AMOXICIILIN AND POTASSIUM CLAVULANATE TABLETS BP

AMOXICIILIN AND POTASSIUM CLAVULANATE TABLETS BP

Reshma Verma

MASTER FORMULA RECORD

AMOXICILLIN AND POTASSIUM CLAVULANATE TABLETS BP          

  • Purpose:

To provide instructions for the preparation of Master formula Record. For Amoxicillin Trihydrate and Potassium Clavulanate 625 mg Tablets BP. 

  • Objective:

To provide a documented procedure for the preparation of Master formula record is that standard manufacturing/packing record which gives complete details of materials used along with their quantities, standard process flow, Area & equipment used, yield and reconciliation, Instruction & precautions or any other information relate to Amoxicillin Trihydrate and Potassium Clavulanate Tablet 625 mg.

  • Scope:

This procedure is applicable for the preparation of Master formula Record for Amoxiciilin  Trihydrate and Potassium Clavulanate 625 mg tablets in QA department .

  • Responsibility:

Follow up                     :  Executive-QA

Overall responsibility    :  Manager-QA 

  • Product Details:
Generic Name Amoxicillin Trihydrate  and Potassium Clavulanate Tablets BP (625mg)
Composition Each film coated tablet contains :

Amoxicillin Trihydrate  BP

Equ. to   Amoxiciilin  Trihydrate    BP                             500mg

Potassium Clavulanate Diluted EP

Eq. to Clavulanic Acid                                                        125mg

Excipients                                                                            q.s

Colour  : Titanium Dioxide IP
Batch size 1,10,000
Shelf life 24 Months
Pack size 1×10’s  Alu-Alu Strip
Mfg License
Category Orally Active Semi Synthetic Penicillin’s
  • LIST OF EQUIPMENT’S:
Sr. No. Name of the Equipment Location/ Section
Platform Balance. Granulation
Vacuum Tray dryer Granulation
Roll compactor. Granulation
Multi Mill. Granulation
Vibro Shifter. Granulation
Octagonal Blender. Granulation
Rotary M/C (27 station). Compression
Automatic Coating Machine. Coating
Disintegration test Apparatus. IPQA
Hardness Tester. IPQA
Alu-Alu Pack Machine. Packing
Vernier Caliper. IPQA
Friability Apparatus IPQA
Water activity meter IPQA
Ink Jet Printing Machine. Packing
Hygrometer. All Section
Strip Packing Machine Packing

 BILL OF MATERIALS:

Sr.

No.

 Item Std Label
Claim		 AR No. Qty.
Reqd.		 Ovgs/Eq. if any Actual
Qty.		 Unit
Amoxiciilin Trihydrate
Equ. to Amoxiciilin		 BP 500mg 55.00 8.250 63.250 Kg
Potassium Clavulanate Diluted
Equ. to Clavulanic Acid		 EP 125mg 13.750 20.625 34.375 Kg
Excipients:-
Magnesium Stearate BP 1.980 0.000 1.980 Kg
MCCP – 112 BP 2.000 0.000 2.000 Kg
Cross Povidone XL-10 BP 1.980 0.000 1.980 Kg
Di Sodium EDTA  BP 1.045 0.000 1.045 Kg
Sylloid 244 FP/Aerosil BP 0.550 0.000 0.550 Kg
Coating Material:-
Colorezy White BP 3.143 0.000 3.143 Kg
Isopropyl Alcohol BP 16.650 0.000 16.650 Kg
MDC BP 25.000 0.000 25.000 Kg

 *Quantity of MCCP-112 will be compensated as per assay of Potassium Clavulanate.

 * Quantity of Amoxicillin and Potassium Clavulanate to be issued by multiplying the standard weight with the factor evaluated after calculating by incorporating the Assay value on as is basis, water content/ loss on drying value and appropriate conversion factors.

 Calculation of Active ingredients;-

  • Qty. of API  ( Amoxicillin Trihydrate required for manufacturing of batch in kg = X            

            Label claim of API x Batch size in NOS x 100×100

    X=……………………………………………………………………………………

         10,00,000 x Assay of API on  Anhydrous basis x (100-water content)

                        

  • Qty. of API  (Potassium Clavulanate Diluted  required for manufacturing of batch in kg = X            

                    Label claim of API x Batch size in NOS x 100

    X=……………………………………………………………………………………

                  10, 00,000 x Assay of API on Anhydrous basis

  

STATEMENT OF THE EXPECTED FINAL YIELD WITH ACCEPTABLE LIMITS AND RELEVANT INTERMEDIATE YIELDS:

Sr. No. STAGE YIELD
Dispensed Material 100 %
After Granulation including in-process and QC samples NLT 99 % of the dispensed Material
After inspection of the Compressed tablets including quantity for in-process and QC samples NLT 98 % of the dispensed Material in terms of number of tablets
After Coating of tablets including in-process and QC Samples NLT 97.5 % of the dispensed Material in terms of number of tablets
Final Yield :

After Stripping and final packing after QC sample for testing and Control Samples

 NLT 97.0 % of the dispensed Material in terms of number of tablets

Note: For any deviation min the final yield of the

The yields specified in the intermediate stage is only to monitor  

  • REFERENCE METHODS FOR PREPARING CRITICAL EQUIPMENTS INCLUDING CLEANING ASSEMBLING   AND CALIBRATION:
    • Specific SOP’s to be strictly followed for:
    • The corresponding equipment’s for Cleaning, Assembling, disassembling and stagnant period of the usage of equipment after cleaning.
    • For activities related to Area cleanliness, Pest control activities, Fumigation, Bio burden estimation, Air Change Controls, Pressure differentials.
    • All the in-process instruments are calibrated and records are available.
    • Accessory instrument installed on the manufacturing equipment and standards for calibration of in-process instruments to be confirmed to ensure calibration from external lab Accredited with NABL. With the availability of calibration certificates with traceability.
  • INSTRUCTIONS FOR LINE CLEARANCE AND INPROCESS CONTROL:
    • IN GENERAL:
    • Check to ensure that the manufacturing area is free from previous product residues and materials, containers, labels and records.
    • Ensure to check that all the records pertaining to area cleaning viz floors, walls, doors, ventilators, glass panels, are recorded, signed and counter signed to confirm the cleanliness of the area.
    • Supporting records and raw data’s pertaining to fumigation, sanitation and bio burden are recorded, signed and counter signed.
    • Ensure that the pressure differentials, humidity and temperature of the blending area is monitored within the predetermined limits and records are available.
    • If required send the swab and rinse solvent samples of the manufacturing equipment collected by QA department.
    • Check to ensure that updated Batch manufacturing record with appropriate signatures and counter checks by QA department for initial checks and in-process checks are available
    • Ensure that only personals including operators, manufacturing chemists and qualified for the appropriate jobs are assigned to perform the respective activities and records of qualification are available.
    • Ensure that personals involved in the manufacturing activities viz. Production Chemists, IPQA and operators are wearing protective apparels, Nose masks, Hand gloves, Head gears & goggles.

Note: In addition to the In-process instructions described above under general, in process instructions for specific areas as under requires to be followed.

DETAILED STEPWISE PROCESSING INSTRUCTIONS FOR HOMOGENITY OR UNIFORMITY IN BLENDER MIXING

    • On receipt of the Excipients namely Microcrystalline cellulose, Cross Povidone XL-10, Magnesium Stearate are  counter checked for dispensed labels tagged on the respective containers, for details of material name, control number, batch number, gross weight, tare weight and net weight.
    • Weights counter checked by production chemist, in balancing scale which is previously calibrated.
  • Dispensing of Active Materials.
    • Owing to the sensitivity of the active ingredients. The active materials Amoxicillin Trihydrate dispensed in the same area immediately before sifting.
    • The temperature and humidity are monitored at temperature of NMT20ºC & Humidity of NMT20%, 30 minutes prior to weighing and the same condition maintained until the completion of weighing of the active material and followed by sifting, serial dilution and blending.
    • Recording of the temperature and humidity parameters recorded and plotted against time for trend analysis.

* Dispensing of Potassium Clavulanate will be done at the time of final blending.

  • Sifting of Active ingredients & Excipients.
    • Maintaining the sifter in the switch off state while loading the active ingredients, to prevent spillage of the active material.
    • Charge the active ingredients in divided portions, in sufficient quantities, to prevent loss due to overflow during vibratory motions.
    • Swtich on the Sifter .
    • The active material Amoxicillin Trihydrate sifted with sieve size 30# .
    • Replace the existing sieve of mesh no. 40# fitted in the sifter with .sieve of mesh number 60#.
    • Check for the sieve integrity of the sieve of mesh number 60# .
    • Check for cleanliness of the fitted
    • Excipients Magnesium stearate  , MCCP-112 ,Cross Povidone XL-10 sifted with  sieve 60#.
    • Take following precautionary measures while sifting the active ingredients.
    • Collect the sieved material in to a double lined LLDPE bag.
    • The container labeled as sifted Excipients, and quarantined in the same area at a appropriate location.
  • Pre-Blending for compaction.
    • Set the rpm mixing is set at 10 rpm and blending activities carried out for a total 20 minutes.
  •    Blending of the powder mixture compromising of the actives  Trihydrate and Excipients   MCCP- 112(1.100kg) Cross Povidone XL-10(0.900kg), Magnesium Stearate (0.900kg) done for a total of 20 Minutes.
  •  Collect the material in to a double lined LLDPE bag.
  • Roll Compactor
  •  Make the Chips of Previously blend Amoxicillin Trihydrate and Excipients Micro Crystalline Cellulose and Cross Povidone and Magnesium Stearate with the help of Roll Compactor.
  •  Milling
  •  Milling the Chips with Screen 2.0mm with the help of Multi Mill.
  • Material collected in a clean LLDPE container and Store in Quarantine.
  • Sifting of Active ingredients & Excipients.
  •  The blend material sifted with sieve size 16# . 
  •  DRYING OF  TRIHYDRATE AND EXCIPIENT:
    • Before the loading into the Vacuum tray drier, the sample for Previously Mixed Excipients with  Trihydrate are taken.
    • Subjected for water content activity.
    •   Quantity of sample taken is recorded
    •  The initial water content activity is recorded.
    • After determination of the water content activity, the sample is disposed with proper destruction.
    • Temperature of the Vacuum tray drier is set at 55ºC to 60 ºC for a period of 120 minutes
    •  Mixed Excipients with  Trihydrate are taken in to trays.
    • Previously sifted cross Povidone &Magnesium stearate  into the trays.
    •  The materials are distributed evenly in the trays.
    •  The ambient temperature of the area and initial temperature of the Vacuum tray drier, when
    • Switched on is recorded
    •  The raise in temperature of the vacuum tray drier is recorded at a interval of 5 minutes.
    •  At the end of 120 minutes, the tray drier to be switched off.
    •  Sample of mixed blend, Cross Povidone & Magnesium stearate  drawn from each trays.
    •  Sample subjected for water activity test.
    •  The water activity for mixed blend, Cross Povidone & Magnesium stearate   should be NMT 0.1%
    •  Results should be recorded.
    •  Trend analysis done for the water activity performed at the bracketing points of 60, 90 minutes and
    • the final at 120 minutes. 
  • SIFTING AND BLENDING PROCESS
    • Sifting of Active and Excipients.
    • Sifting and Blending activities are done in a common controlled area, with 4 persons compromising of 2 operators, production chemist and QA chemist.
    • The temperature & humidity controls are switched on and the parameters for temperature and pressure are adjusted and monitored for a temperature of NMT 20ºC and a humidity of NMT20%.
    • At least one hour before the activities is initiated.
    • The area is monitored with a temperature of NMT 20ºC and a humidity of NMT20%.
    • Record the temperature and humidity parameters displayed in this period.
    • Check to ensure for the cleanliness for the sifter and sieves of mesh size 16# &60 #.
    • Check for any damage of the sieves of mesh size 16# & 60 #.
    • Check for the sieve integrity
    • Check for cleanliness of the sifter machine, for external surface, internal surface and hard to clean areas.
    • During the entire activity of the sifting and blending the area is monitored with a temperature of NMT 20ºC and a humidity of NMT20%.
    • Record the readings of temperature and humidity for the entire period of sifting and blending.
  • Blending:
    • Central line for rpm mixing is set at 10 rpm and blending activities carried out for a total 35 minutes.
    • Blending of the powder mixture compromising of the actives and Excipients done for a total of 35 Minutes.
    • Bracketing for sampling done at the time points of 35 minutes.
    • Transfer sifted Magnesium Stearate to the blender and operate blender for 5 minutes .
    • Sampling at the end of 40 minutes.
  • TABLET COMPRESSION:
    • Cleaning of the Compression machine to be performed after disassembly of the compression Machine.
    • The Disassemble spares to be transferred to the cleaning area for cleaning.
    • The cleaning activities to be performed as per the SOP for Cleaning and operating procedure of the Tablet compression machine.
    • QA department to be intimated for checking by visual for the compression machine before assembling.
    • Each of the individual pieces of the Punches and dies to be inspected by the QA department for the usage of correct dies and punches.
    • Any wear and tear out of the punches
    • Inner portion of the dies for ring formation.
    • Swab/Rinse Solvent  samples (if required) for all critical parts of the compression machine Viz. Hopper, turette, cam way, feed frame , lower and upper punches should be sent to QC for residual trace analysis of the previous products.
    • After clearance the compression machine to be assembled with all the upper and lower punches and dies installed.
    • The QA department should be intimated for final line clearance.
    • QA Personal shall provide line clearance after inspection of the following:
  • Machine Cleanliness:
    •  Exterior surface of the Compression Machine
    • Inner surface of the Hopper.
    • Surface of the
    • Turette
    • Cam way
    •  Feed frame
  • Area Cleanliness
    •  Floor
    •  Walls
    •  Top Ceilings
    •  Inlet and outlet of the AHU’s
    • Dust collector bags.
  • Area Line Clearance:
    • Ensure for the absence of:
    •  Residues of the previous products
    •  Labels and containers of the previous products.
    •  BMR of the previous product.
    • Check that the updated BMR of the running batch updated to the previous stage of Granulation and yield is available.
    •  Check that the correct product with label fixed on the containers is transferred to the compression area.
    • Check to ensure that all the in-process instruments like DT apparatus, Friability apparatus, Digital Vernier and hardness tester are calibrated.
  •  Centre Line Monitoring:
    • The Centre line Parameters of the following to be adjusted as per the specification.
    •  Turette rpm. at 12-15 RPM
    •  Hardness –Not less than 5 Kg/cm2
    •  Thickness – between 5.5 mm 0.2 mm
  • Initial Machine Setting
    •  Ensure that the temperature and Humidity of the tablet compression area is within the predetermined specified limits of NMT 20ºC and a humidity of NMT20%.
    •  Record the parameters of temperature and humidity into the BMR.
    • At this stage recoverable of the previous batches approved by QC department after carrying out tests for Assay and related substance (if any).
    •  The quantity of the recoverable added should not be more than 5 % of the batch size.
    • The recoverable are added by pulverizing to powder using mixing and sifting through sieve of 16 #.
    •  The quantity of the recoverable added and the modified batch size should be recorded in the BMR.
  • Compression of tablets 
    •  After line clearance formalities Transfer sufficient quantity of granules to fill not
    • More than ¾th of the Hooper capacity.
    •  Check for the free flow of the powder from the hopper on to the Turette area enclosed on which the feed frame is mounted.
    • Switch on the tablet compression machine.
    •  Discard the first round of the tablets punched.
    •  Collect the successive compressed tablets of a quantity of 50 tablets and check for: Appearance of the tablets/ Total weight of 50 tablets/ Disintegration Test/Friability
    • Physical dimensions like Hardness, thickness and Length.
    •  After obtaining satisfactory results, QA department should be intimated through Test request form.
    • After repeating the tests as mentioned in step by IPQA chemist and on obtaining results within the            specified limits.
    •  The results to be recorded in the BMR
    • Line clearance is to be given for compression.
    • In-process checks to be performed by both the production and IPQA chemists at the frequent intervals as stated in the BMR to monitor the tablet compression activities.
    •  Environmental monitoring to be done by recording the temperature and relative humidity.
    • Compression activities must be stopped when the last quantity of the granules is near the window level located in the narrow portion of the hopper.
    • And the last round of the tablet to be weighed individually for weight variation.
    •  The remaining granules in the hopper to be collected and quarantined in the recoverable area after appropriate labeling with the product name, B.No, Mfg Date, Expiry date and quantity.
    •  The Compressed tablets should be collected in double lined LDPE bags with their mouth tied firmly with nylon threads.
    •  The LDPE bags must be placed in HDPE drums.
    •  sufficient silica gel bags to be placed on the LDPE bags and the Lid of the drums to be firmly closed.
  •   Product details.
Description Off White Colored, Elongated Shaped, bi-convex, Both side Plain film Coated tablet.
Identification

For  and Clavulanic acid : ( By HPLC)

 The retention time of the principal peaks in the chromatogram of sample preparation should correspond of the standard preparation as obtained in the “Assay”.
Average weight 950mg +3.0 % w/w
Uniformity of weight + 5 % of average wt.
Length 19.91mm + 0.2 mm
Width 9.18+ 0.2 mm
Thickness 5.58 mm + 0.2 mm
Hardness NLT 3kg/cm2
Water NMT – 7.5 %
Related Substance NMT3.0 %
Dissolution

Amoxiciilin Trihydrate

Potassium Clavulanate Diluted

 NLT-85.0%

NLT-80.0 %
Assay : Each Film coated tablet contains :

Amoxicillin Trihydrate BP                                    Equ. to Amoxicillin      500mg

Potassium Clavulanate Diluted BP

Equ. to Clavulanic Acid    125mg

 90.0% -105.0 %

90.0% -105.0 %
  •  Labels containing the contents of:
    •  Name of the Product (in Generic name)
    •  Batch Number (Alphanumeric code of the Generic Name)
    •  Batch Size: (As per the Plan)
    •  Mfg. Date
    •  Expiry date
    •  Gross weight
    •  Tare Weight
    • Net Weight
    • Stage: Compressed tablet
    •  Next Stage: Ready for Coating:
    • Signature of the Chemist & Date:
  •  Raise Test request form To QC for sampling of the compressed tablets for complete analysis.
    •  After analysis and approval of the compressed tablets.
    • The Tablets should be film coated
    •  Note down the gross weight, net weight and loss% of compressed tablet.
  •  BILL OF COATING MATERIAL

        (COATING ACTIVITY)

  • Before film coating, draw at least 5 tablets from each drum in a controlled area of Temperature NMT 20ºC and a humidity of NMT20%.
    • The tablets should be subjected to water activity
    • Check and ensure the coating pan and other equipment’s are clean and record in a checklist.
  • Central Line set parameters of Auto coater
    • Inlet Temperature   :  50ºC
    • Outlet temperature :  40ºC
    • Pan humidity            :  NMT14%
    • RPM of the Pan Cabinet (tunnel) : 2
    • Gun Spray rate     : 80 gm per minute
    • Stirring rate of coating material      : By manual.
  •       Counter checking of Central line parameters
    •    After the auto coater is switched on and parameters are set.
    • Allow for 15 minutes
  • Humidity
    • The humidity is measured with the help of digital hygrometer

The digital hygrometer is fixed to stand and introduce into the coating channel.

    • The visual glass door closed.
    • The instrument is allowed to stabilize for 10 minutes.
    • Reading recorded.
  •  Coating Pan Rpm
  •    Time interval between the glowing of indicator, located in the rear panel of the auto-coater  equipment is measured with the help of Stop clock.
    • RPM should be around 2.
  • Gun Spray

   The gun spray unit compromising of spray guns F1 are isolated by detaching from the Main auto    coater equipment.

    • Disconnect the silicon tubes connected to the individual spray guns,
    • The other side of their open endings dipped into the coating solution after passing through the valves.
    • The Silicon tubes marked with identification corresponding to the spray guns. Switch on the system for, facilitating for the circulation of the coating solution and get discharged from the silicon tubing’s.
    • Collect to measure the volume of the coating solution discharged from the three silicon tubing’s corresponding to the three spray guns.
    • The volume should be around 30 ml
  • Preparation of coating material
    • Coating solution is prepared in the coating area.
    • Coating raw materials are dispensed.
    • Dispensed materials, namely 17K580010-Colorezy White, IPA (Isopropyl alcohol) and MDC (Methylene dichloride).
    • Counter checked for weight dispensed.
    • Transfer the Coating RM to the coating preparation area.
    • Check for the cleanliness of stirrer and cleanliness of the SS 316 drum used for preparation of Coating solution.
    • Isopropyl alcohol dispensed by RM stores to be transferred into a SS 316 drum.
    • Introduce the stirrer into the drum containing IPA & colures white .
    • Switch on the stirrer.
    • Adjust the speed variable knob at 70.
    • Allow stirring for 10 minutes
    • Check to ensure that the solution obtained is of homogeneous consistency free from lumps and precipitation.
    • Add the complete quantity of MDC into the solution and increase the speed variable knob by setting to 100.
    • Allow stirring for a further 15 minutes.
    • Record the time.
  • Coating of the Tablets
    • The capacity of the auto-coater is 105 kg
    •  Coating of the compressed tablets done in one lot.
    •  The specified quantity of the bulk tablets loaded into the auto coater tunnel.
    •  Parameters are set as per the established central line.
    •  Coating done until the complete quantity of the coating solution is consumed.
    •  The parameters are monitored during the complete operation and recorded.
    • After completion of coating, sample drawn from the coating bed at different portions.
  • YIELD OF THE TABLETS AFTER COATING

15.9.1 The total weight of tablets after coating is determined, by  evaluating the  net weight of the total tablets by subtracting the gross weight of the containers individually with their respective tar weights and adding the net weight of tablets in each container.

  •  Finished Product details.
Description A White Colored film coated, elongated shaped tablet, biconvex from both side.
Identification

For  and Clavulanic acid : ( By HPLC)

 The retention time of the principal peaks in the chromatogram of sample preparation should correspond of the standard preparation as obtained in the “Assay”.
Average weight 972mg +3.0 % w/w
Uniformity of weight + 5 % of average wt.
Length 19.91mm + 0.2 mm
Width 9.20+ 0.2 mm
Thickness 5.6 mm + 0.2 mm
Hardness NLT3kg/cm2
Water NMT – 7.5 %
Related Substance NMT3.0 %
Dissolution

Amoxiciilin Trihydrate

Potassium Clavulanate Diluted

 NLT- 85.0%

NLT- 80.0 %
Assay : Each Film coated tablet contains

Amoxiciilin Trihydrate BP                       Equ. to Amoxiciilin       500mg

Potassium Clavulanate Diluted BP

Equ. to Clavulanic Acid    125mg

 90.0% -105.0 %

90.0% -105.0 %

ALLOCATION OF TABLET QUANTITY FOR STRIP PACKING FOR DIFFERENT BRAND NAMES

    •   After the yield calculation at the end of the coating activities, the tablets quantity is allocated to different Brand Names.
    • Quantities corresponding to the brand names weighed and segregated in different drums with appropriate labels.
    • Weighing and distribution of the quantities done under controlled area by monitoring the temperature and Humidity in the presence of Q.A personal.
    • BPR’s issued for individual brands.
    • During strip packing and secondary packing activities like line clearance and .Yield calculations done for individual brands.
    • Recoverable (if any) of good tablets of quantity NMT 5 % of the Batch size of the brand name is permitted to pack only after QC analysis.
    • Appropriate quantity of control samples drawn for each brands.
    • After the end of the packing the BMR issued for the generic and all the BPR’s linked to the BMR are reviewed and filed.
    • The same is captured as soft copy.
  •  ALU-ALU PACKING:

           Bill of Packing Material. 

Sr. No. Packing material Unit Std. Quantity
Printed Foil kg 8.0
Base Foil Kg 32
Mono Carton 1×10 Nos. 11,200
Outer carton Nos. 120
Shipper Nos. 15
Bopp Tape Nos. 2
Cello tape Nos.

 

  • LINE CLEARANCE AND INPROCESS CHECKS DURING STRIP PACKING:
    •  Check for the Area Cleanliness.
    •     Monitor and record the environmental Conditions of temperature and humidity of the strip machine area.
    • Check for the Cleanliness of the external surface of the Strip machine.
  • Check for the Cleanliness of:
    •  Vibrator surface
    • Tablet feeder chute
    • Check for the sealing temperature.
  • Check for the clearance of previous product residues, BMR,s and Other documents , Containers  ,Aluminum strips  packed strips and stereos of the previous products.
  • Check leak test for strips proportional to number of strip units per cutting.
  • Check for Legibility and correct coding of the OPI (Over printing instructions) printed on the Base foil.
  • Check for the quality of Knurling.
  • All the tests performed during the initial machine setting to be checked at frequent intervals as in- process checks during the complete strip packing activities.
  •  STRIP PACKING ACTIVITIES
  • Stripping: Packaging belt should be thoroughly checked to ensure:
    • That there should not any material left behind of the previously run product.
    •   Details like Batch No., Mfg. Date, Expiry Date, Price and any other necessary instructions for labels and printing should be checked well before starting the batch.
    • BPR should be duly signed by competent authorized person and the sample of such product should be kept as record.
  •  Operation specification:
    • Temperature in Alu-Alu Packing Room: NMT 250C
    • Sealing Roller Temperature                 : 1050 – 1150 C
    • Alu-Alu Cutting Frequency : 35 strip per minute
    • Leak Test for the Strip should be performed regularly to check the proper sealing. A report of leak test should maintain.
    • After completion of the packing all the material is to be transfer to the finished goods store along with the complete record.
    • After getting testing certificate from the Q.C. Dept. the material is ready for dispatch.
    • The Consignment should be released by Q.A. department.
  • INSTRUCTIONS FOR IN-PROCESS CONTROLS WITH THEIR LIMITS:
    • REQUIREMENTS FOR STORAGE CONDITIONS OF THE PRODUCTS, INCLUDING THE CONTAINER, LABELLING AND SPECIAL STORAGE CONDITIONS WHEREVER APPLICABLE:
    •  During the different stages of manufacturing and packing, viz. Blending compression coating and primary packing. Following to be considered:
    •  Should be stored in double lined LDPE bags of appropriate size.
    • The mouth of the LLDPE bags should be firmly tied with nylon threads.
    •  The LLPE bags further placed in HDPE containers.
    •  The Net weight of the Semi bulk product to be recorded after weighing the tare weights of the double poly lined bags and the empty drum weights.
    • The Gross, Tare and Net weights of the individual containers to be recorded in the BMR and LOG book.
    •  The same to be counter checked by QA department with appropriate signatures.
    •   Sufficient number of Silica gel bags should be distributed on the LLDPE bags
    • Containing the Bulk product.
    •  The Lids of the containers to be close air tight stored and monitored at a Temperature NMT 20ºC and   a humidity of NMT20%.
    •  As far as possible a minimum time interval to be maintained during each stage.
  • Containers processing the semi bulk products viz. during blending, compression and coating, should be fixed with labels with the following contents:
    • Container Number:
    •  Name of the Product (in generic name)
    •  Batch Number
    •  Batch Size
    •  Mfg. Date
    •  Expiry date
    • Gross weight
    •  Tare Weight
    • Net Weight
    •  Stage of Process:
    • Signature of the Chemist & Date:
    •  The above contents remain the same except *Container No. & **Stage of Process.
    • The Environmental monitoring of temperature, relative humidity and the stagnant time of storage of the semi bulk product after each processing stage to be recorded in Log book.
    •  After Coating the tablets are weighed by distributing to different brand names as per the plan
    • And the containers are relabeled with the following contents:
    •  Name of the Product (in Brand name)
    • Batch Number (Alphanumeric code of the Brand Name)
    •  Batch Size: (As per the Plan)
    •  Mfg. Date
    • Expiry date
    •  Gross weight
    •  Net Weight
    •  Stage: Strip packing:
  • ANY SPECIAL PRECAUTIONS TO BE OBSERVED
      • Ensure that cleaning of area  done as per SOP before start of operation.
      • Mixing, Granulation and Punching should be done as per SOP.
      •  All the equipment and accessories used for manufacturing and punching area should be cleaned as per SOP.
      •  Manufacturing & punching area enter procedure should be strictly followed as per SOP.
      • Striping quality should be checked every half hour interval.
      • Leakages of the field stripped should be checked as per SOP.
      • Individual strip are subjected for visual inspection by trained personnel as per SOP.
      •  Prior to packing: Overprinting of strips and boxes should be done as per SOP.
      •  Blistering and packing should be done in packing area as per SOP.
      • Activities like dispensing, Blending, compression and coating to be carried out at control temperature and relative humidity of NMT20ºC and NMT20 % RH respectively.
  •  Water activity test to be performed at the following stages:
      • Excipients Cross Povidone XL and Magnesium Stearate after drying.
      • Mixed blend  with  Trihydrate after drying.
      •  Semi finished Bulk product immediately after blending and before starting the compression of tablets
      • Tablets after completion of the compression, and once again before charging into the auto-coater tunnel for coating. Composite sample of at least five tablets from each drum to be performed during each case.
      •  The water activity should NMT 0.1%
      •  The Bulk finished product after different stages of process should be stored in double lined LLDPE Bags further stored in Drums with sufficient number of dried Silica gel bags and the drums of the lid closed air tight.
      • During the entire stagnant time the environment to be monitored at controlled temperature and relative humidity.
  • PACKING DETAILS AND SPECIMEN LABELS RELATING TO THE PRODUCT
      •  Printed Alu-Alu foil of 230 mm width for all brands.
      • Each Alu-Alu blister unit contains 10 tablets and packed in a monocarton.
      •  Alu-Alu blister packed in Outer carton.
      •  Configuration of Tertiary packing depends on the carton dimension used, and dimension of the   Shipper-which is different for different customers.
  •  REFERENCE DOCUMENTS
      • BMR & BPR
      •  Relevant SOP’s
      • Log Books and Records
      •  Specifications
      •  Calibration records and approved labels
      •  Chemists and operator qualification records for specific jobs 
  •  ABBREVIATIONS:
  •  QA = Quality Assurance Department
  •  SOP = Standard Operating Procedures
  •  OPI = Over printing Instructions
  • COPIES TO DISTRIBUTION SITES
  DEPARTMENT COPY PERSONAL Signature Date
Quality Assurance Master Copy

Control Copy

 QA Executive.

QA Head

    
Production Department Control Copy Head Production    

 

  •  MATERIAL RECONCILIATION
Sr.

No.

 ITEM DESCRIPTION PTD. FOIL PLAIN FOIL MONO-CARTON OUTER CARTON SHIPPER BOPP TAPE CELLO TAPE
A Standard Quantity
B Quantity Received
C Extra Qty. Taken
D Total Qty. ( B + C)
REJECTION DETAILS
E Rejection During Overprinting
F Rejection during Packing
G Total Qty. Rejected

( E + F )
PACKED QUANTITY DETAILS
H Qty. Returned To Stores in Numbers.
I Total qty. used

D – (G+H)
Reconciliation Done By :

Production
Reconciliation Checked By:

IPQA

FINAL RECONCILIATION OF PRODUCT (Details to be entered after completion of batch packing)

Note:    Write “NA” whenever is Not Applicable.

Sr. No. Description In Nos./% Yield
PACKING
A Batch Size ( In no. of tablets)
B Actual Batch size for packing
C Tablets transferred from manufacturing to packing In kg _________
D Quantity transferred to Finished Goods Stores (In No. of Blisters)
E Total sample qty
F Total quantity packed (D+E)
G Inspection Loss of defoiled tabs
H Packing Loss

Batch Yield = (F/B x 100) = _____________ % (Limit = NLT 97.0 %)

Reconciliation Done By: ___________   Checked By: ___________                   Verified By: ___________ (Production Officer/Executive)

(Department Head)                               (IPQA Officer/Executive)

 Note: – Give justification for % Yield Limit Variation, if any & take approval from QA Head.

Justify by (Head Production) _________________ (QA Head) _____________________

Sign/Date                                  Sign/Date

RECONCILIATION OF DOCUMENTS
Sr. No.   Document Title Observation Checked By (QA)
Environment Control Record.
Formulation Order.
Packaging Order (Primary).
Raw. Material Tags Card sheet.
Area/Equipment Clearance Tags Card Sheet.
Wash Water Analysis Report.
Manufacturing Instructions.
Manufacturing and compression Operation Card.
Bulk Analysis Request And Report.
Packaging Order.
Packaging Instructions.
Packaging Line Clearance Operation & Inspection Record.
Weighing Sheet Corrugated Box.
Printed Packaging Coding & Accountability Record.
Certificate of Analysis – Finished Products.
NCR if any.
Finished Good transfer Slip.
Terminal Inspection Report.
Excess Material  consumption.
Washing of Containers, Equipment and Accessories Record.
Dispatch slip.

BATCH HISTORY

Record Deviation / Incident/NCR:-

Sr. No. Page No. Detail of NCR Corrective Action Preventive Action Done by Verified by

 Production Officer/Executive                                                                     IPQA Officer/Executive

                   Sign & Date                                                                                               Sign & Date

 RELEASE ORDER AND FINISHED GOODS STORES TRANSFER RECORD: We have verified the batch records of the following product and release and batch quantity given against if for Sale and distribution. The batch number given below has been produced and controlled in accordance with the requirement of the tablets claim and all other relevant provision required for production of this.

    Checked by                                                                                               Released By

Sign. Manager-Prod.                                                                                        Sign. Manager-QA

  •  QUANTITY  PER SHIPPER: _____________
Sr.

No.

 Date of Finished Goods Stores transfer Pack Size

 

 Nos. of Box

Packed

 Nos. of shipper Packed Finish Goods Transfer Note

Attached

 Transferred

By (Production)
             
             
Total Quantity    

 

                                                 Executed Batch Packing Record Reviewed By
Production (Officer/Executive) : Date :
IPQA Officer/Executive : Date :

 

MASTER FORMULAS