Month: April 2025

SOP Title: Sampling and Analysis of Water for Chemical Analysis

1. Objective:

To lay down the Procedure for Sampling and Analysis of Water for Chemical Analysis.

2. Scope:

This procedure is applicable for Sampling and Analysis of Water for Chemical Analysis.

.

3. Responsibility:
   • Quality Control: To prepare and review the SOP. To follow the Procedure for Sampling and Analysis of Water for Chemical Analysis as per this SOP.
   • Quality Assurance Department: To review and approve the SOP and Annexure.
4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

5.1	Safety Precautions/Instructions:
5.1.1	Before carry out sampling operation analyst should wear personal protective equipments such as protective hand gloves, nose masks and goggles.
5.2	Procedure for Sampling of Water:
5.2.1	For water sampling, carry the transparent screw cap bottle.
5.2.2	If sampling points located in core area; analyst should ensure itself that over gowning procedure should followed as per requirement of the particular area.
5.2.3	Prior to taking samples from the user points, drain OFF about 2 – 5 litres of water.
5.2.4	Collect the water sample as follows: Purified Water- about 800 ml Treated Water- about 200 ml Raw Water –about 500 ml Soft Water – about 200 ml Potable Water – about 500 ml
5.2.5	Collect the sample and secure the lid tightly leaving a minimum headspace in the bottle.
5.2.6	Affix label or mark with marker pen on the sample bottle with sampling point number and date of sampling.
5.2.7	Bring all the samples to QC Department; make entry in “Water Inward Register” and assign the A. R. No.
5.3	Assigning the A. R. No:
5.3.1	Assigning of A.R Numbering system is as follows. CD/XX/001 CD: Stand for code number of sample. XX: Stand for last two digits of current year 001: Stand for serial number
5.3.2	For Ex.  : PW/24/001 PW : Code number stand for Purified water 24   : Stands for last two digit of year 2024 001  : First serial number of the series.
5.3.3	Water sample codes PW : Code number stands for Purified water RW : Code number stands for Raw water TW : Code number stands for Treated water SW : Code number stands for Soft water PO : Code number stands for Potable water
5.3.4	Define sampling points and their respective location.
5.3.5	For daily water analysis, define water sampling plan.
5.4	Analysis of Water:
5.4.1	Carry out analysis within 2 hrs of sampling. If not then refrigerate the samples at 2 to 8 °C up to 8 hrs.
5.4.2	Perform the analysis as per respective Pharmacopoeia IP/BP/USP or In-House Specification and record the data in their respective AWR.
5.4.3	Get  “Analytical Work Report” from QA.
5.4.4	Analyst should refer Standard Testing Procedure to ensure that all required reagents, chemicals, accessories, equipment or instruments are standardised or validated and available in the laboratory.
5.4.5	Analyst should fill in the necessary details on the Analytical Work Report according to ‘Water Inward Register’ and start the analysis as per Standard Testing Procedure and Specification.
5.4.6	Analyst should refer to the SOP of instrument before operation and update the instrument operation logs immediately after use.
5.4.7	After the analysis, analyst should hand over the Analytical Work Report to Supervisor/Reviewer for data checking.
5.4.8	If Supervisor/Reviewer observed any discrepancy with analysis or analytical data, he / she should consult to Head of the Department for investigation.
5.4.9	Supervisor shall initiate investigation as per SOP “Out of Specification” by filling OOS form.
5.4.10	If due to holiday or any other reason, it is not possible to analyse the sample on the scheduled day of the week, perform sampling and analysis of those points on next working day.
5.5	Seasonal Validation of Water System Plan:
5.5.1	Sampling points coming under Potable Water are SP3, SP4, SP5, SP6 (in RO unit) and Purified water are SP7, UP1, UP2, UP3 and UP4 (in Production area) and UP5 (Quality Control) are allotted one A. R. No.
5.5.2	During Seasonal Validation SP1 and SP2 are considered as Treated Raw Water points.
5.5.3	Seasonal Validation should be carried out in three seasons’ Winter (December to January), Summer (April to May) and Monsoon (July to August).
5.5.4	Samples should be drawn daily on fifteen consecutive working days for all points specified in Annexure of ‘Validation Sampling Plan’.
5.5.5	Carry out the analysis as per the Pharmacopoeia or In House Specification and maintain the records.
5.5.6	Prepare Seasonal Validation trend after completion in analysis as per define Annexure.

 

6. Definition / Abbreviations:

6.1 Definition:

 

6.2 Abbreviations:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
SP	Sampling point
UP	Users Point
No	Number
ml	millilitre
A.R. Number	Analytical reference Number
AWR	Analytical Work Report

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Cleaning of Glassware’s used in Quality Control Laboratory

1. Objective:

To lay down the procedure for Cleaning of Glassware’s used in Quality Control Department.

2. Scope:

This procedure is applicable for cleaning of unclean Glassware’s used for analysis in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Cleaning of Glassware’s used in Quality Control Department as per this SOP.
• Quality Assurance Department: To review and approve the SOP and Annexures.

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

 

Sr. No.	Procedure
5.1	Safety Precautions:
5.1.1	Always wear Personal Protective Equipments such as safety goggles, gloves, masks during washing of glassware’s.
5.1.2	Do not use brushes that are so worn that the spine hits the glass as a result serious scratches may result and scratched glass is more prone to break during analysis.
5.1.3	Inspect the glassware before each use and discard if scratched on inner surfaces, chipped, cracked or damaged in any way.
5.1.4	Do not drop glassware’s from height.
5.1.5	Do not bang glassware’s to sink or tap.
5.1.6	Rubber sink and counter mats can help reduce the chance of breakage and resultant injury.
5.1.7	Visually check glassware’s for any cracks before washing. Broken glassware’s may cause injury.
5.1.8	Protect cleaned glassware’s from dust by placing them in dust free cabinets and cover the glassware with stopper, foil, paraffin or by keeping in tilt position.
5.1.9	Do not collect or touch broken glass pieces with bare hands. It can cause injury. Send the broken glassware for destruction.
5.1.10	Do not shake glassware’s too much vigorously as it may get cracks by pressure.
5.1.11	Do not keep alkaline liquids in volumetric flasks or burettes for longer time as a result stoppers or stopcocks may get stick.
5.1.12	Ensure that the soap has been thoroughly removed from the glassware’s. If soap comes in contact with acid, a film of grease may be formed.
5.1.13	Never use strong alkaline products and hydrofluoric acid as cleaning agents. These materials dissolve glass, leading to damage and eventual breakage.
5.2	General Procedure:
5.2.1	Wear safety goggles, gloves, masks before starting the washing of glassware’s.
5.2.2	Wash the glassware’s as soon as possible after use, so that residue can be removed easily with general detergent (non ionic) solution.
5.2.3	Drain off any non hazardous contents present in flasks, beakers, test tubes etc. in the sink and hazardous contents in the waste containers and then rinse the glassware’s with tap water before transferring them into soap solution.
5.2.4	Drain off hazardous contents from the flask, beakers or any other glassware before giving it for washing.
5.2.5	Remove the markings of pen marker on glassware’s with the methanol/IPA.
5.2.6	Remove the silicon grease on glassware’s with Acetone or use fuming sulphuric acid for about 30 minutes and then rinse with purified water.
5.2.7	Gently scrub inner and outer portions of glassware’s with scrubber or nylon brushes. If thorough cleaning is not possible immediately, soak the glass wares in water and keep.
5.2.8	If adhesive material is not removed or dissolved in water then soak the glass wares in detergent solution (0.1% SLS) or any other soap solution till adhesive material is removed or dissolved.
5.2.9	Preparation of 0.1% SLS: – Dissolve 1gm of SLS in 1000ml water. (Quantity can be prepared as per requirement).
5.2.10	During washing all parts of glassware’s should be gently scrubbed with nylon brush.
5.2.11	Rinse the glassware’s with running tap water; allow the water to run into and over the glassware’s for short time until no foam of soap is produced on shaking. Shake and empty at least six times with tap water.
5.2.12	All the glassware’s should be finally rinsed with purified water twice and kept in tilted position to drain off water completely.
5.2.13	Dry the glass wares in the glassware drying oven at 60 °C ±5°C in tilt Position. Do not dry the glass wares more than the above mentioned temperature limit as it may alter calibration of the glassware’s.
5.2.14	New glassware’s should be soaked in 1% solution of hydrochloric acid or nitric acid for about 5-6 hours before washing as new glassware’s are slightly alkaline in reaction.
5.2.15	If glassware becomes unduly cloudy  or dirty or contains coagulated organic matter then glass wares should be given chromic acid treatment as follow:-

 

5.2.16	Chromic acid solution: Dissolving 84 gm of chromium trioxide in 700 ml water and add slowly, with stirring 400 ml of sulphuric acid. (While preparing solution use personal protective equipments such as goggles, gloves, a mask as chromic acid is classified as a carcinogen).  OR
5.2.17	Dissolving 200 gm of Sodium Dichromate in about 100 ml water, cooling in ice-bath and adding slowly to it, with stirring, 1500 ml of sulphuric acid.
5.2.18	Pour the few ml of chromic acid solution on dirty glassware’s and leave them for minimum 15 minutes.
5.2.19	Add small amount of potable water with shaking. Rinse several times with water or allow to keep in water for about one hour as the chromic acid is highly acidic in nature and finally rinse with purified water twice.
5.2.20	Dry the washed glassware’s in the glassware drying oven at 60 °C ±5°C in tilt Position.
5.2.21	Use the washed glassware within one week of the washing. After one week re-wash the same glassware’s before use even if they are not used.
5.2.22	Store the washed and dried glassware in a designated and clean cupboard with proper labelling.
5.3	For washing burettes, separating funnels:
5.3.1	Remove the stopcock or rubber tip and wash with water/soap solution. Be careful that the tips of the burettes, funnels should not hit the sink or the water tap.
5.3.2	Rinse it under running tap water until all the dirt is removed. Allow the water to run into and over the burettes, separating funnels for short time and then rinse them with purified water.
5.3.3	Shake and empty at least six times with tap Water and two times with purified water. Wash the stopcocks or rubber tips separately. Dry separating funnels and burettes in the glassware drying oven at 60 °C ±5°C.
5.4	For washing Pipettes:
5.4 1	Place the pipettes in the jar containing water or soap solution placing the tips downward immediately after use.
5.4 2	Rinse them with tap water before placing them in jar. Ensure that the water level in the jar is high enough to immerse the maximum portion of the pipettes.
5.4 3	Do not drop them into the jar. This may break the tips and render the pipettes useless for accurate measurements.
5.4 4	At the time of washing, rinse them under running tap water until all the dirt is removed. Allow the water to run into and over the pipettes for short time and then rinse them with purified water.
5.4 5	Shake and empty at least six times with tap Water and two times with purified water. Dry them in the glassware drying oven at 60 °C ±5°C.

 

 

5.5	Glassware Cleaning Validation:-
5.5.1	Design Glassware Cleaning Validation protocol before starting the study.
	Glassware Cleaning Validation for API/Product Residue:-
5.5.2	Choose an available “difficult to clean” API
5.5.3	A standard solution of the API shall be prepared as described in the testing method (Refer STP/GTP).
5.5.4	Select the glassware’s in the laboratory such a way that it will cover minimum and maximum capacity which is generally used for standard/sample preparation. For Example refer below Table:- Glassware Name Capacity (ml) Volumetric Flask 5ml, 10ml, 25ml, 50ml, 100ml, 250ml, 500ml. Conical Flask 50ml, 100ml, 250ml, 500ml. Volumetric Pipette 1ml, 2ml, 5ml, 10ml, 25ml, 50ml. Graduated pipette 1ml, 2ml, 5ml, 10ml, 25ml, 50ml. Test Tubes 5ml, 10ml, 20ml, 50ml, 100ml.
5.5.5	Take each type one glassware as mentioned above. (Note: – Actual glassware’s capacity may vary depend upon the availability glassware’s in the laboratory.)
5.5.6	Each of the selected volumetric flasks/conical flasks/test tubes shall be filled to about 10% of its nominal volume with the Standard solution, close and shake such a way that the inner walls of the flasks will be covered by the liquid. Then Glassware’s shall be emptied and allowed to dry.
5.5.7	Each of the selected pipettes shall be filled with its nominal volume with the Standard solution such a way that the inner walls of the pipettes will be covered by the liquid. Drain the liquid from pipette and allow to dry.
5.5.8	Gently scrub all parts of glassware’s with nylon brush under tap water.
5.5.9	Rinse the glassware’s with running tap water; allow the water to run into and over the glassware’s. Shake and empty the Glassware’s at least six times with tap water.
5.5.10	All the glassware’s should be finally rinsed with purified water twice and kept in tilted position to drain off water completely.
5.5.11	All the cleaned Glassware’s shall then filled and shake with the diluent solution used for the preparation of the Standard Solution.
5.5.12	Take the diluent solution from the Glassware’s and analyse as per testing method of the API/Product used.
5.5.13	Take the readings of standard solution and residual solution.
5.5.14	Calculate the residual amount of API for each cleaned Glassware’s by referring STP/GTP.
5.5.15	Acceptance Criteria:- Traces of the API should not be more than 0.1% of standard solution.
5.5.16	If above criteria is not meeting for any cleaned glassware then increase the rinsing time and perform Glassware cleaning validation again.
	Glassware Cleaning validation For Detergent/Soap Solution Residue:-
5.5.17	Soak the glass wares in detergent solution (0.1% SLS) or any other soap solution for about 30 minutes.
5.5.18	Preparation of 0.1% SLS: – Dissolve 1gm of SLS in 1000ml water. (Quantity can be prepared as per requirement).
5.5.19	Select the glassware’s in the laboratory such a way that it will cover minimum and maximum capacity which is generally used for standard/sample preparation. For Example refer below Table:- Glassware Name Capacity (ml) Volumetric Flask 5ml, 10ml, 25ml, 50ml, 100ml, 250ml, 500ml. Conical Flask 50ml, 100ml, 250ml, 500ml. Volumetric Pipette 1ml, 2ml, 5ml, 10ml, 25ml, 50ml. Graduated pipette 1ml, 2ml, 5ml, 10ml, 25ml, 50ml. Test Tubes 5ml, 10ml, 20ml, 50ml, 100ml.
5.5.20	Gently scrub all parts of glassware’s with nylon brush under tap water.
5.5.21	Rinse the glassware’s with running tap water; allow the water to run into and over the glassware’s for short time until no foam of soap is produced on shaking. Shake and empty at least six times with tap water.
5.5.22	All the glassware’s should be finally rinsed with purified water twice and kept in tilted position to drain off water completely.
5.5.23	All the cleaned Glassware’s shall then filled and shake with the water (diluent solution) used for the preparation of the 0.1% SLS.
5.5.24	Take the water (diluent solution) from the Glassware’s and analyse as per testing method
5.5.25	Take the readings of 0.1% SLS solution/Soap solution and residual solution.
5.5.26	Calculate the residual amount of SLS/Soap solution for each cleaned Glassware’s by referring STP/GTP.
5.5.27	Acceptance Criteria:- No traces of the SLS/Soap solution should be detected.
5.5.28	If above criteria is not meeting for any cleaned glassware then increase the rinsing time or use different detergent and perform Glassware cleaning validation again.
5.5.29	The Glassware Cleaning Validation protocol shall contain the following information; Glassware Cleaning Validation protocol cover page Protocol Pre-approval sheet Introduction Objective Scope Responsibilities Definition and Abbreviation Procedure Observed Deviation/OOS Attachments References Summary and Conclusion Protocol Post-Approval sheet

 

6. Definitions / Abbreviations:

• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
gm	gram
ml	Millilitre
±	Plus or minus
°C	Degree centigrade
%	Percentage
SLS	Sodium Lauryl Sulfate

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Supervision of Work in Quality Control Department

1. Objective:

To lay down the procedure for Supervision of Work in Quality Control Department.

 

2. Scope:

This procedure is applicable for Supervision of Working System as per Good Laboratory Practices

in Quality Control Department.

 

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Supervision of Work in Quality Control Department as per this SOP.
• Quality Assurance Department: To review and approve the SOP and Annexures.

 

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

 

5.1	General Check Points in Quality Control Department:
5.1.1	General Laboratory cleanliness, maintenance, safety and Good Laboratory practice.
5.1.2	Sampling procedure followed as per current SOP of Raw Materials and Packing materials.
5.1.3	Analysis and reporting of Raw materials, Packing Materials, In process, Finished Products and Stability Samples.
5.1.4	Calibration, Validation of instruments, equipments and its labelling.
5.1.5	Reporting and recording of all the activities.
5.2	Sampling Procedure and Status:
5.2.1	Checks for the containers /bags/drums/boxes are sampled were properly cleaned and free from any physical deformity.
5.2.2	Check the equipment used for sampling is same as specified in the current SOP for sampling.
5.2.3	Check the containers /bags/drums/boxes sampled are identified and sampled as per defined sampling plan in current SOP of sampling.
5.3	Labelling Procedure and Status:
5.3.1	Check whether the containers /bags/drums/boxes are labeled as Under Quarantine are identified as Under Test (Yellow), Approved (Green), Rejected (Red).
5.3.2	Check whether affixed sampled label for those containers, bags or drums, boxes from which sample is removed.
5.3.3	Ensure that the approved sticker contains the details: Name, Quantity, Batch No., Potency/Assay, A.R. No., LOD, and Analysed by, date of approval, retest date and initial of approved competent technical person.
5.4	Analysis Procedure and Supporting Data:
5.4.1	Check the sample taken for analysis is entered in respective inward registers.
5.4.2	Check the work sheets for the test performed are as specified in the official procedure or as per in-house specification.
5.4.3	Ensure that the reagents/ solutions were available or not, for the test carried out and check date of preparation of solutions and standardization wherever applicable.
5.4.4	Ensure that the equipment instrument used for analysis is calibrated and in working condition during testing.
5.4.5	Check whether the reagents, solutions and chemicals used are prepared according to the standard procedure and discarded after expiry.
5.4.6	Ensure that all reference samples are prepared from composite samples and are preserved under control temperature and humidity with proper record.
5.5	Stability Studies:
5.5.1	Check the scheduler of stability study meets the requirement as per standard operating procedure.
5.5.2	Check whether the samples charged as per current SOP of stability studies.
5.5.3	Check the format and data recorded during and after completion of the Stability testing.
5.6	Calibration, Validation of Equipments / Instruments:
5.6.1	Check whether all instruments/equipments are categorised with a calibration status label.
5.6.2	Check the validation/calibration is conducted as per current Standard operating procedure.
5.6.3	Check whether the facilities for conducting calibration and validation are certified and adequate.
5.6.4	Check whether the records of calibration and validation are periodically maintained.
5.7	Reporting and Records:
5.7.1	Check whether the reports are generated for the sample tested documented online.
5.7.2	Ensure that the report is complete in all respects and counter checked by the authorized person prior to release.
5.7.3	Ensure that the equipment logs, and other related log books are updated on day to day basis.
5.8	Laboratory Cleanliness, Maintenance and Safety:
5.8.1	Check whether the laboratory is cleaned as per schedule.
5.8.2	Check whether the floor, wall, lights and fans are cleaned and maintained properly.
5.8.3	Check whether there is adequate fire extinguisher and proper ventilation and exit to ensure safety of personal working in laboratory.
5.9	Microbiology/Microbiological Analysis:
5.9.1	Check whether water analysis is carried out daily as per current SOP of water analysis.
5.9.2	Check whether the reports are generated for the sample tested documented online.
5.9.3	Check whether the fumigation is carried out and consumption of chemicals is recorded.
5.9.4	Check whether environmental monitoring is carried out for department as per schedule and recorded.
5.9.5	Check whether seasonal validation is carried out for all sampling points as per plan and reports are generated.

 

6. Definitions / Abbreviations:

• Definitions :

 

• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
A. R. No.	Analytical Reference Number
LOD	Loss  on drying
Qty	Quantity
No.	Number
Mfg.	Manufacturing

 

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Calibration of Instruments and Equipment’s

1. Objective:

To define written procedure for Calibration of Instruments and Equipments in Quality Control

Department.

2. Scope:

This procedure is applicable for Calibration of Instruments and Equipments used for analysis in

Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Calibration of Instruments and Equipments in Quality Control Department as per this SOP.
• Quality Assurance Department: To review and approve the SOP and Annexures.

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

5.1	Principles of Calibration:
5.1.1	To ensure readings from instrument are consistent with other measurements.
5.1.2	To determine the accuracy and precision of the instrument readings.
5.1.3	To establish the reliability of the instrument that it can be trusted.
5.2	General Requirements:
5.2.1	List of all the Equipments/Instruments used in Quality Control Department should be available.
5.2.2	Reference Standards used for calibration should be stored in designated places to prevent contamination and/or deterioration.
5.2.3	The Reference Standards used for calibrations should be traceable to recognised National Standards.
5.2.4	All Reference Standards, Certified Reference Materials, or Reference Materials used for calibration shall be uniquely identified by allocating reference numbers as per SOP “Handling of Reference Standards”.
5.2.5	A certificate of traceability, if applicable, shall be retained to ensure traceability.
5.2.6	All Equipments/Instruments shall be maintained in good operating order and according to manufacturer or maintenance requirements.
5.2.7	Before starting the calibration, ensure that right standard used for calibration, check availability and validity of the required standards.
	Frequency of Calibration:
5.2.8	Calibration Schedule Frequency Allowed variation in days Monthly ± 3 working days Quarterly ± 7 working days Half Yearly ± 7 working days Yearly ± 15 working days (In-House) ± 30 working days (External Party)
5.2.9	All analytical Equipments/Instruments shall be calibrated on their due date of calibration.
5.2.10	All analytical Equipments/Instruments must be re-calibrated prior to use after any major repair, maintenance or service work have been carried out.
5.2.11	All critical Equipments/Instruments must be re-calibrated by the normal procedure if they are moved or if their location is changed. E.g. balance.
5.2.12	Upon the receipt of new Equipment/Instrument, Calibration shall be carried out after completion of qualification prior to use.
5.2.13	Instrument calibration frequency shall be decided based on manufacturer recommendation, criticality of instruments, possibility of variation in instrument internal setting etc. E.g. pH Meter/ Weighing Balance – Daily calibration, HPLC – Quarterly calibration etc.
5.3
5.3.1	Prepare the “Annual Calibration Schedule” as per SOP i.e. Equipment’s/Instruments Calibration, yearly according to the list of calibration to calibrate the equipments/instruments.
5.3.2	Supervisor shall prepare the “Monthly Calibration Schedule” at start of every month as per Annexure by referring “Annual Calibration Schedule”.
5.3.3	Supervisor or analyst shall allocate A. R. No. on the “Instrument/Equipment Calibration Register” and shall give requisition to QA department for calibration formats of instruments on the due date of calibration.
5.3.4	Analytical Reference number shall be given as “CAL/YY/XXX”. Where, ‘CAL’ stands for ‘Calibration’. ‘YY’ stands for ‘Last two digits of Current year’. ‘XXX’ stands for ‘Serial number of calibration in the current year i.e. 001, 002 and so on’.
5.3.5	Calibration format shall be a part of individual instrument/equipment SOP and shall include details of Instrument/Equipment, calibration parameters, observation, acceptance criteria, solution preparation procedure, weight prints, reference standards details etc.
5.3.6	On the day of calibration of instrument, the analyst shall affix the status label on the instrument as “Under Calibration”.
5.3.7	Calibration of instruments/equipments shall be carried out as per procedure defined for calibration in the respective instrument SOP.
5.3.8	Update the “Instrument/Equipment Usage Log Book” as per Annexure.
5.3.9	Affix the “Calibration Status Label” as per Annexure on the Instrument/Equipment calibrated.
5.3.10	Example: If the calibration frequency is 3 months for HPLC instrument, and if calibration is performed on 24/05/2023, then the next due date of calibration shall be 23/08/2023.
5.3.11	Record the calibration data on the calibration format/protocols of respective instruments and also update the monthly and yearly calibration schedule.
5.3.12	Supervisor/Reviewer shall verify all the data of calibration and submit to the QC Head for approval.
5.3.13	If the Instrument/Equipment does not qualifies the calibration criteria, then the analyst shall report to the supervisor or Head of the Department.
5.3.14	Supervisor shall initiate investigation as per SOP “Incident reporting and investigation” by filling incident form.
5.3.15	After completion of investigation, if the error observed as instrument error then affix “Out of Calibration” label on the instrument and intimate Engineering Department or service engineer to rectify the problem.
5.3.16	Recalibrate the Instrument/Equipment after problem is rectified.
5.3.17	If calibration fails because of analyst error then recalibrate the Instrument. Training shall be imparted to analyst and documented.
5.3.18	If calibration fails because of instrument error then impact shall be assessed on previous analysed samples by checking any aberrant results or out of trend results obtained.
5.3.19	If aberrant results observed then same samples shall be reanalysed as a part of investigation and results shall be documented.
5.3.20	During reanalysis, if results found out of specification then detailed investigation shall be done as per SOP “Out of Specification” to confirm OOS results.
5.3.21	If it is confirmed that results are out of specification limit then recall procedure shall be initiated for that batch as per SOP “Product Recall Procedure”.
5.3.22	Any calibration which has been done as a part of investigation or analyst validation shall not be considered as routine calibration.
5.4	Repair/Service Procedure:
5.4.1	Equipments/Instruments that has been subjected to overloading or mishandling gives suspect results or has been shown to be defective or out of calibration shall be taken out of service.
5.4.2	These Equipments/Instruments shall be clearly labelled as “Out Of Service – Do Not Use” to prevent use until repaired and shown by calibration or test performed correctly.
5.4.3	At the conclusion of the repair/service, a service report should be completed by the engineer indicating what work has been undertaken and what work may be required in the future.
5.4.4	All repair/service documentation shall be kept with the instrument history log in order to provide a concise history for each instrument.
5.4.5	The “Instrument/Equipment History Card” shall be updated for any equipment where parts have been changed or replaced during the repair or service.
5.4.6	If required individual instruments are then re-calibrated as per individual calibration procedures.
5.4.7	Details of this re-calibration shall be recorded on calibration logs of respective instrument/equipment.
5.5	Procedure for External calibration:
5.5 1	Based on the calibration schedule, Quality Control Head shall communicate the calibration due date to the external agency 30 days in advance.
5.5 2	Calibration from external agency should be done atleast once in a year or as per current SOP of the Equipments/Instruments.
5.5 3	Any additional repair/servicing will also be conducted as and when necessary by a suitable trained engineer of the related company.
5.5 4	If required necessary parts shall be replaced before calibration.
5.5 5	Flexibility of calibration is ± 30 days from due date for external agency.
5.5 6	Calibration reports from external/outside agencies should be properly checked for correctness, acceptance criteria and traceability certificates and stored in Quality Assurance Department.
5.5 7	When external calibrations are performed, service providers that demonstrate competence, measurement capability, and traceability shall be used.
5.5 8	Calibration certificates from these providers shall contain the measurement results, including a statement of compliance with an identified metrological specification.
5.5 9	On the basis of calibration reports from external agencies, If required supervisor shall prepare “External Calibration Report” as per Annexure .
5.5 10	QC Head shall verify and approve the reports and submit to the QA Department.

6. Definitions / Abbreviations:

• Definitions :
• Calibration: Calibration is the process of testing and adjusting an instrument or test system readout to establish a correlation between the instrument’s measurement of the substance being tested and the actual concentration of the substance. It is the process adjustment or standardization of the accuracy of a measuring instrument, usually by comparison with a certified reference or standard.
• Precision: Precisionis the degree to which repeated measurements under unchanged conditions show the same result.
• Accuracy: Accuracy is the degree of closeness of measurements of a quantity to its actual true value.
• Traceability: is the ability to verify the history, location, or application of an item by means of documented recorded identification.
• Certified Reference Materials: A reference material whose property values are certified by a technically valid procedure and accompanied by or traceable to a certificate or documentation issued by a certifying organization.
• Critical Laboratory Equipment: Analytical instrumentation and equipment affecting the accuracy or precision of a test method.
• Performance Verification: The confirmation of the reliability of a previously validated methods or equipment.

 

 

• Abbreviations :

Abbreviation	Expansion
QC	Quality Control
QA	Quality Assurance
QA	Quality Assurance
SOP	Standard Operating Procedure
A. R. No.	Analytical Reference Number
OOS	Out Of Specification
e.g.	Example
etc	Excreta
i.e.	That is

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Destruction of Laboratory Waste

1. Objective:

To lay down the procedure for Destruction of Laboratory Waste generated in Quality Control Department.

2. Scope:

This procedure is applicable for Destruction of left over samples of Raw materials, In process samples, Finished product, Packing materials, Paper waste, Metal waste, Electronic waste, Chemical waste, Plastic waste and Solvent waste.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Destruction of Laboratory Waste generated in Quality Control Department as per this SOP.
• Quality Assurance Department: To review and approve the SOP and Annexures.

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

 

5.1	Safety Precautions:
5.1.1	Always wear Personal Protective Equipments such as safety goggles, gloves, nose masks when carrying out destruction process.
5.1.2	Before making any slurry refers to MSDS for chemicals and solvents for its chemical compatibility.
5.1.3	Organic liquids that are immiscible with water must not be disposed to the sink.
5.1.4	Never handle broken glass wares with bare hands. Use cut resistant gloves for glassware destruction.
5.1.5	All the waste containers must be properly labelled and closed except when adding contents.
5.2	Destruction of leftover samples of analysis:
5.2.1	After completion of analysis of material or product, if results complies and all the reference data are submitted with necessary verification to concern person or department, Quality Control analyst should take permission from Department Head for destruction of leftover  samples and after granting approval, analyst shall destroy the leftover samples.
5.2.2	If sample is Raw Material in powder form, prepare a slurry and store in the container designated for ‘Leftover Sample Destruction’.
5.2.3	If sample is in solid dosage form packed in market pack, tear off the packing and prepare slurry and store in the container designated for ‘Leftover Sample Destruction’.
5.2.4	If sample is in liquid dosage form in packed form, tear off the packing by opening seal, pour the liquid in water to make it dilute and store in the container ‘Leftover Sample Destruction’.
5.2.5	Neutralise the slurry or liquid sample as per procedure mentioned under point no. 5.4 before sending it to ETP.
5.2.6	‘Leftover Sample Destruction’ container shall be Transfer to ETP Plant when it gets filled up to 80% of its total capacity or end of the day.
5.2.7	If sample is printed Packing Material then shred the sample in small pieces and transfer to the scrap yard.
5.2.8	If sample is containers and closers then cross mark the container by marker pen and damage or de-shape the sample and transfer to the scrap yard for disposal.
5.2.9	Enter all the details such as Name of sample, Batch number, A.R. No., Quantity destroyed and destroyed by in “Leftover Sample Destruction Register” Annexure.
5.2.10	Quality Control Head or Supervisor shall verify the destruction records on the register.
5.2.11	If sample is hazardous form, prepare a slurry and store in ‘Leftover Sample Destruction’ storage container and shall be sent to outside hazardous management party.
5.3	Destruction of chemicals/solvents:
5.3.1	The chemical waste generated during the analysis of samples shall be collected in containers which are clearly labeled as ‘SOLID WASTE’ or ‘LIQUID WASTE’.
5.3.2	These containers shall be emptied into the ‘Leftover Sample Destruction’ container by making slurry at the end of the day or if it gets filled up to 80% of its total capacity before the end of the day.
5.3.3	Highly concentrated acids e.g. Sulphuric, Nitric or Hydrochloric acid should be first diluted with water (adding the acid to the water) to a concentration below 10% , Neutralise it and then send it as hazardous waste for disposal. For example if 50 ml of concentrated Hydrochloric acid is there for disposal then add about 500 ml water to dilute it, Neutralize and transfer to ETP unit.
5.3.4	Expired solid chemicals shall be stored in separate container by making slurry with suitable diluents Neutralize and transfer to ETP unit.
5.3.5	Expired liquid chemicals, Reagent solutions, Volumetric solutions shall be disposed by making slurry with compatible diluents, Neutralize and transfer to ETP unit.
5.3.6	Empty chemical containers, solvent bottles, vials to be stored separately and send to scrap yard for disposal.
5.3.7	Empty chemical containers, solvent bottles, vials should be rinsed with water prior to disposal as the traces of previous solvent may cause harm.
5.4	Neutralization procedure for laboratory waste:
5.4.1	Do not pour concentrated acidic or alkaline solutions directly into drains. Neutralize the solutions before disposal.
5.4.2	If the acid or base is highly concentrated, it is prudent to first dilute it with cold water (adding the acid or base to the water) to a concentration below 10%. Add acid or base in to the water slowly with continues stirring to make it dilute about 10%. Note: Before dilution of any unknown chemical check for the pH to confirm that the solution is acidic or basic by using pH paper strips.
	a.     Neutralization Procedure for Acids and acidic waste:
5.4.3	Sodium hydrogen carbonate is often used for neutralization because even an excess addition does not make the solution too alkaline. Add it into an acidic solution with stirring until bubbling is ceased.
5.4.4	Make a saturated solution of Sodium Carbonate or Sodium Hydrogen Bicarbonate (soda ash) in a beaker or use an inorganic base diluted in water (1:10 ratio). Dilute acid at least 1:10 (1 part acid to 9 parts of water) by slowly pouring and stirring the acid into the water.
5.4.5	Slowly add sodium carbonate or other basic solution into diluted acid with stirring.
5.4.6	Monitor pH with pH indicator strips or pH meter or other pH test method. Ensure pH is between 6 and 9.
5.4.7	Before sending it to ETP, stir the mixture and do a final check of the pH, to confirm proper neutralization.
5.4.8	After confirmation of neutralisation i.e. pH between 6 and 9, send the slurry container to ETP.
5.4.9	Below bases also can be used for neutralization of acids. Example: Ammonium Hydroxide, Calcium Carbonate, Calcium Oxide,  Magnesium carbonate, Potassium Hydroxide, Sodium Bicarbonate, Sodium Hydroxide.
	b.      Neutralization procedure for Bases and Basic waste:
5.4.10	Dilute alkali wastes at least 1:10 (1 part alkali to 9 parts water) by slowly pouring and stirring the base into the water.
5.4.11	Neutralize the diluted alkali solution with a previously diluted inorganic acid like Hydrochloric acid.
5.4.12	Slowly add Dilute hydrochloric acid or other acidic solution into diluted Base with stirring.
5.4.13	Monitor pH with pH indicator strips or pH meter or other pH test method. Ensure pH is between 6 and 9.
5.4.14	Before sending it to ETP, stir the mixture and do a final check of the pH, to confirm proper neutralization.
5.4.15	After confirmation of neutralisation i.e. pH between 6 and 9, send the slurry container to ETP. Into
5.4.16	Below acids also can be used for neutralization of bases. Example: Sulphuric Acid, Boric Acid, Nitric Acid, Acid Aqua Reginal HCL/HNO3 Nitrohydrochloric Acid (3: mixture), Orthophosphoric Acid.
	c.      Neutralisation/ De-activation procedure for Organic Chemical waste:
5.4.17	Organic chemicals (Thiols, Sulfides etc.) can be destroyed by oxidation with sodium hypochlorite.
5.4.18	Use 1:4 ratio of sodium hypochlorite (Approx 5.25%) to organic chemicals or slurry. For example: For 4 litter of organic chemical or slurry use 1 litter Sodium  hypochlorite for neutralisation/ deactivation.
	Note: Calcium hypochlorite may be used as an alternative to sodium hypochlorite.
5.4.19	Stir the mixture, allow it to stand for overnight( at least 8 hours) and sent it next day to ETP for disposal.
	Note: Because sodium hypochlorite solutions deteriorate on storage, it is advisable to have relatively fresh material available. A 5.25% solution of sodium hypochlorite has 25 g of active chlorine per liter. If determination of the active hypochlorite content is justified, it can be accomplished as follows. Ten millilitres of the sodium hypochlorite solution is diluted to 100.0 mL, and then 10.0 mL of this diluted reagent is added to a solution of 1 g of potassium iodide and 12.5 mL of 2 M acetic acid in 50 mL of distilled water. Using a starch solution as indicator, titrate the solution with 0.1 N sodium thiosulfate. One millilitre of titrant corresponds to 3.5 mg of active chlorine. A 5.25% solution of sodium hypochlorite requires approximately 7 ml of titrant.
5.4.20	Refer MSDS before neutralisation/ deactivation of any chemical for any special precaution or any adverse reaction.
5.4.21	Any waste material that require disposal shall be handled in conformance with the respective state or central legislation i.e. Waste Management Act, Water (Prevention and Control of Pollution) Act, Air (Prevention and Control of Pollution) Act, Bio-Medical Wastes (Management and Handling) Rules etc and other application legislation.
5.5	Destruction of broken glassware’s :
5.5 1	Broken glassware’s should be treated as potentially sharp & pointed and a physical hazard which can cause deep cuts on body if not handled properly.
5.5 2	If broken glassware’s is clean, sweep up the pieces with broom or small brush and dust pan.
5.5 3	Transfer broken glassware’s in the designated glass disposal container, e.g. puncture proof, double lined cardboard box. Do not allow the box to be full. It should be closed properly when it is 3/4th full and transfer the container directly to the scrap yard for disposal.
5.5 4	Ensure that discarded glassware’s must not contain any hazardous waste for which it must be cleaned and thoroughly rinsed with water before disposal. Ensure that the contents in the glassware have been completely emptied or drained off in the waste container.
5.5 5	If the glassware holds any chemicals when broken, flush the broken pieces of glassware’s with large quantities of water and then transfer in the designated glass disposal container.
5.5 6	Label the container as “BROKEN GLASSWARE” in bold and paste it in such a way that it is readily visible to laboratory personnel.
5.5 7	After closing the box with tape, transfer the container directly to the scrap yard for disposal.
5.6	Destruction of routine waste:
5.6 1	Collect metal waste separately and send it to the scrap yard for disposal.
5.6 2	Collect electronic waste separately and send it to the scrap yard for disposal.
5.6 3	Collect plastic waste separately and send it to the scrap yard for disposal.
5.6 4	Collect paper waste separately in a dust bin and send it to the scrap yard for disposal.

 

6. Definitions / Abbreviations :

• Definitions :
• Slurry: A thin free flowing paste of any leftover sample prepared with water or any suitable diluent.
• Disposal: The term refers to the act or process of destroying chemicals, chemical waste, containers, and other materials.
• Hazardous waste: Waste that is unwanted, unusable and dangerous or potentially harmful to our health or the environment.
• Harm: Damage to health or environment including the damage that can occur from loss of product quality or availability.

 

 

• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
MSDS	Material Safety Data Sheet
A. R. No.	Analytical Reference Number
No.	Number
e.g.	Example
ml	Millilitre

 

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Sampling, Handling and Analysis of Stability Study Samples

1. Objective:

To lay down the procedure for Sampling, Handling and Analysis of Stability Study Samples.

2. Scope:

This procedure is applicable for Sampling , Handling and Analysis of Stability Study Samples.

3. Responsibility:
   • Quality Control Department: To prepare and review the SOP. To follow the procedure for Sampling and Handling of Stability Study Samples as per this SOP.
   • Quality Assurance Department: To review and approve the SOP and Annexure.
4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

5.1	Sampling and Handling of Samples:
5.1.1	Stability Sample study shall be carried out for first three consecutive batches of Finished Product of every new product.
5.1.2	Quality Assurance Associate shall collect the Finished Product sample for stability study analysis as per approved stability study protocol.
5.1.3	Finished Product should be sampled for Stability Study in a intact pack size.
5.1.4	The real time study shall be carried out for 3 months, 6 months, 9 months, 12 months, 18, months, 24, months and 36 months or as per stability study protocol at  30°C ± 2°C / 65% RH ± 5% RH.
5.1.5	The Accelerated studies shall be carried out for 3 months and 6 months at 40°C ± 2°C / 75% RH ± 5% RH.
5.1.6	Sample quantity should be calculated as per stability period and type of analysis requirement.
5.1.7	For example: For complete physico-chemical single analysis, number of Tablets /Capsules required is 40 and for microbial analysis 40 then total number of units to be sampled for single analysis is 80.
5.1.8	If stability to be performed for 36 month for Real time and 3 and  6 month for Accelerated, total of analysis will be 7+2= 9 and quantity of sample to be withdrawn for Stability Study will be  9 x 80 units =720 nos.
5.1.9	If packing style is not 10 tablets/Capsules per strip, then sample quantity may be slightly more than as above; but any stage it cannot be less than required quantity.
5.1.10	Label the Stability samples as per define Annexure.
5.1.11	Incubate Stability Study Samples to respective stability chambers as per stability protocol and fill up the respective Stability sample Entry Register.
5.1.12	After incubation of stability sample, prepare stability scheduler for respective batches as per define Annexure.
5.1.13	Real time Stability Study Samples details are entered in ‘Finished Product Real Time Stability Sample Entry Register’.
5.1.14	Accelerated Stability Study Samples details are entered in ‘Finished Product Accelerated Stability Sample Entry Register’.
5.1.15	Supervisor shall prepare the “Stability Sample Monthly pull out log” at initial of the respective month, according to the “stability scheduler”.
5.1.16	The Samples shall be withdrawn from the respective chambers at stated interval within + 5 working days of the due day. If the stability period is shorter than 3 months then withdrawn should be completed within + 2 working days from the due date.
5.1.17	As per the stability scheduler, samples shall be pull out at regular intervals and withdrawn quantities shall entered in respective registers.
5.1.18	The samples shall be stored at specified condition until the completion of analysis.
5.1.19	On receipt of sample, Analyst should give requisition for “Analytical Work Report” to the quality assurance department.
5.1.20	Assign Analytical Reference Number (A. R. No.) as “SS/XX/NNN” Where, ‘SS’ stands for ‘Stability Study’ ‘XX’ stands for ‘Last two digits of the current year’. ‘NNN’ stands for ‘Serial number i.e. 001, 002 and so on’.
5.1.21	Analyst should fill in the necessary details on the Analytical work report according to ‘Stability Sample Inward Register’.
5.1.22	Stability Samples shall be tested as per respective specification. Analyst shall refer standard testing procedure and analyse the sample accordingly.
5.1.23	The testing of the stability samples should be completed within 30 days from the due date. If the stability period is shorter than 3 months then testing should be completed within 15 days from the due date. If for some reason, it is not possible to analyse the sample within specified testing window then deviation shall be raised with proper justification and impact shall be assessed.
5.1.24	After the analysis, analyst should hand over the Analytical Work Report to Supervisor/Reviewer for data checking.
5.1.25	If Supervisor/Reviewer observed any discrepancy with analysis or analytical data, he / she should consult to Head of the Department for investigation.
5.1.26	If all the relevant data on Analytical work report complies as per Pharmacopoeia or IHS requirement or both, Supervisor/Analyst should prepare “Stability Summary Report” as per define Annexure.
5.1.27	Quality Control Head shall verify Stability Summary Report.
5.1.28	After verification of Stability Summary Report, Supervisor/QC Head shall hand over the Stability Summary Report to Quality Assurance Department for approval.
5.1.29	Leftover samples should be destroyed as per SOP “Destruction of Laboratory Waste”.
5.1.30	During analysis if analyst observes the results out of specification (OOS) or out of limits, he / she should report to the Supervisor or Head of the Department.
5.1.31	Supervisor shall initiate investigation as per SOP “Out of Specification” by filling OOS form.
5.1.32	After completion of investigation, categorise the observation as analyst error, reagent error, instrument error or material defect.
5.1.33	Based on detailed investigation and type of error decision shall be taken for further course of action or recall of the product.
5.1.34	Update the Stability Sample Inward Register after completion.
5.1.35	If long-term studies are conducted at 25°C ±2°C/60% RH ±5% RH and “significant change” occurs at any time during 6 months testing at the accelerated storage condition, additional testing at the intermediate storage condition should be conducted. In general, “significant change” for a drug product is defined as: –       A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures. –       Any degradation product’s exceeding its acceptance criterion. –         Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, re-suspendability, caking, hardness, dose delivery per actuation); however, some changes in physical attributes (e.g. melting of creams) may be expected under accelerated conditions; and, as appropriate for the dosage form. –       Failure to meet the acceptance criterion for pH. –        Failure to meet the acceptance criteria for dissolution testing at 12 dosage unit.
5.1.36	Incubation shall be maintained at ± 2° C of the Specified temperature and ± 5% of the Specified Relative Humidity. Any deviation as mentioned below must be assessed for impact and reported to the Head of QA Department. Deviation of > ±2° C to ± 5°C from the set point for 48Hours. Deviation of > ±5% RH to ± 10% from the set point for 48Hours. Deviation of > ±5° C from the set point for 24Hours. Deviation of > ± 10% RH from the set point for 24Hours.

 

6. Definitions / Abbreviations :

• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
°C	Degree Centigrade
RH	Relative Humidity
Nos.	numbers
±	Plus or minus
%	Percentage

  

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Sampling, Analysis and Release or Rejection of Packing Materials

  

1. Objective:

To lay down the procedure for Sampling, Analysis and Release or Rejection of Packing Materials.

2. Scope:

This procedure is applicable for Sampling, Analysis and Release or Rejection of Packing Materials in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Sampling, Analysis and Release or Rejection of Packing Materials in Quality Control Department as per this SOP.

• Quality Assurance Department: To review and approve the SOP and Annexures.
• Warehouse Department: To intimate Quality Control Department for Sampling of Packing Materials.

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

5.1	Precautions of Sampling Containers:
5.1.1	Use clean self sealing polyethylene bags for primary and secondary packing materials.
5.1.2	Sampling analyst should wear safety nose mask, gloves at the time of sampling.
5.1.3	Sample only one container/roll/box at a time in a packing material sampling area.
5.2	Receipt and Planning of sampling:
5.2.1	Verify documents like GRN, party COA, supplier challan or invoice from warehouse.
5.2.2	If the documents are correlated to each other; the sampling analyst or supervisor shall enter all details in “Packing Material Inward Register” as per Annexure and assign the Analytical Reference Number and plan for sampling.
5.2.3	Assign Analytical Reference Number (A. R. No.) as “PM/YY/NNN” Where, ‘PM’ stands for ‘Packing Material’ ‘YY’ stands for ‘Last two digits of the current year’ ‘NNN’ stands for ‘Serial number’ i.e. 001, 002 and so on.
5.2.4	If the receipt documents and consignment miss match to each other then sampling analyst should report to Supervisor, Executive or Quality Control Head. If needed necessary correction shall be done on the document from Warehouse person after consultation with Quality Control Head.
5.2.5	Sampling analyst should accompany necessary sampling aids like –Sampling polybags, tie rope, gloves, nose masks, pen marker etc. and accessories like –cutter, scissor knife, tape etc.
5.2.6	Arrange the rolls/containers as per lot /batch number and fill required information in the “Packing Material Sampling and Visual Inspection Report” as per define Annexure.
5.3	Visual Inspection Procedure:
5.3.1	Select the batch or lot size of the consignment received as per Table no. 01– ‘Packing Material Visual Inspection Plan’.
5.3.2	Check the sample size code letter from the ‘general inspection level’ column for the same batch or lot size in Table no. 01.
5.3.3	Check the number of containers/rolls/boxes to be inspected from the ‘sample size’ column in Table no. 01.
5.3.4	Example: If one consignment is received with batch size of 400 rolls, then as per Table no.01, the sample size code letter is ‘H’ and number of rolls to be inspected is 50.

 

5.3.5	During inspection if any defects found then categorize the defects as critical, major and minor as mentioned in Table No. 02 – ‘Class of Defects’.
5.3.6	Defects categories are divided based on criticality to product quality and each defect class is assigned with different AQL level.
5.3.7	Refer Table No. 01 for acceptance or rejection of Packing Materials having defects.
5.3.8	Example: If one consignment is received with batch size of 1000 cartons, then as per Table no.01, the sample size code letter is ‘J’ and number of cartons to be visually inspected is 80. During inspection if some cartons are found with shade variation defect then categorise the defect as per Table No. 02. AQL limit for shade variation is 4.0%. According to the sample size, if 6 or more than 6 cartons are found with shade variation defect then the consignment should be rejected. If 5 or less than 5 cartons are found with shade variation defect then the consignment should be accepted (Refer Table No. 01).

 

Table No. 02                                                   Class of Defects
Defect Class	Description	AQL
Critical	Artwork Code number, damaged rolls, Contamination of glass bottles/vials with insects.	0.010%
Major	pin holes, Ink spreading on cartons, Printed matter not clear	0.65%
Minor	Shade variation, Winding of rolls, grease on the bottle, double code on the label, Uneven outer surface or wavy appearance of glass bottles/vials, dust or any foreign matter.	4.0%

 

Table No. 03                          Sample Quantity for Analysis and Control Sample
Sr. No.	Name of the Packing material	Sample quantity		Total Sample quantity
		For Analysis	Control Sample
1.	PVC	1 meter	1 meter	2 meter
2.	PVDC	1 meter	1 meter	2 meter
3.	Printed Foil	1 meter	1 meter	2 meter
4.	Printed Aluminium tubes	05	01	06
5.	Vials/Bottles	05	01	06
6.	Printed cartons	05	NA	05
7.	Labels/Stickers	05	NA	05
8.	Inserts/Leaflets	01	NA	01
9.	Silica pouch	01	NA	01
10.	Shippers/Corrugated boxes	01	NA	01
11.	Polybags/ Printed bags	01	NA	01
12.	HDPE/ Plastic Containers	01	NA	01

 

5.4	Sampling of Primary Packing Materials:
5.4.1	Check the cleaning of Primary Packing Sampling room for dust. The Primary Packing Sampling room shall be cleaned with wet mop followed by dry mop.
5.4.2	During sampling use the clean accessories and cover the material with fresh polythene.
5.4.3	Material shall not be contaminated, because it will come into direct contact with product and can affect the product quality.
5.4.4	Check the full consignment as per GRN for batch or lot number, quantity, and any external damages at quarantine area. After successful verification and numbering of the containers, boxes to be moved inside the primary packing room one at a time.
5.4.5	Refer Table No. 03 for individual sample quantity for analysis and control samples.
5.4.6	Take samples for visual inspection as per sample size mentioned in the Table no. 01.
5.4.7	Make pool sample by mixing all samples which are collected for visual inspection and randomly pull out samples for analysis as per Table No. 03.
5.4.8	Example 1: If one consignment is received with batch size of 03 boxes of PVC rolls, then as per Table no.01, the sample size code letter is ‘A’ and number of rolls to be visually inspected and sampled is 02.
5.4.9	Example 2: If one consignment is received with batch size of 200 PVC rolls, then as per Table no.01, the sample size code letter is ‘G’ and number of rolls to be visually inspected is 32. From these number of rolls to be sampled for analysis is 02 as per Table No. 03.
5.4.10	Primary Packing Materials like PVC, PVDC, Aluminium plain foil and printed foil should be checked for shade, winding of the role should be uniform and without any folds within the layers, pin holes if any.
5.4.11	If any discrepancy observed then immediately bring it to the notice of the supervisor.
5.4.12	If no defects are found then draw the sample after discarding initial 2-3 meters. Initial 2-3 meters sample should be shredded or cut into 10 to 15 pieces and shall be sent to scrap yard for disposal.
5.4.13	After Sampling completion, affix “UNDER TEST” (yellow colour) label on all containers.
5.4.14	After sampling of packing material, clean primary packing room and Analyst should fill details on “Usage and Cleaning Log of Primary Packing Room” Annexure. Keep the sample for analysis in a designated place in Quality Control Laboratory with proper labeling.
5.4.15	Analyst should refer Standard Testing Procedure to ensure that all required reagents, chemicals, accessories, equipment or instruments are standardised or validated and available in the laboratory.
5.4.16	Analyst should fill in the necessary details on the Analytical Work Report according to “Packing Material Inward Register” and start the analysis as per standard testing procedure and specification.
5.4.17	Ensure that all the instruments are calibrated before use.
5.4.18	Analyst should refer to the SOP of instrument before operation and update the instrument operation logs immediately after use.
5.4.19	After the analysis, analyst should hand over the Analytical Work Report to Supervisor/Reviewer analyst for data checking.
5.4.20	If Supervisor/Reviewer observed any discrepancy with analysis or analytical data, he / she should consult to Head of the Department for investigation.
5.4.21	If all the relevant data on Analytical Work Report complies as per pharmacopoeia or IHS requirement or both, Supervisor/Analyst should prepare “Certificate Of Analysis” as per  SOP “Preparation of Certificate Of Analysis”.
5.4.22	Full report shall contain AWR, Manufacturer COA, Sampling Inspection Report, GRN copy and COA prepared
5.4.23	Quality Control Head shall approve the COA and release the consignment..
5.4.24	After approval of COA, analyst should prepare “APPROVED” labels (green colour) as per Annexure No.  06 with approved by signature on it and affix on all containers in such a way that the under test word on the label should be covered but the details on the under test label should be seen.
5.4.25	Assign Retest Date on the approved label as per SOP “Retesting of Raw Materials and Packing Materials”.
5.4.26	Photocopy of the approved COA shall be provided to the Warehouse Department if required.
5.4.27	Leftover samples should be destroyed as per SOP “Destruction of Laboratory waste”.
5.4.28	During analysis if analyst observes the results out of specification or out of limits, he / she should report to the Supervisor or Head of the Department.
5.4.29	Supervisor shall initiate investigation as per SOP “Out of Specification” by filling OOS form.
5.4.30	After completion of investigation, categorise the observation as analyst error, reagent error, instrument error or material defect.
5.4.31	If error observed after investigation due to analyst error, sampling error or reagent/instrument error is confirmed and no defect in the material then the consignment or lot can be released after preparing COA and affixing approved labels on the consignment.
5.4.32	If material has minor defect that cannot affect the product quality and not covered in any pharmacopoeia or specification such as dimension of cartons, width of foil is slightly extra; weight of container, Grammage, shade variation then material can be used by filling deviation and approval of Quality Assurance Department and alert notice shall be issued to Supplier or Manufacturer.
5.4.33	If material has major defect that can affect the product quality or out of respective Pharmacopoeial requirement for example printed matter of cartons or foils, dimension of foil is less, then material should be considered as Major defect and is rejected.

 

5.4.34	After detail investigation prepare a COA for rejected material with a remark as “Material does not complies with the prescribed standards’’ and affix the label on the material as “REJECTED” (Red colour) with rejected by signature and the reason for rejection as per Annexure No.  07.
5.4.35	Photocopy of Rejected COA shall be provided to warehouse. Photocopy is not necessary if software (ERP) is used for material inventory or control.
5.4.36	Reference samples of rejected Packing Materials shall be destroyed as per SOP “Destruction of Laboratory waste”.
5.4.37	Rejected Packing Material consignment shall be send back to the manufacturer/supplier for further disposal.

 

6. Definitions /Abbreviations:

•  Definitions :
  • Sampling: Sampling is a process of collecting a small portion of material from a bulk of material received in the form of consignment or batch having one or more containers/rolls/boxes.  The sample collected should represent the whole consignment or   batch and should be sufficient to carry out all the testing including reference sample.
  • Consignment: The quantity of a bulk material made by one manufacturer or supplied by an agent at one time in response to a particular request or order. A consignment may comprise of one or more containers/rolls/boxes.
  • Primary Packing Materials: Materials which comes in direct contact with the drug product. Eg. PVC, Foils.
  • Secondary Packing Materials: Materials which comes in direct contact with primary packing materials. Eg. Cartons, leaflets.
  • Tertiary Packing Materials: Materials which comes in direct contact with secondary packing materials. Eg. Corrugated boxes.
  • Critical defects: A defect that can compromise product safety, purity or identity that may be harmful to the consumer.
  • Major defects: A defect that jeopardizes the integrity or function of the package.
  • Minor defects: A defect that does not affect product safety, purity or identity or package integrity of function.

  

• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
√n+1	Under route of n = numbers of containers, bags, drums
COA	Certificate of Analysis
GRN	Goods Received Note
A. R. No	Analytical Reference Number
IMS	Inventory Material system
IHS	Inhouse Specification
OOS	Out Of Specification
ERP	Enterprise Resource Procedures
PVC	Poly Vinyl Chloride
PVDC	Poly Vinyl Dichloride
HDPE	High Density Poly Ethylene

 

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Sampling, Analysis and Release or Rejection of Raw Materials

1. Objective:

To lay down the procedure for Sampling, Analysis and Release or Rejection of Raw Materials.

2. Scope:

This procedure is applicable for Sampling, Analysis and Release or Rejection of Raw Materials in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Sampling, Analysis and Release or Rejection of Raw Materials in Quality Control Department as per this SOP.
• Quality Assurance Department: To review and approve the SOP and Annexures.
• Warehouse Department: To intimate Quality Control Department for Sampling of Raw Materials.

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

 

Sr. No.	Procedure
5.1	Sampling Containers:
5.1.1	Use clean self sealing polyethylene bags for solid raw materials.
5.1.2	Use black polyethylene bags for all light sensitive raw materials.
5.1.3	For liquid materials use clean and dry transparent air tight glass bottles.
5.1.4	For microbiology samples use sterile polyethylene bags.
5.2	Sampling Devices:
5.2.1	For solid raw materials received in big containers/drums/bags use clean and dry stainless steel sampling rods.
5.2.2	For solid raw materials received in small containers /bags use clean and dry stainless steel spatulas.
5.2.3	For liquid samples use clean and dry liquid sampler.
5.2.4	For microbiology samples use clean and dry stainless steel spatulas mopped with 70% IPA.
5.3	Safety Precautions:
5.3.1	Wear Personal Protective Equipments such as nose mask, hand gloves and safety goggles at the time of sampling.
5.3.2	Do not enter the sampling booth when UV light is “ON”.
5.3.3	Sample only one container at a time in a sampling booth.
5.3.4	Do not expose hygroscopic materials for longer time in air as it will absorb the moisture. Cover the samples with double polybag.
5.3.5	Do not expose light sensitive materials for longer time to light as it will degrade the sample. Cover the samples with black polybag.
5.4	Sampling Procedure:
5.4.1	After receiving GRN from Warehouse Department, verify all the documents like GRN, party COA, supplier challan or invoice.
5.4.2	If the documents are correlated to each other, the sampling analyst or supervisor shall enter all details in “Raw Material Inward Register” as per Annexure No. 01 and assign the Analytical Reference Number and plan for sampling.
5.4.3	Assign Analytical Reference Number (A. R. No.) as “ARYYNNNN” Where, ‘AR’ stands for ‘Analytical Raw Material’ ‘YY’ stands for ‘Last two digits of the current year’. ‘NNNN’ stands for ‘Serial number i.e. 0001, 0002 and so on’.
5.4.4	Accompany necessary sampling aids like -poly bags, tie rope or seal, gloves, nose masks, pen marker etc. and accessories like -sampling rod, spatula, spoon, knife, etc  as per the nature of sample and pack size.
5.4.5	Enter the sampling booth through main entry with proper gowning and accessories with safety hand gloves and nose mask.
5.4.6	Operate sampling booth, as per sampling booth SOP.
5.4.7	Ensure the cleaning of area and equipment’s are satisfactory and then switch “ON” the RLAF and UV light of pass box and RLAF.
5.4.8	Run the UV light for minimum 30 minutes.
5.4.9	After 30 minutes switch off the UV light of RLAF and check the differential pressure of RLAF on magnehelic gauze is between 10 mm – 20 mm as well as environment condition, temperature should be NMT 25°C and humidity should be between 45 % RH to 55 % RH.
5.4.10	Verify each container/bag/drum with the documents and its label as per manufacturer COA and also check packing integrity at quarantine area.
5.4.11	Arrange the container/bag/drum as per lot /batch number and fill required information in the “Raw Material Sampling and Visual Inspection Report” as per Annexure No. 02.
5.4.12	If there is any discrepancy with container/bag/drum label and document, then analyst shall report the same to supervisor or quality control head.
5.4.13	After successful verification, move the container/bag/drum inside the sampling booth through pass box one at a time.
5.4.14	If the material is having microbiological test then use sterile sampling bags, sterile gloves and sampling devices mopped with 70% IPA for sampling of both microbiological and chemical analysis sample to avoid contamination in the material.
5.4.15	The person drawing the sample shall ensure that he stands on either side of the container, thereby preventing obstruction of the airflow current to the container being sampled.
5.4.16	All material shall be taken in to sampling booth through material entry door only by SS trolley and ensure that the door is closed after the entry of container.
5.4.17	Bring the container under RLAF and open the container.
5.4.18	Draw the sample as per sampling plan for respective raw materials.
5.4.19	For Active materials: – Perform 100% sampling as per the specifications of the raw materials.
5.4.20	For Inactive materials: – Up to 03 containers, bags or drums, perform 100% sampling and for consignments with 04 to 100 or more containers ,bags or drums, perform sampling by √n+1 method where ‘n’ is the number of containers/bags/drums received.
5.4.21	For sample quantity refer the respective raw material specifications.
5.4.22	For Identification, store sufficient sample quantity (approximately about 0.5 gm) in separate poly bag with proper labelling and numbering as per container/bag/drum for active materials.
5.4.23	For Control/Reference samples, store twice the quantity of analytical sample in separate poly bags with proper labelling as per  SOP “Storage of Reference /Control Samples”.
5.4.24	Ensure the cleaning of sampling booth and accessories are satisfactory and weighing balance is calibrated before sampling.
5.4.25	For operation of balance refer to the SOP displayed near the balance.
5.4.26	Tare the balance to zero by keeping sampling polybags on it.
5.4.27	Open the container/bag/drum with the help of knife or cutter. Open the knot of the polybag inside and insert the sampling rod, hold the sampling rod in cavity close position while` inserting into the material.
5.4.28	When rod reach inside of the material up to ¾ portions, move the inner rod so that cavity will open and powder enter into the cavity; again move it to close the cavity.
5.4.29	Remove the rod from the material and collect the required sample quantity. Sample quantity shall be at least twice the analysis quantity or as per mentioned in respective specification.
5.4.30	For less sample quantity of material use spatula for sampling.
5.4.31	Insert spatula into the material preferably middle position of container/bag/drum and take out the sample as per the respective raw material specification.
5.4.32	Light Sensitive material should be sampled under subdue light
5.5	Example of 100% Sampling:
5.5.1	If the consignment of Paracetamol contains 80 containers, then sample should be drawn from all 80 containers. Total sample quantity required (Reference sample + Analysis + Residual sample) is 80.0 gm and 0.5 gm from each container for individual identification test. Sample Quantity to be drawn from each container = 80÷80 = 1.0 gm + 0.5 g separately for individual identification test. Therefore total sample quantity becomes 80 + (0.5 x 80 = 40) = 120 gm.
	Example of √n+1 method Sampling:
5.5.2	If the consignment of Magnesium Stearate contains 100 containers, then by applying √n+1 method, where n = 100, the number of containers to be sampled is 11. Total sample quantity required (Reference sample + Analysis + Residual sample) is 150.0gm. Sample Quantity to be drawn from each container = 150÷11 = 13.64 gm.
5.5.3	Transfer the sample into the sampling polybag tarred before. Weigh the sample polybag on the balance.
5.5.4	Put the container/bag/drum number on the sample polybag and deface the manufacturer’s approved label on the container/bag/drum by making cross mark with black marker and affix “UNDER TEST” (yellow colour) label as per Annexure No. 04 on the container with a stamp “SAMPLED” for those container/bag/drum from which the sample is removed along with container number on each “UNDER TEST” label.
5.5.5	Reseal the polybag in the container/bag/drum with nylon thread and tightly close the container/bag/drum sampled.
5.5.6	Move all the container/bag/drum of the consignment to the under test area. Affix the “UNDER TEST” label on all the containers/bags/drums.
5.5.7	Follow the procedure for the sampling of all the container/bag/drums of one consignment/batch.
5.5.8	Mix all sample and prepare a composite sample which is sufficient for analysis and reference sample in sampling booth.
	Note: Prepare composite sample in such a manner so that it represents the quality of whole consignment or batch.
5.5.9	If Microbiology testing is required then divide the sample quantity in three polybags i.e. Microbiology Sample, Control Sample and Chemical Analysis Sample as per respective Raw Material Specification.
5.5.10	Visually take note of physical appearance of material while drawing the sample.
5.5.11	Keep the analysis sample with “Raw material sample for analysis’ label as per Annexure No. 03 in a designated place in Quality Control Laboratory.
5.5.12	Hand Over the Control/Reference samples to Quality Assurance Department for storage.
5.5.13	Fill up the log entries and affix “To be cleaned” label on sampling accessories as well as on sampling booth.
5.5.14	For cleaning of sampling booth refer to the SOP No. QC/003 “Operation and Cleaning of Sampling Booth”.
5.6	Cleaning of Sampling Devices:
5.6 1	Transfer all used sampling devices to washing area from the Sampling Booth after sampling.
5.6 2	Laboratory technician must wear the personal protective equipments such as hand gloves, masks for cleaning of sampling devices like spatula and sampling rod.
5.6 3	During washing of the sampling devices, if any residue is visually seen then scrub with nylon brush and rinse with potable water and transfer them in 0.5 % soap solution for 5 minutes and wash thoroughly with potable water  and finally with purified water.
5.6 4	Finally wipe the sampling devices with lint free cloth moistened with 70 % IPA and dry in the oven at 100°C to 105°C for about one hour. Allow to cool, wrap the sampling devices in clean polyethylene bag and affix the “CLEANED” status label with date and signature.
5.6 5	Transfer the sampling devices in sampling tool box or in designated place.
5.6 6	Record the Usage and Cleaning activity in “Usage and Cleaning Record.
5.7	Analysis, Release or Rejection of Raw Materials:
5.7 1	Supervisor/QC Head shall allocate the testing samples to the analysts as per their job responsibility and specialisation.
5.7 2	Refer Standard Testing Procedure before initiating the testing.
5.7 3	Give requisition for “Analytical Work Report” to the Quality Assurance Department
5.7 4	Refer Standard Testing Procedure to ensure that all required reagents, chemicals, accessories, equipment or instruments are standardised or validated and available in the laboratory.
5.7 5	Note: – Use amber colour glassware’s for analysis of light sensitive products.
5.7 6	In case of  non-availability of chemicals, impurities, working standard, instruments or equipments in the laboratory for any specified test then the sample to be send to Government approved outside testing laboratory.
5.7 7	If tests to be carried out as per IHS, copy of the protocol to be enclosed or scan copy to be mailed.
5.7 8	Fill in the necessary details on the Analytical Work Report according to ‘Raw Material Inward Register’ and start the analysis as per standard testing procedure and specification.
5.7 9	In case of active raw materials identification test should be performed on individual container sample.
5.7 10	Ensure that all the instruments are calibrated before use.
5.7 11	Refer the SOP of instrument before operation and update the instrument operation logs immediately after use.
5.7 12	After the analysis, hand over the Analytical work report to Supervisor/Reviewer analyst for data checking.
5.7 13	If Supervisor/Reviewer observed any discrepancy with analysis or analytical data, he / she should consult to Head of the Department for investigation.
5.7 14	If all the relevant data on Analytical work report complies as per Pharmacopoeia or IHS requirement or both, prepare “Certificate Of Analysis” as per specified format.
5.7 15	Full report shall contain AWR, Manufacturer COA, Sampling inspection report, GRN copy and all the instrument prints and COA prepared.
5.7 16	Quality control Head shall verify and approve the COA and release the consignment.
5.7 17	After approval of COA, analyst should prepare “APPROVED” labels (Green colour with approved by signature on it and should affix on the “UNDER TEST” label on all containers in such a way that the under test word on the label should be covered but the details on the under test label should be seen.
5.7 18	Residual samples: After completion of analysis of Raw Material sample, remaining sample quantity shall be stored as residual sample. Make inward for Residual samples as per “Raw Material Residual Sample Register”. Residual sample shall be store the sample as per specified condition at designated place in Quality Control Laboratory.
	Note: Residual sample shall be stored after completion of analysis in designated place and Sample should be stored till one year after date of report approval. Destroy the residual sample after one year.
5.7 19	No need to mention potency/Assay and Water/LOD/LOI on approved label in case of inactive materials.
5.7 20	Assign Retest Date on the approved label as per the SOP “Retesting of Raw and Packing materials”.
5.7 21	Photocopy of the approved COA shall be provided to the Warehouse Department.
5.7 22	Destroy Leftover samples/Residual sample as per SOP “Destruction of Laboratory waste”.
5.7 23	During analysis if analyst observes the results out of specification or out of limits, he / she should report to the supervisor or Head of the Department.
5.7 24	Supervisor shall initiate investigation as per SOP “Out of Specification” by filling OOS form.
5.7 25	After completion of investigation, categorise the observation as analyst error, reagent error, instrument error or material defect.
5.7 26	If material has major defect that can affect the product quality or out of respective Pharmacopoeial monograph then reject the material.
5.7 27	After detailed investigation prepare a COA for rejected material with a remark as “Material does not complies with the prescribed standards’’ and affix the labels on the material as “REJECTED” (Red colour) with rejected by signature and the reason for rejection.
5.7 28	Provide Photocopy of Rejected COA to Warehouse Department. Photocopy is not necessary if software is used for material inventory or control.
5.7 29	Reference samples of rejected raw materials shall be destroyed as per SOP “Destruction of Laboratory waste”.
5.7 30	Rejected Raw Material consignment shall be send back to the manufacturer/supplier for further disposal.
5.7 31	If any raw material is not possible to analyse as per Retest Date due to some reasons then material shall be analysed and released prior to taking into manufacturing.
5.7 32	Sampling and analysis window: Sampling shall be done within 10 days from the date of GRN Receipt. Testing shall be done within 30 working days from the date of sampling. If any sample exceeds analysis completion window then impact shall be assessed by filing deviation.
5.7 33	Re-sampling: Re-sampling shall be done in case of spillage of sample, contamination of samples, and in case of any discrepancies observed during testing. File an incident report and intimate Warehouse department to arrange the material for resampling with required quantity. QC analyst shall perform resampling as procedure mentioned above. Update the resampling quantity in “Raw Material Inward Register”.
5.8	Conditional Release of Raw Materials:
5.8 1	In case of urgent release of any batch of Active or Inactive Raw Material is required, then the Quality Control Head shall intimate the Supervisor or responsible analyst to initiate testing on priority.
5.8 2	Quality Control Head shall identify the specific tests to be carried out on priority as per the specification of respective Raw Material for Conditional Release.
5.8 3	Specific tests such as Description, Identification, Assay, LOD, Water content shall be performed as per Standard Testing Procedure on priority for Conditional Release.
5.8 4	Production Department shall raise the request for Conditional Release by filling “Conditional Release Form” if material is required urgently.
5.8 5	Hand over Conditional Release form to QA Department for assessment and necessary approval.
5.8 6	Raw Materials can be released conditionally by filling Conditional Release form but the product in which the material is used shall be dispatched only after complete testing and approval of COA.
5.8 7	Incase if any raw material having Microbiology test, then material can be released conditionally by performing chemical tests but the product in which the material is used shall be dispatched only after complete testing with micro release and approval of COA.
5.8 8	Approved labels shall be pasted only after approval of COA and the date of release shall be the date of approval.

 

6. Definitions / Abbreviations:

• Inactive material or Excipients: Inactive ingredients are added during the Manufacturing process of pharmaceutical products such as tablets  , capsules, Suppositories, and injections.

• Batch number (Lot number): A distinctive combination of numbers and/or letters which uniquely identifies a batch on the labels, its batch records and corresponding certificates of analysis.

• Sampling: Sampling is a process of collecting a small portion of material from a bulk of material received in the form of consignment or batch having one or more containers/bags/drums.
• Consignment: The quantity of a bulk material made by one manufacturer or supplied by an agent at one time in response to a particular request or order. A consignment may comprise of one or more containers/bags/drums.
• Abbreviations :

Abbreviation	Expansion
QA	Quality Assurance
√n+1	Under route of n = numbers of containers, bags, drums
COA	Certificate Of Analysis
RLAF	Reverse Laminar Air Flow
UV	Ultra Violet
RH	Relative Humidity
GRN	Goods Receipt Note
SOP	Standard Operating Procedure
A. R. No	Analytical Reference Number
gm	gram
IMS	Inventory Material System
IHS	In-house Specification
OOS	Out Of Specification
ERP	Enterprise Resource Procedures
IPA	Isopropyl Alcohol
i.e	That is
LOD	Loss on drying
LOI	Loss on ignition
NMT	Not More Than

  

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Entry Exit Procedure in Quality Control Department

1. Objective:

To lay down the procedure for Entry and Exit in the Quality Control Department.

2. Scope:

This procedure is applicable for Entry and Exit of working personnel and visitors in the Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Entry and Exit of working personnel and visitors in Quality Control Department as per this SOP.
• Quality Assurance Department: To review and approve the SOP and Annexure.

4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

Sr. No.	Procedure
5.1	5.1     Entry and Opening Procedure of the Department:
5.1.1	Person entering first in the Quality Control Department should collect the keys of the Department from the keyboard provided in the change room corridor.

 

5.1.2	Enter in the respective change rooms (Gents OR Ladies).
5.1.3	Keep the personal belongings in the lockers provided with lock and key.
5.1.4	Remove street footwear and keep them on the racks provided on the cross over bench.
5.1.5	Cross over the bench. Wear the company footwear’s dedicated to every individual kept on the racks of the cross over bench.
5.1.6	Collect and wear the clean apron from the cupboard provided in the change room.
5.1.7	Sanitize the hands with the sanitizer provided in the change room and enter through the door.
5.1.8	Person entering first with Department keys should check that the main door of the Department is in locked condition. If not, immediately bring it to the notice of the Quality Control Head, Administration Head and Security personnel.
5.1.9	Open the lock of the main door and ensure that no obnoxious smell or any other foul odour or smell is emitted from the Department. If any obnoxious smell observed, then do not enter into the Department, immediately bring it to the notice of the Quality Control Head, Administration Head and Security personnel.
5.1.10	Switch ‘ON’ the Department lights and air conditioners.

 

Sr. No.	Procedure
5.1.11	Before starting the work, ensure that the cleaning activities are completed in the presence of the house keeping personnel/Supervisor.
5.1.12	Verify AHU or HVAC are in working conditions by checking the temperature and humidity. If not intimate the Engineering Department accordingly.
5.2	5.2     Exit and Closing Procedure of the Department:
5.2.1	At the end of the shift check that the instruments/equipment’s which are not in use are switched OFF and the work benches are cleaned before leaving the Department.
5.2.2	Ensure the regulator valve of LPG cylinder in microbiological section is closed.
5.2.3	Verify that all chemicals, reagents, liquid solvents are properly closed and kept in their respective places after use and all water supply taps are closed.
5.2.4	All reference books should be placed in their designated places in the cupboard.
5.2.5	Ensure lights are Switch ‘OFF’ which are not required.
5.2.6	The person leaving the Department last should cross check that all the above steps have been followed and lock the main door of the Department.
5.2.7	After leaving the Department enter into the respective change rooms, remove company footwear’s, apron and keep them in the designated places.
5.2.8	Cross over the bench, collect your personal belongings from the lockers, wear your street footwear and exit from the change room.
5.2.9	Keep the keys of the Department in the keyboard provided in the change room corridor.

 

5.3	Entry Exit of Visitors in the Department:
5.3.1	All visitors should be accompanied with company employee in Quality Control Department.
5.3.2	Visitors should enter through change room wearing visitor apron and shoe cover or company footwear provided in the change room cupboard.
5.3.3	At the time of exit from the Department visitors should enter into the change room, remove apron, shoe covers or company footwear and keep them in the designated places.
5.3.4	Cross over the bench, wear your street footwear’s and exit from the change room.

 

 Definitions / Abbreviations:

 Abbreviations:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
AHU	Air Handling Unit
No.	Number
HVAC	Heating, Ventilating and Air Conditioning
LPG	Liquid petroleum Gas

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Good Laboratory Practices

1. Objective:

To lay down the procedure for Good Laboratory Practices in Quality Control Department.

2. Scope:

This procedure covers Analytical work, Documentation, Storage of Reagents and General Behavior in Laboratory of Quality Control Department.

3. Responsibility:
   • Quality Control Department: To prepare and review the SOP. To follow the Procedure for Good Laboratory Practices as per this SOP.
   • Quality Assurance Department: To review and approve the SOP.
4. Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure

5.1	General Requirements:
5.1.1	The quality control laboratory should be designed, constructed and maintained in such a way that it prevents entry for insects and rodents.
5.1.2	The interior surface (walls, floor, and ceilings) should be smooth and free from cracks.
5.1.3	Adequate provision is made for equipment and space to carrying out necessary tests.
5.1.4	Proper air ventilation system should be installed to ensure dust free environment.
5.1.5	The laboratories should have adequate lighting and ventilation facility.
5.1.6	Air-conditioning to be installed to maintain temperature and relative humidity for satisfactory functioning of the laboratory equipments or instruments and that will not adversely affect the accuracy of the testing and storage of drugs.
5.1.7	Acid, alkali and solvent resistant tabletops should be provided and should be smooth and free from crevices.
5.1.8	All staff in the laboratory should possess necessary qualification, proper training and shall have adequate, experience for their assigned duties.
5.1.9	A training record of all the personnel working quality control department should be maintained.
5.1.10	All quality related planning should be carried out regularly and organise the quality system audit and follow up action of the corrective actions if any; investigation of technical complaints.
5.1.11	All quality related planning should be carried out regularly and organise the quality system audit and follow up action of the corrective actions if any; investigation of technical complaints.
5.2	Equipment’s:
5.2.1	All analytical instruments should be procured as per cGMP requirement and housed in dust-free environment.
5.2.2	Whenever require conditions of temperature and humidity should be maintained with periodic checks.
5.2.3	Surrounding areas of the Instruments/Equipments and benches should be kept clean and tidy.
5.2.4	AMC visits shall be carried out for sophisticated instruments.
5.2.5	Record environment monitoring of Quality control department wherever applicable.
5.2.6	Spectra, graphs and additional test records shall be signed by the analyst and attached  to the analytical report.
5.2.7	Filter mobile phase/Buffer with 0.45µ filter paper before use. Properly sonicate and degas the mobile phase before use.
5.2.8	Those Instruments required calibration should be calibrated at regular intervals and records of such calibration to be maintained.
5.2.9	The frequency of calibration may differ from instrument to instrument and all Equipment/Instruments records should be maintained.
5.2.10	The records should  contain the following : a)      Name of Equipment or Instrument or apparatus. b)      Manufacturer’s name, model number and ID No. c)      Date of receipt, Location and Qualification history. d)     Manual Copy. e)      Frequency of Calibration and Maintenance Frequency. f)      Log Book. g)  Calibration and maintenance status of the equipment. h)   List of authorised users or operators, if any. i)  List of spares and accessories, if any
5.2.11	For most of the equipments and instruments, Standard Operating Procedures for calibration and calibration schedule should be prepared by the laboratory and a logbook should be maintained.
5.2.12	A progress register for non-functional equipments and action for procurement of spares and accessories, monitoring thereof, should be maintained.
5.2.13	A Standard Operating Procedure for preventive maintenance of machine or equipment or apparatus should be available with the laboratory.
5.2.14	Other equipments such as burettes, pipettes, volumetric flasks, weight boxes, thermometers, etc., should have thorough checked for accuracy of calibration before acceptance for use.
5.2.15	Those equipments, instruments giving abnormal results or defective must be labelled as ‘Out of Order’ till they are repaired and after equipments / instrument are repaired they should be recalibrated before use.
5.2.16	Autoclaves must meet the requirements described for operations, safety and validation procedures, and the validation carried out by the laboratory should be recorded.
5.3	Fume Hood Cabinet:
5.3.1	Work involving the evolution of harmful and obnoxious vapours should be carried out in a Fume Hood.
5.3.2	The exhaust system of the fume hood should be checked frequently to ensure that it is working in order.
5.4
5.4.1	All chemical and reagent receipt, consumption and stock data should be maintained.
5.4.2	All reagents and solutions in the laboratory should be properly identified with a label.
5.4.3	Follow MSDS while handling the chemicals.
5.4.4	Spectra, graphs and additional test records shall be signed by the analyst and attached to the analytical report.
5.4.5	Do not heat organics solvents directly on heating mantle. Use water bath.
5.4.6	Do not use volatile solvents near flame.
5.4.7	The contents of containers where the labels are disfigured or have peeled off must be carefully and thoroughly identified before use or suitably disposed off.
5.4.8	A standardisation register should be maintained along with its raw data for all standard solutions and volumetric solutions.
5.4.9	Standard Operating Procedure for preparation and standardisation on stock solutions, for all standard solutions, volumetric solutions must be available for the guidance of staff.
5.4.10	All bottles, Containers of stock solutions and of standard solutions should bear the following details: 1.      Name of solution 2.      Strength 3.      Date of preparation 4.      Validity period/Use before date, (Based on the stability of the solution) 5.      Prepared by 6.      Checked by
5.4.11	All Volumetric Solutions should be re-standardized at defined interval.
5.4.12	Volumetric solutions, Stock solutions should be discarded immediately if any sedimentation in observed irrespective of declared shelf life.
5.4.13	To avoid contamination of chemicals and reagents special care must be taken with standard solutions.
5.4.14	Quantities of such solutions in excess of requirements should not be returned to stock bottles but should be discarded.
5.4.15	After the use of a reagent, place the bottle at its right place on the shelf in such a way that the label is clearly visible and is in front.
5.4.16	Before putting the bottles back on the shelf wipe the bottle in case some reagent/liquid is spilled down the sides.
5.4.17	In-compatible chemicals should be stored away from each another at specified storage container and conditions.
5.4.18	Do not accumulate chemicals/ reagents / glassware /equipments on benches or in fume cupboards.
5.4.19	After use always return all chemicals/ reagents / glassware /equipments to their designated places.
5.4.20	Heavy containers and bottles of dangerous chemicals should be returned to main chemical store as soon as possible.
5.4.21	When chemicals are transferred from big containers to small bottles for regular use they should be properly marked with all details of the original container.
5.4.22	Any bottle containing chemical that need to be carried a short distance should be supported at the base and neck.
5.4.23	For carrying to longer distances use the special carriers, which are available.
5.4.24	The transfer of solvents and hazardous chemical from bulk containers should be done carefully and with proper device funnels, pumps etc.
5.5	Good Housekeeping, Hygiene Safety:
5.5.1	All personnel working and entering in Quality Control Department should follow entry and exit procedure.
5.5.2	General and specific written down instructions for safety shall be circulated to each staff member and the instructions be revised periodically as appropriate.
5.5.3	Standard Operating Procedure for safety, house-keeping should be prepared in accordance with the various rules and regulations of the Government of India and include the following requirements.
5.5.4	Drinking, eating and smoking shall not be permitted in the laboratories.
5.5.5	Food for human consumption should be prohibited in working or storage areas.
5.5.6	Safety data sheets must be made available to staff before testing is carried out.
5.5.7	Staff must wear laboratory coats or other protective clothing including gloves and face masks and eye protection wherever required.
5.5.8	The staff must be educated in the first aid techniques, emergency care.
5.5.9	The laboratories should have adequate first aid kit and fire fighting equipments located at the right places.
5.5.10	Any person found suffering from illness which may adversely affect the quality and integrity of testing shall be excluded from direct contact with test system.
5.5.11	All the staff must be familiar and trained with the use of fire fighting equipment including fire extinguishers, fire blankets and gas masks.
5.5.12	Microbiologist carrying out sterility tests should wear sterilised garments including headgear, face masks and shoes.
5.5.13	Appropriate facilities for the collection, storage, and disposal of wastes should be made available.
5.6	Reference Materials :
5.6.1	Reference materials are necessary for the testing and, or calibration, validation or verification of a sample or of equipment, instruments or other devices and all such materials should  be avail from  agency authorised by Government of India or any other International body.
5.6.2	The laboratory should prepare working standard by comparing with the reference standards and should be routinely checked for their purity by selecting parameters such as identity, loss on drying or on water, impurity and assay, etc.
5.6.3	Whenever, any new reference material is received by the laboratory, a code number should be assigned and this code number shall be quoted on the laboratory note book and analytical work sheet.
5.6.4	All working standard should have identification code.
5.6.5	A register pertaining to reference and working standards must be maintained by the laboratory. The following details shall be mentioned in the register: (i) Source of supply (ii) Code number of the reference material (iii) Date of receipt (iv) Batch number or identification number of the supplying agency (v) Details like assay value, water content or any other information provided (vi) Storage condition of the material (vii) Date of expiry, if any and date of manufacturing if possible.
5.6.6	All working standards should be checked at appropriate intervals or before use to ensure that it has not deteriorated or decomposed during storage.
5.6.7	These observations should be recorded in a register.
5.6.8	All the reference and working standards shall be stored at appropriate storage condition.
5.6.9	Those require storage between 2-8º C should be stored in a refrigerator.
5.6.10	Wherever recommended the material should not be allowed to be frozen.
5.7	Microbiological Cultures:
5.7.1	Standard Operating Procedure for maintenance of microbial culture and sub-culture must be prepared by the laboratories
5.7.2	If the cultures have become non-viable or mutant, proper procedure should be followed to destroy these cultures by autoclaving under authorised personnel for biological testing.
5.7.3	Preferably not more than five passages may be prepared.
5.7.4	All activities be carried out in a aseptic area by authorised person.
5.7.5	The laboratories should perform standard biochemical tests on the sub-culture as given in literature to ensure their viability.
5.8	Quality system:
5.8.1	The quality system should be designed to ensure the following objectives. a)      The measurements and calibrations should fully conform to the compendia requirements and the methods demonstrably based on validation protocols are followed. b)      It should be effective in providing necessary assurance that the activities or processes or techniques or practices comply with planned arrangements. c)      It helps in early detection and correction of non conformities. d)     Remedial action on the observations by internal and external audits is taken appropriately. e)      It should have a documented quality policy for the organisation.
	Internal quality system audits:
5.8.2	Internal audits are done to assure the integrity of the analysis and such audits should be conducted periodically with a predetermined schedule procedure with appropriate checklist.
5.8.3	Verify that the operations continue to comply with the requirements of quality system and requirements of regulatory authorities.
5.8.4	Internal quality audits shall be carried out by trained and qualified personnel who are independent of the activity to be audited.
5.8.5	The periodicity of quality audit should be fixed by the Head of the laboratory so that each activity is audited at least once in a year.
5.8.6	Head of the laboratory will be responsible for initiation of the corrective action arising from audits and verification of corrective action.
5.8.7	a)   Whenever any non-compliance or any diversion is noticed by the team in implementing quality policy or quality system, protocols, the same will be attended by the Quality Manager.
5.8.8	The problem will be analysed and necessary actions will be taken with proper documentation.
5.8.9	The Quality Manager should maintain all the records of the analysis being conducted which includes test system, the type of analysis, date on which analysis is done, etc.
5.8.10	Quality Manager should also maintain copies of all protocols pertaining to different activities being checked by the audit team.
5.9	Management review:
5.9.1	Quality system reviews should  be conducted by the top management at least once in every twelve months and the agenda of review should generally cover the following: a)      Report or input of internal audits b)      Matter arising from previous reviews c)      Report of external audits, if any d)     Surveillance report, if any e)      Result of proficiency testing f)       Complaints or feedback received from users of laboratory services g)      Details of in-house quality control checks h)      Need of amendment of the quality system and documentation i)        Induction training of new staff j)        Any other requirements of the laboratory.
5.10	Standard Operating Procedures:
5.10.1	Standard Operating Procedures are written procedures for different activities being conducted in a laboratory and should include the following characteristics: a)      They shall be written in a chronological order listing different steps leading to an analysis of drugs or calibration of an instrument. b)      Testing laboratories should have Standard Operative Procedure manuals and have its periodic review. c)      It should be user friendly documents and should include designation of the person responsible for intended activity.
5.10.2	Standard Operating Procedures in addition to those recommended under various activities should also be prepared to the minimum in respect of the following: a)      Sample handling and accountability. b)      Receipt identification, storage, mixing and method sampling of the test and control articles. c)      Record keeping, reporting, storage and retrieval of data. d)     Coding of different studies, handling of data including use of computerized data system. e)      Operation of technical audit personnel in performing and reporting audits, inspections and final report reviews.   f)       Routine inspection of cleaning, maintenance, testing, calibration and g)      Standardisation of instruments. h)      Action to be taken in respect of equipment failure. i)        Analytical data methods. j)        The raw data. k)      Data handling and storage retrieval. l)        Health and safety protection. m)    Storage and maintenance of microbial cultures. n)      Use and storage of reference standards. o)      Monitoring of testing of samples. p)      Method of retention of unexpended samples, their location, maintenance and disposal. q)      Document control. r)       Technical complaints. s)       House-keeping. t)       Corrective and preventing action. u)      Working procedure (test methods). v)      Calibration Manual. w)    Training anual.
5.11	Protocols and specifications archive:
5.11.1	Every laboratory should have a specification archive and current versions of all necessary specifications should be kept as per the requirements of the Act and the rules made there under.
5.11.2	All updates and corrections must be noted from updated volumes of Pharmacopoeias to prevent the use of obsolete sections. Supplements and addendum should also be made available in the laboratory.
5.11.3	The specification archive should contain the following : a)      List of all the pharmacopoeias; b)      A file on patent and proprietary medicines (non-Pharmacopoeial) test methods to specifications prepared and validated by the manufacturer or by the laboratory itself. c)      The test methods should be submitted to the concerned Drug Control Authority. d)     The validated test methods developed by the manufacturer or the laboratory should stand to the requirements of compendial parameters in regard to its precision, accuracy, reproducibility, specificity, linearity, and ruggedness etc.
5.12	Raw data:
5.12.1	Raw data refers to the laboratory work sheet, note books or analysis sheet, Records, memorandum, notes or extract copies thereof that may be the results of general observations and other activities.
5.12.2	Such raw data shall include hand written notes, photographs, software, drawings, computer printouts, spectral charts, dictated observations or recorded data from automated equipments.
5.12.3	The raw data also includes record of environmental monitoring, calibration, records of equipments, integrator output from analytical equipment, including work-sheet used to read note information from Light Emitting Diode (LED) display of any equipment.
5.12.4	A single line shall strike through the data being changed; the correct information shall be recorded along with the old data and the reason of change.
5.12.5	The analyst making the change shall be identified by his signature with date.
5.12.6	In case of automated data collection system, the person responsible shall be identified at the time of data output.
5.12.7	The original entry must be saved and the systems have audit trial for all the data.
5.12.8	Data integrity and security shall be maintained and the data shall not be accessible to any unauthorised person.
5.13	Storage and archival:
5.13.1	The residual sample shall be retained in proper storage condition for a period of one year after the final report.
5.13.2	The laboratory must establish and maintain procedures for the identification collection, indexing, retrieval, storage, maintenance, and disposal of all quality documents.
5.13.3	All the raw data, documentation, Standard Operative Procedures, protocols, and final reports are to be retained and there should be archives for orderly storage and retrieval of all raw data, documentation, protocols, interim and final report.
5.13.4	The archive should provide a suitable environment that will prevent modification, damage, or deterioration and/or loss expeditious.
5.13.5	The condition under which the original documents are stored must ensure their security and confidentiality.
5.13.6	Paper documents shall not be kept for long periods under high humidity and raw data in the form of tape and discs are to be preserved with care.
5.13.7	In case of storage of only optical disc, the life of disc should be longer than the storage time.
5.13.8	Raw data on thermal paper might fade away with time; therefore, a photocopy of the thermal paper shall also be retained in the archive.
5.13.9	Time for which records are retained shall be prescribed in the documents.

 

6. Definitions / Abbreviations:

• Definitions :
• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
ID No.	Identification Number
etc	etcetera
°C	Degree centigrade
LED	Light Emitting Diode

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.