Production

Trimming Machine, Purpose :

Trimming Machine, The purpose of this SOP is to describe the operation procedure of Trimming Machine in order to comply with cGMP standard.

Trimming Machine, Scope :

The scope of the procedure is applicable to the Trimming machine at the Dialysis Fluid Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Trimming machine is a precision machine. It is covered by metal body. This machine consisting of a lever-operated knife and adjustable guides for container surfaces true to required angle.

Operator/Supervisor

[][]Operation and cleaning of the Trimming machine

Executive/ Sr. Executive

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Preparation and timely review of the SOP.

Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Manager, Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure :

Precaution(s) :

[][]Ensure that no unauthorized person gains operational access to the machine.
[][]Care must be taken to ensure that the drive units and accessory parts cannot be switched on inadvertently after servicing or maintenance work.

Instruction :

[][]Use Air (1 to 1.5 bar) during operation of Trimming machine.
[][]Keep the machine dry and cool environment.
[][]Keep the air pipe free from any other instrument, naught and coiling during operation and after completion of job.

Machine Assembling :

[][]Setting of in air pipe line of the machine.
[][]Ensure that the air pipe locks are tightly locked and cleaned.

Machine Operation :

[][]Check the machine that there is no abnormal setting of pipe in the machine.
[][]Connect the main electric supply with the socket.
[][]“On” the electric power.
[][]Then “On” the machine control power.
[][]After completion of assembling
[][]Placed the well required position of HPDE Container.
[][]Machine lever-operate HPDE container up the adjustable knife.
[][]Then Knife cutting the container mouth surfaces true to required.

Machine Dismantling :

[][]First “OFF” the air line valve and then remove the pipe from the source and the machine.
[][]“OFF” the machine control power.
[][]Then “OFF” the electric power.
[][]Remove the main power supply form the socket.

Machine cleaning :

Remove dusts from the machine with a dry lint free cloth.
Clean all the machine parts (air pipe and metal parts) with dry lint free cloth.

Annexure:

Annexure I Equipment Use Log Book

Filter Integrity Test Machine, Purpose :

Filter Integrity Test Machine, The purpose of this SOP is to describe the operation and sanitization procedure of filter integrity test Machine in order to comply with cGMP standard.

Filter Integrity Test Machine, Scope :

The scope of the procedure is applicable to the filter integrity test machine at the DFU Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Filter integrity test machine is a high precision machine. It is covered by special sealing profile with metal body, large size (10 inch) of touch PLC windows. This machine is associated with data control unit with networking system. BPT/ DFT/BDT are loaded into the machine by Supplier.

Responsibilities:

[][]The roles and responsibilities are as follows:

Operator/Supervisor

[][]Operation and cleaning of the filter integrity test machine
[][]Maintaining operation and cleaning log book.

Executive, Production

[][]Checking and ensuring that the operation and cleaning is performed according to the SOP.
[][]Checking the log book.
[][]Preparation and timely review of the SOP.

Manager Engineering

[][]Preparation of maintenance schedule and maintenance of the machine.

Head of Quality Assurance

[][]Ensure that the SOP reflects actual operation, cleaning and maintenance procedure.
[][]Approve the SOP against XX Pharmaceuticals Ltd. Master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

Precaution(s):

[][]Ensure that no unauthorized person gains operational access to the machine.
[][]Care must be taken to ensure that the drive units and accessory parts cannot be switched on inadvertently after servicing or maintenance work.
[][]The cover must be kept in close position during operation.

Instructions:

[][]Use Nitrogen (7 to 8 bar) during operation of filter integrity testing.
[][]Keep the machine dry and cool environment.
[][]Keep the nitrogen and other silicon pipe free from any other instrument, naught and coiling during operation and after completion of job.

Machine Assembling :

[][]Remove the SS cover of the Upper side of the machine.
[][]Setting of in and out pipe line of the machine.
[][]Ensure that the pipe locks are tightly locked and cleaned.

Machine Operation :

[][]Check the machine that there is no abnormal setting of pipe in the machine.
[][]Connect the main electric supply with the socket.
[][]Open the flap of automatic data controller (which is situated on the Upper side of the machine) & on the UPS switch.
[][]On the control power of automatic data controller.
[][]Login the password.
[][]After completion of assembling,
[][]Fix the recommended test method setting.
[][]Fix the pre-pressure on the nitrogen pressure gauge setting.
[][]Fix the main-nitrogen pressure setting.
[][]Log in by the main user.
[][]Select the “Program Test” on PLC.
[][]Press the “Page Down” on the PLC of machine.
[][]Select the “Test Technique” (Like: BPT, DFT, BDT).
[][]Press the “Page Down” On PLC of machine.
[][]Set the minimum and maximum range of nitrogen pressure (3000mbar to 4000mbar) as per recommendation of filter certificate.
[][]Press the “Page Down” on PLC machine.
[][]Then set the Product Name, Batch No., and Filter Identity No. on the PLC of machine.
[][]Press “Page Down” and press “Save” button.
[][]Then check all the pipe line again and plug on the nitrogen out line to the filter housing.
[][]Placed the well wetted (soaked by purified water) filter (02 micron) at “O” ring of the filter housing.
[][]Cover the filter housing and tightly locked with TC clam.
[][]After obtaining required steps lock the solution “In” line “OFF” with dead valve and TC clam tightly.
[][]Then press the “Start” button to start the filter integrity testing.
[][]During operation if we want to change (increase/decrease) any parameter or batch no. we have to Press “Stop” button and then put the data again.

Machine Dismantling :

[][]First “OFF” the nitrogen line valve and then remove the pipe from the source and the machine.
[][]Remove the nitrogen line from the filter housing.
[][]Press the “Main Menu” on the PLC of the machine.
[][]Remove the main power supply form the socket.

Machine cleaning :

[][]Remove dusts from the PLC of the machine with a dry lint free cloth.
[][]Clean all the machine parts (silicon pipe and metal parts) with dry lint free cloth.

Annexure:

Annexure I Equipment Use Log Book

Laminar Air Flow Machine, Purpose :

Laminar Air Flow Machine, The purpose of this SOP is to describe the operation, calibration and cleaning of Laminar Air Flow used for the Filling Area in the Dialysis Fluid unit (DFU) at XX Pharmaceuticals Ltd.

Laminar Air Flow Machine, Scope :

This procedure describes the application of Laminar Air Flow, for the Filling Area of formulated drug product at the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]LAF: Laminar Air Flow

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Production

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Production

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.
[][]Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Ensure the Safety Precaution.
[][]No Water Contact on the switch Board.

Operation

[][]Ensure that all surface area is clean with PVC curtain.
[][]Check the Electric line ON
[][]Ensure that the Laminar Air Flow is cleaned on the day use.
[][]Plug on the electric line. .
[][]Switch on the power its main.
[][]Power on the Laminar Air Flow Light
[][]Switch ON the LAF operation.
[][]Check Pressure Gauge Meter.
[][]Ensure the Reading of air Differential Pressure 150pa-200pa.
[][]Record the Operational data in the Operation Logbook of Laminar Air Flow as per Annexure – II.
[][]Power off the Laminar Air Flow.
[][]Switch off the power from its main.

Cleaning and maintenance:

[][]Clean the outside case of the Laminar Air Flow using a mild detergent or disinfectant (e.g.75% IPA) if required.
[][]Clean the area around the Laminar Air Flow and wipe immediately. Special care should be exercised when cleaning up IPA 75% (usually).
[][]When required, clean all wires and contacts to avoid corrosion.
[][]Inspect the cables of the LAF for any signs of broken insulation.
[][]Inspect the Light Shade Dry Cleaned Cloth.
[][]Rinse through with Purified Water of PVC Curtain.
[][]Make sure that no water Flow to the HEPA Filter, Light Shade.

Annexure:

Annexure I Equipment Use Log Book
Annexure-II: Logbook for daily Operation of Laminar Air Flow.

Purpose :

The purpose of this SOP is to describe the procedure of container Washing and Handling system of Dialysis Fluid Unit at XX Pharmaceuticals Ltd.

Scope :

This SOP is applicable for the Production and Primary Packaging of Dialysis Fluid Unit at XX Pharmaceuticals Limited.

Definition / Abbreviation :

[][]HDPE: High Density Polyethylene

Responsibilities :

[][]The Roles and Responsibilities are as follows :

Operator

[][]To ensure that this procedure is followed.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Precautions :

[][]Ensure the Proper Safety Instruction Are Followed.
[][]Ensure that the Supply the Water (Potable, Hot & Purified).

Empty Container Washing Procedure :

[][]Send the ERP Requisition to the ware house, then they Provide QC passed Containers from General Warehouse.
[][]Places the containers (50pcs) at the Plastic Pallet and transfer to the container washing room.
[][]Ensure that all utility lines like compressed air, electric line, potable water (hot & normal) and purified water are in attendance.
[][]Put off the stopper plug.
[][]Placed the container perpendicularly (3Pcs at a time) at the washing machine then flow the potable water for 30 sec (inner & outer elevation).
[][]Supply the hot water (50 to 60o) into the containers for 30 sec (inner & outer elevation).
[][]Concluding Supply of Purified water into the containers for 30 sec (inner & outer elevation).
[][]After that washed container staging at the cage trolley, then transfer to the filling room.
[][]Ensure that area cleaning activity is recorded in Cleaning Log book
[][]Check and ensure that Containers Cleaning activity is recorded in respective ‘Equipment log book’
[][]Ensure that all Containers are labeled as CLEANED.

Annexure

Annexure-I: HDPE Container (10 L) Washing Record.

Product Changeover, Purpose :

Product Changeover, To lay down the Procedure of Product Change Over to the Production and Packaging Area during Product to Product changeover and Batch to Batch Changeover for Dialysis Fluid Unit(DFU)

(DFU).

Product Changeover, Scope :

This SOP is applicable for the Concern Personnel of Production and Packaging of DFU Unit at XX Pharmaceuticals Limited.

Definition / Abbreviation :

N/A

Responsibilities :

[][]The roles and responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Laundry Man

[][]To provide cleaned garments.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Precautions :

[][]Ensure the proper safety instructions are followed.
[][]Ensure that no previous product is available in the area.

Product to Product Changeover :

[][]Ensure that, all utility lines like compressed air line, steam line, electrical fixtures, air inlet ducts, return air risers, potable water and purified water lines are cleaned and no visible traces of product are present.
[][]Ensure that Outer surface of machine, table, door, floor, walls and ceiling are cleaned.
[][]Ensure that Pre-mixing, Mixing, Storage, Filling Vessel to be clean with plenty of water (First time Potable Water Finally Purified water).
[][]Ensure that area cleaning activity is recorded in ‘Room Cleaning Log Book’
[][]Ensure that all equipments in the area are cleaned according to their respective SOPs and no traces of previous product are visible within the equipment.
[][]Check and ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’
[][]Ensure that Span between equipment usage and cleaning is not more than seventy two hours.
[][]Ensure that Balances in the production area are cleaned and accuracy check is done before use.
[][]Ensure that production utensils like scoops, spatula, sieve stand, punch trolley, pallets, BMR table and tool boxes are cleaned as per procedure.
[][]Ensure that all equipments are labeled as ‘CLEANED’.
[][]Ensure that fresh set of gowns are issued to concerned operators.
[][]Ensure that proper environmental condition is maintained in the area and the records of the same are maintained in the specified formats.
[][]Ensure the correctness of Batch Manufacturing Record / Batch Packaging Record.

Batch to Batch Changeover :

[][]Ensure that previous batch material is removed from the production area.
[][]Ensure that all the equipment and their spares are cleaned according to their respective SOPs.
[][]Ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Material and Man Flow, Purpose :

Material and Man Flow, To lay down the procedure of Material and Man Flow to the Production and Packaging Area for Dialysis Fluid .

Material and Man Flow, Scope :

This SOP is applicable for the Concern Personnel of Production and Packaging of Dialysis Fluid Unit(DFU) of the XX  Pharmaceuticals Limited.

Definition / Abbreviation:

[][]BOM = Bill of Material
[][]QAD = Quality Assurance Department
[][]DFU= Dialysis Fluid Unit

Responsibilities:

[][]The roles and responsibilities are as follows:

Operator

[][]To follow the laid down procedure.

Laundry Man

[][]To provide cleaned garments.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Annexure:

N/A

Precautions :

[][]Do not step on the floor with bare foot.
[][]Rub hands with Disinfectant Solution before entering into the Production Area.
[][]Jewelry, Wrist Watch, Finger Ring & Ear Ring is not allowed to Production Area.
[][]No food is allowed to Production Area.
[][]Shoe>Cover >Cap >Apron >Mask.
[][]After wearing company provided dress, stand in front of the mirror and confirm that, clothing is covering full arms and cap is covering all hairs according to the sample photos displayed.
[][]Proceed towards the DFU Unit.

MAN FLOW ( Starting from D Change ) :

[][]Before entering into the primary change room, Personnel should complete secondary change as per procedure.
[][]Enter into the Primary Change Room.
[][]Rub hands with Disinfectant Solution (70% Iso-Propyl Alcohol).
[][]Open the door of Corridor, turn left side and proceed to the Production as well as Container Washing Area of DFU.

MATERIALS FLOW ( Starting from Ware-House, Solid Block ) :

[][]Collect Materials from Cargo Lobby (less than 25 Kg) for dispensing at the Dispensing Booth (GPR009) of General Block.
[][]Ensure that, around 25 Kgs. in a single Bag / Pack transfers directly to the DF Unit Air-Lock.
[][]Ensure that, all the materials dispensed as per BOM are to be needed to transfer to the Manufacturing Area of the DFU.
[][]Liquid Material (Glacial Acidic Acid) is to be collected from the Flammable Storage Area.
[][]Filled Containers (10L) are to be transferred to the Secondary Packaging Area of General Block by using transfer trolley.
[][]The received Filled Containers (10L) are taken to the Packaging Conveyor for proper Wiping, Labeling and Packaging.
[][]Packed Products as a whole batch are to be taken to the Quarantine Area on Pallets for QA Release.
[][]After getting QA Release Slip, the Finished Goods (as a whole batch) are to be transferred to the Central Ware-House through the Warehouse of Solid Block.

Filter Cleaning, Purpose :

Filter Cleaning, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Cartridge filter in order to comply with cGMP standard.

Filter Cleaning, Scope :

The scope of the procedure is applicable to the Cartridge filter of  Dialysis Fluid  of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]CIP : Clean In Place

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the cartridge filter.
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Annexure:

N/A

Precautions :

[][]Hot purified water should be not more than 60oc.
[][]The wash-down valves are in closed position.
[][]Check for any leakage from discharge valve.

Filter Cleaning:

[][]Remove the Filter housing from the Vessel.
[][]Cleaning of filter Cartridge (1.2, 0.45 & 0.2 micron or 1.0, 0.6 & 0.2 micron).
[][]Clean the Cartridge filter (1.2, 0.45 & 0.2 micron or 1.0, 0.6 & 0.2 micron) with potable water.
[][]Soak the Cartridge filter in hot purified water and retain for 30 minutes.
[][]Wash the Cartridge filter 3 times with purified water.
[][]Allow the Cartridge filter to dry in wash bay.
[][]After drying take the Cartridge filter in a Clean poly bag and Stored in Closed ss Cabinet.
[][]After final cleaning affix the ‘CLEANED’ label.

Dialysis Fluid Filling Machine, Purpose :

Dialysis Fluid Filling Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of filling machine in order to comply with cGMP standard.

Dialysis Fluid Filling Machine, Scope :

The scope of the procedure is applicable to the filling machine at the production area of dialysis Fluid unit of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]LAF = Laminar Air Flow.
[][]PVC = Polyvinyl Chloride.

Responsibilities :

[][]The roles and responsibilities are as follows:

Operator

[][]Operation and cleaning of the filling machine.
[][]Maintaining equipment log book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Plant Operation

[][]To agree the laid down procedure.

Head of Quality Assurance

[][]To approve the SOP

Procedure :

Precautions :

[][]Use face mask, rubber gloves and protective clothing during filling operation.
[][]Turn ON LAF before filling operation.
[][]Connect electric line properly.
[][]Filling vessel valves are in open position.
[][]Check any leakage from discharge valve, silicon pipe and filling piston.

Machine Assembling :

[][]Clean the machine well with lint free cloth.
[][]Assemble the machine change parts and all the connections that are necessary for certain types of Operation.
[][]Attach tightly the silicon pipe (2’’) to the storage vessel (2000L).
[][]Attach tightly the solution transfer pipe (1½’’) to the dosing unit.
[][]Covert the filling machine by the PVC curtain.

Machine Operation:

[][]Lock the chamber lid cover of 200L vessel properly.
[][]Turn the transfer pump ON/OFF key to ON.
[][]Transfer 2000 L solution from storage vessel (2000 L) by opening the gate valve of storage vessel.
[][]This system is done by product filling end times.
[][]Turn the filling machine ON/OFF key to ON.
[][]Placed two containers under the dosing nozzle pipe
[][]Wait for two dosing rotation per container (5Liters/Stroke) then push OFF button.
[][]Look the actual filling volume of the containers.
[][]Push the OFF button of filling machine if container supplies insufficient or any other problems.
[][]Check the solution during filling by looking at the vision area of lid cover.
[][]Transfer or sample the solutions by opening the sampling port valve manually.
[][]Push the OFF button to stop the machine and plug out the main electric line to its main.
[][]Record the machine start time, end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling :

[][]Turn the machine ON/ OFF key to OFF the machine.
[][]Remove the solution transfer pipe and filling pipe manually.
[][]Remove the lid cover and turn OFF the stirring.
[][]Remove the electric industrial plug.

Machine Cleaning :

[][]Clean the machine with lint free cloth to remove dust.
[][]Clean the inner elevation of the filling machine by using potable water.
[][]Clean the inner elevation of the filling machine by using hot water.
[][]Clean the inner elevation of the filling machine by using purified water through pipe.
[][]Clean the outer elevation of the filling machine with potable water by rubbing with a lint free cloth.
[][]Soak with a clean dried lint free cloth to remove the water from the filling machine.
[][]Clean all of the machine parts with potable water, hot water then purified water.
[][]Soak with a clean dried lint free cloth to remove the water from the machine parts.
[][]Affix the clean label on the filling machine as ‘CLEANED’.

Annexure:

Annexure I Equipment Use Log Book

Pre-Mixing Vessel, Purpose :

Pre-Mixing Vessel, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Pre-mixing Vessel in order to comply with cGMP standard.

Pre-Mixing Vessel, Scope :

The scope of the procedure is applicable to the Vessels at the Production area of Kidney Dialysis Fluid (KDF) of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]CIP : Clean In Place

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Pre-mixing Vessel.
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the SOP.

Procedure

Precautions :

[][]Chamber cover is properly locked.
[][]The wash-down valves are in closed position.
[][]Check for any leakage from discharge valve.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Clean the machine well.
[][]Assemble the machine change parts and all the connections that are necessary for certain types of operation.
[][]Attach the vacuum material transfer unit to the lid cover to transfer Liquid material automatically.
[][]Attach the solution transfer unit to the lid cover to transfer solution automatically by pressure.
[][]Attach the vision unit with clamp to the cover of chamber.

Machine Operation:

[][]Lock the chamber cover with chamber cover locking. Check for proper locking.
[][]Turn the machine ON/OFF key to ON. the machine is ON.
[][]Set the impeller Rotation Per Minute (RPM) and process time to desired value at the regulator at SETUP button (user can change the Impeller speed)
[][]Look the actual speed of the impeller.
[][]To off the impeller off button.
[][]To add solution or water open the chamber covers and then transfers the solution or water pneumatically.
[][]To stop the machine immediately, push the EMERGENCY button backward, machine will be stopped immediately.
[][]To check the solution during process OFF the impeller. Lift the lid cover manually and check.
[][]To Transfer or sample the solutions open the discharge valve manually.
[][]Transfer the solution through the Filter Housing control button (manual option is available).
[][]When discharge is complete push the CLOSED button to close the discharge valve.
[][]Transfer the Solution in product to Mixing Vessel (2000L).
[][]Push the OFF button to stop the Machine.

Machine Dismantling

[][]Turn the machine ON/ OFF key to off the machine.
[][]Remove the solution transfer unit.
[][]Remove the Lid Cover and Vision unit.
[][]Remove the Sample Collection unit.
[][]Remove the Filter housing from the Vessel.

Machine Cleaning

Cleaning of Vessel

[][]Fill the Vessel with Potable Water, the inner surface of the vessel well enough to washout the processing materials .Clean the outer surface of the vessel with rubbing & plenty of potable and purified water.
[][]Stir for 5-10 min after sufficient amount of potable water 500L being aggregated at the bottom.
[][]Rub with brush on the top and side walls of the vessel.
[][]Transfer the total wash water to the Manufacturing Vessel 2000L.
[][]Clean the wall and top with the hot potable water.
[][]Rub with brush on the top and side walls of the vessel again.
[][]Fill the Vessel with Purified Water and stir 15 min and then transfer to mixing vessel.
[][]Transfer the total wash water from 500L to the Vessel 2000L, 2000L drainage via filling machine.
[][]Rinse the wall and top of the vessel with hot potable water again.
[][]Clean the top and wall of the vessel with dry lint free cloth.
[][]Rinse the outer and inner wall of the vessel with IPA.
[][]Remove all water from the vessel and pipe line with Compressed air flow.
[][]After final cleaning affix the ‘CLEANED’ label.

Annexure:

N/A

Temperature and Relative Humidity Monitoring, Purpose:

Temperature and Relative Humidity Monitoring, To lay down the procedure for monitoring of Temperature & Relative Humidity (%) at the Packaging area.

Temperature and Relative Humidity Monitoring, Scope:

This SOP is applicable for the Packaging Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Packaging

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure :

Precaution :

[][]Do not use a new hygrometer unless it is calibrated.
[][]When any hygrometer is shifted from one location to another, allow to stabilize the device prior to record the temperature / Relative Humidity (%).
[][]Check the due date of calibration of the hygrometer and magnehelic gauge before taking reading.
[][]Ensure that temperature and Relative Humidity (%) readings are taken before going to operation.
[][]Temperature and Relative Humidity (%) (using Digital Hygrometer)
[][]Ensure that no dust is accumulated over the sensor.
[][]Read the temperature and relative humidity (%) values displayed on the screen of digital hygrometer and record.

Area

[][]Packing Hall, Waste, Cleaner’s, Printing, IPC Room, Office Executive and Packing Material Staging.

Temperature

[][]NMT 25°C

Relative Humidity (%)

[][]NMT 60 %

Frequency

[][]Twice in a shift, first before starting the operation and second after four hours.
[][]If the reading is not within limit at any time of operation, inform the Engineering department immediately.

Material Drying Machine , Purpose :

Material Drying Machine , The purpose of this SOP is to describe the setting, operation and cleaning procedure of Material Drying Machine (Model: Standard) in order to comply with cGMP standard.

Material Drying Machine , Scope :

The scope of the procedure is applicable to the Material Drying Machine (Model: Standard) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Sep Up, Operation and cleaning of the Material Drying Machine (Model: Standard)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure

Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of individual tray and machines inner part during assembling of machine.
[][]Booth side doors are in lock position during operation.
[][]Check the air outlet damper position before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the material dryer machine before assembling.
[][]Assemble the dryer by opening the front side door of the dryer.
[][]Load the tray with material and place into the tray holding rack.
[][]Then set the rack carrying trolley.
[][]Then place the tray holding rack into the machine.
[][]After that closed the door accurately with the help of door locking handle.
[][]Then closed the air outlet damper and tight the screw accurately.

Machine Operation

[][]Switch ON the main power switch.
[][]Open the plastic cover and set the desire temperature of the machine.
[][]Then open the plastic cover and set the desire time of the machine.
[][]At first switch ON the blower of the machine.
[][]Then switch ON the heater of the machine.
[][]After completed the drying time open the air outlet damper for material cooling and check the LOD.
[][]After operation switch OFF the heater and then blower. Unload the tray holding rack from the machine.
[][]Finally switch OFF the main power of the machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’.

Machine Dismantling

[][]Open the both side door of the machine.
[][]Unload the tray holding rack from the machine with the help of carrying trolley.
[][]Remove the tray from the rack.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, product contact parts, tray and other machine parts.
[][]Use hot water to clean all the trays.
[][]Finally rinse the machine body, product contact parts, trays and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Material Pulverization Machine, Purpose :

Material Pulverization Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Material Pulverization Machine (Model: 30B) in order to comply with cGMP standard.

Material Pulverization Machine, Scope :

The scope of the procedure is applicable to the Material Pulverization Machine (Model: 30B) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Sep Up, Operation and cleaning of the Material Pulverization Machine (Model: 30B)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure
Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of sieves, ss container, tray and gasket before assembling of machine.
[][]Check the sieve for its integrity before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the machine before assembling.
[][]Assemble the machine by opening the front side cover of the machine.
[][]Adjust the sieve into the ring with the help of screw.
[][]Then set the sieve ring into the machine.
[][]Close the cover of the machine properly.
[][]Set the filter bag of the machine with the help of spring and clamp.
[][]Place the tray under the filter bag.

Machine Operation

[][]Switch ON the main power switch.
[][]Switch ON the blower by pressing green button of the machine.
[][]Then switch ON the motor by pressing green button of the machine.
[][]Input the material through the hopper of the machine manually.
[][]Sieve the material and collect sieved material through the cover discharge opening.
[][]After operation first switch OFF the motor then switch OFF the blower by pressing red button.
[][]Record the machine operation parameters in the ‘Equipment Log Book’.

Machine Dismantling

[][]Open the front cover of the machine.
[][]Remove the sieve ring of the machine.
[][]Remove the filter bag of the machine.
[][]Remove the tray of the machine.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, product contact parts, tray, container, sieve & filter bag.
[][]Use hot water to clean all the product contact parts such as sieve ring.
[][]Finally rinse the machine body, product contact parts, trays and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Bottle Washing Machine, Purpose :

Bottle Washing Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Glass Bottle Washing Machine (Model: IRW-16) in order to comply with cGMP standard.

Bottle Washing Machine, Scope :

The scope of the procedure is applicable to the Glass Bottle Washing Machine (Model: IRW-16) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set up, operation and cleaning of the Washing Machine (Model: IRW-16)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure

Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of individual water reserve tank and machines inner part during assembling of machine.
[][]Do not touch the hot water tank during operation.
[][]Check the individual bottle washing nozzle working properly.

Machine Assembling

[][]Keep the necessary change parts near the bottle washing machine before assembling.
[][]Assemble the washing machine by bottle holder.
[][]Load the pump 1 with tap water and pump 2 with hot water.
[][]Load the bottle holder with glass bottle.
[][]Set the nozzle’s spray rate of tap water and purified water depending on the glass bottle size.

Machine Operation

[][]Switch ON the main power switch.
[][]Switch ON the heater switch of the machine and wait 20 minutes for hot water (60ºC).
[][]Then press the START button of the main motor.
[][]After press the START button of the pump 1.
[][]Then press the START button of the pump 2.
[][]Open the valve of compressed air line.
[][]After completing the glass bottle washing procedure close the valve of tap water, purified water & compressed air line.
[][]After operation switch OFF the heater, pump 2, pump 1 and then main motor.
[][]Finally switch OFF the main power of the machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’.

Machine Dismantling

[][]Open the cover of the machine.
[][]Remove the bottle holder of the machine.
[][]Drainage the water of pump 1 & pump 2.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Use potable water to clean the machine body, product contact parts and other machine parts.
[][]Use hot water to clean all the parts.
[][]Finally rinse the machine body, product contact parts and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’  label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’.

Annexure:

Annexure I Equipment Use Log Book

Blister Packaging Machine, Purpose :

Blister Packaging Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Blister Packaging Machine (Model: HM-V3) in order to comply with cGMP standard.

Blister Packaging Machine, Scope :

The scope of the procedure is applicable to the Blister Packaging Machine (Model: HM-V3) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set Up, Operation and cleaning of the Blister Packaging Machine (Model: HM-V3)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Annexure:

N/A.

Procedure

Precautions :

Safety

[][]Never run the machine with its door open.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Keep the switches “OFF” during break-time and at the end of the job.
[][]Care must be taken to ensure that the drive units and accessory parts cannot be switched on inadvertently after servicing or maintenance work.

Special Instruction

[][]Be sure that the power switches are “OFF” position.
[][]Beware of the high temperature of “Sealing top mold” during cleaning and if possible, allow it to cool down completely.
[][]Should not use methanol or other organic solvent like ethanol, carbon tetrachloride, thinner, benzene etc. to clean plastic doors and other parts of the machine.
[][]Water should not be used to clean metal parts of the machine.
[][]Care should be taken to ensure that no water enters inside the motor.
[][]Corrosive materials should not be used to clean the machine.
[][]Heavy parts should not dismantle alone, always taken help from others.
[][]Machine chiller purified water level should be check fifteen days interval and purified water should be change every three months interval.
[][]Carefulness should be taken about heavy parts handling.

Machine Assembling

[][]Switch on the main power supply of the machine.
[][]Check the draw in of the base film and the lid foil.
[][]Check Compressed air valve open and air pressure above 6 bars.
[][]Turn control panel key “ON”.
[][]Push reset button and press main button.
[][]Press setup button to show password for entering product list.
[][]Select Specific product from product list and press main button.
[][]Adjust draw off length by pressing inching switch according to advance length.
[][]Check the emergency push buttons, safety switches of the safety guards/glass doors.
[][]Press Main button and enter into information and positioning the machine according to following parameter-
[][]Forming station
[][]Sealing station
[][]Embossing
[][]Cooling station
[][]Perforation / Slitting station.

[][]Set following change parts by push inching switch-
Forming
Perforation / Slitting
Cutter
[][]Set following change parts carefully-
Pre-heating
Guide rail
Sealing upper-lower plate.
Embossing
Cooling Plate
Pulling Station
Feeding Tray

[][]Push reset button and checks the machine accurately by inch the inching switch press.
[][]Set bottom foil & lid foil and cutting shall be adjusted by inching switch on manual mode with press-
Heater.
Chiller.
Draw off.
Sealing lift.
[][]Press “Start” button and run machine to check the pocket forming and batch code embossing.
[][]Insert tablets or capsules on the pocket of PVDC/PVC/ALU film on the guide rail and perform a leak test operation of those strips to ensure proper sealing.
[][]Press manual mode and “OFF” all button only the following button shall “ON”
Heater.
Chiller and
Sealing lift.
[][]Convert manual mode to auto mode for running the machine.
[][]After completed the all parts setting, check that every parts are setting properly & proper place.
[][]Ensure that every screw nuts are tight properly.
[][]Set batch code with the respective digit.
[][]Emboss batch code and show Quality Assurance Officer for approval.

Machine Operation

[][]Ensure that area and equipment are clean and suitable to start the operation.
[][]Before starting the blister machine use surgical gloves, nose mask etc.
[][]Set different change parts like forming plate, sealing plate, code embossing, guid rail, cooling plate etc. in proper position.
[][]Set the top Foil (Alu foil) & Bottom Foil (PVC, PVDC & Alu foil) correctly.
[][]Open the compressed air valve & ensure that the air pressure is above 6 bars. Check & ensure that the compressed air is free from moisture.

[][]Temperature for PVDC preheating 110-140ºc and sealing 150-180ºc and for slitting are 60-80ºc & embossing Alu 70-80 ºc, temperature for Alu sealing 160-180 ºc and embossing 70-90 ºc maintained .
[][]Tablets and Capsules are placed manually to the PVDC forming or Alu forming pocked. Different packs are produced for different products by forming, feeding, sealing, punching and discharging.
[][]Machine should be observed very carefully during blistering operation.
[][]Press the stop button in machine after completes the blister operation.
[][]Record the machine operation start time and end time & other parameters in the ‘Equipment Log Book’ .

Dismantling of Change Parts

[][]Change parts should be removed sequentially from the machine with the help of others.
[][]Feeding Tray should be removed by loosing screw nuts.
[][]Guide Rail should be removed by loosing nuts.
[][]Forming Set (Upper & Lower Plate) should be removed by loosing screw nuts.
[][]Cutter should be removed by loosing nuts.
[][]Sealing Upper Plate should be removed by loosing clamp lock.
[][]Sealing Lower Plate should be removed by loosing screw nuts.
[][]Cooling Plate should be removed by loosing screw nuts.
[][]Perforation/ Slitting should be removed by loosing screw nuts.
[][]Heating Plate (In-case of Alu-PVC) should be removed by loosing nuts.
[][]Embossing Plate should be removed by loosing screw nuts and clamp lock.
[][]Change parts should be kept on clean pallets with “TO BE CLEANED” label.

Machine Cleaning

[][]All documents, previous product container and any materials should be removed from the room.
[][]The dust should be cleaned around the machine with the help of vacuum cleaner.
[][]The surface of the machine should be cleaned with lint free cloths with Purified Water or defined cleaning solution starting from top to downwards sequentially at first ceiling, wall, machine and floor.
[][]Safety covers (Door) should be cleaned by the use of wetted smooth lint free cloth with purified water.
[][]Glass and plastic materials should be cleaned by lint free smooth cloth with purified water.
[][]The machine should be moped with a lint free cloth using purified water.
[][]Finally, the machine should be moped with dried lint free cloth.
[][]Record should be taken in equipment machine log book.
[][]Machine accessories should be transferred to the wash room.
[][]“CLEANED” label should be attached to the machine.
[][]Change parts should be dismantled and kept on a clean trolley or pallets with status label and kept the trolley on the washing room for the cleaning at the end of product run.
[][]After cleaning completion the change parts should be stored in tool store with “CLEANED” label.

Annexure:

Annexure I Equipment Use Log Book

ROPP Cap Sealing Machine, Purpose :

ROPP Cap Sealing Machine, The purpose of this SOP is to describe the Operation and cleaning procedure of ROPP Cap Sealing Machine (Model: PPM-35) in order to comply with cGMP standard.

ROPP Cap Sealing Machine, Scope :

The scope of the procedure is applicable to the ROPP Cap Sealing Machine (Model: PPM-35) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Cap Sealing Machine (Model: PPM-35)
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Ensure that area & equipment are clean and suitable to start the operation.
[][]Use protective suit, surgical gloves, head gear, cotton mask, and safety goggles during sealing operation.
[][]In case of emergency, press the emergency switch to stop the machine.

Machine Assembling

[][]Set the base of the machine by specific nut and attach the bottle adjuster.
[][]Set the sealing wheel according to the neck diameter of the bottle.
[][]Fix the bottle size by moving the base.

Machine Operation

[][]Load the bottle on the SS table.
[][]Fix the plastic stopper and aluminum cap on the empty bottle.
[][]Turn on the main switch of the machine.
[][]Take a bottle on the base.
[][]Seal it by the moving sealing wheel.
[][]Check the leakage by leak test apparatus.
[][]If sealing is accurate then another eight empty bottle have to seal.
[][]Take them again for leak test.
[][]Continue the sealing operation if sealing is accurate.
[][]Turn off the all switch gradually after complete the sealing operation.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Turn the main switch off.
[][]Dismantle the parts like moving sealing wheel, bottle adjuster unit and transfer them to the wash bay.

Machine cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body and holding screw.
[][]Use hot water to clean all the product contact parts & finally rinse with purified water.
[][]Clean and swab all the parts with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’.

Auger Filling Machine, Purpose :

Auger Filling Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Auger filling Machine (Model: GZF30B) in order to comply with cGMP standard.

Auger Filling Machine, Scope :

The scope of the procedure is applicable to the Auger filling machine (Model: GZF30B) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PLC = Programmable Logic Controller.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Auger filling Machine (Model: GZF30B)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Ensure that area & equipment are clean and suitable to start the operation.
[][]Before entering the filling room use protective suit, surgical gloves, head gear, cotton mask, and safety goggles during filling operation.
[][]Do not insert hands inside the hopper during operation; keep the hopper closed after loading.
[][]Make sure that powder is not deposited in hopper, dosing unit and other parts of the machine that must be observed very carefully.
[][]In case of emergency, press the emergency switch to stop the machine.

Machine Assembling

[][]Set the dosing unit by specific nut and attach the supporting parts of dosing unit.
[][]Set the powder hopper with its supporting parts.
[][]Fix the size of the bottle on the machine.
[][]Set the parameters of the machine such as Set Quantity, Actual Quantity and Output on the PLC.

Machine Operation

[][]Load the bottle on the SS table.
[][]Load the powder in hopper and close the lid of hopper.
[][]Turn on the main switch of the machine.
[][]Turn on the vibrator switch.
[][]Mix the powder in the hopper by rotating stick.
[][]Set the filled weight on the PLC.
[][]Adjust the filled weight by pressing leg punch in the empty glass bottle.
[][]Check the fill weight of eight bottles after setting the volts in dose wheel.
[][]Continue the filling operation if fill weight is accurate.
[][]Turn off the all switch gradually after complete the filling operation.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Turn the main switch off.
[][]Collect the powder from the hopper and dosing unit by vacuum cleaner.
[][]Dismantle the parts like hopper, auger and dosing unit and transfer them to the wash bay.

Machine cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the hopper, dosing unit, operation panel and machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts, holding screw and other parts with purified water.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book.

Annexure:

Annexure I Equipment Use Log Book

Capsule Polishing Machine, Purpose :

Capsule Polishing Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Capsule Polishing Machine (Model: SF-40N) in order to comply with cGMP standard.

Capsule Polishing Machine, Scope :

The scope of the procedure is applicable to the Capsule Polishing Machine (Model: SF-40N) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set up, operation and cleaning of the Polishing Machine (Model: SF-40N)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure

Precautions :

[][]Make sure that the main power switch is OFF position before and after operation.
[][]Ensure that area & equipment are clean and suitable to start the operation.
[][]Before entering the capsule polishing room use protective suit, surgical gloves, head gear, cotton mask, and safety goggles during polishing operation.
[][]Do not insert hands inside the hopper during operation.
[][]Make sure that capsule is not deposited in hopper and other parts of the machine that must be observed very carefully.
[][]In case of emergency, press the emergency switch of the main encapsulation machine to stop the machine.

Machine Assembling

[][]Set the capsule polishing brush by specific nut and attach the SS cover of the machine.
[][]Set the capsule hopper.
[][]Fixed the empty capsule shell feeder on the machine.
[][]Set the air pressure of the machine.

Machine Operation

[][]Turn ON the main switch of the machine. Then turn ON the switch of the capsule polishing machine.
[][]Turn on the air pressure valve and adjust the air pressure 0.15 to 0.2 bars.
[][]Load the capsule on the hopper.
[][]Check the capsule is polishing accurately.
[][]Continue the polishing operation if capsule polishing is accurate.
[][]Turn OFF all switch gradually after complete the polishing operation.
[][]Record the machine operation parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Turn the main switch OFF.
[][]Collect the dust from the hopper by vacuum cleaner.
[][]Dismantle the parts like hopper, machine cover, brush and empty shell feeder and transfer them to the wash bay.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the hopper machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts like capsule polishing brush.
[][]Finally rinse the machine body, all product contact parts, holding screw and capsule polishing brush with purified water and dry the brush properly after cleaning.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’  label.
[][]Record the cleaning parameters in the ‘Equipment Log Book.

Annexure:

Annexure I Equipment Use Log Book

Capsule Filling Machine , Purpose :

Capsule Filling Machine , The purpose of this SOP is to describe the setting, operation and cleaning procedure of the Capsule Filling Machine (Model: SF-40N) in order to comply with cGMP standard.

Capsule Filling Machine , Scope :

The scope of the procedure is applicable to the Capsule Filling Machine (Model: SF-40N) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Set up, operation and cleaning of the Capsule Filling Machine (Model: SF-40N)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure :

Precautions :

Safety

[][]Never run the machine with its door open.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Keep the switches “OFF” during break-time and at the end of the job.

Special Instruction

[][]Ensure the Capsule Filling machine is properly cleaned.
[][]Compressed air pressure should be set at 6 kg/cm².
[][]Filters on the dry vacuum must be cleaned regularly. Vacuum should be used for cleaning.
[][]Do not use water or a solvent to wash filters on the vacuum.
[][]Never wash filters with water.
[][]Lubricate all moving parts as per schedule.
[][]Use correct lubricants for all moving parts.
[][]Never repair, adjust, clean or lubricate any moving parts while the machine is in motion.

Machine Assembling

[][]Open the site glass of all sides
[][]Set the desired side pusher and tighten the set screws.
[][]Set the desired race way and tighten the set screws.
[][]Set the desired feeder and tighten the set screws.
[][]Set the block and tighten the set screws.
[][]Adjust the side pusher and down pusher.
[][]Press “up” button on the display and make powder hopper in maximum height.
[][]Install the desired dose filling plate.

Adjust the dosing device.

Align the stop plate with the tamping pin holes. Insert the tamping pins and pull the stop plate to lock around the neck of the pins. Tighten the four set screws.
For alignment of dosing disk with set plate-
Loosen the dosing disk set screws.
Insert six adjustment bars through the holes on the set plate.
Adjust the position of the dosing disk until all six adjustment bars fall freely into the disk holes
[][]Tighten set screws without moving the disk.
[][]Check the alignment with six adjusting bars to see if all bars fall freely without touching the disk hole wall.
[][]Turn the machine 2-3 revolutions by the hand wheel to see the adjustment bars fall freely at all six points.
[][]Adjust the tamping pins into the set plate holes and adjust set screws.
[][]Adjust the closing pin holder and joint plate depending on the capsules size.
[][]Adjust height of dosing disk (0.5mm).
[][]Check the correct setting of change parts listed below
Upper capsule segment
Lower capsule segment
Capsule feeder
Race way
Side pusher
Capsule stopper plate
Size ring
Dose filling plate (for pellet)
Tamping pins (for powder)
Dosing disk (for powder).

Machine Operation

[][]Check the cleanliness of the filling machine. Give clearance to run the machine.
[][]Switch ON the main power switch.
[][]Open compressed air supply valve.
[][]On the control power of automatic data controller.
[][]Race machine through a few steps via the hand wheel of the main drive.
[][]Charge capsule hopper with empty capsule shell.
[][]Clear capsule locking at capsule magazine.
[][]Turn key switch MANUAL MODE to INCHING.
[][]Switch on vacuum Press the illuminated pushbutton VACUUM

Powder Station

[][]Charge powder container with powder
[][]Adjust powder height mechanical tamping pin adjustment
[][]Adjust powder filling level height on dosing disk
[][]Run machine in inch mode for 6-7 turnings until all segments are filled with capsules Press the pushbutton START Subsequent check capsule weight.
[][]If necessary, adjust the capsule weight by adjusting the tamping pin and the powder height.

Pellet Filling Station

[][]Charge pellet hopper with pellet.
[][]Open the shutter > moving it upwards
[][]Start operation of the pellet station.
[][]Run machine through several cycles in inch mode >press the pushbutton START and then check capsule weight with pellets.
[][]Let the machine running >Press the pushbutton START
[][]Check again capsule weight and correct if necessary.
[][]Start machine in automatic mode.

Control machine running

[][]Stop automatic mode > Press key STOP.
[][]Shut Off compressed air supply.
[][]Clean the machine as per current version of SOP.

Machine Cleaning

[][]Take the main switch to OFF position.
[][]Remove the pellet hopper by removing four screws.
[][]Remove pellet doser by removing four nuts.
[][]Remove the discharge chute by removing two nuts.
[][]Rotate the hand wheel, situated at the lower portion of right side of the machine, to bring capsule segment no. 1 to backside of the machine.
[][]Remove the upper capsule segment one by one by removing two nuts using allen key. Clean them with dry cloth, then tape water & finally rinse with purified water and keep them in their respective box.
[][]Remove the lower capsule segment one by one by removing two nuts using allen key from the two centering pins. Clean them with dry cloth, then tape water & finally rinse with purified water and keep them in their respective box.
[][]Loosen two set screws and remove the block of shell doser.
[][]Loosen two set screws and remove the feeder. Clean using compressed air.
[][]Loosen two set screws and remove the race way. Clean using compressed air.
[][]Loosen two set screws and remove the side pusher. Clean using compressed air.
[][]Keep the shell feeder, race way and side pusher in their respective box.
[][]Remove the capsule stopper plate by removing two nuts.
[][]Remove size ring, clean and set the desired size ring.
[][]Remove any loose powder inside the cleaning segment holes by blowing compressed air and by applying vacuum.
[][]Disassemble the upper part of the granules doser, dose controller and dose filling plate. Clean them with organic solvent like isopropyl alcohol. (For pellets).
[][]Loosen the coupling for the agitator screw and driving shaft. (For powder)
[][]Remove dust from the agitator screw, driving shaft and powder tank with clean cloth. Wash them 2-3 times with potable water then rinse with purified water. Wipe them with dry clean cloth. Allow drying in air conditioned room.
[][]Loosen the set screws and remove the fastening plate by lifting and tilting. Clean the fastening plate with cloth, then tape water & finally rinse with purified water and keep them in their respective box
[][]Loosen the set screws and remove the dosing disk and chamber. Clean the dosing disk and chamber with cloth, then tape water & finally rinse with purified water and keep them in their respective box
[][]Loosen the lock screws, turn the adjusting screws all the way up and lift the pin holder to remove thirty pins with the holder.
[][]To remove pins from the holder, loosen the set screws, pull the stop plate forward, and remove pins. Clean them with tape water & finally rinse with purified water and keep them in their respective box
[][]After final cleaning affix the ‘CLEANED’  label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Tablet Coating Machine, Purpose:

Tablet Coating Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Tablet Coating Machine (Model: FC-39) in order to comply with cGMP standard.

Tablet Coating Machine, Scope:

The scope of the procedure is applicable to the Tablet Coating Machine (Model: FC-39) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PLC : Programmable Logic Controller.
[][]CIP : Clean In Place.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Tablet Coating Machine (Model: FC-39)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure: Tablet Coating Machine

Precaution:

[][]Ensure the outlet duct is open.
[][]Ensure the inlet duct is open.
[][]Keep the doors closed during operation and after completion of job.
[][]Check air pressure.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Place the spray gun at the holding arm. Then, enter the spray gun holding arm into the coating pan.
[][]Connect the peristaltic pump with the spray gun.
[][]Test whether coating pan rotates smoothly without any abnormal noise after activation. Check that rotation direction is correct.

Machine Operation.

[][]Switch on the Machine.
[][]Unlock and open the inlet port cover of the machine.
[][]Load tablets into the coating pan. Total tablet load should not exceed the maximum working load and should not be less than the minimum working load.
[][]Securely close the coating pan chamber cover and clamp.
[][]Pan motor ‘‘ON/OFF’ from the PLC.
[][]Warm up the tablets without spraying on the tablet bed.
[][]Start spraying phase by pressing the pump start button in manual mode or Spray key in Auto mode. Adjust dosing volume by changing the rpm of the peristaltic pump.
[][]After spraying, stop the Spray by pressing Pump ON/OFF button. Dry the tablets until required.
[][]Unload the tablets from the coating pan when desired tablet temperature is attained.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Dismantling

[][]Remove the spray system and dismantle.
[][]Remove the pan outlet dumber.

Machine Cleaning: Tablet Coating Machine

[][]Switch off outlet damper, outlet blower, pan motor.
[][]Open all safety doors.
[][]Switch on the peristaltic pump by pressing “Switch on button”.
[][]Wash the inside of tube by spraying with hot water.
[][]Then wash the tube with purified water.
[][]Pass compressed air through tube to dry inside of tube.
[][]Clean the Spray gun nozzle with hot water and soft brush.
[][]Now discharge the water with dissolved materials.
[][]Now hot water is applied inside the chamber through CIP system to remove materials fixed hardly on the chamber surface.
[][]Re-wash the machine with purified water as required through CIP system.
[][]Wash the machine with lint free cloth.
[][]Clean inlet ports, discharge port, mixing chamber and external surface with potable water, hot water & purified water.
[][]Wipe the water droplets with lint free cloth, and dry the machine with compressed air.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Tablet Metal Detector ,Purpose:

Tablet Metal Detector , The purpose of this SOP is to describe the setting, operation and cleaning procedure of MET 30+ Pharmaceutical Metal Detector Machine in order to comply with cGMP standard.

Tablet Metal Detector , Scope:

The scope of the procedure is applicable to the MET 30+ Pharmaceutical Metal Detector Machine at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the MET 30+ Pharmaceutical Metal Detector
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the document

Procedure:

Precaution :

[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Ensure Electric line is properly connected.

Machine Assembling

[][]Set the discharge chute into the main body of the machine.
[][]Set the rejected tablet containing bucket in the lower part of the machine.
[][]Adjust the alignment of the machine with respect to main machine.
[][]Ensure all the settings are properly done.

Machine Operation

[][]Connect electrical cable to the machine.
[][]Switch ON the main power of the machine.
[][]Set the programs from the control panel of the machine.
[][]Pass the tablet through the discharge chute and reject the tablet having metallic content.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Switch OFF the main power of the machine.
[][]Remove the discharge chute.
[][]Remove the bucket from the lower part of the machine.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Spare Parts , Purpose:

Spare Parts , To lay down the procedure for Cleaning, Labeling & Storage of spares in spare parts room at the Production Area.

Spare Parts , Scope:

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure :

General Instructions

[][]Store all the clean and dry spare parts in the lockers or on the racks in separate polythene bags. Never keep any parts in the spare parts room without covering them.
[][]All the equipment parts stored in the spare parts room must be affixed with properly filled status label to identify the parts and its cleaning status.
[][]Production supervisor must regularly check the status label to avoid any error in the labeling.

Storing of utensils and accessories

[][]Store all the clean utensils and accessories in the lockers or in the racks in the separate polythene bags. Never keep any parts in the spare parts room without covering them.
[][]All the equipment parts stored in the spare parts room must be affixed with properly filled status label to identify the parts and its cleaning status.
[][]Record the use of utensils and accessories in the ‘Spares Use Register Book’ (Annexure I).
[][]Production supervisor must regularly check the status label to avoid any error in the labeling.

Storing of Dies and punch boxes

[][]Wipe the outside of the boxes with clean duster, then with 70% IPA solution (if necessary). Clean the dies and punches according to the Tablet Compression Machine SOP.
[][]Record the use of dies and punches in the ‘Spares Use Register Book’ for using dies and punches. Check the condition of punches before issuing and receiving.
[][]Storing of different size change parts of capsule filling machine
[][]Keep the clean and dry machine parts in the spare parts room in separate polybag and affix with properly filled status label.
[][]Record the use of Capsule Filling Machine change parts (e.g. Cutter, forming channel etc.) in the ‘Spares Use Register Book’.

Storing of blister change parts

[][]Wipe the outside of the boxes with clean cloth, then with 70% IPA solution (if necessary).
[][]Keep the clean and dry blister change parts in the locker dedicated for blister change parts.
[][]If there is no spare space in the locker keep the change parts in a polybag with proper status label and then place in clean pallet.
[][]Record the use of Blister parts (e.g. Cutter, forming channel etc.) in the ‘Spares Use Register Book’. Check the condition of blister parts before issuing and receiving.

Annexure:

Annexure I Spare Parts Usage Log Register

Tablet Dedusting Machine, Purpose:

Tablet Dedusting Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of SEJONG Tablet Dedusting Machine in order to comply with cGMP standard.

Tablet Dedusting Machine, Scope:

The scope of the procedure is applicable to the SEJONG Tablet Dedusting Machine at the Production area  of XX  Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the Machine
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A

Procedure:

Precaution :

[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Ensure electric and air line are properly connected.
[][]Machine Assembling
[][]Set the perforated plate in machine.
[][]Fixed the upper lid properly by holding screw.
[][]Ensure all the screws are connected properly.

Machine Operation

[][]Connect electrical cable of Dedusting Machine to the main compression machine.
[][]Connect compressed air line to Dedusting Machine.
[][]Switch ON the main power of Dedusting Machine.
[][]Adjust the vibration level by tuning volume.
[][]During tablet compression tablet passes through the discharge chute of compression machine to the Dedusting machine.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Switch OFF the main power of the Dedusting Machine.
[][]Remove the compressed air line from the Dedusting Machine.
[][]Open the upper lid of the machine.
[][]Remove the perforated plate of the machine.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts, holding screw and other parts with purified water.
[][]Clean and swab all the parts and the machine body with lint free cloth to remove water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Tablet Compression Machine, Purpose :

Tablet Compression Machine, The purpose of this SOP is to describe the setting, operation and cleaning procedure of SEJONG Tablet Compression Machine (Model: MRC-30N) in order to comply with cGMP standard.

Tablet Compression Machine, Scope :

The scope of the procedure is applicable to the SEJONG Tablet Compression Machine (Model: MRC-30N) at the Production area of of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PLC : Programmable Logic Controller.
[][]RPM : Rotation Per Minute.

Responsibilities:

[][]The roles and responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the SEJONG Tablet Compression Machine (Model: MRC-30N).
[][]Maintaining Equipment Log Book.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Annexure:

N/A.

Procedure:

Precaution:

[][]Check for leakage of oil & the connection state.
[][]Check for proper locking of the dies with die setting pin.
[][]Check the assembling of die & punch set.
[][]The cover doors must be kept in close position during operation.
[][]Check the setting components like thickness, weight, hardness & other parameters.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Open the site doors of all side.
[][]Keep available all the dies, punches & other necessary parts near the machine.

Setting of Die

[][]Ensure that the die pockets are cleaned.
[][]Smear the die with food grade oil and place in the die pocket.
[][]Press the die down with finger to locate accurately in the die pocket.
[][]Once the die is located, enter the die insert bar through the upper punch guide hole and allow dropping.
[][]The die will enter in the pocket; apply additional force through die insert bar until the die is fully down on the die pocket.
[][]In order to set the shaped die enter the upper punch first and align the die bore with the upper punch tip and gently push the die with the punch to enter in the die pocket, then apply additional force through die insert bar to fully down the die in the die pocket.
[][]Ensure that the top face of the die is perfectly flash with the die table.
[][]Tighten the die setting pin with the torque after greasing the tip of die setting pin. Ensure that the die is flash with the die table after tightening. Do not run the machine if die setting pin is not properly tightened.
[][]Set all blank dies (D tooling) in respective die pocket in the same procedure by rotating the turret manually with the help of hand wheel.

Setting of lower punch

[][]Take out the change rail and put the lower punch through the lower space of the change rail. At this time grease thinly on the head of punch.
[][]Move the disk (turret) to the next station through rotating with hand wheel. Make the punch movement smoothly not to be stuck in the down rail.
[][]Assemble every punch with same method.
[][]Assemble the change rail.

Setting of upper punch

[][]Ensure that the punch guide holes and punches are clean.
[][]Take out the change rail and put the upper punch through the upper space of the change rail.
[][]Place all the punches in the punch holes by rotating the disk (turret) with the hand wheel and check that each punch is free to move in its guide and capable of dropping in to the cam track by its own weight.
[][]Rotate the turret at least one full turn by hand wheel to recheck to ensure that the upper punches enter the die bores without any friction and they run freely throughout the cam system.
[][]Install the mechanical force feeder, scrapers & other parts of the machine. Ensure that no part is in touch with the main disk (turret). Tighten the bolts of mechanical force feeder. Rotate the machine manually through hand wheel to ensure machine rotates without hindrance.
[][]Install the tablet ejection chute of the machine. Ensure that no part of the machine is in contact with the turret. Tighten the screw of the ejections chute.
[][]Install the side covers.
[][]Install the hopper above the mechanical force feeder.
[][]Connect the coupling with the feeder drive, shaft. Lock the coupling.
[][]Connect the powder sensor with the hopper.
[][]Check that all nut bolts are tightened correctly.
[][]Close all side doors. The machine is ready to use.

Machine Operation

[][]Rotate the machine through hand wheel and check that there is no abnormal sound in the machine.
[][]Ensure the connection of air supplying line.
[][]Switch on the main power on the back of machine.
[][]Again switch on the key of the operation box bottom part by turning the key clockwise.
[][]Login the password.
[][]If the screen is touched and there is no alarm in the machine the screen will be conversed into OPERATION PANEL mode. When the alarm is working, the screen will show SAFETY MESSAGE mode.
[][]Rotate the machine through hand wheel and check that there is no abnormal sound in the machine.
[][]Ensure the connection of air supplying line.
[][]Switch on the main power on the back of machine.
[][]Again switch on the key of the operation box bottom part by turning the key clockwise.
[][]Login the password.
[][]If the screen is touched and there is no alarm in the machine the screen will be conversed into OPERATION PANEL mode. When the alarm is working, the screen will show SAFETY MESSAGE mode.

Operation Panel Setting

Operation condition

[][]FEEDER CONTROL (select AUTO/HAND/INCH mode)
[][]FEEDER CONTROL (RPM control for HAND mode)
[][]DUST COLLECTOR (ON/OFF switch)
[][]TARGET QUANTITY (ON/OFF switch)
[][]POWDER ALARM (powder sensor ON/OFF switch)
[][]BUZZER (ON/OFF switch)
[][]MAIN MOTOR CONTROL (disk RPM control)

Set Panel Setting

[][]In order to set the product condition converse into SET PANEL mode through touching SET PANEL button in bottom of the screen.

Product condition

[][]PRETHICKNESS (Thickness setting in the pre-pressure station)
[][]FILLING DEPTH (Tablet weight setting)
[][]MAIN THICKNESS (Tablet thickness setting)
[][]SELECT CAM (Cam selection)
[][]FEEDER RPM % (In AUTO mode, RPM setting)
[][]POWDER SUPPLY TIME (Time setting from powder shortage alarm to machine stop)
[][]TARGET QUANTITY (Target quantity setting)
[][]OIL LUBRICATION SETTING (Punch lubrication setting)
[][]HELP MODE (Description of touch screen function)

Tablet weight control

[][]In case that the weight is not accurate, generally the weight is adjusted through the touch screen. But, besides of that the small amount of powder filling can be adjusted with the speed of mechanical feeder agitator, also Tablet thickness control
[][]Tablet thickness is adjusted by lower roll’s height and it is operated through touch screen.

Hardness control

[][]Hardness is adjusted by following methods-
[][]Control compressing force in pre & main pressure section

Inch operation

[][]Before starting the production, INCH operation is recommended though the operation box.
[][]Control pre & main thickness with the maximum value.
[][]Set pre & main thickness according to the production data.
[][]If every configuration is ready, check SAFETY MESSAGE screen.
[][]If there is any problem in the machine, solve the problem with proper method.
[][]After setting variables like filling cam selection, pressure, filling depth, penetration depth, tablet thickness and etc run the machine. Especially, for the safety, before starting the product, inching operation should be done.
[][]Inch the mechanical feeder for a few seconds to distribute the granules uniformly within the die bore.
[][]Off the manual mode.
[][]On the auto mode.

[][]Inch the machine one revolution & check the weight.
[][]Adjust the filling depth to get the required weight. (If necessary).
[][]Adjust the thickness controller to get the required hardness and thickness.
[][]Record the machine start & end time and other parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Open the site doors of the machine.
[][]Place a poly bag on powder outlet; remove the material lock from the mechanical force feeder, and on the mechanical force feeder, excess materials will be flown in to the poly bag.
Switch off the machine.
[][]Adjust the filling depth wheel and thickness adjustment wheel at the lowermost position.
[][]Loosen the ejection chute holding screw and remove the ejection chute.
[][]Remove the hoper and powder sensor carefully.
[][]Unlock the feeder drive shaft from the coupling and keep aside. Loosen the mechanical force feeder holding screw then remove the mechanical force feeder.
[][]Remove the upper punch change rail.
[][]Remove the upper punches.
[][]Remove the lower punch change rail.
[][]Punch will automatically come out of the cavity, if required press gently downward and collect the punch.
[][]Remove all the lower punch in the same manner.
[][]Loosen all the die setting pins up to maximum limit.
[][]Enter the die insert bar through the lower punch loading cavity. Then gently apply pressure upward to remove the die. Die will come out of the die pocket. Remove all the dies in the same manner.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the turret, punch holding cam, operation panel and machine body.
[][]Clean all the machine parts with dry lint free cloth. Clean the die bore, die pocket & die table with a flush brush. Use brush to clean any material sticking in the machine parts, pin and knobs.
[][]Use potable water to clean the turret, machine body, cam, punch holding cavity, die, die setting pin and other parts.
[][]Use hot water to clean all the above mentioned body parts & finally rinse with purified water.
[][]Clean and swab all the parts with lint free cloth to remove water.
[][]Close site doors and affix a ‘CLEANED’ label in the machine.

Cleaning of die and punches

[][]Clean the die and punch with lint free cloth to remove any particle in the die and punch.
[][]Flash the die bore with flash brush and use brush to clean any particle sticking with the die and punch.
[][]Clean the die and punch with potable water, use brush if necessary.
[][]Clean the die and punch with hot water and finally rinse with purified water.
[][]Remove any water present in the die and punch with lint free cloth.
[][]Smear the die and punches with food grade oil and store in the die punch cabinet.

Cleaning of mechanical force feeder

[][]Remove the screws of mechanical force feeder and open the cover of feeder housing
[][]Remove the paddle and paddle key from the machine and collect dust particle from the feeder housing with vacuum cleaner.
[][]Clean all the parts with lint free cloth.
[][]Clean all the parts with potable water, use Teflon brush if necessary
[][]Clean all machine parts with hot water and then rinse with purified water.
[][]Remove any water from the parts with lint free cloth.
[][]Assemble the paddle and cover in the feeder housing and take in a poly bag. Attach a ‘CLEANED’ label in the bag and store in the machine parts cabinet

Cleaning of hopper and ejection chute

[][]Clean all the powder with lint free cloth
[][]Use potable water to clean the hopper and the ejection chute, use Teflon brush where necessary.
[][]Clean the mentioned parts with hot water and then rinse with purified water.
[][]Clean and remove out any water remaining in the machine parts with lint free cloth.
[][]Wrap the change parts with poly bag, attach ‘CLEANED’ label in the poly bag and store in the machine parts cabinet.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Cone Blender, Purpose:

Cone Blender, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Cone Blender Machine (Model: DB-150) in order to comply with cGMP standard.

Cone Blender, Scope:

The scope of the procedure is applicable to the Cone Blender Machine (Model: DB-150) at the Production area of General block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Cone Blender Machine (Model: DB-150)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

N/A.

Procedure:

Precaution:

[][]The cone is in lock position.
[][]Keep the hydraulic trolley near to the machine.
[][]Keep the doors of lower chamber closed during operation and after completion of job.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.

Machine Assembling

[][]Lock the double cone.
[][]Change the sieve of dry granulator as specified in Batch Manufacturing Record (BMR).
[][]Open the lid of double cone.
[][]Move the dry granulator to the open end of the double cone.
[][]Ensure the proper adjustment of dry granulator and double cone.
[][]Lift the product container with hydraulic trolley to adjust with the container holder.
[][]Lock the product container with the container holder.
[][]Lift the product container to the granulator head.
[][]Move the product bowl and granulator out to the normal position.
[][]Close double cone cover lid.

[][]Unlock double cone and rotate it.

Machine Operation

[][]Set the parameters such as time & rotation per minute.
[][]Start granulator and transfer the product by passing through the granulator with desired sieve to double cone.
[][]After completion of milling close the lid
[][]Unlock double cone and rotate it.
[][]When the Process stops, the double cone will incline because of product. User have to press “JOG” button to swing or arrange double cone to straight in lock position and then lock it.
[][]Open guard bar and remove lower cone by trolley then move product out.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book

Machine Dismantling

[][]Remove lower cone from the machine.
[][]Remove the dry granulator.

Machine Cleaning

[][]Remove dusts from the machine with a vacuum cleaner. Collect dust from the product cone, dry granulator and operation panel and machine body.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, all product contact parts and holding screw.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, all product contact parts, holding screw and other parts with purified water
[][]Clean and swab with lint free cloth all the parts and the machine body to dry any water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Filter Bag, Purpose :

Filter Bag, The purpose of this SOP is to describe the washing and storage procedure of Filter Bag in order to comply with cGMP standard.

Filter Bag, Scope :

The scope of the procedure is applicable to the Filter Bag at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Washing & Storage of Filter Bag.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Annexure:

[][]N/A.

Procedure

Filter Bag Washing

[][]First wash with potable water.
[][]Clean the filter bag by rubbing.
[][]Soak the filter bag in hot water.
[][]Add 1 % sodium lauryl sulfate (in case of sticky material) with potable water and then soak the filter bag for 30 minutes.
[][]Then wash the filter bag by rubbing with potable water.
[][]Finally wash with purified water.
[][]Hang the filter bag and then allow to dry in wash bay.

Filter Bag Storage

[][]After drying take the filter bag in a cleaned poly bag.
[][]Store the filter bag in HDPE drum.
[][]Place the drum in FBD store room.
[][]Then affix the ‘CLEANED’ label on the drum.

Purpose :

The purpose of this SOP is to describe the setting, operation and cleaning procedure of Rapid Mixer Granulator Machine (Model: M-150) in order to comply with cGMP standard.

Scope :

The scope of the procedure is applicable to the Rapid Mixer Granulator Machine (Model: M-150) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

PLC : Programmable Logic Controller
CIP : Clean In Place

Responsibilities:

The roles and responsibilities are as follows:

Operator

Operation and cleaning of the Rapid Mixer Granulator Machine (Model: M-150).
Maintaining Equipment Log Book.

Executive, Production

To monitor and check the laid down procedure.

Manager, Production

To implement this correctly.

Manager, Quality Assurance

To approve the Document.

Vibratory Sifter, Purpose :

Vibratory Sifter, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Vibratory Sifter Machine (Model: BT-800-3S) in order to comply with cGMP standard.

Vibratory Sifter, Scope :

The scope of the procedure is applicable to the Vibratory Sifter Machine (Model: BT-800-3S) at the Production area of General block of Labaid Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

The Roles and Responsibilities are as follows:

Operator

Operation and cleaning of the Vibratory Sifter Machine (Model: BT-800-3S)
Maintaining Equipment Log Book

Executive, Production

To monitor and check the laid down procedure.

Manager, Production

To implement this correctly

Manager, Quality Assurance

To approve the Document

Procedure

Precautions :

[][]Make sure that the power cable is separated from the socket before and after operation.
[][]The sifter covers and lid are in lock position during operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of sifter, sieves and gasket before assembling of machine.
[][]Check the sieve for its integrity before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the sifter machine before assembling.
[][]Assemble the sifter by putting cover with discharge opening on top of body of sifter.
[][]Then set the clamp to tighten the cover.
[][]Then place required sieve.
[][]On the top of first cover set the second cover with discharge opening.
[][]Set the clamp to tighten the second cover.
[][]Place the required sieve.
[][]Set the third cover with discharge opening.
[][]Set the clamp.
[][]Set the lid cover of sifter.
[][]Set the clamp.

Machine Operation

[][]Connect the power cable to the socket for power supply.
[][]Switch on the machine by pressing green button on the lower part of the machine.
[][]Input the material through the lid opening.
[][]Sieve the material and collect sieved material through the cover discharge opening.
[][]After operation switch off the sifter machine by pressing red button on the lower part of machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Remove the clamp of lid cover.
[][]Remove the lid cover.
[][]Remove the clamp of third cover.
[][]Remove the third cover.
[][]Remove the clamp of second cover.
[][]Remove the second cover.
[][]Remove the sieve.
[][]Remove the clamp of first cover.
[][]Remove the cover.
[][]Remove the sieve.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, product contact parts, clamps and other machine parts.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, product contact parts, clamps and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Dispensing Booth, Purpose :

Dispensing Booth, The purpose of this SOP is to describe the operation and cleaning procedure of Dispensing Booth (Model: Standard) in order to comply with cGMP standard.

Dispensing Booth, Scope :

The scope of the procedure is applicable to the Dispensing Booth (Model: Standard) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Operation and cleaning of the Dispensing Booth (Model: Standard)
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

[][]N/A.

Procedure

Precautions:

[][]The working person must follow safety procedures of works.
[][]For any trouble, disturbance switch OFF the Dispensing Booth.

Machine Operation

[][]Check the machine first physically.
[][]Check electric connection and mechanical set up.
[][]Machine switch on.
[][]Light on and blower on.
[][]Open the door.
[][]After completion desired work clean the Laminar Unit properly.
[][]Close the door and switch off main switch.
[][]Switch ON Dispensing Booth.
[][]Switch ON Light.
[][]Switch ON the Laminar Air Flow.
[][]Increase or decrease air flow by pressing up/down button.
[][]Warm up the Dispensing Booth for 30 minutes before starting dispensing.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Cleaning

[][]Remove dusts from the dispensing booth with a vacuum cleaner and then clean with lint free cloth.
[][]Use wet cloth to clean the booth.
[][]Wipe the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Dust Collector , Purpose:

Dust Collector , The purpose of this SOP is to describe the setting, operation and cleaning procedure of Dust Collector in order to comply with cGMP standard.

Dust Collector , Scope:

The scope of the procedure is applicable to the Dust Collector at the Production area of of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]Setting, operation and cleaning of the it
[][]Maintaining Equipment Log Book

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

[][]Machine Assembling
[][]Open dust collectors lid.
[][]Set the filter bag inside the Machine.
[][]Set the upper lid cover of the Machine.
[][]Connect the dust collecting hose pipe.

Machine Operation

[][]Connect electrical cable of it.
[][]Connect ithose pipe with Tablet Compression Machine.
[][]Switch ON the main power of it from the PLC of the compression machine.
[][]Record the operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Dismantling

[][]Switch OFF the compression Machine.
[][]Remove electrical connection.
[][]Remove dust collecting hose pipe from compression Machine.
[][]Remove the upper lid of the it.
[][]Remove the filter bag.

Machine Cleaning :

[][]Remove dusts from the machine with a duster.
[][]Use potable water to clean the machine body and filter bag.
[][]Finally clean with purified water.
[][]Clean and swab with lint free cloth all the parts and the machine body to dry any water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Water Handling System, Purpose:

Water Handling System, To lay down the procedure of Water handling system at the Production premises.

Water Handling System, Scope:

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the Document.

Annexure:

[][]N/A

Procedure:

Precaution :

[][]During collection of hot water, wear heat resistance gloves.
[][]Before collection check all the point of connection & ensure that no one is open.
[][]Keep all inlet and outlet of circulating loop / storage tank and open ends of S.S. pipelines closed at the day end of work
[][]Always keep the water off-take valves closed at every use point after use.
[][]At the end of the day, ensure that no flexible hose pipe remains attached with the use point.
[][]Potable water should not be use in manufacturing process.

Types :

[][]Three types of water used in Manufacturing area.
Potable Water
Hot Water
Purified Water
Potable Water
[][]Connect pipe with the potable water system.
[][]Check availability of potable water in the line.
[][]Collect potable water from potable water mark water line.
[][]Use Pharma grade container to collect potable water for cleaning purpose.
[][]Transfer potable water to the respective production area by using SS trolley.
[][]After completion of work hang the pipe on the hanger.
[][]Keep both ends close with Alu foil after drain out of remaining water from pipe at the end of the day work.

Hot Water

[][]Connect pipe with the hot water system.
[][]Check availability of hot water in the line.
[][]Collect hot water from hot water mark water line.
[][]Use Pharma grade container to collect hot water for cleaning purpose.
[][]Transfer hot water to the respective production area by using SS trolley.

Purified Water

[][]Before Collection of purified water from the main re-circulation loop of purified water, connect the pipe with 50 Liter storage tank and main loop.
[][]Collect the purified water into the storage tank by turning the valve open.
[][]Circulate the water through the sectional circulation loop for 5 minutes and drain through use points and storage tank outlet.
[][]Transfer purified water to the respective production area by using SS trolley.
[][]After completion of work, disconnect the pipe between the pipe storage tank and main circulating loop and hang the pipe on the hanger.
[][]Keep both ends close with Alu foil after drain out of remaining water from pipe at the end of the day work

Rework Residue , Purpose:

Rework Residue , To lay down a procedure for Handling of Rework Residues from Batch Processed Material /Intermediate product.

Rework Residue , Scope:

This SOP is applicable for the Production Area of XX  Pharmaceuticals Limited.

Definition / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precaution:

[][]Do not add any rework unless it is authorized beforehand by Head of Quality Assurance.
[][]Do not add the rework of a batch to other batch (es) until packing of the batch is completed.
[][]Ensure that rework of different products is not stored in the same container.
[][]Do not store any rework which is less than 0.25 % of the actual batch size.

Rework Residue :

[][]Following stated defects can be considered for storage and addition as rework in a batch leftover granules, chipping / capping defects, lamination, tablets with variations in physical parameters like weight, hardness, thickness, friability or edge broken tablets at the time of compression, coating and inspection. Residue after compression, encapsulation & PFS is also be considered as rework.
[][]Prepare a ‘Rework Residue Addition Note’ as per format (Annexure-I). The rework addition note shall be approved beforehand by Head of Production or his designate and authorized by Head of Quality Assurance.

[][]Process the rework as per Batch Manufacturing Record (BMR) of the specific product from the declared necessary step(s).
[][]Maximum allowable amount for addition of rework in a fresh batch is 5 % of actual batch size.
[][]Rework bulk shall be free from any foreign matter, objectionable color and / or odor.
[][]First batch of any product in which rework is added shall be kept for stability study.

Non-Rework :

[][]Any amount of tablets / capsule(s) which is collected as ‘Rework’ but is less than 0.25 % of the actual batch size shall be considered as ‘non-rework’.
[][]‘Non-rework’ shall be destroyed as per Quality Assurance SOP.

Storage of Rework :

[][]Store the rework in tightly closed double lined polybag with “REWORK’ Label in a container on a pallet in WIP Tablet/Capsule store.
[][]Rework of more than one batch of the same product can be stored in one container with proper status label.
[][]Record the rework generated from the batch(es) and their addition history in ‘Rework Residue
[][]Register’ as per (Annexure II). The register shall be kept in production Executive.
[][]Issue rework residues for use only in the presence of Production Executive.
[][]Rework generated from a batch shall be added to the batch(es) which are manufactured within the next three months. For example, rework generated from a batch manufactured in January shall be added to only the fresh batch manufactured within April, not to be added to the batch manufactured in May and so on. But in that case expiry of the fresh batch where rework is added shall be same as expiry of rework batch. In such cases rework shall not be stored for more than 90 days. If any rework amount is left after the said period, destroy the left over with prior approval of Quality Assurance (QA).

Annexure:

Annexure I – Rework Reside Addition Note.
Annexure II – Rework Residue Register.

Additional Materials Return procedure, Purpose:

Additional Materials Return procedure, To lay down the procedure for return of Additional Part of Raw (Excipient) and Primary Packaging materials to Ware-House.

Additional Materials Return procedure, Scope:

This SOP is applicable for the Production Area  of the XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precaution:

[][]Ensure weighing and counting of the materials is correct.
[][]Returning of Unused Raw Materials (Excipient)
[][]After dispensing unused Raw Material (Excipient) can return to store.
[][]Enter all the details like Product Name, Batch No., Batch size, Name of the material, Quantity to be returned, Material ID No., Lab. Control No. on the ‘Stock Return Note’ (Annexure – I).
[][]Operator shall mention all details in Stock Return Note (SRN) and Executive, Production shall check all of them accordingly.
[][]The SRN shall have triplicate copy. All the copies shall be moved along with the physical stock to the Ware-House and Executive / In-charge, Ware-House shall return the rest 02 (Two) copies to the Packaging after duly signed. One copy shall attach with Batch Manufacturing Record and third copy shall retain in the book as reference copy.

[][]Returning of Unused Primary Packaging Materials
[][]After dispensing unused Primary Packaging Material can return to store.
[][]Individual rolls of Aluminum foil, PVDC and Alu bottom film which is return shall weigh and glass bottle, stopper and Alu cap shall count.
[][]Enter all the details like Product Name, Batch No., Batch size, Name of the material, Quantity to be returned, Material ID No., Lab. Control No. on the ‘Stock Return Note’ (Annexure – I).
[][]Operator shall mention all details in Stock Return Note (SRN) and Executive, Production shall check all of them accordingly.

[][]The SRN shall have triplicate copy. All the copies shall be moved along with the physical stock to the Ware-House and Executive / In-charge, Ware-House shall return the rest 02 (Two) copies to the Packaging after duly signed. One copy shall attach with Batch Manufacturing Record and another copy shall retain in the book as reference copy.

Returning of Raw Materials (Excipient) / Primary Packaging Materials Rejecting Online

[][]When the raw materials (excipient) / primary packaging materials are observe to be defective on-line such as having lumps or foreign materials in case of raw materials (excipient) and sealing problem or pinholes in case of foils keep aside the material.
[][]On line rejected material shall return to warehouse as per handling of on line rejection guideline of QA.

Annexure:

Annexure I – Stock Return Note.

Machine Handling, Purpose :

Machine Handling, To lay down the procedure for handling of machine during breakdown.

Machine Handling, Scope :

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution :

[][]Ensure that proper safety instructions are followed.

Activities:

[][]Shut OFF the main switch of the electric connection.
[][]Inform working Exe. / Sr. Exe., Production about the break-down status of the machine and In-charge is needed to confirm the extent of break-down priority basis.
[][]After checking the nature of break-down, he will intimate Engineering department through ‘Maintenance Request Form’ ( Annexure – I ) Send it to the General Manager, Engineering or his nominee for immediate course of action.
[][]Put off others utility line immediately one by one, so that, the machine turns neutral.
[][]Collect all the processing materials / intermediates and also product into the air-tight container being available before break-down of the machine.
[][]Clean the machine surface and outside by the vacuum cleaner and also the lint free cloth.
[][]Display the label ‘Under Maintenance’ on the front side of the machine for declaring its status.
[][]Involve machine Operator(s) throughout the Maintenance Process for speed up the Engineering job.
[][]Record the total down time of the Machine in the ‘Equipment Log Book along with it’s cleaning for next processing.
[][]Inform Quality Compliance Personnel to verify the extent of machine cleaning for next processing.

Annexure:

Annexure I – Maintenance Request Form 

Material Requisition Procedure, Purpose:

Material Requisition Procedure, To lay down the procedure for raising Requisition of Material to the Ware-House.

Material Requisition Procedure, Scope:

This SOP is applicable for the Production Area  of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To Implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

[][]Material Requisition shall be raised in following cases.
[][]On line rejection: If approved raw material or packing material issued for the batch is rejected on line due to quality defects like black particles in raw material, hard lumps, smudged printing or no  printing on printed materials like foil, carton, insert, label and shipper and color variation beyond acceptable shade.
[][]Material consumed more than standard: In case dispensed raw material is compensated due to spillage, spray pipe leakage during coating, excess coating material and packaging materials required for recovery addition, excess foil consumption during blister pack machine setting, excess carton consumption during manual cartooning, printing problem of carton, catch cover, insert and shipper carton.
[][]Production Executive shall raise ‘Material Requisition’ (Annexure-I) by writing all details with reason in the ‘Remarks’ column and shall sign in ‘Requisitioned by’ row.
[][]Material Requisition (MR) shall have duplicate copy. First copy shall be mentioned as ‘Ware-House Copy’ at right top corner of Material Requisition form. Second copy shall be mentioned as ‘Batch Record Copy’ at right top corner of Material Requisition form.
[][]Head of Quality Assurance (QA) or his/her designate shall justify the reason for MR and will approve accordingly.
[][]Approved Material Requisition shall be sent to dispensing for Issuance.
[][]After Issuance of materials ‘Batch Record’ copy shall be attached with Batch Manufacturing Record (BMR) & Batch Packaging Record (BPR) and ‘Ware-House Copy’ shall be sent to Ware-House for stock adjustment purpose.

Annexure:

Annexure I –Material Requisition.

Equipment Logbook, Purpose:

Equipment Logbook, To lay down the procedure for Maintaining Record of Equipment Usage, break-down, cleaning and change over functions during all Manufacturing Activities.

Equipment Logbook, Scope:

This SOP is applicable for the Production Area of General Block of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Equipment : The implement, which is used at an Operation or Activity.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Use of Equipment Log Book :

[][]Equipment Log Book is to record equipment usage maintenance and cleaning record. The records are maintained to trace back the previous history.
[][]Maintain individual ‘Equipment Log Book’ (Annexure-I) for each equipment.
[][]Equipment log book format is divided in 05 parts
[][]Product Information
[][]Equipment usage details
[][]Cleaning details
[][]Change Over details
[][]Inspection and Approval
[][]Product Information
[][]Product name, Batch no., Batch size shall be recorded in log book.
[][]Each book is dedicated for each equipment
[][]Equipment usage details
[][]Product start time and end time shall be recorded in log book.
[][]This is applicable for each batch activity.
[][]Record the activity / batch operations shift wise in log book.

[][]All break times like Lunch time, Tea time, machine stoppage due to breakdown, machine stoppage at the end of the shift or day and machine stoppage due to power failure, only if restart time is more than 5 minutes.

Equipment cleaning details

[][]The equipment cleaning is applicable in following events.
[][]Batch changeover of the same product and different product.
[][]After cleaning if cleaned equipment is kept idle for more than defined hold time which shall be studied and incorporated in respective equipment SOP.
[][]If equipment is relocated /shifted within the facility as well as for new equipment.
[][]In case of cleaning after maintenance activity.
[][]In case of cleaning after area fumigation.
[][]After usage of equipment, clean it as per the procedure defined in respective equipment SOP.
[][]The type of cleaning shall be mentioned in specified column in log book.
[][]After cleaning is completed, inform QA (Quality Assurance) to inspect and approve for next activity.

Change Over Details :

[][]Change Over is applicable in following events.
[][]Change over is done for product to product change.
[][]Start and end time shall be mentioned in specified column in log book.
[][]After change over is completed, Executive, Production check setting of machine & will take step for next activity.

Inspection and Approval before usage

[][]Before usage Equipment, it is to be checked for its suitability for next activity by Executive, Production and then inspected and approved by Executive, Quality Compliance.
If production is on campaign basis, after every 10th batch, cleaning activity is carried out and details are recorded.
[][]During campaign of same product, equipment shall be cleaned as per respective equipment SOP but prior to start next batch approval shall be taken by Executive, Quality Compliance.

Additional Information at the Remarks Column

[][]Throughout the working day operation, if the operating machine turns ‘Stop’ by either mechanical or electrical reasons, note the total down time for a day at the Remarks column.

Annexure:

Annexure I – Equipment Log Book.

Line Clearance , Purpose:

Line Clearance , To lay down the procedure for Line Clearance at Production Area during Product to Product changeover and Batch to Batch changeover.

Line Clearance , Scope:

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precautions:

[][]Ensure the proper safety instructions are followed.
[][]Ensure that no previous product is available in the area.

Line Clearance during Product to Product Changeover

[][]Ensure that all utility lines like compressed air line, steam line, electrical fixtures, air inlet ducts, return air risers, potable water and purified water lines are cleaned and no visible traces of product are present.
[][]Ensure that door, floor, walls and ceiling are cleaned.
[][]Ensure that area cleaning activity is recorded in ‘Room Cleaning Log book’
[][]Ensure that all equipments in the area are cleaned according to their respective SOPs and no traces of previous product are visible within the equipment.
[][]Check and ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’
[][]Ensure that Span between equipment usage and cleaning is not more than seventy two hours.
[][]Ensure that Balances in the production area are cleaned and accuracy check is done once daily.
[][]Ensure that production utensils like scoops, spatula, pallets, BMR table, tool boxes etc. are cleaned as per procedure.
[][]Ensure that all equipments are labeled as ‘CLEANED’
[][]Ensure that fresh set of gowns are issued to concerned operators.
[][]Ensure that proper environmental condition is maintained in the area and the records of the same are maintained in the specified formats.
[][]Ensure the correctness of Batch Manufacturing Record / Batch Packaging Record.

Line Clearance during Batch to Batch Changeover

[][]Ensure that previous batch material is removed from the production area.
[][]Ensure that all the equipment and their spares are cleaned according to their respective SOPs.
[][]Ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’.
[][]Ensure that floor is cleaned using vacuum cleaner and no visible traces of the previous batch material on the floor.

Annexure:

[][]N/A

Digital Weighing Balance, Purpose:

Digital Weighing Balance, To lay down the procedure for operation, accuracy check and cleaning of the weighing balances at the Production Area.

Digital Weighing Balance, Scope:

This SOP is applicable for 320 g & 60 Kg weighing balance for weighing of materials at the Production Area of XX Pharmaceuticals Ltd.

Definition / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Do not pour liquids on the weighing platform.
[][]Do not use solvents to clean the platform.
[][]Ensure balance is clean before use, including its surrounding area.
[][]Check and ensure the due date of calibration before use.
[][]Check and ensure the level indicator of weighing balance is in the middle, if applicable.
[][]Use hand gloves to hold standard weights for function check and calibration.

Daily Performance Check :

[][]Plug in the power cord.
[][]Level the balance using leveling feet so that air bubble is centered within circle of level indicator.
[][]TO turn the balance ON, short pressing the <O/T> key.
[][]Wait a while so that the stability indicator [*] is displayed.
[][]Zero the balance by pressing the >O/T> key.
[][]Press the 100 mg mass at the centre of the platform and record the value displayed in the daily balance check logbook.
[][]Press the 100 g mass at the centre of the platform and record the value displayed.
[][]Press the 200 g mass at the centre of the platform and record the value displayed.
[][]Print the results by pressing print ( ) button if necessary.
[][]Record the value of those weights in Log Book for ‘Daily Accuracy Check’ (Annexure – I).
[][]If any displayed value is out of acceptable limit, label the balance “DO Not Use” and inform the QA Executive for immediate calibration of the balance.
[][]Balance accuracy check must be performed at the starting of the day.

[][]If the factory remains close for the day(s), put the comments in the remarks column against that day(s) at the day of factory resume.

Operation of 320 g Balances of Mettler Toledo :

To start up:

[][]Level and adjust at each time it is moved to a new location. The balance is exactly horizontal when the air bubble is in the middle of the level glass. Adjust the two front leveling feet appropriately until the air bubble comes to rest exactly in the middle of the glass.
[][]Plug the AC adapter and connect the power supply. Connect the printer to the balance (if available).
[][]Switch on the printer using I/O switch.
[][]Press On/Off ( ) button to on the Electric Analytical Balance. Display will show 0.000g.
[][]Convert the weighing unit from g into mg, press scroll down ( ) button if necessary.
[][]Allow the balance to warm up to enable it to adapt itself to the ambient condition.
[][]Long press for menu ( ) button and select ‘BASIC’ by single press Enter button ( ).
[][]Set date, time and unit using – /+ keys and Enter button ( ) and save the settings using ( ) button.
[][]Press cancel (C) button to return come out of that ‘BASIC’ option and return to its main menu.

[][]Perform the ‘Daily Accuracy Check’ (Annexure – I) at the starting of the day.

Weighing:

[][]Check the machine is clean and calibrated. Then remove all loads from weighing pan.
[][]When zero (0.000 g) reading is displayed, the balance is ready for operation. If the display shows greater than or less than zero, press tare ( O/T ) button to tare the balance.
[][]If the balance is not in the weighing mode, press and hold the ( ) key down until ‘WEIGHING’ in the display.

[][]Use handle/coupling element for the operation of the draft shield door of the both side of the instrument.
[][]Open right/left/upper sliding window of the instrument.
[][]Place empty container/weighing paper on the pan of the balance. Close the sliding window.
[][]The weight is displayed. Allow the reading to stabilize and wait until the instability detector (O) disappears from the left side of the display and the stability beep sounds.
[][]Press tare ( O/T ) button to tare the balance. When zero (0.000 g) reading is displayed, the balance is ready for weighing.
[][]The weighing-in aid is a dynamic graphic indicator which shows the used amount of the total weighing range. It can be recognized at a glance when the load on the balance approaches the maximum load.
[][]Add weighing sample (Maximum 320g) on the container/weighing paper using weighing spoon. Close the sliding window. The net weight is now displayed.
[][]Allow the reading to stabilize and wait until the instability detector (O) disappears for the display and the stability beep sounds.
[][]To get printout of the weight, press print ( ) button.

[][]For performing another weighing press tare ( O/T ) button to tare the balance and follow steps from previous steps To increase or decrease digit, press display resolution ( ) button.
[][]Finally, press and hold On/Off button ( ) button until ‘SHUT OFF’ shows on the display.

Calibration:

Internal Calibration:

[][]Manual Adjustment with Internal weight:
[][]Long press menu ( ) button and press scroll down ( ) button to go to ‘ADVANCED’ option.
[][]Select ‘ADVANCED’ by pressing Enter ( ) button.
[][]Press scroll down ( ) button once to select ‘CAL’ option by pressing Enter ( ) button.
[][]Then select ‘ADJ. INT’ using scroll down ( ) button and then press Enter ( ) button.
[][]Press cancel (C) twice and save the settings if required by scrolling down ( ) button and press Enter ( ) button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration ( ) button to execute ‘Internal Adjustment’.
[][]The balance adjusts itself automatically. The adjusting is finished when the message “ADJ.DONE” appears briefly on the display. The balance returns to the last active application and is ready for operation.

[][]After adjustment, the result of the calibration will be printed out automatically or press print ( ) button for print copy.

External Calibration:

[][]Manual Adjustment with External weight:
[][]Follow the instruction from previous steps
[][]Select ‘ADJ. EXT’ by using scroll down ( ) and then press Enter ( ) button.
[][]Set the adjustment weight (100g) by using -/+ key for External Calibration and press Enter ( ) button.

[][]Then press cancel (C) button twice and save the settings if required by using -/+ key and press Enter ( ) button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration ( ) button to execute ‘External Adjustment’.
[][]The required predefined adjustment weight value flashes on the display.
[][]Place adjustment certified weight on the center of pan. The balance adjusts itself automatically.
[][]When ‘0.00 g’ flashes, remove the adjustment weight.
[][]The adjustment is finished when the message ‘ADJ DONE’ appears briefly on the display. The balance returns to the last active application and is ready for operation.
[][]After adjustment, the result of the calibration will be printed out automatically or press print ( ) button for print copy.

Operation of 60 kg Balances of Mettler Toledo:

[][]Using an Empty container for Weighing:
[][]Press the zero button.
[][]Place an empty container on the scale platform.
[][]Press the Tare button.
[][]Fill the container with material to be weighed.

[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]To clear a tare weight (with the scale in the net weight mode and a tare weight previously entered), press the Clear key (C).

Without using an Empty container for Weighing:

[][]Press the zero button.
[][]Place the material to be weighed on the scale platform.
[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]Perform the ‘Daily Accuracy Check’ (Annexure – I) at the starting of the day.

Acceptance Criteria:

[][]The observed weights should be within ± 0.1% of the certified standard weights.
[][]If the acceptance criteria are not satisfied, follow the procedure for Handling of out of calibration for instrument & equipment.

Calibration:

[][]Perform the routine calibration half year. Recalibration is required in the following cases :
[][]After any minor service has been done or replacement of parts.
[][]When the software or firmware has been upgraded or changed.
[][]If daily check fails

Cleaning:

[][]Place the status label ‘TO BE CLEANED’  on the equipment.
[][]Switch off the balance and unplug from the socket.
[][]Remove all objects from the weighing platform of balance.
[][]Lift up and remove the weighing pan in such a way that there is no damage in weighing system.
[][]Clean the pan including underside using a piece of dry cloth. Use wet cloth and finally clean with disinfection solution
[][]Wipe the display, switch board and cables with dry cloth.
[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’  label on the equipment after approval from Quality Compliance.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure: Digital Weighing Balance

Annexure I – Daily Accuracy Check.

Monitoring of Room Condition, Purpose:

Monitoring of Room Condition, To lay down the procedure for monitoring of Temperature, Relative Humidity (%) and Pressure Gradient at the Production Area.

Monitoring of Room Condition, Scope:

This SOP is applicable for the Production Area of General Block of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure :

Precaution :

[][]Do not use a new hygrometer unless it is calibrated.
[][]When any hygrometer is shifted from one location to another, allow to stabilize the device prior to record the temperature / Relative Humidity (%).
[][]Check the due date of calibration of the hygrometer and magnehelic gauge before taking reading.
[][]Ensure that temperature and Relative Humidity (%) readings are taken before going to operation.

[][]Temperature and Relative Humidity (%) (using Digital Hygrometer)
[][]Ensure that no dust is accumulated over the sensor.
[][]Read the temperature and relative humidity (%) values displayed on the screen of digital/analog hygrometer and record in ‘Temperature, Relative Humidity (%) & Pressure Gradient Records’ (Annexure-I).
[][]Acceptance Criteria:

Pressure Gradient

[][]Read the pressure differential from magnehelic gauge provided and record.
[][]If the reading is not within limit, check whether all the doors are closed.
[][]Observe the second reading.
[][]Even if the second reading is not within the limit, inform the Engineering department for corrective action.

Frequency

[][]Twice in a shift, first before starting the operation and second after four hours.
[][]If the reading is not within limit at any time of operation, inform the Engineering department immediately and take following steps in different areas.
[][]At Dispensing area stop weighing process, close the bags / high density polyethylene (HDPE) drums of raw materials.
[][]At Granulation area, stop transfer process of materials if running and close the SS / HDPE container with lid.
[][]Do not discharge if temperature and relative humidity (%) or pressure gradient are not within limit.
[][]At Blending area, continue blending process if already running.
[][]At Compression area, stop operation and close the tablet SS/HDPE container lid. Do not keep the granules in the hopper during overnight.
[][]Empty the hopper and close the lid of SS / HDPE container.
[][]At Encapsulation area, stop operation and close the capsule SS/HDPE container lid. Do not keep the granules / pellets in the hopper during overnight. Empty the hopper and close the lid of SS/ HDPE container.

[][]At Coating area, continue operation if already running, otherwise stop operation. Do not unload if temperature and relative humidity (%) or pressure gradient are not within limit.
[][]At Powder filling area, stop the operation. Do not keep the granules in the hopper during overnight.
[][]Empty the hopper and close the lid of SS / HDPE container.
[][]At Blister Packing area, close the lid of tablet / capsule container, close the hopper with lid and stop further operation.

Annexure:

Annexure I – Room Condition Monitoring Logbook

Production area Cleaning Procedure, Purpose:

Production area Cleaning Procedure, To lay down the procedure for effective Cleaning of Production area during Product to Product change over, Batch to Batch change over and at the end of day’s operation.

Production area Cleaning Procedure, Scope:

This SOP is applicable for the Production Area of  XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution :

[][]Do not clean/disinfect the area when the process is running.
[][]Keep the cleaning agents at the designated place only with proper labels.
[][]Ensure that after usage the wet mops are washed and hanged in hanger in cleaner store &allowed to dry. Ensure other cleaning tools are also hanged in hanger after use.
[][]After use of cleaning agent wash hands, feet and fingers thoroughly with soap & plenty of water.
[][]Ensure that during cleaning all the product containers are closed.
[][]Check and ensure that disinfectant solution prepared is not stored for use for the next day and the residue is discarded by pouring into drain.
[][]At least two different disinfectants are to be used alternatively on weekly basis.
[][]Do not mop the floor after keeping ‘Cleaned’ equipment in clean equipment storage room.

Cleaning Tools / Agents

[][]Portable vacuum cleaner
[][]Cloth & wiper
[][]Potable water and Purified water
[][]Glass Cleaning agent: ‘Clear View’ (Brand Name)
[][]Disinfectant Savlon (Cetrimide + Chlorhexidine Gluconate) / Dettol (Chloroxylenol) / Clotec (Hypochloride).

Preparation of 2.5 % v/v Savlon/ Dettol/Clotec

[][]To make 10 L disinfectant solution take 0.250 L Cetrimide + Chlorhexidine Gluconate/ Chloroxylenol / Hypochloride in freshly collected purified water to make up volume up to 10 L.
[][]Stir well to mix the solution properly.
[][]Prepare the disinfectant solution separately in separate bucket for use in different floor.
[][]Maintain the ‘Disinfectant Solution Preparation Record’ (Annexure – I).

Product to Product Cleaning Procedure (Type – A Cleaning) for Production Area

[][]Type – A cleaning is defined as cleaning procedure followed during product to product changeover.
[][]If the unit/equipment is used for same product it has to be cleaned after 72 hours.
[][]Place the status label ‘TO BE CLEANED’ (As per Form No. SOP/QCOM/008/XI) in the Area.
[][]Clean the ceiling, walls, outer surface of light fixtures, supply diffusers (SD) and return grills (RG) first with portable Vacuum cleaner to remove loose dust using a platform trolley, then with wet mop.
[][]Clean the machine/equipment in Production area as per SOP.
[][]Clean the doors, compressed air lines and other service lines with dry cloth.
[][]Clean the glasses with ‘Clear View’ solution and wipe.
[][]Clean the control panels, electrical wires with dry cloth.
[][]Clean toolbox, Batch Manufacturing Record table, log books, SOP holders, hygrometer, stool / chair with dry cloth.
[][]Clean the floor first with dry mop, then with potable water and mop with disinfectant solution. Finally clean with purified water.
[][]Ensure after inspection for absence of any residue of previous product. If any residue of previous product or extraneous matter is found, re-clean the area using above procedure until the area is free of any residue/ extraneous matter.

[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’ (As per Form No. SOP/QCOM/008/IX) label in the cleaned area after approval from Quality Compliance.
[][]Record the cleaning activity in ‘Room Cleaning Log Book’ (Annexure – II).

Frequency of Cleaning

[][]During product to product change over.
[][]After 3 days or 72 hours from the date of use of the equipment or area. If any batch is running and 72 hours time exceeds during the batch running period, cleaning shall be done after the batch is finished. If 72 hours time exceeds after cleaning and the equipment or area is not used, use the equipment or area after performing B-type cleaning.

Batch to Batch Cleaning (Type-B Cleaning) for Production area

[][]Type – B cleaning is defined as cleaning procedure followed during batch to batch changeover of a
same product.
[][]Place the equipment status label ‘PARTIALLY CLEANED’ (As per Form No. SOP/QCOM/008/X) in the area.
[][]First clean the floor, ceiling, walls, outer surface of light fixtures, supply diffusers (SD), return grills, (RG) doors and equipment with portable vacuum cleaner to remove the loose dust. [][]Finally clean the floor with wet mop.
[][]Remove ‘PARTIALLY CLEANED’ and affix ‘CLEANED’ (As per Form No. SOP/QCOM/008/IX) label in the area.
[][]Record the cleaning activity in Room Cleaning Log Book.
[][]Frequency of Cleaning
[][]During batch to batch change over

[][]Cleaning at the End of Day’s Operation
[][]Clean external parts of the machine, and operating panel with dry cloth.
[][]Clean the floor first with dry mop, then with potable water and mop with disinfectant solution. Finally clean with purified water.

Annexure:

Annexure I – Disinfectant Solution Preparation Record.
Annexure II – Room Cleaning Log Book.