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 )

Calibration of pH meter, Purpose :

Calibration of pH meter, The purpose of this SOP is to describe the operation, calibration and cleaning of pH meter (Model: Mettler Toledo Seven Compact S220) used for the measurement of pH in the quality control and microbiology laboratory.

Calibration of pH meter, Scope :

This procedure describes the application of pH meter, for the determination of pH, in the analysis of raw materials, intermediates and formulated drug product in the quality control and microbiology laboratory of xx Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.
[][]QC: Quality Control.
[][]pH: The pH is a number which represents conventionally the hydrogen ion concentration of an aqueous solution. It is the measurement of the acidity or alkalinity of an aqueous solution.
[][]Calibration: The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system or values represented by a material measure and the corresponding known values of a reference standard.
[][]KCl: Potassium chloride.

Procedure:

Precaution(s):

[][]Store the electrode in 3M KCl solution; never store it in distilled or demonized water or any solution containing heavy metal ions as it may block the electrode membrane.
[][]Always keep the pH electrode wet and rinse it thoroughly with the sample to be measured before use.
[][]Avoid high humidity environments and static discharges since these are detrimental for a stable pH reading.
[][]Do not measure pH of a solution with high temperature.
[][]Try to avoid special measuring solutions such as Sulphide, high Alkaline, Albuminous solutions those can reduce the life of electrode.
[][]Never stir the electrode vigorously in solution during measurement of pH.
[][]After washing, dry the electrode with tissue paper but do not wipe the end of with tissue paper.
[][]Never stir the electrode vigorously in solution during measurement of pH.
[][]After washing, dry the electrode with tissue paper but do not wipe the end of with tissue paper.
[][]Always use fresh and unused buffer for calibration.
[][]Perform a recalibration:
[][]When reference electrode is changed.
[][]After testing aggressive chemicals (such as strong acid or base).

Calibration:

[][]Switch on the power from its main.
[][]Power on the pH meter and printer.
[][]Remove the electrode from the potassium chloride (KCl) solution, rinse it with purified water and soak the excess water with tissue paper very carefully.
[][]Calibrate the instrument daily before use by the three buffer solutions of pH values 7.00, 4.00 and 10.0.
[][]Immerse the electrode in buffer solution of pH value of 7.00 and stir gently and press [CAL] .
[][]Wait until a stable endpoint has been reached.
[][]Hear the ‘beep’ point.
[][]See the sign (/A) at the right side of the display.
[][]Rinse the electrode with purified water and soak the excess water with issue paper very carefully.
[][]Repeat the steps from 7.1.5 to 7.1.9 for second and third calibration for the standard solution of pH values respectively 4.00 and 10.00.
[][]Select “End”.
[][]Select “Save”.
[][]Select “Data”.
[][]Select “Calibration Data”.
[][]Select “pH”.
[][]Select “Review”.
[][]Select “Expertpro ISM”.
[][]Select “Transfer”.
[][]Select “Exit” for 5 times to reach the main menu.
[][]The slope should be 90% – 105%, i.e. at print data, S(B1/B2) and S(B2/B3) = 90% – 105% and offset value will be ± 30 mV, i.e. at print data, off.(B1/B2) and off.(B2/B3) = ±30 mV.

Electrode condition:

Maintenance of the Reference Electrode:

[][]If the electrode slope value falls rapidly, or if the response becomes sluggish or inaccurate, the following procedure should be performed one by one.
[][]Change the reference electrolyte solution every six months.
[][]Degrease the membrane with cotton wool soaked in soap solution.
[][]Soak the tip of the electrode in 0.1M hydrochloric acid overnight.
[][]If all these fail, the electrode must be replaced with a new electrode.
[][]Any replacement of the electrode must be recorded in the log book
[][]Verify the pH of any check buffer (buffer range: 4-9 pH), if reading is within limit (Certificate value ± 0.05), calibration confirms.
[][]Remove the electrode from buffer solution, rinse it with purified water and soak the excess water with tissue paper.
[][]Rinse the electrode with saturated potassium chloride (KCl).
[][]7.1.26 Record the calibration status in Logbook for daily calibration of pH Meter (Seven Compact S220) as per Annexure – I
[][]Power off the pH meter and printer.
[][]Switch off the power from its main.

Operation

[][]Ensure that working area is clean.
[][]Pour enough sample solution into a measuring beaker so that the level of the sample is above the junction of the electrode.
[][]Ensure that the pH meter is cleaned and calibrated on the day use.
[][]Remove the electrode from the potassium chloride (KCl) solution, rinse it with purified water and soak the excess water with tissue paper very carefully. .
[][]Switch on the power its main.
[][]Power on the pH meter and printer.
[][]Gently stir the sample and dip the pH electrode into the solution.
[][]Press [READ] button and wait until a stable endpoint has been reached.
[][]Hear the “beep” sound.
[][]See the sign (/A) at the right side of the display.
[][]Select “Data”.
[][]Select “Measurement Data”.
[][]Select “Review”.
[][]Select “Partial” by using “↓”.
[][]Select “by measurement mode” by using “↓”.
[][]Select “pH”.
[][]Select “transfer”.
[][]Collect the printed result from the printer.
[][]Select “Exit” for 6 (six) times to reach the main display/menu.
[][]Take the electrode out of the solution and rinse with purified water and soak the excess water by tissue paper.
[][]For additional samples repeat the steps from 7.2.7 to 7.2.20 until the sample has been measured.
[][]After taking the measurement, rinse the electrode with saturated potassium chloride (KCl).
[][]Record the measurement data in the Operation Logbook of pH Meter (Seven Compact S220) as per Annexure – II.
[][]Power off the pH meter and printer.
[][]Switch off the power from its main.

Cleaning and maintenance:

[][]Clean the outside case of the pH meter using a mild detergent or disinfectant (e.g.70% ethanol) if required.
[][]Clean the area around the pH meter and wipe away any spillage immediately. Special care should be exercised when cleaning up concentrated HCl (usually) or concentrated NaOH (usually) used for adjusting the pH of solutions.
[][]When required, clean all wires and contacts to avoid corrosion.
[][]Inspect the cables of the electrodes for any signs of broken insulation.
[][]Inspect the pH electrode for any cracks in its stem or bulb.
[][]Rinse off any salt deposits on the top of the electrode using water.
[][]If contamination of the glass bulb is suspected, restoration can be attempted as follows:
[][]Soak electrode in 0.1 M HCl or 0.1 N HNO3 for 15 minutes.
[][]Oily or greasy deposits may be removed by methanol.
[][]After the cleaning stage, rinse the electrode in distilled water and replace the internal filling solution (4M KCl if appropriate) for at least 1 hour before taking any measurements.
[][]Make sure the electrode is always kept filled with the appropriate filling solution.

Annexure: Calibration of pH meter

Annexure-I: Logbook for daily calibration of Seven Compact S220 pH Meter.
Annexure-II: Operation Logbook of Seven Compact S220 pH Meter.