Certification of Analyst, Purpose :

Certification of Analyst, The purpose of this SOP is to determine the capability of the newly recruited analyst to perform analysis accurately within the specified parameters and to demonstrate the analyst’s ability to perform in quality control laboratory at XX Pharmaceuticals Ltd.

Certification of Analyst, Scope :

This SOP applies to assure that the analysts are familiar with all test parameters, analytical procedures, instruments operation and documentation 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:

Officer/Executive/ Sr. Executive, Quality Control

[][]To follow the instructions of this procedure correctly.
[][]To maintain the records properly as per SOP.

Manager, Quality Control

[][]Responsible for the certification of analyst and verification of results and comparison with acceptance criteria.
[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP is technically sound and reflects the required working practices.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

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

Procedure:

General Precaution(s):

[][]Training should be conducted until the analyst is competent enough to carry out the analysis independently.
[][]Make sure that new employee know about the laboratory safety procedure.
[][]Adequate knowledge on handling of spillages and management of chemicals & reagents in the laboratory.
[][]Hands on waste management in the laboratory.
[][]Understanding the operation, cleaning and calibration procedure of instruments used in the laboratory.

Operation:

[][]Recently approved two specific samples of raw material or finished product or packaging material shall be given to the analyst to perform test for analyst certification.
[][]The samples are to be coded as (A) or (B).
[][]These samples packed in a manner which can prevent exposure to moisture, light and heat.
[][]In-Charge, QC should ensure that the analyst is performing the specified tests following respective method of analysis and specification.
[][]The analytical findings shall be recorded in the respective worksheet and the summary of results shall be entered in the prescribed format (Annexure-I).
[][]In-Charge, QC shall review the results in comparison with the known values for the test carried out and forward to Head of QA for approval.
[][]The analyst shall be considered qualified if the results obtained by him/her within the specification limit and within acceptable limit for certification of analyst.
[][]The details like calculations, chromatograms and spectrums along with comments of Head of QA shall be filed in training file of analyst.
[][]No repeat of the test will be allowed to the analyst.
[][]The result are provided by analyst will be crosscheck to the previous result and check the similarity.
[][]Head of QA will decide for the selection of analyst for routine analysis after review of analysis report. If the analyst is failed to qualify the test analyst will undergo further training.
[][]The certification of analyst shall be applicable to him/her only for carrying out these activities for which he/she is certified.
[][]Re-certification of the analyst shall be carried out once in every three years.
[][]The acceptance criteria for the analytical results shall depend upon the nature of tests carried out and the range provided in the specifications.
[][]Following acceptance criteria may be used for evaluation comparing with approved analyst.
[][]Assay by Spectrophotometer +/- 1% of previous value
[][]Assay by HPLC +/-0.5% of previous value
[][]IR spectra should match with standard and previous spectra
[][]Water content by KF +/-1% of previous value

Annexure:

Annexure-I: Analyst Certification Report.

Water Sampling, Purpose :

Water Sampling, The purpose of this SOP is to describe the procedure for sampling and analysis of water in quality control laboratory.

Water Sampling, Scope :

This procedure is applicable for sampling and analysis in Quality Control Laboratory for purified water, water for injection, purified steam condensate, potable water, drinking water and effluent treatment plant water from different user points used in XX  Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]QC: Quality Control
[][]QA: Quality Assurance
[][]QCom: Quality Compliance
[][]COA: Certificate of Analysis
[][]WFI : Water for Injection
[][]PW: Purified water
[][]ETP: Effluent treatment plant

Responsibilities:

The roles and responsibility is as follows:

Lab Attendant, QC

[][]To collect water sample from different sampling points.

Officer / Executive, QC Officer / Executive, QC

[][]To prepare schedule sampling of water.
[][]To organize the sampling of water.
[][]Analysis of water and preparation of respective test report.
[][]Trend analysis of water.
[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Sr. Executive, QC

[][]Reviewing of test report.

Manager, Quality Control

[][]Approval of test report.
[][]To ensure implementation of the SOP after training.

Head of Quality Assurance

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

Procedure:

Precaution(s):

[][]Use gloves, mask & cap during sampling.
[][]Collect sample carefully to avoid contamination.
[][]Carefully collect water sample with high temperature and close the cap of container freely.

Sample Collection :

[][]Take required number of 500 ml to 1 Liter clean glass containers with cap for sampling.
[][]Open sampling points such as tap fixtures / hosepipe and allow water to run for not less than 1 minute.
[][]Rinse the container with respective water.
[][]Collect approximately 500 ml of water and immediately recap the sample containers after collecting samples. Keep the cap slightly loose when water temperature is above 30°C.
[][]Label the sample container providing information such as name of water, sample point no. / location, time, initial of sampler and date of sampling.
[][]Transfer the sample immediately to laboratory and analyze the sample within 24 hours of sampling. Preserve the sample in refrigerator (2°C to 8°C), if required.
[][]Entry information of sampling in sampling register after sampling.

Test Schedule :

Perform the test as per the following schedule :

Source of Water /Test frequency

Potable Water/ Once in a month
Purified Water/ Once in 14 days
ETP Water /Once in a week
Water for Injection/ Once in a week

Chemical Analysis :

[][]Perform analysis of water as per respective specification and method.
[][]Compile the raw data and prepare the certificate of analysis as per respective annexure with the test results & take approval of the COA.
[][]Share the water test reports with Engineering department and or Production department.
[][]Water test results are to be evaluated on a continuous basis and should be summarized in trend analysis report six monthly in order to identify significant trends.
[][]Inform respective department i.e. Engineering, Production and Quality Assurance Department whenever atypical data found beyond alert limit.
[][]Inform respective department i.e. Engineering, Production and Quality Assurance Department for taking actions whenever data found beyond action limit.

Annexure:

Annexure-I : Format for Certificate of Analysis for Potable water/Drinking water
Annexure-II : Format for Certificate of Analysis for Purified water/Water for injection/Purified Steam Condensate
Annexure-III : Format for Certificate of Analysis for Effluent Water
Annexure-IV : Format for Water Sampling Register
Annexure-V : Water sampling points

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 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.

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

Wash Water, Purpose:

Wash Water, The purpose of this SOP (Standard Operating Procedure) is to define the Sampling and analytical procedure for wash water.

Wash Water, Scope:

This procedure is applicable for sampling of wash water from production equipments and analysis of wash water in the Quality Control laboratory  of XX Pharmaceuticals Ltd.

Definition:

None

Responsibilities:

The roles and responsibility is as follows:

Executive, Production

[][]To co-ordinate to collect the sample as per defined procedure
[][]To send duly filled Wash Water Sampling Advice Form to QC/QA Department.
[][]To maintain the proper documentation.

Sr. Executive/Executive, Quality Assurance

[][]To withdraw the sample as per the defined procedure.

Sr. Executive/Executive, QC

[][]To analyze the sample as per defined procedure
[][]To ensure that this procedure is kept up to date.

Manager, Quality Control

[][]To ensure appropriate personnel from the section are trained on this procedure.
[][]To confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

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

Procedure:

[][]Production personnel clean the equipment as per standard cleaning procedure, intimates QC/QA for wash water sampling with the “Wash Water Sampling Advice Form” in duplicate.
[][]Quality Compliance representative inspects the equipment and its parts for cleanliness and then collects the sample as follows:

Vibratory Shifter:

[][]Attach the sieve on the body of the sifter and wash with 3.0 L of Purified water and collect the sample at the receiver into a clean bowl. Rinse the dismantled parts (Lid, clamp, hopper and silicon gasket) with 2 liters of purified water and collect into the same bowl. Collect approx. 30 ml of the sample into an amber colored bottle for analysis.

Container Blender:

[][]Rinse the colloid mill with 3.0 L of Purified water and collect it into a clean bowl. Collect 30ml of the sample into an amber colored bottle from the bowl for analysis.

Rapid Mixer Granulator:

[][]Rinse the equipment bowl and top lid with 30.0L of Purified water and collect the water into a clean bowl through the discharge taking care that the whole surface of the bowl and top lid is rinsed properly and rinse the dismantled parts (clamp for binder addition, charging port, spray nozzle, vent filter, chopper blade, impeller blade discharge valve and all gaskets) with 5 liters of purified water and collect into the same bowl. Collect approximately 30 ml of sample into an amber colored bottle for analysis.

FBD (Fluid Bed Drier):

[][]Rinse the retarding chamber internally with 10.0 L of Purified water and collect it into a clean bowl. Collect approximately 30 ml of the sample into an amber colored bottle for analysis. Similarly rinse the FBD trolleys with 10.0 L of Purified water each and collect 30ml of the sample separately from the two bowls. Rinse the cartridge filters/FBD bag with 5-liters of purified water and collect the water into the clean bowl. Collect approximately 30 ml of the sample into an amber colored bottle for analysis.

Tablet Coating Machine:

[][]Rinse the pan with 10.0L of Purified water and collect the sample into a clean bowl through the discharge taking care that the whole surface and the Baffles are rinsed properly. Rinse the dismantled parts (Silicon tube, Gun assembly, inlet duct and outlet duct) with 5 liters of purified water and collect into the same bowl. Collect approximately 30 ml of the sample into an amber colored bottle for analysis.

Compression machine:

[][]Rinse the hoppers, butterfly valve, triclover clamp, force feeder, inlet connector, Turret guards, Powder scrapper, Acrylic guards, feeder shaft, Exhaust pipes with 5 liters of purified water and collect in a clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis. Similarly rinse the y – chute, Gravity pipe with 5 liters of purified water and collect in the clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis.

Capsule Filling Machine:

[][]Rinse the capsule loading channel, hopper, Loading ring, Auger, Locking pin assembly with 5 liters of purified water and collect in to clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis.

Capsule polishing Machine:

[][]Rinse S.S cover of polishing Machine and polishing brush with 2 liters of purified water and collect in to clean bowl. Collect approximately 30 ml of this sample into an amber colored bottle for analysis.
[][]While collecting wash water sample, collect Purified water about 30 ml into an amber colored bottle.
[][]Use this as blank.

Note: For the equipments, which are not specified above, use 2.0 L, 5.0 L, & 10.0 L as the rinsing water quantity depending on the size i.e. small, medium & big.

Analysis:

[][]After getting sampling advice form from production department, QC personnel will entry in the wash water register and assign a lab control number as WW-000X/MM/XX(where WW for Wash Water, 000X- Sequential number of four digits, MM-Month and YY-Last two digits of year. For example: WW-0001/08/XX). Then the compliance personnel will collect the sample and send to Quality Control department for analysis.
[][]QC analyses the sample by scanning through 190-400 nm on UV-VIS Spectrophotometer, using Purified water (collected as explained earlier) as blank.
[][]Observe for any abnormal peaks and/or peaks having same wavelength maximum of active material of previous product.
[][]Reject the sample in case of any abnormal peak or if a peak of previous product having more absorbance that of a 10 ppm standard solution of active of previous product and send the information to the concerned department.
[][]Take the spectrum print out on the back side of the wash water report copy (QC copy) and inform production for rewash.
[][]If absorbance is less than that observed in standard graph, intimate the concerned department by sending the original copy of the report after making necessary entries and approving the clean card. Retain the duplicate copy of the report and file it after making necessary entries in the register.

Annexure:

Annexure-I: Wash Water Sampling Advice Form.
Annexure-II: Wash Water Register.

Out Of Specification (OOS), Purpose :

Out Of Specification (OOS), The purpose of this SOP is to define the procedure for handling of OOS results in the Quality Control Laboratory of XX Pharmaceuticals Ltd.

Out Of Specification (OOS),Scope :

[][]This SOP is applicable for all Out of Specification (OOS) results detected during testing of any product or materials in Quality Control Laboratory of general block of XX Pharmaceuticals Limited.
[][]If an out of specification results is generated for dissolution/ Drug release, uniformity of dosage units, weight variation, disintegration test, In process sample and any other test which is used to measure variability in a lot this SOP does not apply. In such cases respective Pharmacopoeial guidelines or criteria shall be apply.
[][]This SOP does not apply to samples of various stages like In process samples, Intermediate samples, scale up batches, method validation, method development, solvents, packaging material, wash water, decontamination samples, evaluation samples, raw material received from new vendor, description and solubility test, tests where tentative limits given.
[][]This SOP does not apply for OOS to tests like Bulk density, Sieve analysis, Particle size and other physical parameters.
[][]This SOP does not apply when system suitability failure, bracketing standard, transcriptional errors or processing method errors (In case of failure due to the integration parameters for the HPLC).
[][]This SOP does not apply to incomplete analysis where result is not derived.
[][]Out of Specification is not applicable for out laboratory testing.

Definitions / Abbreviation:

[][]Standard Operating Procedure (SOP): Standard Operating Procedure. A written authorized procedure, which gives instructions for performing operations.
[][]QC: Quality Control.
[][]CAPA: Corrective action and preventive action.
[][]OOS result: An OOS result is a result from a defined test procedure that fails to meet established specifications or criteria. An OOS result does not constitute a failure unless further investigation confirms this result.
[][]Atypical result: Results that are still within specification but are unexpected, questionable, irregular, deviant or abnormal.
[][]Obvious error : Obvious error can be occurred due to:
Calculation Error
Laboratory error
[][]Laboratory Error: A mistake that occurs within the test laboratory caused by an analyst or piece of equipment. Examples include use of incorrect standards, improper sample or standard preparation, improperly calibrated balances, equipment failure and miscalculations.
[][]Laboratory Investigation: The investigation that is conducted within the laboratory to determine the cause of the OOS results.
[][]Assignable Cause: An identified reason for obtaining an OOS or aberrant/anomalous result.
[][]No Assignable Cause: When no result could be identified.
[][]Review: To check all critical parameters involved in the test which may cause of the OOS results.
[][]Reanalysis: Further analysis with the same dilution of sample or of same aliquots which produced OOS results.
[][]Retest: Re-examining the material from the original sample that was used as the source of the aliquot that produced OOS result.
[][]Resample: A new sample from the original container where possible, required in the event of insufficient material remaining from original sample composite or proven issue with original sample integrity.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]Analysis of any product or materials and to notify the OOS results to supervisor.

Sr. Executive, QC

[][]To ensure the initial investigation of the test parameters and to organize the testing.

Manager, Quality Control

[][]To ensure that this procedure is kept up to date.
[][]To confirm that the SOP reflects the required working practices.
[][]To make decision for re-sampling.
[][]To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Head of Quality Assurance

[][]Approval of the SOP.
[][]To take the final decision to release the batch.
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]The procedure mentioned below shall be followed if a Laboratory result for raw materials sample, In-process Sample or Finished Product sample fails to meet the Specification.
[][]Analyst shall not destroy the sample preparation / solution and shall retain the prepared solutions, Standards and Sample solutions until the investigations have been concluded.
[][]Retain all Glassware, Blend & Finished Product Sample.
[][]Check the whole analysis for compliance (Self-check).
[][]Inform immediately to the Supervisor about the OOS result.
[][]Supervisor will discuss with the analyst about the test method and confirm analyst knowledge of and performance of the correct procedure.
[][]Check if a laboratory error could be the cause of OOS results and inform Manager, QC.
[][]Check and record the present conditions in Notification of out of specification (OOS) result as per Annexure-I.
[][]Follow the Flow Chart (Annexure-II) for OOS Investigation
[][]The QC Manager should assess the data promptly to ascertain if the results may be attributed to laboratory error, or whether the results could indicate problems in the manufacturing process.

[][]It is to be clarified together with the QC Manager whether there is an apparent analytical error. A formal check is to be carried out (Investigation stage 1) using Out of Specification (OOS) Results Investigation Checklist (Annexure – IV) which shall be issued by QC Manager making entry in the Out of specification investigation register (Annexure – III) and assigning sequential number as below:
e.g. OOS-001/xx
Where, OOS is the abbreviation of Out of Specification
001 is the sequential number of Out of Specification investigation
/ is separator
xx is last two digits of year 20xx

[][]At the first step, the QC Manager along with Analyst shall immediately try to find out any obvious Error (Example: Calculation error, Power outage, Equipment failure, Testing Error, Incorrect Instrument Parameters etc.)
[][]If any calculation error is found out, make correction the calculation and release the material/product; analyst shall be re-trained for the error parts.
[][]If the calculation / documentation are correct, proceed with the investigation of the stepwise analysis which may include re-examination of the actual solutions, test units, glassware used in the original measurements and preparations.
[][]The following steps should be taken as part of the investigation:
[][]Discuss the test method with the analyst; confirm analyst knowledge of and performance of the correct procedure.
[][]Examine the raw data obtained in the analysis, including chromatograms and spectra, and identify anomalous or suspect.
[][]Confirm the performance of the instruments.
[][]Determine that appropriate reference standards, solvents, reagents, and other solutions were used and that they meet quality control specifications.
[][]Evaluate the performance of the testing method to ensure that it is performing according to the standard expected based on method validation data.
[][]Document and preserve evidence of this investigation.
[][]Where a transient equipment malfunction or other problem in the dosage form (e.g. incomplete extraction) is suspected, re-inject the retained sample preparations to assign a cause for OOS results.
[][]When laboratory error is identified, determine the source of that error (root cause) generating CAPA as per the SOP for ‘Corrective and Preventive Action’  and take corrective action to ensure that it does not occur again. Recommend on Out of Specification (OOS) Results Investigation Checklist (Annexure – IV) for performing a repeat analysis on the same sample with the same analyst. If the repeat analysis result is passing, void the initial result and approve the batch based on the re-test result.
[][]If no apparent analytical error can be found, i.e. evidence of laboratory error remains unclear, investigation stage 2 should be conducted to determine what caused the unexpected results, which may include re-testing and/or re-sampling and further investigation.
[][]Before further investigations are carried out during the next step, the subsequent procedure has to be written down in the testing protocol (Annexure – IV).
Tasks in testing protocol:
“What” is to be done (retesting, re-sampling, etc.)?
“Who” will be carrying out the investigations (1st analyst, 2nd analyst, etc.)?
“How” will the investigations be carried out, which equipment, which reagents, additional analysis of reference samples (state batch and number of analysis)?
“How often” will the analysis be repeated (final criterion to prevent “analysis” into
“compliance”)?
[][]A justification for the procedure must be given by the QC manager prior to implementation of the testing protocol and the test plan must be approved.
The number of retests should be 3 times or more
[][]The investigation may involve re-testing a portion of the original sample. The sample used for the retesting should be taken from the same homogeneous material / product that was originally collected for the lot/batch, tested and yielded the OOS result. For a liquid, it may be from the original unit liquid product or composite of the liquid product; for a solid it may be an additional weighing from the same sample composite that had been prepared by the analyst.
[][]Decisions to retest should be based on the objectives of the testing and sound scientific judgment. Retesting should be performed by an analyst other than the one who performed the original test.
[][]If the result is within specification (passes), the material/product shall be re-analyzed by first analyst with the same sample and to investigate the first analyst.
[][]If investigation of first analyst found satisfactory then release the material/product
[][]If the material/product fails by the second analyst also, simultaneously analyze after re-sample with the previously approved material/product.
[][]Re-sampling should involve analyzing a specimen from the collection of a new sample from the batch. A re-sampling of the batch should be conducted if insufficient quantity of the original sample remains to perform all further testing or if the investigation shows that the original sample was not representative of the batch. This would be indicated, for example, by widely varied results obtained from several aliquots of the original composite (after determining there was no error in the performance of the analysis). Re-sampling should be performed by the same qualified, validated methods that were used for the initial sample. However, if the investigation reveals that the initial sampling method was in error, a new accurate sampling method must be developed, qualified and documented.
[][]If previously approved material/product passes within the specification and material/product under investigation meets the specification, release the material/product.
[][]In case of material if previously approved material passes within the specification and material under investigation fails to meet the specification, material shall be rejected.
[][]In case of product if previously approved product passes within the specification and product under investigation fails to meet the specification, the laboratory investigation may be extended to review the quality of the materials (raw & primary packaging) used in manufacturing of the finished product. If any problem in quality of the materials is identified which may have potential effect on the OOS scenario, the root cause will be attributed to that problem.
[][]The procedure is then to be implemented and the results be evaluated. The results are to be summarized in Annexure – VI (report level 2).
[][]Conclusion must be drawn and it must be stated which individual values will be entered in the result (on Certificate of Analysis).
[][]The error category of the initial OOS result must also be recorded.
[][]At measures, a statement must be made explaining how similar OOS results are to be avoided in future.
[][]During investigation of an OOS result, review the previous investigation reports to determine whether a similar occurrence has taken place.
[][]When the laboratory investigation does not determine that laboratory error caused the OOS result and testing result appears to be accurate, the laboratory investigation/report to be handed over to QA manager for a full-scale failure investigation as per the SOP for ‘Deviation Procedure’.
[][]In case the process error is identified during failure investigation, suitable corrective action shall be taken. Sample shall then be analyzed as per routine procedure and accordingly release, if the results are okay.
[][]Quality Assurance Manager will initiate the CAPA based on root cause found in the failure investigation. CAPA must be implemented within agreed time lime. All CAPAs must be implemented based on criticality.

Annexure:

Annexure-I: Notification of Out of Specification Result
Annexure-II: Flow Chart for OOS Investigation
Annexure-III: Out of Specification (OOS) Register
Annexure-IV: Out of Specification (OOS) Investigation Checklist
Annexure-V: Out of Specification (OOS) Testing Protocol
Annexure-VI: Out of Specification (OOS) Investigation Report

Shaking Water Bath Calibration, Purpose :

Shaking Water Bath Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Shaking Water Bath (Model: Clifton, NE5-28D).

Shaking Water Bath Calibration, Scope :

This procedure is applicable for Shaking Water Bath (Model: Clifton NE5-28D), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]LED: Light-emitting diode

Responsibilities:

The roles and responsibility is as follows:

Sr. Executive/Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

General precautions or operational safety:

[][]Laboratory coat, hand gloves and safety glasses must be worn while handling the instrument.
[][]Always follow good laboratory practice by ensuring substances being heated offer no risk of a hazard (explosion, implosion or release of toxic or flammable gases) or that these have been addressed. When heating substances where liberating of gases occurs suitable extraction should be used.
[][]If this product is not used in accordance with these instructions, then basic safety protection afforded by the water bath may be affected.
[][]Check the operation of over temperature device regularly.
[][]The main supply cord fitted to this product is a heat resistant type and should be replaced by an equivalent type.
[][]Always use the display or a thermometer to check the temperature. Never touch the liquid within the bath as it may be very hot.
[][]Always disconnect the bath from the electric supply before cleaning.
[][]Allow the liquid in the bath to cool down to 40°C before draining.
[][]Do not operate water bath without water.
[][]Do not open the lid during operation.
[][]Always use the lid when the instrument is not in use to avoid contaminants landing in the bath liquid.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Check the water level, if required, the bath is filled to an appropriate level with purified water prior to switching it on.
[][]Switch on the bath using the ‘O/I’ switch, located at the right side of back of the shaking water bath.
[][]At first display will show “Clifton”.
[][]Press [Enter] button for Menu.
[][]To create a program, select “Do nothing” by using [UP/DOWN] key and press [Enter] button.
[][]Set the required temperature by [UP/DOWN] key and press [Enter] button.
[][]Select “Disable” by using [UP/DOWN] key and press [Enter] button.
[][]Then display will show “Stopped”.
[][]Press [Enter] button for next step.
[][]Set delay start time, ramp time by using [UP/DOWN] key and press [Enter] for next step.
[][]Set the set temperature by using [UP/DOWN] key and press [Enter] button to set the dwell time by using [UP/DOWN] key.
[][]Press [Enter] button.
[][]Select “English” by using [UP/DOWN] key and press [Enter] button for two times.
[][]Display will show a graph.
[][]Press [Enter] button for three times.
[][]Select “Start” by using [UP/DOWN] key and press [Enter] button.
[][]Select “Yes” to conform by using [UP/DOWN] key and press [Enter] button.
[][]Select “Local” by using [UP/DOWN] key and place the beaker containing sample into the shaking water bath and press [Enter] to start the instrument.
[][]LED indicator will illuminate when the bath temperature is either 4°C above or below set temperature.
[][]After completion of work, switch off the bath using ‘O/I’ switch, located at the right side of back of the shaking water bath.

Calibration:

[][]Calibrate the Shacking water bath once in a year.
[][]Fill purified water in water bath to an appropriate level.
[][]Switch on the bath using the ‘O/I’ switch, located at the right side of back of the shaking water bath.
[][]Set the desired temperature against calibrated standard thermometer at 37⁰C, 50⁰C, 90⁰C.
[][]Allow 30 minutes to equilibrate.
[][]Check the temperature using a calibrated standard thermometer and record the temperature in the calibration information sheet for shaking water bath (as per Annexure-I).

Cleaning:

[][]Clean the instrument once in a week or in between when water becomes dirty.
[][]Switch ‘OFF’ the instrument.
[][]Open the lid of the shaking water bath.
[][]Wash the lid properly with purified water.
[][]Remove the water from water bath to reduce potential biological contamination.
[][]Wash the shaking water bath with soapy water and then purified water.
[][]Mop with clean dry cotton cloth.
[][]Use 10% nitric acid on a cloth (wear suitable gloves) to remove any deposits.
[][]Add 1 litre of vinegar to water in the stainless steel tank, gently heat to 50°C for an hour, empty and brush the lime away for descaling. Rinse thoroughly afterwards.
[][]Fill with purified water up to desired level of the shaking water bath.
[][]Close the lid of bath.

Annexure:

Annexure-I: Calibration Information Sheet for Shaking Water Bath.

Calibration of Polarimeter , Purpose :

Calibration of Polarimeter , The purpose of this SOP is to describe the operation, calibration and cleaning of Polarimeter (Model: Rudolph, AUTOPOL IV) used for the determination of the optical rotation in quality control laboratory at XX Pharmaceuticals Ltd.

Calibration of Polarimeter , Scope :

This procedure describes the application of Polarimetric determinations of optical rotation of raw materials (active & excipients), intermediates and drug product etc. in the quality control laboratory of general block at XX Pharmaceuticals Limited.

Definitions/Abbreviation:

Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/ Sr. Executive, Quality Control

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

[][]The equipment should not be set near to room heating equipment or direct sunlight.
[][]Not to spill water or sample on the main body of the instrument.
[][]Use the instrument at an ambient temperature of 5°C to 35°C and RH lower than 90%.
[][]Disconnect the power supply before moving or cleaning of the instrument.

General procedure:

Polarimetry is used to measure the effect that an optically active molecule in solution has on polarized light. Specific Optical Rotation is defined as an Observed Optical Rotation, measured at a specific wavelength and temperature, corrected for the path length of the optical cell and concentration of the solution. The sample is normally presented to the Polarimeter as a solution, contained in a thermally controlled optical cell. A beam of polarised light is then passed through this cell and any rotation of this polarised light is measured via a detector

Reagent quality:

[][]If water is used in the preparation of sample solutions, it must be purified by distillation or deionization process.

Instrument equilibration:

[][]The instrument must be equilibrated before use. The polarimeter (set to required wavelength), must be switched on for a minimum of at least 30 minutes before use.

Preparation and storage of samples:

[][]Sample solutions must be prepared in accordance with the analytical method. Sample solutions must be discarded at the end of the working day, unless solution stability has been demonstrated.

Preparation for measurement:

[][]Connect the power cable and turn the Polarimeter ON.
[][]Press Menu to select the measurement settings.
[][]Press Scale button and select the specific optical rotation.
[][]Press Temperature correction and select off mode.
[][]Press Statistics button and select on (n-1).
[][]Exit from the Menu by pressing Exit button.
[][]Fill the Polarimeter cell with sample blank and place it into the sample chamber.
[][]Press Zero button for zeroing the sample blank.
[][]Then remove the cell from the sample chamber and discard the sample blank and rinse the cell with the sample.
[][]Fill the cell with the sample and press Measure.
[][]Type the Lot ID and press Enter.
[][]Input the sample weight and press Enter.
[][]Type the Sample Name again presses Enter.
[][]When the measurement completed, press Print Option to the results.
[][]Remove the polarimeter cell from the chamber.

Calculation of Specific Optical Rotation:
The specific optical rotation of a sample is calculated as follows:

A=αx100/I x c

Where,
[α] = Specific Rotation at Temperature, T°C and wavelength, λ nm
Α = Observed Rotation in degrees (°)
l = Path length in decimeters (dm)
c = Concentration of analyte (g /100 ml)

Cleaning of the instrument:

Cleaning of the cell:

[][]The cell must be cleaned after use. Thoroughly rinse the cell with the same solvent used for the sample, then rinse with purified water followed by methanol.

Cleaning of the sample compartment:

[][]The sample compartment should be cleaned immediately if anything is spilled into it in order to preserve the black matt finish and prevent corrosion or contamination.
[][]Use a soft cloth impregnated with a soapy solution to rub away any foreign material.
[][]Use a clean soft cloth dampened with water to rinse the cleaned surfaces thoroughly.
[][]Finally dry with a lint free cloth or tissue.

Calibration check with sucrose solution:

[][]Frequency: Yearly
[][]The check consists of determining the specific optical rotation of sucrose solution, using 20% w/v solutions. The method is detailed below. All results and calculations must be recorded on the calibration information sheet for Polarimeter.

Procedure:

Apparatus:

1dm Polarimeter tube.
Thermostat bath 20°C ± 0.2°C.

Reagent:

Sucrose Solution

Loss on Drying:

[][]Accurately weigh approximately 1g of sucrose into a clean dry weighing bottle that has previously been dried at 105°C, cooled in a dessicator for half an hour and weighed.
Dry in an oven at 105°C±2°C for 2 hours, then cool in a desiccator and reweigh.
[][]Calculate the loss in weight as a percentage and record the result on the polarimeter calibration check sheet using the following calculation:

LOD=Weight loss(g)/Weight taken(g)x100

Determination of Specific Optical Rotation at 20°C:

[][]Accurately weigh about 20 g of Sucrose into three separate 100 ml volumetric flasks. Dissolve in 80 ml of water and dilute to 100 ml with water.
[][]Zero the polarimeter using purified water in the 1dm polarimeter tube.
[][]Determine the optical rotation of each solution at 20°C ± 0.5°C in the 1dm tube.
[][]Record and calculate the results obtained for each solution on the polarimeter calibration check sheet using the following calculation:

A=αx100x100/I x c x(100-%LOD)

Where,
[α] = Specific Rotation at Temperature, 20°C and wavelength, 589.3 nm
A = Observed Rotation in degrees (°)
l = Path length in decimeters (dm)
c = Concentration of analyte (g/100 ml)
The specific optical rotation for each solution should be in the range +66.3° to +67.0° (reference the current European Pharmacopoeia).

Calibration check with Quartz Control Plate:

Frequency: Yearly
Apparatus:
Quartz Control Plate
[][]Check that the instrument and the Quartz Control Plate are at room temperature and that the instrument has been on for at least 10 minutes with the Quartz control Plate resting in the back of the sample chamber.
[][]Press Menu button to select Measurement Settings.
[][]Press Scale to select Optical Rotation.
[][]Press Temperature Correction and select Quartz.
[][]Press Statistics and select on (n-1).
[][]Press Exit button to return Manu.
[][]Press zero for zeroing the instrument.
[][]Place the Quartz Control Plate in to the sample chamber.
[][]Press Measure to measure the Quartz Control Plate.
[][]Type the Lot ID and press Enter.
[][]Type the Sample ID and press the Enter.
[][]Type the Sample Name and press the Enter.
[][]When the measurement completed press Print/Send key to print the measurement results.
[][]Remove the Quartz Control Plate form the chamber and return it to its container.
[][]Review the measurement results. Verify the Quartz Control Plate measure is within the tolerance specification.

Annexure:

[][]Annexure-I: Calibration Information Sheet for Polarimeter with Sucrose Solution
[][]Annexure-II: Calibration Information Sheet for Polarimeter with Quartz Control Plate
[][]Annexure-III: Log Book for Polarimeter

Water Purification System, Purpose :

Water Purification System, This purpose of this SOP is to describe the operation of Water Purification System (Model: Barnstead Easy Pure II 7136).

Water Purification System, Scope :

This procedure is applicable for Water Purification System (Model: Barnstead Easy Pure II 7136), installed in the quality control laboratory  of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

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

Responsibilities:

The roles and responsibility is as follows:

Executive/ Sr. Executive, QC

[][]Ensure that the instructions of this procedure are correctly followed

Manager, Quality Control

[][]Ensure that this procedure is kept up to date.
[][]Ensure appropriate personnel from the section are trained on this procedure.
[][]Ensure the instrument safety information is maintained as per manual.
[][]Ensure that the water system is ready for use.
[][]Ensure that the water system is sanitized properly at due time.
[][]Confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

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

Annexure:

N/A

Procedure:

General precaution:

[][]Use a properly grounded electrical outlet of correct voltage and current handling capacity.
[][]Do not locate your EASY pure II directly over equipment that requires electrical service. Routine maintenance of this unit may involve water spillage and subsequent electrical shock hazard, if improperly located.
[][]Replace fuses only with the same type and rating of fuse.
[][]Do not assemble water lines or remove cartridges where spilled water could contact equipment that requires electrical service. Electrical shock could result.
[][]Disconnect from the power supply prior to maintenance and servicing.
[][]Does not use in the presence of flammable or combustible materials; fire or explosion may result. This device contains components which may ignite such materials.
[][]Do not use in the presence of highly corrosive substances such as bleach or acid baths; fire may result.
[][]This device is to be used with water feeds only. Cleaning agents must be used in compliance with instructions in this manual. Failure to comply could result in explosion and personal injury.
[][]Avoid splashing cleaning solutions on clothing or skin.
[][]Ensure all piping connections are tight to avoid chemical leakage.
[][]Ensure adequate ventilation.
[][]Carefully follow manufacturer’s safety instructions on labels of chemical containers and material safety data sheets.
[][]Depressurize system prior to opening cartridge access door or removing top cover.
[][]This unit may be equipped with an ultraviolet lamp. Ultraviolet radiation is harmful to the eyes and skin. Do not observe the lamp directly.

Operation:

[][]Turn main power on at power entry module.
[][]Switch on the Water Purification System located on the upper left side of the instrument.
[][]The Barnstead EASY pure II 7136 control panel incorporates three switches ‘STOP’,’STAND BY’, ‘START’ and a digital display.
[][]Connect the instrument with purified water supply by feed water tubing.
[][]Pressing the ‘START’ when the unit is in either the stop or standby mode will put the instrument into Run Mode.
[][]When the display will show the resistivity 18.2 MΩ-cm at 25°C, the water can be taken from the instrument for different purposes by pushing down the Draw-off Valve Lever.
[][]To reserve the RO water for further use, connect the Water purification system with Barnstead 30 liter Storage reservoir with water inlet tubing.
[][]Push down the Draw-off Valve Lever to transfer the RO water from Water purification system to Barnstead 30 liter Storage reservoir by water inlet tubing.
[][]Use the water from the Barnstead 30 liter Storage reservoir for different purposes by Draw Off Valve.
[][]Use Product water outlet to drain the RO water if necessary.
[][]Finally power off Water Purification System.
[][]Unplug the instrument from the main power connection.

Temperature Monitoring of Refrigerator, Purpose :

Temperature Monitoring of Refrigerator, This purpose of this SOP is to describe the operation of Refrigerator for preservation of reference standard and others temperature sensitive materials in Quality Control Laboratory and Microbiology Laboratory.

Temperature Monitoring of Refrigerator, Scope :

This procedure is applicable for the preservation of reference standard and others temperature sensitive materials into Refrigerator in Quality Control Laboratory and Microbiology Laboratory of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

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

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

[][]Ensure that the instructions of this procedure are correctly followed.

Manager, Quality Control

[][]Ensure that this procedure is kept up to date.
[][]Ensure that the materials are preserved at defined temperature.
[][]Ensure appropriate personnel from the section are trained on this procedure.
[][]Confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

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

Procedure:

Precaution(s):

[][]Do not store articles on the top of the refrigerator.
[][]Do not put a container filled with water on the refrigerator. If spilled, there is a risk of fire or electric shock.
[][]Do not insert your hands into the bottom area under the refrigerator.
[][]Do not overfill the refrigerator with the material.
[][]Do not touch the inside walls of the freezer or products stored in the freezer with wet hands.
[][]Never put fingers or other objects into the water dispenser hole, ice chute and ice maker bucket.
[][]Do not spray inflammable gas near the refrigerator.
[][]Do not store volatile or flammable substances in the refrigerator.
[][]Do not reset the temperature without approval.

Operation:

[][]Connect and switch on the power of Refrigerator.
[][]Set the temperature within 2-8°C.
[][]After stable of the temperature, keep the items into the chamber at specific area.
[][]Check that the chamber temperature is within the setting value by standard calibrated thermometer.
[][]Record the temperature in Temperature log sheet for refrigerator (Annexure-I).
[][]Read the label of the materials to confirm the storage temperature.
[][]Store materials in refrigerator as per label.
[][]Minimize the door opening and closing to protect the chamber temperature increasing.

Cleaning procedure:

[][]Clean the inside walls and accessories with a mild detergent and then wipe dry with a soft cloth.
[][]Wipe the digital panel and display panel with a clean, soft cloth.
[][]Spray water onto the cleaning cloth instead of spraying directly on the outer surface of the refrigerator.
[][]The doors, handles and cabinet surfaces should be cleaned with a mild detergent and then wiped dry with a soft cloth.
[][]Keep the door seals free of grit or grime by cleaning the doors with a mild detergent and damp cloth then wipe with dry, clean and soft cloth.

Maintenance:

[][]If Refrigerator shows any mechanical, electrical or any others problem, inform to the supplier or Engineering Department for maintenance.

Annexure:

Annexure-I: Temperature Log Sheet for Refrigerator.

Vacuum Drying Oven Calibration, Purpose :

Vacuum Drying Oven Calibration, The purpose of this SOP is to describe the operation, calibration and cleaning of Vacuum Drying Oven (Model: VO 200S) used for drying of the raw materials in the quality control laboratory at XX Pharmaceuticals Ltd.

Scope :

Vacuum Drying Oven Calibration, This procedure is applicable for the Vacuum Drying Oven, installed in the quality control laboratory for general block at XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]QC: Quality Control

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

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

Manager, Quality Control

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

Head of Quality Assurance

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

Annexure:

[][]Annexure-I : Log Book for Vacuum Drying Oven
[][]Annexure-II: Calibration Record of Vacuum Drying Oven

Procedure:

Precaution(s):

[][]Wear the temperature resistance gloves to keep or remove materials from Vacuum Drying Oven.

Operation:

[][]Operation in normal mode
[][]Switch on the main switch of the Vacuum Drying Oven.
[][]Open the door and place the samples into the Vacuum Drying Oven.
[][]Press push/turn control key to put on the main power switch in front of the Vacuum Drying Oven. The Vacuum drying oven will start in normal mode with the display of timer, the chamber temperature, alarm temperature (red color indication).
[][]Select operating mode “Normal operation”. Press and hold on the SET key (approx. 3 sec) until the current operating option is flashing.
[][]Select temperature set point. Hold down the SET key and use the push/turn control key clockwise or anticlockwise to select the required temperature set point.
[][]After the SET key has been released the Vacuum drying oven briefly flashes the temperature set point. Set the temperature as per requirement. Heating is indicated by the orange heater symbol.
[][]Select the fan speed. Turn the push/turn control clockwise until the fan symbol is flashing. While the holding down the SET key. Use the push/turn control to set 50% fan speed.
[][]Select the alarm temperature. Turn the push/turn control clockwise until the monitor temperature display is flashing. Hold down the SET key and use the push/turn control to set the alarm temperature.
[][][][]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.
[][]At the end of drying, remove dried materials from Vacuum drying oven.

Operation in cyclic mode :

[][]Press push/turn control key to put on the main power switch in front of the instrument. The Vacuum drying oven will start in normal mode with the display of timer, the chamber temperature and alarm temperature (red color indication).
[][]Hold down 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.
[][]Press and hold down SET key to select the program and rotate push/turn control key at clockwise and select “Ramp timer” mode.
[][]Hold down the SET key and set the work day’s group using the push/turn control. Press push/turn control to select the ramp segment “t1” If the day is not required, it will be off position.
[][]Hold down the SET key and set the time using push/turn control.
[][]Select the ramp segment “t2” using the push/turn control. Hold down the SET key and using the push/turn control set the time.
[][]Turn push/turn control clockwise until the temperature display is flashing. Hold down the SET key and set the required temperature set point using push/turn control.
[][]Select the set point waiting time. Hold down the SET key and set on using the push/turn control. After the SET key has been released the function for set point waiting time is stored.
[][]Select hold time “t3”. Hold down the SET key and set the time using the push/turn control.
[][]Select the cooling time “t4”. Hold down the SET key and set time using push/turn control.
[][]Select program repeats “loop”. Hold down the SET key and set 2 for repeats using the push/turn control.
[][]Select the fan speed to set the air changes. Turn the push/turn control clockwise until the fan
[][]symbol is flashing. Hold down the SET key and set fan speed 50% suing the push/turn control.
[][]Select the alarm temperature. Turn the push/turn control clockwise until the monitor temperature display is flashing. Hold down the SET key and set the alarm temperature using the push/turn control.
[][]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.
[][]Start the program. Turn the push/turn control clockwise until the stop symbol ▀ is flashing. Hold down the SET key and select start ► using the push/turn control. On releasing the SET key the program
starts to run.

Vacuum pump operation:

[][]After setting the drying temperature, switch on the vacuum pump.
[][]After completion of vacuum drying, turn the push/turn control knob until the Open door option is displayed. Press SET key to release the vacuum. Switch off the vacuum pump. Then the door of Vacuum drying oven can be opened.

Calibration:

[][]Frequency: Perform calibration of the instrument once in a year or if the system has been moved, serviced or a malfunction is suspected.

Temperature Calibration

[][]Insert the standard thermometer or thermocouples into the chamber.
[][]Press and hold down SET key until the normal mode light blinking.
[][]Turn push/turn control key clock wise to reach SETUP light.
[][]Select Calibration to rotate push/turn control key.
[][]Use three calibration temperatures as below :
CAL.1 : 30°C
CAL.2 : 100°C
CAL.3 : 200°C
[][]Select the required calibration temperature in SETUP key and set the corresponding calibration correction to 0.0°C.
[][]Measure the deviation from the selected calibration temperature under the steady conditions, using a reference instrument.
[][]Set the calibration correction in SETUP key. If the measured reference temperature is too low, the calibration correction setting is negative sign.
[][]Adjust the temperature if require from adjusting value of calibration temperature (CAL). The correction value should not more than ±0.50C.
[][]Carry out the check measurement using the reference thermometer.
[][]Carry out others two calibration temperatures in the same manner.
[][]Measure the vacuum pressure and input the data on calibration record.
[][]In case of internal calibration, record calibration data in Vacuum drying Oven Calibration Record, as per Annexure-II.

Calibration of pressure for vacuum chamber

[][]Calibrate pressure of vacuum chamber by calibrated multi-functional calibrator using five calibration pressures as below :
CAL.1 : 10 mbar
CAL.2 : 50 mbar
CAL.3 : 100 mbar
CAL.4 : 500 mbar
CAL.5 : 900 mbar
[][]Record calibration data in Vacuum drying Oven Calibration Record, as per Annexure-II.
[][]Cleaning of Vacuum Drying Oven :
[][]Clean the inner part of Vacuum drying oven with a cleaned cloth.
[][]Disinfect the inner surfaces with 70% IPA or ethanol when required.
[][]Clean the outer surfaces with dry cleaned cloth.

Maintenance :

[][]If Vacuum drying oven shows any mechanical, electrical or any others problem, inform to supplier or Engineering Department for maintenance.
[][]After maintenance, recalibrate the Vacuum drying oven.

Muffle furnace, Purpose :

Muffle furnace, The purpose of this SOP (Standard Operating procedure) is to describe the operation and maintenance of Muffle furnace for the determination of Ash, Sulphated ash/residue on ignition and Loss on ignition and other tests (which required higher temperatures and furnace) of the materials under specified condition.

Muffle furnace, Scope :

This procedure is applicable for Muffle furnace (Model: Carbolite, CWF1200), installed in the quality control laboratory for general block of  XX  Pharmaceuticals Limited.

Definitions:

SOP: Standard Operating Procedure.
QC: Quality Control.

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

[][]Do not open the door during operation of Muffle Furnace.
[][]Always wear vinyl/heat resistance gloves to put and to remove the crucible from the furnace using the long tongs.
[][]Ensure that heating elements are isolated from the door and the inner surface of the chamber.

Operation:

[][]Connect the instrument to the main power supply.
[][]Switch ‘ON’ the mains.
[][]Press “■” key button.
[][]Display will show SPºC.
[][]Use “▲” up or “▼” down arrow key button to set the required temperature.
[][]Press “■” key button.
[][]Then display will show SPrr.
[][]Use “▲” up or “▼” down arrow key button to set ram temperature.
[][]Press “■” key button.
[][]Display will show t S.
[][]Use “▲” up or “▼” down arrow key button to set the time (Hr:Min) by a single press.
[][]Machine will automatically increase the temperature according to ramp temperature.
[][]After reach the set temperature, machine will hold that temperature according to set time.
[][]Then display will show ‘End’.
[][]Switch OFF the instrument and mains.

Cleaning procedure:

[][]Insure that main power switch of the equipment is “OFF” position and at room temperature.
[][]Clean the outer surface of the furnace with a damp cloth.
[][]Clean the inner surfaces with dry cleaned cloth or soft nylon brush.

Maintenance:

[][]If Muffle furnace shows any mechanical, electrical or any others problem, inform to supplier or
[][]Engineering Department for maintenance.

Calibration of Digital Hygrometer, Purpose :

Calibration of Digital Hygrometer, This purpose of this SOP is to describe to operate of Hygrometer for the determination of temperature and humidity of Quality Control Laboratory, Microbiology Laboratory, and Product Development.

Calibration of Digital Hygrometer, Scope :

This procedure is applicable for the determination of room temperature and humidity by digital hygrometer used in Quality Control Laboratory, Microbiology Laboratory, and Product Development of  XXP Pharmaceuticals Ltd.

Definitions/Abbreviation:

N/A

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

Manager, Quality Control

[][]To ensure that SOP is kept up to date.
[][]To ensure appropriate personnel from the section are trained on this procedure.
[][]To confirm that the SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

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

Procedure:

Precaution(s):

[][]Keep the sensor’s protective cap closed to extend the sensor’s life when the meter is not in use.
[][]Do not use for cleaning abrasive or solvents on these instruments.
[][]Do not store or use the meter outside the operating/storage environment.
[][]Allow time to stabilize the meter, when moving from one temperature/humidity extreme to other.

Operation:

[][]Check the calibration sticker to ensure that the instrument is within due date of calibration.
[][]Remove the RH sensor protective cap before use.
[][]Press Power button to turn the meter on.
[][]Setting Time-of-Day:
[][]Slid the CLOCK SET switch, located on the back of the unit to the CLOCK SET position
[][]Press HR and MIN button to set the hours and minutes respectively;
[][]Press and hold the button to rapidly advance the display.
[][]Setting 12/24 Hour Display:

[][]Slide the 12HR/24HR switch, located on the back of the unit to the desired position. In 12 hour format, “AM/PM” will appear on the display.
Selecting °C or °F:
[][]To display the temperature reading in Celsius or Fahrenheit, slide the °C/°F switch, located on the back of the unit, to the desired position.

Viewing the Humidity Memory:

[][]To view the humidity memory, press the HUMIDITY MEMORY button. The maximum humidity reading achieved will be displayed (“MAX” will appear on the display)
[][]Press the HUMIDITY MEMORY button a second time, within 10 seconds, to view the minimum humidity achieved (“MIN” will appear on the display)
[][]Press the HUMIDITY MEMORY button a third time, within 10 seconds, to return the current reading.

Clearing the humidity memory:

The maximum and minimum humidity memory may be cleared individually. To clear the desired humidity memory (MIN or MAX), press the CLEAR button while the memory value is being displayed (follow 7.1.7 to view the Humidity Memory)

Viewing the Temperature Memory:

[][]To view the temperature memory, press the TEM MEMORY button. The maximum temperature reading achieved will be displayed in the middle display (“MAX” will appear to the right of the value);
[][]The minimum temperature reading achieved will be displayed in the top display (“MIN” will appear to the right of the value);
[][]Press the TEM MEMORY button a second time, within 5 seconds, to return the current temperature and time-of-day display.

Clearing the humidity memory:

[][]To clear the temperature memory (MIN and MAX), press the CLEAR button while the memory value is being displayed (follow 7.1.9 to view the temperature Memory)
[][]Use annexure-I for recording of temperature and relative humidity, and use annexure-II for recording of temperature only as per requirements.

Calibration Procedure:

[][]Check the temperature and humidity using a digital thermo hygrometer and record the temperature and humidity in the calibration certificate. as per Annexure-V of Engineering.

[][]Calibrate the digital hygrometer once in a year ± 15 days.

Maintenance:

[][]If Humidity meter shows any mechanical, electrical or any others problem, inform to the supplier or
Engineering Department for maintenance.

Annexure

Annexure-I : Temperature and Humidity Record Sheet
Annexure-II : Temperature Record Sheet

Calibration of Potentiometric Titrator, Purpose :

Calibration of Potentiometric Titrator, The purpose of this SOP is to define the current procedure for the operation, calibration and cleaning of Potentiometric Titrate (Mettler-Toledo, Model: T50) within Analytical laboratory at XX  Pharmaceuticals Ltd.

Calibration of Potentiometric Titrator, Scope :

This procedure is applicable to the determination of the potency and/or purity of raw materials (Active & Excipients), intermediates and drug product etc. in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

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

Manager, Quality Control

[][]To 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.
[][]Maintaining calibration schedule of the instrument at the defined intervals.

Head Quality Assurance

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

Procedure:

Precaution(s):

[][]Laboratory coat, safety glasses and must be worn while handling the instrument.
[][]Ensure that the main switch and power supply connector are accessible during use.
[][]There is a chance of liquid spillage at high speed. Always gradually increase the speed to the desired level.
[][]Remove the plug from the main socket during cleaning.

General procedure:

[][]Titration is a technique for determining the potency and/or purity of synthetic raw materials, intermediates, drug substances, excipients and drug products, and for standardizing volumetric solutions. Although less specific than chromatographic techniques it is useful for quality control purposes where more details impurity quantization is not requested. Titration for assay of active substances is frequently used in pharmacopoeia monographs for drug substance and drug product.

[][]Samples are quantified by reaction in solution with a volumetric solution of known strength. A graduated glass tube fifed with a stopcock and fine tip is used to deliver deliver variable amounts of titrant, accurately measured, until the point at which the stoichiometric analytical reaction is complete. The endpoint may be determined use of color indicators or electrochemically. Where electrochemically endpoint detection is employed, automated burettes and endpoint detection may be used.

Automatic Burettes:

[][]This type of burette is found on automatic titration and dilution equipment. These devices are capable of very high precision volumetric measurements.

Automatic Titrates:

[][]Two types of automatic titrates are recorded the electrode potential differences during the course of titration as the expected sigmoid curve. This type is recommended for purchase and use since it offers greater accuracy and precision. In the second type, titrant addition is performed automatically until a pressed potential or pH, representing the endpoint, is reached, at which point the titrant addition ceases.

Indicator electrode:

[][]Choice of indicator electrode depends on the substance being examined and be a glass or metal electrode. The reference electrode is generally a calomel or silver-silver chloride electrode. Ensure that electrodes are in good condition. Electrode for non-aqueous titration must be dedicated and not utilized for any aqueous titration techniques.

Overview of titration chemistries:

[][]Titrimetric analyses utilize one of four basic chemistries, Reduction-oxidation, Complex metric, Precipitation and Acid-base, which may also be subdivided into non-aqueous and aqueous titrations.

Operations:

Manual Operation:

Enter the following parameters
[][]Stirrer
[][]Sensor
Temperature sensor
Potentiometric sensor
Polarized sensor
Conductivity sensor
[][]Burette
Rinse burette
Rinsing several burette at the same time
Dispense
Manual titration
[][]Pump
[][]Auxiliary instrument
[][]Sample Changer

You can determine the following parameters:

[][]Press ‘Manual’ to select Parameters.
[][]To ’Set’ parameters and input data. You would like to use and adjust the parameters.
[][]Press “Start’ to start the parameters procedure.
[][]You can select ‘Stop’ to terminate the procedure at any time.
[][]Press ‘Exit’ to end the manual operation.
[][]Press ‘Home’ and retune to main menu.

Methods:

Loops:

[][]There are the following loop types.
[][]A sample loop is for analyzing a sample.
[][]A calibration loop is for calibrating a sensor.
[][]A titer is for determining the titer of a titrate.

Types of Methods

[][]GT: Method for general titration (contains only sample loops or mixed loops).
[][]Calibration: Method for sensor calibration (contains only calibration loops).
[][]Titer: Method for titer determination(contains only titer loops)
Create a new method for general Titrant:
[][]Press ‘Method’
[][]Choose ‘New’ to create a new method on the basis of a template.
[][]From the available templates, choose method template EP by pressing ( ).Then press ok and exit.
You can modify this method in line with your requirements by inserting removing method functions or modify its parameters.
[][]Press ‘Title’ method function, enter a new method ID. After wards, a new method will be stored under this Method ID. Press ok and exit.
[][]Assign a ‘title’ to your new method.
[][]Press Sample button and input Sample ID, Entry Type, Density, Correction factor, Temperature and Entry in line with your requirements. Press ok and exit.
[][]Press Titrant Stand button and select manual stand. Press ok and exit.
[][]Press stirrer button and select stirrer speed and duration. Press ok and exit.
[][]Press Titration [EQP] [1].Press ok and exit.
[][]Input titrant and concentration by pressing titrant button.Press ok and exit.
[][]Press Sensor key and then input type, sensor and unit. Press ok and exit.
[][]Input stirrer speed by pressing stirrer. Press ok and exit.
[][]Input mode and wait time after pressing pre-dispensing key. Press ok and exit.
[][]Input Control and Mode after pressing control. Press ok and exit.
[][]Input molecular weight of the materials after pressing calculation. Press ok and exit.
[][]After inserting all required method function, you can store the new method in the titrator by choosing ‘Save’.

Annexure:

Annexure-I: Calibration Information of Potentiometric Titrator.
Annexure-II: Log Book for Potentiometric Titrator.

Calibration of Fume Hood, Purpose :

Calibration of Fume Hood, The purpose of this SOP is to describe the operation, calibration and cleaning of Fume Hood (Model: ESCO – EFD-4B1).

Calibration of Fume Hood, Scope :

This procedure is applicable for Fume Hood (Model: ESCO – EFD-4B1), installed in the quality control laboratory of  XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QC: Quality Control
[][]Face velocity: Face velocity is the average air flow speed at the sash opening of the fume hood into the work chamber. The measurement is expressed in m/sec or fpm.

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 the equipment is left clean and tidy after use.

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

[][]Relevant safety data sheet and safety guidelines must be followed when handling chemicals and reagents.
[][]Hazardous and fuming materials must be handled in fume hood.
[][]Wear appropriate personal protective equipment (PPE) while performing laboratory tasks in a fume hood.
[][]Keep head outside of the hood.
[][]Leave the front sash at the safe working height, when not in use.
[][]Follow laboratory procedure on the use of fume hood.
[][]Ensure the exhaust is operating before commencing work.
[][]Do not use the hood as storage area. Items can block airflow and interfere with containment.
[][]Do not leave uncapped bottles of chemicals in the hood.

Operation:

[][]Switch ‘ON’ the fluorescent lamp of the fume cupboard.
[][]Switch ‘ON’ the external exhaust blower/ fan.
[][]Lift the front sash to access in work area but not beyond the working height marked with yellow tape (30 cm).
[][]Work with the sash as fully lowered as possible, utilizing the sash as natural barrier to accidents which may occur in the hood.
[][]Plug in any electrical equipment used within the cabinet with electrical socket.
[][]Work as far into the hood as possible and with slow, deliberate movements, to minimize the external airflow disturbances.
[][]If performance is suspected, or an airflow alarm is triggered, terminate usage, close the sash completely and cease work.
[][]Report any fault regarding operation, maintenance or cleanliness of the cupboard to the supervisor.
[][]Leave the fume cupboard clean & dry after use.
[][]Turn the external exhaust blower/fan switch ‘OFF’.
[][]Turn the fluorescent lamp switch ‘OFF’.

Calibration:

[][]Calibrate the air flow (face velocity) of the fume cupboard six monthly.
[][]Switch ‘ON’ the fan.
[][]Open the window sash by sliding upward, 30 cm from the bottom.
[][]Take the reading by flow meter at left, right & middle of the fuming hood & record it in the calibration information sheet for Fume Hood (as per Annexure-I) for calculation.
[][]When instrument do not complies with the specified limits, label “Out of calibration” and get serviced.

Cleaning procedure:

[][]Clean the instrument once in a month or when required.
[][]Clean the work surface and walls with appropriate disinfectant agent and soap water.
[][]Clean the sash window using an appropriate agent disinfectant and glass cleaner.
[][]Use clean water to finish the cleaning and wash away any residue of disinfectant agent, soapy water and glass cleaner.
[][]Use a damp cloth to clean the exterior surface of the fume hood, particularly on the front and top in order to remove dust.
[][]Use Methyl-Ethyl-Ketone to remove stain or spot on the stainless steel surface as soon as possible.

Annexure:

Annexure-I: Calibration Information Sheet for Fume Hood.

Calibration of Hot plate ,Purpose :

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

Calibration of Hot plate, Scope :

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

Definitions / Abbreviation:

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

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Operation:

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

Calibration:

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

Cleaning procedure:

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

Annexure

Calibration Information Sheet for Hotplate with Magnetic Stirrer

Vortex Mixer , Purpose :

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

Vortex Mixer , Scope :

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

Definitions / Abbreviation:

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

Responsibilities

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Operation:

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

Cleaning procedure:

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

Calibration of orbital shaker, Purpose :

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

Calibration of orbital shaker, Scope :

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

Definitions / Abbreviation:

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

Responsibilities:

Executive, QC

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

Manager, Quality Control

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

Procedure:

Precaution(s):

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

Operation:

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

Calibration:

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

Cleaning procedure:

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

Annexure:

Annexure-I: Calibration Information Sheet for Orbital Shaker.

Calibration of Ultrasonic Bath, Purpose :

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

Calibration of Ultrasonic Bath, Scope :

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

Definitions / Abbreviation:

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

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Operation:

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

Calibration:

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

Cleaning procedure:

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

Annexure:

Annexure-I: Calibration Information Sheet for Ultrasonic bath.

Tap Density Apparatus Calibration, Purpose :

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

Tap Density Apparatus Calibration, Scope :

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

Definitions / Abbreviation:

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

Responsibility

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Operation:

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

[ELECTROLAB TAP DENSITY
ETD-1020 VER 3.0

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

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

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

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

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

Calibration:

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

Cleaning Procedure:

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

Annexure:

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

Electromagnetic Sieve Shaker Calibration, Purpose:

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

Electromagnetic Sieve Shaker Calibration Scope:

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

Definitions / Abbreviation:

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

Responsibilities:

The roles and responsibility is as follows:

Executive, QC

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Operation:

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

Cleaning of the Sieve:

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

Cleaning of the Sieve Shaker:

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

Calibration:

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

Annexure:

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

Karl Fischer Titrator Calibration, Purpose:

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

Karl Fischer Titrator Calibration, Scope:

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

Definitions/Abbreviation:

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

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive,

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Operation:

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

Functional description:

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

Rinse and fill burette:

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

Filling the titration beaker:

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

Performing a volumetric KF titration:

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

Calibration:

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

Cleaning:

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

Annexure

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

Calibration of Refractometer, Purpose :

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

Calibration of Refractometer, Scope :

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

Definitions/Abbreviation:

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

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Operating procedure

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

Calibration with Purified water, Carbon Tetra chloride and Toluene:

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

Cleaning procedure:

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

Annexure:

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

Calibration of Viscometer, Purpose :

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

Calibration of Viscometer, Scope :

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

Definitions/Abbreviation:

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

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/Sr. Executive, Quality Control

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

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

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

Calibration procedure:

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

Operating procedure:

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

Cleaning procedure:

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

Annexure:

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

Calibration of pH meter, Purpose :

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

Calibration of pH meter, Scope :

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

Definitions / Abbreviation:

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

Procedure:

Precaution(s):

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

Calibration:

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

Electrode condition:

Maintenance of the Reference Electrode:

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

Operation

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

Cleaning and maintenance:

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

Annexure: Calibration of pH meter

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

Calibration of FTIR, Purpose:

Calibration of FTIR, The purpose of this SOP is to describe the operation, calibration and cleaning of FTIR Spectrophotometer (Shimadzu, IR Affinity-1) used in the quality control laboratory at XX Pharmaceuticals Limited.

Scope

This procedure is applicable for FTIR Spectrophotometer (Shimadzu, IR Affinity-1), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

Standard Operating Procedure (SOP): Standard Operating Procedure. A written authorized procedure, which gives instructions for performing operations.

[][]QC: Quality Control.

[][]FTIR: Fourier Transform Infrared.

Responsibilities

[][]Executive/ Sr. 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: Calibration of FTIR

General Procedure:

[][]Ensure that the instrument is clean and calibrated.
[][]Connect the instrument properly with the power supply.
[][]Switch “ON” the main switch, power switch of the instrument situated at the backside panel, printer and computer.
[][]Allow the instrument initialize for at least 1 hour.

Disk preparation for solid sample:

[][]Mix 5 to 10 mg of sample with 200 to 400 mg of Potassium Bromide (KBr) [IR Grade].
[][]Grind the mixture to very fine powder with agate mortar.
[][]Pour the mixture into the barrel and carefully insert the plunger with its polished face downward.
[][]Maintain the hydraulic pressure 50 KN to 60 KN of the barrel for 1-2 minutes.
[][]Release the pressure and take out the disk from the barrel.
[][]For sample of liquid material using sealed liquid cell:
[][]Inject the liquid sample (pure or in solution) in sealed liquid cell.
[][]Plug to close both the slots of sealed liquid cell.
[][]For sample of liquid material which converted to solid (Nujol preparation) and measurement using NaCl demountable liquid cell:
[][]Put the cell window on the cell window holder and place the spacer of appropriate thickness on the cell window.
[][]Take 3 to 5 mg of sample with 2 to 3 drop of Nujol in a mortar and mix properly.
[][]Insert sample inside the spacer with a spatula. Put another cell window on the spacer and fit the metal plate on it.
[][]Fasten those plates with the four screws. Do not fix them with excessive force. It is enough to fasten them tightly by hand.

Operation Procedure (FTIR): calibration of FTIR

[][]Double click on “IRsolution” software icon.
[][]Press Measure
[][]Select FTIR Parameters in parameter window as follows:
[][]Data :
[][]Measurement Mode: % Transmitance ,
[][]Resolution: 2
[][]Apodization: Happ-Genzel
[][]No of Scans: 10
[][]Range (cm-1): Min: 400 cm-1 Max: 4000 cm-1
[][]Instrument:
[][]Beam: Internal
[][]Detector: Standard
[][]Mirror speed: 2.8
[][]More:
[][]Mode: Power
[][]Remove sample, if any, from the sample compartment.
[][]Click on Measurement then “Initialize” then “Yes”.

[][]After successful initialization, click BKG then “OK”. Wait till window on the screen is displayed as last Bkg.
[][]After ‘Bkg scan’, put the sample disk in the sample chamber, with the help of sample holder and close the chamber.
[][]Enter the Sample name, Batch No., Sample ID. in comment box and enter the data file location in Data file box.
[][]Click Sample to measure sample. Wait till the actual sample IR scan is displayed.
[][]Click on the spectrum window. Select Calculate  peak table. Type threshold: 60.00.
[][]Click on Calc, OK
[][]Compare the Spectrum in computer screen. View the IR scan of standard, click on Manipulation 2 then “Purity” then “Yes”.
[][]Again view the IR scan of sample, click on Manipulation 2  “Purity”  “Calc”  “OK”.
[][]After comparison with standard and sample then click file and open file as required. Then click Window  “Join visible”  “Calc”  “OK”.
[][]Purity index should be within 0 .9500 – 1.0000.
[][]A disc is rejected if visual examination shows lack of uniform transparency or when transmittance at about 2000 cm-1 (5 µm) in the absence of a specific absorption band is less than 60 % without compensation, unless otherwise prescribed in individual monograph.
[][]For printing of spectrum, click File  “Print preview”. Select respective necessary template and then print.
[][]Close the parameter window and the Software window.
[][]Shutdown PC, switch off Printer.
[][]Power OFF Spectrophotometer.
[][]Take out the liquid cell from the instrument.
[][]Discard the disk /Nujol / liquid sample.
[][]Clean the holder and liquid cell with dry and clean tissue paper.
[][]In case of sealed liquid cell mop and wash with IPA or absolute Ethanol and in case of demountable liquid cell mop and wash with Chloroform or Carbon Tetrachloride.
[][]Keep them in specified desiccator.
[][]Rub mortar, pestle, barrel & plunger with tissue paper to make them free from dust.
[][]Mop them with a tissue paper soaked in absolute ethanol.
[][]Keep them in a desiccator for next operation.
[][]Record all analysis in operation log book as per Annexure-II.

Operation Procedure (ATR):

Running a sample:

[][]Turn on the computer and crick on the respective software on the desktop.
[][]Set the MIRacle/ MIRacle A Base Unit to the instrument.
[][]Before initialization, set FTIR Parameters in parameter window as follows:
[][]Data :
[][]Measurement Mode: % Transmitance ,
[][]Resolution:2
[][]Apodization: Happ-Genzel
[][]No of Scans: 10
[][]Range (cm-1): Min : 700 cm-1 Max : 4000 cm-1
[][]Click on Measurement then “Initialize” then “Yes”. Click “cancel” option for auto adjustment.
[][]Click on Measurement then “Auto adjustment (Fine)” then “Yes”.
[][]After autoadjustment, click BKG then “OK”. Wait till window on the screen is displayed as last Bkg.
[][]Set the clamp to the base. Place sample on the ZnSe crystal- Liquids -place a drop of sample on the ZnSe crystal. Place a small neat solid sample on the ZnSe crystal with a spatula. Adjust the knob of the ATR until the pressure reads 12.
[][]Make sure that no acid sample (pH below 5), strong alkaline sample (pH more than 9) or liquid which give damage to PTFE should not be place on ZnSe prism.
[][]Enter the Sample name, Batch No., Sample ID. in comment box and enter the data file location in Data file box. Click Sample to measure sample. Wait till the actual sample ATR scan is displayed.

Working up the Data:

[][]Compare the Spectrum in computer screen. View the ATR scan of standard, click on Manipulation 2 then “Purity” then “Yes”.
[][]Again view the ATR scan of sample, click on Manipulation 2  “Purity”  “Calc”  “OK”.
[][]After comparison with standard and sample then click file and open file as required. Then click Window  “Join visible”  “Calc”  “OK”.
[][]For printing of spectrum, click File  “Print preview”. Select respective necessary template and then print

Calibration:

[][]Calibrate the FTIR Spectrophotometer at 6 month’s frequency either by following procedure or as per supplier’s protocol:
[][]Power ON the Spectrometer. Wait for at least 1 hour. Power ON PC & Printer.
[][]Double click on “IRsolution” software icon. Press Measure
[][]Select FTIR Parameters in parameter window as follows:
[][]Data :
[][]Measurement Mode: % Transmitance ,
[][]Resolution : 2
[][]Apodization : Happ-Genzel
[][]No of Scans : 10
[][]Range (cm-1) : Min : 400 cm-1 Max : 4000 cm-1
[][]Instrument :
[][]Beam : Internal
[][]Detector : Standard
[][]Mirror speed : 2.8
[][]More :
[][]Mode : Power
[][]Remove sample, if any, from the sample compartment.
[][]Click on Measurement then “Initialize” then “Yes”.
[][]After successful initialization, click BKG then “OK”. Wait till window on the screen is displayed as last Bkg.
[][]After ‘Bkg scan’, place the Polystyrene film in the sample chamber and close the chamber.
[][]Enter the Polystyrene 1 and Wave number verification in comment box and enter the data file location in Data file box.
[][]Click Sample to scan the polystyrene film (0.05 mm thick). Wait till the actual sample IR scan is displayed.
[][]Click on the spectrum window. Select Calculate  peak table. Type threshold: 65.00.
[][]Click on Calc  OK
[][]For printing of spectrum, click File  “Print preview”. Select respective necessary template and then print. Collect Polystyrene spectrum and peak table printed in two pages.

Limit of Wave Number Accuracy

[][]Check the maximum at following wave numbers (cm-1): 3060.0 (±1.5) cm-1, 2849.5 (±1.5) cm-1, 1942.9 (±1.5) cm-1, 1601.2 (±1.0) cm-1, 1583.0 (±1.0) cm-1, 1154.5 (±1.0) cm-1, 1028.3 (±1.0) cm-1.
[][]Resolution of apparatus
[][]Resolution due to transmittance:
[][]Record the Spectrum of a polystyrene film of approximately 35 µm thickness using Measuring Mode: % T.
[][]Measure the percentage transmittance at the transmission maximum at 2870 cm-1 (3.48 µm) and that at the transmission minimum at 2849.5 cm-1 (3.51 µm).
[][]Measure the percentage transmittance at the transmission maximum at 1589 cm-1 (6.29 µm) and that at the transmission minimum at 1583 cm-1 (6.32 µm).
[][]Record the results in calibration information sheet as per Annexure-I.

Acceptance criteria:

[][]The difference between the % transmittance at the transmission maximum at 2870 cm-1 (3.48 µm) and that at the transmission minimum at 2849.5 cm-1 (3.51 µm) must be greater than 18.
[][]The difference between the percentage transmittance at the transmission maximum at 1589 cm-1 (6.29 µm) and that at the transmission minimum at 1583 cm-1 (6.32 µm) must be greater than 10.

Resolution due to Absorbance:

[][]Record the Spectrum of a polystyrene film of approximately 35 µm thickness using Measuring Mode: Abs.
[][]Measure the absorbance at the absorption minimum at 2870 cm-1 and the absorption maximum at 2849.5 cm-1.
[][]Measure the absorbance at the absorption minimum at 1589 cm-1 and the absorption maximum at 1583 cm-1.
[][]Record the results in calibration information sheet as per Annexure-I.

Acceptance criteria:

[][]The difference between the absorbance at the absorption minimum at 2870 cm-1 and the absorption maximum at 2849.5 cm-1 is greater than 0.33.
[][]The difference between the absorbance at the absorption minimum at 1589 cm-1 and the absorption maximum at 1583 cm-1 is greater than 0.08.
[][]If the calibration is not within the specified standards, check the cleanliness of polystyrene film again and repeat the calibration.
Wavelength Repeatability Test:
[][]Repeat the Spectrum of the polystyrene film and Superimposed one after another of the absorption bands at 2849.5 cm–1 (3.51 µm), 1601.2 cm–1 (6.25 µm), 1028.3 cm –1 (9.72 µm).
[][]Acceptance Criteria: Compare the difference within 0.5% of the wave number scale and Purity index should be within 0.9500 – 1.0000
[][]Affix the label “CALIBRATED “on the equipment if all results are satisfactory. If the equipment found out of calibration limit affix “NOT FIT FOR USE” label and inform supplier.

Cleaning procedure:

[][]Clean the instrument with clean dry cloth daily.
[][]Remove your sample from the ATR, by using a cloth that is damped with acetone.
[][]Clean the plunger in the same way, if it made contact with sample.
[][]Never squirt (spray) acetone directly on the platform.

Annexure: Calibration of FTIR

Annexure-I: Calibration Information Sheet for FTIR Spectrophotometer
Annexure-II: Operation Logbook for FTIR Spectrophotometer

Electric Analytical Balance Calibration; Purpose :

Electric Analytical Balance Calibration; The purpose of this SOP is to describe the operation, calibration, cleaning and daily accuracy check of Electric Analytical Balance

Scope :

This procedure is applicable for Electric Analytical Balance , installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

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

Responsibilities:

Executive/Sr. Executive, QC

[][]To ensure that this procedure is followed.
[][]To ensure daily accuracy check of the balances.
[][]To maintain the records properly as per SOP.
[][]To preserve calibration, daily accuracy check record.

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.

Head of Quality Assurance

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

Procedure:

General precautions:

[][]Do not move or replace Balance after calibration. If require, calibrate after movement.
[][]Do not place Balance near to heat generating equipment or direct sunlight.
[][]Clean up any spillage in or around the balance immediately after operations.
[][]Proper protective clothing such as safety glasses, gloves and Laboratory coat must be worn during weighing process.
[][]Do not use sharply pointed objects to operate the keyboard of balance.
[][]Do not use cleaning agents which contain solvents or abrasive ingredients.

Operation:

To start up:

[][]Level and adjust at each time it is moved to a new location. The balance is exactly horizontal when the air bubble is in the middle of the level glass. Adjust the two front leveling feet appropriately until the air bubble comes to rest exactly in the middle of the glass.
[][]Plug the AC adapter and connect the power supply. Connect the printer to the balance.
[][]Switch on the printer using I/O switch.
[][]Press On/Off () button to on the Electric Analytical Balance. Display will show 0.0000g.
[][]Convert the weighing unit from g into mg, press scroll down button if necessary.
[][]Allow the balance to warm up to enable it to adapt itself to the ambient condition.
[][]Long press for menu button and select ‘BASIC’ by single press Enter button
[][]Set date, time and unit using keys and Enter button and save the settings using button.
[][]Press cancel (C) button to return come out of that ‘BASIC’ option and return to its main menu

Weighing:

[][]Check the machine is clean and calibrated. Then remove all loads from weighing pan.
[][]When zero (0.0000 g) reading is displayed, the balance is ready for operation. If the display shows greater than or less than zero, press tare button to tare the balance.
[][]If the balance is not in the weighing mode, press and hold the key down until ‘WEIGHING’ in the display.
[][]Use handle/coupling element for the operation of the draft shield door of the both side of the instrument.
[][]Open right/left/upper sliding window of the instrument.
[][]Place empty container/weighing paper on the pan of the balance. Close the sliding window.
[][]The weight is displayed. Allow the reading to stabilize and wait until the instability detector disappears from the left side of the display and the stability beep sounds.
[][]Press Tare button to tare the balance. When zero (0.0000 g) reading is displayed, the balance is ready for weighing.
[][]The weighing-in aid is a dynamic graphic indicator which shows the used amount of the total weighing range. It can be recognized at a glance when the load on the balance approaches the maximum load.
[][]Add weighing sample (Maximum 120 g) on the container/weighing paper using weighing spoon. Close the sliding window. The net weight is now displayed.
[][]Allow the reading to stabilize and wait until the instability detector (O) disappears from the left side of the display and the stability beep sounds
[][]To get printout of the weight, press print button.
[][]For performing another weighing press Tare button to tare the balance and follow previous steps from to increase or decrease digit, press display resolution button.
[][]Finally, press and hold On/Off button button untill ‘SHUT OFF’ shows on the display.
[][]Fill up the Operation Log book for Semi-Micro Balance (as per Annexure-II).

Daily Accuracy Check:

[][]Perform the Internal and External Calibration as per below mentioned procedure
[][]Take 20 g, 70 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Open one sliding window and place the weights separately at the center of the weighing pan, close the sliding window and allow the reading to be stabilized and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Print the results by pressing print button if necessary.
[][]Record the value of those weights in Log Book for Daily Accuracy Check (as per Annexure-I).

Calibration:

Internal Calibration:

Manual Adjustment with Internal weight:

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

External Calibration:

Manual Adjustment with External weight:

[][]Long press menu button and press scroll down button to go to ‘ADVANCED’ option.
[][]Select ‘ADVANCED’ by pressing Enter button.
[][]Press scroll down button once to select ‘CAL’ option by pressing Enter button.
[][]Select ‘ADJ. EXT’ by using scroll down and then press Enter button.
[][]Set the adjustment weight (100g) by using -/+ key for External Calibration and press Enter button.
[][]Then press cancel (C) button twice and save the settings if required by using -/+ key and press Enter button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration button to execute ‘External Adjustment’.
[][]The required predefined adjustment weight value flashes on the display.
[][]Place adjustment certified weight on the center of pan. The balance adjusts itself automatically.
[][]When ‘0.0000 g’ flashes, remove the adjustment weight.
[][]The adjustment is finished when the message ‘ADJ DONE’ appears briefly on the display. The balance returns to the last active application and is ready for operation.
[][]After adjustment, the result of the calibration will be printed out automatically or press print button for print copy.

Eccentricity:

[][]Take 20 g, 70 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 50g weight at center, Left Rear, Right Rear, right Front, Left Front and center on the pan again separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press print button separately to print each individual reading in same print page.

Linearity:

[][]Use Tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 10 g, 20 g and 50 g on the center of pan separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print ( ) button separately to print each individual reading in same print page.

Sensitivity:

[][]Use Tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 100 g on the center of pan.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print ( ) button separately to print each individual reading in same print page.

Repeatability:

[][]Use Tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 100 g on the center of the pan for ten times separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print ( ) button separately to print each individual reading in same print page.

Result:

[][]Record all the values for calibration in Calibration Information Sheet for Electric Analytical Balance (as per Annexure-III).
[][]Perform the Calibration of the Electric Analytical Balance once after every six months.

Cleaning:

[][]Ensure that no liquid comes into contact with the balance and AC adapter.
[][]Remove all objects from the balance.
[][]Clean the pan with soft brush followed by with soft clean cloth.
[][]Clean all of the parts of the balance with clean dry cloth.
[][]Set the parts of weighing pan carefully.

Annexure:

Annexure-I: Log book for Daily Accuracy Check of Electric Analytical Balance
Annexure-II: Operation Log book for Electric Analytical Balance
Annexure-II: Calibration Information Sheet for Electric Analytical Balance

Calibration of Semi-Micro Balance; Purpose :

Calibration of Semi-Micro Balance; The purpose of this SOP is to describe the operation, calibration, cleaning and daily accuracy check of Semi-Micro Balance (Model: MS205DU).

Scope :

This procedure is applicable for Semi-Micro Balance (Model: MS205DU), installed in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

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

Responsibilities:

Executive/Sr. Executive, QC

[][]To ensure that this procedure is followed.
[][]To ensure daily accuracy check of the balances.
[][]To maintain the records properly as per SOP.
[][]To preserve calibration, daily accuracy check record.

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.

Head of Quality Assurance

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

Procedure:

General precautions:

[][]Do not move or replace Balance after calibration. If require, calibrate after movement.
[][]Do not place Balance near to heat generating equipment or direct sunlight.
[][]Clean up any spillage in or around the balance immediately after operations.
[][]Proper protective clothing such as safety glasses, gloves and Laboratory coat must be worn during weighing process.
[][]Do not use sharply pointed objects to operate the keyboard of balance.
[][]Do not use cleaning agents which contain solvents or abrasive ingredients.

Calibration of Semi-Micro Balance; Operation:

To start up:

[][]Level and adjust at each time it is moved to a new location. The balance is exactly horizontal when the air bubble is in the middle of the level glass. Adjust the two front leveling feet appropriately until the air bubble comes to rest exactly in the middle of the glass.

[][]Plug the AC adapter and connect the power supply. Connect the printer to the balance.
[][]Switch on the printer using I/O switch.

[][]Press On/Off button to on the Semi-Micro Balance. Display will show 0.00000 g.
[][]Convert the weighing unit from g into mg, press scroll down button if necessary.
[][]Allow the balance to warm up to enable it to adapt itself to the ambient condition.
[][]Press menu button and select ‘BASIC’ by pressing Enter button
[][]Set date, time and unit using -/+ keys and Enter button and save the settings.
[][]Press cancel (C) button to return come out of that ‘BASIC’ option and return to its main menu.
[][]Perform the daily accuracy check at the starting of the day.

Calibration of Semi-Micro Balance; Weighing:

[][]Check the machine is clean and calibrated. Then remove all loads from weighing pan.
[][]When zero (0.00000 g) reading is displayed, the balance is ready for operation. If the display shows greater than or less than zero, press Tare button to tare the balance.
[][]If the balance is not in the weighing mode, press and hold the key down until ‘WEIGHING’ in the display.
[][]Use handle/coupling element for the operation of the draft shield door of the both side of the instrument.
[][]Open right/left/upper sliding window of the instrument.
[][]Place empty container/weighing paper on the pan of the balance. Close the sliding window.
[][]The weight is displayed. Allow the reading to stabilize and wait until the instability detector (O) disappears from the left side of the display and the stability beep sounds.

[][]Press Tare button to tare the balance. When zero (0.00000 g) reading is displayed, the balance is ready for weighing.
[][]The weighing-in aid is a dynamic graphic indicator which shows the used amount of the total weighing range. It can be recognized at a glance when the load on the balance approaches the maximum load.
[][]Add weighing sample (Maximum 220 g) on the container/weighing paper using weighing spoon. Close the sliding window. The net weight is now displayed.
[][]Allow the reading to stabilize and wait until the instability detector disappears from the left side of the display and the stability beep sounds
[][]To get printout of the weight, press print button.

[][]For performing another weighing press tare (O/T) button to tare the balance and follow all steps described above. To increase or decrease digit, press display resolution button.

[][]Finally, press and hold On/Off button ( ) button until ‘SHUT OFF’ shows on the display.
[][]Fill up the Operation Log book for Semi-Micro Balance (as per Annexure-II).

Daily Accuracy Check:

[][]Perform the Internal and External Calibration as per below mention Steps under Calibration.
[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Open one sliding window and place the weights separately at the Centre of the weighing pan, close the sliding window and allow the reading to be stabilized and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Print the results by pressing print button if necessary.
[][]Record the value of those weights in Log Book for Daily Accuracy Check (as per Annexure-I).

Calibration:

Internal Calibration:

Manual Adjustment with Internal weight:

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

External Calibration:

Manual Adjustment with External weight:

[][]Follow the previous instruction[Manual Adjustment with Internal weight] for manual adjustment.
[][]Select ‘ADJ. EXT’ by using scroll down and then press Enter button.
[][]Enter the adjustment weight (200g) by using -/+ key for External Calibration and press Enter button.
[][]Then press cancel (C) button twice and save the settings if required by scrolling down button and press Enter button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration button to execute ‘External Adjustment’.
[][]The required predefined adjustment weight value flashes on the display.
[][]Place adjustment certified weight on the center of pan. The balance adjusts itself automatically.
[][]When ‘0.0000 g’ flashes, remove the adjustment weight.
[][]The adjustment is finished when the message ‘ADJ DONE’ appears briefly on the display. The balance returns to the last active application and is ready for operation.

Eccentricity:

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use Tare button to tare the balance before start with a weighing.
[][]Always Press button to tare the balance between the interval of one weight to another and observe whether the instability detector (O) disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 100 g weight at center, Left Rear, Right Rear, right Front, Left Front and center on the pan again separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector disappear from the left side of the display and the stability beep sounds.
[][]Press print button separately to print each individual reading in same print page.

Linearity:

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 20 g, 50 g, 100 g, and 200 g on the center of pan separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Sensitivity

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 200 g on the center of pan.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Repeatability (200 g):

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 200 g on the center of the pan for ten times separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Repeatability (20 g):

[][]Take 50 g, 150 g of certified weight and clean it with a soft cloth.
[][]Use tare button to tare the balance before start with a weighing.
[][]Always press button to tare the balance between the interval of one weight to another and observe whether the instability detector disappears from the left side of the display or not and the balance will give a stability beep sounds.
[][]Place 20 g on the center of the pan for ten times separately.
[][]Allow the reading to be stabilized in each time while weighing and wait until the instability detector (O) disappear from the left side of the display and the stability beep sounds.
[][]Press Print button separately to print each individual reading in same print page.

Result:

[][]Record all the values for calibration in Calibration Information Sheet for Semi-Micro balance (as per Annexure-III).
[][]Perform the Calibration of the Semi-Micro Balance once in every six months.

Cleaning:

[][]Ensure that no liquid comes into contact with the balance and AC adapter.
[][]Remove all objects from the balance.
[][]Clean the pan with soft brush followed by with soft clean cloth.
[][]Clean all of the parts of the balance with clean dry cloth.
[][]Set the parts of weighing pan carefully.

Annexure:

Annexure-I: Log book for Daily Accuracy Check of Semi-Micro Balance
Annexure-II: Operation Log book for Semi-Micro Balance
Annexure-II: Calibration Information Sheet for Semi-Micro balance

Maintenance of Desiccator; Purpose :

Maintenance of Desiccator; The purpose of this procedure is to describe the maintenance (handling and cleaning) of desiccator.

Scope :

This procedure is applicable for all desiccators in the quality control laboratory of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

Desiccant canister: A container with hygroscopic substance which induces or sustains a state of dryness in its area.

Responsibilities:

Officer/ Executive, QC

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

Sr. Executive, QC

[][] To ensure that SOP is followed correctly.

Manager, Quality Control

[][] To ensure that this procedure is kept up to date.
[][] To ensure appropriate personnel from the section are trained on this procedure.
[][] To confirm that SOP is technically sound and reflects the required working practices.

Manager, Quality Assurance

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

Procedure:

Precaution(s):

[][]Do not touch hot samples, while transferring them from Oven/Muffle furnace to desiccator.

Operation

[][]Place about 200 g of silica (desiccant) and/or dessicant canister into the bottom of the desiccator.
[][]Set the sample platform (desiccator plate) to the desiccator.
[][]Apply a smear of grease in between lid & desiccator rim to avoid sticking of lid with the dessicator.
[][]Close the lid properly.
[][]Open the lid to retain the sample to be analyzed and close the lid again.
[][]Remove the sample after required period of time.

Cleaning

[][]Rub the desiccator, sample platform (desiccator plate) and lid with a dry, clean cloth.
[][]Laboratory Attendant will collect the silica (desiccant) to activate (in the oven at about 105°C) and then replace it to the desiccator once in a week or even more frequently when blue color of desiccant turns purple/pink.
[][]Fill up the logbook for desiccant change (as per Annexure-I).
[][]Officer/Executive, QC will check the logbook for proper condition of desiccant or the desiccant change.

Annexure:

Annexure-I: Logbook for desiccant change of desiccator.

Handling of Reference Standard; Purpose :

Handling of Reference Standard; The purpose of this procedure is to provide the instruction for handling of reference standard, impurity standards and standardization & storage of working standard.

Scope :

This procedure is applicable for the management of reference standard and working standard in the quality control laboratory of general block of XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

Chemical Reference Standard:

Primary chemical reference standard is one that is widely acknowledged to have the appropriate qualities within a specified context, and whose value is accepted without requiring comparison to another chemical standard.

Secondary Reference Standard/Working Standard:

A secondary chemical reference standard is a substance whose characteristics are assigned and/or calibrated by comparison with a primary chemical reference standard. The extent of characterization and testing of a secondary chemical reference standard may be less than for a primary chemical reference standard.

[] CRS : Chemical Reference Standard
[] WS : Working Standard
[] USPRS : United States Pharmacopeia Reference Standard
[] BPCRS : British Pharmacopeia Chemical Reference standard
[] ICRS : International Chemical Reference Standard (WHO)
[] EPCRS: European Pharmacopeia Chemical Reference Standard

Responsibilities:

Officer/Executive, Quality Control

[] Handle reference standard properly according to manufacturer’s certificate of analysis and instruction.
[] To standardize working standard
[] ollow the instructions of this procedure correctly.

Sr. Executive, QC

[] To ensure proper handling & storage of reference standard andworking standard.
[] To keep a track of its use, use before date, current pharmacopoeias reference standard lot number and all the related documents.

Manager, Quality Control

[] To approve WS after verification.
[] To ensure appropriate personnel from the section are trained on this procedure.
[] To confirm that SOP is technically sound and reflects the required working practices.

Head of Quality Assurance

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

Procedure:

General Note:

[] Read carefully the label of container before use of CRS.
[] After use sealed properly the CRS.
[] Handle the CRS according to material safety data sheet.
[] Ensure proper storage of CRS and WS.
[] Do not use CRS and WS after expiry.

Handling of Reference Standard:

Use one of the following Reference Standard for analysis of raw materials:
[] Pharmacopoeia Standards
[] Validated Suppliers Standards
[] In-house Reference Standards
[] Ensure that the purity of CRS is equivalent to 99.5% or higher, calculated on the basis of the material in its anhydrous form or free of volatile substances.
[] After receiving of CRS, write down the details in Chemical Reference Standard Details Record (as per Annexure-I).

[]During receiving, check the following points :

[][] Sealing condition (flip off seal for USPRS)
[][] Label on the container
[][] Part No.
[][] Lot No.
[][] Certificate of Analysis with complete information on test method.
[][] Information on optimal storage condition (Temperature and humidity).
[][] Updated material safety data sheet outlining any health hazard associated with the material.

[]Match the lot number of CRS with supplied vial.
[]Preserve all reference standard at 2-80C or according to the label of the container or according to manufacturer’s instruction.
[]Preserve all CRS up to expiry date.

[]Standardization of Working standard:

Determination of Identification:

[][]Use CRS for material identification by IR spectrometry and/or chromatographic methods.
[][]For identification, select a lot of respective raw material, which has been approved recently.
[][]Follow the approved analytical method for identification.
[][]Analyze the physical and chemical test against the reference standard.
[][]Confirm that the result is within specification and prepare the test report in Working Standard Analysis Report (as per Annexure-II).
[][]Use this lot as WS for the next routine analysis.

[]Determination of Assay:

[][]For standardization of WS, select a lot of respective raw material, which has been approved recently.
[][]Standardize this lot against the reference standard.
[][]Perform Water (by KF)/Loss on drying (whichever applicable) in twice as per specification and validated analytical method. The average of two results shall be used to determine the assay value.
[][]If the assay is performed by HPLC inject a blank, five replicate injection of standard solution, one test solution & one end standard. If the assay is performed by UV-Spectrophotometer or Potentiometer, at least analysis two samples. Percent of RSD for peak areas or readings of individual analyses should not be more than 1.0%.
[][]The content should be declared to two digits after decimal point.
[][]Prepare the report in Working Standard Analysis Report as per Annexure-II.
[][]Keep all relevant certificates of analysis, IR spectrum, chromatogram and any data regarding identification, purity and assay.
[][]A history sheet of each Working standards shall be maintained in Working Standard Preparation & Consumption Record (as per Annexure –III).

[]Labeling & Storage of Working Standard:

[][]After analysis kept sample in properly sealed clean and dry amber coloured glass vials/bottles.
[][]Prepare four vials/bottles of each working standard containing about 5 g.
[][]Prepare six vials/bottles of each working standard containing about 4 g in case of moisture sensitive materials.
[][]Affix the label on the WS Vials/bottles as per Annexure IV.
[][]On the opening of the vials/bottles, mention the date of opening on label.
[][]In order to maintain the integrity of the working standard, the dispensed vials/bottles have to be kept at the conditions indicated on the vials/bottles label. If the storage condition is 2ºC to 8ºC, store the dispensed vials/bottles in refrigerator with controlled temperature monitoring system and if the storage condition is recommended as room temperature, store the vials/bottles in a desiccator

[]Validity/Shelf Life and Consumption of Working Standard:

[][]Before preparation of working standard ensures that the manufacturer’s shelf life of respective material is valid up to more than one year.
[][]Use the working standard within one year from the date of standardization.
[][]Use the working standard of moisture sensitive material within two months from the date of opening.
[][]Use the working standard of non moisture sensitive materials within three months from the date of opening.
[][]Before use, keep refrigerated vials in a desiccator to reach at room temperature. After use seal the vial/bottle properly and store as per recommended storage condition.

[]Reference numbering system of Working standard:

[][]Assign working standard reference number in following way:
[][]Put first two letters of working standard i.e. WS.
[][]Put a hyphen (-) after the abbreviation, then a serial number of four digits i.e. 0001, again put a slash and then two digits of month i.e. 01 for January.
[][]Again put a slash (/) and then last two digits of the year i.e. XX for year 20XX.
[][]For example, First working standard prepare on January 20XX will get the Lab. Control No. WS-0001/01/XX

Discard Procedure of CRS & WS:

[][]At the time of issuing a new vial/bottle, the old/used vial/bottle shall be destroyed in following manner:
[][]Empty the contents in waste beaker containing previously prepared 0.4% sodium hypochlorite solution. Shake the dispersion of sample in container with the help of a glass rod and leave it for at least 12 hours. Then neutralize the liquid (pH 6-9) by acid/alkali and dilute the liquid 10 to 20% by fresh water and drain out slowly into designated place and clean the drain with adequate water flushing.
[][]Deface the label of the vial/bottle.
[][]Discard the vial/bottle into the specific container as broken glassware. Record the destruction details in Chemical Reference Details Record (as per Annexure-I) for CRS, and Working Standard Preparation & Consumption Record for WS (as per Annexure-III).

Annexure:

Annexure-I: Chemical Reference Standard Details Record
Annexure-II: Working Standard Analysis Report
Annexure-III: Working Standard Preparation & Consumption Record
Annexure-IV: Label of Working Standard

Calibration of Glassware: Purpose

Calibration of Glassware; The purpose of this SOP is to ensure that all glass wares are properly handled, thoroughly cleaned and calibrated accurately before use.

Scope:

This procedure is applicable for glassware handling, washing and calibration used in the different analysis of quality control laboratory and microbiology laboratory of general block of XX Pharmaceuticals Ltd.

Definitions/Abbreviation:

[] ASTM: American Society for Testing and Materials
[] SOP   : Standard Operating Procedure

Responsibilities:

[] Officer/Executive/Sr. Executive, Quality Control
[] To ensure that this procedure is followed.
[] To maintain the records properly as per SOP.

Manager, Quality Control

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

Head of Quality Assurance

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

Procedure:

Precaution(s):

[] Handle with care during cleaning of Glassware.
[] Before discard of glassware, observe the label on glassware and handle with care as the type of chemical.
[] Wear gloves, mask and protective clothing during glassware handling and cleaning.
[] Do not use laboratory glassware for drinking purpose.
[] Do not handle the hot glassware without heat resistant gloves.
[] Do not put the hot glassware on cold or wet surface or cold glassware on hot surface.
[] Avoid to heat glassware that is etched, cracked, chipped, nicked or scratched.
[] Do not heat directly thin glassware with flaming.
[] Never place the glassware from the freezer into warm water baths.

Handling Procedure:

[] Hold the beakers, bottles, flask the side and bottoms rather than by the tops.
[] Avoid over tighten the clumps.
[] Use always coated clumps to avoid breakage while the clumping glassware.
[] Cool the glassware slowly to prevent breakage.
[] Dispose the broken glass into specific waste bucket.
[] Keep all cleaned glassware at designated place.

Washing Procedure:

[] Transfer all used glassware to washing area.
[] Discard the solution from glassware into a designated container/place.
[] Rinse initially all glassware with sufficient potable water for removal the residual content of solution.
[] For pipette, pass sufficient potable water through the pipette by force at two or three times.
[] Wipe to remove the label with detergent powder or suitable solution.
[] Allow to soak the glassware with diluted detergent for 10-15 minutes to remove any contaminants.
[] Rinse the glassware with sufficient potable water until detergent is removed.
[] Finally rinse with purified water for two or three times for removal any contaminating substances that may be present in the potable water.
[] Discard the rinsing solution.
[] Place cleaned glassware into Glassware drying rack for removal of residual water from glassware.
[] Dry the glassware for QC analysis and sterilize the glassware at 200°C for 1 hour for use in Microbiological analysis.

Calibration Procedure:

Burette Calibration:

[] Take a burette and inspect to ensure smooth tap operation.
[] Observe the tip of the burette, ensure no cracks or chips.
[] Observe markings on burette which is legible.
[] Rinse the burette at several times with purified water.
[] Fill the glassware up to the mark.
[] Dispense into a pre-tarred 100 ml beaker.
[] Record final volume.
[] Record mass of water.
[] Repeat the same procedure for another two times.
[] Calculate the volume delivered from the equation below using recoded weight and density of water at the temperature of calibration.  Take Tabulated Density of water at the temperature of calibration from the Annexure-II.
Volume of Burette= Weight/Tabulated Density of water at the temperature of calibration
[] Record calculated volumes, determine mean and compare the volume with that read from the burette and then determine the error as per Annexure – I.

Limit of error of the calculated volume should be as per following table (as per ASTM E-287)

Calibration of Pipette:

[] Take purified water into a beaker.
[] Record the temperature of the water used.
[] Weigh and tare another 100 ml beaker.
[] Dispense water as per pipette volume into tarred beaker.
[] Record the weight of purified water.
[] Repeat the same procedure for another two times.
[] Calculate the volume delivered from the equation below using recoded weight and density of water at the temperature of calibration.  Take Tabulated Density of water at the temperature of calibration from the Annexure-II.
Volume of Pipette= Weight/Tabulated Density of water at the temperature of calibration
[] Record calculated volumes, determine mean and compare the volume with the nominal volume and then determine the error as per Annexure – I.

Limit of error of the calculated volume should be as per following table (as per ASTM E-969)-

Calibration of Volumetric Flask:

[] Observe the volumetric flask, ensure no cracks or chips.
[] Observe markings on volumetric flask, ensure they are legible.
[] Rinse volumetric flask at several times with purified water.
[] Rinse with acetone and air dry.
[] Tare volumetric flask on balance.
[] Add purified water and fill to mark.
[] Record weight of water.
[] Record the temperature of the water used.
[] Repeat the same procedure  for another two times
[] Calculate the volume delivered from the equation below using recoded weight and density of water at the temperature of calibration.  Take Tabulated Density of water at the temperature of calibration from the Annexure-II.

[] [] Volume of Volumetric Flask= Weight/   Tabulated Density of water at the temperature of calibration

Record calculated volumes, determine mean and compare the volume with the nominal volume and then determine the error as per Annexure – I.

Limit of error of the calculated volume should be as per following table (as per ASTM E-288)

Download All Annexure

Annexure I : Glassware Calibration Record
Annexure II : Density of Water

Packaging Material Sampling and Release, Purpose :

The purpose of this SOP is to describe the procedure for sampling and releasing of packaging materials for pharmaceutical products.

Packaging Material Sampling and Release, Scope :

This procedure is applicable for all packaging materials received at the warehouse of  XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[] SOP: Standard Operating Procedure
[] QC: Quality Control
[] GRN: Goods Received Note
[] COA: Certificate of Analysis
[] ERP: Enterprise Resource Planning
[] Sampling: It is a process of collecting the materials so that the collection shall represent the whole lot.
[] Sampling plan: Description of the number of units and/or quantity of material that should be collected.
[] Consignment: A supply of a material of particular batch intended to be used in different department.
[] Lot: A defined quantity of material made by a specified process cycle having uniform quality.

Responsibilities:

The roles and responsibility is as follows:

Officer/Executive/ Sr. Executive, Quality Control

[] To ensure that the procedure is correctly followed.
[] To maintain the records properly as per SOP.
[] To ensure that this procedure is kept up to date.
[] To confirm that the SOP reflects the required working practices.
[] To arrange training on the SOP to all concerned personnel and to ensure implementation of the SOP after training.

Executive/ Sr. Executive, Warehouse

[] To ensure availability of containers to be sampled in quarantine area.

Executive, Production

[] To arrange machine trial when required and share the report to QC with the concern of Manager,

Production.

Head of Quality Assurance

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

 Procedure:

General Precaution(s):

[] Take sample for microbial testing first followed by other sampling.
[] Sampling should be carried out by trained personnel.

Sampling: Packaging Material Sampling and Release

[] Receive the GRN with Manufacture’s COA from the warehouse and enter the details (GRN no., lab. control no., name of material, code no., invoice/challan no., manufacturer lot no., local batch no., manufactured by, supplied by, pack size, no. of pack, total quantity and received by & date) in the ‘Packaging Material Log Register’ (as per Annexure-I) maintained in QC department for packaging material.
[] Ensure that material is received from Approved Vendor.
[] If the material is not from approved vendor or if the Manufacture’s COA for primary packaging material is not received, inform Supply Chain Management Department.
[] QC Officer/Executive or QC sampler will select the no. of container/packs to be sampled as per sampling plan and sample quantity according to ‘Sampling quantity for Packaging Material’ (as per Annexure-II) and take required no. of “SAMPLED” label.
[] For example, when the total no. of container of inner carton (secondary packaging material) is 25, then no. of container to be sampled will be Ö 25 + 1 = 5 + 1 = 6.
[] If the batch size is 3100 pcs, then 32 pcs of inner cartons will be taken from 6 different containers.

Sampling plan:

[] The n plan

The “n plan” is based on the formula n = 1 + ÖN, where N is the number of sampling units in the consignment. The value of n is obtained by simple rounding. A minimum number of containers needs to be sampled, e.g. if N is less than or equal to 4, then every container is sampled. According to this plan, samples are taken from n sampling units (containers/pack) selected at random.

Sampling plan for primary packaging material

[] In case of primary packaging material, select no. of reels/pack/ container for sampling as per “n plan”.

Collect approximately 1 feet sample of foil/film from each of selected reels of films/foils.

[] In case of bottle/cap/dropper/stopper, take randomly 10 samples from selected containers.
[] In case of Container/Jerry can/Cap for Jerry can; check physical appearance of at least 3 samples from each selected container/pack (selected as per “n plan”) and then take randomly two containers for laboratory test from selected container/pack.

Sampling plan for secondary packaging material

[] For secondary packaging material, select container/pack for sampling as per “n plan”.
[] Samples can be withdrawn from any part of the container (usually from the top layer).
[] Collect sample proportionally from the selected container/pack following ‘Sampling quantity for Packaging Material’ (as per Annexure-II).
[] In case of Shipper carton and Master carton, check physical appearance and text of at least 3 shipper cartons from each selected pack and then take randomly 3 shipper cartons for laboratory test from selected pack.
[] Inform Warehouse before going for sampling to arrange the packaging material containers.
[] Take ‘Sampled’ label, sampling tools, packaging material sampling report, sampling basket and GRN before sampling.
[] Check the physical condition and cleanliness of packaging material containers/packs before opening for sampling.
[] If any container/pack found in damaged condition, intimate warehouse in-charge.
[] Damaged containers/packs whose integrity is doubtful should be sampled and tested separately.
Inform warehouse in-charge to take initiatives for repacking of damaged container/pack if necessary.

 Sampling of packaging materials

[] Check the details given on the GRN with the manufacturers label and ensure that the “Quarantine” label affixed properly by the warehouse personnel on all packaging material containers/packs of a consignment.

[] Check the physical condition of outer pack/container/damage condition.
[] Microbiology personnel will collect sample first in sampling booth for microbial analysis (when applicable).
[] Check the physical condition such as appearance (in case of Shipper carton/Master carton, Container/Jerry can/Cap for Jerry can), winding (in case of foil/film) etc. of the packaging material for any gross abnormalities. Measure internal core diameter, total reel diameter (in case of foil/film) of three reels. [] Record all necessary information in ‘Packaging Materials Sampling Report’ (as per Annexure-IV).
[] Select number of containers/bags/packs and collect sample according to sampling plan. Repair the sampling point properly, close the container/pack and affix the ‘SAMPLED’ label in cascading manner (overlapping upto half of the status bar of the previous label) over the “QUARANTINE” label without hiding any information of the previous label. Affix ‘UNDER TEST’ label on all other containers of the consignment in the same way.

[] Enter the information about the material sampled i.e. date, GRN No., lab. control no., name of  material, code no., invoice no./challan no., manufacturer lot no., manufactured by, sampled quantity, sampled by and remarks (if any)  into the ‘Sampling Register for Packaging Material’ (as per
Annexure-III).
[] Record sampling details in ‘Packaging Materials Sampling Report’ (as per Annexure-IV).
[] If any discrepancy found, immediately inform the warehouse in-charge to take action accordingly.
[] Transfer the collected samples to QC laboratory.

Release:

[] On receipt of the packaging material sample from warehouse, QC will keep them into “Under test sample (packaging material)” labeled rack in sample receiving room or any other designated place with proper labeling.
[] Enter the sampled by (initial) in the ‘Packaging Material Log Register’ (as per Annexure-I).
[] In-charge/Sr. Executive, QC will issue the packaging material work sheet with initial and date on every page to the analyst and enter the worksheet issued by (initial and date) in the ‘Packaging Material Log Register’ (as per Annexure-I).
[] Carry out the physical appearance test very carefully.
[] Test all parameters according to the packaging material specification and the packaging material test method and record the analytical raw data and calculations, and attach the printout of weight(s) in the analyst logbook.
[] Fill up the respective Packaging material work sheet (as per Annexure-V) and attach printout of required raw data.
[] Accordingly prepare the ‘Certificate of Analysis for Packaging Material’ (as per Annexure-VI).
[] Use bracket like [  ] to indicate that the result is taken from manufacturer’s certificate of analysis (COA).
[] Keep a remarks on ‘Certificate’, if any minor observation (variation in dimension, colour etc.) is found for a batch of packaging material.
[] Compile a batch report with COA, test report (packaging material work sheet), packaging materials sampling report (prepared as per Annexure-IV), QC copy of GRN.
[] Keep one retention sample with the bunch if feasible.
[] If it is not possible to keep retention sample with the bunch, keep them into another box/pack with proper labeling.
[] Submit the batch report with respective packaging material specification to Executive/Sr. Executive, Quality Control for checking.
[] Check and verify the test result against Packaging Material Specification. Inform production department for machine trial or practical trial for a particular material, if required.
[] Executive, Production is responsible for machine trial and reporting.
[] On completion of checking/verification, enter the detail in the ERP.
[] Submit GRN, testing report and COA to In-charge/Sr. Executive, QC for checking and approval. Give part release to fulfill the production demand, if required.
[] In-charge, QC/Sr. Executive, QC will check report and approve finally for passed/rejected status of the packaging material.
[] Officer/Executive, QC will prepare status label (Passed/Rejected) after approval of GRN. The expiry and retest should be not applicable for all secondary packaging materials, glass bottle, ampoule, plastic container/cap/dropper/stopper/syringe, polyethylene bag, aluminium cap, sealing foil and alu-lid foil. In case of PVC, PVdC film and Alu-bottom foil; the expiry and/retest should be as per manufacturer’s recommendation. If not mentioned by manufacturer, then the expiry period for PVC, PVdC film and Alu-bottom foil should be five years.

[] Officer/Executive/Sr. Executive, QC will check and sign on the passed label.
[] Only the rejected label will be signed by In-charge/Sr. Executive, QC.
[] After release of consignment entry information regarding a passed/rejected GRN in “Packaging material log register” (as per Annexure-I).
[] After approval send copy of GRN to warehouse/Store.
[] QC Executive or QC sampler will affix status label (Passed/Rejected) in cascading manner (overlapping upto ³/₄ th of the status bar of the previous label) over the “SAMPLED” or “UNDER TEST” label without hiding any information of the previous label.
[] Enclose mail or any other relevant document and approved GRN, with the respective batch document.
[] Keep a copy of GRN with batch document and file it up.

List of Annexes: Packaging Material Sampling and Release Procedure

[] Annexure-I     : Packaging Material Log Register
[] Annexure-II    : Sampling quantity for Packaging Material
[] Annexure-III   : Sampling Register for Packaging Material
[] Annexure-IV   : Packaging Materials Sampling Report
[] Annexure-V    : Packaging Material Work Sheet
[] Annexure-VI   : Certificate of Analysis for Packaging Material

Assigning of laboratory control number; Purpose

The tenacity of this SOP is to define the procedure of assigning Laboratory control number (Lab. Control No.) of all type raw material, packaging material, water, intermediate, bulk and finished product that are analyzed in Quality Control and Microbiology Laboratory.

Assigning of laboratory control number; Scope

This procedure is applicable for all type of raw materials, packaging materials, water, intermediate, bulk and finished products of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[] GRN: Goods Received Note

[] Lab. Control No.: A system of alpha-numerical number which represents request for analysis of materials/ water/ products received from respective department.

[] QC: Quality Control.

[] SAF: Sampling Advice Form

Responsibilities

The roles and responsibility is as follows:

[] Sr. Executive/Executive, Quality Control & Microbiology

[] To confirm that this procedure is followed.

[] To maintain the records properly as per SOP.

Assistant Manager, Quality Control

[] To confirm that this procedure is kept up to date.

[] To check that the SOP reflects the required working practices.

[] Organize training on the SOP to all concerned personnel.

[] To confirm implementation of the SOP after training.

Head of Quality Assurance

[] To ensure the overall implementation of the SOP.

[] Take initiative to Approval of the SOP.

Procedure:

[] All newly delivered samples & the accompanying documents (e.g. test request) must be assigned a separate registration number.

[] Assign Laboratory control number (Lab. Control No.) in following way:

Put first two or three letters according to the abbreviations mentioned below –

• BBW     Boiler Blowdown Water
• BFW     Boiler Feed Water
• CTW     Cooling Tower Water
• DW       Drinking Water
• EM       Environment Monitoring
• ET        Endotoxin Test
• ETP      Effluent Treatment Water
• FP        Bulk Product (Semi-Finished)
• GMB     General Microbiology
• PM       Packaging Material
• PMS     Packaging Material of Source Approval
• PSC     Purified Steam Condensate
• PTW     Potable Water
• PW       Purified Water
• RM       Raw Material
• RMS     Raw Material of Source Approval
• SHC     Sodium Hypochlorite
• ST        Sterility Test
• STB      Stability Sample
• WFI      Water for Injection
• WW      Wash Water

Write down a hyphen (-) after the abbreviation, then serial number consist of three digits i.e. 001, then a  slash and put two digits of month i.e. 08 for month August.

Again write down a slash (/) then last two digits of the year i.e. XX for year 20XX. For example, first raw material received on August 20XX will get the Lab. Control No.: RM-001/08/XX.

GMB will be included before abbreviation of each test in case of microbiology lab control no./lab reference no. and put slash (/) after that.

Record Lab. Control No. in Register against each GRN / SAF.

Record the same in respective documents and status label also.

Specification and analytical method; Purpose

The tenacity of this SOP is to define the procedure for preparation, review & approval of specification & analytical methods in quality control & microbiology laboratory.

Scope

This procedure is applicable for all raw materials (APIs and excipients), water, packaging materials and finished products of  XX Pharmaceuticals Limited.

Definitions/Abbreviation:

[] COA: Certificate of Analysis

[] ERP: Enterprise resource planning

[] PMS: Packaging material specification

[] QA: Quality Assurance

[] QC: Quality Control

Responsibilities

The roles and responsibility is as follows

Officer/Executive/ Senior Executive, Quality Control

[] To confirm that this procedure is followed.

[] To retain the records properly as per SOP.

Assistant Manager, Quality Control

[] To confirm that this procedure is kept up to date.

[] To ensure that the SOP is technically sound & reflects required working practices.

[] Arrange training on the SOP to all concerned personnel.

[] To confirm implementation of the SOP after training.

Head of Quality Assurance

[] Take initiative to approval of SOP.

[] To ensure overall implementation of this SOP.

Procedure

Precaution(s)

There is no significant precaution or special instructions relating to the activities described in this SOP.

Preparation

• Enter code no. in ERP, then assign the specification reference number using the format and the analytical method reference number using the specific format
• Check whether, material is included in different Pharmacopeia [BP/EP/USP] or not.
• Prepare specification & analytical method strictly align with Pharmacopeia if the material is included in BP/EP/USP.
• Prepare specification & analytical method strictly align with Manufacturer’s guides/COA /analytical methods if the respective raw material or packaging material is not encompassed in BP/EP/USP. Include any additional test parameter as internal requirement.
• QC will share rest of the QC test sample & raw data with PD. PD will suggest to include any in-house parameter in specification (as when required/not).
• Compare specification & analytical method received from two or more suppliers; prepare specification & analytical method based on the suitable one based on feasibility study on site. Discuss with the concerned suppliers in case any difference identified.
• For printed packaging material, Officer/Executive, QC will receive copy of artwork & approved shade card/design from QA and then prepare the specification and transfer to QA for approval. After approval of the specification, QC will receive control copy of specification along with artwork and approved copy of shade card/design from QA.
• QC will prepare specification for unprinted packaging materials (Foil, Sachet, PVC/ PVDC Film etc.).
• The issue date & review date should be in the day-month-year (dd-month-yyyy) format i.e. 25-August-20YY.
• Assign two years review time for next revision from date of preparation for specifications and analytical methods.
• For draft specification & analytical method; assign one year review time from date of preparation.
• Follow respective standard format (as per concerned Annexure) for the preparation of specification & analytical method.
• Enter final specification of raw material & packaging material in the ERP.

Review

• Review specification & analytical method from draft to final one & change version no. to next one.
• Review final specification & analytical method with a proper change control procedure when any change   is necessary.
• Review method & specification if there is any change in respective Pharmacopeia. Put a new version number with a new review date.
• If no modification is required at the time of review, then use subsequent review portion assign next expiry date 2 years from the review date and use the same.

Approval

• Check analytical method & specification.
• Manager, QA or Manager, QC will give approval after ensuring that each page of the document has been signed by person who prepared & person who checked specification after its finalization.
• Keep master document in QA department.
• Keep controlled copy in the QC & Microbiology department (as when required).
• Retrieve previous specification & analytical method by revised one after review. Treat previous one as ‘OBSOLETE’.
• Keep the ‘OBSOLETE’ copy in a file after stamping as ‘OBSOLETE’ in red ink
• Discard the ‘OBSOLETE’ specification least after two years from the date of obsolete.

Download All Annexure here

Annexure I Format for Packaging Material Specification

Annexure II Format for Raw Material or Water Specification

Annexure III Format for Finished Product Specification

Annexure IV Format for Analytical Method of Raw Material or Water

Annexure V Format for Analytical Method of Packaging Material

Annexure VI Format for Analytical Method of Finished Product

HPLC analysis and system suitability; Purpose:

The purpose of this SOP is to describe the procedure for HPLC analysis and checking of system suitability.

HPLC analysis and system suitability; Scope

This procedure is applicable to all HPLC analysis that will be carried out in quality control laboratory of XX Pharmaceuticals Limited.

Definitions/Abbreviation

• Standard Operating Procedure (SOP)
• Standard Operating Procedure. A written authorized procedure, which gives instructions for performing operations.
• HPLC: High performance liquid chromatography
• QC: Quality Control
• RSD: Relative standard deviation

Responsibilities

The roles and responsibility is as follows:

Officer/Executive/ Senior Executive, Quality Control

• To ensure that the instructions of this procedure are correctly followed.
• To maintain the records properly as per SOP

Assistant Manager, Quality Control

• To confirm that this procedure is kept up to date.
• To check that the SOP reflects the required working practices.
• To organize training on the SOP to all concerned personnel & to ensure implementation of the SOP after training.

Head of Quality Assurance

• Take initiative to approval of the SOP.
• To confirm the overall implementation of the SOP.

Procedure:

General Precaution(s):

• Ensure that the mobile phase is filtered and degassed properly by sonication before use.
• Suggested injection procedure should be run in one single sequence.

Analytical procedure:

• Prepare desired mobile phase, filtered by 0.22 or 0.45 µm membrane filter & degassed for at least 5 minutes with the help of sonication.
• Equilibrate the column for at least 30 minutes or more until baseline gets stabilized with desired mobile phase & check the baseline to ensure the system is ready for injection.
• Prepare standard solution & assay sample and keep record of weights.
• At first inject blank to confirm the absence of unknown peak at the retention time of Principal peak & then inject standard solution to check retention time of the principal peak of interest. Run chromatogram minimum 2 minutes extra after principal peak elution is over and peak is properly integrated.
• Unless otherwise specified in the individual method, data from five replicate injections of standard are used to calculate RSD, if the requirement is 2.0% or less; data from six replicate injections are used if the RSD requirement is more than 2.0%. Tailing factor of principal peak of interest should be between 0.8 and 1.5 unless otherwise stated in individual method.
• Inject standard & assay preparation solution into the HPLC system as per suggested injection procedure previously mentioned.
• Following are the suggested injection procedure to be followed unless otherwise specified in respective method.

Injection procedure for test homogeneity of Blend/Granules sample

Sample ID with No. of Injection

• Blank: 1 Time
• Resolution or System Suitability solution (If applicable) : 1 Time
• Standard: 5 Times
• Sample-1: 1 Time
• Sample-2: 1 Time
• Sample-3: 1 Time
• Sample-4: 1 Time
• Sample-5: 1 Time
• Sample-6: 1 Time
• End Standard: 1 Time

Injection procedure for Assay

• Blank: 1 Time
• Resolution or System Suitability solution (If applicable) : 1 Time
• Standard: 5 Times
• Sample: 1 Time
• End Standard: 1 Time

Injection procedure for dissolution

• Blank: 1 Time
• Resolution or System Suitability solution (If applicable) : 1 Time
• Standard: 5 Times
• Sample-1: 1 Time
• Sample-2: 1 Time
• Sample-3: 1 Time
• Sample-4: 1 Time
• Sample-5: 1 Time
• Sample-6: 1 Time
• End Standard: 1 Time

Injection procedure for Content Uniformity

• Blank: 1 Time
• Resolution or System Suitability solution (If applicable) : 1 Time
• Standard: 5 Times
• Sample-1: 1 Time
• Sample-2: 1 Time
• Sample-3: 1 Time
• Sample-4: 1 Time
• Sample-5: 1 Time
• Sample-6: 1 Time
• Sample-7: 1 Time
• Sample-8: 1 Time
• Sample-9: 1 Time
• Sample-10: 1 Time
• End Standard: 1 Time
• For injection of more than 12 samples, run end standard after every 12th sample.
• Calculate the result comparing the area of sample solution with the average area of 5th standard (6th standard if six replicate injections required) and respective end standard.

Chromatogram review and documentation:

The custom report covers the following information and can be modified as per the specific need.

• Acquired by
• Sample Name
• Sample ID
• Tray No.
• Vial No.
• Injection Volume
• Data File
• Method File
• Batch File
• Date Acquired

The peak table in custom report for standard covers the following data, however select other data as per requirement.

• Title
• Sample Name
• Sample ID
• Ret. Time
• Area
• Theoretical Plate
• Tailing Factor
• Resolution

The peak table in custom report for sample covers the following data, however select other data as per requirement.

• Title
• Sample Name
• Sample ID
• Ret. Time
• Area
• Result
• Unit

General guideline:

• In the test for Assay, run all Standard & Sample chromatograms minimum 2 minutes extra after the principal peak elution is over & peak is properly integrated or as per the method.
• In Chromatographic Purity/Degradation/Related Substances, run the chromatogram 2.5 times the retention time of principal peak or as specified in individual method. In case of specific impurity analysis, run the chromatogram minimum 2 minutes extra after the principal peak elution is over and peak is properly integrated.

Allowable modification in chromatographic system:

Following are general criteria, which provide extent of allowable variation to get system suitability. The adjustments are allowed only to improve quality of chromatography unless otherwise directed in the respective method/pharmacopoeial monograph.

pH of mobile phase:

pH of aqueous buffer used in mobile phase preparation can be adjusted to within ± 0.2 units of the value or range specified. (Example: If specified pH is 7.0 then allowable limit for adjustment is 6.80 – 7.20)

Concentration of salts in buffer:

Concentration of salts used in the preparation of aqueous buffer employed in mobile phase can be adjusted within ± 10% if the permitted pH variation is met. (Example: If specified concentration is 1.0% then allowable limit for adjustment is 0.90%–1.10%)

Ratio of components in the mobile phase

Following adjustment limits apply to minor components of the mobile phase (specified at 50% or less). The amount(s) of these component(s) can be adjusted + 30% relative. However the change in any component cannot exceed + 10% of absolute (i.e. in relation to the total mobile phase). Adjustment can be made to one minor component in ternary mixture. Examples of adjustments for binary and ternary mixture are given below.

Binary mixtures

Specified ratio of 50:50: 30% of 50 is 15% absolute, but this exceeds the maximum permitted change of + 10% absolute in either component. Therefore, the mobile phase ratio may be adjusted only within the range of 40:60 to 60:40.

Specified ratio of 2:98: 30%of 2 is 0.6% absolute. Therefore the maximum allowed adjustment is within the range of 1.4:98.6 to 2.6:97.4.

Ternary Mixtures

Specified ratio of 60:35:5: For the second component, 30% of 35 is 10.5% absolute, which exceeds the maximum permitted change of + 10% absolute in any component. Therefore the second component may be adjusted only within the range of 25% to 45% absolute. For the third component, 30% of 5 is 1.5% absolute. In all cases, a sufficient quantity of the first component is used to give a total of 100%. Therefore, mixture range of 50:45:5 to 70:25:5 or 58.5:35:6.5 to 61.5:35:3.5 would meet the requirement.

Detector wavelength

• Deviations from the wavelengths specified in the method are not permitted.
• Stationary phase:
• Column length: ±70%.
• Column internal diameter: ±25%.
• Particle size: Maximum reduction of 50%, No Increase    permitted.
• Flow rate: When the particle size is changed, the flow rate may require adjustment, because smaller particle columns will require higher linear velocities for the same performance (as measured by reduced plate height). Flow rate changes for both a change in column diameter and particle size can be made by:

F₂=F₁x [(dc₂2xdp₁)/( dc₁2xdp₂)]

Where F1 and F2 are the flow rates for the original and modified conditions, respectively; dc₁ and dc₂ are the respective column diameters; and dp₁ and dp₂ are the particle sizes.

When column dimensions are changed, the flow rate may be adjusted using the following equation:

F₂=F₁x [(l₂d₂2/( l₁d₁2)]

Where F₁ and F₂ are the flow rates for the original and modified conditions, respectively; l₁ and l₂ are the respective column lengths; and d₁ and d₂ are the diameters.

• Injection volume: Injection volume can be reduced as far as consistent with acceptance precision and detection limits; no increase is permitted.

Column temperature: ±10°C.      F₂=F₁x [(l₂d₂2/( l₁d₁2)]

This is all about

HPLC analysis and system suitability.

HPLC Column Washing Procedure; Purpose

The tenacity of this SOP is to define the procedure for washing of HPLC column to avoid any intrusion on repeated usage & to escalation column lifespan.

HPLC Column Washing Procedure; Scope

This procedure is applicable for all HPLC columns used within quality control laboratory of XX Pharmaceuticals Limited.

Definition: 

• COA: Certificate of analysis
• HPLC: High performance liquid chromatography
• QC: Quality Control
• SOP: Standard Operating Procedure

Responsibilities

The roles and responsibility is as follows

Senior Executive/Executive, Quality Control

• To confirm that the instructions of this procedure are correctly followed.
• To accomplish the HPLC column washing properly in accordance with this SOP.
• To keep record of HPLC column washing time properly.

Manager, Quality Control

• To confirm that this procedure is kept up to date.
• To ensure that the SOP reflects the required working practices.
• To assemble training on the SOP to all concerned personnel and to confirm implementation of the SOP after training.

Head of Quality Assurance

• Take initiative to approval of the SOP.
• To confirm the overall implementation of the SOP.

Procedure

• Use HPLC grade solvents for column washing.
• Freshly prepared, filtered and degassed solvent or solution should be used.
• Purge solvent line to make them free from air bubbles.
• Do not change flow rate at increment greater than 0.2 ml/min.
• Keep column with proper end fitting during storage.
• Do not over make tighter the column end fittings.

Pre-Wash (mobile phase run/ Prior to analysis) procedure

• Set column on column compartment of HPLC.
• Select shipping solvent, from COA of respective manufacturer, If not mentioned in COA, store the column based on column properties like Nitrile /ODS/Amine group etc.
• Run shipping solvent (e.g. Azide solution, 65% Acetonitrile,) mentioned in COA of respective manufacturer for 15-20 minutes.
• Gradually change the organic phase composition depending on the organic phase composition in mobile phase to reach the same in mobile phase. For example, gradually decrease the organic phase from 65% Acetonitrile (in shipping solvent) & finally reach 30% Acetonitrile (in mobile phase). For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents, as appropriate. Accomplish this run within 15 to 20 minutes.
• Change line with mobile phase & execute HPLC analysis.

Post-Wash (mobile phase run /after completion of analysis) procedure

• For mobile phase containing Buffer and counter ion
• Replace mobile phase with purified water. Purge line. Run same for 15-20 minutes.
• Depending on shipping solvent, gradually reach the same. For example, if 65% Acetonitrile is shipping solvent, then start with 100 % purified water and gradually increase the organic phase and finally reach at 65% Acetonitrile. For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents like 15%, 30%, 45% Acetonitrile, as appropriate. Accomplish this run within 55-60 minutes conducting each solvent composition period 15-20 minutes.

For mobile phase without buffer and counter ion

Depending on the shipping solvent, gradually reach the condition from the organic phase composition of mobile phase. For example, if 65% Acetonitrile is shipping solvent and organic phase composition in mobile phase is 30% Acetonitrile, then start with the initial organic phase of 30% Acetonitrile (70% Purified water) and gradually increase the organic phase and finally reach at 65% Acetonitrile. For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents as appropriate. Accomplish this run within 55 to 60 minutes conducting each solvent composition period 15 to 20 minutes.

 For mobile phase containing tri-ethyl amine

• Replace the mobile phase with a mixture of methanol and 0.05% phosphoric acid (50:50 v/v) & run for 30 minutes.
• Depending on the shipping solvent, gradually reach same. For example, if 65% Acetonitrile is storing solvent, then start with 20 to 30% Acetonitrile & gradually increase the organic phase and finally reach at 65% Acetonitrile. For the Gradient HPLC this can be conducted through time program and for Isocratic HPLC, this can be done using intermediate solvents as appropriate. Accomplish this run within 55 to 60 minutes conducting each solvent composition period 15 to 20 minutes.
• Stop run. Remove column from HPLC unit, do end capping properly both ends &  place in respective column box.
• Store column box in an allocated place.
• Record HPLC column washing time after analysis in logbook for operation of HPLC.

HPLC Column Management; Purpose

The tenacity of this SOP is to define proper controlling of all HPLC columns during receive, use and storage period to confirm that the HPLC column performs satisfactorily and gives reproducible results.

HPLC Column Management; Scope

This process is applicable for stock usage of HPLC columns required for Materials and Products analysis in quality control laboratory of general block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[] QC: Quality Control.

[] HPLC: High performance liquid chromatography.

[] CoA: Certificate of analysis.

Responsibilities:

The roles and responsibility is as follows

Officer/Executive/Senior Executive, Quality Control

• To confirm that this procedure is followed.
• To maintain the records properly as per SOP.

Assistant Manager, Quality Control

• To confirm that this procedure is kept up to date.
• To ensure that the SOP is technically sound & reflects the required working practices.
• Organize training on the SOP to all relevant personnel.
• To confirm implementation of the SOP after training.
• Schedule calibration of the instrument at the defined intervals.

Head of Quality Assurance

• Initiative to take approval of the SOP.
• To confirm overall implementation of this SOP.

Procedure:

• Preserve column with appropriate end fitting during storage.
• Prevent the column from any type of mechanical shocks.
• Always use the column in the indicated direction.
• Clean solvent reservoir filter in the mobile phase by sonication in the Methanol for 30 minutes, when required.
• Test sample should be free from any type of particulate matter.
• Stock review and raise requisition

Executive, QC will raise a purchase requisition considering the following elements:

• Product & Method wise dedicated column.
• New method related to Product Development which is in product launch pipeline for commercialization.
• New Pharmacopoeia (BP, USP & EP) requirements.
• Underprivileged system suitability performance of a column that has been triggered from HPLC column usage register and included in retired HPLC column register.
• Executive, QC will make a list for purchasing of new columns on the basis of purchase requisitions to ensure uninterrupted HPLC analysis.
• In-Charge, QC will finally review the list for purchasing of new columns by checking the HPLC column stock and issue and retired HPLC column register status or considering column requirement for new product.

Column receiving

• Executive, QC will receive new column with CoA.
• After receiving a new HPLC column, QC Executive will check the column CoA, specification & physical condition and compare with Purchase Order and Invoice description.
• If complies with ordered description, then assign an individual column serial number (e.g. GQC-H001, where H represents HPLC column and 001 is the serial number) and record necessary information [Column receiving date, Column description (Name, brand, particle size and dimension etc.), Part number/ Catalogue, Manufacturer name, Supplier name, Column Sl. No., Column dedicated for (Product /Material), Column issue date etc.] in the HPLC column stock and issue register.

Column performance check for new column: HPLC Column Management

• Check availability of reference reagents /standards required for performance test. If unavailable, then promptly raise requisition.
• Carry out the column performance test for new HPLC column, as per manufacturer’s instructions. (If particular chemicals as per Manufacturer’s CoA are available.)
• Check column with respect to Manufacturer’s CoA for retention time, theoretical plates using the material provided with the column & method specified by manufacturer.
• In case of emergency carry out performance check only with the available reference standards/reagents.
• Connect the column to HPLC system.
• Flush (condition) specific column with shipping solvent (the details available with manufacturer’s CoA) or methanol for at least 30 minutes with a flow rate of 0.5 ml/min.
• Flush column with mobile phase as mentioned in the technique for respective columns.
• Prepare test solution in mobile phase as recommended in the procedure.
• After column is conditioned, inject 20 µl or as per manufacturer’s CoA & record chromatograph of test solution.
• Calculate tangent (theoretical plates) as per the USP method. The result should meet system suitability parameters.

Theoretical plate: (N) = 16 (t/W)2

Asymmetry (10%) = w/2f

Where, t = Retention time

W = Width of peak measured by extrapolating the relatively straight sides to the baseline

W = Width of peak at 10% of peak height

f = Distance between perpendicular dropped from apex of the peak and leading edge of peak at 10% of peak height

• Keep records of the performance check on the HPLC Column Performance Check Record (as per Annexure-IV).
• Accept column for use if observed values are within limit specified in manufacturer’s CoA.
• Inform manufacturer through Purchase Department, if test result doesn’t comply with the accepted limit mentioned in the manufacturer’s CoA.
• If problem is not resolved, reject same & information Purchase Department regarding rejection.

Material/Product Dedicated Column

• In-Charge, QC will ensure method and/or product wise dedicated columns are available for HPLC analysis.
• Same column can be used for analysis of two or more products in different dosage form where product formulation & active ingredients are same. But prior to use, method shall be validated using same column.
• If dedicated column is not available, instantly discuss with In-Charge, Quality Control.
• Column other than material and/or product dedicated column can be used in case of emergency with the concern of In-Charge, Quality Control.

Column Issue

• Prior to issue a new column, review previous column history & record all information [Initial theoretical plates (Before issue), Column issue date, Issued by, Remarks] in the HPLC column stock and issue register.
• If dedicated column is not available for a new material/product analysis, discuss the matter with In-Charge, QC for alternate decision.
• All decisions shall be recorded in HPLC column stock and issue register (Annexure-I).
• After issue, record the column information in a new page in HPLC Column usage register. (Annexure-II).

Column Care

• Confirm that the integrity of the column packing is not be disturbed by needless opening of the column ends.
• Handle HPLC columns as per manufacturers’ instructions, e.g. avoidance of physical shock, vibration and storage at high temperature.
• For silica-based columns, avoid eluents outside the pH range of 3-8 where possible, except when column manufacturer specifications acclaim otherwise.
• Wash column as per HPLC column washing procedure.
• After use, wash the column to make it free from buffer salts with a suitable solvent (typically 1:1 aqueous/organic solvent for reversed phase columns) about 45 to 60 minutes maintaining a flow rate of 1.5 to 2.0 ml per minute.
• After washing cap or seal column for storage in designated place.
• In case of poor system suitability performance or column blockage caused by precipitation of buffer salts, always incorporate a flush with a solvent/water mixture before switching to pure solvent as per HPLC analysis and system suitability check procedure SOP No.: (SOP/QC/009).
• Record the HPLC column flushing time in HPLC log book. Maintain HPLC column cleaning and storage as per manufacturer’s instructions.

Regeneration of a column

• If the system suitability fails only then do the column regeneration.
• For columns C6, C4, C18, C8, Phenyl, Amino, Polymeric follow the sequence given below with a 1.0 ml flow per minute flow rate.
• Flush with filtered and de-gassed water for 30 minutes. Inject 20 µL of 1.0% of Acetic acid in purified water.
• Flush with Methanol for 30 minutes, inject 20 µL of 1.0% Dimethyl Sulphonic Oxide (spectroscopic grade) in Methanol.
• Flush with

1. Acetonitrile for 15 minutes;
2. Chloroform for 10 minutes;
3. Methanol for 30 minutes sequentially;
4. Isopropanol for 15 minutes;
5. Purified water for 15 minutes

• Check pH of water at inlet and outlet, which should be identical.
• Mobile phase for the compound to be analyzed.

Retired HPLC Column

• After washing, if the HPLC column performance is not improved then In-Charge, QC will review column washing process and column history prior to discarding/retiring a column.
• The column retiring information must be recorded in the respective page of HPLC column usage log sheet (Annexure-II) and retired column register (Annexure-III).
• Keep all retired columns under lock & key in a separate locker in the lab area. Before keeping analyst must ensure that the retired column has been separated from usage stock and de-shaped.
• Periodically the HPLC column usage log sheet and retired column register shall be reviewed and retired column shall be destroyed as per column destruction process and manufacturers’ instructions.
• Retired column storage period should not be less than last test product shelf-life plus one year.

Download All Annexure: HPLC Column Management

Annexure I HPLC Column Stock and Issue Register

Annexure II HPLC Column Usage Register

Annexure III Retired HPLC Column Register

Annexure IV HPLC Column Performance Check Record

Waste Management; Purpose

The purpose of this SOP is to describe the laboratory waste management procedure for disposal of test samples (raw materials, in-process, bulk/ finished product left over samples); expired retention samples (raw materials, finished product); broken glassware and glass container; packaging materials; all Laboratory chemicals & reagents used within the quality control laboratory.

Waste Management; Scope

This procedure is applicable to all laboratory operations associated with the disposal activity in the quality control and microbiology laboratory for general block at XX Pharmaceuticals Limited.

Definitions / Abbreviation

• SOP: Standard Operating Procedure
• QC: Quality Control
• ETP: Effluent Treatment Plant
• MSDS: Material Safety Data Sheet

Responsibilities

The roles and responsibilities are as follows

Senior Executive/Executive, QC & Microbiology

• To ensure that this procedure is followed.
• To identify correct sample for disposal.

 Asst. Manager, Quality Control

• To ensure that this procedure is kept up to date.
• To confirm that the SOP reflects the required working practices.
• Arrange training on the SOP to all concerned personnel.
• To ensure implementation of the SOP into routine use after training.
• To ensure availability of adequate facilities, systems and resources to carry out this process and approve the SOP.

Head of Quality Assurance

• Take initiative to Approval of this SOP
• To ensure the overall implementation of the SOP

Procedure

• Wear rubber gloves, mask, safety glass and footwear during disposal work.
• Carry out the disposal work at the designated place.
• Wash hands thoroughly with soap and water, at the end of the operation.
• Always keep the waste bin covered with lids.
• Destroy any label/carton/ foil before dumping into the bin for disposal.
• Cross mark all label on the container with marker pen or destroy the label of container before disposal.
• Use separate container for collecting the broken glass and transfer to the salvage yard-marking container as “BROKEN GLASSWARE”.
• Do not return left over samples of raw materials, in-process material, bulk/ filled products to the container or work points from which it has been taken.
• Keep all the waste in designated bin.
• Carefully identify the name and check the status label of the sample to be disposed off.
• Check the MSDS of raw materials for the hazardous identification and proper method of disposal.
• Check the container properly for any left out material before disposition of the containers.
• Use the sink of fume cupboard to drain out flammable, toxic, corrosive water-soluble solvent and all mobile phase.
• Never light any type of flames & always place sign “No Flames” to warn others about the presence of Ether. Accumulate water immiscible solvents [like Chloroform, Dichloromethane, Carbon Tetrachloride, etc.) into one bottle & ether (Diethyl Ether waste) in another bottle & evaporate them separately using beaker by placing in fume cupboard.
• Place hazardous solid waste (e.g. tissue paper, filter paper, cotton, contaminated gloves etc.) in dedicated bin/container.
• Dispose liquid samples in sink by using large amount of tap water.
• After completion of test, retain left over samples of raw materials, in-process material, bulk/ finished products with proper identification labeled as “UNDER TEST SAMPLE” in specified place the batch is approved.
• After approval of the batch, transfer the excess samples (tablets, raw materials, capsules) of approved batch to a place labeled as “SAMPLE FOR DISPOSAL” record the disposal details in the Sample Disposal Register (Annexure-I).
• Once in a month or when required, collect and destroy all samples for disposal following the above steps.
• In case of raw materials, in-process material, and bulk/ finished products, empty out the sample from the poly bag into a container containing water, destroy the sample label of poly bag by shredding into “WASTE BIN FOR PAPER” & destroy the ploy bag in to the bin, labeled as “HAZARDOUS SOLID WASTE “.
• Shake dispersion of sample in container with the help of a glass & allow disintegrating. After the complete disintegration, drain out slowly into designated place & clean the drain with adequate water flushing.
• For stability sample after approval of report, analyst shall destroy the samples by dispersing them into a container having sufficient water and destroy the film, foil, de-blistered strips/blisters into a designated bin, labeled as “FILM/ FOILS FOR DISPOSAL”;
• The secondary packaging materials (carton, leaflets, labels, shipper carton, master carton) into “WASTE BIN FOR PAPER” and other packaging materials (i.e. polyethylene bag, cap, plastic stopper, dropper etc.) into another bin, labeled as “PACKAGING MATERIAL FOR DISPOSAL”.
• Shake the dispersion of sample in container with the help of a glass rod and allow to disintegrate. After complete disintegration, drain out slowly into designated place and clean the drain with adequate water flushing.
• In case of ampoules, vials and bottles; break open the glass ampoule, open the vials and bottles, empty the contents in water and discard the broken ampoule and vial into a bin, labeled as “BROKEN GLASSWARE”. Shake the dispersion of sample in container with the help of a glass rod and allow to disintegrate. After the complete disintegration, drain out slowly into designated place and clean the drain with adequate water flushing.
• Collect all types of waste from the respective bins into the different polythene bag by attaching “TO BE DISPOSED” label, weigh the waste content, and send waste to the salvage yard with a waste transfer note.

Download Annexure Here: Waste Management

Annexure I Sample Disposal Register

Test solution and volumetric solution; Purpose

The tenacity of this procedure is to describe procedure for preparation & handling of test solution and volumetric solution.

Test solution and volumetric solution; Scope

This SOP is valid for preparation of chemical reagent in Quality Control Laboratory at XX Pharmaceuticals Ltd.

Definitions

N/A

Responsibilities

The roles and responsibility is as follows

Officer/Executive/ Sr. Executive, Quality Control

• To confirm tests are performed with correct reagent as specified in method.
• To confirm record of reagent preparation in the work sheet.
• To confirm correct storage of reagent.
• To confirm use of reagent within the shelf life.
• To confirm reagents are retained until test results are approved.
• To confirm use of log book.

Assistant Manager, Quality Control

• To ensure reagents are in place and controlled.
• To assess & disposition of expired reagent.
• To maintain record.
• To incorporate sound technical knowledge.

Head of Quality Assurance

• To ensure the overall implementation of the SOP.
• Take initiative to approval of the SOP.

Procedure

Precaution(s):

• Wear protective clothing, gloves and goggles. Avoid contact with skin, eyes & clothing & inhalation of vapor.
• Use a fume hood while preparing solutions.
• Read label instructions of reagent container for any special precaution.

General

• For solution preparation use purified water & analytical grade reagents & chemicals.
• Prepare solution as per respective approved worksheet.
• Calculate expiry date of solutions from date of preparation.
• Check the following things before preparation of any solution.

1. Glassware being used is clean & dried.
2. Required reagents are available.
3. Required instruments are calibrated.

• Wear suitable safety appliances while making concentrated solutions of acid & alkali/any hazardous chemicals/substances.

 General guideline for the preparation of Test Solution

• Enter details in test solution preparation register (as per Annexure-I)
• Assign sequential reference number as below:

1. g.TS-001/09/XX
2. Where, TS is the abbreviation of Test Solution
3. 001 is the sequential number
4. / is separator
5. 09 is the month of preparation (September)
6. XX is last two digits of year 20XX

• Affix respective label on container as per Annexure-III.
• Expiry date of test solutions will be 06 months or as per mentioned in respective worksheet. During usage, any change in physical properties of the solution identified then discard it.
• If a solution is directed to prepare “fresh” then it must be prepared on the same day of use
• Discard the excess solution after expiry/ usage by diluting the solution with doubled quantity of water & then drain it into the drainage, and & entry on the respective worksheet & register.

General guideline for the preparation of volumetric solution

• Analyst shall prepare all type of volumetric solutions as per respective worksheet.
• Enter details in volumetric solution preparation register (as per Annexure-II)
• Assign sequential reference number as below:

1. g.VS001-001/08/XX
2. Where, VS001 is the code no. of 0.1 M Ammonium thiocyanate VS
3. 001 is the sequential number
4. / is separator
5. 09 is the month of preparation (August)
6. XX is last two digits of year 20XX

• Affix respective label on the container as per Annexure-IV.
• Volumetric solutions and standard solution for limit test must not be store for more than three months. If during usage any change in physical properties of the solution identified then discard the solution.
• Where stabilization time is not mentioned, stabilize solution for one hour before standardization.
• Carry out standardization & calculate factor of the solution twice & RSD of two results must be within 0.2%
• Find out the mean factor, which will be within ±5.0% of the labeled factor.
• If factor of prepared solution identified more than ±5.0% variation, do the necessary dilutions/weight adjustments and carry out re-standardization. Report the factor upto four digits after decimal.
• Solution should be re-standardized in 1 month +7 days interval. In case, where extraneous matters, layer separation or hazy solution observed then discard the solution.

Assign re-standardization reference number as below

e.g. Reference No./R1

Where, Reference No. of the volumetric solution subjected to re-standardization

/ is separator

R1 is re-standardization for first time (e.g. R1, R2…..)

Store all the solutions in cleaned dry containers & use amber color containers for light sensitive solutions.

Reject excess solution after expiry/ usage by diluting the solution with doubled quantity of water and then drain it into the drainage, and make entry on the respective worksheet & specific register.

Download all Annexure Here

Annexure I Test Solution Preparation Register

Annexure II Volumetric Solution Preparation and Standardization Register

Annexure III & IV Label for Test Solution & Label for Volumetric Solutions

Chemicals and Reagents Management; Purpose

The tenacity of this SOP is to define the process for order, receipt, labeling, daily issue, stock control, handling, storage, labeling and expiry dating of all laboratory chemicals and reagents, solvents & solutions used within the quality control laboratory at XX Pharmaceuticals Ltd.

Chemicals and Reagents Management; Scope

This procedure is applicable to all laboratory chemicals & reagents, solvents & solutions used in the quality control laboratory at XX Pharmaceuticals Limited.

Chemicals and Reagents Management; Definitions / Abbreviation

[] ACS: American Chemical Society.

[] AR: Analytical Reagent.

[] GR: Guaranteed reagent.

[] MSDS: Material safety data sheet.

[] SOP: Standard Operating Procedure.

[] QC: Quality Control.

Reagent

Reagent is a substance which is added to a system in order to cause a specific chemical reaction, or added to notice if a reaction occurs or not.

Flash point

It is describe as minimum temperature of liquid at which it provides sufficient vapor to form ignitable mixture with the air.

Flammable liquid

Any liquid having Flash Point below 37.8⁰C[100 F]. Less-flammable liquids having flashpoint between 100 F & 200 F are well-defined as the combustible liquids.

HLF:

Highly flammable liquid having Flash Point of less than 32⁰C

Corrosive substance

A corrosive substance can be defined as which destroy or irretrievably damage human tissue when it comes into contact. Normally used corrosives are: Ammonium Hhydroxide, Acetic Acid, Chromic Acid, Hydrochloric Acid, Hydrotropic Acid, Hydrofluoric Acid, Nitric Acid, Perchloric Acid, Potassium Hydroxide, Phosphoric Acid, Sulfuric acid, Sodium Hydroxide.

YTD

Year-to-date. It can be defined as a period, starting from the beginning of the current year, and continuing up to the present day.

Chemicals and Reagents Management; Responsibilities:

The roles and responsibility is as follows

Officer/ Executive, QC

• To raise requisition for & receive all laboratory chemicals & reagents maintaining proper procedure.
• To confirm labeling with proper information, expiry dating of all laboratory chemicals, solvents, reagents and solutions after receipt or preparation.
• To maintain daily issue, usage & all records properly as per SOP.
• To confirm that procedures are followed during preparation of reagents & solutions.
• To confirm that this procedure is followed.

Manager, Quality Control

• To confirm that this procedure is kept up to date.
• To check that the SOP reflects the required working practices.
• To conduct training on the SOP to all concerned personnel & ensure implementation after training.
• To confirm effective assessment for expiry dating of laboratory chemicals, reagents and solvents.
• To track timely procurement of laboratory chemicals and reagents.

Manager, Quality Assurance

• Take initiative to Approval of the SOP.
• To confirm the overall implementation of the SOP.

Procedure:

Precaution(s):

• Follow the relevant MSDS & safety guidelines while handling chemicals & hazardous reagents.
• Proper protective clothing such as safety glasses, gloves & laboratory coat must be worn while handling chemicals in the laboratory.
• Use fume hood while handling acids, bases, hazardous & flammables substances.
• Try to minimum exposure to avoid contamination.
• Use sonication to degas HPLC mobile phase before use.
• Correctly label each unit container of chemicals & reagents.
• Read reagent label very carefully before any type of use.
• Don’t use any chemical or solvent when contaminated or change of physical appearance or precipitation observed.
• Never ingest toxic substances.
• Do not allow highly flammable liquids, toxic substances, corrosive substances to come into contact with the skin and eye.
• Keep away flammables substances from fire or ignition source.

General guidelines

• Never use beakers or measuring cylinders for precise volumetric measurement.
• Always use class a glassware for all volumetric application.
• Allow solutions temperature reduce to room temperature before any dilution to volume.
• Always use clean, inert PTFE stirring bar as magnetic stirrer.
• Reagent quality must be ACS[American Chemical Society] or AR or GR grade or equivalent, unless otherwise specified in relevant analytical method.
• To prepare reagent solutions always use distilled water or purified water (that complies with USP/ BP/ EP requirement).
• To avoid contamination even with best precaution, never return dispensed chemicals to stock bottle.
• Before mixing solutions together, measure each solution individually.
• Highly consumable like Methanol, maintain control of first in first out (FIFO) process.
• Checked Expiry dates of reagent solution be before use.
• To prevent contamination to the entire quantity and allocate the same expiry date as mentioned in the primary container, divide a large quantity of reagent into smaller containers. This is very useful for hygroscopic reagents.
• Light sensitive reagent solution is to be kept in plastic bottles or amber glass.
• Store chemicals in a designated place, away from heat or sunlight, return to the same location after each time of use.
• Never store chemicals or waste in fume hood.

Ordering of reagents and chemicals

• Review laboratory chemicals & reagents stock inventory on Monthly/Six monthly/Yearly basis / as when required.
• Prepare a list for purchasing of new reagents & chemicals to ensure uninterrupted analysis in laboratory operations.

Raise a purchase requisition considering the following elements:

• New method related to new product which is in product launching pipeline for commercialization of new product.
• Reagents or chemicals with short self life expiry.
• Pharmacopoeia (BP, USP & EP) requirements.
• If possible, to avoid powder handling, Order toxic materials in liquid form.
• Place requisition minimum three months earlier to the Procurement Department before the existing stock become nil.

Receipt of reagents and chemicals

• Just after receipt, check integrity of the container & ensure reagents & chemicals are received its standard condition.
• Check label on the bottle & tally with invoice / certificate / MSDS. If any discrepancy is found, report promptly to Store and Procurement Department.
• After receipt, record receiving information at “Reagent and Chemical Receiving Register” as per Annexure-II & “Reagent Stock and Issue Register” for Liquid/Solid as per Annexure-III respectively.
• Use ‘S- serial number’ for solid reagent & L- serial number’ for liquid reagent for reagent code numbering,.
• Affix a reagent label to each unit primary container as per Annexure-VI.
• Record the date of receipt & storage temperature mentioned on the label collected from manufacturer’s label/ certificate of analysis/ invoice. Assign the expiry date if found in manufacturer’s label.
• Allocate the expiry date from the date of opening as follows, unless otherwise stated in manufacturer’s label,
• Store reagents & chemicals in dedicated area where temperature at or below 30°C.
• Keep large quantities solvents in the solvent store at room temperature unless otherwise stated in manufacturer’s label.

Use of reagents and chemicals

• Issue unbroken bottle/container from stock against requisition as per Annexure-I & maintain issue record (issued quantity/ issued by/date/balance amount etc. as required) into the ‘Reagent Stock and Issue Register’ for Liquid or Solid as per Annexure-III.
• On the basis of critical stock position, raise requisition for chemicals & reagents to procurement department.
• Allocate opened date/expiry date sign on the previously affixed label for newly opened container.
• Not issued bottle/containers must not be mix with the opened bottle/container.

 Handling and storage of Toxic substances, highly flammable liquids

Toxic substances:

• All toxic substances/chemicals to be labeled as toxic & handled under fume cupboard.
• For weighing dry toxic powder, use container with lid. Add approximate amount of powder to the container & close lid in a fume hood. Back to the balance & weigh the powder. Back to the fume hood to prepare solution.
• Keep container closed as soon as possible with tightly fitting.
• Low dilute solution (<1% w/v) of toxic substances may be handled in the laboratory with appropriate care to avoid contamination of the area & individuals.
• All vessels/containers used for long-lasting storage of toxic substances/chemicals must be carefully labeled with the contents & hazard type.
• Vinyl/nitrile/latex gloves must be worn while handling toxic substances/chemicals. Properly fitted mask must be use to handle handling solid toxic substances.
• Adequate care should be taken during removing of PPE [Personal Protective Equipment] to avoid contamination of the hand/face.
• All contamination by toxic substances/chemicals must be washed off/cleaned up instantly as per instructions/guidelines/protective measures mentioned on MSDS [Material Safety Data Sheet].
• Disposal of toxic substances/chemicals must be conduct with extra care.

 Highly flammable liquids

• Majority of laboratory solvents and certain flavors, essence & film coating solutions are highly flammable liquids

can cause serious fires & explosions with subsequent injury to personnel & damage to goods.

• Must be stored in the isolated place of Solvent store area.
• An intact bottle shall be transferred to the laboratory by maintaining a record/requisition.
• Stored quantity in the Laboratory/ Production area must not exceed 20 litres.
• To avoid accumulation of vapor, must be stored in a suitable well ventilated place.
• Must be handled in a well-ventilated area such as a fume cupboard in the Laboratory.
• A suitable carrier to be use during carrying of Bottles to minimize the risk of breakage.
• Containers should not store in direct sunlight/near a source of heat/ignition. Store the containers in the isolated place on a metal/solvent resistant tray.
• Never use in the same working area near undressed flame, hot plate/any equipment that is legally responsible to produce a spark.
• Container must be closed at all times other than when the liquid is being transferred from it.

Download all Annexure Here: Chemicals and Reagents Management

Annexure I Requisition Form for Laboratory Chemicals and Reagents

Annexure II Reagent and Chemical Receiving Register

Annexure III Reagent Stock and Issue Register

Annexure IV List of Toxic Laboratory Chemicals

Annexure V List of Flammable Solvents

Annexure VI Label for Reagent

Handling of spillage; Purpose

The tenacity of this SOP is to define the handling of the spillages in the quality control laboratory to make laboratory safe, neat & clean.

Handling of spillage; Scope

This process is applicable to the chemical room, instrument room in the quality control laboratory of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[] MSDS: Material Safety Data Sheet

[] SOP: Standard Operating Procedure

[] QC: Quality Control

[] Spillage: The act of allowing a fluid or material to escape from the container.

Responsibilities

The roles and responsibility is as follows.

Lab attendant, QC

[] To clean-up the spills maintaining proper procedure.

Officer, QC

[] To ensure that this procedure is followed.

Manager, Quality Control

• To confirm that this process is kept up to date.
• To confirm that the SOP is reflects the required working practices.
• Place training on the SOP to all concerned personnel.
• To confirm implementation of the SOP after training.

Head of Quality Assurance

• Take initiative to Approval of this SOP.
• To confirm the overall implementation of the SOP.

 Procedure:

Precaution(s):

• Carefully handle the solvents & chemicals to avoid accidents & spillages.
• Use gloves, mask & eye protector while handling spillage.
• Be watchful while neutralization process of acid or base spills because it may be enthusiastic, cause splashes & yield large amount of heat.
• For spillage of flammable liquids, control all potential source of ignition near spillage area.
• Never generate dust or cause the contaminated powder to become airborne while cleaning of solid spills.
• If broken glass is involved, never pick it up with gloved hand rather than use tongs.
• Ensure that all forms of local exhaust i.e. fume hoods are operating.
• Water shouldn’t be used for chemicals which are water reactive.
• Never use a vacuum cleaner to clean up the spill.
• On spillage, personnel who caused the spill will instantly inform supervisor, all persons in the laboratory to take care & the lab attendant to clean spillage.
• Evacuate the specific area, if required.
• Limit access to spill area until total cleanup is completed.
• For water spillage use only mop with dry cloth.
• Wear suitable PPE[personal protective equipment] e.g. gloves, goggles, masks etc. while cleaning up spills.
• Use tongs to pick-up the broken glass, when spills involve broken glass, place it in plastic dustpan to place them in the bin dedicated for broken glassware.
• Use brush & the plastic dustpan to place materials into polyethylene bags & dispose it as chemical waste when spillage of solids.
• If spillage occurs due to liquids like acids or solvents, mop it up clearly.
• When needed, add adequate quantity of absorbent silica or precalcinated silica granules and let stand for few minutes, collect the material using hand gloves into polyethylene bags & dispose it as chemical waste.
• If needed, use sodium bicarbonate to neutralize acids. Use pH paper to check pH when acid spills have been neutralized. Then mop it up with water.
• For spillage of liquids like alkali, add adequate quantity of water to dilute it, mop with the help of dry cloth and finally wipe with wet cloth.
• In case of Mercury spills, begin cleanup procedure with collecting the droplets of mercury. The large droplets can be consolidated by using scraper or a piece of cardboard. For cleaning up small mercury droplets, pick up with a piece of adhesive tape. Slowly & carefully squeeze mercury onto a damp paper towel. Place paper towel into polyethylene bags & dispose it as chemical waste.
• While cleaning the area where spillage of hazardous chemicals & poisonous take precautions as per MSDS of respective chemicals.
• After bulk of the material is cleaned up, wipe up the area with previously mixed detergent water & then with tap water and then leave the area to dry.
• Rinse tools (plastic dustpan, tongs etc.) off plentiful amount of water.
• Dry tools off & keep in isolated place.
• Dispose of gloves as waste and place goggles back into the dedicated area.

Chemical laboratory safety procedure; Purpose

Chemical laboratory safety procedure, The tenacity of this SOP is to define the general laboratory safety procedure, which will confirm the safe working condition within the Quality Control Laboratory.

Chemical laboratory safety procedure; Scope

This practice is valid for laboratory operations in the quality control laboratory of XX Pharmaceuticals Limited.

Definition

[] MSDS: Material safety data sheet.

[] PPE: Personal protective equipment.

[] QC: Quality Control.

[] SOP: Standard Operating Procedure.

Responsibilities:

The roles and responsibility is as follows

User/Analyst

[] To use personal PPE [Protective Equipment] as per MSDS [Material safety data sheet].

[] To maintain appropriate procedure for safety.

Manager, Quality Control

• To confirm that this procedure is kept up to date.
• To check that SOP reflects required working practices.
• To organize training on the SOP to all concerned personnel.
• To confirm implementation of the SOP after training.
• To achieve the operational control.
• To confirm the availability of suitable PPE & safety equipment.

Head of Quality Assurance

• Take initiative to Approval of the SOP.
• To confirm the overall implementation of the SOP.

Procedure:

Precaution(s):

• Take a note of material hazard facts from the supplier’s information. Review any relevant hazard data in MSDS.
• Do not smoke, drink, chew gum, eat, or apply cosmetics in the laboratory.
• Do not keep food or beverages in the laboratory.
• Always keep the flammable chemicals away from sources of fire.
• Try to avoid unnecessary chemical exposure.
• Never use fume hood for storage.

General procedure

• Wear laboratory coat and dedicated laboratory shoes, before entering into the laboratory. Keep goggles/ eye protector in the pocket of lab coat and & when necessary. This will give protection against corrosive action of chemicals & contaminations.
• Check PPE prior to use & attire appropriate protective equipment as processes dictate & when required to avoid chemical exposure.
• Wear gloves when using any type of hazardous or toxic chemicals & respirator when handling solvents.
• Wash & clean gloves regularly during a hazardous job. Discard soiled gloves as hazardous waste after use. Remove them before leaving laboratory/at the end of the work.
• When handling/transferring solid chemicals only from one container to another, wear gloves dust mask and activity to be perform under fume cupboard.
• Treat anonymous chemicals as hazardous & before starting work, make sure the analysts are familiar with all known hazards of the chemicals & take proper precautions.
• Reject glass apparatus that is damaged, cracked/even scratched.
• Examine all glassware before use. Use washed & clean glassware. Always move gas cylinder on cylinder trolley. Gas cylinder when standing upright position should always be appropriately supported.
• Use fume hood to handle hazardous chemicals, volatile liquid and flammable compounds.
• If solvent extraction is perform by shaking in a separating funnel, release pressure at frequent intervals by reversing funnel. Point the funnel away from the eyes & naked flames.
• Avoid pipetting anything by mouth. Use mechanical pipetting device/pipette bulb/ aspirator.
• Always add the acid to the water when diluting acids; never add water to acid. Add the acid to water slowly.
• Conduct periodical inspection in laboratory refrigerators & storerooms, correctly label all collected samples.
• Confirm all electrical wires are properly insulated. Report all electrical faults to the reporting authority/supervisor.
• Instantly Report all type accidents to the Supervisor/Manager.
• Confirm that all personnel engage laboratory know about the fire exit from the chemical laboratory.
• Confirm eye showers & Fire extinguishers are located at easily accessible points.
• Confirm all personnel/user are aware about the locations & proper use of all safety equipments (e.g. eye shower, First-aid kit, fire extinguishers).
• Wash hands before leaving the laboratory, in case of chemical handling.
• Wash the exposed area with large amount of water in case of spillage of any acid, base or irritant material on skin and seek immediate medical support if required.
• Clearly sealed& labeled the dangerous materials and never leave it on the working bench unattended
• Visitors to laboratory should be under the direct supervision of a accountable personnel.

Spillages

• Spillages must be instantly dealt as per SOP for Handling of Spillages in the QC Laboratory.

Disposal of waste

• Waste must be disposed as per SOP for Waste Management in QC Laboratory.