Document text
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 1TABLE OF CONTENTS
QUERY 1 ................................ ................................ ................................ ................................ ...2
RESPONSE 1 ................................ ................................ ................................ ................... 2
QUERY 2 ................................ ................................ ................................ ................................ ...3
RESPONSE 2 ................................ ................................ ................................ ................... 3
QUERY 3 ................................ ................................ ................................ ................................ ...4
RESPONSE 3 ................................ ................................ ................................ ................... 4
QUERY 4 ................................ ................................ ................................ ................................ ...6
RESPONSE 4 ................................ ................................ ................................ ................... 6
QUERY 5 ................................ ................................ ................................ ................................ ...8
RESPONSE 5 ................................ ................................ ................................ ................... 8
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
FDA-CBER-2021-5683-1149507
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 2QUERY 1
In your validation report for the 5’ -cap assay for drug substance (VAL100136648), the
accuracy study report includes a calculation of
Please explain how y ou obtained the values in
attachment 8.
RESPONSE 1
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
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FDA-CBER-2021-5683-1149508
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 3QUERY 2
Regarding the d ynamic light scattering (DLS) method to determine lipid size and
polydispersit y of drug product (DP): please state whether this DLS method can
LNPs. Please provide
data to support your claim and, if the method does not LNP
provide information describing resolution of and explain how the
is evaluated.
RESPONSE 2
This DL S method
. However, if significant
, DLS would be able to . DLS method
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
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FDA-CBER-2021-5683-1149509
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 4QUERY 3
For container content of DP:
a.You calculate volume of each vial based on vial and DP . Please
describe how was determined.
b.In the verification report [USP 697 (EP 2.9.17) and USP 788 (EP 2.9. l 9) -PF-
07302048 -CMVR -001] from PSG -KZO lab, DP container content was determined by
measuring the total volume after 1.8 mL of sterile 0.9% sodium chloride solution was
added. Please confir m that this method will be used for lot release testing by the
PSG-KZO laboratory and that the container volume specification “Not less than
mL” is the same regardless of test site/method.
RESPONSE 3
a.The density of DP was determined using a represent ative DP sample at
and measuring the
b.PGS-KZO confirms method TM9106A will be used for DP Container Content release
testing. It is also confirmed that the Container Content specification of Not less than
mLis the same regardless of test site/method.
EUA DP specifications initially included USP 697 Container Content for Injections
which was later replaced by Vial Content (volume). Since both the Container
Content for Injections and Subvisible Particulate Matter were compendial, a
combined protocol was executed and documented under V erification report [USP 697
(EP 2.9 .17) and USP 788 (EP 2.9. l 9)- PF-07302048 -CMVR -001]. This verification
report supports method verification of USP 787 [Subvisible Particulate Matter] under
BLA for PGS -KZO.
USP 697 [Container Content for Injection] was replaced with PGS- KZO method
TM9 106A [Vial Content (volume)] , which no longer includes measuring the total
volume after 1.8 mL of sterile 0.9% sodium chloride solution addition . Method
verification of TM9106A is documented in Method Equivalency Report: Method
Equivalency and Verificatio n ofTM9106A, Container Content for PF -07302048
Multi -Dose Vials and USP 697.
Literature References
None
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
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FDA-CBER-2021-5683-1149510
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 5SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
None
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
FDA-CBER-2021-5683-1149511
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 6QUERY 4
Regarding your response (in STN 125742/0.16 dated July 23, 2021) to our IR dated July 9,
2021, about the validation of the CGE Integrit y method:
a.Your response includes the results at
for the DP a nd DS. Please calculate the accuracy at each of the
accordingly values). It appears
that y ou did not include predetermined acceptance criteria for assay accuracy in your
validation protocol; therefore, we assume the accuracy established in this validation
study will be used to support assay transfer or revalidation studies. Please confirm by
stating the accuracy acceptance criteria for integrity measurements of both the DP and
DS in the inte grity assa y.
b.In your response to query 2, it appears that the validation results for the DS RNA
integrit y range evaluation could not meet the pre -specified acceptance criterion at the
higher end ( of product specification corresponding to a RNA i ntegrit y).
Please re -evaluate the DS RNA integrit y range using available batches that are able to
achieve the RNA integrity level of . Alternatively , please adjust y our validation
acceptance criterion based on the available qualification/validation r esults should a
re-validation and/or assay transfer be performed.
RESPONSE 4
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
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FDA-CBER-2021-5683-1149512
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 7Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted supporting documentation
VAL100136603, RNA Integrit y of mRNA Dug Substance and LNP -mRNA Drug Product
Samples by Fragment Analy zer (CGE)
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
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FDA-CBER-2021-5683-1149513
COVID -19 Vaccine (BNT162, PF -07302048)
BLA 125742/0
Response to 02 Aug 2021 FDA IR–Assay Methods and Lot release
PFIZER CONFIDENTIAL
Page 8QUERY 5
Under 21 CFR 610.2(a), manufacturers may be required to submit sampl es from all lots of a
licensed biological product together with the protocols showing results of applicable tests
when deemed necessary for the safet y, purity, or potency of the product. Lots shall not be
distributed until released by the Director, CBER. A brief description of the process follows:
samples and Lot Release Protocols (L RPs) must be submitted to the Product Release Branch
(PRB), Office of Compliance and Biologics Quality (OCBQ) via an electronic portal that is
different from that used for electronic submissions to the product office. If y ou need
instructions on accessing the gateway or where to submit samples, please contact Mr. Joseph
Quander, Chief, Product Release Branch, DMPQ, OCBQ at [email protected].
CBER grants approval to release lots by issuing a letter from the Center Director or his/her
representative, that is sent to the firm’s representative by email.
If you plan to release lots at the time of approval (launch lots), the LRPs need to be reviewed
well before the PDUFA action due date. We recommend submitting L RPs and 20 vials of
final DP for launch lots as soon as possible You will need to use the L RP template that is
currentl y under review; we anticipate providing a description of changes that need to be
made to this template within the next two weeks.
Please state how man y launch lots you plan to submit and let us know if you need additional
information to submit the samples and L RPs.
RESPONSE 5
The applicant understands the general procedures for use of Lot Releas e Protocols (L RPs)
and submitting samples to the Product Release Branch, and Pfizer has experience with this
system for other products. We anticipate that there will be a need to continue to expedite
release following BLA approval, with a cy cle time simila r to that achieved under the EUA
for as long as pandemic conditions prevail.
At the present time we have not produced launch lots.
Literature References
None
SUPPORTING DOCUMENTATION
New or Replaced Supporting Documentation
None
Previously submitted suppor ting documentation
None
090177e197c314fd\Approved\Approved On: 09-Aug-2021 12:41 (GMT)
FDA-CBER-2021-5683-1149514