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BNT162b2

3.2.P.8.3. Stability Data
Thermal — Stress and Cycling

 

TABLE OF CONTENTS
LIST OF TABLES ............csaussnessnsssnsnonsonnennennennennnnontnnesnnnsnnennnsnnenesnnnnnnsonnennennennennorsnonsonsneneane
3.2.P.8.3. STABILITY DATA - THERMAL - STRESS AND CYCLING ........unsenenesene
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BNT162b2
3.2.P.8.3. Stability Data
Thermal — Stress and Cycling

 

LIST OF TABLES
Table 3.2.P.8.3-1. Summary of Drug Product Thermal Stability Studies ......................

Table 3.2.P.8.3-2. Stability Data for Drug Product PPQ Lot EL8723 Stored at 25 +2
°C/60 + 5% RH (Pfizer, Puurs).......uusceeseeseesesneneesnenenensnennnnnnnnnnennennnnn

Table 3.2.P.8.3-3. Stability Data for Drug Product PPQ Lot EL8723 Stored at 30 +2
°C/65 # 5% RH (Pfizer, Puurs)...............u0u0n0sennennnesnennnnnnenennennn nenn

Table 3.2.P.8.3-4. Stability Data for Drug Product Emergency Supply Batch EJ1688
Stored at 25 +2 °C/60 # 5% RH .........unsersersernersenenennnnnnnnnnennnnnnnnnnnnn

Table 3.2.P.8.3-5. Stability Data for Drug Product Emergency Supply Batch EK1768
Stored at 25 +2 °C/60 # 5% RH............cunsenssnsennsnnnnonsnnnsnnnnnnnnnnenennnn

Table 3.2.P.8.3-6. Stability Data for Drug Product Emergency Supply Batch EJ1686
Stored at 25 +2 °C/60 + 5% RH............cunsnesnnennennnnnnnnnsonnnnnnnne nenn

Table 3.2.P.8.3-7. Stability Data for Drug Product Emergency Supply Batch EJ1685
Stored at 25 +2 °C/60 + 5% RH............cunsnesnnennsnnnnonnnnsonnnnnnnnnennenn

Table 3.2.P.8.3-8. Stability Data for Drug Product Emergency Supply Batch EJ0553
Stored at 25 +2 °C/60 + 5% RH............curs0ueeneennennennnnnnnnonnnnnnnnen nenn

Table 3.2.P.8.3-9. Stability Data for Drug Product Emergency Supply Lot EE8493
Stored at 25 +2 °C/60 + 5% RH.........n.cunsenssnnennsnnnnnennnnonnennnnnennnenn

Table 3.2.P.8.3-10. Stability Data for Drug Product Emergency Supply Lot EE8493
Stored 30+2 °C/65 +5 RH ........eneceesenssnnennennennnnnnnnonnnnnnnnennnnnnn

Table 3.2.P.8.3-11. Stability Data for Drug Product PPQ Lot EL3248 Stored at 25 +2
°C/60 + 5% RH (Pfizer, Kalamazoo) ............cuu2cuussonsennnennnenseneennennnnne

Table 3.2.P.8.3-12. Stability Data for Drug Product PPQ Lot EL3248 Stored at 30 +2
°C/65 + 5% RH (Pfizer, Kalamazoo) ...........ccueesesesneesnnnennnnnnnnnenennnnn

Table 3.2.P.8.3-13. Stability Data for Drug Product Emergency Supply Batch EH9899
Stored at 25 +2 °C/60 # 5% RH .........rscnssnesneennennnnnnennnsnnennnennnennnne

Table 3.2.P.8.3-14. Stability Data for Polymun Scientific Drug Product BNT162b2 Lot
BCV40420-A Stored at 25 &2 °C ...nnnnnersnssnrsonsnnnnnenennnnenonsnnnnnsnnenenn

Table 3.2.P.8.3-15. Stability Data for Polymun Scientific Drug Product BNT162b1 Lot
BCV10320-A Stored at 25 £2 °C ....nnesessesesersnnnennnnsnnnnennnnnnnnen nennen

Table 3.2.P.8.3-16. Thermal Cycling Stability Data for Drug Product Emergency
Supply Batch EK1768 .....uueseesessenesenersnenneneeneonensonenenenensnnnnsonnensnnnenenn

Table 3.2.P.8.3-17. Thermal Cycling Stability Data for Drug Product Emergency
Supply Batch EJ1686.......uuenneseneensesnesnennennennnonnnnnnnennennnnnnennnennnonsenann

Table 3.2.P.8.3-18. Thermal Cycling Stability Data for Drug Product PPQ Lot EN1195
Table 3.2.P.8.3-19. Thermal Cycling Stability Data for Drug Product PPQ Lot EL8723
Table 3.2.P.8.3-20. Thermal Cycling Stability Data for Drug Product PPQ Lot EK4242

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BNT162b2
3.2.P.8.3. Stability Data
Thermal — Stress and Cycling

 

Table 3.2.P.8.3-21. Thermal Cycling Stability Data for Drug Product PPQ Lot EL7834....... 29
Table 3.2.P.8.3-22. Thermal Cycling Stability Data for Drug Product PPQ Lot EL9266........ 31
Table 3.2.P.8.3-23. Thermal Cycling Stability Data for Drug Product PPQ Lot EL3249.......33
Table 3.2.P.8.3-24. Thermal Cycling Stability Data for Drug Product PPQ Lot EL8723

(-20 45 °C) eeseenersnensnennennenensnenennensnnenneenenensnenenennensensnnnnsensensenennensesonnensonanen 35
Table 3.2.P.8.3-25. Thermal Cycling Stability Data for Drug Product PPQ Lot EL8723

(210 8 °C) ...ueseesesnennenusnnnnenennnnnesnnenenennennennennenennsnansesnnnnennsunssenssnenensnnansenannn 37
Table 3.2.P.8.3-26. Freeze Thaw Cycling Stability Data for Drug Product PPQ Lot

EL8723 ...neessesessesesnnenenesnennennenennennennenensnnansennnnanensnnnenennonsenennonsesonnansenanen 38

Table 3.2.P.8.3-27. Thermal Cycling Stability Data for Drug Product PPQ Lot ET0384....... 39

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BNT162b2
3.2.P.8.3. Stability Data
Thermal — Stress and Cycling

 

3.2.P.8.3. STABILITY DATA - THERMAL - STRESS AND CYCLING

Data from stability studies on BNT162b2 drug product lots stored at the thermal stress
conditions of 25 + 2 °C/60 + 5% RH and 30 + 2 °C/65 + 5% RH, as well as thermal cycling
studies, are presented for emergency supply and process performance qualification lots
manufactured by Polymun Scientific (with fill and finish at Pfizer, Puurs), mibe (with fill and
finish at Pfizer, Puurs) and Pfizer, Puurs.

Additionally, data from supportive stability studies for one clinical BNT162b2 drug product
lot and one clinical supportive BNT162b1 drug product lot stored at the thermal stress
condition of 25 + 2 °C and manufactured by Polymun Scientific is also presented.

All studies are listed in Table 3.2.P.8.3-1. Results will be provided in Table 3.2.P.8.3-2
through Table 3.2.P.8.3-27.

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BNT162b2
3.2.P.8.3. Stability Data

Thermal — Stress and Cycling

 

Table 3.2.P.8.3-1.

Summary of Drug Product Thermal Stability Studies

 

 

   

 

   
   
 

    
 
 

 

 

 

 

 

 

 

 

 

 

 

 

(Pfizer, Kalamazoo)

 

 

Supply”, Process
performance
qualification

 

 

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.

 

Lot Number Drug Product Stability Study Type Storage Condition Stability Data Data Table Location
Batch Use Start Date Presented
EL8723 Stability, Clinical, January 2021 Thermal Stress 25 +2 °C/60 +5% RH Table 3.2.P.8.3-2
(Pfizer, Puurs) Emergency Supply”,
Process performance 30+2°C/65 +5% RH Table 3.2.P.8.3-3
qualification (Complete)
(February 2021 | Thermal Cycling 1: Ultra frozen vials are placed at 16 weeks Table 3.2.P.8.3-19
for Thermal -20 #5 °C for 4 weeks and then moved to 2 to 8°C (On-going)
Cycling Study 1 | for 12 weeks. Samples will be pulled for testing
and April 2021 | every 2 weeks throughout protocol.
for Thermal Thermal Cycling 2: Ultra frozen vials are placed at 1 month Table 3.2.P.8.3-24
Cycling Studies | 394 5 °C for 4 weeks (1 month) and then moved
2&3) to -90 to -60 °C for the shelf life of the drug
product.
Thermal Cycling 3: Ultra frozen vials are placed at 1 month Table 3.2.P.8.3-25
5+3 °C for 4 weeks (1 month) and then moved to
-90 to -60 °C for the shelf life of the drug
product.
Ultrafrozen vials were cycled between 25 +2 °C/60 | 10 freeze thaw cycles Table 3.2.P.8.3-26
+ 5%RH (for 2 to 7 hours) and -90 to -60 °C (for 24
+2 hours) for a total of 10 cycles
EL3248 Stability, Clinical, December 2020 | Thermal Stress 25 +2 °C/60 +5% RH Table 3.2.P.8.3-11
(Pfizer, Kalamazoo) | Emergency Supply”, Thermal Stress 30+2 °C/65 +5% RH Table 3.2.P.8.3-12
Process performance
qualification
ET0384 Stability, Emergency | February 2021 | Thermal Cycling: Ultra frozen vials are placed at - Release Table 3.2.P.8.3-27
(Polymun/Pfizer, Supply”, Process 90 to -60 °C for 5 months and then a subset of vials
Puurs) performance moved to 2 to 8°C for 1 month. Samples pulled at
qualification 6M for testing at both -90 to -60°C and 2 to 8°C.
This is repeated at 11/12M, 17/18M and 23/24M
EL3249 Stability, Clinical, January 2021 Thermal Cycling: 1 week at -90 to -60°C , followed 8 weeks Table 3.2.P.8.3-23
(Pfizer, Kalamazoo) | Emergency Supply”, by 2 weeksat -20 +5 °C, 4 weeks at2 to 8°C and 1 (Complete)
Process performance week at 25 +2 °C/60 +5% RH.
qualification
EL9266 Stability, Emergency | February 2021 | Thermal Cycling: Ultra frozen vials are placed at - 16 weeks Table 3.2.P.8.3-22

 

 

 

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BNT162b2
3.2.P.8.3. Stability Data

Thermal — Stress and Cycling

 

Table 3.2.P.8.3-1.

Summary of Drug Product Thermal Stability Studies

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Lot Number Drug Product Stability Study Type Storage Condition Stability Data Data Table Location
Batch Use Start Date Presented
EN1195 Stability, Emergency | February 2021 | Thermal Cycling: Ultra frozen vials are placed at - 12 weeks Table 3.2.P.8.3-18
(mibe/Pfizer, Puurs) | Supply“, Process 20 +5 °C for 4 weeks and then moved to 2 to 8°C (On-going)
performance for 12 weeks. Samples will be pulled for testing
qualification every 2 weeks throughout protocol.
EK4242 Stability, Emergency January 2021 Thermal Cycling: 1 week at -90 to -60°C followed 5 weeks Table 3.2.P.8.3-20
(mibe/Pfizer, Puurs) | Supply“, Process by 4 weeks at 2 to 8°C (Complete)
performance
qualification
EL7834 Stability, Emergency January 2021 Thermal Cycling: 1 week at -90 to -60°C followed 10 weeks Table 3.2.P.8.3-21
(Polymun Supply*, Process by 4 weeks at -20 +5 °C and then 4 weeks at 2 to (Complete)
Scientific/Pfizer, performance 8°C. and 1 week at 25 +2 °C/60 +5% RH.
Puurs qualification
EH9899 Stability, November Thermal Stress 25+42°C/60+4+5%RH 1 month Table 3.2.P.8.3-13
(Pfizer, Kalamazoo) | Emergency Supply? 2020 (Complete)
EJ1688 Stability, Emergency | November 2020 Thermal Stress 25 +2 °C/60 +5% RH 1 month (Complete) Table 3.2.P.3.3-4
(mibe/Pfizer, Puurs) | Supply?
EK1768 Stability, Emergency | November 2020 Thermal Stress 25 +2 °C/60 +5% RH 1 month (Complete) Table 3.2.P.8.3-5
(Polymun Supply”, Clinical Thermal Cycling: 2 weeks at -90 to -60°C followed 14 weeks (Complete) Table 3.2.P.8.3-16
Scientific/Pfizer, inventory by 4 weeks at -20 +5 °C and then 8 weeks at2 to
Puurs 8°C. Samples will be pulled for testing every 2
weeks throughout protocol.
EJ1686 Stability, Emergency | November 2020 Thermal Stress 25 +2 °C/60 +5% RH 1 month (Complete) Table 3.2.P.8.3-6
(Polymun Supply*, Clinical Thermal Cycling: 2 weeks at -90 to -60°C followed 14 weeks (Complete) Table 3.2.P.8.3-17
Scientific/Pfizer, inventory by 4 weeks at -20+5 °C and then 8 weeks at2 to
Puurs 8°C. Samples will be pulled for testing every 2
weeks throughout protocol.
EJ1685 Stability, Emergency | November 2020 Thermal Stress 25 +2 °C/60 +5% RH 1 month (Complete) Table 3.2.P.8.3-7
(Polymun Supply®, Clinical
Scientific/Pfizer, inventory
Puurs
EJ0553 Stability, Emergency | November 2020 Thermal Stress 25 +2 °C/60 +5% RH l month Table 3.2.P.8.3-8
(Polymun Supply®, Clinical (Complete)
Scientific/Pfizer, inventory
Puurs
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BNT162b2
3.2.P.8.3. Stability Data

Thermal — Stress and Cycling

 

Table 3.2.P.8.3-1.

Summary of Drug Product Thermal Stability Studies

 

Lot Number

   

Drug Product
Batch Use

Stability
Start Date

   

Study Type

 

Storage Condition

   
 
 

Stability Data
Presented

 

Data Table Location

 

 

 

 

 

 

 

 

EE8493 Stability, Emergency | September 2020 Thermal Stress 25 +2 °C/60 +5% RH Table 3.2.P.8.3-9
(Polymun Supply®, Clinical
Scientific/Pfizer, inventory Thermal Stress 30 +2 °C/65 +5% RH Table 3.2.P.8.3-10
Puurs) (Complete)
BCV40420-A Stability, Clinical May 2020 Thermal Stress 25+2°C 4 months Table 3.2.P.8.3-14
(Polymun Scientific) (complete)
Supportive Lots (BNT162b1)
BCV10320-A Supportive Stability, April 2020 Thermal Stress 25+2°C 3 months Table 3.2.P.8.3-15
(Polymun Scientific) | Clinical (complete)

 

 

 

a. Emergency supply designation applies to US market.
b. A minimum of one PPQ lot will be enrolled in thermal stress and thermal cycling stability programs compliant with ICH Guidelines and further information on lot numbers,
manufacture, stability enrollment and available data will be provided in the future.

TBD = To Be Determined

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BNTI162b2
3.2.P.8.3. Stability Data
Thermal — Stress and Cycling

 

Table 3.2.P.8.3-2. Stability Data for Drug Product PPQ Lot EL8723 Stored at 25 + 2 °C/60 + 5% RH (Pfizer, Puurs)

 

 

 

 

 

 

 

 

 

 

 
  

 

 

 

 

       
    
   

Analytical Appearance pH Dynamic Light Scattering (DLS) Fluorescence Assay
ttribute ; , .
Polydispersity |Encapsulation
Timepoint / Acceptance | White to off-white suspension May contain white to
Criteria? off-white opaque,
amorphous particles
0 WOS Meets (EFVP)
1W WOS Meets (EFVP)
2W WOS Meets (EFVP)
IM WOS Meets (EFVP)
Analytical HPLC-CAD Cell-based Flow Cytometry Capillary Gel
Procedure/Quality Electrophoresis
Attribute i i A Integri
Timepoint / Acceptance
Criteria?

 

a. Acceptance criteria in place at time of testing.
W = Week, M = Month, S = To be Scheduled, NS = Not Scheduled at Time Point; EFVP = Essentially free from visible particulates; LNP = Lipid Nanoparticle; HPLC-CAD
= high performance liquid chromatography-charged aerosol detector, WOS = White to off-white suspension

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BNT162b2
3.2.P.8.3. Stability Data

Thermal — Stress and Cycling

 

Table 3.2.P.8.3-3.

Stability Data for Drug Product PPQ Lot EL8723 Stored at 30 £# 2 °C/65 + 5% RH (Pfizer, Puurs)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Analytical Appearance | pH | Dynamic Light Scattering (DLS) Fluorescence Assay
Procedure Quality Appearance (Visual) Visible Particulates LNP Size LNP RNA RNA Content
ute . F .
Polydispersity | Encapsulation
Timepoint / Acceptance | White to off-white suspension May contain white to
Criteria? off-white opaque,
amorphous particles
0 WOS Meets (EFVP)
1W WwOS Meets (EFVP)
2W WOS Meets (EFVP)
IM WOSs Meets (EFVP)
Analytical HPLC-CAD Cell-based Flow Cytometry Capillary Gel
Procedure/Quality Electrophoresis
Attribute ALC-0315 Content ALC-0159 Content DSPC Content Cholesterol Content In Vitro Expression RNA Integri
Timepoint / Acceptance
Criteria?
0
1W
2W
1M

 

a. Acceptance criteria in place at time of testing. Updated at the 1 month time point.
W = Week, M = Month, S = To be Scheduled, NS = Not Scheduled at Time Point; EFVP = Essentially free from visible particulates; LNP = Lipid Nanoparticle; HPLC-CAD
= high performance liquid chromatography-charged aerosol detector, WOS = White to off-white suspension

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BNTI162b2
3.2.P.8.3. Stability Data

Thermal — Stress and Cycling

 

Table 3.2.P.8.3-4.

Stability Data for Drug Product Emergency Supply Batch EJ1688 Stored at 25 £# 2 °C/60 #5% RH

 

 

 

   

  

White to off-white suspension

  

EFVP

Fluorescence Assay

 

  

       
       
 

Analytical Appearance pH | Dynamic Light Scattering (DLS)
Procedure/Quality Appearance (Visual) Visible Particulates LNP Size LNP
Attribute . .
Polydispersity
Timepoint / Acceptance | White to off-white suspension | May contain white to
Criteria? off-white opaque,

 

 

 

 

 

 

  

RNA
Encapsulation

RNA Content

  

  

 

 

 

 

Timepoint / Acceptance
Criteria?

 

     

 

a. Acceptance criteria in place at time of testing. Current effective acceptance criteria established at the 1 month time point.
W = Week, M = Month, S = To be Scheduled, NS = Not Scheduled at Time Point; EFVP = Essentially free from visible particulates; LNP = Lipid Nanoparticle; HPLC-CAD
= high performance liquid chromatography-charged aerosol detector

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1W White to off-white suspension | EFVP
2W White to off-white suspension | EFVP
1M White to off-white suspension | Meets (EFVP)
Analytical HPLC-CAD Cell-based Flow Cytometry Capillary Gel
Procedure/Quality Electrophoresis
Attribute ALC-0315 Content ALC-0159 Content DSPC Content Cholesterol Content RNA Integrii