Document text
From: Smith, Michael (CBER)
Sent: Thursday, August 5, 2021 1:48 PM
To: Harkins Tull, Elisa <[email protected]>; Aghajani Memar, Neda
<[email protected]>; Devlin, Carmel M <[email protected]>; Rohlfing, Paul
<[email protected]>
Cc: Naik, Ramachandra <[email protected]>; Gottscha lk, Laura
<[email protected]>
Subject: STN 125742.0: 11 Facilities questions
Elisa,
The review team has the below 11 facilities questions, please respond as soon as
possible but no later than COB Wednesday, August 11, 2021.
(P fizer, Chesterfield):
1. Please clarify what critical utilities are used during the
process, and the microbial control for each critical utility (e.g.,
or routine monitoring).
2. The list provided in Table 3.2.A.1- 1 does not include tubing, small parts,
biological safety cabinets, and laminar flow hoods. Please update Table
3.2.A.1 -1 to include all direct product contact equipment.
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 for each equipment.
c. Specify the equipment cleaning verification frequency and the
parameters to be tested (i.e.,
) during routine production.
Drug Substance (Pfizer Andover; Both and
4. Regarding environmental monitoring, please provide the following information:
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150212
a. Please define “at rest” and “in operation”.
b. Please clarify if the total air particulate limits are for “in
operation” conditions.
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
performed.
b. Define the parameters tested at the end of the clean hold time to
verify the equipment remained clean (i.e., ,
).
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, you indicate that the .
b. Table 3.2.A.1- 4 indicates that
c. Table 3.2.A.1 -3 indicates that
Drug Product:
7. Please update Table P.3.1 with the specific analytical test methods for drug
product release and stability testing to be performed at each facili ty.
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 .
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150213
9. Regarding the container closure integrity testing, please submit the
method validation protocol, summary report and assay
performance procedure that is followed at Pfizer Puurs and Pfizer
Kalamazoo.
10.Please submit the container closure integrity 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 integrity methods
for your drug product.
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 yet qualified. Please provide the following information
regarding these tanks:
a. Please provide the equipment numbers and when qualification is expected to be completed (if not previously completed).
b. Please explain whether these tanks were used in the process validation runs included in support of your BLA application. If not,
please provide a justification to explain how the tanks are suitable
for your process operation.
c. Please address the discrepancy regarding the tanks
qualification status with your recent IND amendment (SN0426), which you referenced in Table 5 of your response to Query
16a. According to your IND amendment, 2.3. Introduction to the
Quality Overall Summary Section 2.3.1.1 you claim these tanks are qualified.
d. Please address whether these tanks have been used in the manufacture of EUA BNT162b2 material prior to qualification.
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150214
e. Please provide summaries of your cleaning and sterilization
validations for the tanks. If cleaning and/or sterilization
validations are not complete, please provide a timeframe that you
expect to complete the respective validations. Please provide a
summary of your cleaning verification regime including
acceptance criteria.
f. Please pr ovide BNT162b2 hold time
validations for the tanks including the microbial challenge results and criteria.
Regards,
Mike
- Please confirm receipt of this e -mail and let us know if you have any
questions.
Mike Smith, Ph.D.
Captain, USPHS
Senior Regulatory Review Officer
Food and Drug Administration
Center for Biologics Evaluation & Research
Office of Vaccines Research & Review
Division of Vaccines and Related Products Applications
Tel: 301- 796-2640
[email protected]
THIS MESSAGE IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT IS
ADDRESSED AND MAY CONTAIN INFORMATION THAT IS PRIVILEGED, CONFIDENTIAL, AND
PROTECTED FROM DISCLOSURE UNDER LAW. If you are not the addressee, or a
person authorized to deliver the document to the addressee, you are hereby notified that any review, disclosure, dissemination, copying, or other action based on the content of this communication is not autho rized. If you have
received this document in error, please immediately notify the sender
immediately by e- mail or phone.
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150215
FDA-CBER-2021-5683-1150216