Document text
COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 1TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ..................... 1
(PFIZER CHESTERFIELD ) ................................ ...................... 3
QUERY 1 ................................ ................................ ................................ ................................ ...3
RESPONSE 1 ................................ ................................ ................................ ................... 3
QUERY 2 ................................ ................................ ................................ ................................ ...4
RESPONSE 2 ................................ ................................ ................................ ................... 4
DRUG SUBSTANCE (PFIZ ER A NDOVER- AND )................................ ....8
QUERY 4 ................................ ................................ ................................ ................................ ...8
RESPONSE 4 b ................................ ................................ ................................ ................ 8
QUERY 5 ................................ ................................ ................................ ................................ ...9
RESPONSE 5 ................................ ................................ ................................ ................... 9
QUERY 6 ................................ ................................ ................................ ................................ .12
RESPONSE 6 ................................ ................................ ................................ ................. 12
DRUG PRODUCT ................................ ................................ ................................ ................... 13
QUERY 7 ................................ ................................ ................................ ................................ .13
RESPONSE 7 ................................ ................................ ................................ ................. 13
QUERY 8 ................................ ................................ ................................ ................................ .14
RESPONSE 8 ................................ ................................ ................................ ................. 14
QUERY 9 ................................ ................................ ................................ ................................ .15
RESPONSE 9 ................................ ................................ ................................ ................. 15
QUERY 10 ................................ ................................ ................................ ............................... 16
RESPONSE 10 ................................ ................................ ................................ ............... 16
QUERY 11 ................................ ................................ ................................ ............................... 18
FOLLOW -UP TO FDA’S 2 6 JUL Y 2021 IR RESPO NSE REGARDI NG
MANUFACTURING AND EQ UIPMENT: QUERY 16E ................................ ................ 21
LIST OF TABLES
Table 1. List of Critical Equipment/Materials Used in Manufacturing of the
............................... ................................ ................................ .................... 4
Table 2. Cleaning Validation Results Portable Tank ............................ 6
Table 3. Deviations ................................ ................................ ................................ ............... 7
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 2Table 4. Clean Hold Time Results ................................ ................................ ........... 9
Table 5. Clean Hold Time Results Andover ................................ ........................... 10
Table 6. Tank Qualification Status ................................ ................................ ........... 18
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 3(PFIZER CHESTERFIELD)
QUERY 1
Please clarify what critical utilities are used during the process, and the
microbial control for each critical utility (e.g., or routine monitoring).
RESPONSE 1
are the onl y critical utilities used during the
process.
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
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FDA-CBER-2021-5683-1149548
COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 4QUERY 2
The list provided in Table 3.2.A.1 -1 does not include tubing, small parts, biological safet y
cabinets, and laminar flow hoods. Please update Table 3.2.A.1 -1 to include all direct product
contact equipment.
RESPONSE 2
Additional product -contact parts are listed in the table below. Biological safet y cabinets and
laminar flow hoods are not direct product contact and are not included in the table. Table
3.2.A.1- 1 in Section 3.2.A.1 Facilities and Equipment (Chesterfield) has been updated.
Table 1. List of Critical Equipment/Materials Used in Manufacturing of the
Equipment/
MaterialsProduct Contact/
UseSingle Use /
Multiuse/
DedicatedMaterial of Construct
(MOC )Cleaned /
Sterilized
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 5Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
3.2.A.1 Facilities and Equipment (Chesterfield) -Replaced
Previously submitted supporting documentation
None
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FDA-CBER-2021-5683-1149550
COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 6QUERY 3
Regarding equipment cleaning validation, please provide the following information:
a.Provide the cleaning validation results (or rationale for lack thereof) for the following
equipment
b.Specify the maximum clean hold times and provide clean hold time validation results f or
each equipment.
c.Specify the equipment cleaning verification frequency and the parameters to be tested
(i.e., ) during routine production.
RESPONSE 3
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 7Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
Section 3.2.A.1 Facilities and Equipment Cleaning Validation Summary (Chesterfield)-
Replaced
Previously submitted supporting documentation
None
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 8DRUG SUBSTANCE (PFIZ ER ANDOVER - AND
QUERY 4
Regarding environmental monitoring, please provide the following information:
a.Please define “at rest” and “in operation”.
b.Please clarify if the total air particulate limits are for “in operation” conditions.
RESPONSE 4 a
“At rest” describes the status of a facility with all services functioning, standard processing
equipment installed, and with no personnel or manufacturing activities being performed other
than environmental monitoring.
“In operation” describes the status of a facility with all services functioning, standard
processing equipment installed, but includes routine personnel and production- related
activities being performed or simulated. A facility is considered to be in operation status
from the time of the initial set -up to the start of final clean -up including set -up and
production operations.
RESPONSE 4 b
The total air particulate limits are applied for both at rest and in operation monitoring. A
footnote was added to the Table 3.2.A.1 -4, in 3.2.A.1 Facilities and Equipment (Andover
and Table 3.2.A.1-6, in 3.2.A.1 Facilities and Equip ment ( for clarification.
Literature References
None
SUPPORTING DOCUMENTATION
3.2.A.1 Facilities and Equipment (Andover -Replaced
3.2.A.1 Facilities and Equipment ( -Replaced
Previously submitted supporting documentation
None
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 9QUERY 5
Please supply the following information regarding the dirty and clean hold times of direct
product contact equipment:
a.Please clarify if clean and dirty hold times were performed during process validation, and
please provide the number of replicates perfor med.
b.Define the parameters tested at the end of the clean hold time to verify the equipment
remained clean (i.e., ).
RESPONSE 5
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 10
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BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 11Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 12QUERY 6
Please clarify if the manufacturing areas and direct product contact equipment are product
dedicated or campaign dedicated for BNT162b2 in both and , as there are the
following inconsistencies:
a.In 3.2.A.1.1, you state,
However, in 3.2.A.1.8.1, y ou indicate that the
b.Table 3.2.A.1- 4 ( indicates that
c.Table 3.2.A.1- 3 ( ) indicates that
RESPONSE 6
The response applies to query 6 a, b and c.
Literature References
None
SUPPORTING DOCUMENTATION
3.2.A.1 Facilities and Equipment (Andover -Replaced
3.2.A.1 Facilities and Equipment ( -Replaced
Previously submitted supporting documentation
None
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BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 13DRUG PRODUCT
QUERY 7
Please update Table P.3.1 with the specific anal ytical test methods for drug product release
and stability testing to be performed at each facility.
RESPONSE 7
Section 3.2.P.3.1 Manufacturer(s) is updated to include the anal ytical test methods performed
at each facilit y for releas e and stability . This information is also included within Section
3.2.R Summary of Analytical Procedures, Method Validation and Transfer Reports.
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
3.2.P.3.1 Manufa cturer(s) , replaced
Previously submitted supporting documentation
3.2.R Summary of Analytical Procedures, Method Validation and Transfer Reports
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FDA-CBER-2021-5683-1149558
COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 14QUERY 8
Please indicate what room and building the visual inspection line is located. Please
explain when this inspection machine will be used for inspecting BNT162b2 filled vials
manufactured on Filling Lines .
RESPONSE 8
Inspection L ine is located in the Building at Pfizer Puurs, room . The
Inspection L ine is not intended for use under the commercial BLA and information is
removed from the 3.2.A.1 Facilities and Equipment (Puurs).
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
3.2.A.1 Facilities and Equipment (Puurs) , replaced
Previously submitted supporting documentation
None
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BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 15QUERY 9
Regarding the container closure integrit y testing, please submit the method
validation protocol, summary report and assay performance pro cedure that is followed at
Pfizer Puurs and Pfizer Kalamazoo.
RESPONSE 9
For Pfizer Kalamazoo, the anal ytical method transfer/validation report along with the
analytical procedure covering the method is found in Section 3.2.R Summary
of Anal ytical Procedures, Method Validation and Transfer Reports. The protocol used for
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
Previously submitted supporting documentation
3.2.R Summary of Analytical Procedures, Method Validation and Transfer Reports
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 16QUERY 10
Please submit the container closure integrit y test method validation protocol,
summary report and assay performance procedure that is followed at Pfizer Puurs and Pfizer
Kalamazoo. Please explain when this method will be used as you have two container closure
integrit y methods for your drug product.
RESPONSE 10
Executed test method validation protocols for the anal ysis test method are
provided in lieu of the protocols and summary reports (as all information is captured therein),
covering container closure combinations from both Pfizer Puurs ( USP-1207 Method
Validation - Pfizer Puurs 2mL vial Rev 2.4_Final Report ) and Pfizer Kalamazoo ( USP-
1207 Method Validation - Pfizer Kalamazoo 2mL vial Rev 1.2_Final Report ).
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
USP-1207 Method Validation Pfizer Puurs 2mL vial Rev 2.4_Final Report , new
USP-1207 Method Validation Pfizer Kalamazoo 2mL vial Rev 1.2_Final Report , new
3.2.P.3.1 Manufacturer(s) , replaced
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PFIZER CONFIDENTIAL
Page 17Previously submitted supporting documentation
3.2.P.2.4 Container Closure Sy stem
3.2.P.2.5 Microbiological Attributes
3.2.P.3.5 Shipping Validation
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Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 18QUERY 11
Regarding a recent Information Request response (Response to FDA 26 Jul 2021) STN
125742/0.24, the Agency requires clarification to your Query 16a response regarding new
equipment at Pfizer Kalamazoo. As stated in Table 5 of your 16a response, the
tanks are not y et qualified. Please provide the following
information regarding these tanks:
QUERY 11a
Please provide the equipment numbers and when qualification is expected to be completed (if
not previously completed).
RESPONSE 11a
Equipment (ie, tank) numbers and qualification status are provided in Table 6.Based on
procedures, equipment cannot be used in the process until it is qualified.
Table 6. Tank Qualification Status
Tank Size Tank ID Number Qualification Status Anticipated Qualification
Completion Date
Abbreviations: NA = Not Applicable
The tanks were not included in the BLA application and were submitted as an
amendment to the EUA/IND (SN0426 submitted on 28 Jul 2021) , which is currentl y under
review b y CBER.
QUERY 11b
Please explain wheth er these tanks were used in the process validation runs included in
support of y our BLA application. If not, please provide a justification to explain how the
tanks are suitable for your process operation.
RESPONSE 11b
The tanks were not used for the process validation runs included in the BLA
application.
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COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 19QUERY 11c
Please address the discrepancy regarding the tanks qualification status with y our recent
IND amendment (SN0426), which you referenced in Table 5 of your response to Query
16a. According to y our IND amendment, 2.3. Introduction to the Quality Overa ll Summary
Section 2.3.1.1 y ou claim these tanks are qualified.
RESPONSE 11c
The tanks have been submitted as an amendment to I ND19736 (SN0426 submitted on
28 Jul 2021 ) and also included in Table 5 of response to Query 16a previously submitt ed to
STN 126742/0.24. Query 16 indicated that it was in regard to the BNT162b2 major
manufacturing equipment used at Pfizer Kalamazoo , therefore the tanks that were
recentl y submitted, were added to the table to be complete.
As a clarification relative to the Quality Overall Summary Section 2.3.1 .1 of IND 19736
SN0426 which states that the tanks are status is
in reference to and in support of the tanks are
although of the tanks been full y qualified for use.
The remaining tanks will be qualified prior to being placed into service by
.
QUERY 11d
Please address whether these tanks have been used in the ma nufacture of EUA BNT162b2
material prior to qualification.
RESPONSE 11d
None of the tanks have been used to manufacture EUA BNT162b2 material.
of the tanks has been qualified for use. Change control records are
utilized to document the qualification activities of each individual tank. Tanks can be placed
into service following approval of the amendment to I ND19736 (SN0426 submitted on 28
Jul 2021 ) and after all change control activities have been completed.
QUERY 11e
Please provide summaries of y our cleaning and sterilization validations for the tanks.
If cleaning and/or sterilization validations are not complete, pl ease provide a timeframe that
you expect to complete the respective validations. Please provide a summary of your
cleaning verification regime including acceptance criteria.
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FDA-CBER-2021-5683-1149564
COVID -19 Vaccine (BNT162, PF -0730 2048)
BLA 125742/0
Response to 05 Aug 2021 FDA IR-Facilities Questions
PFIZER CONFIDENTIAL
Page 20RESPONSE 11e
The sterilization validation for the tanks has been provided in the recent IND 19736
amendment (SN0426). An updated Section 3.2.P.3.5 Sterilization in Place (SI P) Validation
[Kalamazoo] is also provided in this response. This updated document is fully aligned with
the content submitted in IND 19736 SN0426, includin g a revised scope of tanks
presented, which focuses only on tanks that contact the sterile drug product. I nformation has
been removed for
and do not contact th e sterile drug product .
A cleaning assessment has been completed for the tanks which determined that
the tanks are covered b y existing cleaning validation. The cleaning validation summary for
the tanks are covered by the data for the BN T162b2 Bulk Hold, and Sterile
Tanks provided in 3.2.A.1 Facilities and Equipment Cleaning Validation Summary –Pfizer,
Kalamazoo.
QUERY 11f
Please provi de BNT162b2 hold time validations for the tanks
including the microbi al challenge resul ts and criteria.
RESPONSE 11f
The hold time validations for the tanks hav e not y et been completed. The h old time
validations will be completed b y .
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supp orting Documentation
3.2.P.3.5 Sterilization in Place (SI P) Validation [Kalamazoo], Replaced
Previously submitted supporting documentation
3.2.A.1 Facilities and Equipment Cleaning Validation Summary –Pfizer, Kalamazoo
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PFIZER CONFIDENTIAL
Page 21FOLLOW -UP TO FDA’S 26 JULY 2021 I RRESPONSE REGARDING
MANUFACTURING AND EQ UIPMENT : QUERY 16E
Regarding the recent Information Request response to the agency on 26 Jul 2021 (Response
to FDA 26 Jul 2021) STN 125742/0.24, to Query 16 e, the following Table 8 has been
updated with additional i nformation for portable tank . Portable tank
has been removed from the table as it was incorrectl y added in the
response to Query 16e. Minor formatting corrections were also made to the table.
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PFIZER CONFIDENTIAL
Page 22Table 8.Drug Product Contact Equipment Summary
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Page 23Table 8.Drug Product Contact Equipment Summary
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Page 24Table 8.Drug Product Contact Equipment Summary
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