BMR - Metro - 0.5 % - IP - 100 ML - 4800 L

KAMLAAMRUT PHARMACEUTICAL LLP.
Batch Manufacturing Record
Large Volume Parenteral (For manufacturing Line - 3) Page 1 of 32

Product Name METROKAP Mfg. Date
Generic Name Metronidazole Injection IP ( 0.5 % W/V ) Exp. Date
Batch No. Fill Volume : 100 ml Batch Size : 4836.0 Kg. ( ≈ 4800 L )
( Theoretical Quantity : 47058 bottles )
BMR No. : BMR/LVP/23/100/I Manufacturing Line No. : 03

Kamlaamrut Pharmaceutical LLP, At : Indrad , Tal. : Kadi ; Dist. : Mehsana ;
Mfg. By :
Gujarat – 382 715.
Mfg. License No. : G/28D/LVP/24

Composition: Each 100 ml contains
Metronidazole IP 0.500 gm
Label Claim :
Sodium Chloride IP 0.790 gm
Water for Injection IP Q.S.
Volume : 100 ml in LDPE Plastic Container by FFS technology
BMR Issue No. : 01 BMR Revision No. : 00
BMR effective Date : 10/01/2023

Shelf Life : 36 Months
Presentation /
: Sterile, A clear and almost colorless to pale Yellow Solution.
Description
Change Control No. : NA Effective Batch No. : NA
Reason for revision : Due to installation of new filling machine in Line – 3 ( FFS Technology )
Reference Document No.: MFR No. : MFR/LVP/23/100/I MFR Effective from : 10/01/2023
BMR Issued By BMR Checked By and Reviewed By Batch Released By

QA Officer / Executive Production Executive / Prod. Manager Asst. Mgr. / Manager - QA
Signature
Date
Name
Prepared By Reviewed Verified By Approved by
Signature
Name Kushal Jiyani Shashin Upadhyay Arpit Nayak Sachin Saple

Executive -
Designation Asst. Manager - QA Sr. Production Officer Manager – QA
Production

BATCH RECORD VERIFICATION FORM
Activity Activity
Page
Sr. No Record Details Checked By Verified
No.
(Mfg. Chemist) By QA
Material Issuance And Verification of raw
1.0 6
material
1.1 Precommencement Checks 6
Raw materials and Primary packing material
1.2 6
Issuance activity
2.0 Material Dispensing 7 – 11
Raw Material and Primary Packing material
2.2 9
Dispensing Activity
2.3 Checks after dispensing 11
2.4 Return Material Status 11
Cleaning and Sterilization of Equipment
3.0 12 – 15
(CIP/SIP)
3.2 Cleaning in place and Steaming in place 13
4.0 Manufacturing Procedure 16 – 19
4.2 Bulk Preparation Method 17
5.0 Filtration 20 - 21
5.2 Bubble Point 20
6.0 Filling Operation 22 – 29
6.2 Filling Operation 23
6.3 Filling Reconciliation 29

Activity Activity
Page
Sr. No Record Details Checked By Verified By
No.
(Mfg. Chemist) QA
7.0 Sterilization Of Product 20 – 32
7.2 Product Terminal Sterilization 31
7.3 Checks after sterilization 31
7.4 Post verification 32

List of Production Equipment
Sr. No. Name of Instrument / Equipment Equipment ID No.

1. Weighing Balance – 100 Kg ( Material received area) - Warehouse EQP / PRD / 63
2. Weighing Balance – 6.0 Kg ( RM Dispensing Room) EQP / PRD / 103
3. Weighing Balance – 60.0 Kg ( RM Dispensing Room) EQP / PRD / 104
4. Dynamic Pass Box (Dispensing Room) – Corridor to Dispensing Room EQP / PRD / 91
Dynamic Pass Box II (Dispensing Room) – Dispensing to Clean EQP / PRD / 92
5.
Corridor
6. Reverse Laminar Air Flow (Dispensing Booth) EQP / PRD / 90
7. Mixing Vessel (Line 3) - Mixing Room – 7000 L EQP / PRD / 93
8. Holding Vessel (Line 3) - Mixing Room – 7000 L EQP / PRD / 94
9. S.S. 316 L Filter press (Line 3) EQP / PRD / 107
10. Nanofog Fogger machine EQP / PRD / 64
11. Filter Integrity Test Apparatus EQP / PRD / 23
12. Bottle Conveyor belt (Line 3) - Filling Room EQP / PRD / 108
13. Filling Machine (Line 3) - Filling Room EQP / PRD / 98
14. EURO Cap Sealing machine (Line 3) - Filling Room EQP / PRD / 99
15. Bottle Conveyor belt (Pre Sterile Room) EQP / PRD / 109
16. Plastic Granule Hopper ( Silo machine ) EQP / PRD / 97
17. Sterilizer (Pre Sterile Area) EQP / PRD / 100
18. Weighing Balance – 2.0 Kg (Pre Sterile Area) EQP / PRD / 110
19. Disinfectant Room LAF EQP / PRD / 71
20. Disinfectant Assembly EQP / PRD / 73
21. Disinfectant – Manufacturing Tank EQP / PRD / 74
22. Disinfectant – Storage Tank EQP / PRD / 75
23. LAF – Garment Folding EQP / PRD / 89
24. Autoclave For Garment Sterilization – Line 3 EQP / PRD / 95
25. Dynamic Pass Box – Autoclave Unloading Area EQP / PRD / 96


List of Production Equipment
Sr. No. Name of Instrument / Equipment Equipment ID No.

26. Hand Dryer – I ( Dispensing Entry & Exit Airlock ) EQP / PRD / 101
27. Hand Dryer – II ( Manufacturing Entry & Exit Airlock ) EQP / PRD / 102
28. Dynamic Pass Box IV – EURO Decartoning to Capping EQP / PRD / 105
29. Digital Micrometer ( Pre Sterile Area ) EQP / PRD / 106
Note : The material of construction of all the vessels & Equipment should be of Stainless Steel ( SS ) 316 L.

1. MATERIAL ISSUANCE AND VERIFICATION OF RAW MATERIAL
1.1 Precommencement Checks:

Check Point Observation
1.1.1 Each materials are released by QC and also within shelf-life.( Validity period ) Yes / No
1.1.2 Material issuance by designated persons. Yes / No
1.1.3 Correct materials accurately weighed into clean, properly labeled containers. Yes / No
1.1.4 Each issuance material ID independently checked and signed by authorized person. Yes / No
1.1.5 SOP and record for cleaning has been verified after issuance of material. Yes / No
1.1.6 SOP and records for calibration of balances used has been verified. Yes / No
Pre commencement Checked By/ Date: ________________ Verified By/ Date: _____________
(Ware house Officer) (Prod. Officer)
1.2 Raw materials and Primary packing material Issuance Activity:
Balance ID No. : RM Store : EQP / PRD / 63 ( Capacity : 100.0 Kg. )
Balance ID No. : PPM Store : EQP / PRD /119 ( Capacity : 150.0 Kg. )
Sr. Std.
Item Qty Issued Checked Verified
No. Ingredients Spec. UOM Qty. A.R. No.
Code In Kg.
Issued by Store by Prod. by IPQA
1 Metronidazole IP (**) Kg. 24.000

Sodium
2 IP (**) Kg. 37.920
Chloride
Di Sodium
3 Hydrogen Ortho USP (**) Kg. 2.284
Phosphate
Citric Acid
4 IP (**) Kg. 1.100
Plastic Granules
5
(LDPE)
IH (**) Kg 1050.00
Note: Ensure that material issuance activity is being performed as per SOP No. : KAPL / SD / 06
Remarks: ________________________________________________________________________
_________________________________________________________________________________

(**) Item Code :
Sr. Name of Material Item Code Mark ( √ ) for Used
No. material
1 Metronidazole RM00000037
2 Sodium Chloride RM00000004
3 Di Sodium Hydrogen Ortho Phosphate RM00000041
4 Citric Acid RM00000016
5 Plastic Granules (LDPE) PMPG000001
PMPG000002
6 Water For Injection RM00000029
2.0 MATERIAL DISPENSING

Sr.
Observation Status
No.
Follow the Clean Room Entry-Exit Procedure as per SOP No.: KAPL /
1 Followed / Not Followed
PRD / 39.
Wear clean & Sterile garments includes Gown, mask, booty, and gloves,
2 Followed / Not Followed
while dispensing the batch.
Ensure area , equipment and SS containers cleanliness before starting the
3 Complies / Does not Comply
dispensing operations
Check and ensure that all equipment’s and other required accessories
4 Cleaned / Uncleaned / NA
including utensils are clean , dry and ready for use
5 Ensure that AHU system should be ON throughout the dispensing process. Complies /Does not Comply
6 Get line clearance from QA for dispensing. Yes / No
Ensure the cleanliness and dryness of the SS container, to be used (if
7 Cleaned / Uncleaned
required) prior to dispensing.
Check the balance calibration status, which is to be used. Verify the
8 OK / Not OK
cleanliness after dispensing.
Ensure by counter checking the weights of all active ingredients, assay, and
9 OK / Not OK
moisture content as provided by QC, before using in the batch.
Ensure that during the dispensing of this product, no other product
10 Complies /Does not Comply
processing should be done in the same area.
Precommencement Checked By : (Production ) ____________ Verified by (QA) : _____________

Date : ____________ Date : _____________

Previous Product: ___________________________________ Batch No. : ________________
Thermo hygrometer ID No. : EQP/PRD/____
Cleanliness and Physical Parameter checks as per SOP No. KAPL / PRD / 06.
Area : Dispensing Room
Time Cleanliness Relative Positive
Temp. Checked Verified
Disinfectant solution: Humidity Pressure
Date (NMT By By
Start End ( NMT (30-35)
27°C) Production (QA)
_____________________ 55% RH ) Pa
Complies /
Does not Comply
Note: Ensure that Dispensing Booth RLAF start before 30 minute of Dispensing Activity as per SOP No. :
KAPL / PRD / 11.
RLAF Balance Calibration (Equipment ID No. EQP / PRD / 103 )
(Equipment ID No. EQP / PRD / 104 )
(Equipment ID No. EQP / PRD / 90 )
Start Time End Time Done by production Checked by QA
( Date & Sign ) ( Date & Sign )

2.2 Raw Material & Primary packing material Dispensing Activity : SOP : KAPL / PRD / 11.
Dispensing Date: ____________ Start Time: _________ Hrs. Completed Time: _______ Hrs.
Dispensing Booth ID No. : EQP / PRD / 90 .
Balance ID No. : EQP / PRD / 103 ( Capacity : 60.0 Kg.)
Balance ID No. : EQP / PRD / 104 ( Capacity : 6.0 Kg.)
Balance ID No. : EQP / PRD / 119 ( Capacity : 150.0 Kg.) – PPM Store
Std. Qty. Qty. Checked

Sr. Item Verified By
Ingredients UOM Required Dispensed A.R. No. By
No. Code QA
In Kg In Kg Prod.
1 Metronidazole IP Kg. ( ** ) 24.000
Sodium Chloride
2 Kg. ( ** ) 37.920
IP
Di Sodium Hydrogen
3
Ortho Phosphate USP
Kg. ( ** ) 2.284
Citric Acid IP
4 Kg. ( ** ) 1.100
Plastic Granules
5
(LDPE)
Kg ( ** ) 1050.00
Remarks: This is the maximum quantity required per batch, considering minimum assay (99.0% w/w)
and the maximum moisture content / Loss on drying (1.00 % w/w) of Sodium Chloride IP. The actual
quantity of Sodium Chloride IP per batch is calculated on the basis of actual assay and moisture
Content / Loss on drying (from QC) as follows:
A* = _9.0 x 100 x 100 x 2.4 Where X = % w/w assay of Sodium Chloride IP ( On dry basis)
( X ) x (100 -Y) Y = % w/w Moisture content of Sodium Chloride IP
A* = _9.0 x 100 x 100 x 2.4 Where 9 = Label claim of Sodium Chloride IP ( mg / ml )

( ) x (100 - ) 2.4 = Batch Size ( 2400 L ) / 1000
= _____________ Kg. to be dispensed
Note : Check the labels of all dispensed materials for completeness and attach on this page.
Checked & attached by/ Date _____________ Verified by/ Date : _______________
(Production) (QA)

Remarks: This is the maximum quantity required per batch, considering minimum assay (99.0% w/w) and
the maximum moisture content / Loss on drying (0.50 % w/w) of Metronidazole IP. The actual quantity of
Metronidazole IP per batch is calculated on the basis of actual assay and moisture Content / Loss on
drying (from QC) as follows:
Q* = _5.00 X 100 X 100 X 4.8 Where A = % w/w assay of Metronidazole IP ( On dry basis)
( A ) X (100 – B ) B = % w/w Moisture content of Metronidazole IP
Q* = _5.00 X 100 X 100 X 4.8 Where 5.00 = Label claim of Metronidazole IP ( mg / ml )

( ) X (100 - ) 4.8 = Batch Size ( 4800 L ) / 1000
= _____________ Kg. to be dispensed.
( Note : Check the labels of all dispensed materials for completeness and attach on this page.)
Checked & attached by/ Date _____________ Verified by/ Date : _______________
(Production) (QA)
Filter Dispensing Activity as per SOP No. : KAPL / PRD / 11.

Sr. Item Quantity Quantity Mark ( √ ) for
Item Unit A.R. No. Issued Used material
No. Code Required
1 Filter Pad – 18.0 ” Nos. 15.0
Filter 30” – 1.2 µ 1.00
2 Nos. OT00000277
Part No. :
Filter 30” – 0.2 µ 1.00
3 Nos. OT00000275
Part No. :
Filter 20” – 0.2 µ 1.00
4 Nos. OT00000276
Part No. :
Frequency: After Completion Of □ New Product □ Filter Chock Up □ Integrity Failure

□ Completion of SIP Cycle □ Exceed the Through put

2.3 Checks after Dispensing:
Sr. No. Observation Status
Ensure that the dispensed qty. of each material as per required qty.
1. Yes / No
mentioned in BMR.
Ensure that all the utensils used during dispensing shall be send for
2. Yes / No
cleaning after dispensing
Production officer to ensure completion of all the records after
3. Complies / Does not comply
completion of dispensing activity.
All the details whatever is necessary should be recorded in Batch
4. Complies / Does not comply
Manufacturing Record.
No over writing is allowed in the Batch Manufacturing Record. If the
5. initial data is wrongly entered, cancel the data by single stroke across Followed / Not Followed
the initial.
Checked by/ Date _____________ Verified by/ Date : _______________

(Production) (IPQA)
2.4 Return Material Status :
Qty. Qty. Returned Received

Sr. Item
Ingredients UOM Dispensed Returned A.R. No. By By
No. Code In Kg In Kg Prod. (Store)
1 Metronidazole IP Kg. ( ** )
Sodium Chloride
2 Kg. ( ** )
IP
Di Sodium Hydrogen
3 Kg. ( ** )
Ortho Phosphate USP
Citric Acid IP
4 Kg. ( ** )
Plastic Granules
5 Kg ( ** )
(LDPE)

3.0 CLEANING and STERILIZATION OF EQUIPMENT (SOP No.: KAPL / PRD / 09.)
Sr.
Observation Status
No.
Complies /
1. Check the cleaning of Mixing Room
Does not Comply
2. Is the positive pressure between the areas as per requirement? Yes / No
Is Temperature and Humidity of Manufacturing Area within limits specified in
3. Yes / No
BMR?
4. Are all the remnants of the previous product removed? Yes / No
Ensure that no person entering in the manufacturing area is suffering from cold Followed /
5.
fever, with open wound. Not Followed
6. Verify drain water from the Jacket of Mixing Vessel Verified / Not verified
7. Check release pressure of Jacket of respective Vessel Verified / Not verified
8. Ensure no solution of previous batch is lying in to Mixing Vessel Verified / Not verified
Complies /
9. Check the all required Utility
Does not Comply
Are all the equipment’s and Accessories to be used in manufacturing of batch
10. Yes / No
clean
11. Are all the equipment’s tagged with “CLEANED” Labels? Yes / No
No over writing is allowed in the Batch Manufacturing Record. If the initial Followed /
12.
data is wrongly entered, cancel the data by single stroke across the initial. Not Followed
Note: Area & equipment are satisfactory / not satisfactory and are released / not released for manufacturing.
Precommencement Checked By / Date: ___________ Verified By/ Date: ___________

(Prod. Officer) (QA Officer)
Previous Product: ____________________________________________ Batch No. : ________________
Thermo hygrometer ID No. : EQP / PRD /____

Area : Mixing Room

Time Cleanliness Relative Positive
Temp. Checked Verified
Disinfectant Solution: Humidity Pressure
Date (NMT By By
Start End ( NMT (35-40)
27°C) Production (QA)
______________________ 55% RH ) Pa
Complies/Does not Comply
3.2 Cleaning in place and Steaming in place (SOP No. – KAPL / PRD / 40. )

______ Batch after CIP/SIP.
A] Mixing Vessel
Manufacturing Process consisting of following

Loop: 1 Mixing Vessel, Filter Press, Product Filter (1.2 µ, 0.2 µ), Product piping prior to Holding Vessel
Loop: 2 Holding Vessel, Product piping, machine Product Filter (0.2 µ), Buffer vessel, FFS Machine
Sr. Check Points Observation
No
( A ) Loop -1
1 Disconnect the loop -1 end point (Mixing to Holding vessel) and close
Done / Not Done
the drain valve of loop-1
2 Connect the SS pipe to loop-1. Done / Not Done
3 Close the jacket inlet- outlet (cooling tower water). Done / Not Done
4 Open the air vent valve and drain valve of jacket for drain the water from
Done / Not Done
jacket.
5 Check SIP cycle/ Solution pass from 1.2 µ filter and 0.2 µ filter, if limit
Verified /
exceeded then change the filter, also check the status of filter integrity test
Not Verified
of 0.2µ filter. (Filter limit:- Max. 350000 L, SIP cycle Limit:- NMT 25)
6 Take approx. 250 L WFI in Mixing Vessel and circulate for 5 minutes &
Done / Not Done
drained.
7 Again take approx. 800 L of WFI. Stir and recirculate it for 05 minutes. Done / Not Done
8 Based on the auto system result and completion of CIP cycle, collect the
Done / Not Done
CIP sample in suitable beaker from SS pipe and send to QC for analysis.
Note: - Above sample is collected by production in presence of QA person.
9 After satisfactory results of CIP carried out SIP as per mentioned below. Done / Not Done
10 Partially open the valve and start steam inlet valve. Done / Not Done
Start the Auto SIP Cycle.
11 Achieve the temperature 121 ͦ C and check the pressure as mentioned
below
1.2µ filter:-1.2 kg/cm2 0.2µ filter:-0.2 kg/cm2 and maintain it for 20 Done / Not Done
minutes then drain the steam condensate by opening the Mixing Vessel
bottom valve. After drain the steam condensate close valve.
12 Reconnect the loop-1 end point (top of Holding Vessel). Done / Not Done
B] Holding Vessel to filling machine ( Loop – 2 ).


Sr. Check Points Observation
No
1 Ensure the Holding Vessel is empty and also that the Filling machine is in
Done / Not Done
static condition.
2 Take conformation from operator that the machine is ready for CIP. Done / Not Done
Note:-Check the mandrel hood proper fit (Check the leakage of WFI and steam during CIP/SIP)
3 Wash the empty vessel by WFI (Approx. 250 L ) Done / Not Done
4 Collect the 250 L (approx.) WFI. Drain the WFI from drain valve. Done / Not Done
5 Again take approx. 800 L of WFI. Stir and recirculate it for 05 minutes. Done / Not Done
6 Open the transfer valve of Holding vessel to filling machine. Done / Not Done
Note:-Check the mandrel hood proper fit (Check the leakage of WFI and steam during CIP/SIP)
7 Based on the auto system result and completion of CIP cycle, collect the CIP
Done / Not Done
sample in suitable beaker from SS pipe and send to QC for analysis.
8 After satisfactory results of CIP start the SIP as per mentioned below. Done / Not Done
9 Reconnect the loop-2 with S.S pipe (Product Pipe). Done / Not Done
10 Close the valve after 0.2µ filter. Sampling valve partially opened. Done / Not Done
11 Open steam valve, achieve the temperature 121° C and pressure 1.2 to 1.3
Done / Not Done
kg/cm2.
12 Open the bottom valve and pass the steam to machine. Done / Not Done
13 Achieve the temperature 121° C of the machine, maintain it for 20 minutes,
Done / Not Done
and check temperature in temperature indicator of machine.
14 Close the steam inlet valve, Drain steam condensate from bottom valve of
Done / Not Done
Holding vessel.
Process Checked By / Date: ___________ Verified By/ Date: ___________


Manufacturing Process consisting of following
Loop: 1 Mixing Vessel, Filter Press, Product Filter (1.2 µ, 0.2 µ), Product piping prior to Holding Vessel
Loop: 2 Holding Vessel, Product piping, machine Product Filter (0.2 µ), Buffer vessel, FFS Machine
Sr. Activity Date Time Done By Checked

No. Start End Prod./QC By QA
CIP of Loop 1 as per SOP No. :
1
KAPL / PRD / 40.
Release
Cond. = _________ µS cm-1 time :
Conductivity, pH, TOC of WFI
pH = _________ ______
2 of Loop 1
Hrs.
Previous Product ______
Traces = _________ (signed by
QC )
SIP of Loop 1 at NLT 121.0 °C
3 for 20 min as per SOP No. : Temp.(°C) Observed temp: ____ °C
KAPL / PRD / 40.
CIP of Loop 2 as per SOP No. :
4
KAPL / PRD / 40.
Release
time :
Cond. = _________ µS cm-1
Conductivity, pH, TOC & Trace
pH = _________ ______
5 Analysis of WFI of Loop 2 Hrs.
Previous Product ______

(signed by
Traces = _________ QC )
SIP of Loop 2 at NLT 121.0 °C
6 for 20 min as per SOP No. : Temp.(°C)
KAPL / PRD / 40. Observed temp: ____ °C
Specific Limit:
WFI : Conductivity ( NMT 1.3 µS cm-1), pH ( 5.0-7.0), TOC ( NMT 500 ppb) , Traces : Should be Nil
Remarks: __________________________________________________________________________________
___________________________________________________________________________________________
___________________________________________________________________________________________

4.0 MANUFACTURING PROCEDURE (SOP No.: KAPL / PRD / 41. )
4.1 Precommencement Checks
Sr. Observation Status
No.
1 Ensure the status of CIP / SIP activity of Loop – 1 &/ or Loop – 2 prior to Verified / Not Verified
mixing operation.
2 Ensure person is with clean, intact and adequate sterile garment and Followed / Not Followed
gloves, while manufacturing the batch.
3 Check the cleaning of Mixing Room as per SOP No. KAPL / PRD / 06. Complies /Does not Comply
4 Is the positive pressure between the areas as per requirement? Yes / No
5 Ensure that AHU system should be ON throughout the dispensing
Complies /Does not Comply
process.
6 Is Temperature (NMT 27°C) and Relative Humidity (NMT 55%) of Yes / No
Manufacturing Area within limits?
7 Ensure by counter checking the weights of all ingredients, assay, and Verified / Not Verified
moisture content as provided by QC, before using in the batch.
8 In case of new product is to be manufactured, are all the remnants of the Yes / No
previous batch removed? (Continue with the existing process, in case of
campaign batches are going to manufactured.
9 Ensure no solution of previous batch is lying in to respective Vessel Complies /Does not Comply
10 Ensure that ONLY QC approved Water for Injection is being used for Complies /Does not Comply
manufacturing purpose.
11 Are all the equipment’s and Accessories to be used in manufacturing of Complies /Does not Comply
batch clean as per the SOP No. KAPL / PRD / 09.
12 All critical aspects during manufacturing like addition of different Followed / Does not followed
ingredients in sequence; pH adjustment etc. must be checked and
recorded by the supervisor
13 Are all the equipment’s tagged with “status” Labels? Yes / No
14 Supervisor to ensure completion of all the records after completion of Complies /Does not Comply
mixing activity
15 Send an intimation slip to QC for bulk analysis after manufacturing is Yes / No
completed.
16 No over writing is allowed in the Batch Manufacturing Record. If the
initial data is wrongly entered, cancel the data by single stroke across the Followed / Not Followed
initial.
Precommencement Checked By / Date: ___________ Verified By / Date: ___________

(Prod. Officer) (Q.A. Officer)

4.2 Bulk Preparation Method (SOP No.: KAPL / PRD / 41. )
Sr
Check points Observation
No
1 Material verification done by production in presence of QA. Yes/No
Take the WFI sample from WFI loop sampling point after drain of 2
2 Yes/No
minutes
After satisfactory results of conductivity, pH and (Check by production and
3 Yes/No
QA) close the valve.
Note:- Before collection of WFI , check the mixing vessel whether it is empty or not, and previous
product must not be present in manufacturing vessel.
4 Ensure that Mixing vessel is empty, previous product must not be present. Yes/No
Close the valve before 1.2 µ filter housing, circulation valve, and sampling
5 Yes/No
valve.
Open WFI valve and take approx. 80% of the Batch Size WFI in Mixing
6 Yes/No
vessel by verification of weight. Based on the batch size calculated (in Kg.).
7 Close WFI valve. Yes/No
Check the jacket cooling valve is opened for maintain the temperature
8 approx. 40 o C. Yes/No
9 Start the stirrer. Yes/No

After achieving the temperature approx. 40 o C of volume vessel, start
10 Material addition in presence of production and QA as per mentioned in Yes/No
BMR.
11 Start the stirrer for 10 min Yes/No
After addition of Materials, remove the empty plastic bags from
12 Yes/No
manufacturing area.
Make the final volume as per require batch size (As per BMR) by opening
13 Yes/No
the WFI Valve.
Check the volume in presence of production and QA also maintain the
14 Yes/No
temperature (approx. 40 ° C).
15 Start the stirring and circulation (at the same time) for 30 minutes. Yes/No
After completion of 30 minutes take the bulk sample by production in
16 Yes/No
presence of QA and send for analysis.
After releasing bulk from QC, check the Holding vessel for no traces of
17 Yes/No
previous product / OR check CIP status on status label.
18 Transfer the bulk solution from Mixing vessel to Holding vessel by closing
the circulation valve. Open the valve before 1.2 µ and 0.2 µ filter and also Yes/No
open the valve after 0.2 µ filter.
19 Inform to operator for start the new batch Yes/No

Previous Product: ___________________________________ Batch No. : ________________
Product manufacturing is / is not continue with previous product.
Dynamic Pass box II (Line 3) Dispensing Room: EQP / PRD / 91 & EQP / PRD / 92
Filter Press (Line 3) : EQP / PRD / 107 Mixing Vessel (Line 3) : EQP / PRD / 93
Sr. Time Done By Checked By
Activity Date Observation
No. Start End Prod./QC QA
Before collection of WFI, Drain WFI pH : ____
from the WFI user point for minimum
5 minutes, send WFI sample for Cond.: ____ µS cm-1 Signed by
1 Analysis. QC
TOC : _____ ppb
Sample Intimation & Release Slip No.: _______________ WFI A.R. No. WFI/LVP - __ / ___________
Start to collect WFI (Approx. 1900
Kg) in to Mixing Vessel. Start the Volume: _____Kg.
2
stirrer after approx. 1500 Kg. of WFI.
Temp. : ____ °C
Temp. at the time of collection.
Cool the WFI up to approx. 40⁰ C.
3
Temp. : ____ °C
Add material in following sequence with stirring, till it gets dissolved.
Material Name Qty
(Kg)
1. Di Sodium Hydrogen Ortho
OK/Not OK
Phosphate IP
Stir solution for minimum 5
OK/Not OK
min.
2. Citric Acid IP
4 Stir solution for minimum 5
min.
3. Metronidazole IP

min.
4. Sodium Chloride IP

min.
Final Volume of Batch Size as 4836 Volume:
5 Kg. ( 4800 L X 1.007 – Sp. Gravity), ___________Kg.
make up with WFI
Stir and recirculate Final Bulk Solution
6 OK/Not OK
for minimum 30 min.


No. Start End Prod./QC QA
Collect Sample of Bulk solution and Color : _______
send it for bulk Analysis.
Clarity : _______
Sample Intimation & Release Slip No.: _______________ pH : _______ ________
Signed by
Bulk A.R. No.: KAPL/B /22 / _____________ ( B.No.) QC
7 Assay : _______
(Metronidazole)
Assay : _______
(Sodium Chloride)
Specific Limit:
WFI : Conductivity ( NMT 1.3 µs / cm -1), pH ( 5.0-7.0), TOC ( NMT 500 ppb)
Bulk: pH ( 5.60 – 6.00 ) , Assay of Metronidazole (98.00% to 102.00%) &
Assay of Sodium Chloride (98.00% to 102.00%)

5.0 FILTRATION
No.
1 Ensure equipment cleanliness before starting the filtration operations. Verified / Not Verified
2 Perform the Filter integrity and get filter integrity verification from QA. Performed / Not Performed
3 Prior to filtration activity, ensure the condition of respective pressure OK / Not OK
gauges of the product filter.
4 Prior to filtration activity, ensure the filter through put and numbers of Cumm. Filter Through put :
sterilization cycles of the filter. ____________________ L
(Limit : Maximum Through put : 3,50,000 L ) Nos. of Sterilization Cycle :

(Limit : Maximum Sterilization Cycle : NMT 25 Cycles) ________ Cycles
5 Production officer to ensure completion of all the records after Followed / Not Followed
completion of dispensing activity.
6 No over writing is allowed in the Batch Manufacturing Record. If the Followed / Not Followed
initial data is wrongly entered, cancel the data by single stroke across the
initial.
7 All the details whatever is necessary should be recorded in Batch Followed / Not Followed
Manufacturing Record.
5.2 Previous Product: __________________________________Batch No. : _______________

Filter Integrity Test Apparatus ID No. : EQP / PRD / 23. (SOP No.: KAPL / PRD / 22.)
No. Start End Prod./Q.C. QA
Perform the Pre Filter
Integrity of 0.2µ Filter from
Mixing Vessel to Holding OK / NOT OK
1
Vessel At ______ Bar
Cartridge Filter No.:
Transfer solution from

Filtration
2 Mixing Vessel to Holding
At ______ Bar
Vessel
Perform the Post Filter
Mixing Vessel to Holding OK / NOT OK
3
Vessel. At ______ Bar
Note : Every batch after CIP & SIP



No. Start End Prod./Q.C. QA
Perform the Pre Filter
Holding Vessel to Buffer OK / NOT OK
4
vessel of Filling machine. At ______ Bar
Transfer solution from

Filtration
5 Holding vessel to Buffer
At ______ Bar
vessel
Perform the Post Filter
Holding Vessel to Buffer OK / NOT OK
6
vessel of Filling machine. At ______ Bar
Note : Only 1st batch after CIP & SIP
Limit for Filtration Pressure: 1.0 to 3.5 bar Limit for Filter Integrity Test : 3.0 to 3.2 bar
Remarks: _________________________________________________________________________

6.0 FILLING OPERATION (SOP No. : KAPL / PRD / 43. )
No.
1 Ensure area and equipment cleanliness before starting the filling operations. Done / Not Done
2 Ensure the status of CIP / SIP activity of Loop – 2 prior to filling operation Done /Not done
3 Ensure the cleanliness of the conveyer belt prior to start of filling operation Done / Not Done
4 Is the positive pressure between the areas as per requirement? Yes / No
5 Complies /
Ensure that AHU system should be ON throughout the filling process.
Does not Comply
6 Is Temperature (NMT 27°C) and Relative Humidity (NMT 55%) of Manufacturing Yes / No
Area within limits?
7 Ensure person is with clean, intact and sterile garment and gloves, while filling the Followed /
batch. Not Followed
8 Ensure color & clarity of solution to be filled prior to filling operation. OK / Not OK
9 Prior to filling operation, ensure that bulk sample has been approved by QC and Approved /
Zero sample has been approved by QC ( 1st batch after CIP/SIP). Not Approved
10 Are all the equipment’s and Accessories to be used in manufacturing of batch clean Yes / No
as per the SOP No. KAPL / PRD / 09.
11 All critical aspects like machine set parameters, empty container weight, Head Followed /
weight of container, fill weight and fill volume etc. must be checked and recorded Not followed
by the supervisor.
12 Ensure by checking the shape of bottle, Embossing of the bottle & code matter on Followed /
bottle. Not followed
13 Supervisor to ensure completion of all the records after completion of mixing Followed /
activity Not followed
14 Send a intimation slip ( in case of Zero sample) to QC for analysis after CIP/SIP is Followed /
completed. Not followed
15 No over writing is allowed in the Batch Manufacturing Record. If the initial data is Followed /
wrongly entered, cancel the data by single stroke across the initial. Not Followed
Precommencement Checked By / Date: ___________ Verified By / Date: ___________


Previous Product: ___________________________________Batch No. : ________________
Thermo hygrometer ID No. : EQP/PRD/____

Area : Filling Room
Time Cleanliness Temp. Relative Positive Checked Verified By
Disinfectant Solution: ( NMT Humidity Pressure By (QA)
Date
Start End 27° C) (NMT (55-60) (Production)
55 %) Pa
Complies / Does not Comply

No.
1 Check the cleaning of Filling Room Complies /
Does not Comply
2 Check the status of CIP/SIP of loop - 2 filling M/C Followed / Not Followed
3 Remove all excess & rejected material of Previous Product from the Filling Removed / Not removed
M/c
4 Destroy all rejected material of Previous Product at respective area. Followed / Not Followed
5 Status board updating for new batch specification Followed / Not Followed
6 Check the all required Utility & Parameter of Filling M/c Complies /
Does not Comply
Precommencement: Checked By / Date: _____________ Verified By / Date: ____________
6.2 Filling Operation as per SOP No. KAPL / PRD / 43.

Holding Vessel (Line 3): EQP / PRD / 94 Filling machine (Line 3): EQP / PRD / 98
Product manufacturing and filling is / is not continue with previous product, analyze Zero sample of Bulk.
Sr. Activity Date Time Observation Done By Checked
No. Prod./Q.C By Q.A.
Collect Zero Sample of Bulk Color : ______________ Release
solution; send Zero bulk ____________ time :
Clarity : ______________
samples for bulk Analysis Hrs. Hrs
pH : ______________ _____ hr.
1
Sample Intimation & Release Slip No.: ___________ Assay : ______________
________
Zero Sample A.R.No.: KAPL/Z/22/_______ (B.No.) (Sodium Chloride) (signed
by QC )
Specific Limit:
Bulk: pH ( 5.60 – 6.00 ) , Assay of Sodium Chloride (98.00% to 102.00%)
Remarks: ____________________________________________________________________________________
Filling Status :

Start On: Date : ________ Time: _____ Hrs. Filling Completion On: (Date) ( _______ Time: ______ Hrs.
Limit of Head Weight (HW) : _______ gm Average Fill Volume: 102.0 ml
_ FW - EW Limit of Fill Volume (FV) 101.0 ml to 103.0 ml

Fill Volume =
Specific Gravity Limit of Filled Bottle Weight ( FW): 113.2 gm to 117.2 gm
Specific Gravity: 1.007 Limit of Empty Bottle Weight (EW): 11.5 gm to 13.5 gm
at 25 ° C
Bottle No. 1 2 3 4 5 6
Code
2 3 M M Y Y
Bottle Code Detail check activity:
Where, 23 – Product Code MM – Month YY – Year

Wall thickness : ( Limit : Between 0.3 mm – 0.6 mm ) (Frequency: At the start of batch filling):
Cavity No. 1 2 3 4 5 6
Observation
Date & Time Performed By Checked By

Production Officer : QA Officer :
Spike Test: (Frequency: At the start of batch filling):

Cavity No. 1 2 3 4 5 6
Observation

Note: Perform the additional spike test in case of any major machine shutdown during batch filling.
Cavity No. 1 2 3 4 5 6
Observation


Note: Check the empty bottle weight and Head weight at the interval of Initial and middle. Check fill weight and
fill volume randomly at the interval of every 60 minutes from each cavity by weighing by manufacturing officer and
shall be verified by QA. Record the results.
Balance ID No.: EQP / PRD/ 110 ( Pre Sterile Area ) – Capacity : 2.0 Kg.
Date Bottle Cavity No. Checked By Verified By

& Wt. Prod. QA
Time 01 02 03 04 05 06
EW
HW
FW
FV
FW
FV
FW
FV
EW
HW
FW
FV
FW
FV
FW
FV
Remarks: _________________________________________________________________________________
EW = Empty Weigh HW = Head Weight ( Limit : Between 1.3 gm to 1.6 gm )

FW = Filled Weight FV = Fill Volume

Balance ID No.: EQP / PRD/ 110 (Pre Sterile Area) – Capacity: 2.0 Kg.

& Wt. Prod. QA
Time 01 02 03 04 05 06
EW
HW
FW
FV
FW
FV
FW
FV
EW
HW
FW
FV
FW
FV
FW
FV
Remarks: _________________________________________________________________________________
__________________________________________________________________________________________


& Wt. Prod. QA
Time 01 02 03 04 05 06
EW
HW
FW
FV
FW
FV
FW
FV
EW
HW
FW
FV
FW
FV
FW
FV
Remarks: _________________________________________________________________________________
__________________________________________________________________________________________


& Wt. Prod. QA
Time 01 02 03 04 05 06
EW
HW
FW
FV
FW
FV
FW
FV
FW
FV
Remarks: Machine Stoppage History:
Sr. Stoppage Time Total Stoppage Reason For Stoppage Sign. Of Prod.
No. From To Time (in hrs.) Chemist

6.3 Filling Reconciliation as per SOP No. KAPL / PRD / 32.
Batch Size X 1000

1. Theo. Fill Qty. = = 47058 Qty.
Average Fill Volume
2. Production Line loss ( Approx. 15.0 L ) = 147 Qty.
3. Expected Fill Quantity = 46911 Qty.
4. Actual Filled Quantity ( a ) = Qty.
5. Rejection Quantity during Filling ( b ) = Qty.
6. No. of Container for Spike test ( c ) = Nos.
7. No. of Sample for Bio burden test ( d ) = No.

Any Other samples withdrawn (Specify )
8.
(e.g. Validation etc.) – ( e ) = Nos.
No. of bottle transfer to sterilization Process – ( f )
9. = Qty.
(f)=a–b -c–d–e
Filling Yield (%) = Act. Filled Qty X 100

10. = __________ X 100 = ___________ %
( NLT : 96.0 % ) Expected Fill Qty
46911
Filling Rejection Qty. Destroyed By / Date Checked By ) / Date Verified By / Date

(Production Officer (QA Officer)
Filling Yield Verification

Calculated By Checked By Verified By
(Prod. Officer) (Prod. Executive) (QA Officer / Executive)
Signature
Date
Name
Remarks: ___________________________________________________________________________________
____________________________________________________________________________________________
7.0 STERILIZATION OF PRODUCT


No.
1 Check and ensure that sterilizer is ready for use and all required utilities are Complies /
available. Does not comply
2 Ensure the status label “READY FOR STERILIZATION” & Chemical indicator Affixed /
tag are affix on each trolley to be sterilized. Not Affixed
3 All critical parameters like Chamber pressure, Jacket pressure, Sterilization load Complies /
details (sterilization temperature and time) etc. must be checked and recorded by Does not comply
the supervisor prior to sterilization cycle.
4 Ensure the placement and position of load probe in the sterilization and container Followed /
prior to sterilization cycle start. Not followed
5 Get line clearance from QA for sterilization activity. Followed /
Not Followed
6 After sterilization cycle, verify the sterilization temperature and time on the print Complies /
out and shall be as per recommendation in BMR and shall be recorded by the Does not comply
production supervisor.
7 No over writing is allowed in the Batch Manufacturing Record. If the initial data is Followed /
wrongly entered, cancel the data by single stroke across the initial. Not Followed
Previous Product: ___________________________________Batch No. : ________________

No.
1 Check the cleaning of Super-heated Steam Sterilizer Complies /
Does not Comply
2 Check the all required Utility & Process Parameter Complies /
Does not Comply
3 Check Nos. of loaded Qty. in every tray & trolley OK / Not OK
4 Ensure FOFI system each trolley is tagged with status
OK / Not OK
*Lot can be differ in case of sterilizer availability
5 Check the printer for its record, setting and stationary requirement.
OK / Not OK
6 Check Placement of Temp. Probe (i.e. for all load temp. probe) in bottle Followed /
Not Followed
Precommencement Checked By/ Date: ______________ Verified By/ Date: _____________

7.2 Product Terminal Sterilization as per SOP No. KAPL / PRD / 44.

Sterilizer ID No. : EQP / PRD /____ Set Temperature: 106.5 °C Set Time: NLT 75 minutes
Critical Temperature: 105.0 °C Over shoot Temperature: 108.5 °C Set Chamber Pressure: 1.15 bar
Stabilization Temperature: 104.0 °C Stabilization Time: 2.0 minutes
Date Sterilization Process Sterilization Time Support Process Done By Checked
Load details Start at (At 108°C for 60 minutes) Pressure End at (Prod.) By
Lot Load From To in (QA)
No. Qty. Chamber
Note: If any control probe defection occurs during Sterilization cycle, then consider any one probe and complete the
Sterilization cycle.
Total Holding Time: ________Hrs. (Start from material addition to last lot sterilization phase start)
(NMT 36 Hours)
Sterilization report (Print –out) checked and attached by _____________
Finished Product Sampling detail after Sterilization Procedure Done By Checked By

(Prod.) (Q.A.)
Lot No. Sample Qty. Sample Intimation Slip No.:
No. of good Qty. send

Total Sterilized Qty. Total Sample Qty.
for Packing
7.3 Checks after sterilization

No.
1 Check the integrity of the probe in container and position of the probe in the Followed /
Not followed
sterilization as per respective SOP after completion of sterilization cycle.
2 Ensure the status label as “STERILIZED” with BLACK in colour is affix on Affixed / Not Affixed
each trolley after completion of sterilization.
3 Ensure that the color of chemical indicator is change that is from white (before Complies /
Does not comply
sterilization) to brown (after sterilization) by production chemist.


No.
4 Supervisor to ensure completion of all the records after completion of Complies /
Does not comply
sterilization activity.
5 No over writing is allowed in the Batch Manufacturing Record. If the initial data Complies /
Does not comply
is wrongly entered, cancel the data by single stroke across the initial.
6 All the details whatever is necessary should be recorded in Batch Manufacturing Complies /
Does not comply
Record.
7 Ensure the generation of intimation slip by manufacturing supervisor and Complies /
Does not comply
withdrawal of QC samples by QA personnel after sterilization cycle. Send the
collected samples to QC as Finished product analysis as per SOP No. KAPL /
QA / 13.
7.4 Post verification

No.
1 Transparency of the filled container Complies / Does not comply
2 Clarity and color of solution OK / Not OK
3 Physical shape of the bottle OK / Not OK
4 Sterilization details in to sterilization print-out Complies / Does not comply
5 Status tag with product Name & Batch No. after sterilization cycle OK / Not OK
Precommencement Checked By/ Date:_ ____________ Verified By/ Date: ____________

Remark : ______________ ______________________________________________________________________
Sterilization Verification
Done By Checked By Verified By
(Production Officer) (Prod. Executive / Prod. Manager) (QA Officer / Executive)
Signature
Date
Name
----- End of Batch Manufacturing Record -----

BMR - Metro - 0.5 % - IP - 100 ML - 4800 L

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KAMLAAMRUT PHARMACEUTICAL LLP.

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 1 of 32

BMR No. : BMR/LVP/23/100/I Manufacturing Line No. : 03

Mfg. License No. : G/28D/LVP/24

Volume : 100 ml in LDPE Plastic Container by FFS technology

BMR Issue No. : 01 BMR Revision No. : 00

BMR effective Date : 10/01/2023

BMR Issued By BMR Checked By and Reviewed By Batch Released By

Prepared By Reviewed Verified By Approved by

Name Kushal Jiyani Shashin Upadhyay Arpit Nayak Sachin Saple

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 2 of 32

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 3 of 32

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 4 of 32

List of Production Equipment

Sr. No. Name of Instrument / Equipment Equipment ID No.

3. Weighing Balance – 60.0 Kg ( RM Dispensing Room) EQP / PRD / 104

7. Mixing Vessel (Line 3) - Mixing Room – 7000 L EQP / PRD / 93

8. Holding Vessel (Line 3) - Mixing Room – 7000 L EQP / PRD / 94

9. S.S. 316 L Filter press (Line 3) EQP / PRD / 107

10. Nanofog Fogger machine EQP / PRD / 64

11. Filter Integrity Test Apparatus EQP / PRD / 23

13. Filling Machine (Line 3) - Filling Room EQP / PRD / 98

16. Plastic Granule Hopper ( Silo machine ) EQP / PRD / 97

17. Sterilizer (Pre Sterile Area) EQP / PRD / 100

19. Disinfectant Room LAF EQP / PRD / 71

20. Disinfectant Assembly EQP / PRD / 73

21. Disinfectant – Manufacturing Tank EQP / PRD / 74

22. Disinfectant – Storage Tank EQP / PRD / 75

23. LAF – Garment Folding EQP / PRD / 89

24. Autoclave For Garment Sterilization – Line 3 EQP / PRD / 95

25. Dynamic Pass Box – Autoclave Unloading Area EQP / PRD / 96

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 5 of 32

Sr. No. Name of Instrument / Equipment Equipment ID No.

29. Digital Micrometer ( Pre Sterile Area ) EQP / PRD / 106

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 6 of 32

1.1 Precommencement Checks:

1.2 Raw materials and Primary packing material Issuance Activity:

Balance ID No. : RM Store : EQP / PRD / 63 ( Capacity : 100.0 Kg. )

1 Metronidazole IP (**) Kg. 24.000

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 7 of 32

2.0 MATERIAL DISPENSING

Precommencement Checked By : (Production ) ____________ Verified by (QA) : _____________

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 8 of 32

Previous Product: ___________________________________ Batch No. : ________________

Thermo hygrometer ID No. : EQP/PRD/____

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 9 of 32

Dispensing Booth ID No. : EQP / PRD / 90 .

Balance ID No. : EQP / PRD / 103 ( Capacity : 60.0 Kg.)

Balance ID No. : EQP / PRD / 104 ( Capacity : 6.0 Kg.)

Std. Qty. Qty. Checked

A* = _9.0 x 100 x 100 x 2.4 Where 9 = Label claim of Sodium Chloride IP ( mg / ml )

= _____________ Kg. to be dispensed

Batch Manufacturing Record

Large Volume Parenteral (For manufacturing Line - 3) Page 10 of 32

Precommencement Checked By : (Production ) Verified by (QA) : _

Previous Product: ___________________ Batch No. :

Checked by/ Date _ Verified by/ Date : ___

Precommencement Checked By / Date: _ Verified By/ Date: _

Previous Product: ____________________________ Batch No. :

Process Checked By / Date: _ Verified By/ Date: _

Precommencement Checked By / Date: _ Verified By / Date: _

5.2 Previous Product: ____________________Batch No. : _

Precommencement Checked By / Date: _ Verified By / Date: _