Document text
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 1TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................1
QUERY 1 ................................ ................................ ................................ ................................ ...2
RESPONSE 1 ................................ ................................ ................................ ................... 2
QUERY 2 ................................ ................................ ................................ ................................ ...7
RESPONSE 2 ................................ ................................ ................................ ................... 7
QUERY 3 ................................ ................................ ................................ ................................ .12
RESPONSE 3 ................................ ................................ ................................ ................. 12
QUERY 4 ................................ ................................ ................................ ................................ .13
RESPONSE 4 ................................ ................................ ................................ ................. 13
Chemical Quality Testing................................ ................................ ............................... 13
Microbiological Quality Testing................................ ................................ .................... 14
QUERY 5 ................................ ................................ ................................ ................................ .15
RESPONSE 5 ................................ ................................ ................................ ................. 15
QUERY 6 ................................ ................................ ................................ ................................ .17
RESPONSE 6 ................................ ................................ ................................ ................. 17
QUERY 7 ................................ ................................ ................................ ................................ .19
RESPONSE 7 ................................ ................................ ................................ ................. 19
LIST OF TABLES
Table 1. List of equipment with Automated Control using Computer Sy stems................... 2
Table 2. Cold Rooms, Freezers, Refrigerators and the Freeze/Thaw
Systems................................ ................................ ................................ ................... 7
Table3. Cold Rooms, Freezers, Refrigerators and the Freeze/Thaw
Systems................................ ................................ ................................ ................... 9
Table4.Water Quality Criteria................................ ................................ .......................... 13
Table5. Clean Hold Times for Product Contact Equipment..............................................15
Table6.PPQ Lot Inspection Process................................ ................................ .................. 17
Table7. Process Validation Inspection Results..................................................................17
Table8.Overview Cleaning Validation Status for BNT162b2 in Puurs ............................ 19
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FDA-CBER-2021-5683-1149618
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 2QUERY 1
Regarding the computer sy stems, please provide the following:
a.A list of the critical BNT162b2 drug substance manufacturing steps that are
computer -controlled with the computer sy stem identified.
b.For each computer s ystem identified in Part 1a, provide a narrative description of the
validation process, certification that the installation and operational qualification (IQ
and OQ) have been completed; explanation of the parameters mon itored,and tests
performed; and a validation data summary .
RESPONSE 1
1a.
The Critical steps in BNT162b2 drug manufacturing include
Table 1.List of equipment with Automated Control using Computer Systems
Critical Step Manufacturing
AreaEquipment /SystemID
(Description)Computer
controlled
Computer systemIQOQPQ
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FDA-CBER-2021-5683-1149619
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 3Table 1.List of equipment with Automated Control using Computer Systems
Critical Step Manufacturing
AreaEquipment /SystemID
(Description)Computer
controlled
Computer systemIQOQPQ
1b.
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FDA-CBER-2021-5683-1149620
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 4
090177e197d5b557\Approved\Approved On: 17-Aug-2021 20:29 (GMT)
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FDA-CBER-2021-5683-1149621
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 5
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FDA-CBER-2021-5683-1149622
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 6Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197d5b557\Approved\Approved On: 17-Aug-2021 20:29 (GMT)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1149623
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 7QUERY 2
For each cold room, freezer, and freeze/thaw s ystem in in
used in the manufacture of the BNT162b2 drug substance, please identify the
equipment with its unique identifier and provide a concise description of the qualifica tion
(e.g., IQ, OQ, performance qualification (PQ)).
RESPONSE 2
Table 2below lists the cold rooms, freezers, refrigerators, and the freeze/thaw
systems associated with the manufacture of the BNT162b2 drug substance.
Table 2. Cold Rooms, Freezers, Refrigerators and the
Freeze/Thaw Systems
Equipment Description IQ OQ PQ
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FDA-CBER-2021-5683-1149624
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 8
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FDA-CBER-2021-5683-1149625
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 9
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FDA-CBER-2021-5683-1149626
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 10
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FDA-CBER-2021-5683-1149627
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Substance (Pfizer Andover;
PFIZER CONFIDENTIAL
Page 11Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197d5b557\Approved\Approved On: 17-Aug-2021 20:29 (GMT)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1149628
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 12QUERY 3
Regarding the recent Information Request (IR) responses (Response to FDA 26 Jul 2021 and
Response to the August 5, 2021 FDA IR) STN 125742/0.24 and STN 125742/0.43, the
Agency has additional inquiries for the Kalamazoo facility . You provided Table 8 (appended
in the Response to August 5, 2021 FDA IR), which lists the BNT162b2 product contact
equipment. Please provide the operational and performance qualification (OQ/PQ) summar y
documents for all new pieces of equipment. In addition, please provide representative
OQ/PQ summary documents for all families or groupings of tanks, regardless of whether
they are existing or new.
RESPONSE 3
The operational and performance qualification (OQ/PQ) summary documents for the new
equipment is contained in COVID Vaccine Formulation Umbrella
Summary System Acceptance and Release Report and COVID Vaccine Formulation
Tank Sy stem Acceptance and Release Repor t. The COVID Vaccine Formulation
Tank Sy stem Acceptance and Release Report isa representative summary document for
all groups of tanks, including existing tanks as the qualification strategy and testing is the
same.
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
COVID Vaccine Formulation Umbrella Summary System Acceptance
and Release Report, New
COVID Vaccine Formulation Tank Sy stem Acceptance and Release Report, New
Previously submitted supporting documentation
None
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FDA-CBER-2021-5683-1149629
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 13QUERY 4
Regarding the equipment utilities at Pfizer -Kalamazoo please provide the following
information:
a.Please provide the WFI/PW water quality criteria and a description of the monitoring
program.
b.Please provide all uses of the compressed air and nitrogen specific to BNT162b2
manufacture. If the respective utility is used in the process, please provide the
monitoring limits.
RESPONSE 4
a. The Water for Injection (WFI)/Purified Water (PW) water quality criteria are presented in
Table 4.
Table4.Water Quality Criteria
Test Purified Water Water for Injection
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FDA-CBER-2021-5683-1149630
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 14Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197d5b557\Approved\Approved On: 17-Aug-2021 20:29 (GMT)
(b) (4)
FDA-CBER-2021-5683-1149631
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 15QUERY 5
Regarding the cleaning validation summary for the direct product -contact equipment at
Pfizer-Kalamazoo, please provide the following information:
a.Please provide the data to support the validated clean hold times for all direct
product-contact equipment.
b.Please explain why the acceptance criterion for residual cleaning agent is higher for
the BNT162b2 ) than it is for the
other equipment ).
RESPONSE 5
a. The data to support the validated clean hold times for all direct product contact equi pment
is provided in Table 5.
Table5. Clean Hold Times for Product Contact Equipment
Equipment Validated Clean Hold Time Test Results
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FDA-CBER-2021-5683-1149632
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 16Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197d5b557\Approved\Approved On: 17-Aug-2021 20:29 (GMT)
(b) (4)
FDA-CBER-2021-5683-1149633
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 17QUERY 6
Regarding visual inspection of the BLA process validation lots of BNT162b2 filled vials at
Pfizer-Kalamazoo, please provide the following information:
a.Please describe which PPQ/process validation lots were 100% visually inspected b y
automated inspection and which lots were 100% visually inspected manually .
b. Please provide the acceptance criteria for the allowable limit of rejects during visual
inspection.
c.Please provide the defect/reject categories and the percentage of the rejects in each
category for each BLA process validation lot.
RESPONSE 6
a. The inspection process for each PPQ/process validation lot is presented in Table 6.
Table6.PPQ Lot Inspection Process
Drug Product Lot Inspection Process
b. The allowable alert limit of rejects for visual inspection are
c. The defect categories and the percentage of defects in each category for each BLA process
validation lot are presented in Table 7.
Table7.Process Validation Inspection Results
Defect
TypeAction
LimitLot Number
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FDA-CBER-2021-5683-1149634
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 18Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197d5b557\Approved\Approved On: 17-Aug-2021 20:29 (GMT)
FDA-CBER-2021-5683-1149635
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 19QUERY 7
Please update section 3.2 A.1 with the current cleaning validation status at Pfizer
Puurs.Please update the status of y our microbiological cleaning validation, outstanding
manual cleaning and an y cleaning validation deviation information, as applicable.
RESPONSE 7
The applicant confirms that cleaning validation for BNT162b2 will be completed by end of
September 2021, including the microbiological cleaning validation, as commit ted via
Response to FDA 26 July 2021 Information Request Regarding Manufacturing and
Equipment, Query 15 (STN 125742.0/25 submitted 30 Jul 2021). As the cleaning validation
approach is still being implemented, a cleaning verification is performed by visualcheck and
the equipment remains dedicated to BNT162b2.
An overview of the cleaning validation status is presented in Table 8.
Table8.Overview Clean ing Validation Status for BNT162b2 in Puurs
Equipment Cleaning Validation
Status
No deviations impacting the cleaning validation have occurred. The Cleaning Validation
Summary (Puurs) will be updated upon completion of the cleaning validation.
Literature References
None
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FDA-CBER-2021-5683-1149636
COVID-19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 13 Aug 2021FDA queries –Drug Product(Pfizer Puurs and Kalamazoo)
PFIZER CONFIDENTIAL
Page 20SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
Response to FDA 26 July 2021 Information Request Regarding Manufacturing and
Equipment , Query 15 (STN 125742.0/25 submitted 30 Jul 2021)
A.1Cleaning Validation Summary (Puurs)
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FDA-CBER-2021-5683-1149637