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BNT162b2
3.2.P.2 Pharmaceutical Development
Introduction
PFIZER CONFIDENTIAL
Page 13.2.P.2. PHARMACEUTICAL DEVEL OPMENT –INTRODUCTION
In this section, the formulation and process development and control strategy for
BNT162b2 drug product are described. The pharmaceutical development of BNT162b2
The pharmaceutical
development section for drug product is organized as follows:
1. Components of the Drug Product
The components of the drug product including physicochemical characteristics of the
drug substance as relevant to the drug product are provided in this section
(Section 3.2.P.2.1 Components of the Drug Product).
2.Drug Product
A discussion of the approach, results and conclusions from the formulation development
and characterization studies is provided in this section ( Section 3.2.P.2.2 Drug Product ).
3.Manufacturing Process Development
a.Development History
A summary of manufacturi ng process changes with justification for changes is
provided in this section ( Section 3.2.P.2.3 Development History ). Comparability
information is included ( Section 3.2.P.2.3 Manufacturing Process Development –
Comparability Assessment of PPQ Lots).
b.Qual ity Attributes (QAs)
This section includes the approach to defining the critical quality attributes ( CQAs )
and the rationale for the criticality decisions ( Section 3.2.P.2.3 Quality Attributes ).
c.Process Risk Assessement Strategy
The process risk assessment strategy and methodology areprovided in this section
(Section 3.2.P.2.3 Process Risk Assessment Strategy ).
d.Process Development and Characterization
This section includes a discussion of the approach, results and conclusions from the
process characterization studies completed for the manufacturing process, including
how critical process parameters (CPPs) and critical material attributes (CMAs) of the
process have been identified, as well as how the operating ranges have been d efined
in order to ensure product quality (Section 3.2.P.2.3 Process Development and
Characterization).
e.Lot Genealogy and Usage
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BNT162b2
3.2.P.2 Pharmaceutical Development
Introduction
PFIZER CONFIDENTIAL
Page 2This section includes a list of lots, along with their use and ingoing drug substance
batch(es) (Section 3.2.P.2.3 Lot Genealogy and Usage ).
f.Control Strategy
This control strategy section includes the approach to developing the control
strategy , the description of elements of control, and the summary of the control
strategy for QAs across drug substance and d rug product. The summary of the
control strategy for QAs includes the attributes, controls implemented and section
references to where the controls are described in greater detail (Section 3.2.P.2.3
Control Strategy ).
g.Analy tical Method Evolution
This secti on describes the anal ytical testing strategy throughout drug product
development history as (Section 3.2.P.2.3
Analy tical Method Evolution ).
4.Container Closure Sy stem
This section describes the selection and suitabili ty of the container closure system
(Section 3.2.P.2.4 Container Closure Sy stem ).
5.Microbiological Attributes
As BNT162b2 is a sterile preservative -free multi- dose product, this section includes
information supporting the integrity of the container closure system (Section 3.2.P.2.5
Microbiological Attributes) .
6.Compatibility
This section includes results of testing the compatibility of BNT162b2 with the diluent
(0.9% sodium chloride [saline ]solution ),components commonly used for preparation
and intramuscul ar administration, as well as results of study
(Section 3.2.P.2.6 Compatability ).
Quality Target Product Profile (QTPP)
A QTPP was established to form the basis for development of BNT162b2 .The development
of the QTPP
The QTPP describes the
drug product in terms of quality characteristics, listing the intended product quality and
performance charac teristics to be achieved at the end of the drug substance and drug product
manufacturing processes and linking these characteristics to the relevant CQAs. The QTPP
forBNT162b2 with associated CQAs (both drug substance and drug product related) is
provided in Table 3.2.P.2 -1.Quality attributes with associated criticality assessment are
discussed in Section 3.2.P.2.3 Quality Attributes.
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BNT162b2
3.2.P.2 Pharmaceutical Development
Introduction
PFIZER CONFIDENTIAL
Page 3Table 3.2.P.2 -1. BNT162b2 Drug Product Quality Target Product Profile and
Quality Attributes
Product Element Product Quality and Performance Characteristics Quality Attributes
Efficacy
Product Type Vaccine based on SARS -CoV -2 S glycoprotein
antigens encoded in RNAIdentity of Encoded RNA
Sequence
In Vitro Expression
RNA Integrity
5’-Cap
Poly(A) TailIndication Prevention of coronavirus disease 2019 (COVID- 19),
which is caused by the virus SARS -CoV -2, in
individuals aged greater than 16years old
Dosage Form Suspension for Intramuscular Injection
Concentrate for solution for injection
Injection, Lipid Complex Concentrate
Dispersion for Dilution for Injection
Concentrate for dispersion for injectionAppearance
pH
Lipid Identities
LNP Size
LNP Polydisper sity
RNA encapsulation
RNA Integrity
In Vitro Expression
ALC -0315 Content
ALC -0159 Content
DSPC Content
Cholesterol ContentDrug Product
Shelf LifeMinimum of at -90- -60°C
Including up to tw o weeks at -20 °C and
Up to 1 month at 2 –8 °C
Form ulation,
Ingredients (Drug
Product)0.5 mg/mL BNT162b2 RNA formulated in lipid
nanoparticles comprising 7.17 mg/mL ALC -0315 ,
0.89 mg/mL ALC -0159 , 1.56 mg/mL DSPC ,and
3.1mg/mL cholesterol in a phosphate buffer
comprising 1.08 mg/mL dibasic sodium phosphate
dihydrate, 0.15 mg/mL monobasic potassium
phosphate, with 10 3mg/mL sucrose, 6 mg/mL
sodium chloride and 0.15 mg/mL potassium chloride
To be diluted with sterile 0.9% sodium chloride
solution, Inj. prior to use.
Dosage Strength 30 µg of RNA per0.3 mL of diluted dosing solution ;
30µg per dose , 6 doses per vialRNA Content
Vial Conten t (Volume)
Safety
Primary Package Type I borosilicate glass vial with a bromobutyl
stopper and an aluminum seal with flip -off capAppearance (Visible
Particulates)
Subvisible Particles
Bacterial Endotoxin s
Sterility
Container Closure IntegrityDrug Product
Quality
RequirementsMeets pharmacopoeial requirements for parenteral
dosage form as well as product -specific requirements
Type Preservative -free, multi -dose vial
Size 2 mL glass vial, 6doses per vial
Tolerability and Clinical Relevance
Com patibility
with Dosing
Com ponentsDiluted drug is stable for duration of dosage
preparation and administrationAppearance
pH
Osmolarity
RNA Integrity
RNA Content
In Vitro Expression
Container Closure Integrity
Vial Content (Volume)Dosing
TolerabilityAcceptable (local) toleration on intramuscular
injection administration
Com patibility
with Co -
administered
DrugsNot planned for co-administration
Abbreviations: LNP = lipid nanoparticle; ALC -0315 = ((4 -hydroxybutyl)azanediyl)bis(hexane -6,1-diyl)bis(2 -
hexyldecanoate) ; ALC -0159 = 2 -[(polyethylene glycol) -2000] -N,N-ditetradecylacetamide ;
DSPC = 1,2 -Distearoyl -sn-glycero -3-phosphocholine
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3.2.P.2 Pharmaceutical Development
Introduction
PFIZER CONFIDENTIAL
Page 4The 3.2.P.2 Pharmaceutical Development sections describe how the BNT162b2 drug product
formulation, presentation, and manufacturing process were developed to ensure the drug
product meets the requirements of the QTPP. CQAs are linked to the product attributes of
the QTPP, bridging the QTPP to the control strategy. Because the drug substance is the
source of the active component of the drug product, some of the QAs of the drug product are
delivered in the drug substance proc ess. The drug product control strategy , presented in
Section 3.2.P.2.3 Control Strategy , is built on the assessment of CQAs for drug substance
and drug product and considers how they are controlled in both the drug substance and drug
product processes.
1WHO Target Product Profiles for COVID -19 Vaccines,
Version 3 - 29April 2020 available at
https://www.who.int/docs/default- source/blue -print/who -target -product -
profiles -for-covid-19- vaccines.pdf?sfvrsn=1d5da7ca_5&download=true
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