BATCH MANUFACTURING RECORD (BMR)

BATCH MANUFACTURING RECORD (BMR)

 TABLE OF CONTENT

• GENERAL PROCESSING INSTRUCTION
• LIST OF EQUIPMENT USED
• DISPENSING OF RAW MATERIAL
• GRANULATION
• COMPRESSION
• COATING
• TABLET INSPECTION
• DOCUMENT RECONCILIATION
• BMR REVIEW
• BATCH RELEASE

1.0 GENERAL PROCESSING INSTRUCTION

All the Activities shall be performed as per current SOPs.

Follow GMP compliance throughout the manufacturing process.

Check and ensure that the balances are in the calibrated state.

Ensure that the product is labeled at all applicable stages of the manufacturing process.

Ensure the area (including waste bins), all vessels, machines, and equipment are cleaned as per respective SOPs & record the Cleaning details in Equipment Log, and affixed them with the respective STATUS labels, before starting the process.

Avoid direct product contact.

Ensure that secondary gowning of the respective areas is followed.

Use nose masks and hand gloves during manufacturing process to avoid direct contact to product intermediate.

Ensure that Material Dispensing labels and other labels (if applicable) are affixed in the BMR.

Checklist and write (Ok) if complies and (Not Ok) if not complies with respective activity.

Processing area conditions:

Room temperature: NMT 25°C.

Relative Humidity: NMT 60 %.

Carry out environmental monitoring, during the processing operation

The integrity of the sieves and screens shall be verified and recorded before and after the completion of the operation.

Wherever applicable calculate the percentage of yield and record.

Do not perform any cleaning activity if the manufacturing process is in progress in the area.

Take the line clearance from QA before starting the operation during batch-to-batch product change over & record in the batch record where applicable.

Don’t overwrite the entry, in case there is a correction, cancel the entry by a single line with the sign & date and make the correct entry.

2.0 LIST OF EQUIPMENT USED

• Weighing Balance
• Vibro Sifter
• Blender (Double Cone/ Cubic/ Octagonal/
• Mass Mixer
• Paste Kettle
• Planetary Mixture
• Rapid Mixer
• Granulator (RMG)
• Multi mill
• Fluidized Bed Dryer (FBD)
• Tray Dryer
• Compression Machine
• Coating Machine
• Metal Detector

DISPENSING OF RAW MATERIAL CHECKPOINTS

• Ensure the absence of batch documents, labels, materials, or any remnants of previous products or batches.
• Cleanliness of floor, ceiling, walls, light fixtures, dustbins, containers, tools, and vacuum cleaners.
• Ensure updation of the status board & ‘CLEANED’ label is affixed on Dispensing Booth.
• Cleanliness of the surrounding area of the dustbins, containers, tools, and Balances.
• Ensure the differential pressure of the area is within the specified limit
• Check the proper gowning of personnel
• Ensure that RLAF is working properly
•  Ensure that RLAF is working properly
• Differential Pressure across HEPA filters is within limits.
• Ensure that the riser filters are cleaned.
• Ensure the cleanliness of the container in which the dispensed material is to be kept.
• Check the raw material for name, appearance, A.R. No., Expiry/retest date, etc.

Note: Mark ‘OK’ if complies & mark ‘Not OK’ if does not comply during line clearance. Write NA if not applicable.

RAW MATERIAL ISSUE NOTE:

• Sr.No
• Item Name
• Actual Qty (Kg)
• A.R.No.
• Gross Wt. (Kg)
• Tare Wt. (Kg)
• Net Wt. (Kg)
• Weight By
• Checked By
• Verified By

LINE CLEARANCE CHECKPOINTS FOR GRANULATION

• Ensure the absence of batch documents, labels, materials, or any remnants of previous products or batches.
• Cleanliness of floor ceiling, walls, drainage, light fixtures, dustbins, containers, tools, and vacuum cleaners.
• Ensure the ‘CLEANED’ label is affixed on each piece of equipment.
• Check the updation of the status board & status label which shows the details of the activity.
• Cleanliness of the surrounding area of dustbins, containers, and tools.
• Ensure the differential pressure of the area is within the specified limit
• Check the proper gowning of personnel
• Ensure the swab/rinse analysis of the equipment to be used has passed.
• Ensure the availability of BMR and filled up to the previous stage.
• Ensure that the equipment Logbook is filled up to the previous stage.
• Batch documents are completed up to this stage

Note: Mark ‘OK’ if complies & mark ‘Not OK’ if does not comply during line clearance. Write NA if not applicable.

Affix weighing tags/ labels of Dispensed Raw Materials after addition to batch, for verification.

SIFTING OF INGREDIENTS 

Sieve the Raw Materials with the sieve size as per the product specifications.

Check Sieve Integrity – Before and After

Dry Mixing:

Transfer the sifted Material for dry mixing in RMG and Mix the material for _____ minutes with slow /fast speed.

Binder Preparation

Binder – I  Preparation (Aqueous Binder)

(a) Take and boil the purified water (_____kg) ____at 80 ⁰C in the Paste Kettle (Equipment No. ________) and cool it till 45 ⁰C temperature and add the materials_________________

(b) Meanwhile, separately Take ____ kg of Purified water in a SS Vessel and add the Starch IP (_____ kg) makes a slurry of starch paste, and add point no. (a) Into (b) in the Paste Kettle, stirring continuously till a smooth paste is formed

Binder – II  Preparation (Non-Aqueous Binder) (If required)

Take______ Lts. of ________in /SS Container, Equipment No.________ Add __________ in  Solvent and mix properly

Starting Time_______________      Completion Time________________

WET GRANULATION

Transfer the binder of point no.4.5 in step no 4.4 in RMG/Mass Mixer/SS Container. Mix by running the machine at medium speed/ high speed/ manually for ___________ minutes for preparing a wet mass of specified properties as per product specifications.

DRYING 

Unload the wet mass of 4.6 and transfer the wet mass into the product container of FBD/Tray of tray dryer & dry the wet mass as follow.

First airs dry the granules for _______________ minutes and then at ________________ °C Till the LOD of granules is between _______ to _________ at 105°C by Halogen Moisture Balance.

The drying Parameter shall be controlled and Monitor

• Drying Temperature (in °C)
• Drying time (in mins.)
• LOAD (%)

MILLING/ SIZING (AFTER DRYING)

(a) Sieve Integrity checked (Before sifting).

(b) Pass the dried granules of Point No. (4.7) through #__________ sieve fitted on Vibro sifter

(c) Mill the retention of step (b) through Multimill fitted with ________ mm screen at slow speed

(d) Sieve Integrity checked (After sifting).

(e) Collect Granules in a Polylined Container.

(f) Record the Dried Granule’s weight.

The Milling/Sizing Parameter shall be controlled and Monitor

• Milling / Sizing Duration (Hrs)
• Sieve #/ Screen(mm

Weight of Dried Granule after Milling/Sizing:__________________________

Sifting of Lubricants

• Set siffer with #________ sieve and sift of below mentioned Qty in the table.
• Collect sifted Material in polyline Containers.
• Check the Sieve Integrity of #____________ after sifting.

Pre-Blending (without Magnesium Stearate)

Load the Milled material and Sifted lubricants_____ Blender (Equipment ID.____) and mix for ____ Minutes at ___RPM Speed.

Blending (with Magnesium Stearate)

Add the Magnesium stearate in the Pre-blended material in ____Blender (Equipment ID. _____ and mix for ___ Minutes at _____RPM Speed.

Moisture Content of Lubricated Granules:_______

The Following Parameter of Blended material shall be controlled and Monitor

• Bulk Density
• Tapped Density
• Compressibility Index
• Hausner Ratio

Unload the Lubricated Blend into Double Polybag in a suitable Container. Weigh the material. Affixed the Status Labels on the Container

Lubricated Granules Reconciliation:

A- Theoretical Weight of the Lubricated Granules

B- Actual Weight of Granules

C – Q.C. Sample

D- In-Process Check loss

F- Process Loss

E- Actual % Yield:(B)x100/A

G- Reconciliation % Yield: (B+C+D+E)x100/A

QC ANALYSIS:

QC Sample Taken By: ________ Qty. of Sample:  ___________

Analytical result of Blend: Pass/ Fail. A R No.: ____________Sign/Date:________

The blend is/is not of standard quality and released or not released for compression.

Sign/Date: (Production)                                                             Sign/Date: (QA)

COMPRESSION:

• Ensure the absence of batch documents, labels, materials, or any remnants of previous products or batches.
• Cleanliness of floor ceilings, walls, light fixtures, dustbins, containers, tools, and vacuum cleaners.
• Ensure the ‘CLEANED’ label is affixed on each piece of equipment.
• Check the updation of the status board & status label which shows the details of the activity.
• Cleanliness of the surrounding area of dustbins, containers, and tools.
• Ensure the differential pressure of the area is within the specified limit
• Check the proper gowning of personnel
• Ensure the swab/rinse analysis of the equipment to be used has passed.
• Ensure the availability of BMR and filled up to the previous stage.
• Ensure that the equipment Logbook is filled up to the previous stage.
• Batch documents are completed up to this stage

Initial Check 

Punch Specification

• Upper Punch
• Lower Punch

Product Specification

• Description –
• Weight of 20 Tablets _____ ± 3 % (Limit: ____ gm to ____ gm)
• Average Weight______ mg ± 2 % (Limit : ____ mg to _____mg)
• Individual Tablets Weight Variation Limit______ mg ± 5 % (Limit : ___ mg to ___ mg)
• Thickness_____ mm ± 0.2 mm  (Limit : _____mm to______mm)
• Dimension (LXW) -Length _____ Width_____Diameter____
• Hardness -NLT ____ kg/cm²
• Disintegration NMT 15 min/NMT 30 min/NMT 01 Hour.
• Friability-NMT 1% W/W

Compression Pre-Startup

Procedure:

Check the dies and punches for compliance with the product specifications.

Adjust the compression parameters per the product specifications.

Reject the first two rounds of tablets at the start of the batch as Recoverable Rejects.

Check for the initial round of tablets equal to the number of stations, for appearance and Embossing, if any.

The tablets should be free from, picking, chipping, and any foreign matter.

Start the compression, if the parameters comply with standards.

In-Process Parameter

Appearance – Every 30 Minutes

Group Wt. of 20 Tabs (g) _____ ± 3 % (Limit: _____ gm to _____ gm) – Every 30 Minutes

Average Weight – ______ mg ± 2 % (Limit : _____ mg to ____ mg) – Every 30 Minutes

Hardness (NLT _____Kg/ cm²)  – Every 01 hrs

Disintegration time  (NMT _____ Min) – Every 01 hrs

Thickness: ______mm to______ mm  – Every 01 hrs

Friability (%) (NMT ______%) – Every 02 hrs

Individual Weight Variation Limit – ____ mg ± 5 % (Limit : ____ mg to _____ mg) – Every 01 hrs

WEIGHT RECORD OF COMPRESSED TABLETS

Sr. No.

Gross Weight (kg)

Tare Weight (kg)

Net. Weight (kg)

Weighed by

Total weight

RECONCILIATION OF COMPRESSED TABLET

A-Theoretical

B- Weight of granules received for compression

C- Weight of Compressed tablets

D-Tablets sent to Quality Control

E-In process Sample

F-Loss during Compression

G-Actual Percentage Yield % (C)x100 /(A)

H-Reconciliation Percentage yield      (C+D+E+F)x100 / (A)

Reconciled By (Production)

Send duly filled analysis requisition to Q.C. Department to collect the sample for analysis.

Requisition analysis sheet sent by………….Date/Sign)

Sampled By………………… (Date/Sign)

Analytical result of Compressed Tablets: Pass/ Fail. A R No.: __________Sign/Date:

The Compressed tablet is released or not released for coating

Sign/Date: (Production)                                                             Sign/Date: (QA)

if complies & mark ‘Not OK’ if does not comply during line clearance. Write NA if not applicable

Sifting Of Coating Material

S. No.

Material Name

Quantity

AR No.

Done By/ On

Mixing of Coating material

Mix Material of S. No. ____in S. No. ______in Purified Water for ____ min. in a mixing vessel.

Add Color ______ in _____lt of the above-prepared solution. Filter the color solution.

Keep the solution for ______min. And proceed with the coating process.

Divide the tablets of the batch into _____(No.) lots equally, having Lot size of ____Kg.

Set coating parameters as per product specifications.

Pre-warm the tablets in a coating pan for a predefined time.

After warm-up start the coating process by starting the coating spray from the gun & note the parameters in the Coating details.

Solution Preparation

Type of Coating: Aqueous/ Non-Aqueous

Color Name:__________________

Coating Pan Setting Details

• No. of Baffles
• No. of Guns
• Gun-to-Gun Distance
• Gun to Tablet Bed Distance
• Tab Av. Weight (uncoated) (mg)

Pre-Coating Preparation Details

• Uncoated Tab. Av. Wt. (mg) (pre-warm-up)
• Warm-up Temp. (^OC)
• Warm-up Time
• Tablet Av. Wt (After warm-up) (mg) (A)
• Pan Speed (RPM)
• Inlet Temp. (_______________^OC)
• Tablet Bed Temp. (___________^OC)
• Av. weight of Tablet (mg) (B)
• Coating weight gain (%) ({B-A}/A x100)

 RECONCILIATION OF COATED TABLET

• A-Theoretical Tablets.
• B-Weight of the Tablet received.
• C-Weight of Coated tablets.
• D-Tablets sent to Quality Control.
• E-In-process Sample.
• F-Loss during Coated.
• G-Actual Percentage Yield % (C)x100 /(A)
• H-Reconciliation % yield     (C+D+E+F)x100 / (A)
• Reconciled By (Production)
• Send duly filled analysis requisition to Q.A. Department to collect the sample for analysis.
• Requisition analysis sheet sent by………….Date/Sign)
• Sampled By………………… (Date/Sign)

Analytical result of Coated  Tablets:

Pass/ Fail ___________________ A R No.: _________ Sign/Date:

The Coated tablet is released or not released for tablet inspection.

Sign/Date: (Production)                                                             Sign/Date: (QA)

TABLET INSPECTION

Instructions:

There should not be any variation in the color of the tablets and tablets should be of smooth surface.

The tablet surface should not have spots & should not be broken.

There should not be any “Blistering” or “Bridging” on the tablets

There should not be any twinning of tablets

Area and Equipment line clearance of Tablet Inspection:

Ensure the absence of batch documents, labels, materials, or any remnants of previous products or batches.

Cleanliness of floor ceilings, walls, light fixtures, dustbins, containers, tools, and vacuum cleaners.

Ensure the ‘CLEANED’ label is affixed on each piece of equipment.

Check the updation of the status board & status label which shows the details of the activity.

Cleanliness of the surrounding area of dustbins, containers, and tools.

Ensure the differential pressure of the area is within the specified limit

Check the proper gowning of personnel

Ensure the swab/rinse analysis of the equipment to be used has passed.

Ensure the availability of BMR and filled up to the previous stage.

Ensure that the equipment Logbook is filled up to the previous stage.

Batch documents are completed up to this stage.

Challenge Test for Metal Detector

Ferrous

Non-Ferrous

SS Block

Dummy Block

RECONCILIATION OF INSPECTED TABLET

A- Theoretical (Standard)

B- Tablets Received for Inspection

C- Inspected Tablets

D- Rejected Tablets

E- Actual percentage Yield (C)x100 /(A)

F- Reconciliation % yield    (C+D)x100 / (A)

Reconciled By (Production)

DOCUMENT RECONCILIATION:

No. of BMR pages

No. of Additional pages

No. of Dispensing  Labels

BMR REVIEW:

Reviewed By Manager-Production and Manager-Quality Assurance

BATCH RELEASE :

All contents of the batch record have been checked, reviewed & found complying/not complying with the proper requirements. As per in-process checks records & data submitted by quality control, the product complies/does not comply with specifications. Hence the batch can/cannot be released for Packing.

                                                                                                                       QA Head/ (Sign/Date)