Product Development

Semi Automatic Disintegration Tester , Purpose:

Semi Automatic Disintegration Tester , The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of Disintegration tester.

Semi Automatic Disintegration Tester , Scope:

This procedure is applicable for Semi Automatic Disintegration tester (Electrolab, Model: ED-2 SAPO) at the Product Development area of XX Pharmaceuticals Limited. This procedure is applicable for Core, Uncoated, Coated tablets and capsules.

Definitions / Abbreviation:

Disintegration Test: The disintegration test is a measure of the time required under a given set of conditions for a group of tablets, Capsule and Other solid dosage forms to disintegrate into particles which will pass through a 10 mesh screen.

Responsibilities:

[][]The roles and responsibility is as follows

Executive, Product Development

[][]To follow the procedure as per SOP.
[][]To maintain the Calibration records.
[][]To ensure cleaning of Disintegration tester maintaining safety rules.

Manager, Quality Assurance

[][]To ensure training and implementation of SOP in department.

Procedure:

Precaution:

[][]Do not switch on the mains if water in the tank is not up to mark.
[][]While placing and removing the basket assemblies do not apply excessive force.
[][]Do not bend the heater while cleaning the water bath.
[][]Do not clean the bath with any strong solvent. Use mild detergents for cleaning.
[][]Lift the machine from the base while lifting or installing.
[][]The external probe should be handled carefully.
[][]To prevent algae propagation in the bath replaces water in the bath at least once in a week.
[][]Remove the external probes when baskets are parked out or removed.
[][]Switch OFF the power supply of the instrument before removing water from the bath.
[][]Do not hold the stirrer while in operation.

Operation: Semi Automatic Disintegration Tester

[][]Ensure the cleanliness of area and the instrument.
[][]Fill the bath with purified water up-to the graduated mark.
[][]Connect the power cord of the instrument to the main power supply.
[][]Check the calibration status of the instrument
[][]Insert the test vessel (jar) in the water bath. Fill the test vessels with purified water / desired media up to 800 ml.
[][]Turn on the power switch provided on the rear side of disintegration tester.
[][]After power on, the instrument will initialize by displaying a power flash screen which will flash twice

DISINTEGRATION
TESTER
ED2-SAPO
VER-1.1

[][]After the power flash screen an idle will be displayed showing the last Mode. Protocol selected for basket A and basket B and the temperature of Jar A, Jar B, and Bath temperature.

Mode: Dual Timer
Proto A: # # Proto B: # #
BATH/ Jar A/ Jar B
# #. /ºC # #. /ºC # #. º

[][]Selection of Registration Mode (For Unknown Disintegration time)
[][]There are two modes: Registration Mode & Dual Timer Mode. Select Registration mode with or keys

Mode: Registration
Proto A: # # Proto B: # #
BATH/ Jar A/ Jar B
# #. /ºC # #. /ºC # #. ºC

[][]Press TEMP key from the front panel a screen will be displayed. Using // key set the temperature to 37.7ºC.
[][]Press TEMP key from the front panel a screen will be displayed. Using // key set the temperature to 37.7ºC.
[][]Press F1 to switch ON the heater. Press TEMP key to register the temperature and come out of the TEMP mode. An idle screen will be displayed. Wait to raise the bath and the jar temperature to desired level.
[][]Assemble the basket-rack.

Operation in Registration Mode

[][]Place six test samples in six tubes. Place the disks if stated in the monographs or in the case of floating products / tablets. Place the disk guides properly to prevent floating of samples.
[][]Press RUN/ HALT key of the respective A or B Jar to run the operation. In Registration mode two separate samples can be tested in two separate jars simultaneously.
[][]Observe the test in each of the tube. If the sample in any of the tube is disintegrated completely just press the key of the respective number. For example if the sample in the number 4 tube of Basket A is disintegrated at first press the number 4 key. Same procedure is followed for all the tubes of each basket.
[][]When Disintegration Time of 6 tablets in one Jar is registered the basket will park out of the media automatically. Press ENTER to return to initial screen.
[][]Observe the disintegration time. To see the time press TIME key. Press F1 to scroll to View Timing mode. Press ENTER. The screen will show the disintegration time of all the six samples. Press F1 key to scroll the screen downward.
[][]To come back into idle screen press ENTER key and press F2 key.

Selection of Dual Timer Mode (For Known Disintegration Time)

[][]When we know the disintegration time of any sample the operation can be done in DUAL TIMER MODE. In this mode there are 10 protocols. An individual sample with its known disintegration time is assigned against each protocol. Select Dual Timer Mode using UP or DOWN keys.
[][]Press TEMP key from the front panel a screen will be displayed. Using BACWARD/UP /DOWN key set the temperature to 37.7ºC.
[][]Press F1 to switch ON the heater. Press TEMP key to register the temperature and come out of the TEMP mode. An idle screen will be displayed. Wait to raise the bath and the jar temperature to desired level.
[][]Press TIME key from the front panel to set the time of a protocol.
[][]When (ARROW) indicates SET TIMER press ENTER button. Using BACWARD/UP /DOWN key adjust the required protocol and time. Press ENTER button to register the time and protocol and come out of the screen.
[][]Press F2 and return to the idle screen.
[][]Assemble the basket-rack.

Operation in Dual Timer Mode

[][]By using BACWARD/UP /DOWN key select different protocols for either jar A or jar B.
[][]Place six test samples in six tubes. Place the disks if stated in the monographs or in the case of floating products / tablets. Place the disk guides properly to prevent floating of samples / disks.
[][]Press RUN/ HALT key of the respective A or B Jar to run the operation.
[][]When the set Time for respective Jar is end up, the basket will park out of the media automatically. Press ENTER to return to initial screen.

Halting / Aborting the Test

[][]Press Run / Halt key to the respective test to be halted.
[][]The respective basket will park out of the media and the display will show the elapse cumulative halt time of the test being halted.

[][]To continue or abort test press Run / Halt key again a screen will be displayed for resuming or aborting the test.
[][]To resume test Press F1.
[][]To abort the test press F2. Press ENTER.

Operation Log Book

[][]Record the information’s in the operational log book- “Operation Log Book of Disintegration Tester (MODEL: ED2-SAPO)”
[][]Calibration of Temperature for Jar A and Jar B
[][]Press TEMP key. Use ▲/◄/▼Key to set the temperature at 37ºC.
[][]Press F1 to switch on the heater. The temperature light will blink.
[][]Press TEMP key to register the temperature and come out of the TEMP mode. An idle screen will display. Wait to raise the temperature at 37.7ºC in the both jars.
[][]When the screen displays a fixed temperature for Jar A and Jar B from temperature sensor, measure the temperature of both Jars by a calibrated thermometer.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: ± 2ºC of the display temperature.
[][]Calibration of Timer for Basket-A
[][]Select the Dual Timer mode by pressing ▼/▲key.
[][]Use ◄ key to select Proto A.[START OF SECTION ONE]
[][]Press the option menu.
[][]Press F1 (scroll) key to select set protocol. Press Enter key.
[][]Press ▼/▲ key to set a specific protocol no. (e.g. 01, 02, 03 …) under Proto A.
[][]Press F1 (scroll) key to enter the Timer option.
[][]Set the timer (5 minutes) by using ▲/◄/▼key.
[][]Press F2 key twice to return to the idle screen.
[][]Press the Run key in the front panel and start the calibrated stop watch to compare the time.

[][]After completion of the specified time (5 minutes) ‘Test is over’ is appeared on the screen with beeping sound.
[][]Press Enter key to return to the idle screen.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 5 minutes.[END OF SECTION ONE]

Calibration of Timer for Basket-B

[][]Use ◄ key to select Proto B.
[][]Follow previous steps [START OF SECTION ONE] TO [END OF SECTION ONE]
[][]Calibration of Stroke/min. for Basket-A
[][]Check the jar temperature. If temperature is not in the desired level, wait for raising the temperature (37.7°C) in the jar.
[][]Follow previous steps
[][]Press the RUN key and start the stop watch to count the no. of strokes per minute.
[][]Press the Halt key twice and then Test A is displayed.
[][]Press F2 to abort. The screen will display ‘Test is over’.
[][]Press Enter key to return to the idle screen.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 29 to 32 Stroke/min.
[][]Calibration of Stroke/min. for Basket-B
[][]Follow previous steps(In case of Proto B, Use ◄ key to select Proto B).
[][]Calibration of Traveling Distance for Basket-A
[][]Follow previous steps
[][]Press Run key to travel the Basket A in upward and downward stroke.

[][]When the basket is in the downward stroke position, Press the power switch (Rear side of the instrument) to off quickly.
[][]Now Mark the position (Xa) of the basket holder by a pencil.
[][]Press the power switch on.
[][]Press the TEMP key.
[][]Press F1 to on the heater. The temperature light will blink.
[][]Press TEMP key to return to the idle screen position.
[][]Wait for the desired setting temperature (37°C). When it reaches to the desired level, Press the Run key. The basket will travel upward and downward stroke.
[][]When it comes to the upward stroke position, Press the power switch (Rear side of the instrument) to off quickly.
[][]Mark the position (Ya) of the basket holder by a pencil.
[][]Now measure the traveling distance between Xa and Ya by a standard certified scale.

Xa – Ya= ## mm.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 55 ± 2 mm.
[][]Calibration of Traveling Distance for Basket-B
[][]Press the power switch (Rear side of the instrument) to on.
[][]Press the TEMP key. Use ▲/◄/▼key to set the temperature at 37ºC.
[][]Press F1 to switch on the heater. The temperature light will blink.
[][]Press TEMP key to return to the idle screen position.
[][]Wait for the desired setting temperature (37.7°C). When it reaches to the desired level Press the Option Key.
[][]Follow steps  (In case of Proto B, Use ◄ key to select Proto B).
[][]Follow steps

Calibration of Basket A to Beaker Bottom Height

[][]Unscrew Basket A from the bottom and remove the basket bottom plate.
[][]Remove one tube (with Blue or Brown indication) and engage the basket to the basket holder.
[][]Insert the measuring scale (6 inch) into the disc from where the tubing has been removed. Care should be taken that the scale touches the bottom of the beaker.
[][]Press the power switch (Rear side of the instrument) to on.
[][]Press the TEMP key.
[][]Press F1 to on the heater. The temperature light will blink
[][]Press TEMP key to return to the idle screen position.
[][]Wait for the desired setting temperature (37°C). When it reaches to the desired level, Follow steps
[][]Press the Run key to travel the Basket A in upward and downward stroke.
[][]When the basket is in the downward stroke position, Press the power switch (Rear side of the instrument) to off quickly.
[][]Measure the Basket A to bottom height during the downward stroke by certified measuring scale.
[][]Keep the records of calibration as per Annexure-I.
[][]Acceptance Range: 25 ± 2 mm.

Calibration of Basket B to Beaker Bottom Height

[][]Follow steps

[][]Set the parts of the instrument and clean the instrument.
[][]Calibration Frequency: 3 months ± 10 days.

Cleaning

[][]After completion of a test clean the basket-rack assembly with potable water and if required with a mild detergent.
[][]Whenever required use a suitable brush to remove any residue of the previous sample from the mesh screen.
[][]Use potable water to clean the jar and bath.
[][]Finally rinse the basket rack assembly, jar & bath with purified water and dry in air.
[][]Cleaning frequency of basket rack assembly & jar : After every test
[][]Cleaning frequency of water bath: Once in a week.
Note: In between when water become dirty change water
[][]After cleaning of the disintegration test apparatus water bath, record it as per Annexure-III

Annexure: Semi Automatic Disintegration Tester

Annexure-I: Operation log book of Disintegration Tester(Model: ED2-SAPO)
Annexure –II: Calibration report of disintegration tester.
Annexure-III: Cleaning record for Disintegration water bath.

Electric Stirrer , Purpose :

Electric Stirrer,  The purpose of this SOP is to describe the Operation, cleaning and maintenance procedure of Electric Stirrer (Model: ES) in order to comply with cGMP standard.

Electric Stirrer , Scope :

The scope of the procedure is applicable to the Electric Stirrer (Model: ES) at the Product Development area of XX Pharmaceuticals Pvt. Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

The roles and responsibility is as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the Electric Stirrer (Model: ES)
[][]Maintaining operation and cleaning log book

Executive/ Sr. Executive Product Development

[][]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.

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:

Machine Assembling

[][]Attach required sieve in the sieve holding clamp of the machine.
[][]Attach bolts and tighten the knobs to ensure that the sieve is properly installed in the machine.
[][]Rotate the shaft clamp to loosen the main shaft.
[][]Push the shaft downward to lower the main shaft and pull the shaft upward to rise the main shaft holding the propeller and sieve.
[][]Rotor the shaft clamp anticlockwise to tighten the main shaft.
[][]Ensure that the main shaft is properly tightened before running the machine. Donot run the machine if the shaft is not properly tightened.
[][]Check for all the bolts to be tightened properly.

Machine Operation

[][]Connect the main electric supply with the socket.
[][]Three lights (Red, Green and Yellow) illuminates to show the proper functioning of the three phase connection of the machine.
[][]Adjust the secondary propeller according to the need of the liquid to be stirred. If secondary propeller is not required adjust it higher than the liquid lavel.
[][]Make sure that both propeller is submerged in the liquid to be stirred.
[][]Push the Forward button to rotate the propeller clockwise and push the backward button to rotate the propeller anticlockwise.
[][]To stop the machine instantly push the stop button.
[][]To switch from forward rotation to backward rotation first push the stop button and when the machine is stop then push the backward button.
[][]Do not switch directly from one rotational direction to another direction.
[][]Display will show the RPM of the machine, do not change any parameter in the inverter. Changing parameters in the inverter will stop the machine immediately.
[][]To change or adjust the machine speed use the speed controlling regulator. Clockwise rotation will increase the RPM and anticlockwise rotation will decrease the RPM.
[][]When the display shows 60 in the screen the machine tends to rotate in 2800 RPM. Do not run the machine more than 1400 RPM that is 30 in the screen.
[][]To stop the machine push the stop button and the machine will stop automatically.

Machine Dismantling

[][]Disconnect the machine from the main electric supply.
[][]Rise the main shaft from the liquid. Remove the remaining liquid(if any) from the sieve holding clamp and remove the solution preparation mug.
[][]Loosen the sieve holding bolts, remove the sieve and take in a poly bag
[][]Loosen the primary propeller with the help of a range, and remove from the machine.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Clean the sieve holding clamp, secondary propeller and the main shaft of the machine with lint free cloth wiped in potable water.
[][]Repeat the procedure twice to remove all solution from the machine.
[][]Clean the secondary propeller and the clamp with brush to remove any part of the solution adhering to the machine.
[][]Rub gently with lint free cloth to remove any solution adhering to the machine.
[][]Wipe the cloth in hot water and rub the machine, Clean all the machine parts with hot water, then finally rinse with purified water.
[][]Clean the motor covering , Main shaft and the base of the machine with potable water, Rub the parts with lint free cloths wipe din potable water than rinse with purified water.
[][]Wipe the machine with dried lint free cloth to remove water from the machine. Use compressed water to remove water as necessary.
[][]Submerge the sieve and the primary propeller in potable water for 10 minutes.
[][]Clean the parts with tap water to remove any part of the solution.
[][]Use brush and lint free cloth to properly clean the parts.
[][]Submerge the parts in hot water, Clean the parts with hot water finally rinse with purified water.
[][]Rub the machine parts with lint free cloths and compressed air to remove water.
[][]Take the dried sieve and the sieve holding bolts in a poly bag attach a cleaned label and store in the cabinet.
[][]Install the propeller in the main shaft. Attach a Cleaned label in the machine.

Annexure:

Annexure – I: Operation and cleaning log book.

Hand Capsule Filling Machine, Purpose :

Hand Capsule Filling Machine, The purpose of this SOP is to define the operation, cleaning and maintenance procedure of manual capsule filling machine. Model: PCF 300

Hand Capsule Filling Machine, Scope :

This SOP is applicable for operation, cleaning and maintenance procedure of manual capsule filling machine in product development laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

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

Operator/Supervisor Product Development

[][]Operation and cleaning of the Manual Capsule Filling Machine
[][]Maintaining operation and cleaning log book

Executive/ Sr. Executive Product Development

[][]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.

Assistant 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:

Machine Assembling

[][]Before operation assemble the machine change parts that are necessary for certain type of operation.
[][]Attach the required type of change parts for the expected operation in the machine

Machine Setup

[][]Tag the filling machine with a Machine Label before use.
[][]Arrange empty capsule shell on the loading tray.
[][]Place the loading tray with empty capsule on the machine.
[][]Grip cam lever and pull towards the front.
[][]Push the inner slide knob.
[][]Depress the lifting plate lever.
[][]Lift the loading tray up.
[][]Separate the capsule bottom half (Bodies) from the cap.
[][]Check the entire cap and bodies are separated.
[][]Keep the loading tray with separated cap on the table carefully.
[][]Release the lever to drop down the bodies to sit in level with the top section.
[][]Place the filling tray on the machine. Ensuring the tray is properly located in holes provided in the top section.
[][]Pour the pre-weighed Powder /Pellet

Machine Operation for powders

[][]Spread the powder using Teflon dispenser over the top section to fill the body uniformly.
[][]If any powder remains on the tray, take aside the excess powder with the powder dispenser on to the platform provided on the right of the tray. Lower the pin plate assembly and lock it in position using pin plate locking lever to compact the powder.
[][]Unlock the lever, open the pin plate and spread the remaining powder (if necessary follow further step: 10.4.1. and 10.4.2.).
[][]Remove the filling tray. Place the loading tray with separated cap on the top section.
[][]Pull out the inner slide knob.
[][]Lower the pressure plate and lock in position with locking lever.
[][]Move the lifting plate lever downward for proper locking of the capsule.
[][]Unlock the pressure plate and take it back to its original position.
[][]Push the inner slide knob.
[][]Depress the lifting plate lever.
[][]Lift the loading tray up with locked capsule.

[][]Empty the locked capsule into a suitable container
[][]Remove the product container. Use plastic bag to wrap under the discharge chute. Clean the sieve to remove the materials that cannot pass though the sieve (If product is very sticky, the sieve might require to be removed for a thorough cleaning with brush and cleaning agent).
[][]Clean the machine after completing the operation of the day or before changing to process other products.

Machine operation for pellets.

[][]Spread the pellets using Nylon brush over the top section to fill the body uniformly.
[][]Remove the filling tray. Place the loading tray with separated cap on the top section.
[][]Pull out the inner slide knob.
[][]Lower the pressure plate and lock in position with locking lever.
[][]Move the lifting plate lever downward for proper locking of the capsule.
[][]Unlock the pressure plate and take it back to its original position.
[][]Push the inner slide knob.
[][]Depress the lifting plate lever.
[][]Lift the loading tray up with locked capsule.
[][]Empty the locked capsule into a suitable container
[][]Clean the machine after completing the operation of the day or before changing to process other products.

Machine Dismantling

[][]Remove the powder tray.
[][]Open the cam lever.
[][]Remove the eccentric pin.
[][]Remove the top section by loosening four screws.
[][]Pull out sliding sheet from the top section.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Wash the powder tray, cam lever, top section with sliding sheet, nylon brush, powder dispenser and the main body (lifting plate assembly, pin plate assembly and pressure plate assembly) with potable water.
[][]Wipe with damp markin cloth by rubbing to remove any adhering materials
[][]Wash with potable water again
[][]Wash with hot water using damp cloth to remove any insoluble material
[][]Wash with hot water and then with purified water.
[][]Wipe with clean, dry markin cloth to remove any water
[][]Dry with compressed air where necessary
[][]Wrap with poly bag, attach “CLEANED” label and store in the accessories cabinet.
[][]Clean eccentric pin with cotton cloth and lubricate it.
[][]Push the sliding sheet into the top section.
[][]Mount the top section onto the main body by four screws.
[][]Assemble the eccentric pin and cam lever.
[][]Keep the loading tray and powder tray with attached “CLEAN” label in accessories cabinet.
[][]Attach “CLEANED” label in the machine in store in the Table.

Annexure: Hand Capsule Filling Machine

Annexure – I: Operation and cleaning log book.

Multi mill , Purpose :

Multi mill , The purpose of this SOP is to describe the Operation and cleaning procedure of Multi Mill (Model: GMP) in order to comply with cGMP standard.

Multi mill , Scope :

The scope of the procedure is applicable to the Multi Mill (Model: GMP) at the Product Development area of  XX Pharmaceuticals Pvt. Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

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

Operator/Supervisor Product Development

[][]Operation and cleaning of the Multi Mill (Model: GMP)
[][]Maintaining operation and cleaning log book

Officer/ Sr. Officer Product Development

[][]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.

Assistant 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:

Machine Assembling

[][]Loosen the knobs of the Discharge covering. Anticlockwise rotation of the knobs will loosen and clockwise rotation will tighten the discharge unit
[][]Remove the discharging unit from the machine. Rotate the covering slightly at any direction and pull downward to remove smoothly.
[][]Rotate the screws of the Mesh holding plate anticlockwise direction to loosen the plate. Rotate the plate anticlockwise and remove from the machine.
[][]Check for the proper tightening of the knife and knife holding shaft.
[][]Set desired mesh on the mesh slot, push upward to set the mesh properly.
[][]Install the mesh holding plate, tighten the mesh holding plate properly. Do not run the machine without properly tightening the knobs.
[][]Install the Discharge unit in the, tighten all the knobs of the discharge unit to properly set the machine.
[][]Check for the proper positioning, functioning and installation of the hopper, feed controlling plate and the hopper covering.

Machine Operation

[][]Connect the main electric supply with the socket.
[][]Three lights (Red, Green and Yellow) illuminates to show the proper functioning of the three phase connection of the machine.
[][]Remove the covering of the hopper to charge the materials in the hoper. Keep the feed control plate fully closed while charging the materials.
[][]Pull the feed control plate outward to control the material entry in the milling zone.
[][]Install the hoper covering, do not run the machine without the covering installed properly.
[][]Push the Forward button to rotate the blades clockwise and push the backward button to rotate the blades anticlockwise.
[][]To stop the machine instantly push the stop button.
[][]To switch from forward rotation to backward rotation first push the stop button and when the machine is stop then push the backward button.
[][]Do not switch directly from one rotational direction to another direction.
[][]Display will show the RPM of the machine, do not change any parameter in the inverter. Changing parameters in the inverter will stop the machine immediately.
[][]To change or adjust the machine speed use the speed controlling regulator. Clockwise rotation will increase the RPM and anticlockwise rotation will decrease the RPM.
[][]When the display shows 28 in the screen the machine tends to rotate in 1400 RPM. Machine can be run in more speed than that, but don’t run the machine in speed more than 28 in display.
[][]To stop the machine instantly push the stop button and the machine will stop automatically.

Machine Dismantling

[][]Disconnect the machine from the main electric supply.
[][]Remove the Hopper cover and the feed control plate from the machine.
[][]Loosen the screws in the hopper than remove the hopper from the machine.
[][]Rotate the knobs in the discharge unit, rotate the discharge unit than pull downward to remove the discharge unit from the machine.
[][]Rotate the knobs in the mesh holding tray anticlockwise to loosen the screws. Rotate the knobs anticlockwise and remove the tray.
[][]Pull the mesh downward to separate the mesh from the machine.
[][]Use a socket set to remove the knife shaft from the machine.
[][]Loosen the screw on the downward of the machine.
[][]Pull the shaft backward. The shaft with the knives will come out.
[][]Remove the pin holding cap on the top of the shaft.
[][]Pull out the pins from the shaft.
[][]Remove the knives and the scrapers by pulling them in outer direction.

Machine Cleaning

[][]After removal and dismantling of all change parts take the change parts in the cleaning bay.
[][]Use vacuum cleaner to remove any remaining powder from the machine body.
[][]Wash the machine body, shaft, basement and motor holding portion wish wet lint free cloth.
[][]Wash the machine with hot water if necessary, then finally rinse the machine with wet cloth submersed in purified water.
[][]Dry the machine with dried lint free cloth. Use compressed air if necessary to remove water from the critical places.
[][]Clean the wire with wet cloth and dry using lint free cloths.
[][]Clean all the change parts with potable water, use cloth to rub well to remove any portion of powder from the machine.
[][]Use hot water to clean all the machine parts, use nylon brush if necessary to remove any remaining quantity of powder dust
[][]Use nylon brush to clean the knives and brush through the knife shaft to remove any portion of powder.
[][]Run the whole procedure twice for knife and knife holding shaft.
[][]Rinse the parts with purified water. Dry all the change parts with lint free dried cloth, Use compressed air to remove water from the critical areas.
[][]Use compressed air to remove the water from the knife holding zone in the shaft.
[][]Attach the knives with the shaft and lock with the pin
[][]Attach pin holding top to keep the pin in position.
[][]Fix the knife shaft in the machine and tighten with the socket set, check for the proper fixing of the machine.
[][]Attach the sieve holding plate and the discharge unit with the machine
[][]Install the hopper, feed control plate and the hopper covering in the machine. Attach a CLEANED label in the machine.
[][]Clean the sieve with potable water, use dump cloth to properly remove powder.
[][]Use hot water to clean the sieve properly, use nylon brush to remove any quantity of powder.
[][]Rinse the sieve with purified water, dry the sieve with dried lint free cloth, use compressed water first to remove the water from the sieve then use lint free cloth to dry the sieve.
[][]Take the sieve in a poly bag, attach a cleaned label in the bag and store in the cabinet for machine change parts.

Annexure:

Annexure – I: Operation and cleaning log book.

Coating Machine , Purpose:

Coating Machine , The purpose of this SOP is to define the operation and cleaning procedure of Coating machine.

Coating Machine , Scope:

This SOP is applicable for operation and cleaning procedure of Coating machine in product development of General Block at XX Pharmaceuticals Limited.

Definition / Abbreviation:

None

Responsibilities:

The roles and responsibility are as follows:

Operator/Supervisor Product Development

[][]Operation and cleaning of the Coating machine
[][]Maintaining operation and cleaning log book

Executive/ Senior Executive, Product Development

[][]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, Quality Assurance

[][]Ensure that the SOP reflects actual operation and cleaning procedure.
[][]Approve the SOP against XX Pharmaceuticals Limited master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure

[][]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

[][]Connect the power cable to the socket for power supply.
[][]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.
[][]Outlet blower ‘‘ON/OFF” by pressing the push button.
[][]Pan motor ‘‘ON/OFF’ by pressing the push button.
[][]Inlet blower” ON/OFF” by pressing the push button.
[][]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.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Switch off outlet damper, blower, pan motor, inlet blower.
[][]Open all safety doors.
[][]Dismantle spray system.
[][]Switch on the peristaltic pump by pressing “Switch on button”.
[][]Wash the inside of tube by spraying with hot water followed by purified water.
[][]Again wash the tube with purified water.
[][]The 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 to remove materials fixed hardly on the chamber surface.
[][]Wash the machine with wet markin cloth.
[][]Re-wash the machine with purified water as required. Finally rinse with purified water.
[][]Clean inlet ports, discharge port, mixing chamber and external surface with damp cloths.
[][]Wipe the water droplets with cloth, and dry the machine with compressed air.
[][]Fix ‘CLEANED’ label on the machine.
[][]Keep the record of machine operation and cleaning according to the Annexure – I of this SOP.

Annexure:

Annexure – I: Operation and cleaning log sheet of Coating machine, Model: FC 15”-E

Compression machine, Purpose :

Compression machine, The purpose of this SOP is to describe the Operation and cleaning procedure of CAMBERT Tablet Compression Machine (Model: KMP DB8) in order to comply with cGMP standard.

Compression machine, Scope :

The scope of the procedure is applicable to the CAMBERT Tablet Compression Machine (Model: KMP DB8) at the Product Development area of XX Pharmaceuticals Pvt. Limited.

Definitions / Abbreviation:

[][]None

Responsibilities:

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

Operator/Supervisor Product Development

[][]Operation and cleaning of the CAMBERT Tablet Compression Machine (Model: KMP DB8)
[][]Maintaining operation and cleaning log book

Executive/ Sr. Executive Product Development

[][]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.

General 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: Compression machine

[][]Machine Assembling
[][]Remove the site glass of all sides
[][]Setting of Die
[][]Ensure that the die pockets are cleaned.
[][]Smear the die with food grade oil and place n the die pocket of the die table.
[][]Press the die down with finger to locate accurately the die in the die pocket.
[][]Once the die is located enter the die bar through the upper punch guide hole and allow to drop from a height of 70 – 80 mm approximately.
[][]The die will enter in the pocket apply additional force through die 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 cavity with the upper punch and gently push the die with the punch to enter in the die pocket, then apply additional force 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 screw with the allen key. Ensure that the die is flash with the die table after tightening. Do not run the machine if die screw is not properly tightened.
[][]Use four blank dies ( four for B tooling and four for D tooling separately) in respective die cavity and install in the same procedure.

Setting of lower punch

[][]Remove the R.H. lower panel to access punch loading plug
[][]Remove the punch loading plug from the middle plate by just pushing it from bottom.
[][]Rotate the turret slowly with the help of hand wheel and align punch guide hole with the punch loading plug cavity.
[][]Insert the punch in to guide hole. Push the punch to its highest position and ensures it drops freely under its own weight. Tighten the punch holding plug with a screw driver.
[][]Carefully rotate the turret by means of the hand wheel until the punch is clear of the loading port.
[][]Set all the lower punch in the same way.
[][]Install the Punch loading plug in the middle plate.

Setting of upper punch

[][]Ensure that the punch guide holes and punches are clean.
[][]Place the punches in the punch holes 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 fly wheel to recheck to ensure that the upper punches enter the die bores without tipping and they run freely throughout the cam system.
[][]In order to set shaped punches (other than round) remove the punch take out plate for upper punch. Then place the punch in the punch holes and observe that the punch is fitted with the die without any friction, than rotate the fly wheel until the upper punch is removed to the punch head fitted position.
[][]Set all the punches in the same manner, then refit the punch take out plate in position.
[][]Rotate the machine manually through fly wheel to ensure that die punch are set correctly and the machine can be run without any friction.
[][]Install the force feeder in front of the machine. Ensure that no part is in touch with the main turret. Tighten the bolts of force feeder. Rotate the machine manually through fly wheel to ensure machine rotates without hindrance.
[][]Install the tablet ejection chute at the right side of the machine. Ensure that no part of the machine is in contact with the turret. Tighten the screw so that the ejection chute.
[][]Install the hopper above the force feeder.
[][]Connect the coupling with the feeder drive, shaft. Lock the coupling.
[][]Check that all nut bolts are tightened correctly.
[][]Install the R.H lower panel and the site glass. The machine is ready to use.

Machine Operation

[][]Rotate the machine through fly wheel and check that there is no abnormal sound in the machine
[][]Connect the main electric supply with the socket.
[][]Turn the machine on off switch to right direction, main drive and feeder drive button light will lights will illuminate to indicate machine is supplied with proper electric supply.
[][]Remove the R.H lower panel and keep the weight adjustment and thickness adjustment wheel at lower position, install the R.H. lower panel.
[][]Keep the speed adjustment knob at low and press the main drive button to ensure that the machine runs without any abnormal noise or hindrance.
[][]Press the main drive off switch, turret will stop.
[][]Remove the lid of the hoper and pour powder in the hoper, Push the feeder drive button feeder will start, wait until powder is transferred to the filling area.
[][]Fix the upper punch penetration wheel at its desired position (from 2 to 6 mm) depending on the punch and product type. Do not change the position of the wheel during operation.
[][]Fix the precompression wheel at its desired position (from 2 to 4), do not change the position of pre compression wheel during operation.
[][]Push the main drive button, turret will start, ensure that the powder are filled accurately in the die cavity.
[][]Rotate the thickness adjustment wheel clockwise until the powders take the shape of tablet.
[][]Adjust the weight of the tablet by rotating the filling depth adjustment wheel clockwise. Clockwise rotation will decrease the tablet weight and anticlockwise rotation will decrease the weight of the tablet.
[][]After desired tablet weight is achieved, adjust the thickness of the tablet. Clockwise rotation of thickness adjustment wheel will decrease the thickness and anticlockwise rotation will increase the thickness.
[][]Tablet hardness will also be adjusted by the thickness adjustment wheel. Clockwise rotation of the wheel will increase the hardness and anticlockwise rotation will decrease the hardness.
[][]Once tablet of desired quality is achieved set the turret speed. Turret speed can be adjusted by the speed adjustment knob. Clockwise rotation of the knob will increase the speed and anticlockwise rotation will decrease the speed.
[][]With any change in the turret speed, feeder speed is also needed to adjust. Clockwise rotation of the feeder speed adjustment knob will increase and anticlockwise rotation will decrease the feeder speed.
[][]Check the tableting parameters (Weight, Hardness and thickness) while turret speed is increased or decreased. Adjust the weight and thickness if necessary.
[][]Rotate the tablet counting key at right side. Counter will start counting the tablets. To watch counting in number of tablet in display place the counter knob at number of tablet position and to watch the turret speed place the counter knob at RPM position.
[][]To stop the turret, press turret off button and to stop the feeder drive, press feeder drive stop button.
[][]To stop the machine instantly, rotate the main switch at left position, machine will stop.

Machine Dismantling

[][]Remove the site glass in front side of the machine.
[][]Remove to material lock from the force feeder, place a poly bag and on the force feeder, excess materials will be flown in to the poly bag.
[][]Switch off the machine, Remove the main power supply form the socket.
[][]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.

[][]Unlock the feeder drive shaft from the coupling and keep aside. Loosen the force feeder holding screw then remove the force feeder.
[][]Remove the upper punches
[][]Remove the lower RH panel and punch loading plug.
[][]Rotate the machine manually and align the lower punch with the punch loading cavity.
[][]Loosen the punch holding plugs. 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 locking screw up to maximum limit.
[][]Enter the die bar from the punch loading cavity. Align the die with the cavity then gently apply pressure upward to remove the die. If necessary apply force through tamping. Die will come out of the die cavity. Remove all the die in the same manner.
[][]Install the lower RH Panel

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]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 cavity & die holding plug with a flush brush. Use brush to clean any material sticking in the machine parts, screw and knobs.
[][]Use potable water to clean the turret, machine body, cam, punch holding cavity operation panel, die cavity and die holding screw.
[][]Use hot water to clean all the above mentioned body parts & finally rinse with purified water.
[][]Clean and sob with lint free cloth all the parts to dry any water in the machine body.
[][]Attach RH panel and site glass and stick 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 hole 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.
[][]Sob 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 force feeder

[][]Remove the screws of 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 particle 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 machine with hot water, then rinse with purified water.
[][]Clean and sob 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.

Annexure: Compression machine

Annexure – I: Operation and cleaning log book.

Container blender, Purpose:

Container blender, The purpose of this SOP is to define the operation and cleaning procedure of container blender.

Container blender, Scope:

This SOP is applicable for operation and cleaning procedure of container blender in product development of XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]None

Responsibilities:

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

Operator/Supervisor Product Development

[][]Operation and cleaning of the container blender
[][]Maintaining operation and cleaning log book

Executive/ Senior Executive, Product Development

[][]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, Quality Assurance

[][]Ensure that the SOP reflects actual operation and cleaning procedure.
[][]Approve the SOP against XX Pharmaceuticals Limited master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

Machine Assembling

[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Place the container at the holding arm of the blender. Then, secure it with the holding arm.
[][]Securely close and lock of inlet ports and outlet port in place.
[][]Test whether container rotates smoothly without any abnormal noise after activation. Check that rotation direction is correct according to the arrow sign.

Machine Operation

[][]Connect the power cable to the socket for power supply.
[][]Turn the machine ON/OFF switch (main switch at the right down corner of the machine) to ON. Control panel light will illuminate and the machine is ON.
[][]Unclamp and open the inlet port cover.
[][]Load raw materials into the chamber. Total material load should not exceed the maximum working volume and the minimum working volume.
[][]Securely close the mixing chamber cover and clamp.
[][]Release the EMERGENCY SWITCH, MIXER STOP SWITCH will light up, indicating that the electricity is supplied to the control system and the machine is ready to perform the process.
[][]Set Timer process according to the timer required for the mixing process.
[][]Activate the mixer.
[][]Observe carefully, there is no abnormal noise generated by the blender.
[][]Ensure that there is no leakage in inlet valve and outlet valve during the mixing.
[][]Check that the timer counts down the time. Once the set time is reaches, the mixer will stop operation accordingly.
[][]Place a collection bin under the outlet port. Plastic or clothing bag might be wrap between outlet port and other collection bin to prevent product dispersion into the room.
[][]Open the outlet valve to discharge the product into a collection bin. Open the inlet port to check whether there is any remaining product inside the container.
[][]Shut the outlet port after all product removed.
[][]In case of manual operation set TIMER OFF/ON selector to OFF. And activate the blender.
[][]Push EMERGENCY SWITCH button to discontinue the electrical supply to the system.
[][]Clean the machine as per above cleaning procedure.
[][]Turn the machine ON/OFF button to OFF. The machine light will be OFF.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]Place the drain tank under the discharge port.
[][]Ensure the discharge port is securely closed.
[][]Check again there is no material inside the container.
[][]Fill the container until half of the mixing chamber with normal water.
[][]Securely close the inlet port.
[][]Activate the machine to rotate at low speed first before accelerate the speed.
[][]After a while, check inside the chamber whether machine residue is fully dissolved and suspended or not. If not, start the blender rotation again.
[][]Repeat the procedure until it is done.
[][]Now discharge the water with dissolved materials.
[][]Now hot water is applied inside the chamber to remove materials fixed hardly on the chamber surface.
[][]Wash the machine with wet marking cloth.
[][]Re-wash the machine with purified water as required. Finally rinse with purified water.
[][]Clean inlet ports, discharge port, mixing chamber and external surface with damp cloths.
[][]Wipe the water droplets with cloth, and dry the machine with compressed air.
[][]Fix ‘CLEANED’ label on the machine.
[][]Keep the record of machine operation and cleaning according to the Annexure – I of this SOP.

Annexure:

Annexure – I: Operation and cleaning log sheet of Container Blender

Wet and Dry Granulator , Purpose:

Wet and Dry Granulator , The purpose of this SOP is to define the operation and cleaning procedure of Wet and Dry granulator.

Wet and Dry Granulator , Scope:

This SOP is applicable for operation and cleaning procedure of Wet and Dry granulator in product development of  XX Pharmaceuticals Limited.

Definition / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility are as follows

Operator/Supervisor Product Development

[][]Operation and cleaning of the Wet and Dry granulator
[][]Maintaining operation and cleaning log book

Executive/ Senior Executive, Product Development

[][]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, Quality Assurance

[][]Ensure that the SOP reflects actual operation and cleaning procedure.
[][]Approve the SOP against XX Pharmaceuticals Limited master documents and current regulatory requirements.
[][]Implementation of the SOP.

Procedure:

[][]Machine Assembling
[][]Before operation assemble the machine accessories that are necessary for operation.
[][]Place the appropriate granulator head that is Wet head or Dry head.
[][]Place the appropriate sieve in the head.
[][]Securely lock the main head body to the driving shaft.
[][]Clamp down or tighten each component in place and insert the desired sieve with correct mesh size.
[][]Tightened the blade, hopper and body.
[][]Switch on the machine check that the granulation head rotates smoothly and there is no abnormal noise heard.

Machine Operation

[][]Switch on Main Breaker to supply main power to the system.
[][]Place a product container underneath the granulation head.
[][]Wrap the discharge chute with lint-free cloth which allows air to flow through. This will make the product flow penetrating into the product container without dispersing in the air.
[][]Press Start (Green push button) to activate the granulation head. The head will start rotating.
[][]Gradually load material into the granulation head from the top side.
[][]Observe that material loading rate should synchronize with granules output rate, that granule present through the discharge chute into the product collection bin.
[][]Loading product faster in the granulation head will results finer particles than the desired.
[][]The granulation rate varies depending on sieve size used and product characteristics.
[][]After charging all material into the machine and all are discharged, press Stop (Red push button) to discontinue the granulation process. The main shaft will stop rotating.

Machine Cleaning

[][]If the machine doesn’t used within 15 days after cleaning, then the machine should be cleaned on the 15th day.
[][]For safety purpose, cut off the main breaker that supply electricity to the machine before commencing the cleaning operation.
[][]Removing Granulation head from the main machine and bring it to the cleaning area.
[][]Disassemble each component for cleaning separately.
[][]Clean each component with fresh running potable water, hot water finally Purified water. Spatula (scraper) and cleaning agent might be required to remove sticky material attached on the surface.
[][]Do not submerge Granulation head into water bath. Water will penetrate into the bearing housing and cause rust, bearing service life of bearing will be lessened and machine will not operate smoothly.
[][]Spatula (scraper) or cleaning brush used with the machine must be made of only of plastic, rubber or materials that do not generate scratches or damage to the mirror-polished surface.
[][]Sieve should be thoroughly clean and ensure that no material stuck in the perforated holes and wire net.
[][]Repeat cleaning if necessary until the granulation head is completely cleaned.
[][]Use soaked cloth to clean the main granulation machine. Care must be taken that no water enters the control box and motor housing.
[][]Wipe each component with clean and dry cloth to remove the remaining water. Start wiping the critical area that is product contact parts first, following by non-product contact area.
[][]Apply compressed air or heated air to expedite the drying rate. Otherwise, leave each component to dry up in the clean operating room.
[][]Re-wash the machine with purified water as required. Finally rinse with purified water.
[][]Fix ‘CLEANED’ label on the machine.
[][]Keep the record of machine operation and cleaning according to the Annexure – I of this SOP.

Annexure:

Annexure – I: Operation and cleaning log sheet of Wet and Dry granulator

Stability Study, Purpose:

Stability Study, The purpose of this SOP is to define the procedures to be followed in the management of stability studies throughout the stability study lifecycle from study initiation to study completion.

Stability Study, Scope:

[][]This procedure is applicable for
[][]Development of New Product.
[][]Reformulation of existing products.
[][]Routine study of commercial batches.
[][]Change of specification of raw and primary packing material.
[][]Process change.
[][]Change of batch size.
[][]Rework reprocess and investigational batches.
of all pharmaceutical products  at XX Pharmaceuticals limited.

Definitions / Abbreviation:

Stability Studies:

[][]Long-term and accelerated (and intermediate) studies undertaken on Development and/or production batches according to a prescribed stability protocol to establish the shelf-life of an finished pharmaceuticals product.

Accelerated Testing:

[][]Studies designed to increase the rate of chemical degradation or physical change of an active substance or pharmaceutical product by using exaggerated storage conditions as part of the formal stability studies.

Long Term Testing:

[][]Stability studies under the recommended storage condition for the re-test period or shelf life proposed (or approved) for labeling.

Development-scale Batch:

[][]A batch of an FPP manufactured by a procedure fully representative of and simulating that to be applied to a full production-scale batch. For example, for solid oral dosage forms, a Development scale is generally, at a minimum, one-tenth that of a full production scale or 100 000 tablets or capsules, whichever is the larger; unless otherwise adequately justified.

Specification:

[][]A list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges or other criteria for the tests described. It establishes the set of criteria to which an FPP should conform to be considered acceptable for its intended use.

Release Specification:

[][]The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that determine the suitability of an FPP at the time of its release.

Shelf-life Specification:

[][]The combination of physical, chemical, biological, and microbiological tests and acceptance criteria that an FPP should meet throughout its shelf life.

Shelf-life:

[][]The period of time during which an FPP, if stored correctly, is expected to comply with the specification as determined by stability studies on a number of batches of the API or FPP. The shelf-life is used to establish the expiry date of each batch.

Expiry Date:

[][]The date given on the individual container (usually on the label) of a product up to and including which the API and FPP are expected to remain within specifications, if stored correctly. It is established for each batch by adding the shelf-life to the date of manufacture.

Bracketing:

[][]The design of a stability schedule such that only samples at the extremes of certain design factors, e.g. strength and package size, are tested at all time points as in a full design. The design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested.

Matrixing:

[][]The design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations is tested at a specified time point. At a subsequent time point, another subset of samples for all factor combinations is tested. The design assumes that the stability of each subset of samples tested represents the stability of all samples at a given time point.

Container Closure System:

[][]The sum of packaging components that together contains and protects the dosage form. This includes primary packaging components and secondary packaging components, if intended to provide additional protection to the pharmaceutical product.

Responsibilities:

The roles and responsibility are as follows:

Senior Executive, Product Development

[][]Reporting and generation of stability protocol and stability report for new products
[][]Identify the need for stability study
[][]Sample storage and withdrawal.
[][]Compile and review the trend of analytical test results.
[][]Time to time revision of the SOP.
[][]Prepare Monthly Stability Schedule of new products.

Senior Executive, Quality Control

[][]Prepare, generate & Review Master Stability Schedule
[][]Timely analysis of stability sample and analytical report generation.
[][]Development and validation of finished products analytical method.

Senior Executive, Quality Assurance

[][]Sampling of the commercial batches for real time stability study.
[][]Schedule, reporting and generation of stability protocol and stability report for commercial products.

Head of Quality Assurance

[][]To approve the stability protocol and stability report.
[][]To approve the shelf life and packing instruction of the products to be marketed.

Procedure

Precaution:

All concerned persons have to follow the SOP. Keep The Stability Samples according to instruction and maintain Stability Schedule of individual Product.

Stability study of Development batches

Stability study protocol of Development batches

[][]Executive product development will generate he stability study protocol after completion of the trial batch of the products according to the Annexure I of this SOP
[][]Individual protocol will be used for individual products. In case of any change in the protocol, due to any stability problem, new version of the protocol will be issued, defining change history at the revision details section of the protocol.
[][]Each protocol will have a unique identification number of 20 digits. As following
GPD/SSP/001/XX/01
Where,
GPD stands for General Product Development. In case of Cephalosporin unit, the code will be CPD which indicates cephalosporin Product Development.
SSP stands for Stability Study Protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20xx, in case of the following years
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.

[][]Executive, Product Development will maintain a log Book according to Annexure II of the SOP to record the Protocol Number. Specific protocol shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the protocol and Manager, Quality Assurance will approve the protocol.

Determining Batch Size

[][]Executive, Product Development will determine the batch size of the products. Batch size of the Development batches will be one tenth of the commercial batch. Commercial batch size will be determined from the yearly sales forecast. Depending on the sales volume, the commercial batch size will be either 50 kg or 30 kg. Therefore, Development batch size will be either 5.0 kg or 3.0 kg respectively.

Design of stability Study

For new product stability study, one trial batch and two Development batches will be stored for stability study, also optimization and validation batches will be stored for stability testing.

[][]1 Trial batch
(batch size: Below 1 kg or decided batch size)

[][]2 Development batches
(batch size: 1/10th of Commercial batches)

[][]Commercial Batches (Ongoing)

Reformulation manufacturing / Process change / Specification Change (API / Excipient) , one trial batch and two Development batch will be stored for stability study, also optimization and validation batches will be stored for stability testing.

[][]1 Trial batch
(batch size: Below 1 kg or decided batch size)

[][]1 Development batch
(batch size: 1/10th of Commercial batches)

[][]Commercial Batches (Ongoing)
(Accelerated & Long Term)

New Source Development (Primary Packaging Material) / Equipment Change

[][]Trial run with new packing material / equipment

[][]Accelerated Stability study on Commercial batches

Number of sample to be stored

Executive, Product Development will store required quantity of sample according to the dosage form .In case of matrixing number of sample to be stored will be generated from the protocol.

Storage condition

[][]Storage condition of stability sample should be as per WHO assigned climatic Zone which is mentioned below:

Climatic Zone	Accelerated	Long term
Zone I	40°C ± 2°C/75% R.H. ± 5% R.H.	21°C ± 2°C/45% R.H. ± 5% R.H.
Zone II	40°C ± 2°C/75% R.H. ± 5% R.H.	25°C ± 2°C/60% R.H. ± 5% R.H.
Zone III	40°C ± 2°C/75% R.H. ± 5% R.H.	30°C ± 2°C/35% R.H. ± 5% R.H.
Zone IVA	40°C ± 2°C/75% R.H. ± 5% R.H.	30°C ± 2°C/65% R.H. ± 5% R.H.
Zone IVB	40°C ± 2°C/75% R.H. ± 5% R.H.	30°C ± 2°C/75% R.H. ±5% R.H.

[][]In case of storage in refrigerator (2°C – 8°C) indicated products storage condition and minimum testing time should be maintained as

Study	Storage condition	Minimum time period
Long term	50 C ± 30 C	12 months
Accelerated	250C ± 20C / 60 ± 5% RH	06 months

[][]In case of storage in freezer (-20°C ± 5°C) indicated products storage condition and minimum testing time should be maintained as  Long term storage condition shall be  (-20⁰ C ± 5⁰ C) for 12 months.

[][]As per WHO guideline Bangladesh is in Zone IVA. So, the stability study shall be done as per Zone IVA for the products marketed in Bangladesh only.
[][]Executive, Product Development will store the sample in the following conditions and for mentioned time period (at minimum) for initial submission to drug authority.

Study	Storage condition	Minimum time period covered by data at submission to Regulatory
Long term	30°C ± 2°C/65% R.H. ± 5% R.H.	12 months
Accelerated	40°C ± 2°C/75% R.H. ± 5% R.H.	6 months

[][]If 30°C ± 2°C/65% R.H. ± 5% R.H. or 30°C ± 2°C/75% R.H. ±5% R.H. is the long term condition there is no intermediate condition.

Bracketing

[][]Bracketing can only be done if the following criteria is meet
[][]Three or more strength of the products are to be stored for stability.
[][]Products are prepared by the same blend or same pellets by only varying the final weight.
[][]Packing materials for all strength are same.
[][]If all the above mentioned criteria are met, Executive, Product development will specify the bracketing design in the section 10 of the stability protocol.
[][]If applied shelf life for all strength will be declared by only assessing the minimum and maximum strength of the product. For example, if a tablet dosage form has three different strengths like 20 mg, 40 mg and 80 mg, only 20 mg & 80 mg strength may be selected for conducting stability study at all time points. The intermediate strength will then be represented by the stability of the extremes tested.

Matrixing

[][]The following factors can typically be matrixed
Strength (same formulation)
Container size
Container fill sizes
Intermediate time points
[][]The following factors should not be matrixed
Initial and final time points
Test parameters e.g. assay, related substances, pH
Dosage forms
Strength of significantly different formulation
Storage condition

[][]Bracketing and matrixing should not be applied together.
[][]Accelerated storage condition should not be matrixing, only long time test frequency may be matrixed.
Matrixing can be done in batches of the same formulation that are manufactured using same process and same machineries.
[][]Certain batches will be exempted from analysis at certain time point. but following time points must be considered for full scale analysis
Initial time point
06 Month time point
24 month time point with 18 month time point in case of the products with 18 month shelf life.

[][]Executive, Product Development will define the matrixing design at the section 10 of stability protocol.

Storage of stability sample

[][]A sample will be considered for stability storage if it meets the following criteria
[][]Batches prepared by same formulation using API from the same source
[][]Batches prepared using same manufacturing process and machinaries
[][]Batches meeting all specification as outlined in section 11 of the stability protocol
[][]Batches packed in the same container closer system

[][]After approval of the stability protocol, executive, product development will store the necessary quantity of sample  in the stability chamber.
[][]Executive product development will maintain the log book of stability sample storage log book (Annexure III).
[][]Individual log book would be maintained for individual stability chamber.
[][]Chamber number, tray number and position of sample stored must be mentioned clearly in the log book.
[][]Stability chamber tray is numbered numerically from 1 to 8 from top to bottom.

Tray and position number like 1A denotes that the sample is stored in 1st tray and in the rear left position of the tray.

Monthly stability schedule

[][]After storing sample in the stability chamber, executive, product development will entry the product name in the stability schedule. (Annexure IV)
[][]Stability schedule will be printed monthly from the live data, and will be stored in the stability chamber room at the beginning of the month.

Withdrawal of stability sample

[][]Based on the stability schedule, operator, product development will withdraw sample from the specific stability chamber.
[][]Sample will be withdrawn on due date whenever possible, but in case of any circumstance sample may be withdrawn within 7 days after the storage date. No sample will be withdrawn before the expected sample withdrawal date.
[][]After withdrawal of every sample, operator, product development will sign in the sample storage log book.
[][]Executive, product development will assign unique lab control number in every sample and maintain the stability sample analysis register (Annexure V) of this SOP.
[][]Executive, product development will analyze the sample and put the report in product master file, he will also put the data in stability trend.(Annexure VI)
Stability study report of Development batches.
[][]After completion of both the accelerated and long term stability testing executive, product development will generate a stability study report according to the Annexure VII of this SOP.
[][]Each report will have a unique identification number of 20 digit. As following
GPD/SSR/001/15/01
Where,
GPD stands for General Product Development. In case of Cephalosporin unit the code will be CPD which indicates cephalosporin Product Development.
SSR stands for Stability Study Report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 2015, in case of the following years 16, 17 etc will be used.
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.

[][]Executive, Product Development will maintain a log Book according to Annexure VIII of the SOP to record the Report number. Specific report shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the report and manager, Quality Assurance will approve the report.
[][]One copy of the report will be provided to quality compliance department for assigning shelf life to the commercial batches.
[][]One copy of the stability report will be generated to the regulatory department for regulatory submission.

Stability study of market sample

[][]A comparative study with the market sample will be done in case of all new products.
[][]Executive, product development will raise requisition for the amount of market sample required to supply chain department.
[][]Executive, product development will store the market sample in stability chamber with the stability batches.
[][]Only accelerated stability study will be done for comparison with the market sample.

[][]Executive, product development will send the sample of market products with the SAF along with the stability batches.
[][]Executive, product development will assign a unique lab control number to the SAF and analyze the sample.
[][]After analysis the analytical reports will be stored in the market products file and the analytical data will be entered in the stability trend (Annexure VI)
[][]After completion of the accelerated stability study a comparative result of the Development batch and market sample will be provided with the accelerated stability report.

Stability study of commercial batches

[][]Stability study protocol of commercial batches

[][]Commercial batches that will undergo stability study are as follows

Batches	Accelerated study	Long term study
Optimization batches	Y	--
Validation batches	Y	Y
Change in the source of active raw materials: First three batch	Y	Y
Change in the source of major excipients: First batch. (Only if the excipients constitute more than 70 % of the total mix)	Y	--
Change in manufacturing process: First three batch after change	Y	Y
Change in manufacturing equipment: First three batches after change.	Y	Y
Change in manufacturing formula: First three batches after change.	Y	Y
Change in batch size.	Y	Y
Reprocess / Rework batch: Specific batch.	Y	--

Y indicates the type of stability study to be conducted. Indicates no stability will be done for this storage condition.

[][]Executive, quality compliance will generate stability study protocol (Annexure I) of commercial batches
[][]Each protocol will have a unique identification number of 20 digit. As following
QCOM/SSP/001/15/01
Where,
GQCOM stands for G Block Quality Compliance.
SSP stands for Stability Study Protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 2015, in case of the following years 16, 17 etc will be used.
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.

 

[][]Assistant manager, quality Assurance  will check the protocol and manager, quality compliance will approve the protocol.
[][]The protocol will be generated by keeping the batch number portion of the protocol blank. Executive, quality compliance will fill the portion while he will store certain batches in stability.
[][]Long term stability testing will continue for shelf life plus one year, for example if the product is assigned with 24 month shelf life tehn the study will be designed for 24 plus 12 that is for 36 month.

Storage of stability sample

[][]After approval of the stability protocol, executive, quality compliance will send the required quantity of sample to product development department along with the protocol and stability sample.
[][]Executive, product development will receive the sample and store the sample in the stability chamber after filling the log book (Annexure III)

Monthly stability schedule

[][]After storing the stability samples, executive, product development will fill the stability schedule (Annexure IV).
[][]At the beginning of the month executive, product development will print the schedule for the specific month and after signing from the department in charge send the schedule to quality compliance department.

Withdrawal of stability sample

[][]Executive, Quality Assurance will generate a Sample Advice Form (SAF) to product development department, based on the stability schedule.
[][]The SAF should be sent on due date, but due to any circumstance it may be sent after the expected date, no sample will be withdrawn before the schedule date.

[][]After receiving the Sample Advice Form from operator, product development will withdraw the sample and provide the sample to quality compliance department. He will sign in the logbook for sample withdrawal.
[][]Executive, quality Assurance will send the Sample Advice Form from along with the sample to quality control department.
[][]Executive, quality control will receive the sample and assign a unique lab control number and analyze the sample. After analysis executive, quality control will store the data in quality control department and put the result in stability trend.

Stability study report of commercial batches

[][]After completion of the accelerated and long term stability study executive quality compliance will generate the stability study report according to Annexure VII of this SOP.
[][]Each report will have a unique identification number of 20 digit. As following
QA/SSR/001/XX/01
Where,
QA Quality Assurance
SSR stands for Stability Study Report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20XX, in case of the following years
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][]Senior executive, product development will check it and assistant manager quality compliance will review. Manager quality assurance will approve the report.
Significant change criteria“Significant change” for an Finished Pharmaceutical Products are:
[][]A change from the initial content of API(s) of 5% or more detected by assay, or failure to meet the acceptance criteria for potency when using biological or immunological procedures.
[][]Any degradation product exceeding its acceptance criterion.
[][]Failure to meet the acceptance criteria for appearance, physical attributes and functionality test
[][]Also, as appropriate for the dosage form:
[][]Failure to meet the acceptance criterion for pH; or
[][]Failure to meet the acceptance criteria for dissolution for 12 dosage units.

Data evaluation procedure

[][]In general, a provisional shelf-life of 24 months will be established provided the following conditions are satisfied:
[][]The API is known to be stable (not easily degradable).
[][]Stability studies, of API, have been performed and no significant changes have been observed.
[][]Supporting data indicate that similar formulations have been assigned a shelf-life of 24 months or more.
[][]Long-term studies to be continued until the proposed shelf-life has been covered, and the results obtained will be submitted to the national medicines regulatory authority.
[][]Alternatively, after the availability of sufficient long term data, shelf life will be declared following any of the following process:
[][]If the Accelerated stability data shows no significant change, the long term data shows little or no variability and the accelerated data also shows little or no variability then shelf life will be declared as double the time of available long term data but, it should not exceed long term data availability time + 12 month (Y = 2X, but should not exceed Y = X + 12 Month, Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 2 x 12 = 24 Month. If 24 month long term data will be available, shelf life will be 24 + 12 = 36 month but not 24 x 2 = 48 month.

[][]If accelerated data shows significant change, but long term data shows no significant change and shows little or no variability, a statistical analysis will be performed with graphical representation with 5% upper and lower acceptance criteria. Available data will be then extrapolated to figure out time to attain the lower acceptance criteria.

[][]If backed by the above graphical representation shelf life will be declared as 1.5 time of available long term data but, it should not exceed long term data availability time + 6 month (Y = 1.5X, but should not exceed Y = X + 6 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 1.5 x 12 = 18 Month. If 24 month long term data will be available, shelf life will be 24 + 6 = 30 month but not 24 x 1.5 = 36 month.

[][]If the Accelerated stability data shows no significant change, the long term data shows variability and the accelerated data also shows little or no variability a statistical analysis will be performed with graphical representation with 5% upper and lower acceptance criteria. Available data will be then extrapolated to figure out time to attain the lower acceptance criteria.

[][]If backed by the above graphical representation, shelf life will be declared as double the time of available long term data but, it should not exceed long term data availability time + 12 month (Y = 2X, but should not exceed Y = X + 12 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 2 x 12 = 24 Month. If 24 month long term data will be available, shelf life will be 24 + 12 = 36 month but not 24 x 2 = 48 month.

[][]If sufficient data are not available to perform the statistical analysis shelf life will be declared as 1.5 time of available long term data but, it should not exceed long term data availability time + 6 month (Y = 1.5X, but should not exceed Y = X + 6 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 1.5 x 12 = 18 Month. If 24 month long term data will be available, shelf life will be 24 + 6 = 30 month but not 24 x 1.5 = 36 month.

[][]If the Accelerated stability data shows no significant change, the long term data shows variability and the accelerated data also shows variability a statistical analysis will be performed with graphical representation with 5% upper and lower acceptance criteria. Available data will be then extrapolated to figure out time to attain the lower acceptance criteria.

[][]If backed by the above graphical representation, shelf life will be declared as double the time of available long term data but, it should not exceed long term data availability time + 12 month (Y = 2X, but should not exceed Y = X + 12 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 2 x 12 = 24 Month. If 24 month long term data will be available, shelf life will be 24 + 12 = 36 month but not 24 x 2 = 48 month.

[][]If sufficient data are not available to perform the statistical analysis shelf life will be declared as 1.5 time of available long term data but, it should not exceed long term data availability time + 6 month (Y = 1.5X, but should not exceed Y = X + 6 Month Where Y = proposed shelf life, and X = period covered by long term data). Such as if a product meets all the above criteria with 12 month long term data, then shelf life will be 1.5 x 12 = 18 Month. If 24 month long term data will be available, shelf life will be 24 + 6 = 30 month but not 24 x 1.5 = 36 month.

Labeling statement for finished product

[][]As the accelerated storage condition is 40°C ± 2°C/75% R.H. ± 5% R.H, and the long term storage condition is 30°C ± 2°C/65% R.H. ± 5% R.H. then the storage condition in final pack should include “ Do not store above 30°C”.
[][]Semi-finished and ready to fill materials
[][]In case of semi-finished and ready to fill material shelf life will be based on manufacturers declared shelf life regardless of date of dispensing.

Photostability Testing

[][]Selection of product/batch
[][]Photostability testing will be conducted for the finished products of which photo sensitivity is known. Products that are not photosensitive will not fall under the criteria of photo stability testing Photostability will be done for the Development batches and the validation batches only.
[][]Photostability will be conducted in following cases
[][]For new products
[][]Any change in the formulation
[][]Any change in the immediate pack
[][]Any change in the marketing pack
[][]From the three Development and trial batch, one Development batch will be stored for photostability, if the result from one batch is not conclusive then two other batch will be stored for photostability.
[][]From the three validation batch, one batch will be stored for photostability, if the result from one batch is not conclusive then two other batch will be stored for photostability.

Design of photostability

[][]Products will be stored in three following types
[][]Fully exposed products (products without any packing, coated if coating is incorporated)
[][]Products in immediate pack (eg. Blister or glass bottle or vial, ampoule)
[][]Products in the marketing pack (eg. Inner carton)
[][]Along with a controlled sample, this will be covered with aluminum foil to assure complete protection light.

Photostability testing protocol of Development batch

[][]Executive, product development will generate photostability testing protocol of Development batch according to Annexure IX of this SOP
Individual protocol will be used for individual products. In case of any change in the protocol, due to any stability problem, new version of the protocol will be issued, defining change history at the revision details section of the protocol.
[][]Each protocol will have a unique identification number of 20 digit. As following
PD/PSP/001/XX/01

Where,
PD stands for Product Development.
PSP stands for photo stability protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20X, in case of the following years
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][]Executive, Product Development will maintain a log Book according to Annexure X of the SOP to record the Protocol Number. Specific protocol shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the protocol and Manager, Quality Assurance will approve the protocol.

Number of sample to be stored

Number of sample stored will follow the following criteria

[][]Sample type/Number of sample
[][]Fully exposed sample /60 pcs
[][]Sample in immediate pack /60 pcs
[][]Sample in marketing pack /60 pcs
[][]Controlled sample /60 pcs

Sample storage procedure

[][]Executive, product development will store sufficient sample in the stability chamber after approval of the protocol
[][]He will provide input in the photostability sample storage log book (Annexure XI), he will provide input regarding the sample withdrawal time at the same time.
[][]Time requirement for sample to be stored should be calculated based on the procedure outlined

Withdrawal of sample

[][]Executive, product development will input the required time in photostability sample storage log book, in case of withdrawal time falling in the off time sample will be withdrawn at next possible time, no sample will be withdrawn before the schedule time.
[][]Operator, product development will OFF the light and withdraw the sample at scheduled time, and after wraping the sample with light protected barrier provide the sample for analysis.

Storage condition and procedure

[][]Executive, product development will define the position number in the tray, the tray is divided in supplied  position
[][]Executive, product development will define the position of each sample in the protocol from the above figure.
[][]He will ON the flurosence lamp and the UV lamp and take three reading of the flurosence light and UV light and from the average data will calculate the time required to attain the sufficient exposure time from the following equation

[][]Time required for flurosence light (H) = 1.2 x 1000000 / average data
[][]Time required for UV light (H) = 200 x 1000000 / average data x 10000
[][]After estimating the required time, executive, product development will determine when UV light will be kept OFF and when the sample will be withdrawn.
[][]Executive, product development will take reading of the both light twice daily, within the scheduled time at 8.30 AM in the morning and 4.30 PM in the evening, to figure out the actual values of light during sample stored.
[][]He will note the values daily in the photostability testing protocol.

Analysis of sample

[][]Executive, product development will analyze the samples along with the controlled sample after the end of the exposer time.
[][]In case of Tablet or Capsule a composite sample of 20 pcs will be analyzed.
[][]In case of other samples (eg. Suspension or vial/ampoule) homogeneous sample must be used for determination.
[][]Following test parameters will be tested after the exposed time
[][]Appearance
[][]Assay
[][]Degradants
[][]Clarity or color of solution (for suspension and vial/ampoule)
[][]Disintegration and dissolution for tablet and capsules.
[][]After completion of the analysis, executive, product development will submit the analytical result for evaluation.

Photostability testing report of Development batch

After completion of both the accelerated and long term stability testing executive, product development will generate a stability study report according to the Annexure II of this SOP.

[][]Each report will have a unique identification number of 20 digit. As following
PD/PSR/001/XX/01
Where,
PD stands for Product Development.
PSR stands for photostability study report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 20XX
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][]Executive, Product Development will maintain a log Book according to Annexure X of the SOP to record the report number. Specific report shall be used for specific products and same number shall never be issued for two products.
[][]Senior executive, product development will check the report and manager, quality assurance will approve the report.
[][]One copy of the report will be provided to quality compliance department for assigning shelf life to the commercial batches.
[][] Photostability study protocol of commercial batch
[][]Executive, quality compliance will generate photostability testing protocol of commercial batch according to Annexure VIII of this SOP
[][] Individual protocol will be used for individual products. In case of any change in the protocol, due to any stability problem, new version of the protocol will be issued, defining change history at the revision details section of the protocol.
[][]Each protocol will have a unique identification number of 20 digit. As following
QA/PSP/001/XX/01
Where,
QA stands for Quality Assurance
PSP stands for photo stability protocol.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
XX stands for the year 20XX.
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][] Executive, Quality Assurance will maintain a log book according to Annexure XIII to record the report number. Specific protocol shall be used for specific products and same number shall never be issued for two products.
[][]Assistant manager, Quality Assurance will check the protocol and Manager, Quality Assurance will approve the protocol.
[][]Quantity of sample stored will be same as the section 7.7.4 of this SOP, storage conditions will be same as the section 7.7.5 of this SOP
[][]Storage of stability sample
[][]After approval of the stability protocol, executive, quality compliance will send the required quantity of sample to product development department along with the protocol and stability sample.
[][]Executive, product development will receive the sample and store the sample in the photo stability chamber after filling the log book.
[][] Withdrawal of stability sample
[][]Executive, quality compliance will generate a Sample Advice Form (SAF) to product development department, based on the stability schedule.
[][] The SAF should be sent on due date, but due to any circumstance it may be sent after the expected date, no sample will be withdrawn before the schedule date.
[][]After receiving the SAF operator, product development will withdraw the sample and provide the sample to quality compliance department.
[][]Executive, quality assurance will send the SAF along with the sample to quality control department.
[][] Executive, quality control will receive the sample and assign a unique lab control number and analyze the sample. After analysis executive, quality control will store the data in quality control department and put the sample in stability trend.

Photostability study report of commercial batch

[][]After completion of the photostability study executive quality compliance will generate the stability study report according to Annexure – IX of this SOP.
[][]Each report will have a unique identification number of 20 digit. As following
QA/PSR/001/XX/01
Where,
QA stands for General Quality Assurance.
PSR stands for Photostability study report.
001 in the numerical serial number, first protocol of the year will bear number 001, second one 002 and continue till the end of the year.
15 stands for the year 20XX
01 stands for the version number. Second version will bear the number 02 and so on.
/ stands for separator in all case.
[][] Senior executive, product development will check it and assistant manager quality compliance will review. Manager quality assurance will approve the report.
[][]Evaluation of data
[][]Sample data will be evaluated against the data of the controlled sample for any change in samples.
[][] Depending on the extent of change special labeling or packaging will be designed to mitigate exposure light.

Labeling information

Depending on the extent of change storage information like “Protect from light” will be incorporated in the marketing pack.

Annexure:

Annexure – I : Stability study protocol.
Annexure – II : Stability study protocol log book for Development batch.
Annexure – III : Stability sample storage log book.
Annexure – IV : Monthly stability schedule.
Annexure – V : Stability Sample analysis register.
Annexure – VI : Stability trend.
Annexure – VII : Stability study report.
Annexure – VIII : Stability study report log book for Development batch.
Annexure – IX : Photostability study protocol of Development batch.
Annexure – X : Photostability protocol logbook of Development batch.
Annexure – XI : Photostability sample storage log book.
Annexure – XII : Photostability study report of Development batch.
Annexure – XIII : Photostability report log book of Development batch.

Correspondence with regulatory affairs , Purpose:

Correspondence with regulatory affairs , The purpose of this SOP is to describe the procedures of the following activities related with the regulatory affairs, Namely
[][]Recipe preparation
[][]Annexure Preparation
[][]Sample sending procedure to DGDA for INN Products.
[][]Annexure amendment as and when necessary.
[][]To comply with the cGMP as well as DGDA requirements.

Correspondence with regulatory affairs , Scope:

This procedure is to be followed for recipe preparation, Annexure preparation, sample sending to DGDA for INN products and Annexure amendment procedure in of XX Pharmaceuticals Limited.

Definition of Terms:

[][]SOP: Standard Operating Procedure
[][]DA: Drug Administration
[][]INN: International Nonproprietary Name
[][]cGMP: Current Good Manufacturing Practice.
[][]QA: Quality Assurance
[][]QC: Quality Control
[][]PD: Product Development
[][]RA: Regulatory Affairs
[][]SCM: Supply Chain Management
[][]COA: Certificate of Analysis
[][]MOA: Method of Analysis
[][]W/S: Working Standard

Responsibilities:

The roles and responsibility are as follows:

Executive / Sr. Executive, PMD

[][]Generation of recipe.
[][]Generate pack size and brand name of the products.

Executive / Sr. Executive, Product Development

[][]Recipe and Annexure Preparation after completion of stability study
[][]Provide sample and stability data of INN products for submission to DA
[][]Provide Annexure amendment form and other related documents for Annexure amendment

Manager, Regulatory Affairs

[][]Recipe, Annexure, INN product sample and Annexure amendment form Submission to DA and provide approved recipe to QA
Update to QA, PD about any changes or requirements of DA

Executive / Sr. Executive, Quality Control

[][]Analysis of INN product sample send to DA

Head of Plant Operation

[][]Review Recipe and Annexure prior send to DGDA

Head of Quality Assurance

[][]Review the Recipe and Annexure prior send to DGDA.
[][]Approve the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements.
[][]Implementation of the SOP

Precaution(s):

[][]All concerned persons have to follow the SOP.
[][]Any deviation from the stated procedure should be documented and reported to the supervisor for corrective measure.

Procedure:

[][]Procedure for product proposal and feasibility testing
[][]PMD will generate the Recipe after finalization of product brief and based on technical feasibility.
[][]Recipe will be submitted according to the Annexure – I of this SOP
[][]Executive / Sr. Executive, PMD will fill the product data sheet and the section 6 and 7 of the Annexure and send to Product Development Department.
[][]Executive / Sr. Executive, Product development will fill the technical data section of the Recipe carefully and send the Recipe to GM Plant for further checking and signing in the particular section.
[][]After signing Product development will send the recipe to Head of QA for checking and signing in the particular section.
[][]After approval of the Recipe regulatory affairs shall conform to QA about the approval.
[][]Procedure for Annexure Preparation
[][]Necessary documents to be provided for product inclusion includes
Application for new product inclusion to the director of DA
Recipe approval form from DA
Product Inclusion fee
For INN products necessary quantity of sample (as described by DA) and analytical method of the product.
Text of the packing materials
Accelerated Stability data of the product.
Annexure.
[][]Regulatory Affairs will provide the application, Recipe approval form and product inclusion fee.
[][]PD will generate the Accelerated Stability Data of the product after completion of six month stability
[][]PD will prepare the Annexure after completion of six month accelerated stability.
[][]Annexure for Non Biological drugs will be filled through Annexure I and for Biological drugs will be filled through Annexure II of DA.
[][]Manufacturing License no for Biological and Non Biological License will be checked before filling the corresponding Annexure.
[][]Brand name and blister/bottle/ampoule/vial per pack must be checked before filling the Annexure
[][]Formulation of the product must be filled according to the Stable pilot batch formulation after completion of six month stability.
[][]Compendial reference must be checked for active materials and excipients while filling the Annexure.
[][]Annexure must be filled as Quantity per tablet/capsule for tablet and capsule dosage forms, Quantity per 100 ml for PFS/Syrup/Suspension/ampoules, Quantity per vial for injectable vials.
[][]After completion of Annexure, Manager QA shall check the formulation according to the stable pilot batch formulation and send it to the RA along with other documents.
[][]Regulatory Affairs will arrange for submission and approval of the Annexure from DA.
[][]After approval of the Annexure ,RA will send copies of the Annexure to QA and PD.

Procedure for Sample Sending of INN Products

Required documents for sample sending to the DA are
[][]Application for approval of INN products to director of DA.
[][]Recipe approval form from DA
[][]Fees for analysis
[][]Required quantity of sample of different dosage forms as required by DA
[][]Method of analysis of the active materials as supplied by the manufacturer.
[][]Certificate of Analysis of the active materials.
[][]Working Standard/ Reference Standard of the active materials.
[][]Method of analysis of the finished product
[][]Sample Chromatogram of the active materials.

[][]Regulatory Affairs will arrange for the submission of application, Recipe approval form and fees for analysis to the DA

[][]Quality control will arrange the MOA supplied by the manufacturer, COA and WS and the sample chromatogram after the initial analysis of the sample to be sent to DA.
[][]Manager, QA will check all the documents and arrangement to send to Regulatory Affairs
[][]Regulatory Affairs will arrange the submission to the DA and after the approval will send copies to QA, PD and QC.

Procedure for Annexure amendment

An Annexure can be amended in following cases (not limited to)
[][]Any change in the formulation than the approved Annexure after the process validation.
[][]Inclusion or exclusion of any excipients than the approved Annexure.
[][]Increase or decrease in the quantity of Excipients than the approved Annexure
[][]After any reformulation work.
[][]PD will arrange the justification of Annexure amendment form according to the Annexure – III

[][]In case of inclusion or exclusion of excipients corresponding row will be left blank.
[][]Head of QA and GM plant operation will check the requirements of the justification of Annexure amendment and the formulation and sign for approval.
[][]PD will generate the revised Annexure following step .
[][]Manager, QA will check the revised Annexure according to the revised formulation (pilot batch or validation batch) and documents to RA.
[][]RA will submit and amend the Annexure accordingly and send approved copies to QA.
[][]QA will send revised approved Annexure to PD and SCM and obsolete the previous Annexure.

Annexure:

Annexure – I: Recipe format
Annexure – II: Annexure format
Annexure – III: Format of Annexure amendment form.