Category: QC SOP

1. Objective:

To lay down the procedure for Procurement and Handling of Primary Standards.

2. Scope:

This SOP is applicable for Procurement and Handling of Primary Standards in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Procurement and Handling of Primary Standards 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	Procurement and Handling of Primary Standards :
5.1.1	Current batch of AR grade Primary Standards should be procured from an authorized supplier of manufactured by Merck, S.D. Fine, Loba, Rankem, Himedia, Fischer etc.
5.1.2	For receipt of Primary Standards refer SOP “Receipt, Storage and Handling of Chemicals in Laboratory”.
5.1.3	Certificate of Analysis should be received with Primary Standards or it can be downloaded from internet and record to be maintained.
	Note: Commercially available very pure chemicals shall be used as primary standards.
5.1.4	Validity of Primary Standards shall be defined as two years after date of opening of the containers, if physical properties are same as initial. If the expiry date of Primary Standard is defined by the manufacturer earlier than two years from the date of opening then assign validity same as manufacturer’s expiry date.
	Example: If the analyst opens Potassium Chloride bottle on 25/04/24, then the date of opening shall be 25/04/24 and the validity shall be 24/04/26.
5.1.5	After receiving the Primary Standards, they should be labelled with detailed information as per Annexure.
5.1.6	Allocate primary standard number to Primary Standard as below: PS/XX/YY/NNN Where: PS: Primary standard XX: Serial Number of the Primary Standard YY: Current year NN : Serial number of received Primary Standard
5.1.7	Primary Standards should be stored in tightly closed container at room temperature or at specified storage conditions on containers or certificate.
	Note: Clean the outer Surface of bottle with tissue paper before use.
5.1.8	Maintain Primary Standard Receipt and Usage Record as per Annexure
5.1.9	Primary Standards after drying under the specified conditions are recommended to use as Primary Standards for standardization of Volumetric Solutions.
5.1.10	Immediately after use of a Primary Standard, it should be restored back to its storage place.
5.1.11	During use or drying of Primary Standards don not put back the withdrawn material from the container.
5.1.12	Primary standards should not be used after the validity period. It should be consider as general chemical and can be used for routine analysis till the expiry/validity period as defined for general chemical after opening.
5.1.13	Expired primary Standard should be destroyed as per SOP “Destruction of Laboratory Waste”.
	If any primary standard shows deterioration e.g. crystallisation, discoloration, sedimentation, precipitation, change in physical appearance shall be discarded regardless of validity.

 

6. Definitions / Abbreviations:

• Definitions :
• Abbreviations :

Abbreviation	Expansion
AR	Analytical Reagent
No.	Number

 

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

 

SOP Title: Analysis  of Samples at Outside Testing Laboratory

1. Objective:

To lay down the procedure for Approval of Outside Testing Laboratory and Analysis  of Samples at Outside Testing Laboratory

2. Scope:

This procedure is applicable for Outside Testing Laboratory for Identification, Selection, Qualification and Approval in the Quality Control Department.

3. Responsibility:
   • Quality Control Department: To prepare and review the SOP. To follow the procedures for Approval of Outside Testing Laboratory 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	Initial selection:
5.1.1	Quality Control Manager and Quality Assurance Manager shall initialize selection process of the Outside Testing Laboratories as per organisation requirement.
5.2	Evaluate the Outside Testing Laboratory for following aspects:
5.2.1	Whether their Laboratory compliance as per GMP requirement.
5.2.2	Whether they have experience with method development and/or method validation according to cGMP requirements.
5.2.3	Whether they have experience of QC activities and approval of QC results according to GMP
5.2.4	1.       Whether they have sophisticated equipment’s for analytical support.
5.2.5	2.       Whether they have technical knowledge and expertise.
5.2.6	Whether they have Quality Risk Assessment system.
5.2.7	3.   On the basis of evaluation study Outside Testing Laboratory to be selected.
5.2.8	Following questionnaires /check list are to be sent to Outside Testing Laboratory and requested them to send their valuable feedback for the following topics:
5.2.9	1) Laboratory Management structure and Organogram. 2) List of analysts and areas of expertise in Quality Control section. 3) Laboratory Quality System – ISO 9001, ICH, GMP, GLP, GCP Copies of Certificates –yes/no. 4) List of Analytical Instruments and Use of Software like LIMS, Chromatography data systems and /or other automated systems – yes/no. 5) Computer System Validation, compliance of software, change control and deviation SOP’s related to software- yes/no. 6) Laboratory notebooks, analytical test records- yes/no. 7) Raw data handling system –facility is available – yes/no. 8) Analysts Training are conducting at regular intervals- yes/no. 9) Document control & Document retention / archiving policy facility is available? 10) Retain sample control facility is available?
5.2.10	On receipt of relevant information’s as per given format and verified all information and all issues are resolved before conducting Audit.
5.2.11	A qualified Quality Auditor, from Quality Assurance and Quality Control Expert would accompany the audit team.
5.2.12	The checklist that was completed during the initial laboratory evaluation should also be verified during the Audit.
5.2.13	The Auditors should focus on the effectiveness of the Laboratory Controls for the following procedures.
5.2.14	1)  Analytical Method Development and Validation if applicable. 2)  Analytical Method Transfer and Validation. 3)  Verification of the accuracy of the analytical test results 4)  Traceability of all instruments, procedures, reference standards, reagents and personnel involved in generating the test results. 5)  Periodic qualification, calibration, monitoring and verification of equipment and instruments. 6)  Quality System Procedures and Practices should  be assessed for: a)         Personnel qualification and training b)         Document control c)         Laboratory deviation investigations d)        Out of Specification (OOS) investigation. e)         Complaints handling.
5.2.15	Based on the Audit report, Outside Testing Laboratories shall be shortlisted.
5.2.16	Those laboratories which complies with the Internal Quality Assessment Audit shall be selected and Agreement shall be done with these laboratories.
5.2.17	Update the list of approved laboratories as per Annexure.
5.3	Periodic Evaluation:
5.3.1	On annual basis, the outside testing lab performance should be assessed for following data.
5.3.2	1) All results are received under agreed timelines. 2) Customer complaints regarding analytical results. 3) Response time for complaints and queries.
5.4	Performance:
5.4.1	a)           If fully satisfied with laboratory performance –rated as satisfactory. b)         If performance is not satisfactory, additional time should be given for improvement. c)         If the laboratory shows a low performance for more than one year, the approval should be reconsidered.
5.5	Analysis  of Samples at Outside Testing Laboratory
5.5.1	Tests which cannot be performed in QC shall be get tested from approved outside contract testing laboratories.
5.5.2	Prior approval shall be taken from Quality Control head before sending samples for outside testing.
5.5.3	Sample shall be sent to contract testing laboratory as per test request form.
5.5.4	On receipt of results from contract laboratory, the test result shall be checked by Quality person for accuracy, Data integrity and supporting documents.
5.5.5	Samples can be sent to outside contract testing laboratories if any In-house instrument goes under breakdown.
5.5.6	Quantity of sample shall be send to contract laboratories as per mentioned in the specification or specific requirement given by contract laboratory.
5.5.7	If there is no discrepancy found in testing reports and supporting data, the results shall be reported in AWR. Testing reports & supporting data shall be attached with AWR. The contract laboratories bill can be approved and send to account department for further processing.

  

6. Definitions / Abbreviations:
   • Definitions:

• Abbreviations:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
GMP	Good Manufacturing Practice
cGMP	Current Good Manufacturing Practice
LIMS	Laboratory Information Management System
ICH	International Conference on Harmonisation
ISO	International Organisation for standardisation
GCP	Good Clinical Practice
GLP	Good Laboratory Practice

 

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

 

SOP Title: Handling of Laboratory Chemicals

1. Objective:

To lay down the procedure for Receipt, Storage and Handling of Chemicals/Solvents in Quality Control Department.

 

2. Scope:

This procedure is applicable for Receipt, Storage and Handling of all the Chemicals/Solvents used for analysis in Quality Control Department and is followed during the purchase of chemicals, storage and routine analysis in Quality Control.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Receipt, Storage and Handling of Chemicals/Solvents 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	Precautions:
5.1.1	Personal Protective Equipments such as hand gloves, nose masks, goggles should be used while working with hazardous, corrosive, flammable, toxic chemicals.
5.1.2	Chemicals coming in contact with eyes can be particularly dangerous, resulting in painful injury or loss of sight. Wear safety goggles or a face shield to reduce the risk of eye contact.
5.1.3	Chemicals coming in contact with skin can cause redness and swelling, rashes and itching. Wear safety gloves reduce the risk of skin contact.
5.1.4	Inhaling chemicals/solvents may result in headaches, eye, nose and throat irritation, drowsiness or collapse may result from exposure to some substances, particularly many solvents.
5.1.5	Wear safety nose masks to avoid the risk.
5.1.6	Strictly follow the precautions, warning mentioned on chemical/reagent bottles or refer Material Safety Data Sheets (MSDS) which provide information concerning the safe handling of chemicals, their storage, hazards, first aid and disposal.
5.1.7	Do not store or expose the chemicals near the flame or excessive heat.
5.1.8	While preparing acid solutions, always add acid to water. Do not add water to acid as this reaction may produce significant heat.
5.1.9	Avoid inhaling or touching chemicals or reagents known to be toxic as it can cause injury or harm to personnel.
5.1.10	Do not draw any liquid into pipette by mouth as the chemical/solvent in the pipette may enter into the mouth. Use rubber bulb or other pipetting aids.
5.2	Receipt of Chemicals/Solvents:
5.2.1	When any chemical or solvent is received, the responsible analyst or officer should verify all the details like name of the chemical, quantity received, Make, grade with the purchase order given to the respective supplier.
5.2.2	Also check if the received chemicals or solvents have any external damages. If any discrepancy is observed then the responsible analyst or officer shall inform the Head of the Quality Control Department and follow instructions given by the Quality Control Head.
5.2.3	If material received is not as per the purchase order, cancel the entry of the same on all copies of challan and invoices (if attached) by drawing single line and duly signed with date and handover or return the material to the supplier.
5.2.4	If the chemical or solvent conforms to the requirement then the analyst shall accept the material and counter sign on the challan and submit to the security personnel for making entry in the Security Inward Register.
5.2.5	Send the challan and invoices to the Warehouse Department for making GRN and then to the Accounts Department.
5.2.6	Enter the details of the chemicals received in “Chemical Receipt Register” as per Annexure and also in the individual “Chemical Stock and Consumption Record” as per Annexure.
5.2.7	Individual index sheet shall be maintained for chemicals coming under one alphabet as INDEX A, INDEX B and so on as per Annexure.
5.2.8	Under Index A, serial number shall be given to the chemicals as A-1, A-2 and so on. For example If Ammonium chloride is received then it will come under index A and the serial number shall be given as A-1. This procedure shall be followed for all the individual index sheets.
5.2.9	Affix the Chemical receipt label as per Annexure on each and every container of the chemical/solvent received and fill in the necessary details on the label with signature of the receiver.
5.3	Storage of Chemicals/Solvents:
5.3.1	Solid chemicals shall be stored in the designated cupboards labelled as ‘Chemicals in Stock’ in alphabetical series at room temperature or as specified storage conditions on containers or certificate.
5.3.2	Liquid chemicals or solvents shall be stored in the designated cupboards labelled as ‘Solvents in Stock’ in alphabetical series at room temperature or as specified storage conditions on containers or certificate.
5.3.3	All the cupboards containing chemicals should have the list of chemicals present in stock.
5.3.4	Refer chemical Compatibility chart available in Laboratory before storing the chemicals.
5.3.5	Highly corrosive, flammable and toxic chemicals like concentrated acids, ammonia, and hydrogen fluoride shall be stored in fuming room.
5.3.6	Primary standards shall be stored in separate cupboard with the list of primary standards in it.
5.3.7	Highly hazardous/ Poisonous chemicals like acetic anhydride shall be kept in separate cupboard with lock and key under Supervisor control.
5.4	Handling of Chemicals/Solvents:
5.4.1	Whenever any new chemical is taken from the stock for use, analyst should enter the date of opening on receipt label and entry should be made on chemical stock and consumption log book.
5.4.2	Chemicals in use shall be kept on the racks of the working table provided in wet chemistry area in alphabetical series.
5.4.3	Acids which are in use shall be kept in sand bath in fuming room.
	Note: Don’t Dip the pipette in the Liquid Reagents and Solvent. Solvent from Bottles Transfer separately in the cleaned beaker and pipette out of it and discard the remaining portion to avoid contamination.
5.4.4	Always use safety masks, goggles, acid resistant gloves while dispensing strong acids or chemicals.
5.4.5	When working with flammable substances carry out the work in fuming room with proper ventilation away from the source of fire.

 

5.4.6	In case of accidental spillage of any acid on hands or face or clothing wash with plenty of water at the eyewash and shower station. If irritation occurs seek medical advice.
5.4.7	For storage, use and handling of any other poisonous or hazardous chemical refer the Material Safety Data Sheet or instructions of manufacturer.
5.4.8	If the expiry date of Chemicals/Solvents is not defined by the manufacturer then all the Chemicals/Solvents should be used within three years after the date of opening.
5.4.9	Example: If the analyst opens Potassium chloride bottle on 25/04/24, then the date of opening shall be 25/04/24 and the validity shall be 24/04/27.
5.4.10	If the expiry date of Chemicals/Solvents is defined by the manufacturer earlier than three years from the date of opening then assign validity same as manufacturer’s expiry date.
5.4.11	Example: If the Ascorbic acid chemical has expiry date as 05/2024 and the analyst opens Ascorbic acid bottle on 18/06/22, then the date of opening shall be 18/06/22 and the validity shall be 31/05/24. Consider the last date of expiry month to assign validity.
5.4.12	Intact chemicals/solvents should be used within five years from the date of manufacturing
5.4.13	If the date of manufacturing is not available then intact chemicals/solvents should be used within five years from the date of receipt.
5.4.14	If any chemicals/solvents shows deterioration e.g. sedimentation, precipitation, crystallisation, discoloration, change in physical appearance shall be discarded regardless of validity.
5.4.15	For destruction of any Chemicals/Solvents, refer current SOP of “Destruction of Laboratory Waste”.

 

6. Definitions / Abbreviations:

• Definitions:
• Chemical: chemicalis a substance, element, chemical compound or mixture of elements that is produced or used in a process (reaction) involving changes to atoms or molecules.
• Corrosive chemicals: Achemical that causes visible destruction of living tissue or irreversible alterations in living tissue by chemical action at the site of contact. Example: Bromine, Acetic acid, Triethylamine.
• Flammable Chemicals: A flammable material can be a solid, liquid or gas. It is defined as any liquid having a flash point below 100^oF. (37.8^oC). Example: Benzene, Methanol and Ethanol.
• Toxic Chemicals: Chemical that causes an undesirable effect in a biological system. Example: Hydrochloric acid, Nitric acid.
• Flash point:It is defined as the lowest temperature at which a liquid can form an ignitable mixture in air near the surface of the liquid. The lower the flash point, the easier it is to ignite the material.
• Hazardous Chemicals: Hazardous chemical is defined as any chemical that is responsible for health hazard, physical hazard or damage to environment. Health hazardchemicals are the ones which causes acute or chronic health effects when exposed to it. Chemicals which cause health hazards are carcinogens, toxic or highly toxic agents, reproductive toxins, irritants, corrosives, sensitizers, hepatotoxins, nephrotoxins, neurotoxins, agents that act on the hematopoietic system (body organs and tissues involved in the formation of blood elements), and agents that damage the lungs, skin, eyes, or mucous membranes. Physical hazard chemicals are the ones that are combustible liquid, a compressed gas, explosive, flammable, an organic peroxide, an oxidizer, pyrophoric, unstable (reactive), or water-reactive.
• Harm: Damage to health or environment including the damage that can occur from loss of product quality or availability.
• Contamination: Deposition of chemicals/solvents in any place where it is not desired, particularly where its presence may be harmful.  The harm may merely interfere with an experiment or procedure or may constitute an actual hazard to personnel.
• Abbreviations:

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
GRN	Goods Receipt Note
MSDS	Material Safety Data Sheet
0C	Degree Celsius
0F	Degree Fahrenheit

 

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

 

SOP Title: Validation of Analysts in Quality Control Department 

1. Objective:

To lay down the procedure for Validation of Analysts in Quality Control Department.

 

2. Scope:

This SOP is applicable for Validation of Analysts in Quality Control Department.

 

3. Responsibility:

• Quality Control: To prepare and review the SOP. To follow the procedures laid down for Validation of Analysts 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	Validation of Analysts:
5.1.1	New appointed analyst should go through all the relevant SOP training before starting actual job.
5.1.2	After completion of SOP training, Analyst should complete analyst Validation for Complex and Non-complex tests before performing routine testing.
5.1.3	Supervisor/Group leader shall allocate approved or routine sample to the analyst for analyst validation based on type of test i.e. Complex test or Non-complex test.
5.1.4	In case of Complex test, approved /already tested sample shall be given for analyst validation.
5.1.5	In case of Non-complex test, routine /under test or approved sample shall be given for analyst validation.
5.1.6	For distinguishing of Complex and Non-complex test refer below table but not limited to;
Complex Test: Assay by HPLC/UV/GC/AAS Water Content Dissolution by HPLC/UV/ AAS Water analysis- Microbiology Uniformity of Content  by HPLC/UV/AAS Environmental Monitoring Related Substances  HPLC/UV/GC Serial culture dilution

 

Non-complex Test: Description Loss on Drying *Calcium/ Fluorides/ Chlorides Solubility #Acetyl Value *Phosphates/ Potassium ● Clarity of Solutions #Acid Value  & Este Value *Sulphates/ Nitrates ● Colour of Solutions #Hydroxyl Value *Oxidising substances Melting Point/ Boiling Point #Peroxide Value Uniformity of weight pH #Saponification Value Physical parameters Freezing Point #Iodine Value Hardness Test Dis illation Range Volumetric titrations Friability Test Optical Rotation Bulk density/Tapped density Disintegration Test Weight per ml / Relative density Refractive Index Bursting strength Conductivity Sulphated Ash/Loss on Ignition Grammage of packing materials Viscosity Thin layer chromatography Thickness of Packing Materials Powder Fineness Arsenic Growth Promotion Test ►Residue on evaporation Heavy Metals Identification of cultures ►Total dissolved solids *Acidity/Alkalinity Test for pathogens Total Organic Carbon *Aluminium /Ammonium   Sulphur Dioxide *Iron / Lead/ Magnesium
5.1.7	Note:    ●    If the analyst is qualified for any one of the test above marked then the analyst can be considered qualified for rest of the tests of same marked.

 

5.1.8	► If the analyst is qualified for any one of the test above marked then the analyst can be considered qualified for rest of the tests of same marked.
5.1.9	#   If the analyst is qualified for any one of the test above marked then the analyst can be considered qualified for rest of the tests of same marked.
5.1.10	*   If the analyst is qualified for Heavy Metal or Arsenic any one of the test then the analyst can be considered qualified for the tests above marked.
5.1.11	For complex test, analyst shall give the request for AWR pages to QA Department as per test before initiating the testing.
5.1.12	For issuance of AWR refer SOP “Control of Documents, Preparation, Approval, Issuance and Maintenance.
5.1.13	After getting AWR from Quality Assurance, new analyst shall initiate the testing with online documentation under the observation of trained analyst.
5.1.14	For Non-complex test, analyst can report all the preparation and results directly on regular AWR sheet issued by Quality Assurance Department.
5.1.15	Analyst shall fill required details in “Analyst Validation and Evaluation Record” concurrently as per Annexure.
5.1.16	If routine/under test sample results found out of specification limit then initiate investigation as per OOS SOP.
5.1.17	Trainer shall monitor new analyst during testing and write observations in analyst validation and evaluation record.
5.1.18	Trainer/Group leader has to write conclusion, whether analyst shall be qualified or not qualified based on results obtained and acceptance criteria.
5.1.19	If new analyst fails to meet acceptance criteria of analyst validation, then Trainer/Supervisor shall investigate the cause of failure and recommend for analyst revalidation with re-training.
5.1.20	Analyst should follow Standard Test Procedure and specification during testing.
5.1.22	Acceptance criteria for standard replicate injections shall remain same as defined in standard test procedure.
5.1.23	If New analyst qualified for Assay By HPLC then analyst shall be considered qualified for Assay by UV/AAS/GC. Same criteria are applicable for rest of the tests.
5.1.24	Analyst should fill the ‘Analyst Validation Log Sheet’ after completion of validation records and certification as per Annexure.

 

6. Definitions / Abbreviations:

• Definitions :
• Abbreviations :

Abbreviation	Expansion
No.	Number
AWR	Analytical Work Record
HPLC	High Performance Liquid Chromatography
GC	Gas Chromatography
AAS	Atomic Absorption Spectroscopy
OOS	Out of Specification
UV	Ultra Violet

 

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

 

SOP Title: Handling and Storage of HPLC Columns    

1. Objective:

To lay down the procedure for Handling and Storage of HPLC Columns in Quality Control Department.

2. Scope:

This SOP is applicable for Handling and Storage of HPLC Columns used for chromatographic analysis in Quality Control Department.

3. Responsibility:

• Quality Control: To prepare and review the SOP. To follow the procedures laid down for Handling and Storage of HPLC Columns 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	Precaution:
5.1.1	Ensure that mobile phase is properly filtered using 0.45µ filters and suitably degas before its use.
5.1.2	Do not cross the maximum and minimum temperature of column specified by manufacturer.
5.1.3	Always affix the column pick nuts when column is not in use.
5.1.4	Handle column carefully to prevent it from any mechanical shock.
5.1.5	Do not keep HPLC column in buffer.
5.1.6	Mobile phase pH should not cross its recommended values (normally).
5.1.7	Read the instruction regarding column packing before handling the column.
5.2	Receipt and Numbering of HPLC Columns :
5.2.1	On receipt of new HPLC column, verify all the details against Purchase Order and check for external damage if any.
5.2.2	If any discrepancy is observed then the responsible analyst or officer shall inform the head of the Quality Control Department and follow instructions given by the Quality Control Head.
5.2.3	If HPLC column received is not as per the purchase order, cancel the entry of the same on all copies of challan and invoices (if attached) by drawing single line and duly signed with date and handover or return the material to the supplier.
5.2.4	If the column conforms to the requirement then the analyst shall accept the material and counter sign on the challan and submit to the security personnel for making entry in the inward register.
5.2.5	Send the challan and invoices to the stores department for making GRN and then to the Accounts Department.
5.2.6	Enter all the details of receipt in ‘Column Inward Register’ as per Annexure.
5.2.7	Assign the in-house Identification Number for the column as -CL/YY/NN. Where, ‘CL’ stands for Column ‘YY’ stands for last two digits of year in which the column is                                               received. ‘NN’ stands for Serial Number.
5.3	Performance Check of HPLC Columns :
5.3.1	Perform system suitability test for new column.
5.3.2	Qualify the column as per the party COA or with the product for which column is dedicated.
5.3.3	Column dedicated to product system suitability shall be as per product system suitability parameters.
5.3.4	COA of column and system suitability Chromatogram/photocopy of Chromatogram shall be attached with the column performance record
5.3.5	Record the details in ‘Column Performance Record’ as per Annexure.
5.3.6	If the column performance qualify the column performance criteria. Then the column can be used for routine analysis.
5.3.7	If column fails to meet system suitability criteria then immediately reject the column and report to supervisor or Head of Department for further course of action.
5.4	Handling and Usage of Column
5.4.1	All the solvents used in analysis or column washing should be of HPLC grade.
5.4.2	Before starting analysis, wash the column for approximately 30 minutes with mixture of 50:50 Distilled Water and Methanol or Acetonitrile in normal direction of the column.
5.4.3	All mobile phase solutions, Standard solutions, Test solutions should be filtered through 0.45 µm or 0.2 µm membrane filter paper before used for analysis.
5.4.4	After completion of analysis, wash column initially with distilled water filtered through 0.45 µm or 0.2 µm membrane filter paper for about 30 minutes.
5.4.5	If buffer is used as Mobile phase while the analysis, Wash the column with water for the removal of buffer deposition.
5.4.6	Make sure that all buffers are washed out of the column before flushing with Acetonitrile or methanol.
5.4.7	Buffer salts are mainly not soluble in organic solvents. To flush buffer from the column, longer duration of water washing is ideal choice. Hot water flushing also can be done for removal of buffers.
5.4.8	Finally washed with 10:90 Distilled Water and Methanol or Acetonitrile.
5.4.9	Silica Cyno, Amino columns are shipped in n-Hexane or n-Heptane by its manufacturer, when such column are to be used for slightly polar eluent then column should be washed with ethanol or n-propanol before equilibration with mobile phase.
5.4.10	Enter all the details of usage in ‘Column Usage Record’ .
5.4.11	After use store the HPLC columns in their designated places with end caps/ pick nuts, when column is not in use.
5.4.12	Always store the column as per recommendation by its manufacturer unless otherwise specified follow In-House column washing instructions.
5.4.13	Routinely monitor the column performance by its theoretical plate count or system suitability parameter.
5.4.14	Always increased or decreased the flow rate gradually to avoid mechanical shock to the stationary phase.
5.4.15	For short term storage: That is overnight, store columns in 10:90 Distilled Water and Methanol or Acetonitrile.
5.4.16	For long term storage: That is 2 days or more, store columns in 100 % Methanol or Acetonitrile.
	Flushing of Reverse phase HPLC columns:
5.4.17	Before starting the analysis flush the column with water, then switch over to mobile phase and saturate the column with mobile phase and perform the analysis.
5.4.18	After completion of analysis, run the mobile phase for about 10 minutes. Switch over     to Water and wash the column with water for about 30 minutes at the flow rate 1.0 ml per minutes/as per specified STP.
5.4.19	Switch over to Methanol/Acetonitrile (used in mobile phase as per specified STP) and wash the column with methanol/Acetonitrile (used in mobile phase as per     specified STP) for about 30 minutes.
5.4.20	Set the flow to 0 ml/minute after completion of washing and remove the column from    the system. Put the end cap and keep the column at respective place.
	Flushing of Normal  phase HPLC columns:
5.4.21	After completion of analysis, run the mobile phase for about 10 minutes.
5.4.22	If Hexane is used in the mobile phase, switch over to 100% Dichloromethane.
5.4.23	Wash the column for about 60 minutes at flow rate 1.0 ml/minute.
	Note: Flow rate can be adjusted, depend upon column pressure.
5.4.24	If hexane is not used in the mobile phase, switch over to 100 % Methanol.
5.4.25	Wash the column with Methanol for about 30 minutes at the flow rate of 1.0 ml/minute.
5.4.26	Store the column in 100% methanol or as per recommended by Supplier/manufactures.
5.4.27	Set the flow to 0 ml /minutes after completion of washing and remove the column from the system. Put the end plug and keep the column at the respective place.
5.5	Discontinuation:
5.5.1	If system suitability parameters found out of limit then wash the column and perform suitability test again. If system suitability parameters not yet meets the acceptance criteria then discard the column and mention that the column is discarded in column usage logbook.
5.5.2	Dedicated columns can be used till it meets the requirements of system suitability of respective method.
5.5.3	Columns with high back pressure and not complying system suitability parameter should be discarded with the approval of Head Quality Control.
5.5.4	After many analysis column may fails to meet system suitability Criteria. In Such case file a incident report and investigate the root cause of system suitability failure. If root cause is found as column deterioration, then attach chromatogram of failure system suitability along with column usage log and discard the column.
5.5.5	Column should be labelled as “Not to used” and stored separately from other columns.
5.5.6	De-phase the discarded column and send to the scrap yard as a metal waste for further disposal.

 

6. Definition / Abbreviations :

• Definition:

 Abbreviations :

 

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
No.	Number
HPLC	High Performance Liquid Chromatography
µm	micrometer
i.e.	That is
%	Percentage

  

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

 

SOP Title: Procurement and Handling of Reference Standards/Impurity Standards         

1. Objective:

To lay down the procedure for Procurement and Handling of Reference Standards/Impurity Standards.

2. Scope:

This SOP is applicable for Procurement and Handling of Reference Standards/Impurity Standards in Quality Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Procurement and Handling of Reference Standards/Impurity Standards in Quality Control Department as per this SOP.
• Quality Assurance Department: To review and approve the SOP and Annexures.

 Accountability:

Head Quality Control Department, Head Quality Assurance Department

5. Procedure:

5.1	Procurement and Handling of Reference Standards/Impurity Standards :
5.1.1	Get the latest list of current lots of Reference Standards or Impurity Standards from the authorised agencies.
5.1.2	Pharmacopoeial grade Reference Standards or Impurity Standards shall be procured from Authorised Agency.
5.1.3	When any Reference Standard/Impurity Standard is received, the responsible analyst or officer should verify all the details like name, quantity received, Make, grade with the purchase order given to the respective agency.
5.1.4	Enter the details of Reference Standard/Impurity Standards received in “Reference Standard/Impurity Standard Receipt and Usage Record”
5.1.5	Assign the In-House Reference Number for Reference Standards and Impurity Standards as below:
5.1.6	For Reference Standards, assign Reference Number as ‘RSG/XX/YY-NN’. RS = Reference Standard G = Pharmacopoeial Grade ( I = IP , U = USP , B = BP  and E = EP) XX = Two alphabet from name of the Reference Standard YY = Last two digits of the current year NN = Serial number of received Reference Standard
5.1.7	For Impurity Standards, assign Reference Number as ‘ISG/XX/YY-NN’. IS = Impurity Standard G = Pharmacopoeial Grade ( I = IP , U = USP , B = BP  and E = EP) XX = Two alphabet from name of the Impurity Standard YY = Last two digits of the current year NN = Serial number of received Impurity Standard
5.1.8	Put the intact vial in a separate container that can easily traceable and label it as per Annexure.
5.1.9	Store the Reference Standard/Impurity Standard in refrigerator at 2°C to 8°C temperature or at specified storage conditions on containers or certificate.
5.1.10	Reference standard should be used during qualification of working standard as a reference. Reference standard also can be used for routine testing in case of unavailability of working standard.
5.1.11	Minimum amount of Reference standard shall be used for routine testing by decreasing at smaller dilutions.
	Note: When vials are removed from low temperature storage, they must be allowed to stand to attain Room temperature before use. Clean the outer Surface of vial with tissue paper before Use.
5.1.12	Wear safety masks, goggles, hand gloves while dispensing Reference Standard/Impurity Standard.
5.1.13	After each withdrawal, reseal the container and maintain “Reference Standard/Impurity Standard Receipt and Usage Record” as per Annexure
5.1.14	If expiry date is not given for reference standard or Impurity Standard then same can be used for up to 5 years from date of Manufacturing or from date of receipt whichever is earlier.
5.1.15	Discard the Reference Standard or Impurity by dissolving in water after its expiry and deface the label of the container.
5.1.16	Maintain list of Reference Standard/Impurity Standard as per Annexure
5.1.17	Immediately after use of Reference Standard/Impurity Standard, it should be restored back to its storage place.
5.1.18	During use of Reference Standard/Impurity Standard, do not put back the withdrawn material in the container.
5.1.19	For destruction of any Reference Standard/Impurity Standard, refer SOP of “Destruction of Laboratory Waste”.

 

6. Definitions / Abbreviations:

• Definitions :

 

• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
AR	Analytical Reagent
No.	Number
IP	Indian Pharmacopoeia
BP	British Pharmacopoeia
USP	United States Pharmacopoeia
EP	European Pharmacopoeia

 

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

 

SOP Title: Preparation and  Standardisation of  Volumetric  Solutions

1. Objective:

To lay down the procedure for Preparation and Standardisation of Volumetric Solutions.

2. Scope:

This SOP is applicable for Preparation and Standardisation of Volumetric Solutions in Quality

Control Department.

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Preparation and Standardisation of Volumetric Solutions 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	Procedure for Preparation of Volumetric Solutions:
5.1.1	Always use personal protective equipments such as Hand gloves, nose masks, and goggles while preparing Volumetric Solutions.
5.1.2	Use analytical grade reagents or highly purified salts for preparation of Volumetric Solutions.

 

5.1.3	As per requirement, Volumetric Solutions should be prepared by accurately weighing a suitable quantity of defined chemical specified in respective Standard Testing Procedure or official monograph (IP, BP, and USP) and dissolving it in purified water/solvent to produce a specific concentration.
5.1.4	A prior calculation is carried out to estimate the approximate weight of the Primary Standard required to make up the known volume of Volumetric Solution.
5.1.5	Weigh accurately the specified quantity of Primary Standard on an electronic balance using a weighing bottle or butter paper.
5.1.6	Transfer the solid to the volumetric flask and rinse the butter paper into the volumetric flask with specified solvent.
5.1.7	Add specified volume of solvent to the flask and swirl the mixture until all of the solute dissolves and then dilute up to the mark.
5.1.8	Invert and shake volumetric flask several times to thoroughly mix the contents.
5.1.9	Store all the Volumetric Solutions in clean and dry borosilicate glass bottles at room temperature or as specified in the respective Standard Testing Procedure or official pharmacopoeia.
5.1.10	Volumetric Solutions which are light sensitive shall be preserved in amber coloured borosilicate glass bottles.
5.1.11	Enter all the preparation details in “Volumetric Solution Preparation Record”

 

5.1.12	Allocate Reference Number for all the Volumetric Solutions prepared as: VS/ZZZ/XX/YY-NN Where ‘VS’ stands for ‘Volumetric Solution’ ‘ZZZ’ stands for ‘Volumetric Solution Number as 001, 002’ ‘XX’ stands for ‘Reference Pharmacopeia i.e. IP, BP, USP, EP, IBU, BU, IU, IB or BU’ ‘YY’ stands for ‘Last two digits of the current year’ ‘NN’ stands for ‘Serial number of preparation’
5.1.13	Example: If 0.1 M Sodium Hydroxide which has Volumetric Solution number as VS/022 is prepared as per BP for the first time in the year 2024, then the reference number shall be VS/022/BP/24-01. If the same solution is prepared for second time in the year 2024, then the reference number shall be VS/022/BP/24-02.
5.1.14	If the Volumetric Solution preparation method is same in two or more Pharmacopoeias, then the Reference Pharmacopeia for the Volumetric Solution number shall be denoted by first letter of Pharmacopoeias used.
5.1.15	Example: If the Volumetric Solution preparation method is same in IP, BP and USP, then the Reference Pharmacopeia for allocating the Volumetric Solution number shall be ‘IBU’ where ‘I’ stands for ‘IP’, ‘B’ stands for ‘BP’, ‘U’ stands for ‘USP’.
5.1.16	All Volumetric Solutions bottles shall be labelled as “Volumetric Solution” indicating the name, concentration of the solution, date of preparation, signature of the person who prepared it, validity and storage conditions as per Annexure.
5.1.17	Supervisor should verify that all the Volumetric Solutions are prepared as per STP or Pharmacopeia and check the “Volumetric Solution Preparation Record”.
5.1.18	All the Volumetric Solutions shall be kept on the racks of the working table provided in wet chemistry area.
5.1.19	Unless otherwise specified, all the Volumetric Solutions should be used within one month from the date of preparation or earlier depending on the solution stability.
5.1.20	Example: If 0.1 M Sodium hydroxide solution is prepared on 01/06/24, then the date of preparation shall be 01/06/24 and the validity shall be 30/06/24.
5.2	Procedure for Standardisation of Volumetric Solutions:
5.2.1	Volumetric Solutions shall be standardized by titration against a primary standard or by titration with a standard solution that has been recently standardized against a primary standard as per the method given in respective specification or pharmacopeia in triplicate.
5.2.2	After use of Primary Standards, enter its usage in Primary Standard Receipt and Usage Record.
	Take the mean of three readings for reporting.
5.2.3	Acceptance Criteria: 1)         The % RSD for three replicate readings should not be more than 0.2% 2)         The actual concentration/ strength of the volumetric Solution should be within 10% of its theoretical value.
	Example: 1 M NaOH Solution has to be prepared then actual molarity should be within 0.9 M to 1.1 M
5.2.4	If any solution does not comply within above mentioned criteria then investigate the cause by filling incidence. Discard the solution if necessary and prepare fresh solution.
5.2.5	Enter all the standardisation details in “Volumetric Solution Standardisation Record”.
5.2.6	All Volumetric Solution Standardisation records shall be counter checked by second analyst or supervisor.
5.2.7	All Volumetric Solution Standardisation
5.3	Procedure to perform Solution Stability Study:
	To assign validity, solution stability study shall be performed every week up to 5 week or it can also be established based on the available historical data.
	Procedure to perform Solution Stability Study Based on Real Time Data:- Prepare three different standard solutions on three different days. Standardize these volumetric standard solutions every week up to 5 week. Record all the preparations and result as per Annexure;
	1)      If all three volumetric solutions are stable for 5 week as per given acceptance criteria then validity shall be assigned one month from the date of solution preparation. 2)      If all three volumetric solutions are stable up to 4 week as per given acceptance criteria then validity shall be assigned 21 days from the date of solution preparation. 3)      If all three volumetric solutions are stable up to 3 week as per given acceptance criteria then validity shall be assigned 15 days from the date of solution preparation. 4)      If all three volumetric solutions are stable up to 2 week as per given acceptance criteria then validity shall be assigned 7 days from the date of solution preparation. 5)      If all three volumetric solutions are stable up to 1 week as per given acceptance criteria then validity shall be assigned 3 days from the date of solution preparation. 6)      If all three volumetric solutions are not stable up to 1 week as per given acceptance criteria then every time fresh solution shall be prepared and shall be used for analysis.
	Procedure to Establish Solution Stability Study Based on Historical Data:- For three different solutions prepared on three different days. Based on evaluation of data conclusion shall be made.
	Acceptance Criteria: 1) The % RSD for three replicate readings should not be more than 0.2% 2) The actual concentration/ strength of the volumetric Solution should be within 10% of its theoretical value.
5.2.8	All the Volumetric Solutions that show evidence of deterioration, e.g. sedimentation, discoloration or crystallization, shall be discarded regardless of validity. Record for discard shall be recorded in Annexure.
5.2.9	All the Volumetric Solutions shall be destroyed as per SOP “Destruction of Laboratory waste”.

  

6. Definitions / Abbreviations :

• Definitions :
• Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance

 

STP	Standard Testing Procedure
No.	Number
%	Percentage
M	Molar

 

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

 

SOP Title: Working Standard Preparation

 

1. Objective:

To lay down the procedure for Working Standard Preparation.

2. Scope:

This SOP is applicable for Working Standard Preparation in Quality Control Department.

3. Responsibility:

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

 Accountability:

Head Quality Control Department, Head Quality Assurance Department.

5. Procedure:

5.1	Working Standard Preparation:
5.1.1	Select the high purity material for Working Standard preparation.
5.1.2	It should be indented from the raw material store or from API Manufacturer.
5.1.3	Select a material of the latest passed batch having highest purity, lowest impurity.
	Note: In case of any manufacturer provides the working standard same shall be used and no further standardization required.
5.1.4	Give “Material Requisition for Working Standard Preparation” as per Annexure No. 01 to Warehouse Department.
5.1.5	Take required quantity of material based on vial filling and analysis of working standard.
5.1.6	In case of low dose materials take minimum required quantity of material based on vial filling and analysis of working standard.
5.1.7	Supervisor/QC Head shall allocate the testing samples to the analysts as per their job responsibility and specialisation.
5.1.8	Analyst should refer Standard Testing Procedure before initiating the testing.
5.1.9	Analyst should give requisition for “Analytical Work Report” to the Quality Assurance Department as per the SOP “Control of Documents, Preparation, Approval, Issuance and Maintenance”.
5.1.10	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.
5.1.11	In case of non-availability of Chemicals, Impurities, Working Standard, Instruments or Equipment’s in the Laboratory for any specified test then the sample to be send to Government Approved Outside Testing Laboratory, by filling “Requisition for Analysis” form as per SOP “Approval of Outside Testing Laboratory and Analysis of Samples at Outside Testing Laboratory” with relevant necessary information.
5.1.12	While preparation of working standard refer the Current reference standard lot number
5.1.13	Analyst should fill in the necessary details on the Analytical Work Report and start the analysis as per Standard Testing Procedure and Specifications.
5.1.14	If working standard qualified within the 3 months of original passed batch testing then, only critical test shall be performed again as mentioned below:
5.1.15	Description: One time sufficient Loss on drying / Water : Single preparation separately by two analyst Assay Test: Single preparation separately by two analyst (In-house Testing) Should be in single (External Testing)
5.1.16	If working standard qualified after 3 months then perform full testing as per STP and qualify for the working standard.
5.1.17	All the test and parameters should be followed as per Raw Material Specifications using Reference Standards or previously standardized Working Standard.
5.1.18	In case of IR and UV Testing, Spectrum obtained shall be compared against the spectrum obtained by the reference standard. Analyze the material for Identification and related impurities (wherever applicable).
5.1.19	LOD/Water value should not be vary more than 0.5 between two analysts.
5.1.20	Assay value should not be vary more than 1.0 % between two analysts.
5.1.21	If material tested from outside lab, perform all tests only single time.
5.1.22	After completion of analysis, assign the Working Standard Number and prepare the “Certificate of Analysis (Working Standard)” as per SOP with details including Reference Standard Number used to prepare Working Standard.
5.1.23	Use the mean value of replicate results during data presentation on “Certificate of Analysis (Working Standard)”. Assign the validity of Working Standard up to one year from the date of approval or Expiry given by manufacturer, whichever is earlier.
5.1.24	After the analysis, analyst should hand over the Analytical Work Report to Supervisor/Reviewer analyst 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 by filling incident or OOS as per SOP “Out of Specification” depending on discrepancies.
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 “Certificate of Analysis (Working Standard)”as per specified format.
5.1.27	In case of any raw material having two pharmacopoeia grades material shall be standardized for both the pharmacopoeias procedures and both pharmacopoeias potency shall be mentioned on the label.
5.1.28	Quality Control Head shall verify and approve the COA.
5.1.29	Pharmacopoeia grade Reference Standards or Impurity Standards shall be procured from Authorised Agency.
5.1.30	Assign Working Standard Number as follows: If the Working Standard prepared as per IP, number should be given as: WS/IP/XXX/YY/NN. If the Working Standard prepared as per BP, number should be given as: WS/BP/XXX/YY/NN. If the Working Standard prepared as per USP, number should be given as WS/USP/XXX/YY/NN. where:- WS: Working Standard IP: Indian Pharmacopoeia BP: British Pharmacopoeia USP: United State Pharmacopoeia XXX : Material Code YY: Last two digits of the current year NN: Serial number of that particular Working Standard
5.1.31	Prepare the 13 vials of the Working Standards in same quantity.
5.1.32	Keep 12 vial for one year i.e. each vial per month and keep One vial as a Reserve Working Standard.
5.1.33	In case of low dose materials prepare Five vials of the Working Standards in same quantity. Keep 4 vial for one year i.e. every 3 month one vial and keep One vial as a Reserve Working Standard.
5.1.34	Store the Working Standards in Refrigerator at 2°C to 8°C or as per respective material storage condition in glass vials with butyl rubber plugs and tightly closed with aluminium seal.
5.1.35	For light sensitive material use amber coloured glass vials.
5.1.36	Label the vials with detailed information and vial number also as 1/ 13, 2 /13 and so on.
5.1.37	Issue the first vial for first months and next for coming months as per serial number. Opened vial is valid for one month from the date of opening.
5.1.38	Discard the each opened vial after use or within 3 days of respective month end. Example: If an Paracetamol  (API) working standard vial no.1 is opened on 15/05/2023, then it should be discard within 3 days i.e. from 14/06/2023 to 16/06/2023.
5.1.39	Allow the Working Standard to equilibrate to room temperature in the original container before it is weighed for a test.
5.1.40	Care should be taken to minimise the exposure of Working Standards to atmospheric condition for longer time. After use, immediately close the vial with cap and keep it as per respective storage condition. Update ‘Working Standard Usage Log Book’’.
5.1.41	Dispensing equipment such as Spatula, butter paper etc. should not be inserted into the Working Standards vials as this may contaminate the material.
5.1.42	Material taken out for weighing that is in excess should not be transferred back to the vial.
5.1.43	All unused vials shall be destroyed at end of one year.
5.1.44	In-case, for any reason new material is not available in stock to prepare new working standard, then unused working standard vials shall be retested as per working standard qualification criteria and shall be used for next one year provided that it should be within the expiry period assigned by manufacturer. Example: If the Paracetamol (API) working standard vial retested on 10/05/2023 and Manufacturer expiry period of Paracetamol is 04/2024 then it cannot be used beyond 30/04/2024.
5.1.45	For destruction of any Working Standards, refer current SOP of “Destruction of Laboratory Waste”.

6. Definitions / Abbreviations:

• Definitions :

 

•    Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance

 

AR	Analytical Reagent
No.	Number
RSD	Relative Standard Deviation
%	Percentage

  

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

 

SOP Title: Preparation and Handling of Laboratory Reagents

1. Objective:

To lay down the procedure for Preparation and Handling of Laboratory Reagents in Quality

Control Department.

2. Scope:

This procedure is applicable for Preparation and Handling of Laboratory Reagents 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 Preparation and Handling of Laboratory Reagents 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:

 

5.1	Precautions:
5.1.1	Always use personal protective equipments such as Hand gloves, nose masks, and goggles while preparing reagents.	QC Associate
5.1.2	Strictly follow the precautions, warning mentioned on chemical/reagent bottles or refer Material Safety Data Sheets (MSDS) which provide information concerning the safe handling of chemicals, their storage, hazards, first aid and disposal.
5.1.3	Do not draw any liquid into pipette by mouth as the chemical/solvent in the pipette may enter into the mouth. Use rubber bulb or other pipetting aids.
5.1.4	While preparing acid solutions, always add acid to water. Do not add water to acid as this reaction may produce significant heat.
5.1.5	All reagents/indicators/standard solutions shall be stored in tightly-closed containers.
5.2	Procedure for preparation of general reagents/indicators/standard solutions:
5.2.1	Use analytical grade chemicals/solvents and prepare reagents as per Standard Testing Procedure or Pharmacopoeia.
5.2.2	As per requirement, Reagent, indicators, limit test standard solutions should be prepared by accurately weighing a suitable quantity specified in individual official monograph (IP, BP, USP or STP) and dissolving it in purified water or prescribed solvents to produce a specific concentration.
5.2.3	Storage of solution is as per Pharmacopoeia /STP requirement.
5.2.4	Store all the solutions in cleaned dry borosilicate glass bottles at room temperature or as specified in respective STP or Pharmacopoeia.
5.2.5	Solutions which are light sensitive shall be preserved in amber coloured borosilicate glass bottles.
5.2.6	Record all the preparation details in “Reagent Preparation Register” as per Annexure.
5.2.7	Allocate reference number for all the general reagents/indicators prepared as ‘GR/XXX/PP/YY-NN’. Where ‘GR’ stands for ‘General Reagent’. ‘XXX’ stands for ‘Reagent Number’. ‘PP’ stands for ‘Reference Pharmacopoeia i.e. IP, BP, USP, EP, ‘YY’ stands for ‘Last two digits of the current year’. ‘NN’ stands for ‘Serial number of preparation i.e. 01, 02 and so on’.
5.2.8	Example: If Ammonia solution which has reagent number as GR/022/BP is prepared as per BP for the first time in the year 2024, then the reference number shall be GR/022/BP/24-01. If the same solution is prepared for second time in the year 2024, then the reference number shall be GR/022/BP/24-02.
5.2.9	If the reagent preparation method is same in two or more Pharmacopoeias, then the Reference Pharmacopoeia for the reagent number shall be denoted by first letter of Pharmacopoeias used. Example: If the reagent preparation method is same in IP, BP and USP, then the Reference Pharmacopoeia for allocating the reagent number shall be ‘IBU’ where ‘I’ stands for ‘IP’, ‘B’ stands for ‘BP’, ‘U’ stands for ‘USP’.
5.2.10	“Reagent Preparation Register” should have the “Index sheet” for reagents/indicators/standard solutions present with reagent number as GR/001/IP, GR/002/BP and so on as per define Annexure.
5.2.11	All reagents/indicators/standard solutions bottles shall be labelled as “Reagent Solution” indicating the name, concentration of the solution, date of preparation, signature of the person who prepared it, validity and storage conditions as per define in Annexure.
5.2.12	Supervisor should verify that all the reagents/indicators/standard solutions are prepared as per STP or Pharmacopoeia and check the “Reagent Preparation Register”.
5.2.13	All the reagents/indicators/standard solutions shall be kept on the racks of the working table provided in wet chemistry area.
5.2.14	Unless otherwise specified, all the reagent solutions should be used within 3 months from the date of preparation.
5.2.15	Example: If Sodium hydroxide solution is prepared on 01/05/24, then the date of preparation shall be 01/05/24 and the validity shall be 31/07/24.
5.2.16	Unless otherwise specified, all the limit test solutions, indicators and standard solutions should be used within one month from the date of preparation.
5.2.17	Example: If Phenolphthalein solution is prepared on 20/04/24, then the date of preparation shall be 20/04/24 and the validity shall be 19/05/24.
5.2.18	If any STP or Pharmacopoeia says ‘Freshly prepared’ then those reagents should be prepared on the day of use and discarded on completion of analysis or used within 24 hours.
5.2.19	All solutions that show evidence of deterioration, e.g. sedimentation, discoloration or crystallization, shall be discarded regardless of validity.
5.2.20	All the reagents/indicators/standard solutions shall be destroyed as per SOP “Destruction of Laboratory waste”.
	Examples of Reagent preparations:
5.2.21	10 % w/v solution of Sodium Hydroxide: Dissolve 10 gram of sodium hydroxide in purified water and dilute it to 100 ml with purified water.
5.2.22	5% v/v solution of Acetic acid: Dilute 5 ml of acetic acid to 100 ml with purified water.
5.2.23	Dilute Sulphuric acid: Add 5.5 ml of sulphuric acid to 60 ml of water, allow to cool and add sufficient water to produce 100 ml.
5.2.24	2 M Sulphuric acid: When solutions of molarity ‘x’ M are required, they should be prepared by carefully adding 54 X ‘x’ ml of sulphuric acid to an equal volume of water and diluting to 1000 ml with water. Where ‘x’ is the required molarity. 98.07 is the molecular weight of sulphuric acid and 1.84 gm/ml is the density of sulphuric acid.
5.2.25	Aluminum Standard Solution (10 ppm Al): Dilute 1 ml of a 1.39 % w/v solution of aluminum nitrate to 100 volumes with water.

6. Definitions / Abbreviations:

• Definitions :
• Reagent: Reagent is a substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs.
• Indicators: Indicators are reagents used to determine the specified endpoint in a chemical reaction which indicates the change in colour, to measure hydrogen-ion concentration (pH) or to indicate the desired change in pH has been effected.
• Buffer solutions: Buffer solutions are solutions that resist change in the activity of an ion on the addition of substances that are expected to change the activity of that ion.
• Carbon Dioxide-Free water: It is the purified water that has been boiled vigorously for 5 minutes or more and allowed to cool while protected from absorption of carbon dioxide from the atmosphere.
• Expression of concentrations:

Molar solutions (M): Molar solutions are solutions that contain 1 gram molecule of the compound in 1 litre of solution.

Normal solutions (N): Normal solutions are solutions that contain 1 gram equivalent weight of the compound in 1 litre of solution

Percentage weight in weight (%w/w): It expresses the number of grams of solute in 100 g of product.

Percentage weight in volume (% w/v): It expresses the number of grams of solute in 100 ml of product.

Percentage volume in volume (% v/v):  It expresses the number of milliliters of solute in 100 ml of product.

Percentage volume in weight (% v/w): It expresses the number of milliliters of solute in 100 g of product.

Parts per million (ppm): “Parts per Million” is a way to quantify very low concentrations of substances. For example, 1 ppm is equivalent to 1 milligram of solute per litre of liquid (abbreviated as mg/L). 1 milligram of solute per millilitre of liquid (abbreviated as mg/ml).

1 mg/ml = 1000 ppm

 

•      Abbreviations :

Abbreviation	Expansion
SOP	Standard Operating Procedure
QC	Quality Control
QA	Quality Assurance
pH	Power of Hydrogen
MSDS	Material Safety Data Sheet
mg	milligram
ml	milliliter
e.g.	example
IP	Indian Pharmacopeia
BP	British Pharmacopeia
USP	United States Pharmacopeia
STP	Standard Testing Procedure

 

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

 

1. Objective:

To lay down the procedure for Preparation of Certificate of Analysis in Quality Control Department.

 

2. Scope:

This SOP is applicable for Preparation of Certificate of Analysis in Quality control Department.

 

3. Responsibility:

• Quality Control Department: To prepare and review the SOP. To follow the procedures laid down for Preparation of Certificate of Analysis 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	Preparation of Raw Material Certificate of Analysis:
5.1.1	On completion of Raw Material analysis, analyst or supervisor should prepare Certificate of Analysis as per respective Analytical Work Report of Raw Material.
5.1.2	Certificate of Analysis comprises of Header, Footer and Body.
5.1.3	Prepare Certificate of Analysis as per following procedure.
5.1.4	Header should contain the following:
5.1.5	1.      Company logo 2.      Company Name (Font: Times new roman, Font style: Bold, font size 22) 3.      Address of the company (Font: Times new roman, Font style: Regular, font size 12) 4.      Department name(Font: Times new roman, Font style: Bold, font size 18) /Page No.    ( Font: Times new roman, Font style: regular, font size 12) 5.      Title as ‘Certificate of Analysis’ (Font: Times new roman, Font style: Bold, font size 16) 6.      Subtitle as ‘Raw Material’ (Font: Times new roman, Font style: Bold, font size 16)
5.1.6	Body contains all the detail information of Raw Material, Tests parameters, Results obtained and Acceptance Criteria as per respective Raw Material Specification.
5.1.7	Body is divided into two parts.
5.1.8	First part contains detail information of Raw Material as follows: 1.         Name 2.         Manufacturer 3.         Supplier 4.         Batch No. 5.         Quantity Received 6.         A.R. No. 7.         GRN No. and Date 8.         Mfg. Date 9.         Exp. Date 10.     Quantity Sampled 11.     Sampled by and Date 12.     Release Date: 13.     Retest Date:
5.1.9	Second part contains Serial Number, Tests, Results and Standard Limits.
5.1.10	Footer contains final conclusion of the analysis as follows: Remark: The sample complies / does not comply with respect to the above tests as perIP/BP/USP/IHSand Raw Material Specification No.:________
5.1.11	After remark, footer contains Analysed by, Checked by and Approved by signatures with date.
5.1.12	Analyst (who performed analysis), Reviewer or supervisor (who checked the Analytical Work Report and COA) and Quality Control Head (who approves the Analytical Work Report and COA) should sign on the COA.
5.2	Preparation of Finished Product Certificate of Analysis:
5.2.1	On completion of Finished Productanalysis, analyst or supervisor should prepare Certificate of Analysis as per respective Analytical Work Report of Finished Product.
5.2.2	Follow the same procedure as mentioned for preparation of Raw Material Certificate of Analysis except the following:
5.2.3	In the header, Title shall be ‘Finished Product’.
5.2.4	Body contains all the detail information of Finished Product, Tests parameters, Results obtained and Acceptance Criteria as per respective Finished Product Specification.
5.2.5	First part contains detail information of Finished Product as follows: 1.         Generic Name 2.         Brand Name 3.         Batch No. 4.         Batch Size 5.         Mfg. Date 6.         Exp. Date 7.         A. R. No. 8.         Quantity Sampled 9.         Sampled by and Date 10.     Release Date
5.2.6	Footer contains final conclusion of the analysis as follows: Remark: The sample complies / does not comply with respect to the above tests as perIP/BP/USP/IHSand Finished Product Specification No.:__________
5.2.7	Finished Product COA shall be approved by QA Head or Designee.
5.3	Preparation of In process Sample Certificate of Analysis:
5.3.1	On completion of In process Sampleanalysis, analyst or supervisor should prepare Certificate of Analysis (If required) as per respective Analytical Work Report of In process Sample.
5.3.2	Follow the same procedure as mentioned for preparation of Raw Material Certificate of Analysis except the following:
5.3.3	In the header, Title shall be ‘In process Sample’.
5.3.4	Body contains all the detail information of In process Sample, Tests parameters, Results obtained and Acceptance Criteria as per respective In process Sample Specification.
5.3.5	First part contains detail information of In process Sample as follows: 1.         Generic Name 2.         Brand Name 3.         Batch No. 4.         Batch Size 5.         Mfg. Date 6.         Exp. Date 7.         A. R. No. 8.         Quantity Sampled 9.         Sampled by and Date 10.     Release Date
	Note: In process COA can be Prepare as per party requirement.
5.3.6	Footer contains final conclusion of the analysis as follows: Remark: The sample complies / does not comply with respect to the above tests as per IP/BP/USP and In process Sample Specification No.:_________
5.4	Preparation of Packing Material Certificate of Analysis:
5.4.1	On completion of Packing Materialanalysis, analyst or supervisor should prepare Certificate of Analysis as per respective Analytical Work Report of Packing Material.
5.4.2	Follow the same procedure as mentioned for preparation of Packing MaterialCertificate of Analysis except the following:
5.4.3	In the header, Title shall be ‘Packing Material’.
5.4.4	Body contains all the detail information of Packing Material, Tests parameters, Results obtained and Acceptance Criteria as per respective Packing MaterialSpecification.
5.4.5	Footer contains final conclusion of the analysis as follows: Remark: The sample complies / does not comply with respect to the above tests as per IP/BP/USP/IHS and Packing Material Specification No.:_______
5.5	Preparation of Working Standard Certificate of Analysis
5.5.1	On completion of Working Standard analysis, analyst or supervisor should prepare Certificate of Analysis as per respective Analytical Work Report of Working Standard.
5.5.2	Follow the same procedure as mentioned for preparation of Working Standard Certificate of Analysis except the following:
5.5.3	In the header, Title shall be ‘Working Standard’.
5.5.4	Body contains all the detail information of Working Standard, Tests parameters, Results obtained and Acceptance Criteria as per respective Working Standard Specification.
5.5.5	First part contains detail information of Working Standard as follows: 1.         Name 2.         WS No. 3.         Source A. R. No. 4.         Evaluated with Reference Standard No. 5.         Reference Standard Lot No. / Batch No. 6.         Date of Qualification 7.         Validity 8.         Storage Conditions
5.5.6	Footer contains final conclusion of the analysis as follows: Remark: The sample complies / does not comply with respect to the above tests as per Specification No.:_________ and certified to be used as Working Standard.

 

 

6. Definition/Abbreviations:

• Definition:

 

• Abbreviations:

Abbreviation	Expansion
No.	Number
COA	Certificate of Analysis
A. R. No.	Analytical Reference Number
IP	Indian Pharmacopoeia
BP	British Pharmacopoeia
USP	United State Pharmacopoeia
Mfg.	Manufacturing
Exp.	Expiry

 

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