-1150003
Genealogy Flowchart
Page 13of 13Prepared By: Approved By:
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REASON: I approve this document.
ac492be7-205f-4142-8f38-a7ec312471dc18 Aug 2021 10:58:042-0400
REASON: I approve this document.
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FDA-CBER-2021-5683-1150004
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Untitled
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rt Method: Untitled Date Printed:
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FDA-CBER-2021-5683-1150007
FE3592 Replicates 1-3
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FDA-CBER-2021-5683-1150008
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FDA-CBER-2021-5683-1150009