LEVOSALBUTAMOL+IPRATROPIUM 500 LTRS-2.5 ML

KAMLAAMRUT PHARMACEUTICAL LLP
Survey No. 53, 56, 57, Nr. Kamla Amrut Industrial Park,
Indrad, Ta: Kadi, Dist.: Mehsana, 382715, Gujarat, India.
BATCH MANUFACTURING RECORD (RESPULES)
GENERIC NAME : Levosalbutamol and Ipratropium Bromide Respirator Solution
BATCH NO. : K1060092 Pack Size : 2.5 ml
BATCH SIZE : 500 Ltrs (185185 Respules) Page 1 of 45
Manufacturing Date : 11/2022 BMR No.
Expiry Date : 10/2024 BMR/2.5/RES/06/D
BMR Issue No. : 04 BMR Revision No. 03

BMR Effective On : 03/11/22
Mfg. License No. : G/25/2437
Manufactured By : KAMLAAMRUT PHARMACEUTICAL LLP.
Each 2.5 ml Respule contains
Levosalbutamol Sulphate IP Eq. to
1.25 mg
Label Claim : Levosalbutamol
Ipratropium Bromide IP Eq. to Ipratropium
500 mcg
Bromide (Anhydrous)
In an Isotonic Solution Q.S.
Shelf Life : 24 Months
Pack : 2.5 ml Plastic Respules by FFS Technology
BMR Issued By (QA) : Date :
REVIEWED BY RELEASED BY
Production Executive / Manager Q.A. Executive / Manager
Signature
Date
Name
AUTHORIZATION PAGE
Prepared By Reviewed Approved by Authorized By
Signature
Date 31/10/22 01/11/22 02/11/22 03/11/22

Name KUSHAL JIYANI NACHIKET PATEL HITESH THAKAR SACHIN SAPLE
Executive - GM - Manager –
Designation Sr. Officer - QA
Production Production QA/QC
BATCH MANUFACTURING RECORD CONTENT

Sr. Page
Particulars
No No.
1.0 Master Formula 4
1.1 Raw Material Master Formula 4
1.2 Primary Packing Material Formula 4
2.0 Raw Material & Primary Packing Material Issuance Activity 5
2.1 Line Clearance Checklist for Raw Material & Primary Packing Material 5
2.2 Raw Material Dispensing Record & Primary Packing Issuance Record 5
3.0 Material Dispensing Activity 6-9
3.1 Line Clearance Checklist for Dispensing Activity of Raw Material 8
3.2 Dispensing Booth Operation 9
3.3 Weighing Balance Calibration Status 9
3.4 Raw Material Dispensing Activity 8-9
4.0 Cleaning In Place & Sterilization In Place 10-12
4.1 Line Clearance Checklist for Cleaning In Place & Sterilization In Place Activity 10
4.2 Cleaning in place of Loop – 1 11
4.3 Sterilization in place of Loop – 1 11
4.4 Cleaning in place of Loop – 3 12
4.5 Sterilization in place of Loop – 3 12
5.0 Manufacturing Procedure 13-16
5.1 Line Clearance Checklist for Manufacturing Activity 14
5.2 Bulk Preparation Method 15-16
6.0 Filtration & Filter Integrity Test 17-18
6.1 Line Clearance Checklist for Filtration & filter Integrity Test 17
6.2 Bulk Filtration Method 18
7.0 Filling Operation 19-30
7.1 Line Clearance Checklist for Filling Operation 20
7.2 Filling Operation 21
In-process Check Details, Separation , Thickness , Parameters, Sampling
7.3 21-40
Plan and Observation
7.4 Filling Reconciliation 41
7.5 Reconciliation of Plastic Granules 42
8.0 Vacuum Leak Test Operation 42-45
8.1 Line Clearance Checklist for Leak Test Operation 42
8.2 Product Leak Test Operation 43
8.3 Post Leak Test Verification 43
8.4 Finished Product Sample Details 44
9.0 Batch Reconciliation 45
List of Production Equipment

Sr. Equipment ID.
Equipment Name
No. No.
1 Mixing Tank – 1 EQP/PRD/01

2 Mixing Tank – 2 EQP/PRD/02
3 Holding Tank – 1 EQP/PRD/03
4 Filling Machine – 1 EQP/PRD/11
5 Autoclave – 1 EQP/PRD/15
6 Super Heated water Spray Sterilizer – 1 EQP/PRD/18
7 RM Dispensing Booth – 1 EQP/PRD/19
8 Plastic Silo – 1 EQP/PRD/21
9 Filter Integrity Test Machine EQP/PRD/23
10 Leak Test Machine with Vacuum Chamber EQP/PRD/24
11 Static Pass Box–1 EQP/PRD/41
15 Dynamic Pass Box–1 EQP/PRD/45
16 Dynamic Pass Box–2 EQP/PRD/46
17 Weight Balance (20 Kg) RM Dispensing Room – 1 EQP/PRD/53
18 Weight Balance (2 Kg) RM Dispensing Room – 1 EQP/PRD/54
19 Weight Balance (220 gm) Pre-sterile Area EQP/PRD/57
20 Weight Balance (100 Kg) Scrap Room EQP/PRD/61
21 Weight Balance (100 Kg) RM Receiving Area EQP/PRD/62
22 Weight Balance (100 Kg) RM Store EQP/PRD/63
1.0 MASTER FORMULA
1.1 Raw Material Master Formula

Sr. Label Amount

Ingredients UOM Overages% Batch Quantity
No. /2.5 ml
Levosalbutamol
1 Sulphate IP Eq. to Kg 1.25 mg 20% 0.300 Kg
Levosalbutamol
Ipratropium Bromide IP
2 Eq. to Ipratropium Kg 500 mcg -- 0.104 Kg
Bromide (Anhydrous)
3 Sodium chloride IP Kg -- -- 4.500 Kg
4 Sulphuric acid BP ml For pH Adjustment -- Q.S.
5 Water for Injection IP Ltrs Q.S. -- 500 Ltrs
Checked By: Verified By:

Sign & Date Sign & Date
(Production) (QA)
1.2 Primary Packing Material Master Formula
Sr. Label Amount

Ingredients UOM Overages% Batch Quantity
No. (mg/2.5 ml)
Plastic Granules Medical

1 Kg --- -- 700 Kg
Grade
(Production) (QA)
2.0 RAW MATERIAL & PRIMARY PACKING MATERIAL ISSUANCE ACTIVITY

(Reference SOP No.: KAPL/SD/06 & KAPL/PRD/11)
2.1 Line Clearance Checklist for Raw Material Issuance Activity Date:___________
Check Point Observation
2.1.1 Ensure that material storage area cleaned Cleaned / Not Cleaned
Check that the Temperature & Relative Humidity of Raw
Material Store area measured with Digital Thermo-
hygrometer is within its Limit and Record it.
Satisfactory /
2.1.2
Temperature: _____________ (Limit : 23.0 to 27.0°C)
Not Satisfactory
Relative Humidity: ______________ (Limit: NMT 60%RH)
Check all the materials proper labeled and segregated

2.1.3 Yes / No
with adequate precautions in order to avoid a mix-up
2.1.4 Check the Weighing Balance Calibration done. Yes / No
Check Each material is released by QC and also within
2.1.5 Yes / No
shelf-life.
Ensure that FIFO or FEFO system followed by store
2.1.6 Yes / No
personnel
2.1.7 Ensure that the issued material is approved by QC. Yes / No
(Production) (QA)
2.2 Raw Material & Primary Packing Material Requisition Slip Date: _________
Sr. Std. Qty. Issue

Ingredients UOM A.R. No.
No. Required Qty.
Levosalbutamol Sulphate IP Eq.
1 Kg 0.300
to Levosalbutamol
Ipratropium Bromide IP Eq. to
2 Ipratropium Bromide Kg 0.104
(Anhydrous)
3 Sodium chloride IP Kg 4.500
4 Sulphuric acid BP ml Q.S.
5 Plastic Granules Medical Grade Kg 700.00

Requisition Raised By (Prod.) Received By (Store) Verified By: (QA)
Note: Transfer the Raw material and Primary Packing Material as per SOP No.: KAPL/PRD/11.
3.0 MATERIAL DISPENSING ACTIVITY Reference SOP No.: KAPL/PRD/11
 Ensure area and equipment cleanliness before starting the dispensing operations.
 Check and ensure that all equipments and other required accessories are clean and ready
for use.
 Ensure that utensils to be used shall be clean and dry prior to dispensing activity.
 Wear cleanroom garment and gloves as per SOP of Entry Exit Procedure while dispensing
material of batch.
 Get line clearance from QA for dispensing.
 Ensure that AHU system should be ON throughout the dispensing process.
 Temperature of area should be 230 C - 270 C and Relative Humidity should be NMT 60 %
RH.
 Verify the required positive pressure readings wherever essential.
 Check the positive pressure on RLAF and shall be within specified limit.
 Check the balance calibration status, which is to be used. Verify the cleanliness after
dispensing.
 Counter check the weights of all active ingredients, assay, and moisture content as
provided by QC, before using in the batch.
 During the dispensing of this product, no other product processing should be done in the
same area.
 Ensure the cleanliness and dryness of the SS container, to be used (if required ) prior to
dispensing.
 Ensure the dispensed qty. of each material as per required qty. mentioned in BMR.
 Ensure that all the utensils used during dispensing shall be send for cleaning after
dispensing.
 Supervisor to ensure completion of all the records after completion of dispensing activity.
 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 initial.
 All the details whatever is necessary should be recorded in Batch Manufacturing Record.
3.1 Line Clearance Checklist for Dispensing Activity of Raw Material
Date: _____________
Check Point Observation

Ensure that all equipments and other accessories are cleaned and Satisfactory /
3.1.1
ready for use Not Satisfactory
Check that the Physical Parameter of the RM Dispensing room is in Satisfactory /
3.1.2
Limit and Record it. Not Satisfactory
Check the Positive pressure of RM Dispensing Room is in limit and Satisfactory /
3.1.3
Record it. Not Satisfactory
3.1.4 Ensure that RLAF ON before the 30 Minutes of the dispensing start OK / NOT OK
3.1.5 Check the Pressure of the RLAF and record it. OK / NOT OK
3.1.6 Check the status label available on the Dispensing Utensils Yes / No
3.1.7 Check the Weighing Balance Calibration done. Yes / No
Ensure that the previous batch material Absent in the RM Satisfactory /
3.1.8
dispensing Room. Not Satisfactory
During the dispensing of this product, no other product processing
3.1.9 OK / Not OK
should be done in the same area.
Check the cleanliness of the RM Dispensing Room and ensure that Satisfactory /
3.1.10
area is cleaned Not Satisfactory
3.1.11 Ensure the sequential Log Book is filled up to stage. Yes / No
(Production) (Quality Assurance)
Previous Product: ___________________________________Batch No. : __________________
Cleanliness & Physical Parameter checks Reference SOP No.: KAPL/PRD/06

Area : Raw Material Dispensing Room-1
Cleanliness Physical Parameter of Dispensing Room
Disinfectant Date Time

Date Time
Solution Temperature (25 ± 2)°C
Humidity (NMT 60%RH)
Positive Pressure (15-20) Pascal

Signature & Date Signature & Date
3.2 Dispensing Booth Operation

Note: Ensure that Dispensing Booth RLAF start before 30 minutes of Dispensing Activity
Equipment: Dispensing Booth-1 Equipment ID No.: EQP/PRD/19

Physical Parameter checks Reference SOP No.: KAPL/PRD/06 & PRD/EQP/09
RLAF Date Positive Pressure
Operation & Physical Start Time (15-20) mmwc
Parameter Checks End Time mmwc
3.3 Weight Balance Calibration Status

Equipment: Weight Balance Reference SOP No.: KAPL/PRD/10
Equipment No. (20 KGS):EQP/PRD/53 Calibrated / Not Calibrated
Equipment No. (2 KGS): EQP/PRD/54 Calibrated / Not Calibrated
3.4 Raw Material Dispensing Activity
Dispensing Date: Start Time: Completed Time:

Sr. Std. Qty. Dispensed Checked Verified
Ingredients A.R. No. Remarks
No. Required Qty. By Prod. By Q.A
Levosalbutamol
1 Sulphate IP Eq. to 0.300
Levosalbutamol
Ipratropium
Bromide IP Eq. to
2 Ipratropium 0.104
Bromide
(Anhydrous)
3 Sodium chloride IP 4.500
4 Sulphuric acid BP Q.S.
Note : Check the labels of all dispensed materials for completeness and attach on this page.
Cleanliness checks After Activity Done Equipment ID No.: EQP/PRD/19

Area : Dispensing Booth & Dispensing Room-1 Reference SOP No.: KAPL/PRD/06
Date: Time: Disinfectant Solution:
Note: *Issue Quantity of active ingredient is calculated on less than 99.00% assay basis or more
than 0.50 % Loss on Drying or water content. If Assay of active ingredient and loss on
Drying are different than calculate the Quantity of the active ingredient as follows:
Calculation-1 :
Dispensed Quantity of Active Ingredients in Kgs = Std. Quantity Required x 100 x 100
(%Assay) x (100- Water or LOD)
= ________________x 100 x 100
( ) x (100 - _______ )
= Kgs
Calculation-2:
= ________________x 100 x 100
( ) x (100 - _______ )
= Kgs
In case of More than One A.R. No. of Active Ingredient to be issued based on Following
Formula, For Active Ingredient (For 1 & 2 Material)
Value of Assay & LOD taken base on below mention calculation from table
A.R No. Quantity A=Assay % B=LOD
1 X = P = G =
2 Y = Q = H =
PX+QY GX+HY
X+Y= = =
X+Y X+Y
= (X+Y = ) x 100 x 100

(A = ) x (100 – (B = ))
= Kgs
Calculation Done By: ___________ Verified By: ___________

(Prod. Officer) (Q.A. Officer)
4.0 CLEANING IN PLACE & STERILIZATION IN PLACE Ref. SOP No.: KAPL/PRD/13 & 16
4.1 Line Clearance Checklist for CIP & SIP Activity
Sr. Observation Status
No.
Check the cleaning of Mixing Room & Holding Room as per SOP Comply /
1
No. KAPL/PRD/06 Not Comply
Satisfactory /
2 Check the Physical Parameter is in Limit and Record it.
Not Satisfactory
Satisfactory /
3 Check the Positive pressure of area is in limit and Record it.
Not Satisfactory
4 Ensure that all the remnants of the previous product removed OK / NOT OK
Ensure that drain water from the coated Jacket of respective
5 OK / Not OK
Tank
6 Check release pressure of Jacket of respective Tank OK / Not OK
Ensure no solution of previous batch is lying in to respective OK / Not OK
4
Tank
Comply /
8 Check the all required Utility for CIP & SIP
Not Comply
Ensure that all equipments and other accessories are cleaned Satisfactory /
9
and ready for use Not Satisfactory
10 Check all the equipments tagged with “CLEANED” Labels Yes / No
Comply /
11 Check the CIP Results
Not Comply
Comply /
12 Check the Print out of SIP
Not Comply
Previous Product: ____________________________________Batch No. : ________________

Area : Mixing Room – 1 & Holding Room – 1
Cleanliness Physical Parameter
Cleaning Time Temperature (25 ± 2)°C
Date
Start End Mixing Humidity (NMT 60%RH)
Room-1
Temperature (25 ± 2)°C

Disinfectant Solution
Holding
Room-1 Humidity (NMT 60%RH)

4.2 Cleaning In Place of Loop – 2
Loop: 1 Mixing Tank – 2, Pressure Pump, 0.2 µ Filter, Product Piping

Time Done By
Checked
Date Activity Prod. /
By Q.A.
Start End QC
Cleaning the Vessel, Transfer Pump

& Process Pipe.
250 ml final Rinse sample shall be collected after filter assembly and send to QC For Analysis.
Check the Conductivity, pH &

Previous product Traces Analysis
pH (5.00 to 7.00)
Conductivity (NMT 1.3 µs / cm) µs / cm
Previous Product Traces (NIL)
4.3 Sterilization In Place (SIP) of Loop - 2
Sr. Start End Done By Checked

Activity Date Hold Time
No. Time Time Prod. By Q.A.
SIP at NLT 121.0

3
°C for 30 minutes
Temperature °C
Temperature
Observation Record OK /
4 Temperature °C
for SIP (10 minutes NOT OK
interval)
Temperature °C
4.4 Cleaning In Place of Loop - 3
Loop: 3 Holding Tank-1, 0.2 µ Filter, Buffer Tank, FFS Machine, Product Filter, Product piping
Time Done By
Checked
Date Activity Prod. /
By Q.A.
Start End QC
Cleaning the Vessel, Transfer Pump

& Process Pipe.
250 ml final Rinse sample shall be collected after filter assembly and send to QC For Analysis.
Check the Conductivity, pH &

Previous product Traces Analysis
pH (5.00 to 7.00)
Previous Product Traces (NIL)
4.5 Sterilization In Place (SIP) of Loop - 3
Sr. Start End Done By Checked

Activity Date Hold Time
No. Time Time Prod. By Q.A.
SIP at NLT 121.0

3
°C for 30 minutes
Temperature °C
Temperature
Observation Record OK /
4 Temperature °C
for SIP (10 minutes NOT OK
interval)
Temperature °C
5.0 MANUFACTURING PROCEDURE (Reference SOP No.: KAPL/PRD/19 & 23)
 Ensure area and equipment cleanliness before starting the mixing operations.
for use.
 Ensure the status of CIP / SIP activity of Loop – 1 prior to mixing operation.
 Ensure person is with clean, intact and sterile garment and gloves, while manufacturing
the batch.
 Get line clearance from QA for mixing operation.
 Ensure that AHU system should be ON throughout the mixing process.
 Temperature of area should be 23°C to 27°C and Relative Humidity should be NMT 60 %
RH.
 Counter check the weights of all ingredients, assay, and moisture content as provided by
QC, before using in the batch.
 During the preparation of the batch, no solution shall be remaining in the mixing tank of
previous batch.
 Ensure that only QC approved Water for Injection is being used for manufacturing
purpose.
 All critical aspects during manufacturing like addition of different ingredients in sequence;
pH adjustment etc. must be checked and recorded by the supervisor.
 Supervisor to ensure completion of all the records after completion of mixing activity.
 Release from QA should be taken for all in-process tests mentioned in batch
manufacturing record.
entered, cancel the data by single stroke across the initial & record in Batch
Manufacturing Record.
 Send BMR to QC for bulk analysis after manufacturing is completed.
5.1 Line Clearance Checklist for Manufacturing Activity
Sr. No. Observation Status

Check the cleaning of Mixing Room as per SOP No.

5.1.1 Comply /Does not Comply
KAPL/PRD/06
Ensure that all equipments and other required
5.1.2 OK / Not OK
accessories are clean and ready for use
Check the status of CIP / SIP activity of Loop – 1 prior
5.1.3 Comply /Does not Comply
to mixing operation
Check the positive pressure of Mixing Room - 1 as per
5.1.4 Yes / No
requirement
Is Temperature and Humidity of Manufacturing Area
5.1.5 Yes / No
within limits specified in BMR?
Ensure no solution of previous batch is lying in to
5.1.6 OK / Not OK
respective Tank
Ensure that the WFI checked & approved by QC for the
5.1.7 OK / Not OK
Manufacturing purpose
Ensure that all the equipments tagged with “status”
5.1.8 Yes / No
Labels
Ensure that no solution of previous batch is remaining in
5.1.9 OK / Not OK
the mixing tank.
5.2 Bulk Preparation Method (Reference SOP No.: KAPL/PRD/19 & 23)
Previous Product: ____________________________Batch No. : ________________
Time Done By Checked

Date Activity
START END Prod. By Q.A.
collection approx 100 L WFI in
Mixing tank and Start the circulation
and collect the WFI Sample from
Circulation Sampling Point and send
WFI sample for Analysis in the
Quality Control Department.
Sample Qty. : Approx 250 ml
Results of WFI Analysis
pH (5.00 to 7.00)

Total Organic Carbon
PPB
(NMT 500 PPB)
WATER FOR INJECTION A.R. NO.: WFI/

Date Activity
Collect the approx 300 L Water For

Injection in Mixing Tank – 2
WFI Initial Temperature (NLT 80°C) °C

Cool it By circulation the cooling
water in the jacket till the
Temperature drops to 25°C to 30°C
Temperature after cooling °C
Add material in following sequence with stirring, till it gets dissolved.
Sodium Chloride IP Kg
Continuous Stirring
Check Clarity of the Solution OK / NOT OK
Ipratropium bromide IP Kg
Continuous Stirring

Levosalbutamol
Kg
Sulphate IP
Continuous Stirring

Check the pH the solution.
If require adjust pH with
1N Sulphuric acid solution.
Initial pH of the Solution
Addition of the 1N H2SO4

Final pH of the Solution
(4.0 to 6.0)
Total 1N H2SO4 Consumption ml
Note: Preparation of 1N Sulphuric Acid IP: Take 10 ml Sulphuric acid IP and make
up the volume 400 ml with Water for Injection which shall be previously cooled at
temperature of 25-30°C.

Date Activity
Make up the volume by Water for

Injection to 500 Ltrs in Mixing Tank
–2
Stir the Final Bulk Solution for
Minimum 30 minute.
Open the sampling point from the
bottom of Mixing Tank - 2 and rinse
the clean container with solution.
Collect the approx 250 ml of sample
and send it for Bulk solution
Analysis to QC Department.

Send 100 ml sample for Bio-burden separately in Sterilized
test tube. Sample Qty. : Approx 100 ml
Results of Bulk Analysis
pH
Assay of Levosalbutamol
Assay of Ipratropium Bromide
pH : 4.00 to 6.00
Bulk Assay of Levosalbutamol: 98.00 to 102%
Analysis
Assay of Ipratropium Bromide: 98.00 to 102%
Limit:
Bioburden: Not More Than 100 CFU/100ml
BULK SAMPLE A.R. NO.:
Note: Bio-burden Result is not required of release for further processing.
Remarks: _________________________________________________________________
6.0 FILTRATION & FILTER INTEGRITY TEST (Reference SOP No.: KAPL/PRD/22)
 Ensure equipment cleanliness before starting the filtration operations.

 Get filter integrity verification from QA.
 Prior to filtration activity, ensure the condition of respective pressure gauges of the
product filter.
 Prior to filtration activity, ensure the filter through put.
 Perform the Filter Integrity test before the Batch Solution Filtration, After completion of
the Filter Integrity Test, filter the Solution for further process. Attach the Filter Integrity
Test Printout.
Previous Product: _______________________________Batch No. : _______________
6.1 Line Clearance Checklist for Filtration & Filter Integrity Test
All equipments and other required accessories are clean and

1. Yes / No
ready for use
Ensure the condition of respective pressure gauges of the

2. OK / Not OK
product filter.

6.2 Bulk Filtration Method

Filter Integrity Test Machine Equipment ID No. : EQP/PRD/23
(Reference SOP No.: KAPL/PRD/20 & PRD/EQP/11)
TIME
Done By Checked
Date Activity
Prod. By Q.A.
START END
Perform the Pre Filter Integrity
test of 0.2µ Filter from Mixing
Tank – 2 to Holding tank – 1
Filter Cartridge No.: At mBar
Transfer solution from Mixing
Pressure: Bar OK / NOT OK
Perform the Post Filter Integrity
test of 0.2µ Filter from Mixing
Filter Cartridge No.:

test of 0.2µ Filter from Holding
Tank – 1 to Filling Machine Buffer
Tank
test of 0.2µ Filter from Holding
Tank – 1 to Filling Machine Buffer
Tank
Filter Cartridge No.:

test of 0.2µ Filter of Filling
Machine - 1
test of 0.2µ Filter of Filling
Machine - 1
Perform the Buffer Air Filter
Integrity test of 0.2µ Filter from
to Filling Machine - 1.
Filter Cartridge No.: At ml/min
Perform the Ballooning Air Filter
Integrity test of 0.2µ Filter from
to Filling Machine - 1.
Filter Cartridge No.: At ml/min
Transfer solution from Holding
tank to Buffer Tank at Filling

Machine
Pressure: Bar OK / NOT OK
Filter Integrity Test Perform
Specific Limit for Filtration Pressure : 1.0 to 2.0 bar
Specific Limit for Filter Integrity Test : 3000 to 3500 mbar
Remarks: __________________________________________________________
7.0 FILLING OPERATION (Reference SOP No.:

KAPL/PRD/26)
 Ensure area and equipment cleanliness before starting the filling operations.
for use.
 Ensure the status of CIP / SIP activity of Loop – 3 prior to filling operation.
 Ensure person is with clean, intact and sterile garment and gloves, while manufacturing
the batch.
 Ensure the cleanliness of the conveyer belt prior to start of filling operation.
 Get line clearance from QA for filling activity.
 Ensure that AHU system should be ON throughout the filling process.
 Temperature of area should be 23 – 27°C and Relative Humidity should be NMT 60 % RH.
 Ensure color & clarity of solution to be filled prior to filling operation.
 Prior to filling operation, ensure that bulk sample has been approved by QC and Zero
sample has been approved by QC (1st batch after CIP/SIP).
 Ensure the removal of WFI pipe line connection from the system after batch preparation.
 All critical aspects like machine set parameters, empty container weight, Head weight of
container, fill weight and fill volume etc. must be checked and recorded by the supervisor.
 Check for the wall Thickness of Respules, Twist Test of Respules, and Separation of
Respules with Leak Check and record all the results in Batch BMR.
 Check the Utility Parameter like electricity power for Machine, Compressed air Pressure
and record it BMR.
 Check the shape, Embossing of Respules.

 Release from QA should be taken for all in-process tests mentioned in batch
manufacturing record.
 Send a Zero sample to QC for analysis after CIP/SIP is completed.
7.1 Line Clearance Checklist for Filling Operation
Previous Product: ______________________________Batch No. : ________________
Ensure area and equipment cleanliness before starting the

7.1.1 OK / Not OK
filling operations.
Ensure the status of CIP / SIP activity of Loop – 3 prior to
7.1.2 Comply / Not Comply
filling operation.
Ensure person is with clean, intact and sterile garment and
7.1.3 YES / NO
gloves, while manufacturing the batch.
Prior to filling operation, ensure that bulk sample has been
7.1.4 OK / Not OK
approved by QC.
7.1.5 Check the cleaning of Filling Room. Comply / Not Comply
7.1.6 Remove all excess & rejected material of Previous Product OK / Not OK
7.1.7 Check the all required Utility & Parameter of Filling M/c Comply / Not Comply
7.1.8 Check the shape & Emboss of the Respules. OK / Not OK

Area : Filling Room – 1

Cleanliness Physical Parameter
Date Cleaning Time Date Time

Start End Temperature 25 ± 2°C
Humidity NMT 60%RH
Disinfectant Solution:
Positive Pressure (55-60)Pascal

7.2 Filling Operation (Reference SOP No.: KAPL/PRD/26)

Analyze Zero sample of Bulk (If required).
Sr.
Activity Date Time Observation
No.
Collect Zero Sample
Color: ___________________
solution; send Zero
sample Analysis
Clarity: __________________
1 (Approx 100 Ampoules) pH : _________________
Zero Sample A.R. No.:
Assay : _________________
Z /__________________

(Quality Control) (Quality Assurance)
Specific Limit:
Zero Sample: pH : 4.00 to 6.00, Assay of Levosalbutamol: 98.00 to 102.00% ,
Assay of Ipratropium Bromide: 98.00 to 102.00%
7.3 In-Process check details, Parameters, Sampling plan and Observations:
7.3.1 In-Process check details:
The In-Process sequence is clarity, Sealing Filled Weight (FW), Empty Weight (EV), Fill Volume
(FV)
Calculate the volume of the contents based on the specific Gravity: 1.0022
Weight and Volume is correlated as per below equation.
Fill Volume: Filled Weight – Empty Weight

Specific Gravity
Observation
Test To check To be done
OK NOT OK
Extractable Extract the solution from each
Within in limit Out of limit
Volume vial in Measuring Cylinder
Empty out the vial Weighing
Empty In case of
each vial on the Weighing Within in limit Out of limit
Weight Not ok
balance.
Inform to
Filled Filled vial Weighing each vial operator for
Within in limit Out of limit
weight on the Weighing balance. Rectification
Filled Weight – Empty Weight
Fill Volume Within in limit Out of limit
Specific Gravity
7.3.2 In – Process Parameter Details:
Sr.
Particulars Acceptable Criteria
No.
1 Clarity of the Filled solution An almost colour less clear solution
2 Sealing of Respules Sealed Vial with No Leakage
3 Filled Volume 2.60 to 2.90 ml
4 Average Fill Volume 2.7 ml
5 Empty Respules Weight 1.5 gm to 1.8 gm
6 Filled Respules Weight 4.41 gm to 4.71 gm
7 Sealing of Respules Properly sealed and no leakage from joints
Head should be twist smoothly and separated
8 Twist of Respules
easily.
Top Middle Bottom
9 Thickness of Respules (mm.)
0.46 ± 0.05 0.52 ± 0.05 0.51 ± 0.05
7.3.3 Separation of Respules with Leak Check – Separation Test:

 At the Start of Filling:
Separation Separation Separation Separation Separation
Cavity Cavity Cavity Cavity Cavity
Test (OK/ Test (OK/ Test (OK/ Test (OK/ Test (OK/
No. No. No. No. No.
NOT OK) NOT OK) NOT OK) NOT OK) NOT OK)
1 11 21 31 41
2 12 22 32 42
3 13 23 33 43
4 14 24 34 44
5 15 25 35 45
6 16 26 36 46
7 17 27 37 47
8 18 28 38 48
9 19 29 39 49
10 20 30 40 50
Done By: Checked By:
(Production) (QA)
 At the Middle of Filling:

No. No. No. No. No.
1 11 21 31 41
2 12 22 32 42
3 13 23 33 43
4 14 24 34 44
5 15 25 35 45
6 16 26 36 46
7 17 27 37 47
8 18 28 38 48
9 19 29 39 49
10 20 30 40 50
(Production) (QA)
 At the end of Filling:

No. No. No. No. No.
1 11 21 31 41
2 12 22 32 42
3 13 23 33 43
4 14 24 34 44
5 15 25 35 45
6 16 26 36 46
7 17 27 37 47
8 18 28 38 48
9 19 29 39 49
10 20 30 40 50
(Production) (QA)
7.3.4 Twist Off test of Respule:

Twist Off Twist Off Twist Off Twist Off Twist Off
(OK/ (OK/ (OK/ (OK/ (OK/
No. No. No. No. No.
1 11 21 31 41
2 12 22 32 42
3 13 23 33 43
4 14 24 34 44
5 15 25 35 45
6 16 26 36 46
7 17 27 37 47
8 18 28 38 48
9 19 29 39 49
10 20 30 40 50
(Production) (QA)
Twist Twist Off Twist Off Twist Off Twist Off

Off (OK/ (OK/ (OK/ (OK/ (OK/
No. No. No. No. No.
1 11 21 31 41
2 12 22 32 42
3 13 23 33 43
4 14 24 34 44
5 15 25 35 45
6 16 26 36 46
7 17 27 37 47
8 18 28 38 48
9 19 29 39 49
10 20 30 40 50
Done By:
Checked By:
Signature &
Signature & Date
Date
(QA)
(Production)
 At the end of Filling:

Twist Twist Off Twist Off Twist Off Twist Off
Off (OK/ (OK/ (OK/ (OK/ (OK/
No. No. No. No. No.
1 11 21 31 41
2 12 22 32 42
3 13 23 33 43
4 14 24 34 44
5 15 25 35 45
6 16 26 36 46
7 17 27 37 47
8 18 28 38 48
9 19 29 39 49
10 20 30 40 50
Done By:
Checked By:
Signature &
Signature & Date
Date
(QA)
(Production)
7.3.5 Thickness of Respules:
Cavity Thickness of Respule Cavity Thickness of Respule

No. Top Middle Bottom No. Top Middle Bottom
1 26
2 27
3 28
4 29
5 30
6 31
7 32
8 33
9 34
10 35
11 36
12 37
13 38
14 39
15 40
16 41
17 42
18 43
19 44
20 45
21 46
22 47
23 48
24 49
25 50
(Production) (QA)
Acceptance Criteria:
Top: 0.46 ± 0.05 Middle: 0.52 ± 0.05 Bottom: 0.51 ± 0.05

1 26
2 27
3 28
4 29
5 30
6 31
7 32
8 33
9 34
10 35
11 36
12 37
13 38
14 39
15 40
16 41
17 42
18 43
19 44
20 45
21 46
22 47
23 48
24 49
25 50
(Production) (QA)
 At the End of Filling:

1 26
2 27
3 28
4 29
5 30
6 31
7 32
8 33
9 34
10 35
11 36
12 37
13 38
14 39
15 40
16 41
17 42
18 43
19 44
20 45
21 46
22 47
23 48
24 49
25 50
(Production) (QA)
7.3.6 In-Process Checks During Filling
Filling Operation
Start Date: _________ Time: _________ Completion Date: ________ Time: _______
Note: Production Chemist check the Empty Ampoule Weight, Filled Ampoule Weight & Fill Volume
at initial time of the batch, during the filling of the batch each 60 minutes ± 10 minutes note down
the fill weight & fill volume & verified by QA Person every 60 minutes ± 10 minutes.
Date Time Clarity of Sealing of Visual Checked Verified By

the Solution Respule Inspection By (PRD.) (QA)
7.3.7 Machine Parameter Check
Check the Compressed Air Pressure and Extruder Temperature actual (zone wise) at
starting of the filling operation and record in following tables.
A) Compressed Air Pressure:
Date & Time Parameter Observation Acceptance Observed Verified

Criteria by by IPQA
Compressed At least
Air Pressure 8kg/cm2
B) Extruder Temperature actual (zone wise):
Date & Time: __________________
Observation at the start of the Filling

Section Parameter LIMIT
TEMPERATURE
ZONE – 1 135° to 160°
ZONE – 2 155° to 190°
ZONE – 3 155° to 190°
ADEPTER 70° to 190°
HEAD – 1 80° to 190°
HEAD – 2 85° to 190°
Extruder HEAD – 3 85° to 190°
HEAD – 4 100° to 175°
HEAD – 5 100° to 175°
HEAD – 6 100° to 175°
HEAD – 7 100° to 175°
HEAD – 8 100° to 175°
HEAD – 9 100° to 175°
F.W. Date & Time

Cavity
E.W. (gm)
No.
(gm) F.V.
(ml)
F.W.
1
F.V.
2 F.W.
F.V.
F.W.
3
F.V.
F.W.
4
F.V.
F.W.
5
F.V.
F.W.
6
F.V.
F.W.
7
F.V.
F.W.
8
F.V.
F.W.
9
F.V.
F.W.
10
F.V.
F.W. Date & Time

Cavity
E.W. (gm)
No.
(gm) F.V.
(ml)
F.W.
1
F.V.
2 F.W.
F.V.
F.W.
3
F.V.
F.W.
4
F.V.
F.W.
5
F.V.
F.W.
6
F.V.
F.W.
7
F.V.
F.W.
8
F.V.
F.W.
9
F.V.
F.W.
10
F.V.
F.W.
11
F.V.
F.W.
12
F.V.
F.W.
13
F.V.
F.W.
14
F.V.
F.W.
15
F.V.
F.W.
16
F.V.
F.W.
17
F.V.
F.W.
18
F.V.
F.W.
19
F.V.
F.W.
20
F.V.
F.W.
11
F.V.
F.W.
12
F.V.
F.W.
13
F.V.
F.W.
14
F.V.
F.W.
15
F.V.
F.W.
16
F.V.
F.W.
17
F.V.
F.W.
18
F.V.
F.W.
19
F.V.
F.W.
20
F.V.
F.W.
21
F.V.
F.W.
22
F.V.
F.W.
23
F.V.
F.W.
24
F.V.
F.W.
25
F.V.
F.W.
26
F.V.
F.W.
27
F.V.
F.W.
28
F.V.
F.W.
29
F.V.
F.W.
30
F.V.
F.W.
21
F.V.
F.W.
22
F.V.
F.W.
23
F.V.
F.W.
24
F.V.
F.W.
25
F.V.
F.W.
26
F.V.
F.W.
27
F.V.
F.W.
28
F.V.
F.W.
29
F.V.
F.W.
30
F.V.
F.W.
31
F.V.
F.W.
32
F.V.
F.W.
33
F.V.
F.W.
34
F.V.
F.W.
35
F.V.
F.W.
36
F.V.
F.W.
37
F.V.
F.W.
38
F.V.
F.W.
39
F.V.
F.W.
40
F.V.
F.W.
31
F.V.
F.W.
32
F.V.
F.W.
33
F.V.
F.W.
34
F.V.
F.W.
35
F.V.
F.W.
36
F.V.
F.W.
37
F.V.
F.W.
38
F.V.
F.W.
39
F.V.
F.W.
40
F.V.
F.W.
41
F.V.
F.W.
42
F.V.
F.W.
43
F.V.
F.W.
44
F.V.
F.W.
45
F.V.
F.W.
46
F.V.
F.W.
47
F.V.
F.W.
48
F.V.
F.W.
49
F.V.
F.W.
50
F.V.
Checked By (Prod.)
Verified By (Q.A.)
41 F.W.
F.V.
F.W.
42
F.V.
F.W.
43
F.V.
F.W.
44
F.V.
F.W.
45
F.V.
F.W.
46
F.V.
F.W.
47
F.V.
F.W.
48
F.V.
F.W.
49
F.V.
F.W.
50
F.V.
Checked By (Prod.)
Verified By (Q.A.)
7.4 Filling Reconciliation (Reference SOP No.: KAPL/PRD/32)

Batch Size X 1000 = 500 x 1000 = 185185 Qty.

A Theoretical Fill Qty. =
Average Fill Volume 2.7
B Production Line loss = 1% = 1851 Qty.
C Excepted Filled Quantity = 183334 Qty.
D Due to flushing of Bulk and Zero solution ml = D+E+F

2.75
E Bulk and Zero sample for analysis ml
=
F Sample for Bioburden Test ml
G Bulk Operational Loss = (D + E + F) / 2.75 =
H Actual Filled Quantity = Qty.
I Rejection Quantity during Filling = Qty.
J No. Ampoules are used for Empty Weight = Qty.
K No. of Sample for Other Requirement (If Required) = Qty.

No. of Ampoules transfer to Sterilization & Leak Test Process
L = Qty.
(L = H–I–K)
Act. Filled Qty X 100
M Filling Yield = = = %
Expected Fill Qty
Checked By Verified By
Filling Rejection Qty. Destroyed By Sign& Date Sign& Date
(Production) (QA)
Filling Yield Verification

Calculated By Checked By Verified By
(Prod. Officer) (Prod. Executive) (Q.A Officer / Executive)
Signature
Date
Name
7.5 Reconciliation of Plastic Granules
Primary Issued Used Remain Checked Verified

Sr.
Packing A.R. No. Qty. Qty. Qty.
No. By (Prd.) By (QA)
Material (Kg.) (Kg.) (Kg)
Plastic
1
Granules
8.0 VACUUM LEAK TEST OPERATION (Reference SOP No.: KAPL/PRD/32 &
PRD/EQP/08)
Equipment ID No.: EQP/PRD/18
 Perform the Leak test on the filled Ampoules in Super Heated water Spray Sterilizer by
keeping ampoules in inverted position in perforated SS Trays.
 Transfer the trays in Inspection Department (Packing Department). Ensure that
Temperature inside Sterilizer is Room Temperature.
 Label the Trolley with trays are labeled as “Ready for Leak Test”.
 Ensure that sterilizer is cleaned. & Check Nos. of loaded Qty. in every tray & trolley.
 All critical parameters like Leak Test Load details must be checked and recorded by the
production chemist prior to start the leak test operation.
entered, cancel the data by single stroke across the initial & record in Batch Manufacturing
Record.
8.1 Line Clearance Checklist for Leak Test Operation
Previous Product: _____________________________________Batch No. : ________________

8.1.1 Check the cleaning of Sterilizer Comply / Not Comply
8.1.2 Check the all required Utility & Process Parameter Comply / Not Comply
Ensure the status label “READY FOR LEAK TEST” is affix on
each trolley to be Check for Leak.
8.1.4 Check Nos. of loaded Qty. in every tray & trolley OK / Not OK
All critical parameters like load details must be checked and
8.1.5 OK / Not OK
recorded by the production chemist prior to start.
Check the printer for its record, setting and stationary
8.1.6 OK / Not OK
requirement.
8.1.7 Check Placement of Temperature Probe in bottle OK / Not OK
8.2 Product Leak Test Operation (Reference SOP No.: KAPL/PRD/32)
Leak Test Criteria:

OPERATION INWARD POSITION UPRIDE POSITION
Date of Leak Test Operation
No. of Filled Ampoules
Cycle No.
Temperature of the Chamber

(Ambient Temperature)
Vacuum Applied : -0.700 Kg/Cm2 for 30 Minutes
Vacuum Hold Started at
Vacuum Hold Completed at
Leak Test Carried Out By
Checked By
8.3 Post Leak Test Verification
Sr.
Observation Status
No.
After Leak Test cycle, verify the Leak Test Vacuum and hold
time of the Vacuum in chamber.
Ensure the status label “LEAK TESTED” is affix on each trolley
after completion of sterilization.
8.3.3 Check the Transparency of the Ampoule. OK / Not OK
Check Physical Shape of Ampoule & Clarity & colour of the
8.3.4 OK / Not OK
solution
8.3.5 Report (Print –out) checked and attached by Production YES / NO
8.4 Finished Product Sample detail
Sample Sampled By
Lot No. Purpose
Qty. (Q.A.)
For Finished Product Analysis Samples for Chemical Analysis
For Sterility Test Analysis Sample Quantity.
BET test Sample Quantity
Good Quantity Send Checked By

Total Sample Qty. Done By (Prod.)
for Packing (Q.A.)
Remark: ____________________________________________________________________
Checked By Verified By
(Prod. Exe. / Manager) (Q.A Executive)
Signature
Date
Name
9.0 BATCH RECONCILIATION (Reference SOP No.: KAPL/PRD/32)
Total Leak Tested Ampoules Transfer for the Packing Qty.

Sr.
Manufactured for (As per Batch Packing Record) Total Net Pack Qty.
No.
1 Qty.
2 Qty.
3 Qty.
4 Qty.
Total Net Pack Quantity (1+2+3+4) Qty.
A Theoretical Filled Quantity = 185185 Qty.
B Expected Fill Quantity = 183334 Qty.
C Actual Filled Quantity = ____________ Qty.
D Total Net Pack Quantity = ____________ Qty.
E Good Qty. Transfer to F.G. Store = ____________ Qty.
Net Pack Qty. x 100

F Batch Yield (%) = = ____________ %
Theoretical Filled Qty.
Remarks: __________________________________________________________
Batch Yield Verification

Calculated By Checked By Verified By
(Packing Officer) (Prod. Exe. / Manager) (Q.A Officer / Executive)
Signature
Date
Name

LEVOSALBUTAMOL+IPRATROPIUM 500 LTRS-2.5 ML

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LEVOSALBUTAMOL+IPRATROPIUM 500 LTRS-2.5 ML

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KAMLAAMRUT PHARMACEUTICAL LLP

Manufacturing Date : 11/2022 BMR No.

Expiry Date : 10/2024 BMR/2.5/RES/06/D

BMR Issue No. : 04 BMR Revision No. 03

BMR Issued By (QA) : Date :

Production Executive / Manager Q.A. Executive / Manager

Prepared By Reviewed Approved by Authorized By

Date 31/10/22 01/11/22 02/11/22 03/11/22

BATCH MANUFACTURING RECORD CONTENT

List of Production Equipment

1 Mixing Tank – 1 EQP/PRD/01

1.0 MASTER FORMULA

1.1 Raw Material Master Formula

Sr. Label Amount

4 Sulphuric acid BP ml For pH Adjustment -- Q.S.

5 Water for Injection IP Ltrs Q.S. -- 500 Ltrs

Checked By: Verified By:

1.2 Primary Packing Material Master Formula

Sr. Label Amount

Plastic Granules Medical

2.0 RAW MATERIAL & PRIMARY PACKING MATERIAL ISSUANCE ACTIVITY

Check Point Observation

Check all the materials proper labeled and segregated

Sr. Std. Qty. Issue

4 Sulphuric acid BP ml Q.S.

5 Plastic Granules Medical Grade Kg 700.00

3.0 MATERIAL DISPENSING ACTIVITY Reference SOP No.: KAPL/PRD/11

3.1 Line Clearance Checklist for Dispensing Activity of Raw Material

Check Point Observation

Previous Product: ___________________________________Batch No. : __________________

Cleanliness & Physical Parameter checks Reference SOP No.: KAPL/PRD/06

Disinfectant Date Time

Humidity (NMT 60%RH)

Positive Pressure (15-20) Pascal

Checked By: Verified By:

3.2 Dispensing Booth Operation

Equipment: Dispensing Booth-1 Equipment ID No.: EQP/PRD/19

3.3 Weight Balance Calibration Status

3.4 Raw Material Dispensing Activity

Dispensing Date: Start Time: Completed Time:

Cleanliness checks After Activity Done Equipment ID No.: EQP/PRD/19

= (X+Y = ) x 100 x 100

Calculation Done By: ___________ Verified By: ___________

Previous Product: ____________________________________Batch No. : ________________

Temperature (25 ± 2)°C

Positive Pressure (45-50) Pascal

Loop: 1 Mixing Tank – 2, Pressure Pump, 0.2 µ Filter, Product Piping

Cleaning the Vessel, Transfer Pump

Check the Conductivity, pH &

Conductivity (NMT 1.3 µs / cm) µs / cm

Previous Product Traces (NIL)

4.3 Sterilization In Place (SIP) of Loop - 2

Sr. Start End Done By Checked

SIP at NLT 121.0

4.4 Cleaning In Place of Loop - 3

Cleaning the Vessel, Transfer Pump

Check the Conductivity, pH &

Conductivity (NMT 1.3 µs / cm) µs / cm

Previous Product Traces (NIL)

4.5 Sterilization In Place (SIP) of Loop - 3

Sr. Start End Done By Checked

SIP at NLT 121.0

5.0 MANUFACTURING PROCEDURE (Reference SOP No.: KAPL/PRD/19 & 23)

Previous Product: _________________Batch No. :

Calculation Done By: _ Verified By: _

Previous Product: ____________________Batch No. :

Previous Product: ____________Batch No. :

Previous Product: _________________Batch No. : _

Previous Product: ______________Batch No. :