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Inspection Waiver -STN 125742/0 Page 1 of 5
_____________________________________________________________________________________________
Food and Drug Administration
Center for Biologics Evaluation and Research
Division of Manufacturing and Product Quality
From: Kathleen R. Jones , CMC / Facility Reviewer, OCBQ/DMPQ/MRB1
Laura Fontan, CMC / Facility Reviewer, OCBQ/DMPQ/MRB1
Gregory Price, CMC / Facility Reviewer, OCBQ/DMPQ/MRB1
CDR Donald Erte l, Team Lead, OCBQ/DMPQ/MRB1
Nicole Li, CMC / Facility Reviewer , OCBQ/DMPQ/MRB1
To: Administrative File STN: 125742/0
CC: Michael Smith , RPM, CBER/OVRR/DVRPA/CMC3
Laura Gotts chalk , RPM, CBER/OVRR/DVRPA/CMC3
Carolyn Renshaw, Deputy Director, CBER/OCBQ/DMPQ
Iryna Zubkova, RPM, OCBQ/DMPQ/ARB
Applicant : BioNTech Manufacturing GmbH in partnership with Pfizer, Inc.
Product : COVID- 19 Vaccine (BNT162b2; PF- 07302048) COMIRNATY
Indication: Prevention of COVID -19 in adults ≥ 16 years of age
Subject: Inspection Waiver for Pre-License Inspections (PLI) of manufacturing and
testing facilities listed herein for Biologics License Application (BLA) STN
125742/0
Due Date:
16 January 2022
The following information provides justification to support the waiver recommendations: Inspection history:
Location Activity Most Recent
Inspection
Pfizer Inc.
875 Chesterfield Parkway West
Chesterfield, MO 63017
(referred to as Pfizer,
Chesterfield )
FEI#: 1940118 Manufacturing of
, drug substance release
and stability testing, d rug p roduct
release and stability testing Surveillance
ORA
August 2019
NAI
Pharmacia & Upjohn Company
LLCa
7000 Portage Road
Kalamazoo, MI 49001 LNP production , bulk drug product
formulation, fill and f inish, primary
packaging, s econdary packaging,
drug product release and stability
testing Surveillance
ORA/OBPO
May 2021
VAI
(b) (4)
FDA-CBER-2021-5683-1150226
Inspection Waiver -STN 125742/0 Page 2 of 5
Location Activity Most Recent
Inspection
(referred to as Pfizer,
Kalamazoo)
FEI#: 1810189
Pfizer Ireland Pharmaceuticals
Grange Castle Business Park
Clondalkin, Dublin 22
Ireland
(referred to as Pfizer, Grange
Castle)
FEI#: 3004145594 Drug product release and stability
testing Surveillance
ORA/OBPO
November 2019
VAI
Hospira Zagreb Ltdb
Prudnička cesta 60
10291 Prigorje Brdovečko
Croatia
FEI#: 3010630287 Drug product release testing
(sterility) PAI
CDER
November 2019
VAI
SGS Lab Simon SA
Vieux Chemin du Poète 10
Wavre, 1301
Belgium
FEI#: 3004186644 Drug product release testing
(sterility)
Surveillance
ORA
September 2017
VAI
a Pharmacia & Upjohn Company LLC is a wholly owned subsidiary of Pfizer Inc.
b Hospira is a wholly owned subsidiary of Pfizer Inc.
NAI = No Action Indicated VAI = Voluntary Action Indicated
CDER = Center for Drug Evaluation and Research ORA = Office of Regulatory Affairs
OBPO = Office of Biological Products Operations
For the subject BLA, the following manufacturing facilities are proposed for an
inspection waiver .
Pfizer, Chesterfield:
The Pfizer , Chesterfield facility will be used to manufacture the and
for drug substance and drug product release and stability testing. In August 2019, ORA
performed t he most recent inspection, which covered the quality system, facilities, and
equipment operations and was classified as NAI .
Since the last inspection, changes were made to the facility, which include d updates
and commitments to update the manufacturing area a s part of the
investigational new drug application and E mergency Use Authorization (EUA) request
for the same BNT162b2 product as the subject BLA. For instance, t he
manufacturing area classification was updated to a “controlled, not classified ”
area and improvements were made to provide better facility, equipment, and quality
control .
(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150227
Inspection Waiver -STN 125742/0 Page 3 of 5
For the manufactured at the facility , there are production and
process controls t hat mitigate risk to the product, such as the perform ance of all open
manufacturing operations in a at the establishment and t he
. Regarding t he release and stability testing of
BNT162b2 drug substance and drug product performed in the Pfizer
at Pfizer, Chesterfield, the establi shment
has been registered as an analytical testing facility and laboratory system controls
include environmentally monitored stability chambers and qualified, maintained, and
calibrated instruments and equipment.
Pfizer, Kalamazoo:
The Pfizer , Kalamazoo site will be used for lipid nanoparticle production (LNP) , bulk
drug product formulation, drug product filling and finish, primary and secondary
packaging, and drug product release and stability testing. The site is currently used to manufacture the same BNT162b2 product under an EUA dated December 11, 2020.
The BNT162b2 manufacturing operations occur in the same facility and under the same quality system s as other FDA- regulated products , including non-biological finished drug
products ( sterile injectables, liquids & semi- solids) , active pharm aceutical ingredients ,
medical devices, and three licensed biological products. Specifically :
• T he BNT162b2 bulk drug product formulation occurs in the manufacturing
area (B uilding ), which is where two FDA licensed biological products were
previously manufactured.
• The BNT162b2 drug product is filled on existing Lines , which have been
previously used to fill other FDA -regulated products and are now primarily dedicated
to BNT162b2.
• A utomated visual inspection of the vialed BNT162b2 can be conducted on Line
AVI
machine, of which can accommodate other FDA -regulated product flows filled
in vials or ampoules.
In May 2021, ORA/ OBPO performed the most recent inspection, which was a Level I
surveillance inspection with comprehensive focus on the BNT162b2 drug production
operations that covered the quality system, production system, facilities & equipment
system, packaging and labeling system, and cursory coverage of the laboratory system.
Throughout the inspection, the inspectors reviewed and observed the following critical
activities: receipt operations for the mRNA , LNP operations,
specific formulation operations , sterile filtration, aseptic filling, automated visual
inspection, capping, labeling and packaging into vial boxes, loading / unloading of
ultralow temperature freezers, and packaging of the packed vial boxes into styrofoam
boxes for distribution. Additionally, for filling Lines , the inspectors reviewed the
routine media fills and the three specific BNT162b2 media fills , which passed
specifications with no concerns noted. The inspectors noted and BNT162b2
vaccine lots were filled on L ines , respectively , and there were no reported
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b)
(4)
(b) (4)
(b) (4)
(b) (4)
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(b) (4)
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(b) (4)
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(b) (4)
(b) (4)
(b) (4)
FDA-CBER-2021-5683-1150228
Inspection Waiver -STN 125742/0 Page 4 of 5
recalls for any of the licensed biological products since the previous ORA/ OBPO
surveillance inspection conducted in Oct ober 2017. Furthermore, the inspectors
followed up on six complaints related to BNT162b2 and determined there were no
concerns with the associated investigations or conclusions. Regarding the release and
stability testing of the drug product, coverage of the laboratory system included observation of sterility operations, review of bioburden testing, incubations of environmental monitoring plates, plate counting operations, and a walk -through of
endotoxin testing with no deficiencies identified. At the conclusion of the inspection, an
FDA Form 483 was issued to the firm , and the inspection was classified as VAI based
on the adequacy of the firm’s response to the FDA Form 483.
Pfizer, Grange Castle:
The Pfizer , Grange Castle facility will be used for drug product release and stability
testing for BNT162b2. This site has an acceptable compliance history with the last four
US FDA inspections classified as VAI . In November 2019, ORA/ OBPO performed t he
most recent inspection , which covered vaccine products and laboratory controls. The
observations from the most recent inspection do not indicate concerns regarding the laboratory or drug product testing.
Hospira Zagreb Ltd.:
The Hospira Zagreb Ltd. facility will be used for sterility release testing of t he finished
BNT162b2 drug product. This site has an acceptable compliance history with the last
two US FDA inspections classified as VAI . In November 2019, CDER performed the
most recent inspection, which included the laboratory controls. The observations from the most recent inspection do not indicate concerns regarding sterility testing in the
microbiology laboratory of the facility.
SGS Lab S
imon SA :
The SGS Lab Simon SA facility will be used for sterility release testing of the finished
BNT162b2 drug product. This site has an acceptable compliance history with the last
inspection conducted in 2017 by US FDA. The 2017 inspection, which covered sterility
testing, was classified as VAI based on the adequacy of the firm’s response to an FDA
Form 483 issued to the firm .
Recommendation: Waive PLI s of aforementioned facilities.
FDA-CBER-2021-5683-1150229
Inspection Waiver -STN 125742/0 Page 5 of 5
Concurrence signatures:
Xiao Wang , Ph.D.
CMC Reviewer
Laboratory of DNA Viruses
Division of Viral Products
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research ________________________________
Lori Peters, MS
Branch Chief, Manufacturing Review Branch I
Division of Manufacturing and Product Quality
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research ________________________________
Ramachandra Naik, Ph.D.
Chair
CMC Review Branch 3
Division of Vaccines & Related Products Applications
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research ________________________________
Jerry P. Weir, Ph.D.
Director, Division of Viral Products
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research ________________________________
John A. Eltermann, Jr. , RPh, MS
Director , Division of Manufacturing and Product Quality
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research ________________________________
FDA-CBER-2021-5683-1150230