SOPs

Calibration of Hot plate ,Purpose :

Calibration of Hot plate, The purpose of this SOP is to describe the operation, calibration and cleaning of Hotplate with Magnetic Stirrer (Model: Fisherbrand – FB65312).

Calibration of Hot plate, Scope :

This procedure is applicable for Hotplate with Magnetic Stirrer (Model: Fisherbrand – FB65312), installed in the quality control laboratory for general block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]RPM: Rotations per minute.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of hotplate maintaining safety rules.

Manager, Quality Control

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

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Laboratory coat and thick rubber gloves must be worn while handling the instrument.
[][]Ensure that the main switch and power supply connector are accessible during use.
[][]Remove the plug from the main socket during cleaning.
[][]Never use sharp objects or harsh or abrasive cleaning agents when cleaning.
[][]Spillage must be cleaned up immediately after use.
[][]Do not heat beakers with any type of liquid adhering to backside.
[][]Never touch the top of the plate when the instrument is on.
[][]Never keep the heater in ‘on’ condition, when not in use.
[][]Do not use hotplate until reported faults are repaired.

Operation:

[][]Ensure the equipment is clean, calibrated and free from any dust particle.
[][]Connect the instrument to the main power supply.
[][]Switch ‘ON’ the mains.
[][]Place the beaker containing the solution in the center of the plate.
[][]For stirring option, immerse the Teflon stirring bar into the solution to be stirred.
[][]Switch ‘ON’ the instrument.
[][]Set the required stirring speed (RPM) of stirring bar by means of speed regulator knob. Turn the speed regulator knob clockwise or counter-clockwise to increase or decrease speed respectively.
[][]After stirring is over, slowly decrease the speed to zero by turn knob counter-clockwise.
[][]For heater, set the temperature by rotating the temperature setting knob to the required. It will take 5 to 10 minutes to stabilize. Turn the knob clock wise to increase the temperature or counter clock wise to decrease the temperature.
[][]After heating is over, decrease the set temperature to zero by turn knob counter-clock wise.
[][]Bright red light will flash until surface cools.
[][]After completion of work, switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains when not required.

Calibration:

[][]Calibrate the hotplate once in a year.
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the instrument.
[][]Set the desired temperature using temperature setting knob.
[][]Check the temperature using a duly calibrated thermometer and record the temperature in the calibration information sheet for hotplate with magnetic stirrer (as per Annexure-I).
[][]When instrument do not complies with the specified limits, label “Out of calibration” and get serviced.

Cleaning procedure:

[][]Switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains.
[][]Ensure that the surface of the plate is in room temperature.
[][]De-dust the instrument with a clean dry cloth every day.
[][]Once in a week wet mop the instrument.
[][]Wet mop using a cloth moistened in mild detergent solution and then wipe with a cloth wetted with water.
[][]Afterwards wipe the surface with a clean dry cloth to remove traces of detergent.
[][]Allow to dry the instrument before using it again.

Annexure

Calibration Information Sheet for Hotplate with Magnetic Stirrer

Vortex Mixer , Purpose :

Vortex Mixer , The purpose of this SOP is to describe the operation and cleaning of Vortex mixer (Model: Fisherbrand- ZX Classic), for better or error free use.

Vortex Mixer , Scope :

This procedure is applicable for Vortex mixer (Model: Fisherbrand- ZX Classic) used for mixing the solution or dissolving the various substances into solvent, installed in the quality control laboratory of XX  Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Cephalosporin Quality Control.

Responsibilities

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of vortex mixer maintaining safety rules.

Manager, Quality Control

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

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Do not press the test tube hardly on the mixing head.
[][]Do not vortex any materials for long time.
[][]Maintain the level of test solution into test tube/Vial/test flask to avoid overflow during vortex.
[][]Set the speed control to the minimum, before turning on the mixer.
[][]Disconnect vortex mixer from power source before attempting any cleaning or maintenance procedures.
[][]Never operate without a shaking head securely attached.
[][]Always wear eye protector during use of vortex mixer.
[][]Always have lids on the tubes when solvents and flammables are used on the mixer.
[][]Shake hazardous samples in appropriate containment vessels.
[][]Replace rubber attachments with new ones when these show progressive signs of wear out.
[][]Do not immerse the unit or pour liquids over it as electrical shock may occur.

Operation:

[][]Switch ‘ON’ the mains.
[][]The yellow light will be illuminated.
[][]Use the ‘continuous’ key to select the automatic vortex or manual vortex.
[][]Set the desired speed with the help of the ‘control’ knob.
[][]In case of automatic vortex option, touch test tube/vial on the mixing head to start the vortex automatically.
[][]For manual vortex, place the test tube on the mixing head and then press ‘continuous’ button.
[][]Adjust the vortex speed by turning ‘control’ knob clockwise to increase speed or anti-clockwise to decrease speed.
[][]Vary the speed and/or the angle of contact and pressure against the mixing attachment to achieve the desired mix.
[][]On completion, turn the ‘control’ knob anticlockwise to the minimum.
[][]Remove the test tube at the end of vortex.
[][]Stop the vortex by press ‘continuous’ button.
[][]Switch ‘OFF’ the mains.

Cleaning procedure:

[][]Switch ‘OFF’ the mains and disconnect the power plug.
[][]After each use, wipe down the mixer with a soft, dry cloth.
[][]Keep the unit clean by immediately blotting any spills. Remove the shaking head, if required. Clean the head with mild detergent. Dry thoroughly, before replacing the head on the unit.
[][]Clean the outer surface of the instrument properly with a non-abrasive cloth or sponge, moistened in mild detergent water, once in a week or when required.
[][]Never use harsh or abrasive cleaning agents.
[][]Allow to dry before use it again.

Calibration of orbital shaker, Purpose :

Calibration of orbital shaker, The purpose of this SOP is to describe the operation, calibration and cleaning of Orbital Shaker (Model: Stuart SSL1), used for shaking flask, bottle and beaker to dissolve solids in liquid.

Calibration of orbital shaker, Scope :

This procedure is applicable for Orbital Shaker (Model: Stuart SSL1), installed in the quality control laboratory XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Cephalosporin Quality Control.
[][]RPM: Rotations per minute.

Responsibilities:

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the records properly as per SOP.
[][]To ensure cleaning of orbital shaker maintaining safety rules.

Manager, Quality Control

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

Procedure:

Precaution(s):

[][]Laboratory coat and safety glasses must be worn while handling the instrument.
[][]Ensure that the main switch and power supply connector are accessible during use.
[][]There is a chance of liquid spillage and splashing if containers are over filled and shaken at high speed. Always gradually increase the speed to the desired level. Never set the speed beyond the maximum limit.
[][]Remove the plug from the main socket during cleaning.
[][]The shaker should not be operated at the maximum RPM without a load.
[][]Do not leave the shaker unattended when starting the unit. Be sure all flasks are firmly seated in the platform and securely clutch between screwing bars.
[][]Ensure the speed controller knob are turned off before switch on the instrument.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Place the apparatus on a firm level surface ensuring the platform is free from vibration.
[][]Fit the flasks or bottles or beakers to be shaken between two rubber cushioned horizontal screwing bars and adjust to hold them tightly.
[][]Switch ‘ON’ by pressing the ‘control’ knob.
[][]Red dot in the display shows RPM is selected; this can be adjusted by turn the ‘control’ knob to the right up to desired shaking speed (in rpm). Once the correct speed is displayed press the ‘start/stop’ button to begin motion.
[][]In order to use the timer and RPM press the ‘mode’ button. The red dot on the display moves over to time. The display will show the last stored time in minutes.
[][]Select the desired count down time using the control knob. When the display shows the correct time in minutes.
[][]Rotation can be paused at any time by pressing the ‘start/stop’ button.
[][]Rotation will start again by pressing ‘start/stop’ button and the timer will continue to count down.
[][]The timer can be adjusted without halting the unit. When the timer reaches zero, the unit will be automatically halted and alert will sound.
[][]Press ‘start/stop’ button to revert back to the last time and speed values set or select new value.
[][]The shaking will stop automatically after the desired period and sounds an alert.
[][]Switch OFF completely by pressing the ‘control’ knob. The display will show OFF

Calibration:

[][]Calibrate the orbital shaker once in a year.
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the instrument by pressing ‘control’ knob.
[][]Set the desired time (most commonly used time range) using time setting button.
[][]Check the time using a calibrated stop watch and record the time in the calibration information sheet for Orbital shaker as per Annexure-I.

Cleaning procedure:

[][]Clean the instrument once in a week or when required.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Clean the instrument properly with a non-abrasive cloth moistened in detergent water.
[][]Never use harsh or abrasive cleaning agents.
[][]Allow to dry before use it again.

Annexure:

Annexure-I: Calibration Information Sheet for Orbital Shaker.

Calibration of Ultrasonic Bath, Purpose :

Calibration of Ultrasonic Bath, The purpose of this SOP is to describe the operation, calibration and cleaning of Ultrasonic Bath (Model: Clifton DU-14), used for degassing liquids, dissolving solids in solutions and cleaning laboratory apparatus.

Calibration of Ultrasonic Bath, Scope :

This procedure is applicable for Ultrasonic Bath (Model: Clifton DU-14), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
QC: Quality Control.
[][]Sonication: The act of applying sound energy (usually of the ultrasound type) to agitate particles in a sample.

Executive, QC

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To maintain the records properly as per SOP.
[][]To ensure cleaning of ultrasonic bath maintaining safety rules.

Manager, Quality Control

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

Head of Quality Assurance

[][]To ensure the overall implementation of the SOP.
[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Never put hands in the bath during operations.
[][]Always maintain the liquid level above the minimum level mark.
[][]Disconnect the power supply before moving, emptying or cleaning of bath.
[][]Never operate the unit when dry.
[][]Allow the liquid in the bath to cool down before draining.
[][]Never block or restrict ventilation slots.
[][]Do not place item directly on the bottom of the bath, always make use of the stainless steel basket to suspend the item.
[][]Do not use cleaning fluids which contain concentrations of halogen ions, low pH values or high temperatures when operating the bath for cleaning purposes as these will all increase the risk of corrosion.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Fill the bath with purified water above the ‘MIN’ level mark.
[][]Switch on the bath using the ‘ON/OFF’ switch, located at the rear of the bath.
[][]Place the stainless steel basket into position.
[][]Switch ‘ON’ the heater and press ‘■’ menu button to display “SP1”. Set the desired temperature using ▲ or ▼ key button. Maximum setting 69° C.
[][]After setting temperature, display will flash the temperature four times and then it will be automatically set.
[][]Press ‘■’ menu button twice to display “t”. Set the time using ▲ or ▼ key button.
[][]After setting time, display will flash the time four times and then it will be automatically set or press ‘■’ menu button to set manually.
[][]Place the glassware containing sample onto the stainless steel basket, to prevent touching the bottom of the tank.
[][]To start sonication, press and hold ‘Ο’ button until the Time LED is blinking.
[][]Instrument will stop after set time finished.
[][]Wait until the operation process is completed.
[][]To stop sonication, press and hold ‘Ο’ button until the Time LED is off.
[][]Use suitable tongs to remove the hot glassware from the bath.
[][]Allow the bath to cool.
[][]After completion of work, switch off the bath.
[][]Finally switch off the instrument.

Calibration:

[][]Calibrate the water bath once in a year.
[][]Fill purified water in the bath above the ‘MIN’ level mark.
[][]Switch ‘ON’ the mains.
[][]Switch ‘ON’ the mains of instrument.
[][]Set the desired temperature. Follow operation procedure 7.1.5 to 7.1.6.
[][]Allow 30 minutes to equilibrate.
[][]Check the temperature using a calibrated thermometer/digital thermometer and record the temperature in the calibration information sheet for Ultrasonic bath (as per Annexure-I).
[][]Set the desired time. Follow operation procedure 7.1.7 to 7.1.8
[][]Check the time using a calibrated stop watch and record the time in the calibration information sheet for Ultrasonic bath as per Annexure-I.

Cleaning procedure:

[][]Clean the instrument once in a week or in between when water becomes dirty.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Remove the basket from the ultrasonic bath.
[][]Wash the basket properly with purified water.
[][]Drain the water from the ultrasonic bath.
[][]Wipe the inner surface of the bath with a non-abrasive cloth moistened in water.
[][]Use 10% nitric acid on a cloth (wear suitable gloves) to remove any scale or deposits.
[][]Fill purified water in the bath above the ‘MIN’ level mark.
[][]Put the basket in to the bath.

Annexure:

Annexure-I: Calibration Information Sheet for Ultrasonic bath.

Tap Density Apparatus Calibration, Purpose :

Tap Density Apparatus Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Bulk density apparatus (Model: Electrolab ETD-1020) used for the Bulk density test of raw materials in the quality control laboratory at XX Pharmaceuticals Limited.

Tap Density Apparatus Calibration, Scope :

This procedure is applicable for Bulk density apparatus (Model: Electrolab ETD-1020), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]USP: United State Pharmacopoeia

Responsibility

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Use mask, gloves and safety goggles during handling the instrument.
[][]Disconnect the power supply before cleaning of the instrument.
[][]Prior to use, user must ensure that equipment is calibrated.
[][]Avoid any dust gathering on the bearings.
[][]Do not lubricate the bearings.
[][]Keep the shaft of the cylinder holder and the tip of the cylinder holder clean.
[][]Do not press the cylinder holder when the tapping base of cylinder holder is not touching the anvil.
[][]Place the cylinder in the holder only when the holder is placed on the anvil.

Operation:

[][]Ensure that working area is clean.
[][]Connect power cord of the instrument to mains and switch ‘ON’ the instrument.
[][]Instrument will initialize itself and the display will flash and show the start up screen.

[ELECTROLAB TAP DENSITY
ETD-1020 VER 3.0

[][]Set the mode of operation as USP or USER using the ‘DIGIT SCROLL’ key on the front panel.
[][]In USP mode, instrument will stop after every program and validation; report is available at the end of test.
[][]In USER mode, instrument will stop after the set tap value and no validation and result screen will be available. This method is used only when no. of taps are specified in the method.
[][]Press the ‘METHOD’ key to toggle between USP-I and USP-II method and select the required method.
[][]Press ‘SET’ key to set the test parameter.
[][]Display reads

[TAP COUNT 1: # # # # ▲▼◄
SET : EXIT / Enter : SCROLL

[][]Set the TAP COUNT 1.
[][]Enter the Tap count 1 within 1 to 9999 using the ‘UP/DOWN’ & ‘DIGIT SCROLL’ key.
[][]Press ‘ENTER’ key to go next parameter.
[][]Similarly set TAP COUNT 2 and TAP COUNT 3.
[][]In USP method, set TAP COUNT 1 as 250 taps, TAP COUNT 2 as 500 taps and TAP COUNT 3 as 500 taps.
[][]Set the date and time using the ‘UP/DOWN’ & ‘DIGIT SCROLL’ key.
[][]Select the print option & press ‘SET’ key to scroll back to main menu.
[][]Pass a quantity of material sufficient to perform the test through 20-mesh screen to break up any agglomerates.
[][]Transfer about 100 g sample into a dry 250 ml graduated cylinder with 2 ml accuracy.\
[][]Alternatively transfer a small quantity (less than 100 g) of sample into a 100 ml cylinder with 1ml accuracy to minimize the sample quantity.
[][]Press the ‘START’ key.
[][]Weigh the test sample and enter the weight of test sample.
[][]Press the ‘ENTER’ key to register the weight.
[][]Level the sample without tapping or compacting.
[][]Read the unsettled apparent volume to the nearest graduated unit and enter the volume using the ‘UP/DOWN’ & ‘DIGIT SCROLL’ key.
[][]Press the ‘ENTER’ key to register the volume.
[][]Fix the measuring cylinder into the holder provided for holding the measuring cylinder on the instrument.
[][]Lock the holder assembly.
[][]Press the ‘START’ key again to run the test.
[][]Display will show the elapsed taps and drops per minute.

ELAPSED TAP: # # #
Drops / Min. : # # #

[][]After programmed TAP COUNT 1 is over, measure the tapped volume to its nearest graduated unit.
[][]Enter the measured tapped volume using ‘UP / DOWN’ & ‘DIGIT SCROLL’ Keys.
[][]Press ‘ENTER’ key to register the value.
[][]Press ‘START’ key to continue TAP COUNT 2 program.
[][]Measure the tapped volume at the end of TAP COUNT 2 program and enter the value using ‘UP / DOWN’ & ‘DIGIT SCROLL’ Keys.
[][]The difference between the two counts will be displayed as a result.
[][]If the result after the completion of TAP COUNT 2 is less than 2.0%, press ‘STOP’ key to end the operation and to get the results.
[][]If the result is more than 2.0%, then press ‘START’ key again to start the TAP COUNT 3 program to get a new value.
[][]Repeat the operation till the difference between two succeeding measurements is less than 2.0%.
[][]Press ‘STOP’ key once the desired difference is obtained instrument will display the results.
[][]The results of Bulk density or initial density, tapped density and Hausner ratio and compressibility index will be displayed one after another by using ‘DOWN’ key.
[][]The results shall be recorded separately or taken as a print out.
[][]After operation enter usage details in Operation Logbook of Bulk Density Apparatus as per Annexure – II.

Calibration:

[][]Calibration of Drop distance
[][]Calibrate the instrument once in a year or whenever there is a major maintenance.
[][]Disconnect the instrument from mains.
[][]Gently disassemble the sample holder assembly.
[][]Remove the top cover by unscrewing the holding screws given on the bottom of the instrument i.e. the screws given on the four sides and one screw given on the backside near the power switch. The places are marked for convenience.
[][]Place the sample holder in the slot of USP I and manually rotate the cam wheel so that the holder is at the highest position.
[][]The stem of the holder is now on the top of the highest position of the cam (which is marked as a groove on the wheel.
[][]Measure the distance from base to the bottom of the holder (h1) using a suitable vernier caliper.
[][]Rotate the wheel to get the lowest position, the position from which it started to raise again.
[][]Measure the distance from base to the bottom of the holder (h2) using a suitable vernier caliper.
[][]The difference between the h1 and h2 gives the drop distance.
[][]Record the observations in the calibration information sheet (Annexure –I).
[][]Repeat the same procedure on the USP-II slot.
[][]Record the observations in the calibration information sheet (Annexure –I).
[][]When the distance is not within the prescribed limit, change the teflon bottom of the stem to get the required height.
[][]Carefully replace the top cover and close.
[][]Calibration of Drop rate
[][]Connect the instruments for main and proceed for the calibrations for drops rate.
[][]Switch ‘ON’ the mains.
[][]Select USP-I or USP-II method using ‘METHOD’ key
[][]The indicator light glows in USP-I or USP-II on the front panel
[][]Using ‘SCROLL BAR’ keys, select the USER method and press ‘SET’ key.
[][]Enter the number of taps to 100
[][]Press ‘START’ key and simultaneously start the stopwatch.
[][]Record the time at which the tapping stops in the calibration information sheet (Annexure –I).
[][]Similarly perform the test using 250, 750 and 1250 taps and note the timings
[][]Calculate the drops per minute in both USP-I and USP-II method.
[][]Record the drops per minute in the calibration information sheet (Annexure –I)
[][]If the instrument is out of calibration, inform the Manager, Quality Control.

Cleaning Procedure:

[][]Clean the instrument after every use.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Remove the cylinders from the apparatus and clean the cylinder.
[][]Clean the apparatus with cotton cloth.
[][]Clean the surrounding areas of instrument with a cloth dampen in water.

Annexure:

Annexure-I: Calibration Information Sheet for Tap Density Apparatus.
Annexure-II: Operation Logbook of Tap Density Apparatus

 

Electromagnetic Sieve Shaker Calibration, Purpose:

Electromagnetic Sieve Shaker Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Electromagnetic sieve shaker (Model: Electrolab EMS-8) used for the sieve analysis in the quality control laboratory at XX Pharmaceuticals Ltd.

Electromagnetic Sieve Shaker Calibration Scope:

This procedure is applicable to the Electromagnetic sieve shaker (Model: Electrolab EMS-8), used for conducting sieve analysis and particle size distribution using test sieves, in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]ASTM: American Society for Testing and Material.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Use mask, gloves and safety goggles during handling the instrument.

Operation:

[][]Check the machine is clean and calibrated.
[][]Ensure that the working bench is clean.
[][]Switch on the power from its main and power on the instrument.
[][]Display indicates: ELECTRO – MAGNETIC
[][]SIEVE SHAKER EMS-8
[][]Ensure all the sieve diameter and pore size should be as per ASTM standard. Keep received certificate in appropriate place.
[][]Use certified sieve.
[][]Select the sieves required as per monograph/ procedure.
[][]Check the integrity of the sieves.
[][]Ensure the sieve numbers are matching with the ASTM number given on the sieves.
[][]Place the sieves in the descending order of sieve No. on the collecting pan.
[][]Set the sieves on the instrument, shaker ensures that the value of the amplitude is set at the lowest.
[][]Set the desired time (Maximum 99 minutes) by pressing the time key provided below the “TIME” display.
[][]Set the desired amplitude (power level 5 to 20) by pressing the power key provided below the “POWER” display.
[][]Select Continuous or intermittent mode by pressing “CONTNUOUS” or “INTERMITTENT” key respectively.
[][]Weigh the sample and evenly spread the same on the top sieve and close the sieve.
[][]Place the sieve sets on the base of the holder firmly and lift the assembly to touch the top of the holder.
[][]Tight the assembly and then press “START” key to start the operation.
[][]The shifter works during the time and with the power level programmed. In case of intermittent mode, the shifter will start vibrate at interval of 0.5 second.
[][]After completion of this process carefully remove the sieve set.
[][]Collect the samples retained on each sieve and on the collection pan and weigh the quantity of sample retained on each sieve.
[][]Calculate the percentage of the sample retained on each sieve and put the analysis data in the report sheet of electromagnetic sieve shaker.
[][]Check the integrity of the sieves again, if not ok label it as rejected and discard the same as scrap.

Cleaning of the Sieve:

[][]Do not use dissolvent or any hard material for cleaning.
[][]For sieves less than 500 micron use ultrasonic and detergent. The sieves should be gently cleaned by keeping it in ultrasonic for 4 to 5 minutes.
[][]Cleaning with soft brush followed by ultrasonic cleaning can be used for sieves having mesh size more than 500 micron.
[][]After cleaning sieves should be rinsed thoroughly and left to dry in an upright position.

Cleaning of the Sieve Shaker:

[][]Switch ‘OFF’ the instrument and switch ‘OFF’ from the mains.
[][]Clean the outer surface of the instrument with Isopropyl alcohol and dry it with tissue paper.
[][]Clean the surrounding areas of instrument with a cloth dampen in water

Calibration:

[][]Calibration frequency: once in a year and after every maintenance.
[][]Check the time with calibrated and certified clock at 10, 20, 50, 70 and 90 minutes. The tolerance should be ± 1 minute.
[][]After completing the calibration, maintain the calibration record of Sieve shaker as per Annexure-I.

Annexure:

Annexure–I: Calibration Information Sheet for Electromagnetic Sieve Shaker.
Annexure–II: Operation logbook for Electromagnetic Sieve Shaker.
Annexure–III: List of Sieves.

Karl Fischer Titrator Calibration, Purpose:

Karl Fischer Titrator Calibration, The purpose of this SOP is to describe the operation, standardization of titrants, calibration, cleaning and maintenance of Karl Fischer Titrator (Model: Mettler Toledo V20 Compact) used for the determination of the water content in the quality control laboratory at XX Pharmaceuticals Ltd.

Karl Fischer Titrator Calibration, Scope:

This procedure is applicable to the Karl Fischer Titrator, used for the determination of water content, in the analysis of raw materials, intermediate and formulated drug product, installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]KF: Karl Fischer

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive,

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

Manager, Quality Control

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

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Use mask, gloves and safety goggles during handling the Karl Fischer reagent and methanol under Fume Cupboard.
[][]Do not change stirring speed between the pre-titration and the titration.
[][]Always take some more volume of liquid sample by a syringe and then inject the desired volume.
[][]Clean and dry syringes and needles before use. Rinse the syringe with the sample solution itself 2 – 3 times and then take the test sample. This will remove the moisture from syringe if any.
[][]While testing various samples of which the moisture contents are roughly known, test the sample having lowest moisture first and then go on to the next in order to avoid contamination.
[][]If moisture content of samples are unknown and very small sample to obtain pilot reading and then adjust the size of sample accordingly. Keep next sample ready and if some time is lapsed between two titrations. Press START, get to the end point then add sample immediately. This will eliminate the error due to lapse of time.
[][]If fresh KF reagent is added to the old stock in KF reservoir, mix the solution in reservoir properly and recalibrate the reagent for new factor.
[][]Keep the titration cell tightly closed with stopper and only open for an instant to add sample fast.
[][]When renewing the reagents, clean the titration cell thoroughly with methanol (or another suitable solvent) and may be dried in an even at approximately 70⁰C.
[][]Adjust the filling rate of dispensing burette to avoid the introduction of air bubbles in the burette.

Operation:

[][]Check the cleanliness of the instrument.
[][]Check the calibration status of the Karl Fischer Titrator.
[][]Check the clarity and color of the titrant.
[][]Switch ON the instrument. The instrument always performs a self-test before the display of the Titrator name appears.

Functional description:

[][]The control panel consists of an integrated touch screen and four additional keys, which are located next to the touch-sensitive surface of the display.
[][]Reset, the current task is aborted Info, calls to the online help for the current contents of the current dialog.
[][]Home, always returns to the Home screen (the blue Home keys are located at the bottom right and left of the touch screen).

Rinse and fill burette:

[][]To fill the burette and tubes with titrant and remove any air bubbles from the system, the burette should be rinsed three times with titrant. To do that, use the manual operation “Rinse burette”. Press Home if the home screen is not already displayed.
[][]Select the Manual button to open the Manual operations dialog and press Burette button.
[][]In the Burette dialog, use the Rinse button to access the parameters for the rinse process.
[][]Select the relevant titrant.
[][]For the “Cycles” parameter, enter “3” for three rinse cycles.
[][]Press Start to start the rinse procedure.
[][]When all rinse procedures will be completed, use the ok button to return to the Rinse dialog. The burette should be filled and the hoses should be free of air bubbles.

Filling the titration beaker:

[][]To fill the titration beaker with solvent, the solvent manager must be attached to the solvent bottle.
[][]In the Pump dialog (Home>Manual>Pump), select the “Fill” value for the “Action” parameter.
[][]The “Reset counter” parameter will be activated.
[][]Press Start.
[][]Titration beaker will be filled with solvent.

Performing a volumetric KF titration:

[][]Fill dried Methanol in glass vessel.
[][]In the Home screen, use the Methods button and select the method type “KF vol”. In the subsequent dialog, select the “Mix Time” and enter required time.
Select start button.
[][]Start analysis dialog will be displayed. In this dialog select Number of sample and put “3” and then press Ok.
[][]Select Start button. The system will perform a pre-titration as a basis for a water-free solvent.
[][]As soon as the continually determined drift value falls below a regulated required value, the system automatically switches to Standby mode. In the Standby mode the Start Concentration button will be activated.
[][]Press the Start Concentration button, weigh about 10 mg of purified water as a standard and add into the titration vessel and then enter the sample weight.
[][]Press Sample ID and put the sample ID.
[][]Confirm with Ok. The analysis will be started automatically.
[][]Perform 3 samples analysis and press Result>Statistic>Print.
[][]Average water content and relative standard deviation (RSD) of 3 samples will obtain on the print out.
[][]Standard value of RSD is not more than 2%.
[][]Press Reset and select start button.
[][]Start analysis dialog will be displayed.
[][]When Start button will be selected in the Start analysis dialog, the system first always performs a pre-titration as a basis for a water-free solvent.
[][]As soon as the continually determined drift value falls below a regulated required value, the system automatically switches to Standby mode. In the Standby mode the Start sample button will be activated.
[][]Press the Start sample button, add the sample and then enter the sample weight.
[][]Press Sample ID and put the sample ID.
[][]Confirm with Ok. The analysis will be started automatically.
[][]After completing titration, the Result dialog will be displayed and printed automatically.

Calibration:

[][]Fill dried Methanol in glass vessel.
[][]Select start button.
[][]Start analysis dialog will be displayed. In this dialog select Number of sample and put “3” and then press Ok.
[][]Select Start button. The system will perform a pre-titration as a basis for a water-free solvent.
[][]As soon as the continually determined drift value falls below a regulated required value, the system automatically switches to Standby mode. In the Standby mode the Start Concentration button will be activated.
[][]Press the Start Concentration button, weigh about 100 mg of Di-sodium tartrate dihydrate as a standard and add into the titration vessel and then enter the sample weight.
[][]Press Sample ID and put the sample ID.
[][]Confirm with Ok. The analysis will be started automatically.
[][]Perform 3 samples analysis and press Result>Statistic>Print.
[][]Average water content and relative standard deviation (RSD) of 3 samples will obtain on the print out.
[][]Standard value of RSD is not more than 1%.
[][]Record the result in the “Calibration Information Sheet for Karl Fischer Titrator” as per Annexure-I.
[][]Affix the label “CALIBRATED” on the instrument if all test results are satisfactory. If the calibration result is out of limit or any discrepancy is during calibration, affix “UNDER Maintenance” label and inform the respective supplier.
[][]Calibrate the instrument once in every six month.

Cleaning:

[][]After completion of the testing, press Drain>Start button for removing the solution from the test compartment and wash with methanol which is used for water determination. Wipe the knob of sample compartment with tissue paper.
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]If the drift of the KF solution remains too high, fill the drying tubes with fresh molecular sieve or regenerate molecular sieve in a drying oven at 105 – 150⁰C for at least 24 hrs. Before regeneration rinse the molecular sieve used on the waste bottle with purified water as it contain SO2.
[][]Collect the waste solution into waste beaker at the same time all waste to be thrown to avoid corrosion.
[][]Clean the outer surface of the instrument with Isopropyl alcohol and dry it with tissue paper.

Annexure

Annexure-I: Calibration Information Sheet for Karl Fischer Titrator.
Annexure-II: Operation logbook for Karl Fischer Titrator.

Calibration of Refractometer, Purpose :

Calibration of Refractometer, The purpose of this SOP is to describe the operation, calibration and cleaning of Refractometer (Model: Rudolph J257) used for the determination of the refractive index of raw materials in the quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Refractometer, Scope :

This procedure is applicable to the Refractometer (Model: Rudolph J257), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.
[][]QC: Quality Control.
[][]Refractive index: The refractive index of a medium with reference to air is equal to the ratio of the sine of the angle of incidence of a beam of light in the air to the sign of the angle of refraction of the refracted beam in the given medium.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

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

Manager, Quality Control

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

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of the SOP.

Procedure:

Precaution(s):

[][]Clean off samples with water and then with methanol or a suitable solvent as soon as the measurement is completed in a way to avoid possible scratching in the prism.
[][]Do not use the strong solvents such as N,N- Dimethylformamide or N,N-Dimethylacetamide, Cresol, Phenols and other tar acids.
[][]Never use any hard or metallic objects on the prism surface (where the sample to be measured is placed) as scratches quickly spoil the definition of the borderline.
[][]Disconnect the power supply before moving or cleaning of the instrument.
[][]When not in use, keep the instrument in a safe place.
[][]Prior to use, user must ensure that equipment is calibrated.

Operating procedure

[][]Check the machine is calibrated.
[][]Plug the instruments into an acceptable power source.
[][]Turn the instrument ON.
[][]Wait about 30 minutes to warm up the Refractometer.
[][]Carefully clean the polished surface of the fixed prism with water and then with methanol and dry before applying a sample.
[][]Place a few drops of sample on the polished face of the lower Measuring prism.
[][]Lower the sample cover.
[][]Select the option “measure when stable”.
[][]Press the “Read” button to obtain the sample reading.
[][]Take print out of the result.
[][]Record the operation in the logbook.

Calibration with Purified water, Carbon Tetra chloride and Toluene:

[][]Plug the instruments into an acceptable power source.
[][]Turn the instrument ON.
[][]Wait about 30 minutes to warm up the Refractometer.
[][]Carefully clean the polished surface of the fixed prism with water and then with methanol and dry before applying a sample.
[][]Determine the refractive index of the purified water, Toluene and Carbon Tetrachloride at 20°C.
[][]Place a few drops of sample on the polished face of the lower Measuring prism.
[][]Lower the sample cover.
[][]Select the option “measure when stable”.
[][]Press the “Read” button to obtain the sample reading.
[][]Take print out of the result.
[][]Compile the result & take approval for the calibration information sheet (Annexure-I).
[][]Affix the label “CALIBRATED” on the instrument if all test results are satisfactory.
[][]If the equipment found out of calibration limit affix “UNDER Maintenance” label and inform the respective supplier.
[][]Calibration frequency: Once in a year.

Cleaning procedure:

[][]After completion of the testing switch off the instrument and switch off the mains.
[][]Clean the prism surface with purified water or alcohol or xylene or a solvent which will remove sample residue.
[][]Finally clean with purified water.
[][]Wipe it with tissue paper.

Annexure:

Annexure-I: Calibration Information Sheet for Refractometer with Water, Carbon Tetrachloride and Toluene
Annexure-II: Logbook for Refractometer

Calibration of Viscometer, Purpose :

Calibration of Viscometer, The purpose of this SOP is to describe the operation, calibration and cleaning of viscometer (Model: Brookfield LVDV-II+Pro) used for the measurement of viscosity in the quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Viscometer, Scope :

This procedure is applicable to the Brookfield viscometer, installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.
[][]Viscosity: Viscosity is measure of fluid’s resistance to flow.
[][]FSR: Full Scale Viscosity Range.
[][]cP: Centipoise

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

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

Manager, Quality Control

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

Head of Quality Assurance

[][]Approval of the SOP.
[][]To ensure overall implementation of this SOP.

Procedure:

Precaution(s):

[][]To measure high viscosity, choose a small spindle or select slow speed.
[][]Remove spindle before cleaning.
[][]Prior to operation check the labeling of the viscometer. The label is adjusted using the two leveling screws on the base. Adjust so that the bubble label on the top of the instrument within the circle.
[][]Viscosity measurements should be accepted within the equivalent % of Torque Range from 10% to 100% for any combination of spindle/speed rotation.
[][]Viscosity measurements should be taken under laminar flow conditions, not under turbulent flow conditions.

Calibration procedure:

[][]Switch on the power from its main and power on the viscometer.
[][]Transfer the viscosity standard fluid (Standard Fluid 10, Standard Fluid 500 & Standard Fluid 5000) into 600 ml beaker.
[][]Immerse the beaker along with the spindle into water bath for 1 hour at set temperature 25.0°C.
[][]After 1 hour, check the temperature of the viscosity standard fluid with an accurate thermometer.
[][]Lower the DV-II+ into measurement position of the guard leg.
[][]Attach the spindle to the viscometer. In case of disk – shaped spindle, avoid trapping air bubbles beneath the disk by first immersing the spindle to an angle and then connecting to it to the viscometer.
[][]Measure the viscosity reading normally at 25.0°C ± 0.1°C, must rotate the spindle at least five times before readings are taken.
[][]The viscosity reading should be equal the cP value on the fluid standard to within the combined accuracies of the viscometer & viscosity standard i.e. ± (1% of full scale viscosity range + 1% viscosity Standard Fluid stated value at 25ºC).
[][]Calculate the Full scale viscosity is determined from following equation:
[][]Full scale viscosity [cP] = TK * SMC * 10000/ RPM
Where,
TK = spring torque constant of viscometer (for LVDV-II +Pro model TK value is 0.09373 )
SMC = spindle multiplier constant for spindle [SMC value for the four spindle LV1 (entry code: 61), LV2 (entry code: 62), LV3 (entry code: 63), LV4 (entry code: 64) and LV5 (entry code: 65) are respectively 6.4, 32, 128, 640 and 1280.] [][]RPM: Rotation per minute Compile the result & take approval for the calibration information sheet (Annexure-I).
[][]Carry out the test once in a year.
[][]Affix the label “CALIBRATED” on the instrument if all test results are satisfactory.
[][]If the equipment found out of calibration limit affix “UNDER Maintenance” label and inform the respective Supplier.

Operating procedure:

[][]Check the machine is clean & calibrated.
[][]Make the switch ON of the viscometer.
[][]Let the machine initialize for 10 minutes before performing Auto zero.
[][]Attach the spindle with the lower shaft of the viscometer.
[][]Set the spindle no. by pressing SELECT SPINDLE button.
[][]Set speed by pressing SET SPEED button.
[][]Select the data parameters by pressing SELECT DISPLAY button.
[][]Insert and center spindle in the test materials until the fluid’s level is at the immersion groove on the spindle‘s shaft.
[][]Press the motor ON/OFF/ESCAPE key and turn the motor ‘OFF’ when changing a spindle or changing samples.

Cleaning procedure:

[][]After completion of the testing switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Remove the spindle from the instrument.
[][]Clean the spindle with respective solvent in which solution of sample is prepared.
[][]Clean the spindle with methanol.
[][]Wipe it with tissue paper.
[][]Place the clean spindle at its respective place in the box.

Annexure:

Annexure-I: Calibration Information Sheet for Digital Viscometer
Annexure-II: Calculation Sheet for Viscometer Calibration
Annexure-III: Range for LV Spindle cP (m PaºS )