Document text
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
1 of 79
TABLE OF CONTENTS
Summary ............................................................................................................................... 1
Administrative Data ............................................................................................................... 2
Persons Interv iewed ............................................................................................................. 3
Background and History ....................................................................................................... 3
Drug Product Manufacturing Overview ................................................................................ 5
Walkthrough .......................................................................................................................... 6
Quality Systems .................................................................................................................. 10
Facilities and Equipment Systems ..................................................................................... 22
Equipment Qualification ...................................................................................................... 24
Materials System ................................................................................................................ 53
Production System .............................................................................................................. 54
Packaging and Labeling Systems ...................................................................................... 71
Laboratory Control System ................................................................................................. 72
Recall Procedures .............................................................................................................. 76
Refusals ............................................................................................................................... 76
General Discussion with Management .............................................................................. 76
Exhibits Collected ............................................................................................................... 77
Attachments ........................................................................................................................ 78
SUMMARY
(Written by LF)
This FY 21 pr
e-license inspection at the Pfizer Manufacturing Belgium NV site located at
Rijksweg 12, 2870 Puurs, Belgium was conducted for BLA STN 125742/0,
COMIRNATY ™ (COVID -19 Vaccine (BNT162b2, PF-07302048) ), i
ndicated for the
prev
ention of COVID -19 in adults 16 years of age and older . Pfizer Manufacturing
Belgium NV (also known as Pfizer Puurs) will produce the BNT162b2 drug product,
including the steps of Lipid Nanoparticle (LNP ) fabrication/ formulation bulk drug product,
fill/finish, and labelling/ packaging.
The i
nspection was conducted from June 24 through July 2, 2021 and the inspection
team included Laura Fontan (CSO/lead inspector) and Zhongren Wu (CSO) both from
OCBQ/DMPQ, Anissa Cheung (CSO) from OVRR/DVP, and Susan Jackson (CSO)
from ORA/OMPTO/OBPO/BPIS. The scope of the inspection covered the following
systems: Quality, Facilities /Equipment, Production, Materials , Packaging/labeling, and
FDA-CBER-2021-5683-1150420
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
2 of 79 Laboratory Control. The inspection was performed according to eNSpect operation
identification number 201736.
The previous Pfizer Puurs inspection was conducted November 9 through 16, 2017. At
the end of the previous inspection, no FDA Form 483, Inspectional Observations , was
issued .
During the recent inspection, no FDA Form 483, Inspectional Observations , was issued,
however there were some discussion items, which are listed at the end of this inspection report.
Documents reviewed included: SOPs, batch records, complaint reviews, devi
ation
investigations, change controls, training records, area cleaning and maintenance, facility
layouts , equipment qualifications, cleaning validation, st
erilization validation, medi a fills,
environmental monitoring, visual inspection, contamination prevention, and laboratory
assays.
No sam
ples were collected, and no refusals were encountered during this inspection.
ADMINISTRATIVE DATA (Written by LF)
Inspected firm: Pfizer Manufacturing Belgium NV
Location: Rijksweg 12
Puurs , Belgium 2870
Phone:
FAX:
Mailing address: Rijksweg 12
Puurs, Belgium 2870
Dates of inspection: 06/24/2021, 06/25/2021, 06/28/2021, 06/29/2021, 06/ 30/2021,
07/01/2021 and 07/02/2021
Days in the facility: 7
Participants: Laura Fontan (LF), Consumer Safety Officer
Zhongren Wu (ZW), Consumer Safety Officer
Anissa Cheung (AC), Consumer Safety Officer
Susan Jackson (SJ), Consumer Safety Officer
(b) (4)
FDA-CBER-2021-5683-1150421
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
3 of 79 PERSONS INTERVIEWED
(Written by LF)
During the opening meeting on June 24, 2021, we (LF, ZW, AC and SJ) presented our
credentials to Luc Van Steenwinkel , Site Leader, who identified himself as the most
responsible official for the site.
On June 30, 2021, Inspector Cheung ( AC) discussed her clos
ing remarks with
Pieter Verbelen, Launch Excellence
Director and At
the final close-out meeting on July 2,
2021, we (LF, ZW and SJ ) di
scussed our closing remarks with site leadership which
included Luc Van Steenwinkel, Site Leader and
See Exhibit LF-1a-d for a li
st (prepared by the firm) of those present at the opening and
closing meetings, as well as participants in the inspection.
Each member of the inspection team contributed to the establishment inspection report
(EIR). The sections of the EIR written by each team member are denoted by their
initials.
BACKGROUND AND HISTORY
(Written by LF)
• Pfizer Manufacturing Belgium NV, having its corporate address at Rijksweg 12, B -
2870 Puurs, Belgium was incorporated under the laws of the Kingdom of Belgium on
the 9th day of September 1960.
• Operations started in 1963.
• The current was built in 1980.
Commercial manufacturing started in 1982. Since 1982 several extensions and
facility modifications have been implemented, which include the
in 2011. In 2015, a
was implemented.
• In 1998 a w as built for the manufacturing and
packaging of w as used for
manufacturing at that time
• In 2013 the w as finished
was performed in
2014/2015 and started in 2015.
• In 1999 t echnology was int roduced and
In this ar ea Xalatan manufactured.
Xalatan is a product on the US market.
• In 2004, a was constructed about 1 mile from the
manufacturing pl ant. This building contains
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(b) (4)
FDA-CBER-2021-5683-1150422
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
4 of 79 • The the facility where
are aseptically filled was built in 1998
In 2012, the facility was finished,
was
performed in 2013 and started in January 2014.
• In 2013, a w as built for the manufacturing
of a vaccine against pneumococcal infections . This has been
operational since end of 2014.
• From 2017 to 2020, a wide range of projects were started, which included:
o C onstruction project s at the Puurs Plant:
o Expansion and optimization projects , such as the
o C ontinuous improvements projects such as :
and an I ntegr ated M anufacturing
Excellence (IMEx) program
• In 2018, Pfizer Manufacturing Belgium NV started building
C onstruction works continued in June 2020
and i n March 2021 with
• In 2020 several expansions were made to provide for the COVID -19 vaccine with the
installation and validation of formulation booths F or the packagi ng and
cold chain of COVID -19 vaccine, the freezer farm and shipping lines were installed.
In 2021, w ere added to scale up the capacity for the
COVID -19 vaccine.
Further history is det
ailed in Exhibit LF-2 . The opening presentation is attached in
Exhibit LF-3 .
Hours of Operation:
Aseptic Manufacturing, Packaging, Warehousing:
Operations:
(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)
(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-2021-5683-1150423
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
5 of 79
Administrative: Week: Monday through Friday - flex time (core time between 9 am to 5
pm)
Employees:
Manufact ur
ing Operations:
Packaging and Warehouse:
Q
uality Operations:
Support Functions: Engineering, Site Technical Services, Launch Excellence, Supply
Chain Management, OPEX, EHS & site services:
Enabling Functions: BT, HR, Finance, Procurement:
Total: DRUG PRODUCT MANUFACTURING O
VERVIEW
(Section written by AC)
The manufacturing process for BNT162b2 drug product includes lipid nanoparticle (LNP) producti
on and bulk
drug product formulation f ollowed
by fill and finish ( Exhibit AC -1).
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150424
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
6 of 79 Sterile filtration of the bulk drug product
then f illed aseptically into vials
A
stopper is inserted i nto each vial immediately after filling,
followed by capping of the stoppered vials. After the filling operation, the vials are
automatic
ally inspected, labeled, and frozen at -90 to - 60°C.
All manufacturing operations and in-process holds ar e conducted at unl
ess
other
wise speci
fied and the worst -case hold times are challenged during the process
validation runs.
WALKTHROUGH
(Writt
en by AC)
On the first day of inspection (June 24), we (AC, LF, ZW and SJ) started the facility
walkthrough in the war
ehouse w
here all the raw materials are received through the
s
ystem. Then we moved to the r
oom at t
o
observe t
he
also showed us
the r
oom.
and
Thomas Deproost (Sr Manager Aseptic Mfg,
ac
companied us on the walkthrough of the LNP production
W
e started at the
P
fizer personnel stated that all
operations
are captured under the electronic batch record, and they showed us how
dat
a was captured in the electronic batch record.
On June 30, Jan Dams (Sr Project Manager, Asept
ic Mfg), Abo Steels (Team
Leader
Production), and Koen Vastenavondt (Operational director, Aseptic Mfg led a
walk
through of the freezer farm located at Building. ul
tra-low
freez
ers are placed in this
I observed the transfer of pizza boxes (firm’s terminology for vaccine storage
box) from to the designated pizza boxes
pizza boxes/bundle) will be stored in
(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) (6), (b) (7)(C)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4), (b) (6), (b)
(7)(C)
(b) (4), (b) (6), (b) (7)(C)
(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)
(b) (4)
FDA-CBER-2021-5683-1150425
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
7 of 79 for the transfer to
tr
ansport box is filled with dry ice
The temperature probe is located t o
monitor the temperature There are packaging lines located
and I observed the operation on Line packing pizza boxes into the
shipping box (softbox
). pizza boxes are packed softbox and a probe is
placed
softbox with dry ice
Facility W
alkthrough
(Written by SJ)
During the inspection, I participated in a walk -through of the
ar
ea and observed f ormulation booths w here COVID 19 vaccine i s
I observed the for the lipid component of the
vaccine and I observed filling and visual inspection of batch
A
walk -through of G
rade areas and the filling operation
including visual inspection for COVID 19 mRNA vac cine batch were observed.
In addition to the walk -through of the production areas we w
ent to the
incoming goods warehouse, freezer farm where the COVID 19
mRNA vacci
ne is
Warehouse Walkthrough
(Written by ZW)
On 6/24/2021, Inspectors Fontan, Jackson,
Cheung and I conducted the walk -through
inspection of the warehouses,
located in with
assistance from guided u s
and answered questions. He stated that the warehouse is temperature-controlled, and
the temperature is monitored through
stated that the inventory is also computer -based and governed by a
All incoming materials will be checked per the checklist
for any damages. I noticed there are used in the receiving area.
s
tated all the are from shippers and they are or
will be rejected. I confirmed that the accepted
stated that all the external will be
acceptance into the warehouse. He stated that there are no physical compartments for
quarantine, and release. The regulatory status of the raw material is maintained by the
however, for the rejected materials, they are
area. I inspected this area and checked the construction
and I did not identify any issues.
(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)
(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) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)
(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150426
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
8 of 79 Per the concept using the i s important in his
warehouses, because
The vaccine
manufactur
ing-related raw materials such as
and gl
ass vials used in the filling line, are stored in the warehouses.
On the are
the
expl
ained that the warehouse personnel are respons ible for
I
conducted a i nspection of the fr eezer . The fr eezer
has a size of It is in the There is a
and the
to keep the temperature balanced. The door is locked,
and open only to authorized personnel ac
cording to
With
his perm
ission, I tried and w
as rejected to enter the The
door c
loses automatically
This freezer in 2015 and r
equalified in Currently, the
are
stored here. While
t
he freezer I inspected the labels and packaging integrity of
and verified the lot numbers without concerns.
The
room
is We interviewed
and
st
ated t
hat the can be conducted at or in a
W
e observed a few
s
ection of the room designated as the ar
ea
We also observed the which has the
capacity of According to when
t
he is set at We also
observed the which is under qualification. Currently, the
is more commonly used, according to
At the room
, I requested to review the batch record. s
tat
ed that
batch records ar
e digital. He demonstrated that the batch record for the pr
oces s
is filled out on the I had no issues with the
pr
ocess.
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150427
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
9 of 79 Walkthrough of
(Written by LF)
On June 28, 2021, SJ and I went t o the Room to witness
fi
lling of BNT162b2 batch We were accompanied by
and T he 2
mL vials enter
T
he vials are
The was
operating
the
vials I was told that the was
There is also
an SOP for aft
er such an event. The
direct product
contact equipment used in the filling
The di
rect product contact equipment and miscellaneous parts
needed for filling are
The filler has
st
opper s
also enter I was told that each batch uses
of
stoppers . The ty
pically batches at a
time, howev
er,
the direct product contact fi lling parts are per
batch
in a At the line is a capper
Gr
ade
The capper rej
ects
These rejects were enter
ed into the batch record. The capper was
operating at a speed of The validated maximum speed for the 2ml vial
is is
performed every
and doc
umented on a rec
ord that is reviewed as part of the batch
record. The capped vials are then inspected using the automated visual
inspection machine. No concerns w
ere noted.
On July 1, 2021, I went into
accom
panied by
Piet
er Verbelen, Launch Excellence Director and
to w
itness BNT162b2 steril e
filtration operations in The BNT162b2 bulk in
was lot is
in room
The sterile filtration in the room
and then When I was in Room operations personnel were
in
preparation for sterile filtration. is t
o
bulk drug product
sam
ples are taken from filtration. See Exhibit LF-4
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4), (b) (6), (b)
(7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4), (b) (6), (b) (
(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) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150428
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
10 of 79 S ample port No concerns were
noted.
On July
2, 2021, I inspected t he freezer farm located at Bui lding with
Abo Steel
s,
Team Leader Production, and
Koen Vas
tenavondt, Operational director, Aseptic Mfg B
NT162b2 filled
vials f
its inside each freezer. I watched the product being
with the product pizza boxes
each containing 195 vials. fit inside each freezer
A i
s used to transport the frozen vial bundles to
be packaged for shipping. The is kept cold using at the
I watched two operators load bundles into the
wh
ile checking/scanning batch numbers on each bundle during
transfer . I also watched the loading of pizza
boxes into one softbox with
dry ice .
The shipping logger is instal
led the shipping box has an expiration of
and
provides live monitoring of temperature in the box and GPS tracking. See
Exhibit LF-5.
QUAL
IT
Y SYSTEMS
Quality System
(Written by SJ)
All SOPs requested in the FDA Pre-Request List were translated from Dutch to English
for the inspection.
Coverage of the Quality System included the review of the following written procedures:
Quality Manual
SOP version Quality Manual effective 10-June 2021 describes the Quality
Management System at the Pfizer Manufacturing Belgium NV (Pfizer Global Supply
(PGS) Puurs facility ). The Quality Manual addresses the Quality Management System
(QMS) requirements for design, development, manufacturing, packaging, testing, disposition, storage, distribution and post market surveillance of all drug products, medicinal products, biological products,
The Quality Manual describes the senior management responsibilities to include the
development and maintenance of the Quality Policy ensuring a suitable and effective
QMS is in place. Senior management is also responsible for adequate resources and that roles, responsibilities and authorities are defined, communicated, implemented throughout the organization.
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150429
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
11 of 79 The Quality Manual describes the QMS documentation process and contains
Quality Manual and Organization
Master Standard Operating Procedures (Master SOP)
Standard Operating Procedures SOP and /or Work Instructions
Forms
Records
SOP version Organization effective May 27, 2021 details the key roles and
responsibilities of management. The SOP gives the site management organizational
chart, quality management organizational chart and key roles and responsibilities of the senior management such as the Site Leader, Site Quality Operation Lead, Site Data
Integrity Lead and the Release Operation Manager and Manager of COVID Project. The
SOP also gives additional roles and responsibilities of the Site Quality Review Team (SQRT). Management Review
(Written by SJ)
SOP version Management Revi
ew Process effective 18 May 2020, describes
the process used to review the quality management system at documented, planned
intervals by top management at the site to ensure continuing suitability, adequacy, and
effectiveness. The Site Quality Review Team (S -QRT) meets on a fr
equency
and the scope of their review is site quality and compliance metrics (QMS processes). Actions
from the management review are and
incorporated i nto
the CAP
A system.
Internal Audi
t
(W
ritten by SJ)
SOP version Internal Audi
ts Quality effective 05 March 2021, this procedure
manages the periodic site self -audit. Internal audits are a system -based audit which are
conducted at a frequency such that each system is audited and
the
associat
ed sub systems are audited E
xamples of
systems include but are not limited to quality, production, facilities and equipment, laboratory control materials, and validation. Example of a subsystem includes but is not
limited to the following: change control, production areas, supplier qualification, utilities, complaint management etc.
I reviewed the internal audit plan for the 2021 which included the system and subsystem for T
he internal audit plan documents that an audit of
i
s scheduled in and an audit of
i
s scheduled for 2021.
ex
plained the internal audit process and provided evidence of the
(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)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
FDA-CBER-2021-5683-1150430
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
12 of 79 executed internal audits for for 2021. Additionally, I requested to verify that
during the internal audits electronic data is retrieved and reviewed as part of the audit.
pr
esented executed internal audit agenda/scope and audit
concl
usions t hat stated that all elements of the audit were executed including the review
of electronic records and data.
Change Management
(
Written by SJ)
SOP Change Managem ent, effective 09 December 2020, details the
introduction of a new change, change or decommissioning of an existing product,
validation process, direct impact system and quality management system. Every change is identified in one of four groups consisting of : product, process, systems and
QMS.
All changes are c ategori zed as either a permanent change, emergency change,
procedural change and planned change and they are managed by the site change
management procedures in SOP The SOP describes and defines the primary action within a permanent change as change description, impact assessment (IA)/action
plan, pre-approval, implementation, and closure. Other changes such as procedural
change, planned temporary change and emergency change are also described. QA is
required to approve changes
All changes are managed in
Deviat
ion
(Written by SJ)
SOP- version Devi ation Reporting effective 19 May 2021, manages reporting
and documenting unplanned incidents for drug products activities, including but is not
limited to production, testing, distribution in support of Pfizer Products at Pfizer Puurs. All unplanned incidents are documented in
To
document an incident in an
ar
ea specific SOP is followed based on the incident type. The following are the area-
specific SOPs:
• SOP- M
anufacturing Investigation
• SOP- M anufacturing Investigation for Uti
lity Issues
• SOP- Manufacturing Investigation from Environmental Monitoring Issues
The SOPs appeared acceptable.
Review of Deviations/OOSs Investigation
(Written by AC)
I reviewed m ore than
50 product or process -related deviations. The majority of these
were recurrent. One deviation involved multiple final DP batches that demonstrated
lower than expected
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150431
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
13 of 79 Deviation was created due to the
T
hree DP batches
were reject
ed. This issue was communicated to the agency late last year, and
during this ins
pection the firm provided additional data to further support that the
w
as the root cause. Pfizer
identified that the impurities present in
c
aused the Current ly, as a corrective action,
is
impl emented
T
he firm
provided DP manufactured with
pr
oduced with the process and all
release test r
esults are within specifications with no significant detection of
Five deviat
ions were reviewed that were related to the as
say
The root cause of these deviations was either
due to the operat
or error or issues with the I
checked the training
records of all the operators that are qualified for performing this test and the records indicated that they finished the training and are fully qualified to perform the assay. In
response to these deviations and further improving the robustness of this assay, the
fi
rm has
a plan in place to implement a revised as
say
A change
control reques
t was created in May 2021
T
he rev ision of
as
say appears acceptable.
(Written by
LF)
Proc
ess Record PR was discovered on Dec ember 3, 2020 and reported on
December 4, 2020. In-process bioburden s amples were taken
on
November 17, 2020. T he sample was taken
The
results f
rom the w
ere
exceeding the l
imit of
The corrective action
taken after the event was to perform a cleaning and
disinfec
tion of the (
December
21, 2020). A detail ed cause and
effect analysis was performed including machine, method, human, materials,
measurement system, and environmental factors. The detailed root cause analysis for
the incident included:
• Reviewing the process and all bioburden and endotoxin results from
Batch Al
l
other results met the expected limits.
• Review of sample flow and testing analysis
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150432
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
14 of 79 • Description of process and incident step by step including sampling and
transportation, bioburden analysis, disinfection of preparation of
materials , env
ironmental control ex
ecution of bioburden analysis and
reading of bioburden results
• Frequency of the issue, including historical bioburden and endotoxin data in the
of r
eoccurrence of identified microorganism
(Stenot
rophomonas maltophilia) , raw materials used during the
batch, and
witnes
sing of the set -up of and
Many
of the potential root causes came f rom witnessing the set -up of
w
as removed and a was connected. The main root cause
was i
dentified as O
perators that cleaned up
a s
pill on the floor, attached the without disinfecting their gloves.
Contribut
ing
fac
tors were:
• Possibility of contamination from the environment
• Part of product path is
• ar
e not able to withstand the gener
ated by the
system
Four
corrective actions were listed and were completed. All other bioburden and
endotoxin result
s, tests, E
M data and
r
elease resul
ts for the batch were within the expected limits, so it was concluded that
there was no quality impact to this lot. The investigation appeared thorough.
Subsequent lots produced through di
d not have bioburden or endotoxin
results that exceeded limits. The information appears acceptable.
PR ID was created
May 21,2021, occur
red May 20, 2021
Short description: Non-inspected COVID vials were labelled and pack aged (batch
This
issue was discovered during
C
orrec
tive actions were identified and implemented. An effectiveness check was
required. The investigation was approved for extension
No concerns noted.
CAPA
(Wri
tten
by SJ)
Corrective and prevent iv e action role, responsibility and process are described in SOP
v
ersion The procedure applies to all actions A
correction
is defined as The CAPA system
manages correction from systems such as deviations, complaints, AP R, and internal
(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)
(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-2021-5683-1150433
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
15 of 79 and external audits. The CAPA flow for corrective action and preventive action requires
a root cause analysis and then the implementation of the defined corrective action and
preventive action. When a defined effectiveness check has been identified for a
corrective action, a successful effectiveness check is required before the CAPA can be
closed.
Biological Product Deviation Report ing (BPDR)
(Written by SJ)
SOP version Biological
Product Deviation Report (BPDR) describes the
requirement, responsibilities and the workflow for potential incidents that require a BPDR. In the event of an incident impacting a product
t
he Release Site Quality Operations Leader (SQOL) is r esponsible for
preparing the draft BPDR with input from the A
dditionally,
m
ust be identified in the BPDR. SOP des
cribes the timeframe for
reporti
ng BPDR to CBER as no later than 45 days from the date of discovery.
Document M
anagement
(
Written by SJ)
The written procedure SOP -
v
ersion Document Management manages GMP
related documents within the Pfizer Puurs facility. GMP related documents can be
managed
or they can be
managed f
or
storage and
management of the electronic versions of documents. SOP - det
ails a
high-level workflow for the creation of a new document. Periodic review of GMP documents is set at a minimum of
how
ever the review of the Quality
Manual and the Organization SOP requires a review frequency of All
documents identified as pertaining to GMP are required to have three approval s by
three different persons. One of these approvals must be from the Quality Unit.
i s used when making GMP related fill -in documents.
ensur
es a unique sequential number is shown on documents and the document has a
limited s
helf life of after printing.
GMP documents that are managed in applications are as
follows
: Master Batch Record managed within the
Lot Plans
managed in and
Maintenance Records managed within
Document control
(
Written by ZW)
The firm handles the document control per SOP - “
Document and record
management”
, effective date 9/28/2020.
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
FDA-CBER-2021-5683-1150434
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
16 of 79 show ed me the flow chart indicating how the
document or record is determined to be GMP related and the sub-SOP to be followed.
Currently, most of the documents, such as are For the
documents, such as they are issued by the QA unit and will be
reconciliated.
Electronic
Batch Record (EBR) system
(Written by LF)
The COVID -19 vacci ne manufacturing process is conducted using a
batch records. The end goal is to have a batch
record, however , currently manufacturing steps are initiated in
pres
ented an overview of the EBR system.
The curr
ent pr
ocess es in include:
M
aster Batch records (MBR) are maintained under change control and
c
urrently approved master record exists for each product at a specific time. In order to
change an E
BR the initiator must request a change and qualified authors (Site
Technical Services) design/configure, test and prepare the MBR updates. Any changes are verified by a qualified secondary author, the production authority and the quality authority. These steps are described in Work Instruction SOP -
The EBR s do not al
low any blanks , and steps cannot be skipped. The limits are
c
hecked based on configured values, such as
can also be set for requirements before use such as
preparation required and expiry times. The electronic signatures
are configured based on the role.
During batch record execution, measured
val
ues are inputted by
The limits for the
v
alues ar e part of the batch record and i f an exception
is triggered. Exceptions are also triggered by
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4), (b) (6), (b) (7)
(C)
(b) (6), (b) (7)(C)
(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-2021-5683-1150435
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
17 of 79 Deviations can be initiated by production and are added to exceptions.
The ex
ceptions are reviewed according to SOP - Evaluation of batch records of
product
produced in Puurs, Ver. All exceptions are reviewed by production and
quality. Automatically generated alarms are also reviewed by quality.
Unauthorized persons cannot acces s the application. In addition,
in w
hich is linked to
The shows
The data is reviewed during the batch record review.
The discussed in procedure
P
olicy is validated. has
specific roles
defined for access to the different based on an
employee’s function and training. No concerns were identified.
Quality
Agreements
(Written by SJ)
During the inspection, I reviewed the Quality & Technical Agreement
f
or contract manufacturing between Pharmaci a & Upjohn Company
LLC,
Pfizer Manufacturing Belgium NV, Biotherapeutics Pharmaceutical Sciences (ARD
& ACMF aka Wyeth Pharmaceutical), Pfizer Biotherapeutics Pharmaceutical Science (ARD Chesterfield) and BioNTech Manufacturing GmBH. The agreem
ent was signed by
all the
manufacturing sites and BioNTech. The agreement delineates responsibilities
between Pfizer and BioNTech. The specific responsibilities for each manufacturing site
identified in the agreement was however not delineated. Quality agreements were
discussed with who also
presented the overview of Quality Agreements.
I request
ed to review the quality agreement between the Pfizer Manufacturing Puurs
and Pfizer
Andover Clinical Manufacturing (ACMF) the supplier of the drug substance
for the US market. ex
plained that there is
as it relates to the COVID 19 mRNA drug substance.
The quality agr
eement between the Pfizer Manufacturing Belgium and Pfizer Ireland
Pharmaceutical Grange Castle dated 03 September 2020 was reviewed during the
inspection. Pfizer Pharmaceutical Grange Castle is a contract testing site for the COVID
19 vaccine and drug product testing. This quality
agreement delineates the responsibilities of the Pfizer Puurs and Pfizer Grange Castle. No objections were noted.
Before the closeout of the inspection,
addressed the issue of reporting responsibilities to the US FDA. presented
an amended quality agreement between the Pfizer manufacturing sites and BioNTech
(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) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150436
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
18 of 79 signed 29 June 2021. The quality agreement was updated to clarify the relationship for
COVID 19 vaccine also explained that in
the Pfizer Purrs site written procedure SOP version Biological Product
Deviation Report (BPDR) states that if there is an incident impacting a product
i
t is the responsibility of the release site
Quality Operations Leader to prepare the draft BPDR with input from
No objection was noted.
Pest Cont
rol
(Written by SJ)
SOP version Pest Cont
rol effective June 29, 2020, describes the
procedures for implementing and maintaining a site pest control program. The site pest control coordinator is responsible for ensuring that an adequate pest control program is
established, implemented, and maintained for each building in Pfizer Puurs. An external
global cont
ractor is responsible for managing and implementing the pest control
program. The list of authorized biocides used the external contractor is documented in
SOP Form There are three ty pes of pest control treatments performed
by the external contractor: emergency, follow -up, and routine treatment. The routine
treatment is performed times per year. pr
esented
the schemat
ic of pest control traps locations, detector types and executed routine
treatment proof of service. During the inspection, I walk ed through the warehouse,
controlled areas, classified areas and the facility and no objectionable
conditions were noted as it relates to pest control.
Training
(Wri
tten by SJ)
SOP version GMP Training describes the GMP training program for Pfizer
employees, contingent workers, third party resources and contractors with direct or
indirect impact on the quality of product. SOP details the scope, roles, and
responsibilities. This GMP training SOP details the training for new hires (on boarding phase), development phase for current co-workers (developing phase) and the maintenance of a general awareness with current co-workers (ongoing phase).
GMP orientation for new hires is an introduction to GMP concepts via
followed by
The developing phase consists of
The
ongoing phase involves
During the inspection, the training records for a select number of employees in the
COVID 19 vaccine formulation area, vaccine filling, visual inspection (AQL) and QC
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150437
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
19 of 79 laboratory were reviewed for specific position-related training and GMP refresher
training. No deficiencies were noted during the review of these training records.
Annual Product Review
(Written by AC)
No Annual Product Review is written for BNT162b2 DP; however,
explained that a continued process verification (CPV) program
for BNT162b2 DP is established. It consists of T
he objective of is to
continue monitoring the after process validation.
sampling after
process validation is considered. During CPV reports are written on a regular
basis.
The purpose of CPV is to gather
product data from to assess whether the process
remains in a controlled state and to give the opportunity to act proactively in case the
process shows a trend to go out of control.
C
PV has no endpoint and continues for the whole life cycle of
BNT162b2 DP. A is used to for the obtained
data and control limits are set based on the Any out -of-control data from
will initiate Product SME will review and the
SME is responsible to review and put comments to explain why
test results will be recorded and documented in the future Annual Product
Review.
In addition, described
the Quali
ty Performance Report (QPR) that the QA performs T
he
recent one
was performed between 2021. No outstanding finding was
observed in this report. The report includes information to monitor the following items:
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150438
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
20 of 79 Consumer Complaints
(Written by ZW)
explained to me the procedures for handling
complaints.
She stated that the firm uses a triage system to categorize the nature of
each complaint. The following are a few representative examples of the categories:
I
reviewed the SOP “Complaint handling”, version effective date.
walked me through the process flow chart. According to this SOP, once a complaint is
received,
the firm will determine the investigation priority depending on the nature of the
complaint, with three levels of urgency such as “Expedited”, “High” and “Normal”. The
time f
rame is set for calendar day
s for Expedited and High, and calendar days for
Normal. The investigation procedures consist of
I
requested
to review the most recent trending analysis data. show
ed me the
analysis
between December 2020 and May 2021. She stated that the complaints
is
used in the trending analysis, and as more vaccine
is manuf
actured, i
s decreasing, as shown in the container category, from
approximately
The fir
m provided the complaint list prior to the inspection, in the pre-request package. I
noted that since December 2020, there are approximately 11,000 complaints filed. As of May 2021, the firm has manufactured approximately
doses. I randomly
selected the
following consumer complaints to evaluate how the firm conducted the
complaint investigation ( Table ZW-8 ):
ZW Table 8.
Complaint investigations
Doc ID Date
received Date
closed Category Batch # Summary
5/10/2021 6/25/2021 Container EW4811 A customer complained of container
leakage during the reconstitution and
the samples were returned for
evaluation. The firm started the
investigations including but not
limited to trending analysis, batch
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150439
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
21 of 79 Doc ID Date
received Date
closed Category Batch # Summary
record review, deviation investigation
review, and retained sample
inspection without issues. No root cause was found. And no CAPA is
taken.
6/16/2021 Open
12/18/2020 12/19/2020 Foreign
objects Not
available A customer was asking for the
process to report a product with
particles in it. When the firm called
the customer, there was no answer.
1/6/2021 2/17/2021 EJ0724 Small black particles were found
after dilution. The customer was not
able to return the sample. The firm
performed the internal investigation including but not limited to review of
batch record, deviation investigation
and retained samples. No root
cause was found and no CAPA was
taken.
12/17/2020 1/29/2021 EK4175 After the reconstitution *, the
customer found a film/sediment on
the outside of
the vial and the
contents did not contain enough to
draw up even one dose. The
performed the investigation and no
root cause can be identified.
1/7/2021 2/19/2021 External
cause
investigation EL1484 The effectiveness of the vaccine was
questioned. Four clinicians received the first dose and then tested COVID -positive. The expiry of the
vaccine is
April 2021.
The complaint
sample was not returned. The firm’s internal investigation found no
quality is sues.
After the inspection, I was able to review
this complaint in more depth
and noted
rel
ated to the batch EL1484.
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4), (b) (6), (b)
(7)(C)
(b) (4)
(b) (4), (b) (6), (b) (7)(C)
FDA-CBER-2021-5683-1150440
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
22 of 79 Doc ID Date
received Date
closed Category Batch # Summary
4/15/2021 5/28/2021 Product
appearance EW2246 After reconstitution, the customer
found discoloration upon visual
inspection, with whiti
sh dispersion.
The firm performed the internal
investigation including but not limited
to review of batch record, deviation
investigation and retained samples.
No root cause was found and no
CAPA was taken.
*Note: “Reconstitution” is the term used in the Pfizer complaint documents. I interpret
this as the dilution of the drug product vial.
I have no concerns with my review of the consumer complaints.
FACILITIES AND EQUIPMENT SYSTEMS
Facility Changes
(Written by ZW)
Since the last FDA inspection in 2017, particularly since the start of the COVID -19
pandemic, t
he firm has added more people and mult
iple facilities and equipment. T here
are currently
approximately employees and that number was approximately
i
n 2017. T
he following table shows the major changes related to the current application
and because of the time constraint, I focused my review and evaluation on the major
c
hanges, specifically (
Table ZW1).
Table ZW1. Major
changes
Category Facilities or Equipment Location
(b) (4), (b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150441
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
23 of 79 Category Facilities or Equipment Location
Per Pieter Verbellen, Di rector Launch Excellenc
e, the firm currently uses f
or
preparation/for
mulation of the bulk liquid. The filling process and vial inspection are
performed at
No c
oncerns wer
e ident
ified regarding changes to the facilities and equipment.
Preventive Maintenance of HEPA Filter s
(Written by SJ)
SOP
V
ersion F ilter (Qualified) effective January 7, 2021 describes
the preventive maintenance (PM) program on HEPA filters. It should be noted that the
filling operation is (Gr
ade /ISO and
the is a
Grade /ISO T
he PM progr am is managed by the
T
he frequency for PM on the IS OH EP
A filter s is every PM is
perfor
med in house and the parameters used during the HEPA
filter PM are as follows:
T
he PM program for HE PA
filters was discussed with
and The
review of PM includes
t
he work order for the ISO H
EPA filter in along with the
traceabi
lity of the in-house equipment used to measure the key parameters of t he HEPA
filters. All equipment used in the HEPA filter PM was traceable back to a standard and
within calibration at time of use. During the initial IQ/OQ/PQ of in
May
2020, filters were replaced as it failed new filters were
installed and retested as part of the initial IQ/OQ/PQ; the HEPA filter retest results met
all specifications . No objectionable conditions were noted for the ISO HEPA
filter PM
records
reviewed.
(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) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150442
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
24 of 79 Validation
(Written by LF)
SOP- Systems Validation ver. ef
fective May 28, 2021, describes the general
approach for the validation of systems. The procedure pertains to direct impact systems that support the manufacturing, storage and distribution that include facilities, utilities,
equipment and related automation. Lab equipment and computer systems were not
within the scope of this procedure. Lab equipment validation is covered under SOP -
Laboratory Equipment Qualification and Computer systems are covered under
SOP- Computer Systems Validation. System validation includes verification (IQ
and OQ) and Performance Qualification (PQ) of a system.
The general approach for steri
lization validation is discussed in SOP - S
ter ilization
Validation ver. effecti ve Mar ch 14, 2019. This procedure includes sterilization of
Periodic
requalif
ication of these processes is required N
o concerns
noted.
EQU
IPM
EN
T QUALIFICATION
Qualification of the
w
arehouses and computer security
(Written by ZW)
The
w
arehouse is also called
From a door
, which is w e
observed
a ret
rieve or place on
Fr
om the ground to the ceiling, there are
T
he on
the
f
or locations and materials.
On 6/25/2021, I reviewed the qualification of the system for the warehouse,
with
She stated that the
was
implem
ented in 2014. Since then, more improvements have been made and
the quali
fication of the was conducted and approved in March 2018. She
showed me the qualification report. I reviewed the report of
and it appears all the acceptance criteria were met. I asked about the security
measures in s
tated that only authorized personnel have access to the
and the computer security is governed by the
I further requested
and reviewed the policy for computer security. This document describes the computer
configuration, policies for account lockout, audit and network security. For example, the
password must have
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150443
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
25 of 79 The account will be locked out after I have no issues
with
the computer security measures.
Temperatur
e mapping of the war
ehouse
(W
ritten
by ZW)
The w
arehouse has st orage
The capacity is Because of limited
time, I focused my review on the qualification of the w
arehouse.
wal
ked me through the
temper
ature mapping process. She stated that the w
arehouse has
the size
of The stored materials are placed
on ar
e installed on the
For the temperature mapping, a total of m
onitoring probes were distributed
throughout
the warehouse, including the worst -case locations on the
F
or monitoring, m
onitoring probes
are positioned throughout the warehouse.
s
tated that temperature mapping studies were conducted:
I
requested and audited the data for temperature mapping, which is documented in
“P
erformance Qualification Report for
dat
ed 1/21/ 2021. For
each study, the temperat
ure was monitored for The
firm
also conducted the
The temperature was
set at and al
arm limits were set at The locations of the monitoring
probes were adequately identified in the report. I reviewed the temperat ure
and checked the The firm also identified the
Based on the mapping study, m
onitoring probe locations are
determined I also reviewed the attached deviation
reports and the audit trail report. I had no issues with the documents I reviewed.
The substances such as are stored in a
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150444
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
26 of 79 Qualification of the freezer
(Wr
it
ten by ZW)
The freezer has w
orking is
instal
led
appears to have adequate space and is organized. The
stored materials are placed on Per the t
emperature is monitored
and contr
olled by a facility
system.
I rev
iewed the qualification document for the freezer w
ith
She stated that temperature readings and
t
he mos
t recent requalification/temperature mapping was performed in as
documented in “Combined revalidation/requalification report for the
appr
oved on The freezer has a temperature set at
According to moni
toring probes
were dis
tributed in the mapping study and the testing period
w
as
T
he monitoring probes were placed as follows:
The
study identified the The firm also conducted the
I audited the temperature
I
had no is
sues.
The emergency power backup system for the freezer and
other facilities will be
discuss
ed later in this report.
B
uilding for the storage of the finished products, “Freezer Farm”
(Writt
en by ZW)
I conducted the inspection of the B
uilding on 6/28/2021 ( Exhibit ZW-1 ) . The
is a bui
lding located on the side of the campus. On the way to the
I noticed approx imately
stated that the firm purchases the
from t o ensure the uninterrupted supply. The is
at the and added to the (more
discussion later in this report).
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150445
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
27 of 79 To enter the bui lding, I needed to go through a door, which is
locked and opened only to the authorized personnel I
noted there were
at
the entrance.
Mr. Jan
Dams, Senior Project Manager and Mr. Abo Steels, Team Lead assisted me
during the i
nspection. They answered questions and provided documents. Mr. Luc Van
Steenwinkel, the site head, was also present during the walk -through inspection.
Currently, the B
uilding is a facility for the COVID BNT 162b2
vaccine. I noted that there are adequate spaces for the equipment such as ultra-
freezers and the storage arranged in an organized
fashion for inspection and cleaning ( Exhibit ZW-1 ). The area appeared
clean, and no cracks were noted between the doors and frames. The and
m
ouse traps were also found in the ar
ea as a pest control measure. The firm
uses an external contractor for the pest control, per Mr. Dams.
According to Mr. Dams, there are approximately
aut
horized people worki ng in the
B
uilding. I asked what procedures have been taken to ensure the security of
the freezers which are Mr. Steels
stated that the firm has
several procedures
such as:
F
or the training, Mr. Steels stated that each new hire is required to take training based
on his or
her job responsibilities and they are not allowed to go to places beyond their
job description. I randomly picked one employee, f
rom
the and
r
equested to
audit her training records and training materials. I noted that is
a
Her training records show that she has had on -job trainings (OJT) and
S
OP trainings since February 2021. The GMP training slides
instructed employees
I had no issues with the training documents I reviewed.
Freezer Farm
(
Wr
itten by ZW)
According to Mr. Steels and Mr. Dams, there are currently approximately ultra-
f
reezers (Exhibit ZW-1) in the Building, and freezers
I noted that all the freezers appear new. Per Mr. Steel
s, the firm started
the purchase of freezers in 2020 and qualifications of freezers in 2020. The
B
uilding is also called “Freezer Farm”. It has a size of
(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) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4), (b) (6), (b) (7)(C)
(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)
(b) (4)
FDA-CBER-2021-5683-1150446
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
28 of 79 Per Mr. Steels, each freezer has a attached to the freezer and this
is
equivalent to that displayed on the found
in the
T
he freezer temperature is also displayed Mr. Steel
s
stated that each freezer is monitored for temperature through a
called and the temperature reading is taken every
My audit of the freezer qualification started with a randomly selected freezer
fr
om the floor. Mr. Steel
s s
howed me, the current
temperature,
and the temperature for the last five days, of this freezer, managed on the
I noted there are w
ith a
difference around Mr. S teels
explained that there are
r
espectiv ely. The on
the r
epresent s the worst case, normally t
han the
bas
ed on the temperature mapping study and real -time monitoring.
I then requested to review the temperature monitoring for the month January and February 2021,
and I noted there are two temperature excursions on 1/14/2021 and
2/4/2021. M
r. Steel
s ex
plained that the tem perature excur sion on 1/14/2021 is due to
the loading of the vaccine Lot T
his lot was unloaded, and
freezer w
as cleaned on 2/4/2021, resulting in another excursion. I reviewed the records
without discrepancies noted. This freezer was cleaned on 2/4/2021.
Mr. Steel
s s
tated that the freezer is maintained at W hen the
vaccine vials, which are kept af
ter packaging, are loaded to the
freezer, the freezing process takes approximately Lot i
s curr ently
stored in the freezer Mr. Steel
s stated that the turnover is
approximatel
y bec
ause of high demand. No iss ues were identified.
Freezer quali
fi
cation and temperature mapping
(Writte n by ZW)
The qualification procedures and acceptance criteria are described in the document
“
Form: performance qualification protocol”, and in
“FORM: Template System Acceptance and Release Report (SARR)”,
respectively. The temperature mapping is performed for
freezers. The freezer has and tem
perature monitoring probes are
placed i
n the
The freezer temperatures should stay within
predetermined working temperature T
he
freezer is monitored for
I
randomly selected the following three freezers (Table ZW2) and reviewed temperature
mapping data:
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150447
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
29 of 79 Table ZW2. Qualification of the ultra-freezers
Freezer Mapping date
The qualification s tudy has dat a sets plus
audit trail) for each freezer. I noted that the temperatures stay within the specifications during the tests. For the test,
temperature monitoring probes show the temperature increases up to W
hen
the
the temperature drops to Per Mr. Steels, the
freezers, generally I
had no issues with the documents I reviewed.
I also selected randomly and inspected a cleaned freezer
t
hat is ready
to rec
eive vaccines. After the door opens, there are
The freezer appeared to be in good conditions and no
ice build-up was observed. According to Mr. St
eels, each freezer, when fully loaded,
should tak
e pizza boxes (195 vaccine vials per box)
Temperature moni
toring probe calibration
(Written by ZW)
I requested and reviewed the calibration documents for the temperature monitoring probes.
s
tated that the probe calibration is
performed
and all the temperature monitoring probes
are calibrated I randomly selected the calibration reports of the following three probes:
• cal
ibrated on 3/16/2021
• calibrated on 5/12/2021
• calibrated on 5/28/2021
There are temperature set points such as and
the failure limits
are the
set point I
reviewed all three reports and noted that the observed
temperature outputs are at most f
rom the set points. I had no issues.
and
Alarm system
(Written by ZW)
and Mr. Abo S teels explained to me the
alarm
system for the us
ing The procedures for the alarm handling
are governed with SOP “H
andling of alarms ef
fective date
(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)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150448
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
30 of 79 10/13/2020. Mr. Abo stated that the alarm system is on the and the
al
arm messages are sent to the responsible person. According to the procedure,
the alarm message is
The working temperature
for the is W
hen the temperature increases to or
beyond f
or the alarm system will be activated. Per t
he
window will avoid false alarms and gives operators enough time to perform
regular activities such as
The firm performed the validation for the alarm system and the report is documented in
Document ID: “
Ver
ificatie test plan/rapport alarmen
op/ALERT”,
with approval date 2/3/2021. It appears that all the pre-determined
parameters were met.
Softbox qualific
ation
(Written by ZW)
Inside the B
uilding and before entering the section, are the
shipping lines
for the vaccine products. The vaccine vials, packaged in the flat “pizza
box”, 195 vials per box, are shipped as a bundle of pizza boxes in the
Softbox, or bundles in the Softbox. There are s
hipping lines: l
ines
for the S
oftbox and f
or the Softbox. I observed S
oftbox
shipping lines were in operation during my walk -through inspection. The pizza boxes in
bundles are kept in athe storage ultra-freezer and the Softbox. I observed an operator picked up the bundle
with the and placed the bundle inside the Softbox, and then added the dry
ice to fill the Softbox. Each shipping line has dry ice
operator checked the packaging conditions, and the
logger. More discussions later in this report) on top of the payload and closed the
Softbox. operator attached the shipping label and the Softbox was placed in a
shipping ready area.
Softbox is a packaging therm
al container manufactured by a UK based company called
Softbox Sy
stems. I reviewed the following documents (Table ZW3) to evaluate the
qualification of the most often used Softbox (for pizza boxes) as a shipper to maintain
the temperature at for no less than Because of
the time
constraint, I did not request and review the Softbox qualif
ication.
Table ZW3. S
oftbox qualification
Doc ID Document Approval
date Authorship Summary
Thermal
performance
qualification
protocol, 10/14/20 Pf izer A total of shipments in
Softbox will be executed from
The
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(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-2021-5683-1150449
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
31 of 79 Doc ID Document Approval
date Authorship Summary
transportation of
ULT product from
using a
passive dry ice
thermal container minimum load will each consist of
representing the
worst case. The shipper will be transported via and
the Softbox shipper should mai ntain
t
emperatures for a
minimum of One
temperature monitoring device (TMD) is packed with each shipper
and the temperature reading is taken at intervals, with
alarm set outside
Thermal performance
qualification
report ,
transportation of ULT product from
using a
passive dry ice
thermal container 10/30/20 Pf izer The total transition time is
and TMD shows the Softbox
shi
pper
maintain the temperature
between
During my in- depth review of this
document after the inspection, I noted that there is no data for
as planned in
the protocol
However, more studies show that
the Softbox
maintains the
temperature for more than
See doc below.
Technical
assessment for OQ data on
Softbox
ULT
for transport
of products 1/20/21 Pf izer The firm performed
T
he
firm demonstrated that the SoftBox
is capable to maintain the temperatures between
for up to The
Softbox is
mimicking the worst case,
However, I
noted that the
temperature, indicated here
between may not
represent the worst case, as the
product may be kept in places
where temperature exc ursions
beyond may occur.
stated that the firm has
performed another study for
t
emperature profile, and
provided the document
see below.
(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)
(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)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150450
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
32 of 79 Doc ID Document Approval
date Authorship Summary
ULT dry -
ice shipper
tem
perature
control packaging
system
temperature
control profile 2/1/21 This study shows the Softbox
shipper maintains for
appr
oximately under
the
t
emperature
conditions.
shipping study report summary for project
BNT162b2 6/16/21 Pf izer The firm stated that this document
evaluates the impact of the
on
the drug product utilizing a worst -
case
drug
products from batch
are included in the study.
This is a study. Test samples are exposed to
After the shipment, the
firm performed the tests including but not limited
The results are
within specifications.
testing of a
U
LT dry -
ice shipper 8/4/20 performed the
of the
Soft
box shipper. The Softbox was
load. tested the
Softbox with the following elements:
O
n completion, the
Softbox shows
ULT dry -
ice shipper
temperature control packaging
system
temperature
profile 7/15/20 This document has instructions on
how to pack the Softbox.
is added to the
Softbox The
document also defines the
profile as
(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)
(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)
(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)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150451
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
33 of 79 During my inspection, I noted that each Softbox was packed with
pizza boxes, while for the Softbox qualification, is used with
dry ice. My concern was, if pizza boxes are shipped, dry ice may have to be used, then the cooling capability might be compromised.
s
tated that
that is not
the case. The Softbox is always filled with dry ice, as in
the qualification study. If pizza boxes are shipped, will be
During
my review of the Softbox photos ( Exhibit ZW-1 , ), I noted that the dry ice
is to the Softbox . No issues we re identified.
Shipping control
strategy
(Written by ZW)
gav
e a presentation about the shipping process (Exhibit ZW -3). She
s
tated that each Softbox s
hipper is packed with a logger, which is linked to the
Controlant
Platforms for live temperature monitoring and GPS tracking. Controlant
tracks the movement of the Softbox the moment it leaves the Puurs facility until
reachi ng the final destination. The critical data such as the temperature and location
can be seen real time. Any excursions will be notified The logger also has a
If the Softbox is
Controlant will be notified. Controlant is a contractor located in
Iceland (Holtasmari 1, 201 Kopavogur, Iceland). No issues were identified.
Dry ice (W
ritten by ZW)
explained to me that each shipping line is equipped with
dr
y ice to ensure the dry ice supply .
has a capacity of al
so stated that the firm has
can also dr y ice in
case that all the fail.
Emergency
power backup system
(Written by ZW)
I requested and reviewed the emergency power backup system. Because of the temperatur
e sensitive nature of this vaccine, the uninterrupted power supply for the
ultra-low temperature freezers should be assured.
and as
sisted me in the revi ew process.
stated that at the Pfizer Puurs site, there are power sources:
suppl
ies the electricity regularly to the plant. In case of power failure,
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
FDA-CBER-2021-5683-1150452
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
34 of 79 expl ained that the i s a
When there is power failure, the
s
o there is no
interruption of the power supply. The are linked to the
ens
ure at any moment.
st
ated that there are for the
freezer
farm and the most recently qual
ified in
June 2021. When power fails, the
I select
ed (
Table ZW4) to review their qualification documents
(preventive maintenance work orders and qualification report, particularly if the
response time is within the specified time frame when there is power failure (or
shutdown)):
Table ZW4. qualification
I
found no discrepancies from the documents I reviewed.
(
Written by ZW)
On the first day of the inspection on 6/24/2021, I conducted the inspection of the
fac
ility, with I nspectors Fontan, Cheung and Jackson.
are required to enter
ex
plained the manufacturing processes from formulation,
f
illing to vial inspection and packaging. I observed the
formulation process/lipid nanoparticle (LNP) formati on, the formulation booth
and
the filling process I revisited the on
6/30/2021 with Inspector
Fontan and observed the and the
process using the N
o issues were
identif
ied.
Qualifi
cation of the
(Written by ZW)
One of the critical processes in BNT162b2 manufacturing is the formulation process in
which and this process is
performed using the
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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-2021-5683-1150453
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
35 of 79
I
interviewed f
or the qualification of
the H
e stated that the
The is manufactured by and
the is
developed by
The c
onsists of
To verify/qualify the firm uses such
as
I reviewed the following
documents without issues noted (Table ZW5):
Table ZW
5. Qualification of the
Doc ID Document Date Summary
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(b) (4)
FDA-CBER-2021-5683-1150454
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
36 of 79 st ated that it takes about The
have to be
I asked how
the is
monitored f
or each s
tated that each is
connected to
a and then I requested and reviewed the
documents. The calibration is performed by
I
requested the initial calibrat ion of the The were initially
calibrated in May 2020 and it appears that the and
the certificate was issued to I reviewed the certificates without
concerns. The illustrated servi ce procedures can be seen in Exhibit ZW-2 . I had no
issues with the documents I reviewed.
(W
ritten by ZW)
The firm utilizes a number of
I requested and reviewed
the follow
ing qualification documents (Table ZW6) without concerns.
Table ZW6. Qual
ification of the
Doc ID Doc title Date Summary
Compressed air
(Written by ZW)
I noted that the compressed air is used to
during the
I
requested to review the qualification of the compressed air.
as
sisted me with reviewing the documents and
answered my
questions. He stated that the firm monitored the compr essed
air
by monit
oring the I reviewed the
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150455
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
37 of 79 Doc ID: “System acceptance and release report: compressed
air of (
mac hine ID , the approval date
9/25/2020. This report documents the verification activities, such as
I also requested and
reviewed the maintenance records from January 2021 to June 2021. The
maintenance log shows the testing results for
I asked about and was told it is considered to be similar to
I compared the testing results against the specifications without issues
noted.
st
ated that the is also used
B
ecause of the time constraint, I did not request and review the
qualification documents.
S
terilization
(Written by LF)
I discussed the sanitization with
N
o concerns were noted.
Water pur
if
ication system
(Written by ZW)
The firm water system for purif ied water and water -for-injection (WFI) for the
facility. I conducted the walk -through inspection on 7/2/2021, and met
st ated that there are
wat
er
is processed with the
I checked these and examined
piping configuration for any possible without concerns. The equipment appeared in good maintenance conditions without leakages or wetness on the floor. I
also inquired about the
and
the shelf life and found no issues. The
water quality is monitored with I noted
the on the as
(Table ZW -7) and they met
both USP and internal specifications for the purified water
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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-2021-5683-1150456
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
38 of 79 Table ZW7. of the purified water
The
monitoring data are
ar
e also equipped with the
I
asked about the
stated the purified water is
I randomly selected and audited three r
ecords for the
without issues. Per
the has
been
and it will occur
The WFI facility is housed in W
FI is generated by
the
process and stored in a I
inspected the and the and they appear in good working condition.
WFI is kept a t
I also inspected the of the
and found no issues.
At the user point in the room of
I
noted the
st
ated that if the required W FI has not yet been
reached the When the required WFI has been
reached, the At the user point, the WFI is
befor
e use.
I have no is
sues with the purified water. See below for the WFI qualificati ons.
WFI Qualification
(Written by ZW)
I requested and reviewed the “ Initial environmental control
qualification report for WFI in
approved on 7/14/2020. The protocol for the qualification was approved on
5/15/2020.
T
he
specifications are as follows:
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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-2021-5683-1150457
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
39 of 79
The firm performed the performance qualification in June 2020 and the
samples were collected I reviewed the testing results, and they met the
specification.
I had no issues with the water purification system.
Cleaning Validation (Written by LF)
I reviewed the cleaning program with
and Bojan Wijremblewski, SME, Cleaning Validation.
The cleaning validation program is governed by SOP - V effective February
24, 2020. The SOP is attached in Exhibit LF- 6 . a cleaning validation,
a cleaning procedure needs to be in place that can be validated. The procedure must be in at least draft form and must include the following:
I
f a new analytical method is required, the
Cl
eaning validation studies are divi ded into ini tial validation, verification, revalidation and
routine requalification. Initial validation, verification, and revalidation are triggered by a
change control. The routine requalification is based on
For product monitoring, a
approach i
s used. The is based on
which is used for the cleaning studies.
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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-2021-5683-1150458
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
40 of 79
Ini
tial cleaning validation is performed for
I
f this cannot be confirmed a
complete cleaning validation is performed. For a list of all the products manufactured on filling line i
ncluding the category of product,
and allow
able see Exhibit LF-7.
The i
s required to be implemented cleaning
validation. The used for validation may be
The is part of the microbiological
cleaning validation covered in ‘Rational e: Cleaning validation:
Microbiological cleaning validation approach”, approved 29 Apr 2020. This document
describes equipment storage conditions, specific manufacturing area cleaning
procedures, preventive measures,
analytical methods used and approach for potential microbial
contamination after cleaning and during storage. The storage conditions for formulation equipment are summarized below:
Equipment Storage Conditions
Formulation materials -Stored in Grade
-Stored in Grade
-Stored in Grade
During a walkthrough of the f
illing area, I observed the
stor
age of cleaned equipment used for filling the BNT162b2 COVID vaccine in
designat
ed for the COVID vaccine in Room The used for
w
as Room
Twelve documents were review
ed related to the cleaning validation of equipment used
for the manufacture of the BNT162b2 COVID 19 Vaccine in
T
he of i
s performed
The are replaced with
during the execution of the The C
leaning Sequence consists of
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150459
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
41 of 79
The
are
performed in and the
are performed in
ar
ea (Room ). See Exhibit LF-8 P
hoto.
All the product contact parts for the r
emain in place for
The pr
oduct contact parts are made of
Multiple tests are performed on the
The c leaning was performed for
successful repetitions.
Most of the equipment that is used for the of BNT162b2 is as indicated
in t
he list below.
during these tests.
i
s used in production.
The table below summarizes the cleaning validation testing required for the
equi
pment.
Equipment Stage/
Production use Type
Cleaning Test Runs
(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)
(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-2021-5683-1150460
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
42 of 79 Equipment Stage/
Production use Type
Cleaning Test Runs
The samples taken were
with
The cleaning validation executed to
date, met the required limits, however is still ongoing.
Refer to D iscussion Item LF -1. See Exhibit LF-9 , memo and Exhibit
LF-10,
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150461
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
43 of 79 Microbiological Cleaning Validation
(Written by LF)
Microbiological cleaning validation testing is performed
protocols. The equipment listed below was
chosen to verify that endotoxin and bioburden can be
using the current cleaning procedures.
Equipment Type Cleaning/Location Test Runs Sampling
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150462
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
44 of 79 Equipment Type Cleaning/Location Test Runs Sampling
Bioburden were taken at
with
Bioburden acceptance criteria for
the testing is The endotoxin limit is The
m
icrobiological cleaning validation executed to date, met the required limits,
Refer to Discussion Item LF -1. See Exhibit LF-11 ,
Microbiological cleaning memo.
T
he cleaning
validation for the parts consisted of testing to demonstrate
the
with
the same limits used for
The cleaning validation
was successful and validated a of The cleaned par
ts are
In addition, verification tests were performed for the
The testing verified that the
on t
he equipment is
s amples were taken from
No concerns were noted.
Sterilization Validation
(Written by LF)
Sterilization validation summaries for all direct product -contact
equipment were
reviewed. Processing equipment is sterilized
ar
e validated by perf orm ing
The pr
ocess is validated to show
(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)
(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-2021-5683-1150463
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
45 of 79 The product ar e sterilized
test locations are chosen according to
For the ty
pe, there are however,
were
determined to be (i.e., no worst -case could be
determined). v
alidation run was performed for with a
minimum of three validation runs for the t
ype.
In addition, three validation runs were successfully performed to confirm that the
af
ter the
R
equalification of the of
the ty
pe is performed
The
bulk drug product is sterile filtered
T
he bulk drug product is filt ered using
filters The
s
terilizing filters are us
ing a
F
ilter integrity tests are performed on
w
hen I
observed part of the set up during a walkthrough on July 1, 2021.
In addition, a biobur
den sample is collected from
B
ioburden is also tested during
See Exhibit
LF-4 for a picture of the
The st
erilization process is controlled by a
(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)
(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)
(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)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150464
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
46 of 79 The is set up according to SOP - v er. The phases
consi
st of:
Dur
ing various ar
e f or
certain durations.
For the validation,
wer e placed in locat ions including
The acceptance criteria are listed in the table
below.
A analysis is also performed evaluating the attained
for the
and the
resul
ts of the instruments.
Prev
iously, w
as validated and used for the BNT162b2 process (Mar
2019 and Sep
2020). The was updated per change control
and
change existing
This change control referred to A
n additional change control
i
ncluded This was in preparation to
Int
egrity of
these f
ilters are controlled by int egrity testing. was
used f
or the w
hen I observed part of the set up during a walkthrough on July
1, 2021.
w
as transferred from
Seven sterilization validation documents were reviewed for the i
n
for of
(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)
(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)
(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-2021-5683-1150465
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
47 of 79 Sterilization Validation Summary of Formulation Equipment at Puurs:
Validation Testing
performed Acceptance Criteria Acceptance
Criteria Met
R
evalidation
Rev
alidation
Performed
Sep 2020 Yes
R
evalidation
Rev
alidation
Performed
Jan 2020 Yes
Revalidation
Performed
Feb 2021
Reports
Mar/Jun 2021 Yes
No Concerns were noted.
Stoppers
(Written by LF)
I discussed the stopper processing with
and
T
he
ar
ea has s topper processor in room t hat is dedicated to
the ar
ea. The stopper processor has stopper
and of
these are dedicated to BNT162b2 and the s toppers. There
are also stopper processors in the
During validation, the stopper processors are evaluated for
No concerns were noted.
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(b) (4)
FDA-CBER-2021-5683-1150466
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
48 of 79 St erilization
(Written by LF)
The direct product contact parts of the
If the analysis concludes that the revalidation runs are
not reproducible a failure investigation will be perfor med, and corrective actions will be
taken. Ten validation documents were reviewed for the
sterilization.
The ster
ilization/depyrogenation validation studies to support the BNT162b2 process at
Puurs are summarized below.
Depyrogenation/Sterilization at Puurs
Validation Testing
performed Acceptance Criteria Acceptance
Criteria Met
Vial Depyrogenation
Last revalidation
June 2020 Yes
Stopper
Depyrogenation and
SterilizationYes
Jun
2020
Yes
Decontamination-
Rev
alidation
Aug 2020 Yes
(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)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150467
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
49 of 79 Validation Testing
performed Acceptance Criteria Acceptance
Criteria Met
Sterilization
Yes
Sterilization
Yes
No Concerns were noted.
Sterilization
(Written by LF)
T
he direct product contact parts
ar
e cleaned and sterilized
the following
actions must be performed
(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-2021-5683-1150468
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
50 of 79
The
decontamination is performed via a
comprised of a
loc ated in the clean room
During the decontamination,
The decontamination consists of
T
he sterilization of the
is a pr ocess. The
is regulated on During the
sterilization the has to
D
uring validation, a worst -case The worst -case
used the following parameters:
The PQ protocol
attached in Exhibit LF-12 contains a system description and diagrams.
S
eventeen validation document s were reviewed for the i
n s upport of
vial depyrogenation, decontamination, stopper depyrogenation,
(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)
(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-2021-5683-1150469
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
51 of 79 sterilization. The sterilization/depyrogenation validation studies to support the
BNT162b2 process at Puurs are summarized below.
Depyrogenation/Sterilization at Puurs for
Validation Testing
performed Acceptance Criteria Acceptance
Criteria Met
Vial Depyrogenation
Initial qualification
June 2020
(3 runs) using
2mL vial Yes
Stopper
Depyrogenation and
Sterilization
Requalification
performed Yes
Requalification
performed Yes
Te
sting
performed
September 2020
Yes
S
tudy
Oct 2020 Yes
Yes
(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-2021-5683-1150470
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
52 of 79 Validation Testing
performed Acceptance Criteria Acceptance
Criteria Met
Testing
performed July
and August 2020
Sep
tember 2020 Yes
A
ugust 2020
performed August
2020 Yes
exec
uted August
and Sept 2020
Yes
(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-2021-5683-1150471
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
53 of 79 No concerns were noted.
MATERIALS SYSTEM
Supplier Management
(Written by SJ)
Management of suppliers is performed according to SOP version Supplier
Management effective December 14, 2020. The supplier management process
includes selection, qualification, use and ongoing performance review of all vendors in the supply chain. The supplier management process also includes the management of Quality/Technical Agreements, quality risk assessment for all supplier s of production
materials and or providers of outsourced services within a QMS -process.
SOP
S
upplier Qualification and Re-Assessment effective 28 April 2021 describes
the ini
tial qualification and requalification of suppliers of production materials. The initial
qualification requires a quality risk assessment, audit, and quality agreement. The Pfizer
site must fi rst determine if the supplier is on the supplier list per SOP - A
quality
risk assessment is performed per SOP t
hen an audit of the supplier which is a
is performed according to SOP Suppliers are assigned one of
in the qualification process:
A supplier is when there is a quality risk assessment, onsite
audit, and a quality agreement between the supplier and Pfizer.
The list of raw materials for BNT162b2 drug product contained mat
erial
numbers.
The supplier qualification history for each raw material supplier associated
with the material number was reviewed from the system which manages the
raw material supplies. pr
esented the process
flow for t
he supplier qualification. pr
esented each
supplier status as it pertains to the risk assessment, frequency of the onsite audits, last
onsite audit date prior to the manufacture of the PPQ batches and the quality agreement between the supplier and Pfizer. All suppl iers for BNT162b2 drug product
met the requirements for qualified status.
(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) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
FDA-CBER-2021-5683-1150472
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
54 of 79 Material control
(Written by ZW)
I reviewed the firm’s procedures for the incoming materials with
and M
s. Annelien Everaert, Q uality Lead Operation. SOP -
“
Check of raw materials batch record”, effective date 3/25/2021, is one of the
SOPs
that handles the incoming materials. Briefly, the firm uses a checklist to check
the conformity such as
This SOP also has instructions on how to enter the information into the
I reques
ted to review the documents for particularly the batch
which was used in the validation batches for this application. st
ated
that
the was suppl ied by and the
was performed at I reviewed the following documents
without
discrepancies noted:
• Rec
eipt- dated
10/
16/2020
• f
or release of raw materials (batch record), dated 12/2/2020
• SOP- Receipt
approv
ed 5/20/2020 (version )
I
also requested and reviewed one randomly selected lot of the glass vials, lot
t
o evaluate the procedures for of the containers. The checklist
used is
Form and the glass vial supplier is w
ith COA. The firm
checked
I reviewed t
he following documents without issues:
• Form - Chec
klist for release of dev
ices, dated 10/26/2020
• SOP Inspection of vials, approved 2/11/2021 (version )
PROD UCTION SYSTEM
Manufacturing codes
(Written by ZW)
presented to me the
SOP for batch number assignment (effective date Aug. 24, 2020).
st
ated the batch numbers are and
used in
the
The batch number for each material has
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150473
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
55 of 79 The materials can be
For the finished product, the batch number
starts
with two lett
ers, followed by four digits, such as
s
tat
ed she is able to
but not the
Pr
ocess V
alidation
(
Written by AC)
To support EUA for BNT162b2, process validation approach was executed
Pfizer named this validation as
P
erformance Qualification (PPQ)
under
EUA in the US. PPQ required
The first PPQ DP batch generated at Puurs was lot # at
and the lot was filled and finished at the l
ine. During
pr
ocess val
idation at Puurs, an additional P
PQ DP batches (also called
process validation lots, PV) were manufactured
and
fill
ed/finished in f
ill lines t
o demonstrate that the
process at Puurs can consistently produce drug product (DP) lots of acceptable quality
through the above-mentioned manufacturing steps ( Exhibit AC -2).
Due to the DP batch an additional PPQ run with a
was performed
No adverse effects on product quality are
anticipated
No additional sampling or were
performed dur
ing the process validat ion of the DP
batch In addition, no
was included in this validation run
All PPQ batches were executed according to the defined protocols and eval uated with
predet
ermined acceptance criteria. Additional sampling was performed during the PPQ
lots, to
gather additional
product data.
Validation of was included in the design of process validation
protocol. However, PPQ lot from was challenged with the
worst -case cumulative holds (E
xhibit AC -3). Additional discussion
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(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)
(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-2021-5683-1150474
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
56 of 79 on the validation of is included in the section of Discussion with Management.
All required process controls including process parameters and l
imits
were m
et for all PPQ lots. Although deviations were raised during process validation, all
of them were adequately addressed. Some deviations led to initiation of investigations and CAPA was implemented if needed.
Pfizer
also performed a process vali dation study to validate the
i
n the DP manufacturing process.
w
as executed
in this validation study. The firm emphasized that it is not a common
practice to dur
ing the DP manufacture; however, it is just a
procedure to P
fizer is
planning to t
o validate
T
he validation protocol
includes the
T
he approved validation master plan for the COVID -19 vacci ne DP
Pr
otocol) stated that lots are included in stability studies (Exhibit AC -4).
However
, PP
Q batches
were not put on stability, leaving PP
Q batch with the
put
on stability. The firm explained that the stabilit y studi es were
monitored by St. Louis
, Chesterfield site, so they with David
Cirelli
(Research Fellow Analytical R&D) from Andover,
and Paul Rohlfing (Execut ive
Director Vaccine CMC) to address this issue. David and expl ained that a
D
P PPQ batch generated at the Kalam azoo site was put on stability and another
DP PPQ batch from Puurs was also put on stability, therefore based on the firm’s
practice of i
n validating the process, Pfizer believed that
sufficient stability data will be generated from the P
PQ batches from
different
manufacturing since all hav
e
The number of PPQ batches put on stability study are further discussed under the
section of Discussion with Management.
Reprocessi
ng/R
ewor
k Process
(Written by AC)
An SOP- version Carrying out rework processes was used to guide the firm
doing the repr
ocessing of A total of
was
obs erved at the during
The
rewor
k included F
or the
reprocessing step, the firm
proc
ess validation plan for the formulation of COVID -19 vaccine. The step will
T
he outcomes of this validation study support
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150475
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
57 of 79 step has no significant impact on final product
quality
. Additional information on was reviewed in the BLA and the
assessment is discussed in the BLA review memo.
Media F
ills
(Written by SJ)
SOP version Media Fil
l effective June 22, 2021 is a general procedure
which describes that the purpose of the media fill is to evaluate the capabilities of
aseptic processing activities. This procedure details that media fill process validation is
performed for
Initial validation consists of a minimum of three suc
cessful media fills,
performed
on
Routine requalif ication of each
different aseptic/line is completed on a
R
evalidation
i
s performed
Revalidation should
occur in the case of a
that concludes the need for requalification.
Media fill study design is documented in the Master Batch Record and in the media fill
protoc
ol.
is the medium utilized in media fill qualification.
Interventions performed during aseptic production are simulated during the
media fill qualification studies. Interventions incorporated into the media fill batch record
represent all the allowed interventions during production activities. All media
fills are observed and documented by a qualified observer which is a representative of the Quality Authority.
SOP also details the media fill
T
his SOP
also describes the media fill evaluation, the criteria for pass/fail when contamination is
detected and media fill investigation.
BNT162b2 dr
ug product is filled the w as i
nstalled and
qualified
for use in the year 2020, while the w
as installed and
(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)
(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-2021-5683-1150476
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
58 of 79 qualified for use in 2014. Three media fills were conducted as part of the
quali
fication for f
illing runs and three media fills for fi lling.
Exhibit S
J-1 is a copy of all media fills conducted on filling line t o support
BNT162b2 (BLA 125742)
drug product. The list gives details as to
The list of media fills provided by the firm, showed there
were no contaminated media fill units. The validation on f
or run
consisted of The number of vials filled
for di
d not meet the criteria of greater than v
ials. A root cause analysis
was initiated as Deviation see Exhibit SJ -2. The root cause for this deviation was
identified as a failure of the
The media fill validation and the root cause investigation were
discussed with and
ex
plained that even
though Medi a Fil
l di
d not
meet the requirement for greater than v
ials, all
vials from the batch were and met the requirement for sterility/no growth. In addition, the media fill run on
r epresented the worst case as
m
edia fill was the last batch filled after a run greater than other
media fill batches were also filled final batch of the
Media Fill Protocol and Report for the Introduction of a New Vial Filling Line
and C
OVID 19 Vacci ne, were reviewed,
and no objections noted, see Exhibit SJ -3. The report describes the results for the
introduction of a liquid filling process on a new line, all media fills were specifi c for
COVID 19 vaccine.
In addition to the overall protocol and summary , Media Fill Report for the COVID 19
Vaccine Product -Specific Media Fill on the V
ial
Filling Line
were reviewed, and no objections were noted see Exhibit SJ -4.
Media fil
l batch records for and
the filling section of the batch record for
PPQ batch w
ere reviewed. The media fill batch record review included
evaluation of
The media fill batch record and
the filling section of a commercial COVID
19 vac
cine mRNA batch batch of a on w ere reviewed.
The asepti
c operations performed were executed per the
media fills records reviewed. It should be noted that is
not simulated as
part of
the media fills and hence was not reviewed during media fill review.
i
s performed at the and i
s not
performed The media fills are designed to incorporate the
use of the same w
hich is also used in the COVID 19 mRNA vaccine
commercial batches and was used in the COVID 19 vaccine PPQ batches. No
(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)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(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-2021-5683-1150477
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
59 of 79 objections were noted with the media fill design and simulation of aseptic filling
operation.
Environmental Monitoring (Written by SJ)
SOP
R
outine EM Program and S OP R outine EM Program
desc
ribes the types of environmental monitoring, sampling locations,
frequency and
the alert and action limits for classification rooms. The firm performs
active air sampling, passive air sampling, surface monitoring and particle monitoring. The Grade
m
onitori ng includes the active air sampling by
passive air sampling utilizing
S
urface sampling also includes m
onitoring which
is managed under SOP Particle monitoring for non-viable particulates is
described in SOP . are
equipped with a
c
onsisting of partic le counters that are controlled
Environment
al monitoring f requency, alert and action limits for are
pr
ovided in t
he tables below:
Frequency and Limits for Gr
ade Area
Grade
Test Performer Frequency Alert limit Action limit
Frequency and Limits G
rade A
reas
Grade Rooms
Test Performer Frequency Alert limit Action limit
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150478
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
60 of 79 Grade Rooms
Test Performer Frequency Alert limit Action limit
Frequency and Limit Grade Areas
Grade
Test Performer Frequency Alert limit Action limit
Frequency and Limit Grade Areas
Grade
Test Performer Frequency Alert limit Action limit
Frequency and Limit for
G
rade Area
Test Performer Frequency Action Level
(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-2021-5683-1150479
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
61 of 79 Test Performer Frequency Action Level
Frequency and Limits Grade Areas
Test Performer Frequency Alert level Action level
Frequency and Limit s Grade Rooms
Test Performer Frequency Alert level Action level
Frequency and Limits – Grade
Grade – Grade – Grade
Test Performer Frequency Alert level Action level
(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-2021-5683-1150480
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
62 of 79 Grade – Grade – Grade
Test Performer Frequency Alert level Action level
Frequency and Limit
Material transfer from the to grade
Test Performer Frequency Alert level Action level
ECO = environmental monitoring team
In addition to the review of the environmental monitoring SOPs mentioned above the
rationale f
or environmental monitoring sampling locations in
and t
he EM trends for f
rom March 2020 to March 2021 were reviewed.
No adverse trends were identified in the Grade Review of EM trends in
G
rade and ar
eas including the Grade ar
ea from April 2020 –
April 2021 revealed no objectionable trends. It should be noted that the same sampling and the same number of sampling sites as documented in the EM rational e were
monitored dur ing the PPQ batch
A list of environmental monitoring excursions prepared by the firm was presented for review.
The list included the investigation number, room classification and of the
organism identification. There was a total of ten excursions, none of the excursions
were identified in in the Grade ar
eas. All ten excursions were in the
Grade areas
, no mold organism was identified and although the individual excursions
reached the action limit, no adverse trend was identified.
Disinfec
tant Efficacy
(Written by SJ)
The list of disinfectant s used in the Grade ar eas of and
ar
e as follows:
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150481
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
63 of 79 I reviewed disinfectant efficacy study Performance Qualification
Protoc
ol and Result, approved by Quality on August 30, 2019. The study results show
that the use of tec
hnique met acceptance criteria of
D
isinfectant efficacy study Q A approved on December 23, 2016
descri
bes the qualification of
met
hod on surfaces found in Puurs Belgium manufacturing site. ef ficacy
met the
criteria for The disinfectant efficacy study
approv
ed by QA December 23, 2016 descr ibes the qualification of f
or
using the m
ethod and surfaces. m
et the
acceptanc
e criteria of
D
isinfectant efficacy study describes the for
des
cribes the efficacy study for
f
or and des cribes the
for All test results met the criteria for the category for which the
study was performed. No objectionable conditions were noted for the studies reviewed.
Visual inspection and automated inspec
tion machines
(Writ
ten
by LF)
Filling lines use automated vial inspection machines
w
hich
undergo multi
ple phases of validation including
followed by phase 1 and phase 2 performance qualifications (PQs).
The phase 1 PQ tests determine the machine per
formance by:
The
goal of the phase 1 testing is to identify
c
an be seen in Exhibit LF-13. Phase 2 PQ testing focuses on
batch quality control by increased AQL testing and def
ect
trending to a
ssess process variability at batch scale. Multiple PQ documents were
presented and reviewed. :
f
illing line inspects vials using the and the
The f
illing line also uses i
nspection
machine, however the
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150482
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
64 of 79 The used for filling line
i
s a ins
pection machine that can
The PQ protocol described the inspection stations that are used for the COVID -
19 vaccine inspection which occur in the following order:
Stations Detection
The used for filli ng line
is a used for
It consists of
Vials are
Any rejected vials are
and
are r
ejected. Any non-tested vials (usually due to ar
e also
rejected.
AQL t
esting performed during validation for the cons
isted of a sample size of
v
ial requiring critical defects m
ajor defects and minor defects
Visual
Ins
pection
(Written by LF)
On June 24, 2021, we (LF, AC, SJ, ZW) witnessed filling on
in
Room
The filling of Batch was in progress. The aut
omated
visual inspection machine was processing vials at a speed of I
requested the Elect ronic Batch Record (EBR) results for the inspection of batch
The parts of the batch record provided included the verification (set up)
process for the i
nspection machine and the the AQL
sampling performed, and the end verification performed for the
I was also provided the EBR reports for the inspection. The
r
eport included a summary of the following results for the Batch:
•
• Inc
oming t
otal vials:
• I
nspect
ed vials:
• % good: 96.3%
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150483
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
65 of 79 • Total rejected: (3.7%)
• Rejected categories summarized in the report included:
•
T
he r
ecord report from the EBR was also requested for Batch
The r
eport included
t
otal rejected vials at
total rejected vials at the
The for Batch
was which was deemed acceptable. No concerns were noted.
Production in
(W
ritten
by LF
)
We (ZW and LF) observed operator perform the
R
oom on June 30, 2021. The
w
as perf
ormed using a
t
he operator confirmed i
n
the EBR.
This information is transferred into the batch record
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(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)
(b) (4)
FDA-CBER-2021-5683-1150484
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
66 of 79 The r oom is also used for the E xtensive c leaning of all
surfaces and floors in the room is required A picture of
the is attached in Exhibit LF-10.
No concerns w
ere noted.
In process bioburden and endotoxin results
(Written by LF)
In process bioburden and endotoxin results for
w
as requested as a
pre-request
prior to the start of the inspection.
was provided for lots made from Oct ober 30, 2020
to May 21, 2021 The complete list is provided in Exhibit LF-14. Information
was provided from the manufacturing steps listed below and the results were all within
the action limi ts except for Lot m
anufactured on Nov ember 12, 2020. The
deviation related to this excursion was reviewed and found acceptable. Refer to the
Deviation section under Quality Systems. No concerns noted.
In Process Testing (IPT) Step Action limit
M
anagement
(Written by LF)
The management program at Pfizer Puurs is described
in SOP - ver.
M
anagement effective: June 18, 2021. The SO P covers
management of f
or
ar
e cleaned with T he
are decontaminated t
o
ar
e visually checked
If a
i
s discovered in a an immediate assessment is conducted per SOP -
to determine immediate action and whether opening an investigation is
appropriate.
(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)
(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-2021-5683-1150485
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
67 of 79 The integrity of the i s also ver ified using a
s
urface monitoring is conducted for each In the case of
any excursions, a deviation is always opened. A trend analysis is carried out
t
o evaluate any f
ound in the P
reventive actions are also review ed,
and additional preventive actions are defined, if deemed necessary. No concerns were
identified.
Contaminat
ion
and Cross -Contamination Controls
(Written by LF)
The
B
uilding is a dedicated multi -product f acility for vaccine manufacturing.
Formulati
on of BNT162b2 for use is performed in the
B
uil
ding. Currently, the m
anufactured in the
F
ormulation Area are t
he COVID vaccine (BNT162b2).
uses
In general, operations personnel are
filled on filling line i
s the
COVID Vaccine (BNT162b2). Introduction of new product families, updates to
manufacturing processes, and changes to the facility design or equipment are assessed via the site change management process.
The following
procedures pertaining to cross contamination were reviewed:
• SOP- MSOP: Cross contamination management ver. effective June
28,2021
• SO
P- SOP: Process Design and Qualifi cation ver. effective February 23,
2021
• SOP- MS
OP: Product Introduction and Product Related Changes, ver.
effecti
ve June 7, 2018
• C
ross contamination risk management for COVID vac cine,
m
anufacturing ver. effective: June 25, 2021
• Qual
ity Risk Management: Potential Cross -Contami nation
Pl
ant, ver. effective: June 28, 2021
SOP- outli
nes the cross- contamination assessments required based on health-
based exposure limits and risk assessment, and segregation requirements based on
product class. Quality Risk Management (QRM) System proactively assesses the potential risks and implements necessary controls such as:
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150486
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
68 of 79
Tox
icologists in Pfizer ’s Techni cal Review Committee (TRC) assign the product class to
each Pfizer
drug substance. The TRC is a multi -disci plinary group within Global Quality
Operations and Environmental and Health and Saf ety comprised of experts that
characterize the hazards of molecules and classify them into a product class. The rules for the implementation of the segregation are listed in Appendix 1 of SOP - The
SOP i
s attached in Exhibit LF-15. Segregation practices are evaluated based on
process step such as
The
products are grouped
based on risk, as follows:
Ri
sk assessment Cross contamination risk management for COVID
v
accine, manuf
acturing in l
isted above was
review
ed. The assessment classified the COVID vaccine as
(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-2021-5683-1150487
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
69 of 79 f
ormulation for the COVID vaccine is performed in
C
OVID vaccine filling is performed on Vial Filling Line (as proposed in the BLA
125742/0) and V
ial Filling Line
T
he active ingredient in the COVID vac cine (mRNA) was determined to be
The m
anufacturi
ng
activities in the ar ea are currently broken down as follows:
Ac
cording to Risk assessment cleaning activities are finalized for COVID
v
accine on the v
ial
line. The risk assessment is attached in Exhibit LF -16.
Cleaning activities are also finalized for the COVID Vaccine
on
vial filling line Cleaning validation is
Note: The vial line is
The cleaning validation activities for
the v
ial filling line and the l
ine are finalized.
T
he risk
assessment contains further detail regarding the
amount of each drug product,
There
is also an assessment of risk and risk reduction for procedures performed
t
o the Grade f
illing i
s
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150488
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
70 of 79
Q
uality Risk Management: Potential Cross -Contami nation
ver
. ef
fective: June 28, 2021, listed above w as reviewed. The risk assessment is
attached in Exhibit LF-17. The ar
ea consists of
pr
oducts
COVID
c
an be formulated in the ar
ea.
COVID is filled on the f illing lines, as previously
mentioned, on f
illing line N
ote:
Filling on w
as authorized as part of EUA 27034 and the
is
The manufacturing activities in the
area are currently broken down as
follows
:
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150489
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
71 of 79 Product contact COVID formulation and filling equipment are
The f
illing line is used for
COVID vacci
ne filling line is
Addi
tional controls in place include:
• Electronic batch record (EBR) control by
• is onl y performed using
C
OV
ID vaccine for f ormulation and filling.
• Formulation booths (R
oom and
f
illing line are used in a
w
hich are documented in the EBR.
• af
ter performing any processing
activ
ities and
f
illing
• A
of the cleaning process is performed after each cleaning and
documented in the EBR.
• The i
s used on a basis,
No
concerns
w
ere noted.
PACKAGING AND LABELING SYSTEMS
(Written by ZW)
I conducted a walkthrough of the
pack aging l
ine on 7/2/2021. As mentioned
earlier, the
firm has pac
kaging lines for the BNT162b2 vaccine.
B
ecause of time constraint, I did not inspect the
pac
kaging line.
I met and
T
hey explained the packaging process and answered my
questions. Per t
he pac
kaging line currently is operating
I obs
erved that the packaging line is
The filled vials are i
nto the packaging
T
he label is applied to each vial and checked for accuracy.
s
tated that the labels are t
he lot # and expiry are added
The labeled vials are loaded
square flat
“pizza box”, 195 vials per box.
v
erify the count before he the pizza
(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)
(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) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150490
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
72 of 79 box. pastes the label on the box and packs boxes
The bundle is then placed in a f
or transport to
the w
arehouse in the Building The c
an take up to
(
to fill one ultra-freezer). From the w
arehouse to the freezer
farm
, a temperature-controlled truck is used for transportation, and the deliver time
takes I reviewed the on the
truck from randomly selected days . No issues were noted.
LABORATO
RY CO
NTROL SYSTEM
Walkthrough of the Labor
atory
(Written by AC)
The one analytical assay that I observed in the laboratory was
T
he operator performed this assay for DP sample
was
qualified as the reference standard The reference standard can be
us
ed This reference is used for the generation of
f
or the
w
as used for the of the tested samples. The
i
s calibrated and the calibration events are documented. Under the
system, I saw that analysts are required to review the raw data. Only if all
system/assay suitability checks fulfilled the acceptance criteria to demonstrate assay validity, the lab results can be approved. I did not identify issues of concerns regarding the execution of the assay and analyses of the raw data.
Review
of E
ndotoxin assay
(Written by AC)
Endotoxin testing for BNT162b2 drug product i
s performed using a
Due to
s
tep is performed
The verification was performed using
t
o monitor endotoxin
content v
erification reports
w
ere generated to ensure the sample used
w
ith the bacterial endotoxin test for
In
the verification study report, the prepared samples were
T
he
(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)
(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)
(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)
(b) (4)
FDA-CBER-2021-5683-1150491
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
73 of 79 data demonstrated that the sample the final readout
and supported that the verified is within the
N
o issue of concern was identified for this assay.
Stability
Study of BNT162b2 Drug Product
(Written by AC)
The current proposed shelf life for the BNT162b2 drug product stored at the real -time
conditi
on of -90 to -60°C is m
onths. Data from the stability studies consists of
l
ots
l
ots and lots
manufactured by Pfizer Puurs, Pfizer Kalamazoo,
were presented during the inspection ( Exhibit AC -5). All results,
generated to date, met the acceptance criteria at the time of testing. However, results of
some of the
stability time points are not updated in a timely manner when this inspector
reviewed their DP stability data onsite. After discussion with the Pfizer’s stability team,
they provided the updated stability results for the batches on June
29, 2021 and all updated stability results met the acceptance criteria at the time of
testing.
Bioburden Test
Met
hod Verification
(Written by SJ)
Document M
ethod Verification Report for
in the Bioburden Test
by on
the
The method verification was conducted per
The m
ethod was executed with
and us
ing
and us ing
T he acceptance criteria for the method verification
are described as the from the product must be at
least of
The bioburden test for
met all pre-established criteria hence the method was verified as acceptable.
The routine bioburden test method is described in
v
ersion effective
June
22, 2021. This method details the steps for routine bioburden testing via
and results interpretation. The routine
bioburden test method is in line with steps used in the bioburden method verification. No objectionable conditions were noted.
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150492
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
74 of 79 Sterility Test Method Qualification
(Written by SJ)
Document approved by January 2021 docum
ents the
sterility test method via f
or COVID 19 MRNA vaccine. The method
verification was performed utilizing three different batches of the COVID 19 mRNA
vaccine,
T
he result
s
of the study for the COVID 19 mRNA vaccine
were successful in that both product and was compar able.
v
ersion effective May 10, 2021 details the routine sterility test method for
COVID -19 vaccine dr
ug product in vials. This sterility test method was
reviewed, and no issues were noted.
s terility test method was
validated for the COVID -19 mRNA vaccine. Document
approv
ed by Quality 01 May 2021 V alidation Project Report for the Method Verification
for Sterility Testing on Comirnaty Drug Product (vial) or COVID 19
mRNA, BTN162b2 D
rug Product (Vial) using the
This sterility test follows the
method however
is utilized. The i
s
a method f
or the detection of the presence of microorganisms
of the validation demonstrated the of the
met
hod for sterility testing T
he raw data to support the
paramet
ers used to define were as follows:
were reviewed. No objections
were noted.
validation study demonstrated that the presence of the COVID 19 mR NA
vaccine product in the test sample
The
raw data reviewed details the three batches of COVID 19 mRNA vaccine were
utilized in testing and the study was There
were two deviation investigations during this study, the deviations were investigated, and a root cause was identified for each deviation.
(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)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150493
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
75 of 79 The validation of the m ethod with a
m
et all specifications to be used as
a method for COVID 19 mRNA vaccine.
The sterility test method is des cribed in v ersion This
method ut
ilizes the and read out of results with
as
executed in the validation study.
During t
he inspection, I discussed sterility test failur e with
I
questioned if there were any sterility test failures for COVID -19
mRNA
vaccine and requested the associated deviations investigations.
s
tated there were no sterility failures at the site. I requested a signed statement that
there is no sterility test failure for COVID 19 mRNA batches.
provided a signed document attesting to no sterility failure for
COVID -19 mRNA vaccines at the site see Exhibit SJ -5.
Sample (W
ritten by AC)
SOP- des
cribes the procedure for
C
OVID samples for analysis by
R
elease samples are
and s
tability samples are
The protocol contains information on
different sections: request of pr
eparation of the accompanying documents,
and preparation for All sections provide clear instructions, and I did not
identify issues of concern on this protocol.
Sample ret
ention program
(Written by ZW)
I reviewed the procedures for the reserved samples with
She stated that she follows the SOP - for the
sample
retention. For each lot of the vaccine, the firm has gr
oups of the retained
samples:
Currently the vaccine shelf life is months. The s
amples are kept for
and t
he samples for respectively. No issues were noted.
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150494
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
76 of 79 RECALL PROCEDURES
Product return and recall
(Written by ZW)
I reviewed the following recall and product return SOPs with
and
• SOP- “
Market action management”, effective date 4/21/2021 SOP -
“E
valuation of r eturned goods COVID -19 vaccine”, effective date 6/28/2021.
Accor
ding to there are no product returns or recalls since the launch of
the vaccine. I reviewed the procedures without issues.
REFUSALS
(Written by LF)
We (LF, SJ , ZW, and AC) encountered no refusals during the current inspection.
No FDA Form 483 Observations was issued to the firm.
GENERAL DISCUSSION WITH MANAGEMENT
We discussed various issues with Management during the inspection which may require their attention including the following.
(Written by AC)
1. validation protocols were used to cover all test conditions and
sam
pling plans needed to validate the s
upporting that
the dr
ug product manufacturing process consist ently produces BNT162b2 drug
product lots of acceptable quality under the commercial manufacturing range of
T
hree batches
m
anufactured at f
illing lines were included in the validat ion studies. All
bat
ches were put on stability, but bat
ches w as
put on stability. The firm explained that the decision to put bat
ch on
stability was based on a and product lots
produced at the Puurs and Kalamazoo sites. I advised them that in general
i
s acceptable to be used for the design of process validation, but it is
strongly recommended to get concurrence on your proposed f
rom
the agency prior to the execution of the study. This decision is product -specific and
depends also on the level of characterization of the product. In addition, it is
recommended to include at least three lots of your product in validating the worst -
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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-2021-5683-1150495
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
77 of 79 case of the hold time T he firm acknowledged these
suggesti
ons.
2. For the
release analytical assay s Puurs
analytical laboratories, I suggested
The firm acknowledged the suggestion.
(Written by LF)
1. Microbiological cleaning validation relating to equipment used for form ulation and
filling of the COVID 19 Vaccine is not complete. The c
leaning validation for the
is
also not complete. Memos provided by
and
(Exhibit LF-11, Microbiological cleaning validation
status) and (
Exhibit LF-9 ,
cl
eaning validation of were provided by the firm to summarize
the status of the cleaning validation, estimated compl etion and next steps. During the
discussion at the firm, I stated that FDA would cover the completion of these items as part of the review activities associated with BLA 125742/0.
EXHIBI
TS C
OLLECTED
LF-1a-d List of Personnel with whom We Interacted, opening and closing meeting
attendees
LF-2 History of Business
LF-3 Opening Presentation
LF-4
and
LF-5 W
arehouse T
our
LF-6 Cleaning Validation SOP -
LF-7 List of Products fi lled on
LF-
8
LF-9 m
emo
LF-10
LF-
11 Microbiological Cleaning Validation Status Memo
LF-12 PQ protocol (Doc ID: S terilization of
LF-13
Visual Inspection
LF-14 In process bioburden and endotoxin results
LF-15 SOP - MSOP: Cross contamination management ver.
LF-16 C ross contamination risk management for COVID vaccine,
manuf
acturing in ver.
LF-17 Q
uality Risk Management: Potential Cross -Contamination
ver.
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(b) (6), (b) (7)(C)
(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)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150496
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
78 of 79 SJ-1 Copy of the List of Media Fills
SJ-2 Root Cause Analysis for Deviation associated with Media Fill
SJ
-3 Media Fill Protocol & Report for Introduction to New Fill Line f
or COVID 19
mRN
A Vaccine
SJ-4 Media F
ill Protocol & Report for Introduction of COVID 19 mRNA Vaccine
SJ-5 No Sterility Test Failure for COVID 19 mRN A Vaccine Signed Statement
AC-1 COVID -
19 mRNA LNP Process Flow Diagram,
AC-2 Drug Product Process Validation Strategy,
AC-3 Cumulative Target/Challenges,
AC
-4 COVID -19 Vaccine, Pfizer Puurs Master Validation Plan,
AC-5 Summ ary Table of BNT162b2 Drug Product Stability Studies,
ZW
-1 Photos collected,
ZW-2 PM
ZW-3 Presentation shipping qualification,
ATTACHMENTS
None
The signatures of the FDA representatives are on the following page(s).
(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-2021-5683-1150497
Establishment Inspection Report FEI: 1000654629
Pfizer Manufacturing Belgium NV EI Start: 06/24/2021
Puurs, Belgium EI End: 07/02/2021
79 of 79
Signature Page
Laura Fontan, CSO, CBER/OCBQ/DMPQ/B1
Zhongren Wu, CSO, CBER/OCBQ/DMPQ/B1
Anissa Cheung, CSO , CBER/ OVRR /DVP
Susan Jackson, CSO, ORA/OMPTO/OBPO/BPIS
FDA-CBER-2021-5683-1150498