Batch Manufacturing Record(BMR)
Product Name: Atorvastatin calcium equivalent to Atorvastatin 10 mg,Batch Size:2000000 tablets
Composition
Each film-coated tablet contains: Atorvastatin calcium equivalent to Atorvastatin 10 mg
Checklist of BMR
Check Points
Batch release and composition
Checklist of BMR
General instruction
Line clearance check for dispensing
Dispensing sheet of Raw Material
Dispensing sheet of Coating Material
Calculation of Material
General instruction for manufacturing
Equipment required for manufacturing
Manufacturing Process
Line clearance of granulation
Affix dispensing label
Manufacturing process
Line clearance check for blending
Blending
Weight and reconciliation record of blend
Analysis requisition sheet for blend analysis
Compression Process
Compression general instruction
Line clearance for compression
Initial checks for compression parameters & metal detector performance record
Start-up checks
In-process checks(RH.S)
In-process checks(L.H.S.)
Uniformity of weight
Weight record of compressed tablets. Reconciliation
Analysis requisition sheet
Coating process
Line clearance for the coating process
Affix coating material dispensing label
Coating process & parameter record
Weighing record of coated tablet. Reconciliation of coated tablet
Analysis Requisition sheet
Tablet inspection
Reconciliation of inspected tablet
Documentation reconciliation
General Instructions
Dispensing of Raw material
Use a nose mask and hand gloves during the operation.
Check for line clearance, and cleanliness of the area equipment and record the observations
Check the temperature %RH & differential pressure of dispensing area (20-25°c , 50±20% NLT 1.2 mm of water)
Check for the approved label and necessary details (material name, item code, manufacturer’s name, B.no, MFG, EXP, A.R No, retest date, etc.) on the raw material container before weighing.
Check and transfer the raw material required for the batch near the dispensing booth.
Operate dispensing booth as per current SOP. Dispense the excipients first, and remove them from the dispensing area prior to active ingredient dispensing.
Make necessary entries in the manufacturing work order and the store ledgers
Attach the duly filled dispensed material label to the dispensed raw material and transfer the dispensed material to dispensed material quarantine area.
Drug Master Files (DMFs) and it submission
Line clearance check for Dispensing of Raw Materials
Is the temperature 20-25°c? Actual Temperature
Is the Humidity 50±20%RH?
Is the pressure differential NLT actually 1.2
Is the room clean where the material to be dispensed kept?
Is the LAF table cleaned and switched on at least 15 minutes before starting dispensing?
Are all the materials of the previous batch/ product been completely removed including dust bins?
Is the balance clean and calibrated?
Do all the materials to be dispensed have approved status?
Are all the dispensing devices clean & ready for use?
Are polybags of various sizes required for dispensing materials available?
Is the copy of said BMR relevant to dispensing available?
Isopropyl Alcohol: 8.00 kg
Polyvinyl Pyrrolidone K 30(Kollidon K 30) : 1.0 kg
Lubricant
Colloidal Anhydrous Silica (Aerosol 200): 1.0 kg
Croscarmellose sodium (Ac-di-SD-711) : 1.4 kg
Magnesium Stearate : 0.6 kg
Coating material issue note:
Opadry pink: 1. kg
purified water: 5.0 kg
Water contents shall be compensated based on the actual %of water in API. If the assay of the API is more than 100% the standard quantity of Atorvastatin calcium shall be taken Atorvastatin calcium should be micronized& the particle size of Atorvastatin calcium should be d90 below 50 microns.
Theoretically, 10.85 mg of Atorvastatin calcium is equivalent to 10 mg of Atorvastatin.
Quantity of Microcrystalline Cellulose to be adjusted based on actual assay & % w/w water content of Atorvastatin calcium
Calculation of material required for a single A.R no for the standard batch size
Calculation of Atorvastatin calcium(For Single A.R.No)
A.R.No of Atorvastatin calcium ,Assay on Dried Basis (ODB)——-%w/w ,LOD——–%w/w
The standard quantity of Atorvastatin calcium for batch on 100% Basis(Q)in Kgs i.e. 2.17 Kgs for 200000 tablets batch size as per BMR.
Actual Quantity to be issued Std Qty (Q) *100*100
against of Atorvastatin calcium (Q1)in Kgs = Assay on (ODB)*(100-LOD)
Note: if the quantity of Atorvastatin calcium is insufficient for the batch then proceed with under mentioned calculation.
Calculation of material required if the material available is not sufficient from one Batch or Lot, then the calculation of the next Lot/Batch shall be performed as under.
From first A.R No. quantity of batch available (Q1) which is insufficient for the batch & in this case remaining quantity shall be taken from another batch A.R No along with Q1 for 100% assay basis by the following expression.
A.R No of Atorvastatin calcium, Assay on Dried basis (ODB) ——%w/w, LOD——-% w/w
Quantity available Atorvastatin calcium = Kg
Available Quantity on 100% basis of Atorvastatin = Quantity available * 100*100/Assay (ODB)*(100-LOD)
calcium in Kgs(Q1)————————————— = Kgs
Further, use the following expression to calculate the quantity of additional Atorvastatin calcium quantity required from the next batch or Lot
A.R No. of Atorvastatin calcium ————– Assay on Dried basis (ODB) ——%w/w LOD——-% w/w
Quantity required of Atorvastatin calcium another lot or batch at 100% basis in Kgs (Y)=Std. Quantity reqd. for the batch – Quantity for 1st lot/batch. = ———-Kgs.
Available Quantity to be
issued against Atorvastatin = Std. quantity (Y)*100*100
calcium (Y1)in Kgs ————– = Kgs
Assay on (ODB)*(100-LOD)
Total Quantity issued in Kgs
Note: if more than two batches are required then the calculation follows these steps.
Adjustment or statement batch size in Kgs.
The actual quantity of Atorvastatin calcium is to be calculated on the basis of assay and water of the drug and the quantity is to be compensated with microcrystalline cellulose (Avicel PH101).
The actual quantity of Atorvastatin calcium – Standard quantity of Atorvastatin calcium = Kgs
Standard qty. of microcrystalline cellulose -quantity =Kgs
General instruction for Manufacturing
During the operation, all personnel of the manufacturing area should wear clean uniforms, caps, nose masks, and hand gloves.
Check the relative humidity, temperature, and pressure difference and record where ever necessary & should be Temp 20-25ºc & RH 50±20%, PD -NLT 1.2 mm water.
Check the line clearance, cleanliness of the area, and equipment.
Cross-check the weight of the material before taking it up to manufacturing against the dispensing label and status label.
In case of any deviations in the process, intimate to the QA and take approval from the QA for the same.
Whenever there is a machine breakdown during processing, rectify the machine and take again line clearance from QA before starting the operation.
Holding time
Dispensed materials: 15 days from the date of dispensing.
Blend: Compression to be completed within 15 days from the date of quality control approval.
Compressed tablets: To be coated within 30 days from the date of compressed tablets’ approval by QC.
Coated tablets: Packing is to be completed within 45 days from the date of approval by QC.
Equipment Required
S.S Scoops & Inprocess plastic containers
Dispensing cabinet
Vibratory sifter
Fluid bed processor
Conta blender
Tablet compression machine
Deduster
Metal Detector
Dust collector
Lifting & positioning device
Friability Apparatus
Digital hardness tester
Disintegration test apparatus
Vernier caliper
Balance
Auto coater machine
Solution preparation tank
Colloidal mill
Tablet inspection machine
Line Clearance for Granulation
is the temperature 20-25°c? Actual Temperature
is the Humidity 50±20%RH actual
is the pressure differential NLT 1.2 Actual
is the room clean, where the material to be processed is kept & where the processing is to be done?
Does all the equipment have cleaned status labels & is the cleaning in the validity periods?
Are all the materials of the previous product/batch been removed including the dust bin
Are all the documents /papers for the previous product/batch been removed
Is the BMR for the same product & required batch available?
Are all the materials issued of the required batch & product only?
Manufacturing Process
Sifting
Sievesintegrity checked (Before sifting) Set sifter with 40 sieves and sift & mix Atorvastatin Calcium Micronized Standard Quantity 2.17 kg Calcium Carbonate (PPT)(Calopake extra light) Standard Quantity 1.0kg
Set the sifter with 40 # sieves & mix with Microcrystalline Cellulose (Avicel PH 101) Standard Quantity 10.93kg
Lactose Monohydrate (Pharmatose 200M)
Standard Quantity 10.93kg
Collect sifted material in a polyline container and Check the sleeve integrity # 40 after sifting
Preparation of binding solution
Collect in an SS vessel Isopropyl Standard Quantity 8.00kg
Add slowly into isopropyl alcohol following material under stirring Polyvinyl Pyrrolidone K 30(Kollidon K 30)___Kgs
Standard Quantity 1.000kg
Stir the solution until the Polyvinyl Pyrrolidone K 30(Kollidon K 30) is completely dissolved
Granulation
Set FBP & load in top spray product container,sifted materials from 10 min at 20 rpm
Mixing starting at Mixing over at Blower speed
Set the parameters as given in the following table
Parameters
Inlet temperature:30°-65°c
Bed temp.:20°-35°c
Blower speed:20-40Hz
Peristaltic pump speed:20-80 rpm
Granulate material by spraying with binder and with continuous drying. Dry the granules till the LOD of the granules is NMT 3.0% by halogen moisture balance
Granulation Time
From________To_____________LOD(NMT 3.0%)
Upload the dried granules in polyline containers
Line clearance for Blending
is the temperature 20-25°c? Actual Temperature
is the Humidity 50±20%RH actual
is the pressure differential NLT 1.2 Actual
is the room clean, where the material to be processed is kept & where the processing is to be done?
Does all the equipment have cleaned status labels & is the cleaning in the validity periods?
Are all the materials of the previous product/batch been removed including the dust bin?
Are all the documents /papers for the previous product/batch been removed
Is the BMR for the same product & required batch available?
Are all the materials issued of the required batch & product only?
Blending
Set sifter with 40# sleve for lubricant and sift Colloidal Anhydrous Silica____Kgs
Croscarmellose sodium___________Kgs
Set sifter with 60# sleve and sift Magnesium Stearate ________ Kgs
Collect sifted material in a polyline container and Check the sleeve integrity # 40 after sifting
Blending
Fit IPC container to Conta Blender.
Load dried granules & lubricants in a conta blender. Mix it for 15 minutes at 9 RPM speed.
Total Blending time(Std time 15 min.)
Weigh the material. Affix the label on the IPC. Transfer it to blend hold room
Lubricant Granules Reconciliation
Theoretical weight of the lubricated granules
Actual weight of granules
QC samples
In-process check loss
Process loss
Actual percentage yield B*100/A = —– = —— Kgs
Reconciliation yield (B+C+D)*100/A = —– = —— %
Send dully filled analysis requisition to QC Department to collect the sample for analysis
Blend Analysis Test Report
A.R No
Description: White color granule powder
Essay: Atorvastatin calcium 95-105% of LC
Report: The sample complies/does not comply with the specification number
Compression
Bring approved blend into the Compression area
Attach metal detector unit after de-duster of compression M/C at both sides (LHS & RHS). Check the performance of the metal detector at every start of the operation & every 4 hours during compression using 0.2 mm ferrous & 0.4 mm Non-ferrous blocks & record the observation.
Compress the blend using upper punches 7.0 mm round, standard, concave embossed with «10» & lower punch 7.0 mm round, standard, concave plain. Set the parameters of compressed tablets as per the parameters mentioned below
Destroy the compressed tablets of the initial two rotations
Carry out the initial checks before starting the operations as specified in the specification given.
Check and enter the individual weight of 37/45 tablets from RHS & LHS separately in the formats provided
Check the record of the Thickness & Hardness, DT, Friability, and group wt of 20 tablets.
Check and enter the uniform weight of 20 tablets from LHS as well as RHS in the prescribed format.
Collects the tablets in a double polythene cover-lined, tightly closed, container. weigh each container & record the weight in the given format
Line Clearance Checks for Compression Process
is the temperature 20-25°c? Actual Temperature
is the Humidity 50±20%RH actual
is the pressure differential NLT 1.2 Actual
is the room clean, where the material to be processed is kept & where the processing is to be done?
Does all the equipment have cleaned status labels & is the cleaning in the validity periods?
Are all the material of the previous product/batch been removed including the dust bin
Are all the documents /papers for the previous product/batch been removed
Is the BMR for the same product & required batch available?
Are the bags fixed to dust collectors’ dedicated ones
Do the bins containing granules for the compression are of the relevant product/batch number and do bins have released status?
Are the metal detector challenged?
Is the startup test as per BMR?
Initial Checks
Description: White to off-white, round-shaped coated tablets embossed with «10» on one side and plain on another side.
Weight of 20 tablets:2.90gm /±3.0%
Average weight:145.00mg ±3.0%
Thickness:3.60mm±0.2mm
Diameters:7.10 mm
Hardness: NLT 20Kgs
Disintegration time: NMT 15 min
Friability: NMT 1%
Performance Checks for Metal Detector
Frequency: at every start of the operation & every 4 hours during compression
Size of Metal Block : 0.2 mm (ferrous) & 0.4 mm (Non ferrous)
Reconciliation of compressed Tablet
Stage
Theoretical
Weight of granules received for compression
Weight of the compressed tablet
Tablets send to Quality Control
In process sample
Loss during compression
Actual percentage yield
Reconciliation percentage yield
Reconciled by (Production)
Send dully filled analysis requisition to Q.C Department to collect the sample for analysis
The requisition analysis sheet was sent by
Coating Process
is the temperature 20-25°c? Actual Temperature
is the Humidity 50±20%RH actual
is the pressure differential NLT 1.2 Actual
is the room clean, where the material to be processed is kept & where the processing is to be done?
Does all the equipment have cleaned status labels & is the cleaning in the validity periods?
Are all the materials of the previous product/batch been removed including the dust bin
Are all the documents /papers for the previous product/batch been removed
Is the BMR for the same product & required batch available?
Ensure that the container containing tablets for coating has released status
Is the startup test as per BMR?
Coating Process
Room Temperature :20-25°c
Pressure Differential :NLT 1.2
Relative Humidity :50±20%
Preparation of Solution
In the solution preparation tank add and prepare the solution of the following materials
Opadry Pink
Std. Qty. 1.000 Kgs
Purified water
Std. Qty. 5.00 Kgs
Stir the solution for 1 hour
Coating
Load the tablets in a coating pan. Start the hot water blower, and set the supply air temperature at 65 -80°c. Start the exhaust fan, and warm the tablet bed to 45°c.
When the exhaust temp reaches 45°c, adjust the spray gun, and start the peristaltic pump with the coating solution. Spray the solution on a rolling tablet bed; simultaneously keep on drying the tablets. continue coating till the solution gets exhausted.
Continue coating as per the following parameters
Pan speed :3-6 rpm
Peristaltic pump :6-15 min
inlet temperature :65°c-80°c
Exhausted temperature :45°c-55°c
Upload the tablet in a polyline container and weigh it. Check & record the above parameters of coated tablets
Parameters:
Description: Pink, circular, biconvex film-coated tablets with«10» embossed on one side and plain on another side.
Weight of 20 tablets:3.00±3.0%(2.91-3.09 gms)
Average tablet:150 mg± 3.0%
Thickness:3.70±2.0mm
Disintegration Test: NMT 30 min
Reconciliation of Coated Tablet
Stage
Theoretical
Tablet received for coating
QC sample
In the process check the loss
Loss during coating
Actual percentage yield
Reconciliation percentage yield
Reconciled by (Production)
Send dully filled analysis requisition to Q.C Department to collect the sample for analysis
The requisition analysis sheet was sent by to Inspection
Use a nose mask and hand gloves during the operation.
Check for line clearance, and cleanliness of the area equipment and record the observations
Transfer the coated tablet into the tablet inspection area.
Transfer the required qty. of tablets into the hopper of the tablet inspection machine
Inspect each tablet for any defects and segregate the goods and rejected one
Keep the inspected tablets in a double polyethylene bag lined drum, weigh and record
Line clearance (Tablet Inspection)
is the temperature 20-25°c? Actual Temperature
is the Humidity 50±20% RH actual
is the pressure differential NLT 1.2 Actual
is the room clean, where the material to be processed is kept & where the processing is to be done?
Does all the equipment have cleaned status labels & is the cleaning in the validity periods?
Are all the materials of the previous product/batch been removed including the dust bin
Are all the documents /papers for the previous product/batch been removed
Are the remnants of the previous batch/product removed?
Is the area clean & dirty?
Are relevant status labels affixed?
Equipment clean (check visually or wash water reports)?
Tablet Inspection Record
Container No
Weight of tablets
Wt. of tablets after inspection
Rejected tablets
Reconciliation of inspected tablets
Stage
Theoretical
Tablet received for inspection
Inspected tablets
Rejection Tablets
Actual percentage yield
Checked by
Document Reconciliation
No. of BMR pages
No. of additional pages
No. dispensing labels
BATCH RELEASE
REMARKS: All content of the batch record has been checked, reviewed & found to comply/not compiling with the proper requirements .as per in-process check records & analytical data submitted by quality control the product complies/does not comply with specifications. Hence the batch can/cannot be released for further manufacturing stage.
QA Head
