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 ................................ .................... 3
3.2.P.8.1.1. Drug Product Shelf Life at Recommended Storage Temperature ................ 3
3.2.P.8.1.1.1. I n-use Period of Drug Product ................................ .......................... 3
3.2.P.8.1.2. Stability Batches and Studies ................................ ................................ ........ 3
3.2.P.8.1.3. Protocol for Testing at the Long Term Condition ( -90 to -60 C)............. 10
3.2.P.8.1.4. Protocol of Testing at the Accelerated Condition ................................ .......11
3.2.P.8.1.5. Protocol for Testing at the Thermal Stress Conditions ............................... 15
3.2.P.8.1.6. Summary of Stability Data ................................ ................................ .......... 19
3.2.P.8.1.6.1. Summary of Stability Data at the Long Ter m Storage
Condition ( -90 to -60 C)................................ ................................ ............... 19
3.2.P.8.1.6.2. Summary of Stability Data at the Accelerated Storage
Condition ................................ ................................ ................................ .......... 20
3.2.P.8.1.6.3. Summary of Stability Data at the Thermal Stress Storage
Conditions ................................ ................................ ................................ ........ 22
3.2.P.8.1.6.4. Summary of Stability Data at the Thermal Cy cling Storage
Conditions ................................ ................................ ................................ ........ 23
3.2.P.8.1.6.5. Summary of Photostability Stability in Drug Product Vials .......... 24
3.2.P.8.1.7. Shelf L ife and Conclusions ................................ ................................ ......... 24
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Page 2LIST OF TABLES
Table 3.2.P.8.1-1. Summary of On -going Stability Studies ................................ ..................... 5
Table 3.2.P.8.1-2. Protocol for BNT162b2 DP at the L ong Term Condition of - 90 to -
60°C ................................ ................................ ................................ .......... 10
Table 3.2.P.8.1-3. Protocol for BNT162b2 Earl y Clinical and Non -clinical and
Stability DP at the Long Term Condition of -70 ± 10°C .......................... 11
Table 3.2.P.8.1-4. Protocol for BNT162b2 DP at the Accelerated Condition of -60 to -
30°C ................................ ................................ ................................ .......... 12
Table 3.2.P.8.1-5. Protocol for BNT162b2 DP at the Accelerated Condition of -40 ±
5°C ................................ ................................ ................................ ............ 12
Table 3.2.P.8.1 -6.Protocol for BNT162b2 DP at the Accelerated Condition of -20 ±
5°C ................................ ................................ ................................ ............ 13
Table 3.2.P.8.1 -7. Protocol BNT162b2 DP at the Accelerated Condition of 5 ± 3°C........... 14
Table 3.2.P.8.1-8. Protocol for BNT162b2 DP Manufactured b y Polymun Scientific at
the Accelerated Condition of 5 ± 3°C................................ ....................... 14
Table 3.2.P.8.1 -9.Protocol for BNT162b2 DP at the Thermal Stress Condition of 25 ±
2°C/60 ± 5% RH ................................ ................................ ....................... 15
Table 3.2.P.8.1-10. Protocol for BNT162b2 DP at the Thermal Stress Condition of 30 ±
2°C/65 ± 5% RH ................................ ................................ ....................... 16
Table 3.2.P.8.1 -11.Protocol for BNT162b2 DP at the Thermal Stress Condition of 25 ±
2°C ................................ ................................ ................................ ............ 16
Table 3.2.P.8.1 -12.Protocol for BNT162b2 Emergency Suppl y DP Th ermal Cy cling
Studies (L ots EK1768 and EJ1686) ................................ .......................... 17
Table 3.2.P.8.1 -13.Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lots
EL8723, EN1195 and EL9266) ................................ ................................ 17
Table 3.2.P.8.1 -14.Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lot
EL3249) ................................ ................................ ................................ ....18
Table 3.2.P.8.1 -15.Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lot
EK4242) ................................ ................................ ................................ ....18
Table 3.2.P.8.1 -16.Protocol for BNT162b2 PPQ DP Thermal Cy cling Studies (Lot
EL7834) ................................ ................................ ................................ ....19
Table 3.2.P.8.1-17. Summary of Emergency Use and PPQ Drug Product Stability
Results for 5C Storage ................................ ................................ .............. 22
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Page 33.2.P.8. STABILIT Y
3.2.P.8.1. STABILITY SUMMARY AND CONCLUSION
The initial commercial shelf life of the BNT162b2 drug product is 6 months when stored at
the intended storage condition of -90 to -60 °C. The initial shelf life is based on the currentl y
available data from stabi lity studies utilizing material from emergency supply ,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
suppor t 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 6 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 performed using anal ytical methodology and phase appropriate
specifications in place at time of testing. The analy tical procedures used in the s tability
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 initial shelf life of the BNT162b2 is 6 months when stored at the long term storage
condition of -90 to -60 ° C. The shelf life claim is based on up to 9months of available
stability data for clinical and non -clinical drug product lots andup to 6month 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
lotsenrolled in the stability studies areconsidered to be predictive of the stability of the
commercial materials ba sed 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 fo r 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). 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 performanc e qualification lots.
3.2.P.8.1.1.1. In-use P eriod 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 been
initiated on bothemergency 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 Biotechno logical Products, Stability Testing of Biotechnological/Biological
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Page 4Products). 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 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 dru g 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 sta bility of the
commercial materials based on comprehensive 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 manufactu red 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 initial 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 Life and Conclusions .
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Page 5Table 3.2.P.8.1 -1. S ummary of On -going Stability Studies
LotNumber Stability Study Start Drug Product
Batch UseStudy Type Storage Condition Data
Available Study
Status
EN6199
(Pfizer, Kalamazoo,
Line Stability, Emergency
Supplya, Process
performance qualificationFebruary 2021 Long Term -90 to -60 C 1 month On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 1 month On-going
Accelerated 5 3 C 1 month On-going
EL3249
(Pfizer, Kalamazoo,
Line Stability, Clinical,
Emergency Supplya,
Process performance
qualificationDecember 2020 Long 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 Cycling Thermal 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 Stability, Emergency
Supplya, Process
performance qualificationFebruary 2021 Thermal Cycling Thermal 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.8weeks On-going
EL9267
(Pfizer, Kalamazoo,
Line Stability, Emergency
Supplya, Process
performance qualificationJanuary 2021 Long Term -90 to -60 C 1 month On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 1 month On-going
Accelerated 5 3 C 1 month On-going
EL3248
(Pfizer, Kalamazoo, Line Stability, Clinical,
Emergency Supplya,
Process performance
qualificationDecember 2020 Long 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 Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal Stress 30 2 C/ 65 5 % RH 1 month Complete
EM4965
(Polymun
Scientific/Pfizer, Puurs)Stability, Emergency
Supplya, Process
performance qualificationFebruary 2021 Long Term -90 to -60 C 1 month On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 1 month On-going
Accelerated 5 3 C 1 month On-going
EL7834
(Polymun
Scientific/Pfizer, PuursDecember 2020 Stability,
Emergency
Supplya, Process Long 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
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(b)
(4)
(b)
(4)
(b)
(4)
(b)
(4)
(b)
(4)
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Page 6Table 3.2.P.8.1 -1. S ummary of On -going Stability Studies
LotNumber Stability Study Start Drug Product
Batch UseStudy Type Storage Condition Data
Available Study
Status
performance
qualificationThermal Cycling Thermal 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)Stability, Emergency
Supplya, Process
performance qualificationMarch 2021 Long Term -90 to -60 C 1 month On-going
Accelerated -20 5 C 1 month On-going
Accelerated 5 3 C 1 month On-going
Thermal Cycling Thermal 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)Stability, Emergency
Supplya, Process
performance qualificationDecember 2020 Long 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 Cycling Thermal Cycling: 1 week at -90 to -
60°C followed by 4 weeks at 2 to 8 °C5 weeks Complete
EP2166
(Pfizer, Puurs)Stability, Emergency
Supplya, Process
performance qualificationJanuary 2021 Long Term -90 to -60 C 2 months On-going
Accelerated -20 5 C 2 months On-going
Accelerated 5 3 C 2 months On-going
EL8713
(Pfizer, Puurs)Stability, Emergency
Supplya, Process
performance qualificationJanuary 2021 Long Term -90 to -60 C 2 months On-going
Accelerated -20 5 C 2 months On-going
Accelerated 5 3 C 2 months On-going
EM6950
(Pfizer, Puurs)Stability, Emergency
Supplya, Process
performance qualificationJanuary 2021 Long Term -90 to -60 C 2 months On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 2 months On-going
Accelerated 5 3 C 2 months On-going
EL8723
(Pfizer, Puurs)Stability, Clinical,
Emergency Supplya,
Process performance
qualificationJanuary 2021 Long Term -90 to -60 C 2 months On-going
Accelerated -60 to -30 C Release On-going
Accelerated -20 5 C 2 months On-going
Accelerated 5 3 C 2 months On-going
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal Stress 30 2 C/ 65 5 % RH 1 month Complete
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Page 7Table 3.2.P.8.1 -1. S ummary of On -going Stability Studies
LotNumber Stability Study Start Drug Product
Batch UseStudy Type Storage Condition Data
Available Study
Status
Thermal Cycling Thermal 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)Stability, Emergency
Supplya, Clinical, Process
performance qualificationDecember 2020 Long 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
EH9899
Pfizer, Kalamazoo)Stability, Emergency
SupplyaNovember 2020 Long Term -90 to -60 C 3 months On-going
Accelerated -20 5 C 3 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)Stability, Emergency
SupplyaNovember 2020 Long Term -90 to -60 C 3 months On-going
Accelerated -20 5 C 3 months On-going
Accelerated 5 3 C 3 months Complete
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 3 months On-going
Accelerated -20 5 C 3 months On-going
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal Cycling Thermal 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 3 months On-going
Accelerated -20 5 C 3 months On-going
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
Thermal Cycling Thermal 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 November 2020 Long Term -90 to -60 C 3 months On-going
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Page 8Table 3.2.P.8.1 -1. S ummary of On -going Stability Studies
LotNumber Stability Study Start Drug Product
Batch UseStudy Type Storage Condition Data
Available Study
Status
(Polymun
Scientific/Pfizer, Puurs)Stability,
Emergency
Supplya, Clinical
inventoryAccelerated -60 to -30 C 3 months On-going
Accelerated -20 5 C 3 months On-going
Accelerated 5 3 C 3 months Complete
Thermal Stress 25 2 C/ 60 5 % RH 1 month Complete
EJ0553
(Polymun
Scientific/Pfizer, Puurs)November 2020 Stability,
Emergency
Supplya, Clinical
inventoryLong Term -90 to -60 C 3 months On-going
Accelerated -60 to -30 C 3 months On-going
Accelerated -20 5 C 3 months On-going
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 6months On-going
Accelerated -60 to -30 C 6month s 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 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 6months 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
inventoryLong 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 August 2020 Stability, Clinical Long Term -70 10 C 6months Complete
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Page 9Table 3.2.P.8.1 -1. S ummary of On -going Stability Studies
LotNumber Stability Study Start Drug Product
Batch UseStudy Type Storage Condition Data
Available Study
Status
(Polymun Scientific) Accelerated 5 3 C 3 months Complete
BCV40620 -E
(Polymun Scientific)July 2020 Stability,
NonclinicalLong Term -70 10 C 6months Complete
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 9 months On-going
Accelerated -40 5 C 9 months 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 103.2.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.
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.8.1-3.
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 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 11Table 3.2.P.8.1 -3. 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 lotsBCV40620 -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.
3.2.P.8.1.4. Protocol of Testing at the 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 lotsaccordi ng to the protocol indicated in
Table 3.2.P.8.1-4 .
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.8.1-5.
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Page 12Table 3.2.P.8.1 -4.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
Table 3.2.P.8.1 -5. 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 -6.
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Page 13Table 3.2.P.8.1 -6.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 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 , 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
Testing 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 .8.1-7.
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.8.1-8.
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Page 14Table 3.2.P .8.1-7.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 test ing 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
Table 3.2.P.8.1 -8. 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.
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Page 153.2.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 -9and
Table 3.2.P.8.1-10 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
placed on 25 2C/60 ± 5% RH stability ).Process performance qualification lotsEL8723
and EL3248 were also each placed on formal stability according to the protocols indicated in
Table 3.2.P.8.1-9 andTable 3.2.P.8.1-10.
Additionally , testing at 25 2 Cis currently being performed on one clinical lot according
to the protocol indicated in Table 3.2.P.8.1-11.
Table 3.2.P.8.1 -9.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
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Page 16Table 3.2.P.8.1 -10.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
Table 3.2.P.8.1 -11.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- 12.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 -13through Table 3.2.P.8.1-16.
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Page 17Table 3.2.P.8.1 -12. 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 s tudy).
-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
Table 3.2.P.8.1 -13. 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)
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Page 18Table 3.2.P.8.1 -14. 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)
Table 3.2.P.8.1 -15. 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 weeks, 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)
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Page 19Table 3.2.P.8.1 -16. 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 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)
3.2.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 Long-Term .
Up to 9month sof data are currently available for thelotsmanufactured b y 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 nine month time point
for clinical lot sBCV40420-A, through the 6month time point for clinical lot s 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
6months 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.
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Page 203.2.P.8.1.6.2. Summary of Stability Data at the Accelerated Storage Condition
Accelerated -40 ± 5C Stability
Results from stability studies on BNT162b2 DPstored 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 Accelerated .All data remained within the clinical acceptance criteria in
place at the time of tes tingthrough the nine month time point for clinical lot BCV40420 -A
and through the 3 month time point for non- clinical lot CpVVAC/270320. The - 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.
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 for one lot and 3 months of available data for the other two. Five
performance qualification lots have also been enrolled in formal stability programs at the -60
to -30 C conditi on 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 points 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 sixmonth sof data
arecurrentl y available for emergency suppl y lots EE8492 and EE8493 , with the others
having up to 3 months of data currentl y available. Up to three month sof data are available
for the process performance qualification lots. All data generated to date were also within the
stated specifications at the accelerated condition of -20 ± 5 °C through at least the 1 month
time point. L ot EE8493 was out of specification at the 3 and 6 month time points and lot
EK4242 was out of specification at the 3 month time point for at the accelerated -
20 ± 5°C condition. The -20 ± 5 C accelerated condition provides additional supportive data
for the long -term storage under recommended condition ,supports temporary temperature
excursions from the recommended storage condition , and supports storage of the drug
product for up to 1 month at-20 ± 5 C.
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Page 21Accelerated 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 for clinical and th enon -clinical lots
manufactured b y Polymun Scientific. Up to t hree month sof data are also currentl y 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 3 months of data are currently available for the emergency suppl y and process
performance qualification lots. The stability results at the accelerate d condition of 5 ±3°C
are summarized in Table 3.2.P.8.1-17. 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 c ommercial specification , as discussed in
Section 3.2.P.5.6 Justification of Specification(s) (modRNA). 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 l ots. I n addition, Section P.5.6 Justification of Specification(s)
(modRNA) presents the trend anal ysis data for drug product stability lots that both meet the
tightened release acceptance criterion and are manufactured using either
from an updated process or from . These data demonstrate that 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.
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Page 22Table 3.2.P.8.1 -17.Summary of Emergency 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
through 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 3M (on -going) Within specification
through 3M
EL8723 2M (on -going) Within specification
through 2M
EM6950 2M (on -going) Within specification
through 2M
EL8713 2M (on -going) Within specification
through 2M
EP2166 2M (on -going) Within specification
through 2M
EK4242 3M (on -going) Within specification
through 1M
EN1195 1M (on -going) Within specification
through 1M
EL8734 3M (on -going) Within specification
through 3M
EM4965 1M (on -going) Within specification
through 1M
EL3248 3M (on -going) out of
specification at 1M and 3M
EL9267 1M (on -going) Within specification
through 1M
EL3249 3M (on -going) Within specification
through 1M
EN6199 1M (on -going) Within specification
through 1M
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
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Page 23stressed stability conditions and does not impact the overall stabilit y 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 .
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 p eriod stability .
All 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 Condi tions
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 av ailable through
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(b) (4)
(b) (4)
(b) (4)
(b) (4)
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3.2.P.8.1. Stability Summary and Conclusion
PFIZER CONFIDENTIAL
Page 24the 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 p oints (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 q ualification lot thermal cy cling studies are presented 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 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 re mained within the acceptance criteria in place at the time of
testing through time points tested to date.
3.2.P.8.1.6.5. Summary 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
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 control and the light 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 initi al shelf life for the BNT162b2 DP is 6 months 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 perform ance 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.
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(b) (4)
(b) (4)
(b) (4)
(b) (4)
(b) (4)
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3.2.P.8.1. Stability Summary and Conclusion
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Page 25Up to 9 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
Up to 9 months of current available stability data on two clinical lots of BNT162b1
drug product
Comprehensive comparability assessments performed during dev elopment.
Understanding of the mRNA platform to support the initial shelf life
Additionally , the initial in -use period for the thawed, undiluted vial is room temperature for
not more than 2 hours, which is further discussed i n (Section 3.2.P.2.6 Compatibil ity).
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 b eyond the 6 months initial 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 batch es of commercially representative material.
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FDA-CBER-2021-5683-1149272