Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

BATCH RECORD ISSUANCE Issued By: _____________________________________________________________________________________________ Print Name Signature Date

1. SIGNATURE: 1.1 Sign below if your initials appear in this document.

Printed Name

Signature

Initials

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

2. REFERENCES:

Document or SOP number

OPE-XXXX 3. LIST OF SUPPLIES:

Title
Operation of XXXX conductivity meter in the Manufacturing Areas..

Item Description
15mL Polypropylene Conical tubes 4. RAW MATERIAL AND COMPONENTS:

Part Number
60505

Amount Required
As Required

Verify that the correct materials are provided. Attach Materials Management kit label to the batch record.

Material Description
10 XXXX Filter

Part Number
10073

Storage Condition
15 - 30C

Amount Required
1.

Verified By

The following materials are required for all lot sizes.

Production Stock Supply Maintained in Manufacturing Stock Area

Material Description Clarified Harvest Part Number 41021 Storage Condition 10 - 25C Amount Required As Needed Amount Used Batch # Exp. Date Entered By Verified By ..

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

5. EQUIPMENT: Record the Serial or ID Number and the calibration due date of the equipment needed to perform the procedure.

Equipment Name

Equipment Serial or ID Number

COL-10175

Calibration Due Date

Recorded By/Date

Verified By/Date

Peristaltic Pump Conductivity Meter Spectrophotometer

P-10006 IN-10002 Y-10490.

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

6. PROCEDURE: NOTE: For Development sample handling information refer to TP-BDS12-0003-0101 For QC sample handling information refer to TP-BDS12-0003-0102 Consult Supervisor for Out-of-Range, Program Issues, and Development Labels

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Perform Verify By/Date By/Date

Step # 6.1
6.1.1

Operational Description Preliminary Operations

Flush WFI drop if needed (TGP-2300)

Data Entry
WFI Flush Date WFI Flush Time WFI Fill Date

6.1.2

Fill 50L Carboy or Bag with WFI (TGP-2300)

WFI Fill Time 50L Carboy Autoclave Run # 50L Carboy Use By Date

6.1.3 Verify 250L process tank has been CIPed 6.1.4 Standardize and Install Rosemont pH probe (MFG-2276)

CIP Date CIP Time Standardization Date # Of Vol. Per # Of Vol. Per Temp Sample Samples Sample Samples Sample (C) Needed (mL) Taken (mL) Endo. 2-8 2-8 -10 -10 -10

6.2

Load Sample Preparation

TR #

Sample Load as Follows 6.2.1 Note: 15ml PET tube for endo

Biobur. Develop Develop Develop

6.3

Chrom. System and Column Prep.

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Perform Verify By/Date By/Date

Step #

Operational Description

Data Entry

NOTES If a program cannot be used, run 6.3.1 manually per Program Guide. (Appendix A) 6.3.2 Record from the column logbook Column Volume Skid Cleaning Date 6.3.3 Record from the chrom. skid logbook *Note: If > 30 days, re-clean per TCP-2311 & record date L

6.3.4 Run WFI Flush program 6.3.5 Install Filter (10073) housing on skid

Disconnect (TCP-2310) WFI 6.3.6 Inlet Cleaning Manifold Outlet Cleaning Manifold Column Manifold Connect 6.3.7 (TCP-2310) *Note: Check boxes as completed

Inlet 1: Inlet 2: Inlet 3: Inlet 4: Inlet 5:

Buffer xxx Buffer xxx Buffer xxx Buffer xxx Buffer xxx

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Perform Verify By/Date By/Date

Step #

Operational Description

Data Entry

Outlet 1: 50L Carboy Label as Pre-Elution, LN, Init/Date Outlet 2: 250L Tank with no foam diptube Label as Elution, LN, Init/Date Column Top: Top of Column Column Bottom: Bottom of Column
6.3.8 6.3.9 6.3.10 6.3.11 Calculate the Following Run XXXX System Prime program (Appendix A) Run XXXX Pre-Cycle program (Appendix A) Record from Upstream (TP-BDS12-xxxx-xxxx) Bior. Vol. (L) X Raw Column Capacity: Col Vol. (L) X Raw Amount of TRM-1 (g) / Raw = Number of Cycles Needed: Col Cap. (g) # of Cycles # of Cycles (Round UP) Resin Cap. (g/L) = X.x Col Cap. (g) Raw TRM-1 Concentration Amount of TRM-1 in Load: Bior. Conc. (g/L) = X.xx Amount of X (g) g/L

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Perform Verify By/Date By/Date
X.xx # of Cycles X X Load Vol. 5L XXX

Step #

Operational Description
X.xx

Data Entry
X.x WFI Flush Vol. (L) Raw Volume to Load for Each Cycle: Bior. Vol. (L) + Raw

Connect (TCP-2310) *Note: Check boxes as completed 6.3.12

Filter (10725) to Skid Bubble Trap Tee to Filter (10725) Pressure Gauge to Tee Load Tubing to Tee Thread Tubing through Load Pump Y-tubing set (60285) to Load Tubing Load Bags to Y-tubing set

6.4

Cycle Process

NOTES Repeat steps 6.4.1 thru 6.4.14 for all cycles needed. Record required information in Section 6.5 Cycle Data Table 6.4.1 (CDT) for all cycles run start at Table 1. N/A any cycles not needed. If a program cannot be used, run manually per Program Guide. (Appendix A)

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Perform Verify By/Date By/Date

Step #

Operational Description
Run XXXXXX Process (Appendix A)

Data Entry

6.4.2 Enter variables as they are displayed on OIT Load Volume 6.3.11 File name add cycle # 6.4.3 Record Filename on CDT(1) Take Sample of Buffer (OPE-2258 & OPE-1434) 6.4.4 Buffer xxxxxxx 2 x ~25ml Record pH and Cond. on CDT (2) Take Column Effluent Sample (OPE-2258 & OPE-1434) Note: Post Equilibration 6.4.5 2 x ~25mL Record pH and Cond. on CDT (3) Record Buffer Used Vol. On CDT (4) Confirm Zero UV 6.4.6 (TCP-2310) Record on CDT (5) Load Column Open Bubble Trap Hand Valve 6.4.7 Note: Change filter (10725) if pressure > 30 psig Record Load Volume on CDT (6) 6.4.8 Wash Column Close Bubble Trap Hand Valve

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Perform Verify By/Date By/Date

Step #

Operational Description

Data Entry

Elute Column (TCP-2310) 6.4.9 (Follow in Order) Switch to Outlet 1 (Elut < 0.XAU) Switch to Outlet 2 (Elut 0.X AU) Switch to Waste (Elut 0.X AU) Perform Elut. Vol. Calc. on CDT (7) Take Elution Sample (OPE-1434) Turn on tank agitator, mix for at least 3 minutes (avoid foaming) 6.4.10 Record mixing Speed on CDT (8) Record mixing Time on CDT (9) 1 x ~20mL Record pH on CDT (10) Adjust pH If pH < X.x 6.4.11 Adjust pH to X with Tris-base Record Volume used on CDT (11) Take Sample (OPE-1434) 6.4.12 1 x ~20mL Record pH on CDT (12) 6.4.13 Strip Column Print Chromatogram & Event Log (14) Label as: 6.4.14 XXXXXX Purification Include: Cycle #, LN, Initials & Date

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation 6.5 Cycle Data Table Cycle 1

Ref. #
(1) (2) (2) (3) (3)

CYCLE 1

Parameters File Name Buffer pH Buffer Cond Equil. pH Equil. Cond Equil Range Met?

Data Entry

Units

Perform By/Date Verified By/Date

mS/cm YES End Start YES L End Start = Total L Hz/Rpm Start End = Total L

(4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14)

Equil. Buffer Vol Zero UV1? Load Volume ElutionA (Event Log) Mixing Speed Mixing Time Initial Pool pH Vol. of Tris-baseB Adjusted Pool pH Adj. Pool Vol (A+B) Chrom. Printed

L YES

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation 6.5 Cycle Data Table Cycle 2

Ref. #
(1) (2) (2) (3) (3)

CYCLE 2

Parameters File Name Buffer pH Buffer Cond Equil. pH Equil. Cond Equil Range Met?

Data Entry

Units

Perform By/Date Verified By/Date

mS/cm YES End Start YES L End Start = Total L Hz/Rpm Start End = Total L

(4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14)

Equil. Buffer Vol Zero UV1? Load Volume ElutionA (Event Log) Mixing Speed Mixing Time Initial Pool pH Vol. of Tris-baseB Adjusted Pool pH Adj. Pool Vol (A+B) Chrom. Printed

L YES

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation 6.5 Cycle Data Table Cycle 3

Ref. #
(1) (2) (2) (3) (3)

CYCLE 3

Parameters File Name Buffer pH Buffer Cond Equil. pH Equil. Cond Equil Range Met?

Data Entry

Units

Perform By/Date Verified By/Date

mS/cm YES End Start YES L End Start = Total L Hz/Rpm Start End = Total L

(4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14)

Equil. Buffer Vol Zero UV1? Load Volume ElutionA (Event Log) Mixing Speed Mixing Time Initial Pool pH Vol. of Tris-baseB Adjusted Pool pH Adj. Pool Vol (A+B) Chrom. Printed

L YES

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation 6.5 Cycle Data Table Cycle 4

Ref. #
(1) (2) (2) (3) (3)

CYCLE 4

Parameters File Name Buffer pH Buffer Cond Equil. pH Equil. Cond Equil Range Met?

Data Entry

Units

Perform By/Date Verified By/Date

mS/cm YES End Start YES L End Start = Total L Hz/Rpm Start End = Total L

(4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14)

Equil. Buffer Vol Zero UV1? Load Volume ElutionA (Event Log) Mixing Speed Mixing Time Initial Pool pH Vol. of Tris-baseB Adjusted Pool pH Adj. Pool Vol (A+B) Chrom. Printed

L YES

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Performed By/Date Verified By/Date

Step # 6.6

Operational Description Chromatography Skid and Column Cleaning and Storage

Store Column Perform per Program Guide (Appendix A) Print Storage Chromatogram Label as XXX Storage

Data Entry

6.6.1

6.6.2

Run Skid Clean & Store Program (TCP-2311)

6.7
6.7.1

Viral Inactivation
Calculate Total Adjusted Pool Volume: Total Pool Volume: Cycle Cycle 1 2 + + Note: From Cycle Data Table 6.5 (13) Cycle 3 Cycle 4 Total (L) =

Mixing Speed 6.7.2 Turn on tank agitator, mix for at least 3 minutes (avoid foaming) Mixing Start Time Sampling Start Time Sample 6.7.3 Sample XXXX Pool as Follows Develop A280 6.7.4 XXXX Pool Sample Initial pH # Of Samples Needed Vol. Per Sample (mL) # Of Samples Taken Vol. Per Sample (mL) Temp (C) -10 2-8

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Performed By/Date
mS/ cm

Step #

Operational Description
(OPE-2258 & OPE-1434) Take 1 x ~15mL sample Record pH and Cond. Viral Inactivation (OPE-2258 & OPE-1434) Lower pH to X.x with Buffer xxx Take 1 x ~20mL sample Record pH and Cond. Hold at pH X.xx for X minutes pH Neutralization (OPE-1434) Raise pH X with Tris-Base Take 1 x ~20mL sample Record pH Stop tank agitation Filtration Post Viral Inactivation Connect

Data Entry
Initial Conductivity Adjusted pH Adjusted Conductivity Vol of Buffer xxxx used Viral Inactivation Hold Start Time Viral Inactivation Hold End Time Neutralized pH mS/ cm L

Verified By/Date

6.7.5

6.7.6

Volume of 1M Tris-Base Used

6.8

6.8.1

*Note: Check boxes as completed

Tank bottom outlet to tubing spool piece Other end of spool piece to filter (10847) Other end of filter (10847) to KA3 filter on bag (10715) Position bag in 200L BPC

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Performed By/Date Verified By/Date

Step #

Operational Description
Filter and Transfer NOTES Transfer by pressure or pump Check boxes as completed If By Pressure

Data Entry

Connect flex hose from Clean-Air to tank through vent

filter

Pressurize tank to 10 5 psig Open tank bottom outlet Purge air from filters (10847 and KA3 on 10715)
Tank Pressure If By Pump Psig

6.8.2

WARNING: Depressurized the tank before removing tubing

Thread tubing through pump Open tank bottom outlet Process at 2-7L/min Purge air from filters (10847 and KA3 on 10715)
Pump Speed Sample 6.8.3 Take Viral Inactivated Samples Develop Develop A280 6.8.4 Store material at RT can store 4 days Storage Start Date Storage Start Time # Of Vol. Per # Of Samples Sample Samples Needed (mL) Taken L/min Vol. Per Sample (mL) Temp (C) -10 -10 2-8

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Performed By/Date Verified By/Date

Step #
6.8.5

Operational Description
Determine XXXXXX Concentration (TMC-2358) Record on TP-BDS12-0003-0180 Batch Record Complete Proceed to TP-BDS12-0003-0120

Data Entry

6.8.6

7. COMMENTS: (INCLUDE STEP NUMBER REFERENCE)

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

A. APPENDICES: Manual Program Guide XXXXXXX System Prime

Step #
A.1.1

Step Name
Prime Inlets Prime BT & Filter Prime Top of Column

Flow Rate
X L/hr

Gradient (%B)
100 0 0 0 0

Inlet Valve Open

4 3 2 1 1

Inlet Valve Closed

S/1/2/3 4/5 4/5 4/5 4/5

BT
Bypass

Filter
Bypass

Column
Bypass

Outlet
Waste

Volume
XL each XL

A.1.2 A.1.3 A.1.4 A.1.5

X L/hr

Inline

Inline

Bypass

Waste

Open Column Top Bypass Valve X L/hr 0 1 4/5 Inline Inline Downflo w Waste XL

Close Column Top Bypass Valve

Manual Program Guide XXXXX Pre-Cycle

Step #
A.2.1

Step Name
Pre-Cycle

Flow Rate
247 25 L/hr

Gradient (%B)
0 0 0 100

Inlet Valve Open

1 2 3 4

Inlet Valve Closed

4/5 4/5 4/5 S/1/2/3

BT
Inline

Filter
Inline

Column
Downflo w

Outlet
Waste

Volume
XCV each

Production Batch Record

Document No.: Title: Part Number(s):

Chromatography Capture and pH Inactivation

Manual Program Guide XXXXXX Process

Step #
A.3.1 A.3.2 A.3.3 A.3.4 A.3.5 A.3.6 A.3.7

Step Name
Equilibrate Load Wash Pre-Elution Elution Strip Storage

Flow Rate
X L/hr X L/hr X L/hr X L/hr X L/hr X L/hr X L/hr

Gradient (%B)
0

Inlet Valve Open

1

Inlet Valve Closed

4/5

BT
Inline Inline Inline Inline Inline Inline Inline

Filter
Inline Inline Inline Inline Inline Inline Inline

Column
Downflo w Downflo w Downflo w Downflo w Downflo w Downflo w Downflo w

Outlet
Waste Waste Waste 1 2 Waste Waste

Volume
XCV Load (Variable) XCV XCV XCV XCV XCV

P202 External Load Pump 0 0 0 100 100 2 3 3 4 5 4/5 4/5 4/5 S/1/2/3 S/1/2/3

8. MANUFACTURING REVIEW BY: Signature: Printed Name: Date: