Document text
BNT162b2
3.2.P.8.1. Stability Summary and Conclusion
PFIZER CONFIDENTIAL
Page 1TABLE OF CONTENTS
LIST OF TABLES ................................ ................................ ................................ ..................... 2
3.2.P.8.1. STABILITY SUMMARY AND CONCLUS ION ................................ .................... 4
3.2.P.8.1.1. Drug Product Shelf Life at Recommended Storage Temperature ................ 4
3.2.P.8.1.1.1. In-use Period of Drug Product ................................ .......................... 4
3.2.P.8.1.2. Stability Batches and Studies ................................ ................................ ........ 4
3.2.P.8.1.3. Protocol for Testing at the Long Term Condition ( -90 to -60C)............... 12
3.2.P.8.1.4. Protocol of Testing at the Accele rated Condition ................................ .......14
3.2.P.8.1.5. Protocol for Testing at the Thermal Stress Conditions ............................... 18
3.2.P.8.1.6. Summary of Stability Data ................................ ................................ .......... 23
3.2.P.8.1.6.1. Summary of Stability Data at the Long Term Storage
Condition ( -90 to -60C)................................ ................................ ................. 23
3.2.P.8.1.6.2. Summary of Stability Data at the Accelerated Storage
Condition ................................ ................................ ................................ .......... 23
3.2.P.8.1.6.3. Summary of Stability Data at the Thermal Stress Storage
Conditions ................................ ................................ ................................ ........ 27
3.2.P.8.1.6.4. Summary of Stability Data at the Thermal Cy cling Storage
Conditions ................................ ................................ ................................ ........ 28
3.2.P.8.1.6.5. Summary of Photostability Stability in Drug Product Vials .......... 29
3.2.P.8.1.7. Shelf L ife and Conclusions ................................ ................................ ......... 29
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Page 2LIST OF TABLES
Table 3.2.P.8.1-1. Summary of On -going Stability Studies ................................ ..................... 6
Table 3.2.P.8.1-2. Protocol for BNT162b2 DP at the L ong Term Condition of - 90 to -
60°C ................................ ................................ ................................ .......... 12
Table 3.2.P.8.1-3. 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) ...............................................................................13
Table 3.2.P.8.1-4. Protocol for BNT162b2 Earl y Clinical and Non -clinical and
Stability DP at the Long Term Condition of -70 ± 10°C..........................13
Table 3.2.P.8.1-5. Protocol for BNT162b2 DP at the Accelerated Condition of -60 to -
30°C ................................ ................................ ................................ .......... 14
Table 3.2.P.8.1-6. Protocol for BNT162b2 DP at the Accelerated Condition of -40 ±
5°C ................................ ................................ ................................ ............ 15
Table 3.2.P.8.1 -7.Protocol for BNT162b2 DP at the Accelerated Condition of -20 ±
5°C ................................ ................................ ................................ ............ 16
Table 3.2.P.8.1-8. 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) ................................ ................................ ............... 16
Table 3.2.P.8.1 -9. Protocol BNT162b2 DP at the Accelerated Condition of 5 ± 3°C........... 17
Table 3.2.P.8.1-10. Protocol for BNT162b2 DP at the Accelerated Condition of 5 ±3°C
Inverted Vial Orientation (L ots EL7834, EK4242, EL 1491, EL3249
and EL3248) ................................ ................................ ............................. 18
Table 3.2.P.8.1-11. Protocol for BNT162b2 DP Manufactured b y Polymun Scientific at
the Accelerated Condition of 5 ± 3°C................................ ....................... 18
Table 3.2.P.8.1 -12.Protocol for BNT162b2 DP at the Thermal Stress Condition of 25 ±
2°C/60 ± 5% RH................................ ................................ ....................... 19
Table 3.2.P.8.1-13. Protocol for BNT162b2 DP at the Thermal Stress Condition of 30 ±
2°C/65 ± 5% RH................................ ................................ ....................... 19
Table 3.2.P.8.1 -14.Protocol for BNT162b2 DP at the Thermal Stress Condition of 25 ±
2°C ................................ ................................ ................................ ............ 20
Table 3.2.P.8.1 -15.Protocol for BNT162b2 Emergency Suppl y DP Thermal Cycling
Studies (L ots EK1768 and EJ1686) ................................ .......................... 20
Table 3.2.P.8.1 -16.Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lots
EL8723, EN1195 and EL9266) ................................ ................................ 21
Table 3.2.P.8.1-17. Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lot
EL3249) ................................ ................................ ................................ ....21
Table 3.2.P.8.1 -18.Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lot
EK4242) ................................ ................................ ................................ ....22
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Page 3Table 3.2.P.8.1 -19.Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lot
EL7834) ................................ ................................ ................................ ....22
Table 3.2.P.8.1-20. Summary of Emergency Use and PPQ Drug Product Stability
Results for 5C Storage ................................ ................................ .............. 26
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Page 43.2.P.8. STABILIT Y
3.2.P.8.1. STABILITY SUMMARY AND CONCLUSION
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- clinica l 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 date has been perfo rmed 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.
3.2.P.8.1.1. Drug Product Shelf Life at Recommended Storage Temperature
The shelf life of the BNT162b2 is 9months when stored at the long term storage condition
of -90 to -60 ° C. The shelf life claim is based on up to 12months of available stabil ity data
forclinical and non -clinical drug product lots andup to 9month sof available stability data
for the emergency suppl yand process performance qualification lots, along with scientific
rationale and the understanding of the mRNA platform. All drug product lots enrolled in the
stability studies areconsidered to be predictive of the stability of the commercial materials
based on comprehensive comparability assessments performed during development.
Additionally , the stability data generated to date on the emergency suppl y 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 (wi thin the 6 month
shelf life). This is based on current available stability data for the accelerated conditions of -
20±5 °C and 5± 3°C on emergency suppl y and process performance qualification lots.
3.2.P.8.1.1.1. In-use P eriod of Drug Product
The initial in -use period fo r 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 been
initiated on both emergency use lots and PPQ lots in order to further support the in -use
period. Available d ata from these studies isprovided 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 .
3.2.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: Quality of Biotechnological Products, Stability Testing of Biotechnologic al/Biological
Products). To date, thirteen process performance qualification lots (with one additional PPQ
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Page 5lot being placed on a thermal cy cling stabilit y study onl y), eight emergency supply lots,
seven clinical lot sand 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 dr ug product studies) .
Both the clinical and non -clinical drug product lots manufactured b y Polymun Scientific
using the BNT162 b2 construct are considered to be predictive of the stability of the
commercial materials based on comprehens ive comparability assessments performed during
development. The emergency suppl y lots were manufactured using the commercial process.
Therefore, the clinical and non -clinical drug product lots manufactured b y Polymun
Scientific , as well as the emergency supply lots, areconsidered 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 in Table 3.2.P.8.1-1. At this time, stability studies are on- going. Data from these
studies will be used to confirm the shelf life of the drug product. Further information on
confirmation and extension of the drug product shelf life is discussed in Section 3.2.P.8.1.7
Shelf L ife and Conclusions.
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Page 6Table 3.2.P.8.1 -1. S ummary of On -going Stab ility Studies
LotNumber Stability Study
Start Drug Product Batch Use Study Type Storage 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)
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Page 7Table 3.2.P.8.1 -1. S ummary of On -going Stab ility Studies
LotNumber Stability Study
Start Drug Product Batch Use Study Type Storage 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 3month s On-going
Accelerated -20 5 C 3month s On-going
Accelerated 5 3 C 3month s 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 8Table 3.2.P.8.1 -1. S ummary of On -going Stab ility Studies
LotNumber Stability Study
Start Drug Product Batch Use Study Type Storage 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 6months On-going
Accelerated -20 5 C 6months 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 6months On-going
Accelerated -20 5 C 6months Complete
Accelerated 5 3 C 3 months Complete
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Page 9Table 3.2.P.8.1 -1. S ummary of On -going Stab ility Studies
LotNumber Stability Study
Start Drug Product Batch Use Study Type Storage 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 6months On-going
Accelerated -20 5 C 6months 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 2020Stability, Emergency Supplya, Clinical
inventoryLong Term -90 to -60 C 6months On-going
Accelerated -20 5 C 6months 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 6months Complete
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
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Page 10Table 3.2.P.8.1 -1. S ummary of On -going Stab ility Studies
LotNumber Stability Study
Start Drug Product Batch Use Study Type Storage 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 6months 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 11Table 3.2.P.8.1 -1. S ummary of On -going Stab ility Studies
LotNumber Stability Study
Start Drug Product Batch Use Study Type Storage 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 123.2.P.8.1.3. Protocol forTesting at the Long Term Condition (-90 to -60 C)
Vials from drug product lots were stored at t he recommended storage condition of -90
to -60C.Testing is currently being performed on thirteen PPQ lots and eight emergency
supply lots according to the protocol indicated in Table 3.2.P.8.1-2.
Vials from a subset of PPQ drug product lots were stored at the recommended storage
condition of - 90 to -60C in the inverted vial orientation for comparison to storage at the
upright vial orientation. Testing is currently being performed on 5 PPQ lots a ccording to the
protocol indicated in Table 3.2.P.8.1-3.
Additionally , testing at -70 ± 10 C is being performed on seven clinical lot sand one
non-clinical lot according to the protocol indicated inTable 3.2.P.8.1-4 .
Table 3.2.P.8.1 -2.Protocol for BNT162b2 DP at the Long Term Condition of -90
to -60°C
Analytical Procedure Test Interva labe
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 4,
EK4242 and EL1491 .
b. Testing not performed at the 2Mtime point forlotsEH9899, EJ1688 , EK1768, EJ1686 and EJ1685 .
c. Being performed at 3 Mand 6M time points for EE8493, EE8492 and EJ0553.
d. Being performed at 3 Mtime 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 13Table 3.2.P.8.1 -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 3.2.P.8.1 -4. Protocol for BNT162b2 Early Clinical andNon- clinical and
Stability DP at the Long Term Condition of -70 ± 10°C
Analytical Procedure Test Interval (m onths)abd
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
Sterilityc0, 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 lotsBCV40 620-A, BCV40620 -E, BCV40720 -A, BCV40720 -C, BCV40720 -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 143.2.P.8.1.4. Protocol of Testing at t he Accelerated Condition
To study the effects of temporary excursions above the recommended storage temperature,
drug product is being stored under the accelerated condition sof -60 to -30 C, -40 ± 5C, -20
5Cand 5 3 C.Stability data obtained from the accelerated storage condition sare also
presented in support of the shelf life claim.
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 3.2.P.8.1-5.
Additionally , testing at -40 5 C is currently being performed onone clinical lotandone
non-clinical lot according to the protocol indicated in Table 3.2.P.8.1-6 .
Table 3.2.P.8.1 -5.Protocol for BNT162b2 DP at the Accelerated Condition of -60
to -30°C
Analytical Procedure Test Intervalab
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 15Table 3.2.P.8.1 -6. Protocol for BNT162b2 DP at the Accelerated Condition 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 3.2.P.8.1 -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 3.2.P.8.1 -8.
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Page 16Table 3.2.P.8.1 -7.Protocol for BNT162b2 DP at the Accelerated Condition of -20 ±
5°C
Analytical Procedure Test Interva l 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 1 W, 2W or 2M time point for emergency supply lot EE8493, EJ0553 , EJ1685, EJ1686,
and EK1768 or process performance qualification lots EL1491, EK4242, EL7834, EL3248 , and 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 andEK1768.
W = Week, M = Month, LNP = Lipid Nanoparticle
Table 3.2.P.8.1 -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
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PFIZER CONFIDENTIAL
Page 17Testing at 5 3 C is currently being performed on thirteen process performance
qualification lots and eight emergency suppl y lots according to the protocol indicated in
Table 3.2.P.8.1 -9.
Vials 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 3.2.P.8.1 -10.
Additionally , testing at 5 3 C is currently being performed on seven clinical lot sand one
non-clinical lot according to the protocol indicated in Table 3.2.P.8.1-11.
Table 3.2.P.8.1 -9.Protocol BNT162b2 DP at the Accelerated Condition of 5 ± 3°C
Analytical Procedure Test Intervalabcd
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 suppl y 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 = We ek, M = Month, LNP = Lipid Nanoparticle
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Page 18Table 3.2.P.8.1 -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 3.2.P.8.1 -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 lot sBCV40820 -P, BCV40720 -P, BCV40720 -C, BCV40720 -A,
BCV40620 -E and BCV40620 -A. pH performed on the final 3M time point.
3.2.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 isbeingstored under thermal stress conditions at 252C/60 ± 5% RH and
302 C/65% ± 5 RH and tested per the protocols indicated in Table 3.2.P.8.1 -12and
Table 3.2.P.8.1-13 for emergency suppl y lots (lot EE8493 only placed on 30 2 C/65% ±
5RH stability and lots EE8493, EJ0553 , EJ1685 , EJ1686 ,EK1768, EH9899 and EJ1688
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Page 19placed on 25 2C/60 ± 5% RH stability ).Process performance qualification lotsEL8723
and EL3248 were also each placed on formal stability according to the protocol s indicated in
Table 3.2.P.8.1-12 andTable 3.2.P.8.1-13.
Additionally , testing at 25 2 Cis currently being performed on one clinical lot according
to the protocol indicated in Table 3.2.P.8.1-14.
Table 3.2.P.8.1 -12.Protocol for BNT162b2 DP at the Thermal Stress Condition of
25 ± 2 °C/60 ±5% RH
Analytical Procedure Test Intervalab
Appearance (V isible) 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 3.2.P.8.1 -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 20Table 3.2.P.8.1 -14.Protocol for BNT162b2 DP at the Thermal Stress Condition of
25± 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 3.2.P.8.1-15. Thermal cy cling studies are also in
progress for process performance qualification lots according to the protocols indicated in
Table 3.2.P.8.1 -16through Table 3.2.P.8.1-19.
Table 3.2.P.8.1 -15. Protocol for BNT162b2 Emergency Supply DP Thermal Cycl ing
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 21Table 3.2.P.8.1 -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 3.2.P.8.1 -17. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies (Lot
EL3249)
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 22Table 3.2.P.8.1 -18. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies (Lot
EK4242)
Thermal Cycling Conditions:
-Day 0, all inventory placed at -90 to -60°C for 1week
-At T= 1 week, 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 3.2.P.8.1 -19. Protocol for BNT162b2 PPQ DP Thermal Cycling Studies (Lot
EL7834)
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 testi ng 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 233.2.P.8.1.6. Summary of Stability Data
3.2.P.8.1.6.1. Summary of Stability Data at the Long Term Storage Condition (-90
to-60C)
Results from stability studies on BNT162b2 DP stored at the long term condition of -70±
10C are currentl y available for seven clinical lotsandone non- clinical lot of BNT162b 2
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 qualification and
emergency use lot s.All results are provided in Section 3.2.P.8.3 Stability Data -Long -Term .
Up to 12month sof data are currentl yavailable for thelotsmanufactured by Polymun
Scientific stored at the long term condition of -70 ± 10C. All data remained within the
clinical acceptance criteria in place at the time of testing through the 12month time point for
clinical lot BCV40420 -A(study still on -going) ,through the 6month time point for clinical
lots BCV40620 -A, BCV40620 -E, BCV40720 -A, BCV40720 -C, BCV40720-P and
BCV40820 -P (all studies have completed )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 , purit y, or strength for the drug product.
Thirteen process performan ce 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 for two emergency suppl y lots. All other
PPQ/emergency suppl y lots have up to 6 months of current available stability data .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
todate have also been provided in Section 3.2.P.8.3 Stability Data -Long Term 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
shelf life of the drug product through the 9 month time point when stored at the long term
condition 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.
3.2.P.8.1.6.2. Summary of St ability Data at the Accelerated Storage Condition
Accelerated -40 ± 5C Stability
Results from stability studies on BNT162b2 DP stored at the accelerated condition of -40±
5C are presented for one clinical lotand 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 the time of testing through the twelve month time point for
clinical lot BCV40420A , 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 -
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Page 24clinical lot C oVVAC/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
month 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 -30C Stability
Three lotsof emergency supply drug product have been placed on formal stability at the
accelerated condition of - 60 to -30 C, with up to sixmonth sof 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 Accelerated . 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 sfor all lots and provide additional
supportive data for the long-term storage under recommended condition.
Accelerated -20 ± 5C Stability
Results from stability studies on BNT162b2 DP stored at the accelerated condition of -20 ±
5C are presented for thirteen process performance qualification lots and eight emergency
supply lots. Results are provided in Section 3.2.P.8.3 Accelerated . Up to six months of data
are currentl y available for the emergency suppl y lots and for the process performance
qualification lots.
All data generated to date remained within the acceptance criteria in place at the time of
testing through the six month time point for emergency suppl y lot EE8492, EJ1685, EJ1686
andEK1768. 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, EM6950, 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 (w ith
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 withi n 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 temperature excursions f rom
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
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Page 25provided in Section 3.2.P.8.3 Stability Data -Accelerated for the attribut es of LNP
polydispersit 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 ± 3C are presented for seven clinical lots, one non-clinical lot, eight emergency suppl y
lotsand thirteen process performance qualification lots. Results are presented in
Section 3.2.P.8.3 Accelerated .
Up to sixmonths of data are currentl y available f or clinical and the non-clinical lots
manufactured b y Polymun Scientific. Up to six month sof data are also currently available
for emergency suppl y lots and for process performance qualification lots.
was out of clinical specification at the 3 , 4and 6 month time point sfor
clinical dru g product lot BCV40420-A. The twomonth time point for clinical drug product
lots BCV40720- A and BCV40720- C were out of specification for , as well as
the 3 month stime 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 month stime points for lot
BCV40420 -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 time point (studies have completed).
Up to 6months of data are currently available for the emergency suppl y and process
performance qualification lots. The stability results at the accelerated condition of 5 ±3°C
are summarized in Table 3.2.P.8.1-20. All lots were within the stated specifications through
at least the one month time point with the exception of EH9899 and EL3248. L ot EH9899
and L ot EL3248 were both manufactured using a using the original
process, process revision. I n addition, lot EL 3248 was released at
, a level now below the proposed commercial specification , as discussed in
Section 3.2.P.5.6 Justification of Specification(s). Both of these lots expire in 2021
(31MAR2021 for lot EH9899 and 30APR2021 for lot EL 3248), 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 Specification(s) presents the trend
analysis data for drug product stability lots that both meet the tightened release acceptance
criterion and are manufactured using either from an updated
process
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Page 26or from . These data demonstrate th at drug product stored at 5 ± 3°C for
31 day s meet the specification of greater than or equal to based on the
proposed commercial acceptance criteria at drug product release.
Table 3.2.P.8.1 -20.Summary of Em ergency Use and PPQ Drug Product Stability
Results for 5C Storage
Lot # ALC -0315 Lipid Source RNA Integrity at
Release (% )Available 5 °C Data 5 °C Data Summary
EE8492 3 months (complete) Within specification
through 1M
EE8493 3 months (complete) Within specification
through 1M
EJ0553 3 months (complete) Within specification
throu gh 1M
EJ1685 3 months (complete) Within specification
through 3M
EJ1686 3 months (complete) Within specification
through 1M
EK1768 3 months (complete) Within specification
through 3M
EJ1688 3 months (complete) Within specification
through 3M
EH9899 3 months (complete) out of
specification at 2W and 3M
EL1491 6M(on-going) Within specification
through 3M
EL8723 3M(on-going) Within specification
through 3M
EM6950 3M(on-going) Within specification
through 3M
EL8713 3M(on-going) Within specification
through 2M
EP2166 3M(on-going) Within specification
through 3M
EK4242 6M(on-going) Within specification
through 3Ma
EN1195 3M(on-going) Within specification
through 3M
EL7834 6M(on-going) Within specification
through 3M
EM4965 3M(on-going) Within specification
through 3M
EL3248 6M(on-going) out of
specification at 1M and 3M
EL9267 3M(on-going) Within specification
through 2M
EL3249 6M(on-going) Within specification
through 1M
EN6199 3M(on-going) Within specification
through 2M
a. Some d ata fro
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Page 27 results were out of specification at the 3 month time point for lot EE8493
(and the 1 month time point was not reported due to an investigation that led to the testing for
the time point being invalidated, however as all other lots were within specifications through
at least the one month time point for there is no overall impact on the
stability program). over time for emergency supply lots
EE8492, EE8493, EJ0553, EJ1685, EK1768, EJ 1688 and EH9899 with lot EJ0553 , EJ1686
and EH9899 out of specification at the 3 month time point. PPQ lots EN6199, EL 9267,
EL3249, EL8713 were out of specification at the 3M time point for and lots
EL7834 and EL1491 were out of specification at the 6 month time point for PPQ
lots EL 1491 and EL3249 were also out of specification at the 6 month time point for
Changes can be expected at accelerated stability conditions and does not impact the overall
stability strategy for this material. The 5 ± 3 C accelerated condition provides additional
supportive data for the long -term storage under recommended condition , supports storage of
the drug product for up to 1 month at 5 ± 3 C andsupports temporary temperature
excursions from the recommended storage condition for up to one month.
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.
3.2.P.8.1.6.3. 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 month sof available data .All data remained
within the clinical acceptance criteria in place at the time of testing through the twoweek s
(half month) time point . At the one month 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 stability strategy for this
material.
Process performance qualification and e mergency supply lots have been exposed to the
thermal stress condition sof 25 ± 2 °C/60 ± 5% RH and 30 ± 2 °C/65 ± 5% RH. There is up
toone month of available data for process performance qualification and emergency suppl y
lotspresented in Section 3.2.P.8.3 Thermal – Stress and Cy cling .
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Page 28
Changes can be expected at stressed stability conditions and does not
impact the overall stability strategy for this material. This stability data provides further
support to the current in -use period stability .
ll other attributes remained within the specifications in place at the time of
testing. Changes can be expected at stressed stability conditions and does not impact the
overall stability strategy for this material. This stability data provides further support to the
current in- use period stability .
3.2.P.8.1.6.4. 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
that have completed with 14weeks of data available. These studies were performed to
provide further support to the in -use period for the drug product. Results available through
the 14 week time points for emergency 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 cycling studies are presented in
Section 3.2.P.8.3 Thermal – Stress and Cy cling . Lots EN1195, EL 9266 and EL8723 are
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Page 29enrolled 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 weeks 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.
all data generated 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.
3.2.P.8.1.6.5. Sum mary of Photostability Stability in Drug Product Vials
One process validation drug product lot, EL8734, wassubjected to the ICH photostability
condition (option 2). Drug product vials w ereexposed 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
theduration 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 control and the lig ht exposed samples were within the specifications
in place at the time of testing.
all results generated were within the
proposed commercial specifications.
3.2.P.8.1.7. 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 9 m onth shelf life).
The shelf life is based on:
Up to 9months 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 up to 6 months of data at the -20 ± 5°C storage condition and at
the 5± 3°C storage condition.
Up to 12months 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.
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Page 30Understanding of the mRNA platform to support the shelf life .
Additionally , the initial in -use period for the thawed, undiluted vial is 5 days at 2-8 °C
followed b y storage at room temperat ure for not more than 2 hours, which is further
discussed i n Section 3.2.P. 2.6 Compatability .
These stability studies are currently on-going and data from these studies will be used to
confirm the 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 9 months shelf life, as data allows, at the intended
storage condition of -90 to -60 °C and/or bey ond the 2 weeks at the stora ge 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.
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