Search Results for: calibration

Leak Test Apparatus Operation, Calibration and Cleaning

Quality Assurance, SOPs

Leak Test Apparatus , Purpose :

Leak Test Apparatus , The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of leak test apparatus.

Leak Test Apparatus , Scope :

This procedure is applicable for leak test apparatus (Model: Electrolab, LT-101P ) used in the In Process Check of General Block at XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

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

Executive, Quality Assurance

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

Asst. Manager, Quality Assurance

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Laboratory coat must be worn while handling the instrument.
[][]Disconnect the power supply before moving or cleaning of the instrument.
[][]Prior to use, user must ensure that equipment is calibrated.
[][]Preparation of Rhodamine B Dye Solution:
[][]Prepare a 2 liters solution of Rhodamine B dye by dissolving 0.5 gm of the dye in water. Take 800 ml water in a 1000 ml beaker and make it colored by adding about 5 ml of the dye solution.

Operating Procedure:

[][]Place the sample in the desiccators which is filled with Rodamin solution to the desired level.
[][]Connect the vacuum tubing between desiccators and the Vacuum Inlet Nozzle provided on the back panel of the instrument.
[][]Switch ON the power switch, then LCD screen displays LEAK TEST APPARATUS followed by SERIAL NUMBER of the instrument and changes over to Vacuum in mm, Hg and Time.
[][]Press the SET key to change to vacuum and input required data by using UP, DOWN and SHIFT keys.
[][]To change HOLD TIME press the SET key and input required data by using UP, DOWN and SHIFT keys.

[][]To show USER ID on screen, press SET key. To setup USER ID press UP or DOWN key.
[][]To change SAMPLE ID press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]To change No. of samples press the SET key and input required data by using UP, DOWN and SHIFT keys
[][]To change BATCH NO. press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]After all the data is entered, press the ENTER key and then press the RUN key to run the program which is set for required test. Then vacuum release takes place for three seconds and the pump starts and the vacuum built up which is displayed on the LCD screen. If no vacuum builds up then press desiccator top lid for a few seconds.
[][]When vacuum release reaches zero place automatically then press the print key to get full details of the test.
[][]Leak test parameters

Type of product/Pressure/Time

[][]Tablet, Capsule, Vial/450 mm-hg/5 minutes
[][]Powder for Suspension/450 mm-hg/2 minutes

Procedure for setup time, date and serial number:

[][]Switch ON the instrument and press up arrow key until hear a buzzer sound, then shows password.
[][]Enter password.
[][]The password is four digit 8824 and press enter key.
[][]Date format is 2013 02 16 (Year Month Day) and Time format is 12:15(Hours, Minutes).
[][]Input necessary data by using up, down and right shift key, Date and time can be changed.
[][]To show Serial No. on screen press Enter key
[][]Input necessary data by using up, down and right shift key, Serial No. can be changed.
[][]When all data is entered completing then press Enter key.
[][]Switch OFF the instrument.
[][]Switch ON the instrument after few minutes and check the above recorded data and verify.

Calibration procedure:

[][]Calibrated stopwatch and start timer of leak test apparatus and stop watch simultaneously.
[][]Note the reading at intervals of 60 seconds, 180 seconds and 300 seconds respectively.
[][]Acceptance criteria: 10 seconds for each interval.
[][]Vacuum gauge calibration done by external party.
[][]Frequency of calibration: Twelve months (for timer, vacuum gauge and vacuum holding capacity).

Cleaning procedure:

[][]After completion of the testing, switch off the instrument.
[][]Cleaning of leak test apparatus by using purified water and clean outer and inner surface with the help of lint free cloth.
[][]Place the apparatus for dryness for half an hour.
[][]Change the desiccator Rodamin solution twice in a week or as per required.

Annexure:

Annexure-I: Log Book of Leak Test Apparatus.

Leak Test Apparatus Operation, Calibration and Cleaning Read More »

Calibration of Friability Tester With Operation & Cleaning

Product Development, SOPs

Calibration of Friability Tester, Purpose :

Calibration of Friability Tester, The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of friability tester.

Calibration of Friability Tester, Scope :

This procedure is applicable for friability tester (Model: Electrolab, EF-1W ) used in Product Development Laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PD: Product Development

Responsibilities:

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

Executive, PD

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

Sr.Executive, PD

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Make sure the knob is properly fitted on the shaft to assure the drum is held in position.
[][]Do not hold the drum while they are rotating.
[][]Do not use abrasive, aggressive material or solvents to clean the drum and the tray. If required use mild detergent.
[][]Do not use wet drum. Make sure the drum is dry when in use.
[][]Replace the fuse with the correct rating whenever required.

Operating Procedure:

[][]Turn on the power switch of Friabilator.
[][]After power on, the drum would initialise itself to the loading position and the instrument will initialise the weighing scale and the following display will be shown:

ELECTROLAB
EF 1 W FRIABILATOR

[][]The instrument is then ready for the setting of test parameter and to run the test and following display will be shown on the screen:

ELECTROLAB EF 1 W
SET = menu, START = run
[][]Press SET key to set the test parameter as the following way.
[][]The first parameter for the test is MODE selection. Select the Time or Count mode using the MODE key on the front panel. The desired value for the selected mode can be set using or & DIGIT SCROLL keys. Set Count 100 and Time 4 minutes. Press the ENTER key to go to the next parameter.
[][]The next parameter is RPM setting. The desired value from 20 RPM to 50 RPM can be set using the key or and DIGIT SCROLL keys. Set 25 RPM. Press the ENTER key to go the next parameter.
[][]The next parameter is for drum selection. Using the or keys the Friability or the Abrasion drum can be selected. Select the Friability drum. Press the ENTER key to go the next parameter.
[][]The next parameter is for selecting the Scale Connection Option. This option can be enabled (Y) or disabled (N) using or key. If no printer is connected select disabled (N) mode. Press the ENTER key to go to the next parameter.
[][]The next menu is for Clock setting. The default setting for this menu would be the current time. The Time can be adjusted using or key & DIGIT SCROLL key. Press the ENTER key to go to the next parameter.
[][]The next menu is for Date setting. The default setting for this menu would be the current date. The Date can be adjusted using or key & DIGIT SCROLL key. Press the ENTER key to go to the next parameter.
[][]The next menu is for the selection of the option to the last test result. Select No (N) by using or key. Press the ENTER key to go to the next parameter.
[][]The next menu is for the Sound option. Select Yes (Y) using or key.
[][]Press the SET key to exit from the SET menu.
[][]After weighing the test samples as per specific Standard Test Procedure, slide them gently into the drum through the side slit and press START key, input the weight of tablets, press ENTER to run the test.
[][]After the test is over, the drum rotates in the reverse direction, discharging all the test samples into the tray located below the drum.

[][]The drum would now initialize itself to the loading position. Carefully slide the tray out and remove the loose dust from the test samples, i.e. deduct the test samples. After deducting weight the sample, input the weight of deducted tablets, press ENTER, % friability will be displayed on the screen.
[][]Press SET key for performing a new test.

Calibration procedure:

[][]Ensure that the instrument is clean before use, including surrounding area.
[][]Check and ensure due date of calibration.
[][]Switch ON the power supply.
[][]Set the time 4.0 minutes by selecting TIMER key and start the machine and calibrated stopwatch simultaneously.
[][]Note the actual time shown by a calibrated stopwatch.
[][]Take three such readings and calculate the mean time.
[][]Set 100 counts (rotation) by selecting COUNT key (some tablets may be placed into the drum for ease of counting) and start the instrument.
[][]Record the number of rotation.
[][]Take three such readings and calculate the mean of rotation per minute.
[][]Record the observations in the Calibration report (Annexure –II).
[][]After completion of calibration switch ‘OFF’ the main supply.
[][]After completion of the calibration activity, affix the duly filled and signed calibration status label on the instrument.
[][]Calibration Frequency: Every three-month ±07 days of due date and after maintenance job.

Cleaning procedure:

Remove the knob by pressing gray colored button and open the drum.
Clean the drum with suitable dry duster or cloth.
If required use water and dry in air.
Place the drum properly and replace the knob.

Annexure:

Annexure-I: Log Book Of Friability Tester.
Annexure-II: Calibration Report Of Friability Tester

Calibration of Friability Tester With Operation & Cleaning Read More »

Calibration of Moisture Analyzer with Operation, and Cleaning

Product Development, SOPs

Calibration of Moisture Analyzer, Purpose :

Calibration of Moisture Analyzer, The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of Moisture Analyzer.

Calibration of Moisture Analyzer, Scope :

This procedure is applicable for Moisture Analyzer (Model: METTLER TOLEDO, MJ33) used in the Product Development of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

The roles and responsibility is as follows:

Operator / Supervisor, Product Development

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

Executive / Senior Executive, Product Development

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Keep sufficient free space around the instrument to avoid heat accumulation and over- heating.
[][]Never cover, plugged, taped over or tampered with any way the vent over the sample.
[][]Do not place any combustible material on, under or next to the instrument during operation.
[][]Be very careful to touch sample, sampling pan, sampling pan holder and heating module just after the operation.

Operating Procedure:

[][]Switch on the main power. Instrument shows “OFF” in display.
[][]Press the “ON/OFF” key to switch the instrument on.
[][]The instrument performs a self-test. Wait until the display shown 0.000 g.

Temperature setting

[][]Press the temperature setting key
[][]In display temperature reading shall be blinking.
[][]Select the desire temperature by pressing scroll button
[][]Press enter key to conform the temperature.
[][]Open the heating module (Top lid) for tare and close the heating module.
[][]Again open the heating module and put the sample on sample pan as mentioned in BMR or test procedure.
[][]Close the heating module and wait for buzzed.
[][]Record the moisture content from the display.
[][]Press the “ON/OFF” key to switch off the instrument.
[][]Wait sufficient time to cool down the instrument in ambient temperature before cleaning.

Calibration Procedure:

Balance calibration

[][]Ensure that the sample pan is in position.
[][]Switch ON the power supply. The display shows “OFF”.
[][]Press the “ON/OFF” key to start the instrument.
[][]The instrument performs a self-test. Wait until the display shown 0.000 g.
[][]Select standard weight of 1g, 5g and 10 g for calibration.
[][]Open the heating chamber and place 1g standard weight on the balance pan at center position.
[][]Repeat previous step no.for 5g. & 10 g.
[][]Record the observations in the calibration report (Annexure–II)

Temperature calibration

[][]Press menu key twice. Display shows “Temperature adj.”
[][]Select “Yes” using scroll keys.
[][]Press “enter” key to start process. Display shows “Remove pan holder”
[][]Open the heating chamber and Remove the sample pan holder from the sample chamber.
[][]Display shows “Insert adjustment kit”. Place the temperature adjustment kit (standard thermometer) in the sample chamber.
[][]Close the heating module to start heating to temperature 100deg. C. The display shows the temperature.
[][]Wait 15 minutes, instrument gives audio signal sound.
[][]Note down the actual temperature on standard thermometer in calibration report (Annexure-II)
[][]Press enter key. The heating module automatically starts calibration at 160deg. C.
[][]Again wait for 15 minutes, instrument gives audio signal sound.

Acceptance Criteria

[][]For balance calibration ± 0.1 % & for temperature calibration ± 30 C.
[][]After completion of calibration switch “OFF” the main supply.
[][]After completion of the calibration activity, affix the duly filled and signed calibration status label on the instrument.
[][]Calibration Frequency
[][]Every six month ± 10 days of due date and after maintenance job.

Cleaning Procedure:

[][]Disconnect the instrument from the power supply before cleaning.
[][]Open the heating module and remove the sampling pan by sampling pan holder.
[][]Clean the sampling pan with soft brush.
[][]Clean exteriors of the instrument by clean dry cloth.
[][]Set the parts of weighing pan carefully and close the heating module

Annexure:

Annexure-I: Log Book Of Moisture Analyzer.
Annexure-II: Calibration Report of Moisture Analyzer.

Calibration of Moisture Analyzer with Operation, and Cleaning Read More »

Semi Automatic Disintegration Tester Operation, Calibration and Cleaning

Product Development, SOPs

Semi Automatic Disintegration Tester , Purpose:

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

Semi Automatic Disintegration Tester , Scope:

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

Definitions / Abbreviation:

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

Responsibilities:

[][]The roles and responsibility is as follows

Executive, Product Development

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

Manager, Quality Assurance

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

Procedure:

Precaution:

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

Operation: Semi Automatic Disintegration Tester

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

DISINTEGRATION
TESTER
ED2-SAPO
VER-1.1

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

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

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

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

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

Operation in Registration Mode

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

Selection of Dual Timer Mode (For Known Disintegration Time)

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

Operation in Dual Timer Mode

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

Halting / Aborting the Test

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

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

Operation Log Book

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

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

Calibration of Timer for Basket-B

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

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

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

Calibration of Basket A to Beaker Bottom Height

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

Calibration of Basket B to Beaker Bottom Height

[][]Follow steps

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

Cleaning

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

Annexure: Semi Automatic Disintegration Tester

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

Semi Automatic Disintegration Tester Operation, Calibration and Cleaning Read More »

Calibration of Hardness Tester with operation & cleaning

SOPs

Calibration of Hardness Tester, Purpose :

Calibration of Hardness Tester, The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of Hardness Tester.

Calibration of Hardness Tester, Scope :

This procedure is applicable for Hardness Tester (Model: ERWEKA, TBH125 ) used in Product Development Laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]PD: Product Development

Responsibilities:

The roles and responsibility is as follows:

Executive, PD

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

Sr. Executive, PD

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Check the power supply before connecting the machine.
[][]Keep the tester clean.
[][]Always switch off the machine at the end of work.

Operating Procedure:

[][]Turn on the power switch of Hardness Tester.
[][]After power on, the instrument is powered up and the following display will be shown:

ERWE

A TBH

UP DOWN

STOP FORWARD

UP DOWN …. Key

[][]Continue with Start/ Enter key, then following display will be shown:

ZERO

JAW

[][]Start zeroing with the Start/Enter key. The jaw will move to the counter-jaw, measure the Zero point, and then return to the initial position.

[][]The main menu will only be displayed if a correct zero point is detected.

NUM

0006

[][]Instrument Settings: In order to setup the instrument and enter configuration details and other parameters of the TBH125 instrument proceed as follows:
[][]Pause (PAUS):The pause time of the hardness tester between measurement cycles shall be entered using right arrow keys. Setting pause time will be 0-10 time units (approximately 10 seconds).
[][]Hardness (UNIH): Breaking force such as Newton, Strong Cobb or Kilopond by using the right arrow keys.
[][]Diameter and Thickness (UNID): Select mm or inch by using the right arrow keys.
[][]Hours (HOUR): Enter current time hours by using the right arrow keys.
[][]Minutes (MINU): Enter current time minutes by using the right arrow keys.
[][]Day (DAY): Enter current date by using the right arrow keys.
[][]Month (MONT): Enter current month by using the right arrow keys.
[][]Year (YEAR): Enter current year by using the right arrow keys.
[][]Newton Factor (NFCT): This internal calibration factor will be set by using the right arrow keys.
[][]Language (LANG): Language will be selected by using the right arrow keys.
[][]Auto On: Use the “Auto On” button to activate the automatic function of the diameter. This means that the nominal diameter needs not to be entered when measuring the diameter.
[][]Date Format (DAFT): Select date format in European or US format
[][]EURO = day : month : year
[][]USA = year : month : day
[][]By using left arrow keys.
[][]Method (METH): Select between the speed or force method for actual measurement by using the left arrow keys and then press Start/ Enter key.
[][]Hardness (HARD): By using the right arrow keys select whether the hardness measurement is going to be performed or not (on/off) and then press Start/ Enter key.
[][]Diameter (DIAM): By using the right arrow keys select whether the diameter measurement is going to be performed or not (on/off) and then press Start/ Enter key.
[][]Thickness (THIC): By using the right arrow keys select whether the thickness measurement is going to be performed or not (on/off) and then press Start/ Enter key.
[][]Speed (SPED): The speed of the breaking process can be set in millimeter per second, from 0.5 to 3 mm/s by using the right arrow keys. The default value is 2.3 mm/s.
[][]Force (FORC): The default value of force of the breaking process is 0020 N/s.
[][]Results (REST): When select “REST” a list of individual values appear, which will be stored until the instrument is switched off or a new test is run, and which can be printed again in the printer menu.
[][]Statistics (STAT): When selecting ‘STAT’ a statistic evaluation of the current test appears. It will be stored until the instrument is switched off or a new test is run, can be printed again in the printer

Calibration procedure:

[][]Ensure that the instrument is clean before use, including surrounding area.
[][]Check and ensure due date of calibration.

Diameter Calibration (DIAM):

[][]By Using Start/Enter key to select diameter.
[][]Clean the jaw and counter jaw with a brush and then press Start/ Enter key to start.
[][]The jaw moves to the counter jaw, measures zero point, and then returns to the initial position.
[][]A gauge block of 10.00mm is preset. Insert gauge block and start measurement using the Start/Enter key. The jaw moves to the gauge block and registers the second point.
[][]Three different control measures must be performed in succession to test the accuracy of the test station.
[][]A gauge block of 5.00mm is preset. Insert gauge block and start measurement using the Start/Enter key.
[][]The actual value will appear on the display, continue to the control measurement using the Start/ Enter key.
[][]Thickness Calibration (THIC): The thickness calibration is not applicable because of previously performed diameter calibration.

Hardness calibration (HARD):

[][]Select hardness using Start/Enter key.
[][]The calibration weight to be adjusted.
[][]The jaw moves to the calibration position and stop. The path is set in the menu COPS for the calibration position.
[][]Place mount calibration device on the jaw.
[][]Place the device with the weight receptacle on the right side while ensuring that the printer connection is free.
[][]The actual weight is displayed (not exactly zero because of the weight of the plate).
[][]Zero the device with the help of left and right arrow keys.
[][]Carefully placed the desired weight on instrument.
[][]Press Start/ Enter key to confirm and finish the calibration.
[][]The Linearity of the load cell is verified with three different control weights. Make sure that the weights are positioned carefully and stable on the plate.
[][]Use Start/Enter key to confirm. The actual is displayed. Use Start/ Enter key to continue.
[][]When calibration is finished remove the weighing plate and reposition the instrument. Use Start/ Enter key to confirm. The jaw moves back to origin.
[][]The display returns to calibration menu. When quitting the calibration menu with the key a calibration printout is performed automatically.

Calibration Frequency:

Cleaning procedure:

[][]Before starting each day operation, clean the overall instrument by a lint-free dry cloth.
[][]Clean the star feeder using a clean cloth.
[][]Use the brush to remove the tablet debris from the transport way after each operation.

Annexure:

Annexure-I: Log Book of Hardness Tester.

Calibration of Hardness Tester with operation & cleaning Read More »

Dissolution Tester Calibration with Operation and Cleaning

SOPs

Dissolution Tester Calibration, Purpose :

Dissolution Tester Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Dissolution Tester (Model: Electrolab, EDT 14Lx).

Dissolution Tester Calibration, Scope :

This procedure is applicable for Dissolution Tester (Model: Electrolab, EDT 14Lx), installed in the quality control laboratory at XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]Dissolution test: Dissolution test is a means to monitor the rate of release of a drug substance from a dosage form to ensure consistency of manufacture and compliance with release specifications.
[][]RPM: Rotations per minute
[][]LED: Light emitting diode
[][]Concentricity: The quality of having the same center (as circles inside one another).
[][]Wobble: Move sideways or in an unsteady way.
[][]NMT: Not more than.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/ Sr. Executive, Quality Control

[][]To ensure that the instructions of this procedure are correctly followed.
[][]To ensure cleaning of dissolution tester 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

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

Procedure:

General precautions or operational safety:

[][]Do not start the heater if there is no water in the tank.
[][]Always maintain the liquid level within the tank above the minimum level mark using purified water only.
[][]Disconnect the power supply before moving, emptying or cleaning of bath.
[][]Spillage must be cleaned up immediately after use.
[][]Do not use any aggressive material or strong solvent to clean the jar and water bath.
[][]Locate the system on a level bench without movement or distortion.
[][]Do not hold the stirrer while in operation.
[][]For lifting up the stirrer, make sure the paddles are stop.
[][]Do not disturb the sensor tube while cleaning the tank.
[][]External probe should be handled with care.
[][]Use sinkers if the dosage form unit floats. Close the vessels with the cover during Operation.

System Operation:

[][]After the System is set up, switch on the power.
[][]After Power On, the Instrument will initialize itself; the logo screen will flash for 3 seconds and then idle screen will be displayed.
[][]The idle screen displays the current status of the instrument indicating the Date, Time, RPM, Bath Temperature, External probe and loaded protocol number.
[][]Press F3 Key to login.
[][]Username and Password needs to be added.
[][]Press F1 key to enter the username & password or F3 Key to go back to the previous screen.
[][]The idle screen will be displayed.
[][]If security is disabled then the adjacent idle screen will be displayed.

ELECTROLAB
EDT 14Lx
DISSOLUTION
TEST APPARATUS

[][]Press F1 or F2 Key from front panel to enter MENU or PREPARE
[][]Menu Press F1 Key from front Panel to enter menu screen.
[][]Menu <Configure>
[][]Press 1 from alphanumeric keypad to enter configuration menu.
[][]If F3 key is pressed the previous screen will be displayed.
[][]Menu <Configure> l sampling l
[][]Press 1 from alphanumeric keypad to enter sampling menu.
[][]Menu <Configure>l sampling l [ Manual] [][]Press 1 to select manual sampling though syringe manifold or 2 to select manual sampling though pipette.
[][]Menu <Configure>l Individual Probe l
[][]Press 2 to enter individual probe screen. Press 1 from alphanumeric keypad to select the individual probes. The number of probes can be selected either to 6/8/12/14 using up or Down arrow key, press enter to save the No. of probes and return back to configure screen.
[][]Press 2 to select option number.
[][]Press F3 key to return back to the Configure screen.
[][]Menu <Configure>l Temp Gradient l
[][]Press 3 to enter temp gradient.
[][]Set Temp gradient up to 1.5° C using increment & decrement key.
[][]Temperature Controller set.

F1 key: To ‘ON’ the temp Controller.
F2 key: To ‘OFF’ the temp Controller.
F3 key: To ‘SAVE’ & to return back to the Configure screen.

[][]Menu <Configure>l communication l
[][]Press 4 from front panel to enter Communication.
[][]Select RS232 for printer/PC and ETHERNET for LAN connection using 1 or 2 numeric keys.
[][]Press F3 key to go back to configure screen.
[][]Menu <Configure>l Stirrer l
[][]Press 5 in configure screen.
[][]Press 1 to ON the Stirrer and press 2 to OFF the stirrer.
[][]Menu <Configure>l Auto Disp. l
[][]Press 7 to enter auto dispenser screen.
[][]Press 1 or 2 numeric keypad to activate auto dispenser.
[][]Menu <Configure>l Instur. No. l
[][]Press 8 to enter instrument number.10 alphanumeric character serial numbers can be entered.
[][]Press F1 keys to save the entered serial number and F3 to go back to previous screen.
[][]Menu <Protocol>
[][]Press 2 to enter protocol menu.
[][]Menu< Protocol >l Load Protocol l
[][]Press 1 to enter Load Protocol.
[][]20 Programmable protocols can be loaded
[][]Protocol No- Can be loaded using UP/Down key & to register the No. Enter key needs to be pressed.
[][]Press F1 to load next protocol and Press F2 to load previous protocol.
[][]Press F3 to go back to the protocol screen.
[][]Menu< Protocol >l Edit Protocol l
[][]Press 2 to enter Edit Protocol.

[][]Select the protocol which needs to be editing using Up/down arrow and press ‘enter’ key.
[][]The respective protocol details such as Drug name, Media name, pH value, Temperature, Media volume , Power fail, Apparatus, Time Table, Sampling Info, details need to be entered.
[][]The protocol details can be edited using alphanumeric keypad.
[][]The next parameters can be selected for editing before saving the previous parameter by pressing F3 key from front panel.
[][]To select different apparatus press enter key and select the desired apparatus using numeric keys.
[][]To edit time table parameters press Enter key. The sampling time interval, action and total number of samples (1 to 24) can be set as per user requirement using shift & alphanumeric keys.
[][]For the single time point, action table will have only one sampling option. Infinity (min) can be selected after last sample.
[][]For the multiple time point, action table will have only two sampling options media change and sample. Infinity (min) can be selected after last sample.
[][]Press F3 to save & go back to main menu screen.
[][]Menu <Settings >
[][]Press 3 to enter settings
[][]Menu <Settings > l Clock l
[][]Press 1 alphanumeric keypad to enter Clock setting screen
[][]Set Date and Time using ▲▼◄► arrow keys
[][]Press F1 from front panel to save the entered date and time, the idle screen will be displayed
[][]Press F1 from front panel to go back to the setting screen.

[][]Menu <Settings > l Wake Up l
[][]In this parameter the sleep mode time and date are set. The instrument will start automatically at the set time and date for attaining the bath temperature.
[][]Press 2 from setting screen to enter the wakeup setting screen.
[][]Wake up time and date needs to be added using Up/Down and Side arrow keys.
[][]Press F1 key to turn ON the wake up parameter, the LCD display light will be turn OFF automatically and idle screen will be displayed. Or press the F2 key to OFF the wakeup alarm.
[][]Menu <Jar Tamp >
[][]Press 6 from main menu screen to observe the jar tamp attained by individual jar.

To set RPM

[][]Press RPM key from front panel.
[][]Press numeric key to register the RPM range from 20 to 300 RPM.
[][]Press F1 key to Turn-on the motor & F2 key to Turn off.
[][]If RPM is out of range an error screen will be displayed.
[][]To Set Temperature
[][]Press Temperature key from front panel.
[][]Press numeric key to register the temperature range from 200 C to 400 C.
[][]Press F1 to turn On & F3 to turn off heater.
[][]If temperature is out of range an error screen will flash for 3 seconds.
[][]To prepare the test
[][]Load the appropriate protocol no. & press F2 key to start preparing the test.
[][]Batch No. & A.R. No. will be displayed. Using down arrow and enter key, add the batch No. & A.R No. (Lab. Control No.) up to ten digits. Press enter key to register the number.

[][]It will display checking connection where the instrument establishes link with the syringe/peristaltic pump and sample/fraction collector.
[][]After the connection between the instruments is done, sample collector will initialize & ‘Lift Not Park’ Indication will be display (If lift is not parked).
[][]‘Wait for the temperature’ indication will be display till the set temperature is achieved. User can also access MENU to cheek jar temperature.
[][]Ready indication will glow on front panel when jar temperature reach to set point & start indication will be displayed.
[][]Press START key form front panel to start the test.
[][]‘Drop the tablet and press START’ message will be displayed immediately if paddle or 45 was selected and if basket or paddle over disk was selected then ‘Press lift up, Load Apparatus’ will be displayed on screen.
[][]Press Enter to start the test, run screen will be displayed. Current status of the test and sample timing are displayed throughout the test.
[][]After completion of work, switch ‘OFF’ the instrument.
[][]Switch ‘OFF’ the mains when not required.
[][]Fill up the operation log book for Dissolution tester as per Annexure-III.

Physical Calibration

[][]Frequency: Perform mechanical calibration of the dissolution tester once in every six months or if the system has been moved, serviced or a malfunction is suspected.

Temperature Calibration:

[][]Switch on the mains.
[][]Set the temperature to 37°C by following the temperature setting procedure given in operation.

[][]Ensure that the jars are filled with water.
[][]Allow the instrument to stabilize.
[][]Measure the temperature of the water bath and of each jar with a calibrated thermometer and compare the result against the digital display on the apparatus.
[][]Record the observation as per Annexure-I.
[][]Acceptance Criteria: 37°C ± 0.5°C.

RPM Calibration:

[][]Switch on the mains.
[][]Set the RPM to 50 as per procedure given in the operation.
[][]Start the stirrer and measure the RPM by using calibrated tachometer.
[][]Record the observation as per Annexure-I.
[][]Similarly check the RPM 75, 100, and 150 and record the observations.
[][]Acceptable criteria: ± 4% of set value.

Time Calibration:

[][]Switch on the mains.
[][]Set the desired time (30 and 45 minutes) by following the temperature setting procedure given in operation.
[][]Check the time using a calibrated stop watch and record the observations as per Annexure-I.
[][]Acceptable criteria: ± 2% of set value.

Chemical Calibration (Performance Verification Testing)

[][]Frequency: Perform chemical calibration of the dissolution tester once in a year or if the system has been moved, serviced or a malfunction is suspected.
[][]For USP Dissolution Apparatus 1 (basket) and Apparatus 2 (paddle):
[][]If the instrument is outside calibration, a label of “Out of calibration” is placed.
[][]Apparatus must be calibrated with the following :
[][]Disintegrating Type – USP Prednisone Tablets 10 mg at 50 rpm
[][]Non-disintegrating Type – USP Salicylic Acid Tablets 300 mg at 100 rpm
[][]Checking Standards in the on line-USP and printing Lot-Specific Standard Certificates. Verifies Standard Lots are current within expiry.

Disintegrating Type – USP Prednisone tablets 10 mg at 50 rpm:

[][]Follow the directions for storage and use on the label of the reference standard.
[][]If drying instructions are included on the label, only dry sufficient quantity required for the test (use a clean, dry vessel when drying and not the original container).
[][]Standard solutions must be prepared on the day of use.

Prednisone standard preparation:

[][]Accurately weigh 20 mg Prednisone standard into a 100 ml volumetric flask containing 5 ml methanol.
[][]Sonicate to dissolve and dilute to volume with distilled or purified water and mix well.
[][]Further dilute 5.0 ml of this solution to 100 ml with distilled or purified water and mix well.
[][]Dissolution medium preparation and de-aeration:
[][]Filter the dissolution medium (Distilled or purified water 500 ml) with the aid of a vacuum through a 0.45 µm-porosity membrane filter into a suitable filtering flask.

Test procedure:

[][]Using a volumetric flask, measure 500 ml distilled or purified water into each of the six vessels.
[][]Allow medium to equilibrate for approximately 30 minutes before test is commenced.
[][]When dissolution bath has equilibrated, check the temperature of each vessel is 37.0°C ± 0.5°C.

[][]Carefully weigh 6 de-dusted USP Prednisone Tablets 10 mg.
[][]Drop one previously de-dusted tablet into each of the vessels via the sample holes in the lids, raising the stirrer shaft fully before dropping the tablet into the vessel, and pushing the shaft fully down when the tablet has reached the bottom.
[][]Operate the apparatus at 50 rpm for 30 minutes.
[][]After 30 minutes withdraw approximately 50 ml midway between the surface of the dissolution medium and the top of the blade, not less than 1cm from the vessel wall.
[][]Filter through a Whatman Number 1 filter paper, discarding the first few ml of filtrate.
[][]Scan the standard from 300-200 nm to obtain the maximum absorbance at the optimum wavelength (approximately 242 nm).
[][]Determine the absorbance of the six samples at that wavelength in fixed mode.
Calculate the percentage prednisone dissolved for all 12 stations using the following calculations:

% Dissolved =
Absorbance of Sample x Standard Concentration (mg/l) x Standard Potency x 100 DIVIDED BY
Absorbance of Standard x Sample Concentration if 100% dissolved (C100)

Acceptance Criteria:

[][]Check the percentage released limit of USP dissolution calibration tablets (Disintegration type: Prednisone tablets) from the respective batch certificate provided by USP.
[][]If any one station is outside of specification, place an “Instrument out of calibration, DO NOT USE” label on the instrument.
[][]Inform In-charge, QC; if the results do not meet the criteria.

Test interpretation:

The apparatus shall be suitable if the individual calculated values at each indicated speed are within the range specified in the tablet obtained with the each lot of tablets.

Note: An amount of alcohol not to exceed 5% of the total volume of the standard solution may be used to bring the prednisone standard into solution prior to dilution with dissolution medium.

Recording of Results:

[][]All relevant information on the calibration must be completed on Annexure-II.
[][]When all the results have been checked affix a Calibration label to the instrument.

Cleaning procedure

[][]Lift the stirrer unit by using “lift UP” key.
[][]Immerse the replenishment tubes in a vessel of the instrument or a beaker outside of the instrument containing purified water.
[][]Press F1 Key [Menu] from front panel.
[][]Press 5 from alphanumeric keypad to enter Run.
[][]Again press 2 for cleaning cycle.
[][]Iterations of cleaning cycle will be displayed, press F3 to save the command.
[][]Batch No.:, A. R. No.:, User Name: will be displayed. Press Enter 3 times.
[][]Display will be showed Press UP to edit/Press Enter to proceed, again press Enter.
[][]It will display checking connection where the instrument establishes link with the syringe/peristaltic pump and sample/fraction collector. At that time wait for few seconds.
[][]Press START
[][]ABORT STOP will be displayed on the LED screen.
[][]To start the cleaning cycle, press Start.
[][]After completion of cleaning cycle display will show checking connection Press START
[][]ABORT STOP
[][]Press F3 to stop the cleaning cycle and start the empty tube cleaning.
[][]Before start the empty tube cleaning, the replenishment tube should be placed in the open air from vessel or beaker.

[][]Remove the test vessels from their place and discard the medium.
[][]Wash each vessel with purified water and then set them inside the dissolution bath number wise.
[][]Remove basket/ paddle apparatus from the dissolution tester. Wash them with purified water and dry with tissue paper and keep at dedicated place.
[][]Clean and replace the water from dissolution bath fortnightly (once in every two weeks) or if necessary.
[][]Remove all vessels from the dissolution bath.
[][]Remove the basket/ paddle apparatus from the stirrer unit.
[][]Remove the circulating pipe which is provided at the right rare side of the dissolution bath.
[][]Start the circulation pump from the option menu and drain the dirty water in a waste water bucket.
[][]Insert the circulating pump in its proper place.
[][]Wash the dissolution bath with raw water, detergent solution and then again with raw water sequentially until no foam of detergent remains in the bath.
[][]Wash the bath finally with purified water and fill the bath with the same up to the level mark.
[][]De-dust the outer surface of the instrument with a clean dry cloth every day.

Annexure: Dissolution Tester Calibration

Annexure-I: Physical Calibration Information Sheet for Dissolution Tester
Annexure-II: Chemical Calibration Information Sheet for Dissolution Tester
Annexure-III: Operation Log book for Dissolution Tester

Dissolution Tester Calibration with Operation and Cleaning Read More »

Calibration of Semi-micro Osmometer with operation & cleaning

Quality Control, SOPs

Calibration of Semi-micro Osmometer, Purpose:

Calibration of Semi-micro Osmometer, The purpose of this SOP is to describe the operation, calibration and cleaning of Semi-micro Osmometer (Brand: KNAUER; Model: K-7400) used in the quality control laboratory of XX Pharmaceuticals Limited.

Calibration of Semi-micro Osmometer,Scope:

This procedure is applicable for Semi-micro Osmometer, installed in the quality control laboratory general block of Labaid Pharmaceuticals Limited.

Definitions / Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure.
QC: Quality Control.

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/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):

[][]Prior to use, user must ensure that equipment is calibrated.
[][]To ensure a fixed sample volume, always introduce the solutions with a clean and dry pipette into the measuring vessel.
[][]Handle the thermistor always very carefully. All abrasive materials should be kept away from it.
[][]Solutions containing proteins, such as sera, can only be measured once. Freezing causes denaturisation of the protein so that repetition of the measurement with the same sample would result in increased values. Thus, in the case of sera, only one measurement is possible for one sample.
[][]Only real osmolalities can be measured. It is not possible to prepare other standard solutions by dilution of a calibration solution since the activity coefficient of the solution changes with dilution.
[][]In this case Store the water which is used for the zero point calibration in glass bottles.
[][]If the same salt solution is measured several times, it must be mixed after thawing (stir briefly). During the thawing process ice floats to the top of the solution. As ice does not contain salt, the top layer of the solution is diluted while thawing.
[][]Calibration solutions can become more concentrated if the bottle is opened frequently. So, use KNAUER calibration solutions in glass ampoules.
[][]Prior to the measuring, a little bit water condensed in the cooling compartment should be removed with a dry cloth.

Operation:

[][]Preparing the Osmometer K-7400
[][]Switch ON the instrument at least 5 minutes before use.
[][]Press the vibrator key to check the stirrer. It will run for a second.
[][]Optionally a thermo printer can be connected to the RS232 socket. The result of each measurement will be printed automatically.
[][]After a calibration, an outprint of Calibration will be found automatically.
[][]In case of interrupted runs (caused by any error), the screen displays the corresponding error message.

Preparing a Measurement

[][]Place 0.15 ml sample or calibration solution into a clean, dry measurement vial.
[][]Put the vial all the way into the adapter. The meniscus of the liquid must be horizontal.
[][]Place the measuring head on the instrument in such a way that the vial extends into the cooling cavity.
[][]Thus the instrument is ready for calibrating or measuring.

Calibration:

[][]Prepare the instrument for a measurement of deionised water.
[][]Set the first field in the second row of the CALIBRATE screen to „0000“.
[][]Press the start key.
[][]After finishing the run on the screen is displayed 0000 mOsmol > -0.81°C<.
[][]To accept this value, press the START key again.
[][]Wait for the warming up to the stand-by temperature.
[][]Prepare the instrument for a measurement of a 300 mOsm/kg calibration solution.
[][]Activate the second calibration field and select “0300” and repeat steps
[][]For a 4 point calibration, repeat the procedure for calibration fields

Measuring Samples:

[][]Prepare the instrument for a measurement of a sample solution.
[][]Press the START key to start the measurement run.
[][]The instrument detects the freezing point depression and if the crystallisation occurred properly displays the corresponding osmolality on the main screen.
[][]The printer output is given automatically.
[][]If no crystallisation (temperature increase) takes place after the automatically start of the vibrator the measurement will be stopped with the error message “> ERROR < NO FREEZE”.
[][]If the crystallisation (temperature increase) takes place before the start of the vibrator the measurement also will be stopped with an error message> ERROR < FREEZE.
[][]Do not remove the measurement vessel from the adapter before the sample is molten. Otherwise the danger of damaging the measuring head is given. The sample melting can be accelerated by warming up with the fingers.

Cleaning procedure:

[][]Measuring vessel and thermistor should be cleaned occasionally with KNAUER cleaning solution supplied with the instrument. (Dilution: 1: 10 solution in purified water of 40±5°C)
[][]Clean and dry the measuring vessels with alcohol or acetone because remaining solvent vapours could cause false results.

Annexure:

Annexure-I: Operation Logbook for Semi-micro Osmometer.

Calibration of Semi-micro Osmometer with operation & cleaning Read More »

Calibration of HPLC System With Operation & Cleaning

SOPs

Calibration of HPLC, Purpose:

Calibration of HPLC, The purpose of this SOP is to describe the operation, calibration and cleaning of High Performance Liquid Chromatography system with DAD & RID (Brand: Agilent; Model: 1260 Infinity) used in the quality control laboratory at XX Pharmaceuticals Limited.

Calibration of HPLC, Scope:

This procedure is applicable for Agilent PC based Quaternary Gradient Automated High Performance Liquid Chromatography System, installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP : Standard Operating Procedure.
[][]QC : Quality Control.
[][]HPLC : High performance liquid chromatography
[][]DAD : Diode Array Detector
[][]RID : Refractive Index Detector

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/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.

Procedure:

General Precaution(s):

[][]Prior to use, user must ensure that instrument is calibrated.
[][]Be sure that the drain valve is open before purging and tightly closed after purging.
[][]Before shutting down the system ensure that column is thoroughly washed and kept in appropriate solvent.
[][]Mobile phase, Diluting solvents and other solutions, which are used in HPLC, should be freshly prepared.
[][]Degas the mobile phase before using.
[][]Rinse the flow lines after completion of analysis as per solvent used in the system.
[][]Make sure that the solvent filter/diffuser is completely immersed in solvent.
[][]Update the solvent bottle before run.
[][]During set up the flow rate at priming, do not press Run/Stop to start the pump.
[][]Purge the pump with fresh diluent (filtered and degassed).
[][]Clean the solvent diffuser/filter once in a week.
[][]Fill up & attach Labels of the solvent reservoirs properly.

Operation of DAD:

[][]Switch ‘ON’ the power of Quaternary Pump, Autosampler, Thermostatic Column Compartment, Detector, CPU, Monitor if already not switched on.
[][]Wait until all the modules are initialized and are ready for next operation.
[][]Set specified column in the column compartment.
[][]Computer and Software Log in
[][]Double click on the icon of HPLC_DAD (online) from Desktop.
[][]Click Download to instrument/Upload from instrument/New method from instrument.

Purging Lines

[][]Insert the solvent tubing into the appropriate reservoirs.
[][]Gently shake the filters in the reservoirs to remove any bubbles that may be trapped.
[][]Open the purge valve of pump by half (1/2) turning anticlockwise.

[][]Go to the Agilent modular controller screen.
[][]Click Switch On to switch on all the modules.
[][]Right Click on the mouse over Quat. Pump module.
[][]Click Method.
[][]Enter flow rate 5.00 ml/min.
[][]Enter the % of composition of the desired purging line.
[][]Press OK/Apply.

Update the Solvent Bottle

[][]Right Click on the mouse over Quat. Pump module.
[][]Click Bottle Fillings.
[][]Enter the Solvent Volume of respective Bottles and enter the Total volume of the Bottle.
[][]Click OK.

[][]Create a new Method
[][]Click Method from menu.
[][]Click New Method.
[][]Click Method from menu.
[][]Click Entire Method…
[][]Click OK > OK >OK.
[][]Select Quart. Pump.
[][]Enter Flow rate, % of solvent ratio, stop time and maximum pressure Limit (Max. 400).
[][]For Gradient flow enter the time program.
[][]Select Sampler.

[][]Click OK.
[][]Click desire method.
[][]Click Add Method.
[][]Click OK>OK> OK>OK> OK.
[][]Click Method from menu.
[][]Click Save Method As…
[][]Select location and enter Method Name.
[][]Click OK.

Create a new Sequence

[][]Click Sequence from menu.
[][]Click New Sequence Template.
[][]Click Sequence from menu.
[][]Click Sequence Table…
[][]Enter Sample Location, Sample Name, Method Name and Data File.
[][]Click OK.
[][]Click Sequence from menu.

[][]Click Sequence Parameters…
[][]Locate the Data File Path.
[][]Click Post-Sequence Command/macro.
[][]Select STANDBY from dropdown list.
[][]Click OK.
[][]Click Sequence from menu.
[][]Click Save Sequence Template As…
[][]Select location and enter Sequence Name.
[][]Click OK

Run Samples

[][]Select the created Method.
[][]Select the created Sequence.
[][]Insert the solvent tubing into the appropriate reservoirs.
[][]Click Switch On to switch on all the modules.
[][]Wait for Base line stable.
[][]After getting the Baseline stability click RunControl from menu.
[][]Click Run Sequence.
[][]Instrument will be run as per selected Method and Sequence; and data will save as per selected location.

Data Processing

[][]Double click on the icon of HPLC DAD (offline) from Desktop.
[][]Select desire Sequence file from Data Analysis window.
[][]Double click a file of Navigation Table.
[][]Click Graphics form Menu.
[][]Click Signal Options.
[][]Click Compound Names.
[][]Click OK.
[][]Click Edit or Set Integration Events Table.
[][]Remove the unexpected peak either using Area or Height rejection or using time integration event program.
[][]Click OK.
[][]Click Calibration from Menu.
[][]Click Calibration Settings
[][]Enter Amount Units.
[][]Click OK.
[][]Click Calibration from Menu.
[][]Click New Calibration Table…
[][]Enter Default Amount (Standard wt. in mg).
[][]Click OK.
[][]Enter Compound Name in Calibration Table.
[][]Click OK.
[][]Click Method from Menu.
[][]Click Save Method As Save As New Master Method.
[][]Select location and enter Method Name.
[][]Click OK.
[][]Click Sequence from menu.
[][]Click Sequence Table
[][]Select the desire processing Method and Fill down.
[][]Select Sample Type as Calibration using drop down list for standard injections.
[][]For first Standard select Replace both for Update RF & Update RT using drop down list.
[][]Enter Multiplier.
[][]Click Reprocess.
[][]Click OK.
[][]Sequence will be processed as per selected processing method.

Report Print

[][]Select Data/Set of Data.
[][]Select Review.
[][]Click File from Menu.
[][]Clock Load Template.
[][]Select Template.
[][]Click Open.
[][]Click Print Report from Menu.

Operation of RID:

[][]Switch ‘ON’ the power of Quaternary Pump, Autosampler, Thermostatic Column Compartment, Detectors, CPU, Monitor if already not switched on.
[][]Wait until all the modules are initialized and are ready for next operation.
[][]Set specified column in the column compartment.
[][]Computer and Software Log in
[][]Double click on the icon of HPLC_RID (online) from Desktop.
[][]Click Download to instrument/Upload from instrument/New method from instrument.

Purging Lines

[][]Flow the operation steps
[][]Update the Solvent Bottle
[][]Flow the operation steps

Stabilization of RID detector

[][]Insert the solvent tubing into the appropriate reservoirs. Be sure that the detector waste lines and the sample loop waste line drain into the appropriate container.
[][]Right Click on RID window.
[][]Click Open Purge Valve.
[][]Right Click on RID window.
[][]Click Switch Recycling On.
[][]Wait for baseline stability.
[][]After baseline stability right Click on RID window.
[][]Click Close Purge Valve.
[][]Right Click on RID window.
[][]Click Switch Recycling Off.

Create a new Method

[][]Flow the operation steps
[][]Select DAD.
[][]Deselect Signals and UV Lamp if they are not previously deselected.
[][]Click OK.
[][]Click RID.
[][]Enter the Optical Input Temperature.
[][]Click OK.
[][]Select RID1 A, Refractive Index Signal.
[][]Click Add Method.
[][]Flow the operation steps

Create a new Sequence

[][]Flow the operation steps
[][]Run Samples
[][]Flow the operation steps
[][]Data Processing
[][]Double click on the icon of HPLC_RID (offline) from Desktop.
[][]Flow the operation steps
[][]Click File from menu.
[][]Click Load Signals…
[][]Select a standard file.
[][]Select RID1 A, Refractive Index Signal.
[][]Click OK.
[][]Flow the operation steps

Report Print

Flow the operation steps

Shut Down

[][]Click “Off” icon to stop Instrument.
[][]Carryout system suitability test every day before analysis.
[][]Fill up the column information logbook after analysis.
[][]Wash the column following as per HPLC Column Washing Procedure
[][]Exit from the “OpenLab Chemstation’’ software.
[][]Put off the power of equipment and computer.
[][]Record in the Logbook for operation of HPLC (as per Annexure-IV).

Operation of Queue Planner:

[][]When two or more sequence to be run with the same column and same mobile phase/mobile phase composition; Queue Planner is required.
[][]Save individual method and sequence for individual operation.
[][]Click RunControl from menu.
[][]Click Queue Planner.
[][]Insert/Append sequence when required. Use Up/Down button to rearrange the sequence.
[][]Click Save As.

[][]Select location and enter file name.
[][]Click Add to back of queue.
[][]During using of Queue Planner keep wash method and STANDBY at the last sequence only.

Calibration of HPLC:

Calibrate the HPLC at every 6 month’s frequency either by following procedure or as per supplier’s protocol:
[][]Quaternary Pump : 1260 Qart Pump VL
[][]Check the LED is on.
[][]Turn on the power.
[][]Set Flow Rate at 0.500 ml/min and 5.000 ml/min.
[][]Check flow rate, average value, STD, accuracy and precision.
[][]Record the value in Calibration Information Sheet for Pump Flow and Accuracy of Quaternary Pump VL (Annexure-I).
Set the following parameters:
Injection Volume : 0.0 µl
Flow Rate : 2.0 ml/min
Wavelength : 265 nm
Run Time : 26.0 min
Column Temperature : 40.0 °C
Evaluated Compound : Acetone
[][]Set the following Gradient Program and record the data:
Gradient Pump A/ Pump B
Initial 00% /100%
Step 1 20% /80%
Step 2 40% /60%
Step 3 60% /40%
Step 4 80%/ 20%
[][]Check the height, noise, drift and composition for various compositions.
[][]Record the Height, Noise, Drift and Composition in Calibration Information Sheet for Gradient Composition (Annexure-I).
[][]Thermostatic Column Compartment: 1260 TCC
[][]Check the LED is on.
[][]Turn on the power.
[][]Set Flow Rate 1.0 ml/min.
[][]Set column temperatures at 80.0°C and 40.0°C.
[][]Check the Column Temperature Accuracy and Column Temperature Stability from Column Compartment Display in 4 munities interval.
[][]Record the value in Calibration Information Sheet for Thermostatic Column Compartment (Annexure-II).

[][]Variable Wavelength Detector: 1260 DAD VL
[][]Check the LED is on.
[][]Turn on the power.

Set the following parameters:
Pump Flow Rate : 1.0 ml/min
Run Time : 2.0 min
Injection volume : 15 µl
Column Temperature : 40.0°C
Sample : Caffeine Std
Evaluated Compound : Caffeine
[][]Evaluating Standard Concentration : 25.0 µl/ml (form Certificate of Analysis)
[][]Set wavelengths at 205 nm, 245 nm and 273 nm.
[][]Check the area of the chromatograms for respective wavelengths.
[][]Record the value in Calibration Information Sheet for Variable Wavelength Detector (Annexure-III).
[][]Set the following parameters:
Flow Rate : 1.0 ml/min
Run Time : 24.0 min
Noise Evaluation Start Time : 3.0 min
Noise Evaluation Duration : 20.0 min
Injection Volume : 0.0 µl
Column Temperature : 40.0°C
[][]Check the Noise and Drift.
[][]Record the Noise and Drift in Calibration Information Sheet for Noise and Drift of Variable Wavelength Detector (Annexure-III).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 7.0 min
Injection Volume : 10.0 µl
Noise Evaluation Start Time/Duration : 3.00 min/3.00 min
Evaluation Standard Concentration : 25 µg/ml (Certificate of Analysis)
Sample : Caffeine Std
Evaluation Compound : Caffeine
Detector Path Length : 10 mm
Wavelength : 273 nm
[][]Check the signal to noise ratio.
[][]Record the Signal to Noise in Calibration Information Sheet for Signal to Noise of Variable Wavelength Detector (Annexure-III).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 2.0 min
Injection Volume : 20.0 µl

Sample : Caffeine Std
Wavelength : 273 nm
Evaluation Compound : Caffeine
[][]Check the area and height and find the R/F, R/F average, R/F STD and Coefficient of Determination.
[][]Record the linearity in Calibration Information Sheet for Response Linearity of Variable Wavelength Detector (Annexure-III).
[][]Refractive Index Detector: 1260 RID
[][]Check the LED is on.
[][]Turn on the power.
Set the following parameters:
Flow Rate : 1.0 ml/min
Run Time : 24.0 min
Noise Evaluation Start Time : 3.0 min
Noise Evaluation Duration : 20.0 min
Injection Volume : 0.0 µl
Column Temperature : 40.0°C
[][]Check the Noise and Drift.
[][]Record the Noise and Drift in Calibration Information Sheet for Noise and Drift of Refractive Index Detector (Annexure-IV).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 7.0 min
Injection Volume : 10.0 µl
Noise Evaluation Start Time/Duration : 3.00 min/3.00 min
Evaluation Standard Concentration : 25 µg/ml (Certificate of Analysis)
Sample : RID Std kit
Evaluation Compound : Glycerin
Detector Path Length : 10 mm

[][]Check the signal to noise ratio.
[][]Record the Signal to Noise in Calibration Information Sheet for Signal to Noise of Refractive Index Detector (Annexure-IV).
Set the following parameters:
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Run Time : 2.0 min
Injection Volume : 20.0 µl
Sample : RID Std kit
Evaluation Compound : Glycerin
[][]Check the area and height and find the R/F, R/F average, R/F STD and Coefficient of Determination.
[][]Record the linearity in Calibration Information Sheet for Response Linearity of Variable Wavelength Detector (Annexure-IV).
[][]High Performance Autosampler: 1260 ALS
[][]Check the LED is on.
[][]Turn on the power.
Set the following parameters:
Injection Volume : 20 µl
Run Time : 2.0 min
Flow Rate : 1.0 ml/min
Column Temperature : 40.0°C
Wavelength : 273 nm
Sample : Caffeine Std
Evaluated Compound : Caffeine
Standard Concentration : 25 µg/ml (from Certificate of Analysis)
[][]Check the Area and Height of six chromatograms and calculate average value, standard deviation and %RSD.
[][]Record the value in Calibration Information Sheet for High Performance Autosampler (Annexure-V).
Set the following parameter:
Injection Volume : 20 µl
Run Time : 2.0 min
Flow Rate : 1.0 ml/min
Column Temperature : 40.0 °C
Wavelength : 273 nm
Sample : Caffeine Std
Evaluated Compound : Caffeine
Standard Concentration : 25 µg/ml (from Certificate of Analysis)
[][]Check the Carry Over of Injection.
[][]Record the Carry Over in Calibration Information Sheet for Injection Carry Over of High Performance Autosampler (Annexure-V).
[][]Cleaning procedure
[][]Clean the instrument daily as follows
[][]Switch ‘OFF’ the instrument and switch ‘OFF’ the mains.
[][]Clean the outer surface of the instrument with dry clean cloth.
[][]Clean the surrounding areas of instrument with a cloth dampen in water then wipe with a dry cotton cloth.
[][]Remove any dirt or spot with isopropyl alcohol and then dry with tissue paper.
[][]After completion of each analysis, clean the HPLC as follows
[][]Transfer the used glassware for washing.
[][]Clean the plunger seal by injecting distilled water three to four times with syringe.
[][]Remove the column and replace with joints for the cleaning of tubings & flush with 6N nitric acid, distilled water and then with methanol.
[][]Remove the air in suction pipe by purging the line and flushing with distilled water for some time.
[][]Clean the suction filter by sonicating it into nitric acid for 10 to 15 minutes and then wash it with water, when required.
[][]Replace the joints with column and wash the column first with distilled water and then with methanol.
[][]Switch “OFF” the pump, detector(s), injector and column compartment.
[][]Finally enter fill-up the Logbook for Operation of HPLC (Annexure-VI).

Annexure: Calibration of HPLC

Annexure-I: Calibration Information Sheet for Quaternary Pump VL
Annexure-II: Calibration Information Sheet for Thermostatic Column Compartment
Annexure-III: Calibration Information Sheet for Variable Wavelength Detector
Annexure-IV: Calibration Information Sheet for Refractive Index Detector
Annexure-V: Calibration Information Sheet for High Performance Autosampler
Annexure-VI: Logbook for Operation of HPLC

Calibration of HPLC System With Operation & Cleaning Read More »

Calibration of Oven Operation with Operation & Cleaning

Quality Control, SOPs

Calibration of Oven , Purpose :

Calibration of Oven , The purpose of this SOP is to describe the operation, calibration and cleaning of Oven (256 L) (Brand: Memmert, Model: UNE 600) used for drying of glassware in the quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Oven , Scope :

This SOP applies for operation, cleaning and calibration of Oven (256 L) (Brand: Memmert, Model: UNE 600) in quality control laboratory of  XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure.

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, Quality Control

[][]To follow the instructions of this procedure correctly.
[][]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.

Manager, Quality Control

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

Annexure:

N/A

Procedure:

General Precaution(s):

[][]Do not wipe with damped cloth at on position.
[][]Do not overload the chamber with glassware.
[][]Do not keep the items those may produce inflammation with air.
[][]Keep glassware to avoid the touch of inner surface of the chamber.
[][]Avoid opening the door for long period.
[][]Do not move the oven at on position. Severe vibrations may cause serious damage of the temperature probes.

Operation:

[][]Connect the instrument to the main power supply.
[][]Switch ‘ON’ the mains.
[][]Press push/turn control key to put on the main power switch in front of the instrument. The oven will start in normal mode with the display of timer, the chamber temperature, alarm temperature (red color indication).
[][]Hold down the SET key and turn the push/turn control key at the clockwise or anti clockwise for setting date, local time, operating temperature, alarm temperature. After setting, SET key will be released the display briefly flashes the set point.
[][]The display then changes to the actual current temperature and starts to the setting temperature. The temperature will be automatically increased at setting temperature and display the setting temperature digitally.
[][]Observe the display temperature until stable position.
[][]Hold down the SET key (appr. 3 seconds) to select the operation mode, if require. The current operating mode will be flashed on the display. There are three operating mode in the oven:

Normal Operation
Weekly Programmer
Ramp time Programme Operation

[][]Select the required programme and set as per operation manual.
[][]Select the fan speed to set the air changes.
[][]Turn the push/turn control at clockwise until the fan symbol flashing to move the air slider opens and closes the air valve to control the supply and discharge of air.
[][]Check the chamber temperature using by a calibrated digital thermometer, when the setting Temperature reaches.
[][]Keep the glassware’s inside the oven.
[][]The oven will automatically control the Temperature.
[][]The instrument will automatically adjust the temperature. When the temperature exceed the setting temperature, “off” light will illuminate and if the temperature decrease the “on” light will illuminate.

Cleaning Procedure :

[][]Switch off the oven and disconnect the power plug.
[][]Remove all glassware’s from the chamber of oven.
[][]Clean inside & outside of the chamber with dry cloth.
[][]Reload all items into the chamber when reach to dry the chamber surface.
[][]At the end of cleaning, connect the power plug and switch on the oven.
[][]Clean the chamber once in a month.
[][]Clean the outer surface of the oven every day.

Calibration Procedure:

[][]Switch ‘ON’ the mains of instrument.
[][]Set the desired temperature. Follow above operation procedure
[][]Allow sufficient time to equilibrate the set temperature.
[][]Check the temperature using a calibrated thermometer/data logger and record the temperature in the calibration certificate as per Annexure-V of Engineering SOP
[][]Carry out others two calibration temperatures in the same manner.
[][]Calibrate the oven once in a year ± 15 days.

Maintenance :

[][]If oven shows any mechanical, electrical or any others problem, inform to supplier or Engineering Department for corrective action.
[][]After corrective action, recalibrate the oven if it is necessary.

Calibration of Oven Operation with Operation & Cleaning Read More »

Atomic Absorption Spectrophotometer Calibration

Quality Control, SOPs

Atomic Absorption Spectrophotometer Calibration, Purpose :

Atomic Absorption Spectrophotometer Calibration, The purpose of this SOP is to describe the operation and cleaning procedure of Atomic Absorption Spectrophotometer Model No. – A Analyst 400 with Graphite Furness HGA 900 used for analysis of the finished product & raw materials in the Quality Control Laboratory at XX Pharmaceuticals Ltd.

Atomic Absorption Spectrophotometer Calibration, Scope :

This procedure is applicable for the Atomic Absorption Spectrophotometer, 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.

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/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.
[][]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):

[][]Care must be taken in handling the instrument opening, putting sample, and closing especially.
[][]Ensure optimum fluid level, otherwise flame will not ignite.
[][]All the solutions must be prepared carefully.
[][]The detection chamber must be clean and free from any dust of foreign particles.
[][]The selection of correct hollow cathode lamp of a particular atom must be present on a correct position of the lamp holder.
[][]The Air conditioning system and air exhauster must be open during operation of the Instrument.

Operation

[][]Procedure for getting concentration of a particular atom in Flame Method
[][]Ensure proper cleaning of the machine before operation.
[][]Turn on the computer and printer.
[][]Turn on the switch of the instrument.
[][]Turn on the switch of air compressor.
[][]Let open the exhaust switch for a few minutes of the compressor to expel moisture from it.
[][]Close the exhaust switch to retain huge amount of compressed air in it.
[][]Set the accessories apparatus of the flame mode.
[][]Turn on the switch of the Flame mode.
[][]Turn on the operating software on the computer.
[][]Align and optimize the instrument.
[][]Turn the screw of the acetylene gas cylinder and ensure its proper flow to the ignition chamber.
[][]Method setting: A method set by following way-
[][]At first click to file manager.
[][]Then go to new and click to method.
[][]Select the element (test element) from starting condition and click OK.
[][]Click on spectrometer at define element & write the method name in method description.
[][]Then select AA/AA-BG (as per method) from signal option.
[][]Click on setting and select the time, delay time & replicates.
[][]Click on sampler and select Air from Oxidant.
[][]Click on calibration and select Linear Through zero then select results unit (ppb, ppm etc) from equation & units.
[][]Click on standard concentration & select Blank and standard (1, 2, 3 etc).
[][]Then check sequence setting: set the number of standard and samples sequentially and save it.
[][]Then check sequence setting: set the number of standard and samples sequentially and save it.

[][]After completion the program, arrange & displayed the results window, the calibration window, the manual analysis control window and the flame control window from monitor window bar.
[][]Click “ON” button on the right side of the Flame option.
[][]Then follow the instruction of the software and input information accordingly.
[][]After completion of the calibration curve input sample according to software instructions.
[][]After completing analysis print the output or it may be saved.
[][]Turn off the software.
[][]Turn off the gas flow.
[][]Turn off the main instrument and expel air from compressor.
[][]Turn off the Switch of the computer.

Cleaning

[][]Clean all parts of the machine with cotton cloth using methanol after use.
[][]Procedure for getting concentration of a particular atom in Graphite Method
[][]Ensure proper cleaning of the machine before operation.
[][]Turn on the computer and printer
[][]Turn on the switch of the instrument
[][]Turn on the switch of air compressor
[][]Let open the exhaust switch for a few minutes of the compressor to expel moisture from it
[][]Close the exhaust switch to retain huge amount of compressed air in it.

[][]Set the accessories apparatus of the Graphite mode.
[][]Check the cooling system, the water level retain between maximum and minimum level.
[][]Turn on the switch of the Graphite mode.
[][]Turn on the operating software on the computer.
[][]Align and optimize the instrument.
[][]Turn the screw of the Argon gas cylinder and ensure its proper flow to the ignition chamber.
[][]Method setting: A method set by following way-
[][]At first Click to file manager.
[][]Then go to new and click to method.
[][]Then go to new and click to method.
[][]Then select the element (test element) from starting condition and click OK.
[][]Then go to spectrometer at define element & write the method name in method description and select AA/AA-BG from signal option. (as per method)
[][]Click on setting and select the time, delay time, BOC time & replicates.
[][]Click on sampler and go to Furness program & select Temperature, Ramp time, Hold time, internal flow & gas type.
[][]Click on Autosampler and select sample volume, Diluent location, matrix modifiers volume & location.
[][]Click on calibration and select Linear Through zero from calibration equation.
[][]Then select result unit (ppm, ppb etc) from equation and unit.
[][]Click on standard concentration & select Blank and standard (1, 2, 3 etc).
[][]Click on calculate standard volume & select stock standards, location & concentrations. Select the location of blank & reagent blank. Then click to OK and save it.
[][]Then click on Displayed the sample information editor. Write sample location and sample ID then save as in sample information file.
[][]Click on Auto (Automated analysis control)
[][]Click on Open from results data set name (for Data save).

[][]Click on analyze.

[][]After completion the program, arrange & displayed the results window, the calibration window, the automated analysis control window and the Furness control window from monitor window bar.
[][]Then click on analyze all
[][]Then follow the instruction of the software and input information accordingly
[][]After completion of the calibration curve automatically input sample according to software instructions.
[][]After completing analysis print the output or it may be saved.
[][]Turn off the software.
[][]Turn off the gas flow.
[][]Turn off the main instrument and expel air from compressor.
[][]Turn off the Switch of the computer.

Cleaning

[][]Clean all parts of the machine with cotton cloth using methanol after use.
[][]Procedure for getting concentration of a particular atom in MHS Method
[][]Ensure proper cleaning of the machine before operation.
[][]Ensure proper cleaning of the machine before operation.
[][]Set the MHS part with AAS properly.
[][]Set the sample tube on the flame chamber properly.
[][]Turn on the computer and printer.
[][]Turn on the switch of the instrument.
[][]Turn on the switch of air compressor.
[][]Let open the exhaust switch for a few minutes of the compressor to expel moisture from it.
[][]Close the exhaust switch to retain huge amount of compressed air in it.
[][]Turn on the switch of apparatus of the Graphite mode.
[][]Check the cooling system, the water level retain between maximum and minimum.
[][]Turn on the switch of the Flame mode.
[][]Turn on the operating software on the computer.
[][]Align and optimize the instrument.
[][]Turn the screw of the Argon & acetylene gas cylinder and ensure its proper flow to the ignition chamber.
[][]Method setting: A method set by following way-
[][]At first Click to file manager.
[][]Then go to new and click to method.
[][]Select the element (test element) from starting condition and click OK.
[][]Then go to spectrometer at define element & write the method name in method description.
[][]Click on setting and select the time, delay time, BOC time & replicates.
[][]Then click on sampler and go to Furness program & select Temperature, Ramp time,
[][]Hold time, internal flow & gas type.
[][]Click on calibration and select Linear Through zero from calibration equation.
[][]Then select result unit (ppm, ppb etc) from equation and unit.
[][]Click on standard concentration & select Blank and standard (1, 2, 3 etc).
[][]Then check sequence setting: set the number of standard and samples sequentially and save it.
[][]After completion the program, arrange & displayed the results window, the calibration
[][]window, the manual analysis control window and the flam control window from monitor window bar
[][]Then click “ON” button on the right side of the Flam option.
[][]Then follow the instruction of the software and input information accordingly
[][]After completion of the calibration curve input sample according to software instructions.
[][]After completing analysis print the output or it may be saved.
[][]Turn off the software.
[][]Turn off the gas flow.
[][]Turn off the main instrument and expel air from compressor.
[][]Turn off the Switch of the computer.

Cleaning

Clean all parts of the machine with cotton cloth using methanol after use.

Calibration:

Calibration for Flame System:
Wavelength Accuracy Using Ni:

Test Conditions:

[][]Open the default Nickel method (File-New-Method-Ni)
[][]Open the continuous Graphics window so the system will set up for Nickel.
[][]Ensure the lamp has been on for 15 minutes before measuring g absorbance with the Nickel standard.

Test prerequisites:

[][]Burner position Optimized and Nebulizer adjusted using Copper.

Test Steps:

[][]Under the tool bar, double click on the instrument icon in the ‘Spectrometer status panel’ to open the diagnostic/spectrometer window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]A graphic plot of the peaked positions for the prism and Grating will be displayed

The Prism Tolerance is ±190 motor steps
The Grating Tolerance is +380, -260 motor steps

Sensitivity and Precision Using Ni:

Apparatus:

Volumetric flask with stopper, 1000 ml
Glass pipette 3 ml
Beaker 10 to 200 ml

Reagents:

1000 ppm Ni AAS standard solution.
Nitric acid

Preparation for 3ppm Ni standard solution:

[][]Pour a small quantity of 1000 ppm Ni AAS standard solution in the beaker. Use it to rinse the 3 ml pipette and the beaker, then discard it.
[][]Pour another 5ml (minimum) 1000ppm Ni AAS standard solution into the beaker.
[][]Pipette 3 ml standard from the beaker into the 1000 ml volumetric flask.
[][]Half fill the volumetric flask with de-ionized water.
[][]Pour 10 ml (approximately) of nitric acid into the volumetric flask.
[][]Fill the volumetric flask with de-=ionized water exactly to the mark.

Note: 3ppm Ni standard should be produced before the day of test.

Test Steps:

Edit the Nickel default method and enter/verify the following parameter:
Signal type: A
Read time:10.0
Replicates: 10

[][]While in the method editor, go to the calibration/ standard concentrations page. Enter blank for calibration blank ID and Nickel standard for standard ID.
[][]In the ‘Flame Control’ window, select the ‘Flam On/off’ icon to light the flame.
[][]In the ‘Manual Analysis Control’ window, aspirate blank and select ‘Analysis Blank’. 10 Replicates will be measured and autozero will occur.
[][]Aspirate a 3ppm Ni standard and select ‘Analysis Sample’. 10 Replicates will be measured.
[][]The results will be displayed in the result window. Record the values for mean absorbance and relative standard deviation (RSD).The value should meet following requirements.

Mean Absorbance ≥ 0.200
RSD ≤ 0.3%

[][]Return to the ‘Flame Control’ window and extinguish the flame by pressing Flame On/Off.

Wavelength Accuracy Using As:

Test Conditions:

[][]Open the default Arsenic method (File-New-Method-Ni)
[][]Open the continuous Graphics window so the system will set up for Arsenic.
[][]Ensure the lamp has been on for 15 minutes before measuring absorbance.

Test prerequisites:

[][]Burner position Optimized and Nebulizer adjusted using Copper.

Test Steps:

[][]Under the tool bar, double click on the instrument icon in the ‘Spectrometer status panel’ to open the diagnostic/spectrometer window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]A graphic plot of the peaked positions for the prism and Grating will be displayed.
The Prism Tolerance is ±200 motor steps
The Grating Tolerance is ±380 motor steps

[][]Select the ‘X’ in the upper right hand corner to exit the ‘Optical position’ window. Select the X in the Upper right corner to close the window.

AA-BG Baseline Noise at 1 Abs. Using As:

Test Steps:

Edit the Arsenic default method and enter/verify the following parameter:

Signal type:AA-BG
Read time: 2
Replicates: 99

[][]In the Manual Analysis Control window, select the ‘Analyze blank’ button. The system will take 99 readings and perform an autozero.
[][]Insert the 1.0 A neutral density filter into the filter holder.
[][]In the Manual Analysis Control window, select the ‘Analyze Sample’ button. When the reading is complete, record the SD value. It should be ≤ 0.005.

AA Baseline Noise and Drift using Cu:

Test prerequisites:

[][]Burner position Optimized and Nebulizer adjusted using Copper.
[][]Copper lamp should be warmed up at least 15 minutes.

Test Steps:

[][]Open the default Copper method (File-New-Method-Ni)
[][]Open the continuous Graphics window so the system will set up for Copper.
[][]Edit the Copper default method and enter/verify the following parameter:
Signal type: AA
Read time: 0.5
Replicates: 99

[][]In the Manual Analysis Control window, select the ‘Analyze blank’ button. The system will take 99 readings and perform an autozero.
[][]In the Manual Analysis Control window, select the ‘Analyze Sample’ button. Data collection for 99 replicates will begin.
[][]At the end of 99 replicates, record the standard deviation (SD) value in the table below. It should be ≤0.001. Record the mean absorbance value as well.
[][]Wait 15 minutes and repeat the measurement. Record the mean absorbance value for the second measurement.
[][]Calculate the difference between the absorbance measurements. It should be ≤ 0.002 Abs.

Wavelength Accuracy Using Cu:

Test Steps:

[][]Under the tool bar, double click on the instrument icon in the ‘Spectrometer status panel’ to open the diagnostic/spectrometer window.
[][]Select the ‘Optical Position’ button at the button of the diagnostics window.
[][]A graphic plot of the peaked positions for the prism and Grating will be displayed.

The Prism Tolerance is ±120 motor steps
The Grating Tolerance is ±380 motor steps

[][]Select the ‘X’ in the upper right hand corner to exit the ‘Optical position’ window. Select the X in the Upper right corner to close the window.

Copper Capacitance:

The Optical position box also displays two capacitances values. Cap: in the upper left corner. The first value is the cap: used for peaking and the last value is the Final Cap: Record the Final Cap. It should be ≥1.0 pF

Flame Sensitivity and Precision using Cu:

Apparatus:

Volumetric flask with stopper, 1000 ml
Glass pipette 2 ml
Beaker 10 to 200 ml

Reagents:

1000 ppm Cu AAS standard solution.
Nitric acid.

Preparation for 2ppm Cu standard solution:

[][]Pour a small quantity of 1000 ppm Cu AAS standard solution in the beaker. Use it to rinse the 2 ml Pipette and the beaker, then discard it.
[][][][]Pour another 5ml (minimum) 1000ppm Cu AAS standard solution into the beaker
Pipette 2 ml standard from the beaker into the 1000 ml volumetric flask.
[][]Half fill the volumetric flask with de-ionized water.
[][]Pour 10 ml (approximately) of nitric acid into the volumetric flask.
[][]Fill the volumetric flask with de-=ionized water exactly to the mark.

Note: 2ppm Ni standard should be produced before the day of test.

Test Steps:

[][]Edit the Copper default method and enter/verify the following parameter:
Signal type: AA
Read time:10.0
Replicates: 10
[][]In the ‘Flame Control’ window, select the ‘Flam On/off’ icon to light the flam.
[][]In the ‘Manual Analysis Control’ window, aspirate blank and select ‘Analysis Blank’. 10 Replicates will be measured and autozero will occur.
[][]Aspirate a 2ppm Cu standard and select ‘Analysis Sample’. 10 Replicates will be measured.
[][]The results will be displayed in the result window. Record the values for mean absorbance and relative standard deviation (RSD).The value should meet following requirements.
Mean Absorbance ≥ 0.250
RSD ≤ 0.30%
[][]Select the Spectrometer- Setting tab and enter/verify the following parameter:
[][]Signal type: AA

Read time:0.1
Replicates: 10

[][]In the ‘Flame Control’ window, select the ‘Flam On/off’ icon to light the flam.
[][]In the ‘Manual Analysis Control’ window, aspirate blank and select ‘Analysis Blank’. 10 Replicates will be measured and autozero will occur.
[][]Aspirate a 2ppm Cu standard and select ‘Analysis Sample’. 10 Replicates will be measured.
[][]The results will be displayed in the result window. Record the value for relative standard deviation (RSD).The value should meet following requirements.
RSD ≤ 3.0%
[][]Return to the ‘Flame Control’ window and extinguish the flame by pressing Flame On/Off.

Calibration for Flame System:

Chromium Baseline Noise For Furness:

Test Steps:

[][]Click on the File pull down menu, then on Open. Select Method.
[][]Click on Browse. Go up 2 levels and double-click on Service. Then double click on Method.
[][]Double click on HGA Cr Test method. Select the Method Ed icon to open the Method Editor window.
[][]In the spectrometer section, select set. Select 2.7 Slit Width and 0.8 Slit Height. Select OK. Click on the file pull down menu, then on Save. Select Method. Close the Method Editor window.
[][]Click on the Tools pull down menu and then select Continuous Graphics. This will set up the Lamp. Close the Continuous Graphics window.
[][]Open the Align lamps window. Look at the Bar Graph status window and verify that the Cr HCL Lamp current is 15 mA and the Slit is se4t to 2.7/0.8. Also verify that the Background corrector is On. Allow the lamp to warm up for 30 minutes.
[][]Close the Align Lamps window.
[][]From the Tools pull down menu open the windows Results, Peaks and Automated Analysis. Arrange and align the windows as desired.
[][]Open the Furness control window and select the Furness ON/Off button to run at least one dry firing (without any sample) to make sure that there is no residual signal (Peak area less than 0.005) from any previous injections or tube contamination.
[][]Make sure position 3 of the Autosampler is empty. Type in 3 as the sample lactation in the setup page of the Automated Analysis window, click on the Analyze tab and then on the Analyze Samples button to measure 5 Furness dry firings (without any sample).
[][]Ensure that the AA and BG signals do not diverge from the baseline. Realign the Furness into the optical beam if necessary.
[][]The standard deviation of the mean dry-firing result in integrated absorbance (Peak area) for the Cr wavelength must not exceed a maximum value of 0.002. Record the result.

Chromium Characteristic Mass and Precession:

Test Steps:

[][]Use the same method as in the previous test. Demonized water should be in position 1 and Cr standard should be in position 2 of the Autosampler.
[][]Type in 2 as the sample lactation in the setup page of the Automated Analysis window, click on the analyze tab and then on the Analyze Samples button to measure 5 furnace firings using 20 µl sample injections.
[][]Calculate the characteristic mass using the Calculate characteristic mass tool from the Analyses pull down menu.

Characteristic Mass Result:

The characteristic mass (m0) results in pg and calculated from the mean integrated absorbance (Peak area) values should lie within the following ranges:

Element: Cr

Lower Limit (pg): 2.3

Target Value (pg): 3.0

Upper Limit (pg): 3.8

Note: If the characteristic mass exceeds the lower limit, check for possible contamination of the water used for sample preparation. Prepare a new solution if required.

Precision:

[][]The relative standard deviation (%RSD) of the mean sample solution readings calculated from the integrated absorbance (peak area) values for Cr must not exceed the maximum value of 2.0%.
[][]Record the results in the OQ Test Certificate on page 40.
[][]AS-800 Autosampler Linearity
[][]Click on the File pull down menu, then on Open. Select Method.
[][]Verify that you are in the Service\Methods directory. If not, click on Browse. Go up 2 levels and double-click on Service. Then double click on Method.
[][]Double click on HGA AS-800 Lin method.
[][]Select the Method icon to open the Method Editor window.
[][]In the spectrometer section, select Set. Select 2.7 Slit Width and 0.8 Slit Hight. Select OK.
[][]On the right side of the Method window select the Settings tab.
[][]In the Lamp Current section, select Use current (mA) and then type 15 in the Lamp Current box.
[][]Click on the File pull down menu, then on Save. Select Method.
[][]Close the Method Editor window.
[][]Clock on the Tools pull down menu and then select Continuous Graphics. This will set up the Lamp. Close the Continuous Graphics windows.
[][]Open the Align lamps windows. Look at the Bar Graph status window and verify that the Cr HCL Lamp current is 15mA and Slit is set to 2.7/0.8. Also verify that the Background Correction is ON. Allow the lamp to warm up for 30 minutes (if not already warmed up).
[][]Close the Align Lamps window.
[][]From the Tools pull down menu open the windows Results, Peaks, Examine Calibration and Automated Analysis. Arrange and align the windows as desired.
[][]Click on the Analyze tab of the Automated Analysis window and then on the Calibration button top start the calibration.
[][]When the calibration is finished check the Correlation Coefficient Result in the Examine Calibration window.
[][]The Correlation Coefficient Result Cr must exceed the minimum value of 0.999.

Annexure: Atomic Absorption Spectrophotometer Calibration

Annexure-I: Calibration Information Sheet for Wavelength Accuracy, Sensitivity and Precision using Ni
Annexure-II: Calibration Information Sheet for Wavelength Accuracy and AA-BG Baseline Noise at 1 Abs. using As
Annexure-III: Calibration Information Sheet for Baseline Noise, Wavelength Accuracy, Copper Capacitance, Flame Sensitivity and Precision using Cu
Annexure-IV: Calibration Information Sheet for Baseline Noise, Characteristic Mass and Precession, Autosampler Linearity using Cr
Annexure-V: Operation logbook for Atomic Absorption Spectrophotometer

Atomic Absorption Spectrophotometer Calibration Read More »

error: Content is protected by www.pharmaguideline.co.uk !!