125742 S55 M2 drug product stability

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BNT162b2
2.3.P.8 Stability
PFIZER CONFIDENTIAL
Page 1TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................1
2.3.P.8. STABILITY ................................ ................................ ................................ .................. 3
2.3.P.8.1. Stability  Summary  and Conclusion ................................ ................................ ..3
2.3.P.8.1.1. Shelf L ife at Recommended Storage Temperature ............................. 3
2.3.P.8.1.2. Stability  Batches and Studies ................................ .............................. 3
2.3.P.8.1.3. Protocol for Testing at the Long Term Condition ( -90 to -60C) .....11
2.3.P.8.1.4. Protocol of Testing at the Accelerated Condition ............................. 13
2.3.P.8.1.5. Protocol for Testing at the Thermal Stress Conditions .....................17
2.3.P.8.1.6. Summary  of Stability  Data ................................ ................................ 22
2.3.P.8.1.6.1. Summary  of Stability  Data at the Long Term 
Storage Condition ( -90 to -60C)................................ ..................... 22
2.3.P.8.1.7. Summary  of Stability  Data at the Accelerated Storage 
Condition ................................ ................................ ................................ .......... 22
2.3.P.8.1.8. Summary  of Stability  Data at the Thermal Stress Storage 
Conditions ................................ ................................ ................................ ........ 25
2.3.P.8.1.9. Summary  of Stability  Data at the Thermal Cy cling Storage 
Conditions ................................ ................................ ................................ ........ 25
2.3.P.8.1.10. Summary  of Photostability  Stability  in Drug Product Vials ........... 26
2.3.P.8.1.11. Shelf L ife and Conclusions ................................ ............................. 26
2.3.P.8.2. Post Approval Stability  Protocol and Stability  Commitment ........................ 27
2.3.P.8.3. Stability  Data ................................ ................................ ................................ ..28
LIST OF TABLES
Table 2.3.P.8-1. Summary  of On -going Stability  Studies ................................ ............ 5
Table 2.3.P.8-2. Protocol for BNT162b2 DP at the L ong Term Condition of  -90to -
60°C................................ ................................ ................................ .. 11
Table 2.3.P.8-3. Protocol for BNT162b2 DP at the L ong Term Condition of - 90 to -
60°C I nverted Vial Orientation (L ots EL7834, EK4242, EL 1491, 
EL3249 and EL3248) ................................ ................................ ....... 12
Table 2.3.P.8-4. Protocol for BNT162b2 Earl y Clinical and Non -clinical and Stability  
DP at the L ong T erm Condition of - 70 ± 10°C ................................ 12
Table 2.3.P.8-5. Protocol for BNT162b2 DP at the Accelerated Condition of -60 to -
30°C................................ ................................ ................................ .. 13
Table 2.3.P.8-6. Protocol for BNT162b2 DP at the Accelerated Condition of -40 
± 5°C................................................................................................. 14
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2.3.P.8 Stability
PFIZER CONFIDENTIAL
Page 2Table 2.3.P.8 -7. Protocol for BNT162b2 DP at the Accelerated Condition of -20 
± 5°C................................ ................................ ................................ . 15
Table 2.3.P.8-8. Protocol for BNT162b2 DP at the Accelerated Condition of -20 ±
5°C I nverted Vial Orientation (L ots EL7834, EK4242, EL 1491, 
EL3249 and EL3248) ................................ ................................ ....... 15
Table 2.3.P.8 -9. Protocol BNT162b2 DP at the Accelerated Condition of 5 ± 3°C... 16
Table 2.3.P.8-10. Protocol for BNT162b2 DP at the Accelerated Condition of 5 ± 3°C 
Inverted Vial Orientation (L ots EL7834, EK4242, EL 1491, EL3249 
and EL3248) ................................ ................................ ..................... 17
Table 2.3.P.8-11. Protocol for BNT162b2 DP Manufactured b y Polymun Scientific at 
the Accelerated Condition of 5 ± 3°C ................................ .............. 17
Table 2.3.P.8 -12. Protocol for BNT162b2 DP at the Thermal Stress Condition of 25 ±
2°C/60 ± 5% RH................................ ................................ ............... 18
Table 2.3.P.8-13. Protocol for BNT162b2 DP at the Thermal Stress Condition of 30 ± 
2°C/65 ± 5% RH................................ ................................ ............... 18
Table 2.3.P.8 -14. Protocol for BNT162b2 DP at the Thermal Stress Condition of25 ± 
2°C................................ ................................ ................................ .... 19
Table 2.3.P.8 -15. Protocol for BNT162b2 Emergency  Suppl y DP Thermal Cycling 
Studies (L ots EK1768 and EJ1686) ................................ ................. 19
Table 2.3.P.8 -16. Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lots 
EL8723, EN1195 and EL9266) ................................ ........................ 20
Table 2.3.P.8 -17. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies 
(LotEL3249) ................................ ................................ .................... 20
Table 2.3.P.8 -18. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies 
(LotEK4242) ................................ ................................ .................... 21
Table 2.3.P.8 -19. Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies 
(LotEL7834) ................................ ................................ .................... 21
Table 2.3.P.8-20. Post-Approval Commercial Stability  Protocol for Drug Product 
Stored at - 90 to -60 ° C................................ ................................ ...... 27
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2.3.P.8 Stability
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Page 32.3.P.8. STABILITY
2.3.P.8.1. Stability Summary and Conclusion
2.3.P.8.1.1. Shelf Life at Recommended Storage Temperature
Thecommercial shelf life of the BNT162b2 drug product is being extended to 9 months 
when stored at the intended storage condition of -90 to -60 °C. The shelf life is based on the 
currentl y available data from stability  studies utilizing material from emergency  suppl y, 
process performance qualification, clinical and one non- clinical lot of drug product. The 
stability  data generated to date on the emergency  supply  and process performance 
qualification lots also support an additional storage condition at -20 ± 5°C for up to 2 weeks, 
as well as short term storage at 5± 3°C for up to one month (within the 9 month shelf life). 
Drug product stability  lots, from multiple global manufacturing sites, have been enrolled in 
stability  programs and are being monitored in accordance with the approved protocols. All 
testing to d ate has been performed using anal ytical methodology  and phase appropriate 
specifications in place at time of testing. The analy tical procedures used in the stability  
programs were developed to monitor the composition, strength, purit y, safety and general 
quality  attributes of the drug product.
In-use Period of Drug Product
The initial in -use period for the thawed, undiluted vial is room temperature for not more than 
2 hours  (Section 3.2.P.2.6 Compatibility ). Formal thermal cy cling stability  studies have be en 
initiated on both emergency use lots and PPQ lots in order to further support the in -use 
period. Available data from these studies is provided in Section 3.2.P.8.3 Thermal Stress and 
Cycling. The in -use shelf life of undiluted and diluted vials is defined in Section 3.2.P.2.6 
Compatibility .
2.3.P.8.1.2. Stability Batches and Studies 
The stability  program is designed to follow I CH guidelines for stability  of drug product (ICH 
Guideline Q1A: Stability Testing of New Drug Substances and Products; ICH Guideline 
Q5C: Qua lity of Biotechnological Products, Stability  Testing of Biotechnological/Biological 
Products). To date, thirteen process performance qualification lots (with one additional PPQ 
lot being placed on a thermal cy cling stabilit y study onl y), eight emergency su pply lots, 
seven clinical lots and one non -clinical lot lots have been placed on stability and stored under 
long term, accelerated, and thermal stress conditions. The drug product lots placed on 
stability , to date, were packaged in commercial glass vials or glass vials representative of 
commercial packaging (for earl y non -clinical and clinical drug product studies).
Both the clinical and non -clinical drug product lots manufactured b y Polymun Scientific 
using the BNT162b2 construct are considered to be predi ctive of the stability  of the 
commercial materials based on comprehensive comparability  assessments performed during 
development. The emergency  suppl y lots were manufactured using the commercial process.
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Page 4Therefore, the clinical and non-clinical drug produc t lots manufactured b y Polymun 
Scientific, as well as the emergency  supply  lots, are considered predictive of the stability  of 
the commercial materials.
A summary  of all drug product lots on stability  studies and current available stability  data are 
shown inTable 2.3.P.8-1 .
Stability  Summary  and Conclusion. At this time, stability  studies are on -going. Data from 
these studies will be used to confirm the initial shelf l ife of the drug product. Further 
information on confirmation and extension of the drug product shelf life is discussed in 
Section 3.2.P.8.1. Stability  Summary  and Conclusion, Section 3.2.P.8.1.7 Shelf L ife and 
Conclusions.
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Page 5Table 2.3.P.8 -1. Summary of On -going Stability Studies 
Lot Number Stability Study 
Start Drug Product Batch Use Study Type Storag e Condition Data 
Available Study 
Status
EN6199
(Pfizer, 
Kalamazoo, Line February 2021 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C 3month s On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 3month s On-going
Accelerated 5 3 C 3month s On-going
EL3249 
(Pfizer, 
Kalamazoo, Line December 2020 Stability, Clinical, Emergency Supplya, 
Process performance qualificationLong Term -90 to -60 C Upright Vials 6month s On-going
-90 to -60 C Inverted Vials 6month s On-going
Accelerated -20 5 CUpright Vials 6month s On-going
-20 5 C Inverted Vials 6month s On-going
Accelerated 5 3 CUpright Vials 6month s On-going
5 3 C Inverted Vials 6month s On-going
Thermal 
CyclingThermal Cycling: 1 week at -90 to -
60°C , followed by 2 weeks at  -20 ±5 
°C, 4 weeks at 2 to 8 °C and 1 week at 
25 ±2 °C/60 ±5% RH.8weeks Complete
EL9266
(Pfizer, 
Kalamazoo, Line February 2021 Stability, Emergency Supplya, Process 
performance qualificationThermal 
CyclingThermal Cycling: Ultra frozen vials are 
placed at -20 ± 5 °C for 4 weeks and 
then moved to 2 to 8 °Cfor 12 weeks. 
Samples will be pulled for testing 
every 2 weeks throughout protocol.8weeks On-going
EL9267
(Pfizer, 
Kalamazoo, Line January 2021 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C 3month s On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 3month s On-going
Accelerated 5 3 C 3month s On-going
EL3248 
(Pfizer, 
Kalamazoo, Line December 2020 Stability, Clinical, Emergency Supplya, 
Process performance qualificationLong Term -90 to -60 C Upright Vials 6months On-going
-90 to -60 C Inverted Vials 6months On-going
Accelerated -20 5 CUpright Vials 6month s On-going
-20 5 C Inverted Vials 6month s On-going
Accelerated 5 3 CUpright Vials 6 month s On-going
5 3 C Inverted Vials 6month s On-going
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
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(b) (4)
(b) (4)
(b) (4)
(b) 
(4)
(b) 
(4)
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Page 6Table 2.3.P.8 -1. Summary of On -going Stability Studies 
Lot Number Stability Study 
Start Drug Product Batch Use Study Type Storag e Condition Data 
Available Study 
Status
Thermal Stress 30 2 C/ 65 5 % RH 1 month Complete
EM4965 
(Polymun 
Scientific/Pfizer, 
Puurs)February 2021 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C 3 month s On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 3month s On-going
Accelerated 5 3 C 3month s On-going
EL7834
(Polymun 
Scientific/Pfizer, 
PuursDecember 2020 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C Upright Vials 6month s On-going
-90 to -60 C Inverted Vials 6 months On-going
Accelerated -20 5 C Upright Vials 6month s On-going
-20 5 C Inverted Vials 6month s On-going
Accelerated 5 3 C Upright Vials 6month s On-going
5 3 C Inverted Vials 6month s On-going
Thermal 
CyclingThermal Cycling: 1 week at -90 to -
60°C  followed by 4 weeks at -20 ±5 
°C and then 4 weeks at 2 to 8 °C. and 1 
week at 25 ±2 °C/60 ±5% RH.10weeks Complete
Photostability Dark Control and Light Exposed Complete
EN1195
(mibe/Pfizer, 
Puurs)March 2021 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C 3 months On-going
Accelerated -20 5 C 3 months On-going
Accelerated 5 3 C 3 months On-going
Thermal 
CyclingThermal Cycling: Ultra frozen vials are 
placed at -20 ± 5 °C for 4 weeks and 
then moved to 2 to 8 °C for 12 weeks. 
Samples will be pulled for testing 
every 2 weeks throughout protocol.6weeks On-going
EK4242
(mibe/Pfizer, 
Puurs)December 2020 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 CUpright Vials 6 months On-going
-90 to -60 CInverted Vials 6 months On-going
Accelerated -20 5 CUpright Vials 6 months On-going
-20 5 CInverted Vials 6 months On-going
Accelerated 5 3 CUpright Vials 6 months On-going
5 3 CInverted Vials 6 months On-going
Thermal 
CyclingThermal Cycling: 1 week at -90 to -
60°C  followed by 4 weeks at 2 to 8 °C5 weeks Complete
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Page 7Table 2.3.P.8 -1. Summary of On -going Stability Studies 
Lot Number Stability Study 
Start Drug Product Batch Use Study Type Storag e Condition Data 
Available Study 
Status
EP2166
(Pfizer, Puurs)January 2021 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C 3months On-going
Accelerated -20 5 C 3months On-going
Accelerated 5 3 C 3months On-going
EL8713
(Pfizer, Puurs)January 2021 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C 3months On-going
Accelerated -20 5 C 3months On-going
Accelerated 5 3 C 3months On-going
EM6950
(Pfizer, Puurs)January 2021 Stability, Emergency Supplya, Process 
performance qualificationLong Term -90 to -60 C 3months On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 3months On-going
Accelerated 5 3 C 3months On-going
EL8723
(Pfizer, Puurs)January 2021 Stability, Clinical, Emergency Supplya, 
Process performance qualificationLong Term -90 to -60 C 3months On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 3months On-going
Accelerated 5 3 C 3months On-going
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal Stress 30 2 C/ 65 5 % RH 1 month Complete
Thermal 
CyclingThermal Cycling: Ultra frozen vials are 
placed at -20 ± 5 °C for 4 weeks and 
then moved to 2 to 8 °Cfor 12 weeks. 
Samples will be pulled for testing 
every 2 weeks throughout protocol.8weeks On-going
EL1491
(Pfizer, Puurs)December 2020 Stability, Clinical, Emergency Supplya, 
Process performance qualificationLong Term -90 to -60 CUpright Vials 6 months On-going
-90 to -60 CInverted Vials 6 months On-going
Accelerated -20 5 CUpright Vials 6 months On-going
-20 5 CInverted Vials 6 months On-going
Accelerated 5 3 CUpright Vials 6 months On-going
5 3 CInverted Vials 6 months On-going
EH9899
Pfizer, 
Kalamazoo)November 2020 Stability, Emergency SupplyaLong Term -90 to -60 C 6 months On-going
Accelerated -20 5 C 6 months On-going
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
EJ1688
(mibe/Pfizer, 
Puurs)November 2020 Stability, Emergency SupplyaLong Term -90 to -60 C 6 months On-going
Accelerated -20 5 C 6 months Complete
Accelerated 5 3 C 3 months Complete
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Page 8Table 2.3.P.8 -1. Summary of On -going Stability Studies 
Lot Number Stability Study 
Start Drug Product Batch Use Study Type Storag e Condition Data 
Available Study 
Status
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
EK1768
(Polymun 
Scientific/Pfizer, 
PuursNovember 2020 Stability, Emergency Supplya, Clinical 
inventoryLong Term -90 to -60 C 6 months On-going
Accelerated -20 5 C 6 months Complete
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal 
CyclingThermal Cycling: 2 weeks at -90 
to -60°C followed by 4 weeks at -20 ±
5 °C and then 8 weeks at 2 to 8 °C. 
Samples will be pulled for testing 
every 2 weeks throughout protocol.14weeks Complete
EJ1686
(Polymun 
Scientific/Pfizer, 
Puurs)November/
December 2 020Stability, Emergency Supplya, Clinical 
inventoryLong Term -90 to -60 C 6 months On-going
Accelerated -20 5 C 6 months Complete
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal 
CyclingThermal Cycling: 2 weeks at -90 
to -60°C followed by 4 weeks at -20 ±
5 °C and then 8 weeks at 2 to 8 °C. 
Samples will be pulled for testing 
every 2 weeks throughout protocol.14weeks Complete
EJ1685
(Polymun 
Scientific/Pfizer, 
Puurs)November 2020 Stability, Emergency Supplya, Clinical 
inventoryLong Term -90 to -60 C 6months On-going
Accelerated -60 to -30 C 6months On-going
Accelerated -20 5 C 6 months Complete
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
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Page 9Table 2.3.P.8 -1. Summary of On -going Stability Studies 
Lot Number Stability Study 
Start Drug Product Batch Use Study Type Storag e Condition Data 
Available Study 
Status
EJ0553
(Polymun 
Scientific/Pfizer, 
Puurs)November 2020 Stability, Emergency Supplya, Clinical 
inventoryLong Term -90 to -60 C 6months On-going
Accelerated -60 to -30 C 6months Complete
Accelerated -20 5 C 6 months Complete
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
EE8493
(Polymun 
Scientific/Pfizer, 
Puurs)September 2020 Stability, Emergency Supplya, Clinical 
inventoryLong Term -90 to -60 C 9months On-going
Accelerated -60 to -30 C 6month s Complete
Accelerated -20 5 C 6 months Complete
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal Stress 30 2 C/ 65 5 % RH 1 month Complete
EE8492
(Polymun 
Scientific/Pfizer, 
Puurs)September 2020 Stability, Emergency SupplyaLong Term -90 to -60 C 9months On-going
Accelerated -20 5 C 6 months Complete
Accelerated 5 3 C 3 months Complete
EE3813c
(Polymun 
Scientific/Pfizer, 
Puurs)August 2020 Stability, Clinical Long Term -70 10 C 6months Complete
Accelerated 5 3 C 3 months Complete
ED3938d
(Polymun 
Scientific/Pfizer, 
Puurs)August 2020 Stability, Clinical inventory Long Term -70 10 C 6months Complete
Accelerated 5 3 C 3 months Complete
BCV40720 -C
(Polymun
Scientific)August 2020 Stability, Clinical Long Term -70 10 C 6months Complete
Accelerated 5 3 C 3 months Complete
BCV40720 -A
(Polymun 
Scientific)August 2020 Stability, Clinical Long Term -70 10 C 6months Complete
Accelerated 5 3 C 3 months Complete
BCV40620 -E July 2020 Stability, Nonclinical Long Term -70 10 C 6months Complete
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Page 10Table 2.3.P.8 -1. Summary of On -going Stability Studies 
Lot Number Stability Study 
Start Drug Product Batch Use Study Type Storag e Condition Data 
Available Study 
Status
(Polymun 
Scientific)Accelerated 5 3 C 3 months Complete
BCV40620 -A
(Polymun 
Scientific)July 2020 Stability, Clinical Long Term -70 10 C 6months Complete
Accelerated 5 3 C 3 months Complete
BCV40420 -A
(Polymun 
Scientific)May 2020 Stability, Clinical Long Term -70 10 C 12months On-going
Accelerated -40 5 C 12months On-going
Accelerated 5 3 C 6 months Complete
Thermal Stress 25 2 C 4 months Complete
CoVVAC/270320
(Polymun 
Scientific)March 2020 Stability, non -clinical toxicologybLong Term -70 10 C 6 months Complete
Accelerated -40 5 C 3 months On-going
Accelerated 5 3 C 6 months Complete
a.   Emergency supply designation applies to US market.
b.   -40 °C study started in April 2020.
c.  This lot number is equivalent to BCV40820 -P
d.  This lot number is equivalent to BCV40720 -P.
RH = Relative Humidity
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Page 112.3.P.8.1.3. Protocol for Testing at the Long Term Condition (- 90 to -60 C)
Vials from drug product lots were stored at the recommended storage condition of -90 
to -60C. Testing is currently  being performed on thirteen PPQ lots and eight emergency  
supply  lots according to the protocol indicated in Table 2.3.P.8-2.
Vials from a subset of PPQ drug product lots were stored at the recommended storage 
condition of - 90 to -60C in the inverted vial orientation for comparison to storage at the 
upright vial orientation. Testing is currentl y being performed on 5 PPQ lots according to the 
protocol indicated in Table 2.3.P.8-3.
Additionally , testing at -70 ± 10 C is being performed on seven clinical lots and one 
non-clinical lot according to the protocol indicated in Table 2.3.P.8-4.
Table 2.3.P.8 -2. Protocol for BNT162b2 DP at the Long Term Condition of 
-90to -60°C
Analytical Procedure Test Intervalabe
Appearance (Visible) 0, 1Wf, 2W, 1M, 2M, 3M, 6M, 9M, 12M, 18M, 
24M Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry  (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Subvisible Particles 0, 3Md, 6M, 12M, 18M, 24M
Container Closure Integrity Test 0, 12M , 24Mc
Endotoxin 0, 12M, 24Mc
Sterility 0, 12M, 24M
a. Testing not performed at the 1W, 2W or 2M timepoint for lot EE8493, EJ0553, EL3249, EL3248, EL783, 
EK4242 and EL1491.
b. Testing not performed at the 2M time point for lots EH9899, EJ1688, EK1768 , EJ1686 and EJ1685. 
c. Being performed at 3 and 6M time points for EE8493, EE8492 and EJ0553.
d. Being performed at 3 time points for EE8493, EE8492 and EJ0553.
e. Testing not performed at the 1W or 2W timepoint for lot EN1195
f.  1W testing performed on lots EH9899, EJ1688, EK1768, EJ1686 and EJ1685
W = Week,   M = Month,   LNP = Lipid Nanoparticle
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Page 12Table 2.3.P.8 -3. Protocol for BNT162b2 DP at the Long Term Condition of -90 
to -60°CInverted Vial Orientation (Lots EL7834, EK4242, EL1491, 
EL3249 and EL3248)
Analytical Procedure Test Interval
Appearance (Visible) 0,6M, 12M, 18M, 24M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry  (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Subvisible Particles
Container Closure Integrity Test 0, 12M, 24M
Endotoxin
Sterility
W = Week,   M = Month,   LNP = Lipid Nanoparticle
Table 2.3.P.8 -4. Protocol forBNT162b2 Early Clinical and Non -clinical and 
Stability DP at the Long Term Condition of -70 ± 10°C
Analytical Procedure Test Interval (m onths)abcd
Appearance (Visible & Visible Particles ) 0, 1, 3, 6, 9, 12, 18, 24
LNP Size
LNP Polydispersity
RNA Encapsulation
RNA Content
ALC -0315 Content
ALC -0159 Content
DSPC Content
Cholesterol Content
RNA Integrity
Subvisible Particles 0, 12, 24
pH
Sterilityd0, 24
a. For BNT162b2 lot BCV40420 -A, a 4 month time point was added and tested
b. For BNT162b2 lot CoVVAC/270320, a 2 week and 2 month time point were tested. Study ends at 6 month time point.
c. Sterility testing not performed on non -clinical lot CoVVAC/270320.
d. For BNT162b2 lots BCV40620 -A, BCV40620 -E, BCV40720 -A, BCV40720 -C, BCV4 0720 -P & BCV40820 -P, only 
testing on 0, 1, 3 and 6 months is being performed. Sterility is being performed on 6M end point rather than 24M for this 
lot.
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Page 132.3.P.8.1.4. Protocol of Testing at the Accelerated Condition
To study  the effects of temporary  excursions above t he recommended storage temperature, 
drug product is being stored under the accelerated conditions of -60 to -30 C, -40± 
5C, -20 5 C and 5  3 C. 
Testing at - 60 to -30 C is currentl y being performed on five process performance 
qualification and three emergency suppl y lots according to the protocol indicated in 
Table 2.3.P.8-5.
Additionally , testing at -40  5 C is currently  being performed on one clinical lot and one 
non-clinical lot according to the protocol indicated in Table 2.3.P.8-6 .
Table 2.3.P.8 -5. Protocol for BNT162b2 DP at the Accelerated Condition of
-60to -30°C 
Analytical Procedure Test Interval ab
Appearance (Visible) 0, 1M, 3M, 6M, 12M, 18M, 24M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry  (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Subvisible Particlesc6M, 12M, 18M, 24M
a. Testing not performed at the 12M, 18M and 24M timepoint for emergency supply lot EE8493, EJ0553 and EJ1685. 
b. 6M, 12M, 18M and 24M only time points being performed on PPQ lots EN6199, EL9267, EM4965, EM6950, and 
EL8723 
c. Testing being performed on PPQ lots only as well as 6M time point for emergency supply lot EE8493
W = Week,   M = Month,   LNP = Lipid Nanoparticle
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Page 14Table 2.3.P.8 -6. Protocol for BNT162b2 DP at the Accelerated Cond ition of -40 
± 5°C
Analytical Procedure Test Interval (m onths)a
Appearance (Visible & Visible Particles ) 0, 1, 2, 3, 6, 9, 12, 18, 24
LNP Size
LNP Polydispersity
RNA Encapsulation
RNA Content
ALC -0315 Content
ALC -0159 Content
DSPC Content
Cholesterol Content
RNA Integrity
pH 0, 12, 24
Subvisible Particles
Sterilityb0, 24
a. For BNT162b2 lot BCV40420 -A, a 4 month time point was added and tested
b. For BNT162b2 lot CoVVAC/270320, bioburden is being tested at final time point
Testing at -20  5 C is currentl y being performed on thirteen process performance 
qualification lots and eight emergency  suppl y lots according to the protocol indicated in 
Table 2.3.P.8 -7. 
Vials from a subset of PPQ drug product lots were stored at the accelerated storage condition 
of -20 5 C in the inverted vial orientation for comparison to storage at the upright vial 
orientation . Testing is currentl y being performed on 5 PPQ lots according to the protocol 
indicated in Table 2.3.P.8 -8.. 
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Page 15Table 2.3.P.8 -7. Protocol for BNT162b2 DP at the Accelerated Condition of -20 
± 5°C 
Analytical Procedure Test Interval abc
Appearance (Visible) 0, 1W, 2W, 1M, 2M , 3M, 6M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Subvisible Particlesd0, 6M
a. 1W testing performed on emergency supply lot EE8492 only.
b. Testing not performed at the 1W, 2W or 2M time point for emergency supply lot EE8493, EJ0553, EJ1685, EJ1686, 
and EK1768 or process performance qualification lots EL1491, EK4242, EL7834, EL3248, an d EL3249. 
c. Testing not performed at the 1W or 2W time point for emergency supply lots EJ1688 and EH9899 and process 
performance qualification lot EN1195.
d. Testing not performed on emergency supply lots EJ1685, EJ1686 and EK1768.
W = Week,   M = Month,    LNP = Lipid Nanoparticle
Table 2.3.P.8 -8. Protocol for BNT162b2 DP at the Accelerated Condition of -20 ±
5°C Inverted Vial Orientation (Lots EL7834, EK4242, EL1491, EL3249 
and EL3248)
Analytical Procedure Test Interval
Appearance (Visible) 0, 1Ma, 6M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC-0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry  (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Subvisible Particles 0, 6M
a. 1 month testing not being performed on lot EL1491.
W = Week,   M = Month,   LNP = Lipid Nanoparticle
Testing at 5  3 C is currently  being performed on thirteen process performance 
qualification lots and eight emergency  suppl y lots according to the p rotocol indicated in 
Table 2.3.P.8 -9. 
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Page 16Vials from a subset of PPQ drug product lots were stored at the accelerated storage condition 
of 5 3 C in the inverted vial orientation for comparison to storage at the upright vial 
orien tation . Testing is currentl y being performed on 5 PPQ lots according to the protocol 
indicated in Table 2.3.P.8 -10. 
Additionally , testing at 5 3 C is currently being performed on seven clinical lots and one 
non-clinical lot according to the protocol indicated in Table 2.3.P.8-11
Table 2.3.P.8 -9. Protocol BNT162b2 DP at the Accelerated Condition of 5 ± 3°C 
Analytical Procedure Test Interval abcd
Appearance (Visible) 0, 1W, 2W, 1M, 2M, 3M, 6M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD ( ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Subvisible Particlese0, 6M
a. 1W testing performed on emergency supply lots EE8492, EJ1685, EJ1686, EK1768, EJ1688 and EH9899 
only.
b. 1M, 3M and 6M testing only performed on process performance qualification lots EL3249, EL3248, 
EL7834, EN1195, EK4242 and EL1491.
c. 2M and 6M testing not perfomed on emergency supply lots EH9899, EJ1688, EK1768, EJ1686, EJ1685. 
d. 1M and 3M testing only performed on emergency supply lots EJ0553 and EE8493. Emergency supply lot 
EE8492 ends at 3M time point.
e. Testing not performed on emergency supply lots EJ0553, EJ1685, EJ1686, EK1768, EJ1688 and EH9899. 
W = Week,   M = Month,   LNP = Lipid Nanoparticle
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Page 17Table 2.3.P.8 -10. Protocol for BNT162b2 DP at the Accelerated Condition of 5 ±
3°C Inverted Vial Orientation (Lots EL7834, EK4242, EL1491, EL3249 
and EL3248)
Analytical Procedure Test Interval
Appearance (Visible) 0, 1Ma, 6M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry  (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Subvisible Particles 0, 6M
a. 1 month testing not being performed on lot EL1491.
W = Week,   M = Month,   LNP = Lipid Nanoparticle
Table 2.3.P.8-11. Protocol for BNT162b2 DP Manufactured by Polymun Scientific 
at theAccelerated Condition of 5 ± 3 °C
Analytical Procedure Test Interval (m onths)abd
Appearance (Visible & Visible Particles ) 0, 1, 2, 3, 6
LNP Size
LNP Polydispersity
RNA Encapsulation
RNA Content
ALC -0315 Content
ALC -0159 Content
DSPC Content
Cholesterol Content
RNA Integrity
pH 0, 6c
a. For BNT162b2 lot BCV40420 -A, a 4 month time point was added and tested
b. For BNT162b2 lot CoVVAC/270320, testing was also performed at the 2 week and 6 week time points
c. pH testing not performed on non -clinical lot CoVVAC /270320
d. Study ends at the 3M time point for BNT162b2 lots BCV40820 -P, BCV40720 -P, BCV40720 -C, BCV40720 -A, 
BCV40620 -E and BCV40620 -A. pH performed on the final 3M time point.
2.3.P.8.1.5. Protocol for Testing at the Thermal Stress Conditions
To study  the effects of temporary  excursions above the recommended storage temperature, 
drug product is being stored under thermal stress conditions at 25 2 C/60 ± 5% RH and 
302 C/65% ± 5 RH and tested per the protocols indicated in Table 2.3.P.8 -12and
Table 2.3.P.8-13for emergency  suppl y lots (lot EE8493 only  placed on 30 2 C/65% ± 
5RH stabil ity and lots EE8493, EJ0553, EJ1685, EJ1 686,EK1768, EH9899 and EJ1688 
placed on 25 2C/60 ± 5% RH stability ). Process performance qualification lots EL 8723 
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Page 18and EL3248 were also each placed on formal stability  according to the protocols indicated in 
Table 2.3.P.8 -12andTable 2.3.P.8-13.
Additionally , testing at 25 2 Cis currently  being performed on one clinical lot according 
to the protocol indicated in Table 2.3.P.8 -14.
Table 2.3.P.8 -12. Protocol for BNT162b2 DP at the Thermal Stress Condition of
25 ± 2°C/60 ±5% RH
Analytical Procedure Test Intervalab
Appearance (Visible) 0, 1W, 2W, 1M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry(In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
a. 1W timepoint not performed on lot EE8493.
b. 3W testing also performed on PPQ lot EL3248
W = Week,   M = Month, LNP = Lipid Nanoparticle
Table 2.3.P.8-13. Protocol for BNT162b2 DP at the Thermal Stress Condition of
30 ± 2°C/65 ±5% RH
Analytical Procedure Test Intervalab
Appearance (Visible) 0, 1W, 2W, 1M
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry(In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
a. 1W timepoint not performed on lot EE8493. 
b. 3W testing also performed on PPQ lot EL3248
W = Week,   M = Month, LNP = Lipid Nanoparticle
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Page 19Table 2.3.P.8 -14. Protocol for BNT162b2 DP at the Thermal Stress 
Condition of25 ± 2°C
Analytical Procedure Test Interval (months)
Appearance (Visible & Visible Particles ) 0, 0.5, 1, 2, 3
LNP Size
LNP Polydispersity
RNA Encapsulation
RNA Content
ALC -0315 Content
ALC -0159 Content
DSPC Content
Cholesterol Content
RNA Integrity
pH 0, 3
Thermal cy cling studies are in progress for emergency  suppl y lots EK1768 and EJ1686 
according to the protocols indicated in Table 2.3.P.8 -15. Thermal cy cling studies are also in 
progress for process performance qualification lots according to the protocols indicated in 
Table 2.3.P.8 -16through Table 2.3.P.8 -19.
Table 2.3.P.8 -15. Protocol for BNT162b2 Emergency Supply DP Thermal Cycling 
Studies (Lots EK1768 and EJ1686)
Thermal Cycling Conditions:
-Day 0, all inventory placed at -90 to -60°C for 2 w eeks
-At T=2w eeks, samples pulled for testing and all other inventory transferred to - 20 ± 5°C for 4 w eeks. 
Samples will be pulled and testing will occur at the 2 and 4 week time points while at the -20 ± 5°C condition 
(week 4 and 6 of study).
-At T=6 w eeks, all remaining inventory will be transferred to 2 to 8°C for 8 w eeks. Samples will be pulled 
and testing will occur at the 2, 4, 6 & 8 w eek time points while at the 2 to 8°C condition (week 8, 10, 12 & 
14 of study).
Analytical Procedure Test Interval (weeks) a 
Appearance (Visible) 0, 2, 4, 6, 8, 10, 12, 14
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD ( ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
a. Thermal cycling being initiated for lots EK1768 and EJ1686
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Page 20Table 2.3.P.8 -16. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies (Lots 
EL8723, EN1195 and EL9266)
Thermal Cycling Conditions:
-Day 0, all inventory (previously frozen to ultra cold temperatures of -90 to -60°C after manufacture) placed 
at -20 ± 5°C for 4 w eeks
-At T=4 w eeks, samples pulled for testing and all other inventory transferred to 2 to 8°C for 12 w eeks. 
Analytical Procedure Test Interval (weeks)
Appearance (Visible) 0, 2, 4, 6, 8, 10, 12, 14, 16
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Table 2.3.P.8 -17. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies 
(LotEL3249)
Thermal Cycling Conditions:
-Day 0, all inventory placed at -90 to -60°C for 1 w eek
-At T=1 w eek, inventory transferred to -20 ± 5°C for 2 w eeks. 
-At T=3 w eeks, samples pulled for testing and all remaining inventory transferred to 2 to 8°C for 4 w eeks. 
-At T=7 w eeks, samples pulled for testing and all remaining inventory transferred to 25 ± 2°C/60 ± 5%RH 
for 1 w eek
Analytical Procedure Test Interval (weeks) 
Appearance (Visible) 0, 3, 4, 5, 6, 7, 8
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
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Page 21Table 2.3.P.8 -18. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies 
(LotEK4242)
Thermal Cycling Conditions:
-Day 0, all inventory placed at -90 to -60°C for 1 w eek
-At T=1 w eek, all other inventory transferred to 2 to 8°C for 4 w eeks, with testing occurring weekly while at 
2 to 8°C 
Analytical Procedure Test Interval (weeks) 
Appearance (Visible) 0, 2, 3, 4, 5
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
Table 2.3.P.8 -19. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies 
(LotEL7834)
Thermal Cycling Conditions:
-Day 0, all inventory placed at -90 to -60°C for 1 w eek
-At T=1 w eek, inventory transferred to -20 ± 5°C for 4 w eeks. 
-At T=5 w eeks, samples pulled for testing and all remaining inventory transferred to 2 to 8°C for 4 w eeks. 
-At T=9 w eeks, samples pulled for testing and all remaining inventory transferred to 25 ± 2°C/60 ± 5%RH 
for 1 w eek
Analytical Procedure Test Interval (weeks)
Appearance (Visible) 0, 3, 5, 6, 7, 8, 9, 10
Appearance (Visible Particulates)
Dynamic Light Scattering (LNP Size)
Dynamic Light Scattering (LNP Polydispersity)
Fluorescence Assay (RNA Encapsulation)
Fluorescence Assay (RNA Content)
HPLC -CAD (ALC -0315 Content)
HPLC -CAD (ALC -0159 Content)
HPLC -CAD (DSPC Content)
HPLC -CAD (Cholesterol Content)
Cell-based Flow  Cytom etry (In vitro expression)
Capillary Gel Electrophoresis (RNA Integrity)
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Page 222.3.P.8.1.6. Summary of Stability Data
2.3.P.8.1.6.1. Summary of Stability Data at the Long Term Storage Condition (-90
to -60C)
Results from stability  studies on BNT162b2 DP stored at the long term condition of -70 ± 
10C are currentl y available for seven clinical lots and one non -clinical lot of BNT162b2 
material . Results from stability  studies on BNT162b2 DP stored at the long term condition of 
-90 to -60 C are also currently  available for process performance qualifica tion and 
emergency  use lots . All results are provided in Section 3.2.P.8.3 Stability  Data -Long Term . 
Up to 12 months of data are currentl y available for the lots manufactured by Polymun 
Scientific stored at the long term condition of - 70 ± 10C. All data remained within the 
clinical acceptance criteria in place at the time of testing through the 12month time point for 
clinical lots BCV40420 -A, through the 6 month time point for clinical lots BCV40620- A, 
BCV40620 -E, BCV40720 -A, BCV40720 -C, BCV40720 -P and BCV40820- P and through 
the 6 month time point for non -clinical lot CoVVAC/270320 (study  has completed). Overall, 
the data indicate that there have been no significant changes in terms of quality , purity , or 
strength for the drug product.
Thirteen process performance qualification and eight emergency  lots of emergency  have 
been placed on formal stability  at the long term condition of -90 to -60 C, with up to 
9months of  data available at this time . Overall, the data generated to date indicate that there 
have been no significant changes in terms of quality , purit y, or strength for the drug product.   
Additionally , figures showing data generated to date have also been provided in Section 
3.2.P.8.3 Stability  Data -Long Term for the attributes of LNP po lydispersity , LNP size, RNA 
content, RNA encapsulation, lipid content, RNA integrit yand IVE and show that there are no 
significant trends that would impact the shelf life of the drug product through the 9 month 
time point when stored at the long term cond ition of -90 to -60 C. 
Inverted vial orientation stability studies have also been initiated on 5 PPQ lots with 6 month 
data available at this time. Results generated to date support that there is no change in the 
critical quality attributes of the drug product when the vials are stored either inverted or 
upright at the long term condition of -90 to -60 C.
2.3.P.8.1.7. Summary of Stability Data at the Accelerated Storage Condition
Accelerated -40 ± 5C Stability
Results from stability  studies on BNT162b2 DP stored at the accelerated condition of -40 ± 
5C are presented for one clinical lot and one non -clinical lot. Results are provided in 
Section 3.2.P.8.3 Stability  Data -Accelerated .  All data remained within the clinical 
acceptance criteria in place at t he time of testing through the 12month time point for clinical 
lot BCV40420-A, with the exception of , which was out of clinical 
acceptance criteria at the 12 month time point, and through the 3 month time point for non -
clinical lot CpVVAC /270320. As this is considered an accelerated storage condition, there is 
no impact that clinical lot BCV40420A was out of clinical acceptance criteria at the 12 
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Page 23month time point and t he -40 ± 5 C accelerated condition provides additional supportive 
data for the long -term storage under recommended condition and supports temporary  
temperature excursions from the recommended storage condition for up to six months .
Accelerated -60 to -30C Stability
Three lots of emergency  supply  drug product have been place d on formal stability  at the 
accelerated condition of -60 to -30 C, with up to six months of stability  data currently  
available at this time. Five performance qualification lots have also been enrolled in formal 
stability  programs at the - 60 to -30 C condition with release data available at this time.
Results are provided in Section 3.2.P.8.3 Stability  Data -Accelerated . All data generated to 
date remained within the acceptance criteria in place at the time of testing, as well as the 
proposed commer cial specifications, through the 6month time points and provide additional 
supportive data for the long -term storage under recommended condition.
Accelerated -20 ± 5C Stability
Results from stability  studies on BNT162b2 DP stored at the accelerated cond ition of -20 ± 
5C are presented for thirteen process performance qualification lots and eight emergency  
supply  lots. Results are provided in Section 3.2.P.8.3 Stability  Data -Accelerated . Up to six
months of data are currently  available for emergency  suppl y lots EE8492 and EE8493, with 
the others having up to 3 months of data currently  available. Up to three month sof data are 
available for the process performance qualification lots. 
All data gener ated to date remained within the stated specifications at the time of testing 
through the six month time point for emergency  supply  lot EE8492, EJ1685, EJ1686 and
EK1768. Lot EE8493 is out of the proposed commercial specification  
at the 3 month time point and lots EJ1688, EJ0553 and EH9899 are out of  
specification at the 6 month time point. 
Additionally , all data generated to date remained within the acceptance criteria in place at the 
time of testing, as well as the proposed commercial specifications, through the 6 month time 
point for process performance qualification lot EL7834, through the three month time point 
for process performance qualification lots EL 4965, EP2166, EL 8713, E M6950, EL 8723, 
EN6199, EL3249 (with  out of specification at the 6 month time point), EL 9267, 
EL3248 and EL1491 (with  out of specification at the 6 month time point), and 
through the 1 month time point for process performance qualification lots EN1195 (with 
 out of specification at the 2 and 3 month time points) andEK4242 (with out of 
specification results for  at the 3 month time point) .
All data generated to date for emergency  supply  and process performance qualification lots 
were within the proposed commercial specifications through at least the 1 month time point 
and the - 20 ± 5 C accelerated condition provides additional supportive data for the long -
term storage under recommended condition, supports temporary  temperatu re excursions from 
the recommended storage condition, and supports storage of the drug product for up to 
2weeks at -20 ± 5 C. Additionally , figures showing data generated to date have also been 
provided in Section 3.2.P.8.3 Stability  Data -Accelerated for the attributes of LNP 
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Page 24polydispersit y, LNP size, RNA content, RNA encapsulation, lipid content, RNA integrit yand 
IVEand show that there are no significant trends that would impact the additional shelf life 
claim of the drug product through the 2 week time point when stored at the -20 ± 5 C 
accelerated condition . 
Inverted vial orientation stability  studies have also been initiated on 5 PPQ lots with up to 6 
month data available at this time. Results generated to date support that there is no change in 
the critical qualit y attributes of the drug product when the vials are stored either inverted or 
upright at the -20 ± 5 C accelerated condition.
Accelerated 2 to 8 C Stability
Results from stability  studies on BNT162b2 DP stored at the accelerated condition of 
5 ± 3C are presented for seven clinical lots, one non- clinical lot, eight emergency  suppl y 
lots and thirteen process performance qualification lots. Results are presented in 
Section 3.2.P.8.3 Accelerated.
Up to six months of data are currentl y available for clinical and the non -clinical lots 
manufactured b y Polymun Scientific. Up to six months of data are also currently available 
for emergency  suppl y lots and for process performance qualification lots. 
was out of clinical specification at the 3, 4 and 6 month time points for 
clinical dru g product lot BCV40420 -A. The two month time point for clinical drug product 
lots BCV40720
-A and B CV40720- C were out of specification for , as well as 
the 3 months time point for clinical drug product lot BCV40420 -A (but within specifications 
at the 3 month time point for lot BCV40720 -A and at the 4 and 6 months time points for lot 
BCV4042 0-A).  was also out of the clinical specifications at the 3 month time 
point for clinical lot BCV40720 -P. Clinical lots BCV40620 -A, BCV40620- E and 
BCV40820 -P were within all specifications in place at the time of testing through the 
3month ti me point (studies have completed).
Up to 6months of data are currently  available for the emergency  suppl y and process 
performance qualification lots. All lots were within the stated specifications through at least 
the one month time point with the exception of EH9899 and EL3248. Lot EH9899 and Lot 
EL3248 were both manufactured using a   using the original process, 
 process revision. I n addition, lot EL3248 was released at  
, a level now below the proposed commercial specification , as discussed in 
Section 3.2.P.5.6 Justification of Specifications. Both of these lots expire in 2021 
(31MAR2021 for lot EH9899 and 30APR2021 for lot EL3248), prior to implementation of 
allowable storage at 5 ± 3°C for 31 day s. All lots that meet the proposed commercial 
specification for  and utilize the improved  process for , 
are within specification at all timepoints tested to date, which are 1M for some lots and 2M 
for other lots. In addition, Section P.5.6 Justification of Specifications presents the trend 
analysis data for drug product stability  lots that both meet the tightened release acceptance 
criterion and are manufactured using  either f rom an updated  process 
or from . These data demonstrate that drug product stored at 5 ±3°C for 
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Page 2531 day s meet the specification of greater than or equal to , based on the 
proposed  commercial acceptance criteria at drug product release. 
Additionally , figures showing data generated to date have also been provided in Section 
3.2.P.8.3 Stability  Data -Accelerated for the attributes of LNP poly dispersity , LNP size, 
RNA content, RNA encapsulation, lipid content, RNA integrit yand IVE. and show that there 
are no significant trends that would impact the additional shelf life claim of the drug product
through the 1 month time point when stored at the 5 ± 3 C accelerated condition . 
Inverted vial orientation stability studies have also been initiated on five PPQ lots with up to 
6 month data available at this time. Results generated to date support that there is no change 
in the critical quality  attributes of the drug product when the vials are stored either inverted 
or upright at the 5 ± 3 C accelerated condition.
2.3.P.8.1.8. Summary of Stability Data at the Thermal Stress Storage Conditions
To support short term temperature excursions, drug product was exposed to the thermal stress 
condition of 25 ± 2 °C. Results for one clinical lotispresented in Section 3.2.P.8.3 Thermal –
Stress and Cy cling . There is currentl y up to four months of available data. All data remained 
within the clinical acceptance criteria in place at the time of testing through the two weeks 
(half month) time point. At the onemonth time point and bey ond, drug product lot 
BCV40420 -A was out of specification for . Changes can be expected at 
stressed stability  conditions and does not impact the overall stabilit y strategy for this 
material.
Process performance qualification and emergency  supply  lots have been exposed to the 
thermal stress conditions of 25 ± 2 °C/60 ± 5% RH and 30 ± 2 °C/65 ± 5% RH. There is up 
to one month of available data for process performanc e qualification and emergency  suppl y 
lots presented in Section 3.2.P.8.3 Thermal –Stress and Cy cling.
2.3.P.8.1.9. Summary of Stability Data at the Thermal Cycling Storage Conditions
Two emergency  suppl y drug product lots, EK1768 and EJ1686 , have thermal cy cling studies 
initiated, with up to 14weeks of data available at this time. These studies are being 
performed to provide further support to the in -use period for the drug product. Results 
available through the 14week time points for emer gency  suppl y lots are presented in 
Section 3.2.P.8.3 Thermal – Stress and Cy cling. All data generated to date remained within 
the acceptance criteria in place at the time of testing through the 14week time points
(completion of the studies).
Additionally ,process performance qualification lots have thermal studies initated at this time 
to provide further support to the in -use period for the drug product. Results available to date 
for the process performance qualification lot thermal cy cling studies are pre sented in 
Section 3.2.P.8.3 Thermal – Stress and Cy cling. Lots EN1195, EL 9266 and EL 8723 are 
enrolled in the same thermal cy cling study  design and have up to 8 weeks of data available. 
Thermal cy cling study  for lot EL 3249 and EL7834 have completed with 8 w eeks of available 
data for EL3249 and 10 weeks for EL7834. Thermal cy cling study  for lot EK4242 has also 
completed, with up to 5 weeks of available stability  data. The  are 
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Page 26 over time for lot EK4242, however all data genera ted to date remained within 
the acceptance criteria in place at the time of testing through the completion of the study . All 
other thermal cy cling data also remained within the acceptance criteria in place at the time of 
testing through time points tested to date
2.3.P.8.1.10. Summary of Photostability Stability in Drug Product Vials
One process validation drug product lo t, EL8734, was subjected to the ICH photostability  
condition (option 2). D rug product vials were exposed to a light source that provides an 
overall illumination of not less than 1.2 million lux hours and an integrated ultraviolet energy  
of not less than 200 watt hours/m2, per I CH Q1B. Dark control vials were wrapped in 
aluminum foil to prevent exposure to light. All samples were stored inverted, at 2 to 8 °C for 
the duration of the stud y, as it is not feasible to maintain the samples at the intended storage 
condition of - 90 to -60 °C for this study  and the 2 to 8 °C condition is considered a worse 
case exposure condition.
Results for both the dark cont rol and the light exposed samples were within the specifications 
in place at the time of testing. There was a  
generated on the samples exposed to light as compared to the dark 
control samples, however that is not unexpected and all results generated were within the 
proposed commercial specifications.
2.3.P.8.1.11. Shelf Life and Conclusions
The shelf life for the BNT162b2 DP is 9months when stored at the recommended 
temperature of -90 to -60 C. Additionally , the stability  data generated to date on the 
emergency  use and process performance qualification lots also support an additional storage 
at -20 ± 5°C for up to 2 weeks as well as short term storage at 5± 3°C for up to one month 
(within the 6 month shelf life).
The initial shelf life is based on:
Up to 6 months of current available stability  data on emergency  supply  lots and 
process performance qualification lots at both the -90 to -60 °C intended storage 
condition, as well as the -20 ± 5°C storage condition, and up to 3 months at the 5± 
3°C storage condition.
Up to 12 months of current available stability  data on seven lots of clinical drug 
product .
Up to 6 months of current available stability  data on one lot of non- clinical drug 
product
Comprehensive comparability  assessments performed during development.
Understanding of the mRNA platform to support the shelf life .
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Page 27Additionally , the initial in -use period for the thawed, undiluted vial is room temperature for 
not more than 2 hours, which is further discussed in Section 3.2.P.2.6 Compatibility .
These stability  studies are currently  on-going and data from these studies will be used to 
confirm the initial shelf life of the BNT162b2 DP, as well as extend the shelf life based on 
the acceptability  of the data. 
The shelf life will be extended bey ond the 9months shelf life, as data allows, at the intended 
storage condition of -90 to -60 °C and/or bey ond the 2 weeks at the storage at -20 ± 5°C or 
5± 3°C storage for up to one month using real time stability  data on a minimum of three 
batches of commerciall y representative material.
2.3.P.8.2. Post Approval Stability Protocol and Stability Commitment
The commercial shelf life of the drug product will be established based on the I CH stability  
studies that are being carried out per protocols detailed in Section 3.2.P.8.1 Stability  
Summary  and Conclusions.
Post-approval, a minimum of one lot of BNT162b2 drug product will be enrolled in the 
commercial stability  program at the long term storage condition of - 90 to -60 C each year 
that drug product is manufactured. The protocol is provided in Table 2.3.P.8-20 for the long 
term storage conditions of - 90 to -60C.
Table 2.3.P.8 -20. Post-Approval Commercial Stability Protocol for Drug Product 
Stored at -90 to -60 °C
Analytical Procedure/ Quality Attribute Test Intervals (Months)a
Appearance (Visible) 0, 6, 12, 18, 24
Appearance (Visible Particulates)
pH
Subvisible Particulate Matter
Dynamic Light Scattering (DLS) LNP Size
LNP Polydispersity
Fluorescense Assay RNA Encapsulation
RNA Content
HPLC -CAD ALC -0315 Content
ALC -0159 Content
DSPC Content
Cholesterol Content
Cell-based Flow  Cytom etry In Vitro Expression
Capillary Gel Electrophoresis RNA Integrity
Container Closure Integrity Test Annually through end of shelf life
Sterility 0, End of shelf life
Endotoxin
a.Additional test intervals may be included for the purpose of extending expiry.
Abbreviations: LNP = Lipid Nanoparticle
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Page 282.3.P.8.3. Stability Data 
Stability  data for long term conditions, accelerated condition, thermal stress and phostability  
studies are provided in Section 3.2. P.8.3.Stability  Data .
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